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Patil S, Subtirelu R, Teichner E, Kata R, Gerlach A, Ayubcha C, Alnemri A, Werner T, Alavi A, Newberg AB. CT, MRI, and PET Imaging in Patients with Traumatic Brain Injury. PET Clin 2025; 20:133-145. [PMID: 39547731 DOI: 10.1016/j.cpet.2024.09.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2024]
Abstract
Traumatic brain injury (TBI) is a major health concern in the United States and worldwide. Neuroimaging is a critical element in the clinical evaluation of TBIs, as computed tomography (CT) and MR imaging are commonly used to identify structural changes that may aid in treatment decision-making and long-term patient monitoring. This article reviews the utility of CT and MR imaging while focusing on the emerging applications of PET in TBI. Pertinent research findings in the molecular imaging of cerebral metabolism, tau and β-amyloid, neurotransmitters, and neuroinflammation are discussed.
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Affiliation(s)
- Shiv Patil
- Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA; Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA
| | - Robert Subtirelu
- Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA
| | - Eric Teichner
- Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA; Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA
| | - Rithvik Kata
- Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA; Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA
| | - Alexander Gerlach
- Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA
| | - Cyrus Ayubcha
- Harvard Medical School, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Ahab Alnemri
- Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA
| | - Thomas Werner
- Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA
| | - Abass Alavi
- Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA
| | - Andrew B Newberg
- Marcus Institute of Integrative Health, Thomas Jefferson University, Philadelphia, PA, USA; Department of Radiology, Thomas Jefferson University, Philadelphia, PA, USA.
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Czobit C, Samavi R. Generative Adversarial Networks for Neuroimage Translation. J Comput Biol 2024. [PMID: 39729343 DOI: 10.1089/cmb.2024.0635] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2024] Open
Abstract
Image-to-image translation has gained popularity in the medical field to transform images from one domain to another. Medical image synthesis via domain transformation is advantageous in its ability to augment an image dataset where images for a given class are limited. From the learning perspective, this process contributes to the data-oriented robustness of the model by inherently broadening the model's exposure to more diverse visual data and enabling it to learn more generalized features. In the case of generating additional neuroimages, it is advantageous to obtain unidentifiable medical data and augment smaller annotated datasets. This study proposes the development of a cycle-consistent generative adversarial network (CycleGAN) model for translating neuroimages from one field strength to another (e.g., 3 Tesla [T] to 1.5 T). This model was compared with a model based on a deep convolutional GAN model architecture. CycleGAN was able to generate the synthetic and reconstructed images with reasonable accuracy. The mapping function from the source (3 T) to the target domain (1.5 T) performed optimally with an average peak signal-to-noise ratio value of 25.69 ± 2.49 dB and a mean absolute error value of 2106.27 ± 1218.37. The codes for this study have been made publicly available in the following GitHub repository.a.
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Affiliation(s)
- Cassandra Czobit
- Electrical, Computer and Biomedical Engineering, Toronto Metropolitan University, Toronto, Canada
| | - Reza Samavi
- Electrical, Computer and Biomedical Engineering, Toronto Metropolitan University, Toronto, Canada
- Vector Institute for Artificial Intelligence, Toronto, Canada
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Jacquens A, Csaba Z, Soleimanzad H, Bokobza C, Delmotte PR, Userovici C, Boussemart P, Chhor V, Bouvier D, van de Looij Y, Faivre V, Diao S, Lemoine S, Blugeon C, Schwendimann L, Young-Ten P, Naffaa V, Laprevote O, Tanter M, Dournaud P, Van Steenwinckel J, Degos V, Gressens P. Deleterious effect of sustained neuroinflammation in pediatric traumatic brain injury. Brain Behav Immun 2024; 120:99-116. [PMID: 38705494 DOI: 10.1016/j.bbi.2024.04.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 04/15/2024] [Accepted: 04/22/2024] [Indexed: 05/07/2024] Open
Abstract
INTRODUCTION Despite improved management of traumatic brain injury (TBI), it still leads to lifelong sequelae and disability, particularly in children. Chronic neuroinflammation (the so-called tertiary phase), in particular, microglia/macrophage and astrocyte reactivity, is among the main mechanisms suspected of playing a role in the generation of lesions associated with TBI. The role of acute neuroinflammation is now well understood, but its persistent effect and impact on the brain, particularly during development, are not. Here, we investigated the long-term effects of pediatric TBI on the brain in a mouse model. METHODS Pediatric TBI was induced in mice on postnatal day (P) 7 by weight-drop trauma. The time course of neuroinflammation and myelination was examined in the TBI mice. They were also assessed by magnetic resonance, functional ultrasound, and behavioral tests at P45. RESULTS TBI induced robust neuroinflammation, characterized by acute microglia/macrophage and astrocyte reactivity. The long-term consequences of pediatric TBI studied on P45 involved localized scarring astrogliosis, persistent microgliosis associated with a specific transcriptomic signature, and a long-lasting myelination defect consisting of the loss of myelinated axons, a decreased level of myelin binding protein, and severe thinning of the corpus callosum. These results were confirmed by reduced fractional anisotropy, measured by diffusion tensor imaging, and altered inter- and intra-hemispheric connectivity, measured by functional ultrasound imaging. In addition, adolescent mice with pediatric TBI showed persistent social interaction deficits and signs of anxiety and depressive behaviors. CONCLUSIONS We show that pediatric TBI induces tertiary neuroinflammatory processes associated with white matter lesions and altered behavior. These results support our model as a model for preclinical studies for tertiary lesions following TBI.
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Affiliation(s)
- Alice Jacquens
- Université Paris Cité, Inserm, NeuroDiderot, 75019 Paris, France; Sorbonne University, GRC 29, AP-HP, DMU DREAM, Department of Anaesthesiology and Critical Care Medicine, Pitié-Salpêtrière Hospital, 47-83, boulevard de l'Hôpital, 75013 Paris, France.
| | - Zsolt Csaba
- Université Paris Cité, Inserm, NeuroDiderot, 75019 Paris, France
| | - Haleh Soleimanzad
- Physics for Medicine Paris, Inserm, ESPCI Paris, PSL Research University, CNRS, 75005 Paris, France
| | - Cindy Bokobza
- Université Paris Cité, Inserm, NeuroDiderot, 75019 Paris, France
| | | | | | | | - Vibol Chhor
- Université Paris Cité, Inserm, NeuroDiderot, 75019 Paris, France
| | - Damien Bouvier
- Université Paris Cité, Inserm, NeuroDiderot, 75019 Paris, France
| | - Yohan van de Looij
- Université de Genève, Service Développement et Croissance, Département de Pédiatrie, Faculté de Médecine, 1211 Genève, Suisse; Centre d'Imagerie Biomédicale, Section Technologie d'Imagerie Animale, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Suisse
| | - Valérie Faivre
- Université Paris Cité, Inserm, NeuroDiderot, 75019 Paris, France
| | - Siaho Diao
- Université Paris Cité, Inserm, NeuroDiderot, 75019 Paris, France
| | - Sophie Lemoine
- Genomics Core Facility, Département de Biologie, École Normale Supérieure, Institut de Biologie de l'ENS (IBENS), CNRS, INSERM, Université PSL, Paris, France
| | - Corinne Blugeon
- Genomics Core Facility, Département de Biologie, École Normale Supérieure, Institut de Biologie de l'ENS (IBENS), CNRS, INSERM, Université PSL, Paris, France
| | | | | | - Vanessa Naffaa
- Université Paris Cité, Inserm, NeuroDiderot, 75019 Paris, France
| | - Olivier Laprevote
- Université de Paris, CNRS, CiTCoM, 75006 Paris, France; Hôpital Européen Georges Pompidou, AP-HP, Service de Biochimie, 75015 Paris, France
| | - Mickael Tanter
- Physics for Medicine Paris, Inserm, ESPCI Paris, PSL Research University, CNRS, 75005 Paris, France
| | - Pascal Dournaud
- Université Paris Cité, Inserm, NeuroDiderot, 75019 Paris, France
| | | | - Vincent Degos
- Université Paris Cité, Inserm, NeuroDiderot, 75019 Paris, France; Sorbonne University, GRC 29, AP-HP, DMU DREAM, Department of Anaesthesiology and Critical Care Medicine, Pitié-Salpêtrière Hospital, 47-83, boulevard de l'Hôpital, 75013 Paris, France
| | - Pierre Gressens
- Université Paris Cité, Inserm, NeuroDiderot, 75019 Paris, France
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Walter AE, Savalia K, Yoon J, Morrison J, Schneider ALC, Diaz-Arrastia R, Sandsmark DK. Change in Enlarged Perivascular Spaces over Time and Associations with Outcomes After Traumatic Brain Injury. Neurotrauma Rep 2024; 5:738-748. [PMID: 39144451 PMCID: PMC11319858 DOI: 10.1089/neur.2024.0026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/16/2024] Open
Abstract
Enlarged perivascular spaces (EPVs) can be seen on magnetic resonance imaging (MRI) scans in various neurological diseases, including traumatic brain injury (TBI). EPVs have been associated with cognitive dysfunction and sleep disturbances; however, their clinical significance remains unclear. The goal of this study was to identify MRI burden of EPVs over time following TBI and to explore their relationship with postinjury outcomes. Individuals with TBI underwent postinjury data collection at Day 1 (blood), 2 weeks (blood, MRI, outcomes), and 6 months (blood, MRI, outcomes). EPV burden was assessed using T1 and FLAIR sequences on representative slices in the centrum semiovale, basal ganglia, and midbrain. Serum blood was assayed to measure concentrations of neurofilament light (NfL) and glial fibrillary acidic protein (GFAP). Thirty-two participants with TBI were included (mean age 36.8 years, 78% male, 50% White). Total EPVs count did not significantly change from 2 weeks (23.5 [95% confidence interval or CI = 22.0-32.0]) to 6 months (26.0 [95% CI = 22.0-30.0], p = 0.16). For self-reported measures of sleep, there were no significant associations between EPVs count and Insomnia Severity Index (2 weeks: β = -0.004; 95% CI = -0.094, 0.086; 6 months: β = 0.002; 95% CI = -0.122, 0.125) or the subset of sleep questions on the Rivermead Post-Concussion Symptoms Questionnaire (2 weeks: β = -0.005; 95% CI = -0.049, 0.039; 6 months: β = -0.019; 95% CI = -0.079, 0.042). Functional outcome, determined by 6 months incomplete recovery (Glasgow Outcome Scale-Extended [GOS-E < 8]) versus complete recovery (GOS-E = 8), was significantly associated with a higher number of EPVs at 2 weeks (odds ratio = 0.94, 95% CI = 0.88-0.99). Spearman correlations showed no significant relationship between EPVs count and GFAP or NfL. This study used commonly acquired MRI sequences to quantify EPVs and investigated their utility as a potential imaging biomarker in TBI. Given the minimal change in EPVs over time, this period may not be long enough for potential recovery or may indicate that EPVs are structural findings that do not significantly change over time.
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Affiliation(s)
- Alexa E. Walter
- Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Krupa Savalia
- Departments of Neurology and Neurological Surgery, University of California Davis, Davis, California, USA
| | - Jason Yoon
- Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Justin Morrison
- Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Andrea L. C. Schneider
- Departments of Neurology and Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Ramon Diaz-Arrastia
- Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Danielle K. Sandsmark
- Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
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Rahmani F, Batson RD, Zimmerman A, Reddigari S, Bigler ED, Lanning SC, Ilasa E, Grafman JH, Lu H, Lin AP, Raji CA. Rate of abnormalities in quantitative MR neuroimaging of persons with chronic traumatic brain injury. BMC Neurol 2024; 24:235. [PMID: 38969967 PMCID: PMC11225195 DOI: 10.1186/s12883-024-03745-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Accepted: 06/26/2024] [Indexed: 07/07/2024] Open
Abstract
BACKGROUND Mild traumatic brain injury (mTBI) can result in lasting brain damage that is often too subtle to detect by qualitative visual inspection on conventional MR imaging. Although a number of FDA-cleared MR neuroimaging tools have demonstrated changes associated with mTBI, they are still under-utilized in clinical practice. METHODS We investigated a group of 65 individuals with predominantly mTBI (60 mTBI, 48 due to motor-vehicle collision, mean age 47 ± 13 years, 27 men and 38 women) with MR neuroimaging performed in a median of 37 months post-injury. We evaluated abnormalities in brain volumetry including analysis of left-right asymmetry by quantitative volumetric analysis, cerebral perfusion by pseudo-continuous arterial spin labeling (PCASL), white matter microstructure by diffusion tensor imaging (DTI), and neurometabolites via magnetic resonance spectroscopy (MRS). RESULTS All participants demonstrated atrophy in at least one lobar structure or increased lateral ventricular volume. The globus pallidi and cerebellar grey matter were most likely to demonstrate atrophy and asymmetry. Perfusion imaging revealed significant reductions of cerebral blood flow in both occipital and right frontoparietal regions. Diffusion abnormalities were relatively less common though a subset analysis of participants with higher resolution DTI demonstrated additional abnormalities. All participants showed abnormal levels on at least one brain metabolite, most commonly in choline and N-acetylaspartate. CONCLUSION We demonstrate the presence of coup-contrecoup perfusion injury patterns, widespread atrophy, regional brain volume asymmetry, and metabolic aberrations as sensitive markers of chronic mTBI sequelae. Our findings expand the historic focus on quantitative imaging of mTBI with DTI by highlighting the complementary importance of volumetry, arterial spin labeling perfusion and magnetic resonance spectroscopy neurometabolite analyses in the evaluation of chronic mTBI.
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Affiliation(s)
- Farzaneh Rahmani
- Department of Radiology, Washington University School of Medicine, Saint Louis, MO, USA
| | - Richard D Batson
- Endocrine & Brain Injury Research Alliance, Neurevolution Medicine, PLLC, NUNM Helfgott Research Institute, Portland, Oregon, USA
| | | | | | - Erin D Bigler
- Department of Neurology, Department of Psychiatry, University of Utah, Salt Lake City, UT, USA
| | | | | | - Jordan H Grafman
- Departments of Physical Medicine & Rehabilitation, Neurology, Cognitive Neurology and Alzheimer's Center, Department of Psychiatry, Feinberg School of Medicine, Department of Psychology, Weinberg College of Arts and Sciences, Northwestern University, Chicago, IL, USA
| | - Hanzhang Lu
- Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Alexander P Lin
- Center for Clinical Spectroscopy, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Cyrus A Raji
- Department of Radiology, Washington University School of Medicine, Saint Louis, MO, USA.
- Department of Neurology, Washington University School of Medicine, Saint Louis, MO, USA.
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Chung S, Bacon T, Rath JF, Alivar A, Coelho S, Amorapanth P, Fieremans E, Novikov DS, Flanagan SR, Bacon JH, Lui YW. Callosal Interhemispheric Communication in Mild Traumatic Brain Injury: A Mediation Analysis on WM Microstructure Effects. AJNR Am J Neuroradiol 2024; 45:788-794. [PMID: 38637026 PMCID: PMC11288603 DOI: 10.3174/ajnr.a8213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2023] [Accepted: 01/27/2024] [Indexed: 04/20/2024]
Abstract
BACKGROUND AND PURPOSE Because the corpus callosum connects the left and right hemispheres and a variety of WM bundles across the brain in complex ways, damage to the neighboring WM microstructure may specifically disrupt interhemispheric communication through the corpus callosum following mild traumatic brain injury. Here we use a mediation framework to investigate how callosal interhemispheric communication is affected by WM microstructure in mild traumatic brain injury. MATERIALS AND METHODS Multishell diffusion MR imaging was performed on 23 patients with mild traumatic brain injury within 1 month of injury and 17 healthy controls, deriving 11 diffusion metrics, including DTI, diffusional kurtosis imaging, and compartment-specific standard model parameters. Interhemispheric processing speed was assessed using the interhemispheric speed of processing task (IHSPT) by measuring the latency between word presentation to the 2 hemivisual fields and oral word articulation. Mediation analysis was performed to assess the indirect effect of neighboring WM microstructures on the relationship between the corpus callosum and IHSPT performance. In addition, we conducted a univariate correlation analysis to investigate the direct association between callosal microstructures and IHSPT performance as well as a multivariate regression analysis to jointly evaluate both callosal and neighboring WM microstructures in association with IHSPT scores for each group. RESULTS Several significant mediators in the relationships between callosal microstructure and IHSPT performance were found in healthy controls. However, patients with mild traumatic brain injury appeared to lose such normal associations when microstructural changes occurred compared with healthy controls. CONCLUSIONS This study investigates the effects of neighboring WM microstructure on callosal interhemispheric communication in healthy controls and patients with mild traumatic brain injury, highlighting that neighboring noncallosal WM microstructures are involved in callosal interhemispheric communication and information transfer. Further longitudinal studies may provide insight into the temporal dynamics of interhemispheric recovery following mild traumatic brain injury.
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Affiliation(s)
- Sohae Chung
- From the Department of Radiology (S. Chung, A.A., S. Coelho, E.F., D.S.N., Y.W.L.), Center for Advanced Imaging Innovation and Research, NY University Grossman School of Medicine, New York, New York
- Department of Radiology (S. Chung, A.A., S. Coehlo, E.F., D.S.N., Y.W.L.), Bernard and Irene Schwartz Center for Biomedical Imaging, NY University Grossman School of Medicine, New York, New York
| | - Tamar Bacon
- Department of Neurology (T.B., J.H.B.), NY University Grossman School of Medicine, New York, New York
| | - Joseph F Rath
- Department of Rehabilitation Medicine (J.F.R., P.A., S.R.F.), New York University Grossman School of Medicine, New York, New York
| | - Alaleh Alivar
- From the Department of Radiology (S. Chung, A.A., S. Coelho, E.F., D.S.N., Y.W.L.), Center for Advanced Imaging Innovation and Research, NY University Grossman School of Medicine, New York, New York
- Department of Radiology (S. Chung, A.A., S. Coehlo, E.F., D.S.N., Y.W.L.), Bernard and Irene Schwartz Center for Biomedical Imaging, NY University Grossman School of Medicine, New York, New York
| | - Santiago Coelho
- From the Department of Radiology (S. Chung, A.A., S. Coelho, E.F., D.S.N., Y.W.L.), Center for Advanced Imaging Innovation and Research, NY University Grossman School of Medicine, New York, New York
- Department of Radiology (S. Chung, A.A., S. Coehlo, E.F., D.S.N., Y.W.L.), Bernard and Irene Schwartz Center for Biomedical Imaging, NY University Grossman School of Medicine, New York, New York
| | - Prin Amorapanth
- Department of Rehabilitation Medicine (J.F.R., P.A., S.R.F.), New York University Grossman School of Medicine, New York, New York
| | - Els Fieremans
- From the Department of Radiology (S. Chung, A.A., S. Coelho, E.F., D.S.N., Y.W.L.), Center for Advanced Imaging Innovation and Research, NY University Grossman School of Medicine, New York, New York
- Department of Radiology (S. Chung, A.A., S. Coehlo, E.F., D.S.N., Y.W.L.), Bernard and Irene Schwartz Center for Biomedical Imaging, NY University Grossman School of Medicine, New York, New York
| | - Dmitry S Novikov
- From the Department of Radiology (S. Chung, A.A., S. Coelho, E.F., D.S.N., Y.W.L.), Center for Advanced Imaging Innovation and Research, NY University Grossman School of Medicine, New York, New York
- Department of Radiology (S. Chung, A.A., S. Coehlo, E.F., D.S.N., Y.W.L.), Bernard and Irene Schwartz Center for Biomedical Imaging, NY University Grossman School of Medicine, New York, New York
| | - Steven R Flanagan
- Department of Rehabilitation Medicine (J.F.R., P.A., S.R.F.), New York University Grossman School of Medicine, New York, New York
| | - Joshua H Bacon
- Department of Neurology (T.B., J.H.B.), NY University Grossman School of Medicine, New York, New York
| | - Yvonne W Lui
- From the Department of Radiology (S. Chung, A.A., S. Coelho, E.F., D.S.N., Y.W.L.), Center for Advanced Imaging Innovation and Research, NY University Grossman School of Medicine, New York, New York
- Department of Radiology (S. Chung, A.A., S. Coehlo, E.F., D.S.N., Y.W.L.), Bernard and Irene Schwartz Center for Biomedical Imaging, NY University Grossman School of Medicine, New York, New York
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Gimbel SI, Hungerford LD, Twamley EW, Ettenhofer ML. White Matter Organization and Cortical Thickness Differ Among Active Duty Service Members With Chronic Mild, Moderate, and Severe Traumatic Brain Injury. J Neurotrauma 2024; 41:818-835. [PMID: 37800726 PMCID: PMC11005384 DOI: 10.1089/neu.2023.0336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/07/2023] Open
Abstract
Abstract This study compared findings from whole-brain diffusion tensor imaging (DTI) and volumetric magnetic resonance imaging (MRI) among 90 Active Duty Service Members with chronic mild traumatic brain injury (TBI; n = 52), chronic moderate-to-severe TBI (n = 17), and TBI-negative controls (n = 21). Data were collected on a Philips Ingenia 3T MRI with DTI in 32 directions. Results demonstrated that history of TBI was associated with differences in white matter microstructure, white matter volume, and cortical thickness in both mild TBI and moderate-to-severe TBI groups relative to controls. However, the presence, pattern, and distribution of these findings varied substantially depending on the injury severity. Spatially-defined forms of DTI fractional anisotropy (FA) analyses identified altered white matter organization within the chronic moderate-to-severe TBI group, but they did not provide clear evidence of abnormalities within the chronic mild TBI group. In contrast, DTI FA "pothole" analyses identified widely distributed areas of decreased FA throughout the white matter in both the chronic mild TBI and chronic moderate-to-severe TBI groups. Additionally, decreased white matter volume was found in several brain regions for the chronic moderate-to-severe TBI group compared with the other groups. Greater number of DTI FA potholes and reduced cortical thickness were also related to greater severity of self-reported symptoms. In sum, this study expands upon a growing body of literature using advanced imaging techniques to identify potential effects of brain injury in military Service Members. These findings may differ from work in other TBI populations due to varying mechanisms and frequency of injury, as well as a potentially higher level of functioning in the current sample related to the ability to maintain continued Active Duty status after injury. In conclusion, this study provides DTI and volumetric MRI findings across the spectrum of TBI severity. These results provide support for the use of DTI and volumetric MRI to identify differences in white matter microstructure and volume related to TBI. In particular, DTI FA pothole analysis may provide greater sensitivity for detecting subtle forms of white matter injury than conventional DTI FA analyses.
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Affiliation(s)
- Sarah I. Gimbel
- Traumatic Brain Injury Center of Excellence, Silver Spring, Maryland, USA
- Naval Medical Center San Diego, San Diego, California, USA
- General Dynamics Information Technology, Falls Church, Virginia, USA
| | - Lars D. Hungerford
- Traumatic Brain Injury Center of Excellence, Silver Spring, Maryland, USA
- Naval Medical Center San Diego, San Diego, California, USA
- General Dynamics Information Technology, Falls Church, Virginia, USA
| | - Elizabeth W. Twamley
- University of California, San Diego, San Diego, California, USA
- Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, San Diego, California, USA
| | - Mark L. Ettenhofer
- Traumatic Brain Injury Center of Excellence, Silver Spring, Maryland, USA
- Naval Medical Center San Diego, San Diego, California, USA
- General Dynamics Information Technology, Falls Church, Virginia, USA
- University of California, San Diego, San Diego, California, USA
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Kim S, Ollinger J, Song C, Raiciulescu S, Seenivasan S, Wolfgang A, Kim H, Werner JK, Yeh PH. White Matter Alterations in Military Service Members With Remote Mild Traumatic Brain Injury. JAMA Netw Open 2024; 7:e248121. [PMID: 38635266 PMCID: PMC11161843 DOI: 10.1001/jamanetworkopen.2024.8121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Accepted: 02/25/2024] [Indexed: 04/19/2024] Open
Abstract
Importance Mild traumatic brain injury (mTBI) is the signature injury experienced by military service members and is associated with poor neuropsychiatric outcomes. Yet, there is a lack of reliable clinical tools for mTBI diagnosis and prognosis. Objective To examine the white matter microstructure and neuropsychiatric outcomes of service members with a remote history of mTBI (ie, mTBI that occurred over 2 years ago) using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI). Design, Setting, and Participants This case-control study examined 98 male service members enrolled in a study at the National Intrepid Center of Excellence. Eligible participants were active duty status or able to enroll in the Defense Enrollment Eligibility Reporting system, ages 18 to 60 years, and had a remote history of mTBI; controls were matched by age. Exposures Remote history of mTBI. Main Outcomes and Measures White matter microstructure was assessed using a region-of-interest approach of skeletonized diffusion images, including DTI (fractional anisotropy, mean diffusivity, radial diffusivity and axial diffusivity) and NODDI (orientation dispersion index [ODI], isotropic volume fraction, intra-cellular volume fraction). Neuropsychiatric outcomes associated with posttraumatic stress disorder (PTSD) and postconcussion syndrome were assessed. Results A total of 65 male patients with a remote history of mTBI (mean [SD] age, 40.5 [5.0] years) and 33 age-matched male controls (mean [SD] age, 38.9 [5.6] years) were included in analysis. Compared with the control cohort, the 65 service members with mTBI presented with significantly more severe PTSD-like symptoms (mean [SD] PTSD CheckList-Civilian [PCL-C] version scores: control, 19.0 [3.8] vs mTBI, 41.2 [11.6]; P < .001). DTI and NODDI metrics were altered in the mTBI group compared with the control, including intra-cellular volume fraction of the right cortico-spinal tract (β = -0.029, Cohen d = 0.66; P < .001), ODI of the left posterior thalamic radiation (β = -0.006, Cohen d = 0.55; P < .001), and ODI of the left uncinate fasciculus (β = 0.013, Cohen d = 0.61; P < .001). In service members with mTBI, fractional anisotropy of the left uncinate fasciculus was associated with postconcussion syndrome (β = 5.4 × 10-3; P = .003), isotropic volume fraction of the genu of the corpus callosum with PCL-C (β = 4.3 × 10-4; P = .01), and ODI of the left fornix and stria terminalis with PCL-C avoidance scores (β = 1.2 × 10-3; P = .02). Conclusions and Relevance In this case-control study of military-related mTBI, the results suggest that advanced magnetic resonance imaging techniques using NODDI can reveal white matter microstructural alterations associated with neuropsychiatric symptoms in the chronic phase of mTBI. Diffusion trends observed throughout widespread white matter regions-of-interest may reflect mechanisms of neurodegeneration as well as postinjury tissue scarring and reorganization.
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Affiliation(s)
- Sharon Kim
- Program in Neuroscience, Uniformed Services University of Health Sciences, Bethesda, Maryland
- School of Medicine, Uniformed Services University of Health Sciences, Bethesda, Maryland
| | - John Ollinger
- National Intrepid Center of Excellence, Walter Reed National Military Medical Center, Bethesda, Maryland
| | - Chihwa Song
- National Intrepid Center of Excellence, Walter Reed National Military Medical Center, Bethesda, Maryland
| | - Sorana Raiciulescu
- Department of Preventive Medicine and Biostatistics, Uniformed Services University of Health Sciences, Bethesda, Maryland
| | - Srija Seenivasan
- Program in Neuroscience, Uniformed Services University of Health Sciences, Bethesda, Maryland
- School of Medicine, Uniformed Services University of Health Sciences, Bethesda, Maryland
| | - Aaron Wolfgang
- School of Medicine, Uniformed Services University of Health Sciences, Bethesda, Maryland
- Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
- Directorate of Behavioral Health, Walter Reed National Military Medical Center, Bethesda, Maryland
| | - Hosung Kim
- USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles
| | - J. Kent Werner
- School of Medicine, Uniformed Services University of Health Sciences, Bethesda, Maryland
- Department of Neurology, Walter Reed National Military Medical Center, Bethesda, Maryland
| | - Ping-Hong Yeh
- National Intrepid Center of Excellence, Walter Reed National Military Medical Center, Bethesda, Maryland
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9
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Jacquens A, Delmotte PR, Gourbeix C, Farny N, Perret-Liaudet B, Hijazi D, Batisti V, Torkomian G, Cassereau D, Debarle C, Shotar E, Gellman C, Mathon B, Bayen E, Galanaud D, Perlbarg V, Puybasset L, Degos V. MRI volumetry and diffusion tensor imaging for diagnosis and follow-up of late post-traumatic injuries. Ann Phys Rehabil Med 2024; 67:101783. [PMID: 38147704 DOI: 10.1016/j.rehab.2023.101783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 05/02/2023] [Accepted: 05/29/2023] [Indexed: 12/28/2023]
Abstract
BACKGROUND Traumatic Brain Injury (TBI) is a major cause of acquired disability and can cause devastating and progressive post-traumatic encephalopathy. TBI is a dynamic condition that continues to evolve over time. A better understanding of the pathophysiology of these late lesions is important for the development of new therapeutic strategies. OBJECTIVES The primary objective was to compare the ability of fluid-attenuated reversion recovery (FLAIR) and diffusion tensor imaging (DTI) magnetic resonance imaging (MRI) markers to identify participants with a Glasgow outcome scale extended (GOS-E) score of 7-8, up to 10 years after their original TBI. The secondary objective was to study the brain regionalization of DTI markers. Finally, we analyzed the evolution of late-developing brain lesions using repeated MRI images, also taken up to 10 years after the TBI. METHODS In this retrospective study, participants were included from a cohort of people hospitalized following a severe TBI. Following their discharge, they were followed-up and clinically assessed, including a DTI-MRI scan, between 2012 and 2016. We performed a cross-sectional analysis on 97 participants at a median (IQR) of 5 years (3-6) post-TBI, and a further post-TBI longitudinal analysis over 10 years on a subpopulation (n = 17) of the cohort. RESULTS Although the area under the curve (AUC) of FLAIR, fractional anisotropy (FA), and mean diffusivity (MD) were not significantly different, only the AUC of FA was statistically greater than 0.5. In addition, only the FA was correlated with clinical outcomes as assessed by GOS-E score (P<10-4). On the cross-sectional analysis, DTI markers allowed study post-TBI white matter lesions by region. In the longitudinal subpopulation analysis, the observed number of brain lesions increased for the first 5 years post-TBI, before stabilizing over the next 5 years. CONCLUSIONS This study has shown for the first time that post-TBI lesions can present in a two-phase evolution. These results must be confirmed in larger studies. French Data Protection Agency (Commission nationale de l'informatique et des libertés; CNIL) study registration no: 1934708v0.
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Affiliation(s)
- Alice Jacquens
- Sorbonne University, GRC 29, AP-HP, DMU DREAM, Department of Anaesthesiology and Critical Care Medicine, AP-HP, Pitié-Salpêtrière Hospital, 47-83, boulevard de l'Hôpital, 75013, Paris, France.
| | - Pierre-Romain Delmotte
- Sorbonne University, GRC 29, AP-HP, DMU DREAM, Department of Anaesthesiology and Critical Care Medicine, AP-HP, Pitié-Salpêtrière Hospital, 47-83, boulevard de l'Hôpital, 75013, Paris, France
| | - Claire Gourbeix
- Sorbonne University, GRC 29, AP-HP, DMU DREAM, Department of Anaesthesiology and Critical Care Medicine, AP-HP, Pitié-Salpêtrière Hospital, 47-83, boulevard de l'Hôpital, 75013, Paris, France
| | - Nicolas Farny
- Sorbonne University, GRC 29, AP-HP, DMU DREAM, Department of Anaesthesiology and Critical Care Medicine, AP-HP, Pitié-Salpêtrière Hospital, 47-83, boulevard de l'Hôpital, 75013, Paris, France
| | - Bérenger Perret-Liaudet
- Sorbonne University, GRC 29, AP-HP, DMU DREAM, Department of Anaesthesiology and Critical Care Medicine, AP-HP, Pitié-Salpêtrière Hospital, 47-83, boulevard de l'Hôpital, 75013, Paris, France
| | - Dany Hijazi
- Sorbonne University, GRC 29, AP-HP, DMU DREAM, Department of Anaesthesiology and Critical Care Medicine, AP-HP, Pitié-Salpêtrière Hospital, 47-83, boulevard de l'Hôpital, 75013, Paris, France
| | - Valentine Batisti
- Sorbonne University, GRC 29, AP-HP, DMU DREAM, Department of Anaesthesiology and Critical Care Medicine, AP-HP, Pitié-Salpêtrière Hospital, 47-83, boulevard de l'Hôpital, 75013, Paris, France
| | - Grégory Torkomian
- Sorbonne University, GRC 29, AP-HP, DMU DREAM, Department of Anaesthesiology and Critical Care Medicine, AP-HP, Pitié-Salpêtrière Hospital, 47-83, boulevard de l'Hôpital, 75013, Paris, France
| | - Didier Cassereau
- Laboratoire d'Imagerie Biomédicale, Sorbonne Université, 15 rue de l'Ecole de Médecine, 75006, Paris, France; ESPCI, 10 rue Vauquelin, 75005, Paris, France
| | - Clara Debarle
- Physical Medicine and Rehabilitation Department, Centre Hospitalier Saint-Anne, 1 rue Cabanis, GHU Paris psychiatrie et neurosciences, 75014, Paris, France
| | - Eimad Shotar
- Department of Interventional Neuroradiology, Pitié-Salpêtrière Hospital, Paris, France
| | - Celia Gellman
- Icahn School of Medicine at Mount Sinai, NYC Health + Hospitals/Elmhurst, Internal Medicine Residency Program, United States
| | - Bertrand Mathon
- Department of Neurosurgery, APHP - Sorbonne University, La Pitié-Salpêtrière Hospital, 47-83, Boulevard de L'Hôpital, 75651 Cedex 13, Paris, France
| | - Eleonor Bayen
- UGECAM-IdF, groupe hospitalier Pitié-Salpêtrière, service de médecine physique et de réadaptation, Paris France
| | - Damien Galanaud
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service de Neuroradiologie, 75013, Paris, France
| | | | - Louis Puybasset
- Sorbonne University, GRC 29, AP-HP, DMU DREAM, Department of Anaesthesiology and Critical Care Medicine, AP-HP, Pitié-Salpêtrière Hospital, 47-83, boulevard de l'Hôpital, 75013, Paris, France; BRAINTALE SAS, Paris, France
| | - Vincent Degos
- Sorbonne University, GRC 29, AP-HP, DMU DREAM, Department of Anaesthesiology and Critical Care Medicine, AP-HP, Pitié-Salpêtrière Hospital, 47-83, boulevard de l'Hôpital, 75013, Paris, France
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10
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Vinh To X, Kurniawan ND, Cumming P, Nasrallah FA. A cross-comparative analysis of in vivo versus ex vivo MRI indices in a mouse model of concussion. Brain Res 2023; 1820:148562. [PMID: 37673379 DOI: 10.1016/j.brainres.2023.148562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 08/01/2023] [Accepted: 08/31/2023] [Indexed: 09/08/2023]
Abstract
BACKGROUND We present a cross-sectional, case-matched, and pair-wise comparison of structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and neurite orientation dispersion and density imaging (NODDI) measures in vivo and ex vivo in a mouse model of concussion, thus aiming to establish the concordance of structural and diffusion imaging findings in living brain and after fixation. METHODS We allocated 28 male mice aged 3-4 months to sham injury and concussion (CON) groups. CON mice had received a single concussive impact on day 0 and underwent MRI at day 2 (n = 9) or 7 (n = 10) post-impact, and sham control mice likewise underwent imaging at day 2 (n = 5) or 7 (n = 4). Immediately after the final scanning, we collected the perfusion-fixed brains, which were stored for imaging ex vivo 6-12 months later. We then compared the structural imaging, DTI, and NODDI results between different methods. RESULTS In vivo to ex vivo structural and DTI/NODDI findings were in notably poor agreement regarding the effects of concussion on structural integrity of the brain. COMPARISON WITH EXISTING METHODS ex vivo imaging was frequently done to study the effects of diseases and treatments, but our results showed that ex vivo and in vivo imaging can detect completely opposite and contradictory results. This is also the first study that compares in vivo and ex vivo NODDI. CONCLUSION Our findings call for caution in extrapolating translational capabilities obtained ex vivo to physiological measurements in vivo. The divergent findings may reflect fixation artefacts and the contribution of the glymphatic system changes.
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Affiliation(s)
- Xuan Vinh To
- The Queensland Brain Institute, The University of Queensland, Australia
| | | | - Paul Cumming
- Department of Nuclear Medicine, Bern University Hospital, Bern, Switzerland; School of Psychology and Counselling, Queensland University of Technology, Brisbane, Australia
| | - Fatima A Nasrallah
- The Queensland Brain Institute, The University of Queensland, Australia; Centre for Advanced Imaging, The University of Queensland, Australia.
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11
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Asturias A, Knoblauch T, Rodriguez A, Vanier C, Le Tohic C, Barrett B, Eisenberg M, Gibbert R, Zimmerman L, Parikh S, Nguyen A, Azad S, Germin L, Fazzini E, Snyder T. Diffusion in the corpus callosum predicts persistence of clinical symptoms after mild traumatic brain injury, a multi-scanner study. FRONTIERS IN NEUROIMAGING 2023; 2:1153115. [PMID: 38025312 PMCID: PMC10654678 DOI: 10.3389/fnimg.2023.1153115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Accepted: 08/23/2023] [Indexed: 12/01/2023]
Abstract
Background Mild traumatic brain injuries (mTBIs) comprise 80% of all TBI, but conventional MRI techniques are often insensitive to the subtle changes and injuries produced in a concussion. Diffusion tensor imaging (DTI) is one of the most sensitive MRI techniques for mTBI studies with outcome and symptom associations described. The corpus callosum (CC) is one of the most studied fiber tracts in TBI and mTBI, but the comprehensive post-mTBI symptom relationship has not fully been explored. Methods This is a retrospective observational study of how quantitative DTI data of the CC and its sub-regions may relate to clinical presentation of symptoms and timing of resolution of symptoms in patients diagnosed with uncomplicated mTBI. DTI and clinical data were obtained retrospectively from 446 (mean age 42 years, range 13-82) civilian patients. From patient medical charts, presentation of the following common post-concussive symptoms was noted: headache, balance issues, cognitive deficits, fatigue, anxiety, depression, and emotional lability. Also recorded was the time between injury and a visit to the physician when improvement or resolution of a particular symptom was reported. FA values from the total CC and 3 subregions of the CC (genu or anterior, mid body, and splenium or posterior) were obtained from hand tracing on the Olea Sphere v3.0 SP12 free-standing workstation. DTI data was obtained from 8 different 3T MRI scanners and harmonized via ComBat harmonization. The statistical models used to explore the association between regional Fractional Anisotropy (FA) values and symptom presentation and time to symptom resolution were logistic regression and interval-censored semi-parametric Cox proportional hazard models, respectively. Subgroups related to age and timing of first scan were also analyzed. Results Patients with the highest FA in the total CC (p = 0.01), anterior CC (p < 0.01), and mid-body CC (p = 0.03), but not the posterior CC (p = 0.91) recovered faster from post-concussive cognitive deficits. Patients with the highest FA in the posterior CC recovered faster from depression (p = 0.04) and emotional lability (p = 0.01). There was no evidence that FA in the CC or any of its sub-regions was associated with symptom presentation or with time to resolution of headache, balance issues, fatigue, or anxiety. Patients with mTBI under 40 had higher FA in the CC and the anterior and mid-body subregions (but not the posterior subregion: p = 1.00) compared to patients 40 or over (p ≤ 0.01). There was no evidence for differences in symptom presentation based on loss of consciousness (LOC) or sex (p ≥ 0.18). Conclusion This study suggests that FA of the CC has diagnostic and prognostic value for clinical assessment of mTBI in a large diverse civilian population, particularly in patients with cognitive symptoms.
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Affiliation(s)
- Alexander Asturias
- Imgen Research Group, Las Vegas, NV, United States
- Touro University Nevada, Henderson, NV, United States
| | - Thomas Knoblauch
- Imgen Research Group, Las Vegas, NV, United States
- Touro University Nevada, Henderson, NV, United States
- School of Integrated Health Sciences, University of Nevada Las Vegas, Las Vegas, NV, United States
| | - Alan Rodriguez
- Imgen Research Group, Las Vegas, NV, United States
- Touro University Nevada, Henderson, NV, United States
| | - Cheryl Vanier
- Imgen Research Group, Las Vegas, NV, United States
- Touro University Nevada, Henderson, NV, United States
| | - Caroline Le Tohic
- Kirk Kerkorian School of Medicine at UNLV, Las Vegas, NV, United States
| | - Brandon Barrett
- Kirk Kerkorian School of Medicine at UNLV, Las Vegas, NV, United States
| | - Matthew Eisenberg
- Kirk Kerkorian School of Medicine at UNLV, Las Vegas, NV, United States
| | | | - Lennon Zimmerman
- Kirk Kerkorian School of Medicine at UNLV, Las Vegas, NV, United States
| | | | - Anh Nguyen
- Touro University Nevada, Henderson, NV, United States
| | - Sherwin Azad
- MountainView Hospital, HCA Healthcare, Las Vegas, NV, United States
| | - Leo Germin
- Clinical Neurology Specialists, Las Vegas, NV, United States
| | | | - Travis Snyder
- Imgen Research Group, Las Vegas, NV, United States
- Touro University Nevada, Henderson, NV, United States
- MountainView Hospital, HCA Healthcare, Las Vegas, NV, United States
- SimonMed Imaging, Scottsdale, AZ, United States
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12
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Anderson JFI, Oehr LE, Chen J, Maller JJ, Seal ML, Yang JYM. The relationship between cognition and white matter tract damage after mild traumatic brain injury in a premorbidly healthy, hospitalised adult cohort during the post-acute period. Front Neurol 2023; 14:1278908. [PMID: 37936919 PMCID: PMC10626495 DOI: 10.3389/fneur.2023.1278908] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Accepted: 09/21/2023] [Indexed: 11/09/2023] Open
Abstract
Introduction Recent developments in neuroimaging techniques enable increasingly sensitive consideration of the cognitive impact of damage to white matter tract (WMT) microstructural organisation after mild traumatic brain injury (mTBI). Objective This study investigated the relationship between WMT microstructural properties and cognitive performance. Participants setting and design Using an observational design, a group of 26 premorbidly healthy adults with mTBI and a group of 20 premorbidly healthy trauma control (TC) participants who were well-matched on age, sex, premorbid functioning and a range of physical, psychological and trauma-related variables, were recruited following hospital admission for traumatic injury. Main measures All participants underwent comprehensive unblinded neuropsychological examination and structural neuroimaging as outpatients 6-10 weeks after injury. Neuropsychological examination included measures of speed of processing, attention, memory, executive function, affective state, pain, fatigue and self-reported outcome. The WMT microstructural properties were estimated using both diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) modelling techniques. Tract properties were compared between the corpus callosum, inferior longitudinal fasciculus, uncinate fasciculus, anterior corona radiata and three segmented sections of the superior longitudinal fasciculus. Results For the TC group, in all investigated tracts, with the exception of the uncinate fasciculus, two DTI metrics (fractional anisotropy and apparent diffusion coefficient) and one NODDI metric (intra-cellular volume fraction) revealed expected predictive linear relationships between extent of WMT microstructural organisation and processing speed, memory and executive function. The mTBI group showed a strikingly different pattern relative to the TC group, with no relationships evident between WMT microstructural organisation and cognition on most tracts. Conclusion These findings indicate that the predictive relationship that normally exists in adults between WMT microstructural organisation and cognition, is significantly disrupted 6-10 weeks after mTBI and suggests that WMT microstructural organisation and cognitive function have disparate recovery trajectories.
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Affiliation(s)
- Jacqueline F. I. Anderson
- Melbourne School of Psychological Sciences, The University of Melbourne, Parkville, VIC, Australia
- Department of Psychology, The Alfred Hospital, Melbourne, VIC, Australia
| | - Lucy E. Oehr
- Melbourne School of Psychological Sciences, The University of Melbourne, Parkville, VIC, Australia
| | - Jian Chen
- Developmental Imaging, Murdoch Children's Research Institute, Melbourne, VIC, Australia
| | - Jerome J. Maller
- General Electric Healthcare, Melbourne, VIC, Australia
- Monash Alfred Psychiatry Research Centre, Melbourne, VIC, Australia
| | - Marc L. Seal
- Developmental Imaging, Murdoch Children's Research Institute, Melbourne, VIC, Australia
- Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia
| | - Joseph Yuan-Mou Yang
- Developmental Imaging, Murdoch Children's Research Institute, Melbourne, VIC, Australia
- Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia
- Neuroscience Research, Murdoch Children's Research Institute, Melbourne, VIC, Australia
- Department of Neurosurgery, Neuroscience Advanced Clinical Imaging Service (NACIS), The Royal Children's Hospital, Melbourne, VIC, Australia
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13
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Brennan DJ, Duda J, Ware JB, Whyte J, Choi JY, Gugger J, Focht K, Walter AE, Bushnik T, Gee JC, Diaz‐Arrastia R, Kim JJ. Spatiotemporal profile of atrophy in the first year following moderate-severe traumatic brain injury. Hum Brain Mapp 2023; 44:4692-4709. [PMID: 37399336 PMCID: PMC10400790 DOI: 10.1002/hbm.26410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 06/04/2023] [Accepted: 06/12/2023] [Indexed: 07/05/2023] Open
Abstract
Traumatic brain injury (TBI) triggers progressive neurodegeneration resulting in brain atrophy that continues months-to-years following injury. However, a comprehensive characterization of the spatial and temporal evolution of TBI-related brain atrophy remains incomplete. Utilizing a sensitive and unbiased morphometry analysis pipeline optimized for detecting longitudinal changes, we analyzed a sample consisting of 37 individuals with moderate-severe TBI who had primarily high-velocity and high-impact injury mechanisms. They were scanned up to three times during the first year after injury (3 months, 6 months, and 12 months post-injury) and compared with 33 demographically matched controls who were scanned once. Individuals with TBI already showed cortical thinning in frontal and temporal regions and reduced volume in the bilateral thalami at 3 months post-injury. Longitudinally, only a subset of cortical regions in the parietal and occipital lobes showed continued atrophy from 3 to 12 months post-injury. Additionally, cortical white matter volume and nearly all deep gray matter structures exhibited progressive atrophy over this period. Finally, we found that disproportionate atrophy of cortex along sulci relative to gyri, an emerging morphometric marker of chronic TBI, was present as early as 3 month post-injury. In parallel, neurocognitive functioning largely recovered during this period despite this pervasive atrophy. Our findings demonstrate msTBI results in characteristic progressive neurodegeneration patterns that are divergent across regions and scale with the severity of injury. Future clinical research using atrophy during the first year of TBI as a biomarker of neurodegeneration should consider the spatiotemporal profile of atrophy described in this study.
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Affiliation(s)
- Daniel J. Brennan
- CUNY Neuroscience Collaborative, The Graduate CenterCity University of New YorkNew YorkNew YorkUnited States
- Department of Molecular, Cellular, and Biomedical SciencesCUNY School of Medicine, The City College of New YorkNew YorkNew YorkUnited States
| | - Jeffrey Duda
- Department of RadiologyUniversity of Pennsylvania Perelman School of MedicinePhiladelphiaPennsylvaniaUnited States
- Penn Image Computing and Science LaboratoryUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUnited States
| | - Jeffrey B. Ware
- Department of RadiologyUniversity of Pennsylvania Perelman School of MedicinePhiladelphiaPennsylvaniaUnited States
| | - John Whyte
- Moss Rehabilitation Research Institute, Einstein Healthcare NetworkElkins ParkPennsylvaniaUnited States
| | - Joon Yul Choi
- Department of Molecular, Cellular, and Biomedical SciencesCUNY School of Medicine, The City College of New YorkNew YorkNew YorkUnited States
- Department of Biomedical EngineeringYonsei UniversityWonjuRepublic of Korea
| | - James Gugger
- Department of NeurologyUniversity of Pennsylvania Perelman School of MedicinePhiladelphiaPennsylvaniaUnited States
| | - Kristen Focht
- Widener University School for Graduate Clinical PsychologyChesterPennsylvaniaUnited States
| | - Alexa E. Walter
- Department of NeurologyUniversity of Pennsylvania Perelman School of MedicinePhiladelphiaPennsylvaniaUnited States
| | - Tamara Bushnik
- NYU Grossman School of MedicineNew YorkNew YorkUnited States
| | - James C. Gee
- Department of RadiologyUniversity of Pennsylvania Perelman School of MedicinePhiladelphiaPennsylvaniaUnited States
- Penn Image Computing and Science LaboratoryUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUnited States
| | - Ramon Diaz‐Arrastia
- Department of NeurologyUniversity of Pennsylvania Perelman School of MedicinePhiladelphiaPennsylvaniaUnited States
| | - Junghoon J. Kim
- CUNY Neuroscience Collaborative, The Graduate CenterCity University of New YorkNew YorkNew YorkUnited States
- Department of Molecular, Cellular, and Biomedical SciencesCUNY School of Medicine, The City College of New YorkNew YorkNew YorkUnited States
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14
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van Velkinburgh JC, Herbst MD, Casper SM. Diffusion tensor imaging in the courtroom: Distinction between scientific specificity and legally admissible evidence. World J Clin Cases 2023; 11:4477-4497. [PMID: 37469746 PMCID: PMC10353495 DOI: 10.12998/wjcc.v11.i19.4477] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 05/26/2023] [Accepted: 06/13/2023] [Indexed: 06/30/2023] Open
Abstract
Interest and uptake of science and medicine peer-reviewed literature by readers outside of a paper’s topical subject, field or even discipline is ever-expanding. While the application of knowledge from one field or discipline to others can stimulate innovative solutions to problems facing modern society, it is also fraught with danger for misuse. In the practice of law in the United States, academic papers are submitted to the courts as evidence in personal injury litigation from both the plaintiff (complainant) and defendant. Such transcendence of an academic publication over disciplinary boundaries is immediately met with the challenge of application by a group that inherently lacks in-depth knowledge on the scientific method, the practice of evidence-based medicine, or the publication process as a structured and internationally synthesized process involving peer review and guided by ethical standards and norms. A modern-day example of this is the ongoing conflict between the sensitivity of diffusion tensor imaging (DTI) and the legal standards for admissibility of evidence in litigation cases of mild traumatic brain injury (mTBI). In this review, we amalgamate the peer-reviewed research on DTI in mTBI with the court’s rationale underlying decisions to admit or exclude evidence of DTI abnormalities to support claims of brain injury. We found that the papers which are critical of the use of DTI in the courtroom reflect a primary misunderstanding about how diagnostic biomarkers differ legally from relevant and admissible evidence. The clinical use of DTI to identify white matter abnormalities in the brain at the chronic stage is a valid methodology both clinically as well as forensically, contributes data that may or may not corroborate the existence of white matter damage, and should be admitted into evidence in personal injury trials if supported by a clinician. We also delve into an aspect of science publication and peer review that can be manipulated by scientists and clinicians to publish an opinion piece and misrepresent it as an unbiased, evidence-based, systematic research article in court cases, the decisions of which establish precedence for future cases and have implications on future legislation that will impact the lives of every citizen and erode the integrity of science and medicine practitioners.
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Affiliation(s)
| | - Mark D Herbst
- Diagnostic Radiology, Independent Diagnostic Radiology Inc, St Petersburg, FL 33711, United States
| | - Stewart M Casper
- Personal Injury Law, Casper & DeToledo LLC, Stamford, CT 06905, United States
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15
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To XV, Vegh V, Owusu-Amoah N, Cumming P, Nasrallah FA. Hippocampal demyelination is associated with increased magnetic susceptibility in a mouse model of concussion. Exp Neurol 2023; 365:114406. [PMID: 37062352 DOI: 10.1016/j.expneurol.2023.114406] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 04/04/2023] [Accepted: 04/06/2023] [Indexed: 04/18/2023]
Abstract
Structural and functional deficits in the hippocampus are a prominent feature of moderate-severe traumatic brain injury (TBI). In this work, we investigated the potential of Quantitative Susceptibility Imaging (QSM) to reveal the temporal changes in myelin integrity in a mouse model of concussion (mild TBI). We employed a cross-sectional design wherein we assigned 43 mice to cohorts undergoing either a concussive impact or a sham procedure, with QSM imaging at day 2, 7, or 14 post-injury, followed by Luxol Fast Blue (LFB) myelin staining to assess the structural integrity of hippocampal white matter (WM). We assessed spatial learning in the mice using the Active Place Avoidance Test (APA), recording their ability to use visual cues to locate and avoid zone-dependent mild electrical shocks. QSM and LFB staining indicated changes in the stratum lacunosum-molecular layer of the hippocampus in the concussion groups, suggesting impairment of this key relay between the entorhinal cortex and the CA1 regions. These imaging and histology findings were consistent with demyelination, namely increased magnetic susceptibility to MR imaging and decreased LFB staining. In the APA test, sham animals showed fewer entries into the shock zone compared to the concussed cohort. Thus, we present radiological, histological, and behavioral findings that concussion can induce significant and alterations in hippocampal integrity and function that evolve over time after the injury.
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Affiliation(s)
- Xuan Vinh To
- The Queensland Brain Institute, The University of Queensland, Australia
| | - Viktor Vegh
- The Centre for Advanced Imaging, The University of Queensland, Australia; The ARC Centre for Innovation in Biomedical Imaging Technology, Brisbane, Australia
| | - Naana Owusu-Amoah
- The Queensland Brain Institute, The University of Queensland, Australia
| | - Paul Cumming
- Department of Nuclear Medicine, Bern University Hospital, Bern, Switzerland; School of Psychology and Counselling, Queensland University of Technology, Brisbane, Australia
| | - Fatima A Nasrallah
- The Queensland Brain Institute, The University of Queensland, Australia; The Centre for Advanced Imaging, The University of Queensland, Australia.
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16
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Lima Santos JP, Jia-Richards M, Kontos AP, Collins MW, Versace A. Emotional Regulation and Adolescent Concussion: Overview and Role of Neuroimaging. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:6274. [PMID: 37444121 PMCID: PMC10341732 DOI: 10.3390/ijerph20136274] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 06/16/2023] [Accepted: 06/29/2023] [Indexed: 07/15/2023]
Abstract
Emotional dysregulation symptoms following a concussion are associated with an increased risk for emotional dysregulation disorders (e.g., depression and anxiety), especially in adolescents. However, predicting the emergence or worsening of emotional dysregulation symptoms after concussion and the extent to which this predates the onset of subsequent psychiatric morbidity after injury remains challenging. Although advanced neuroimaging techniques, such as functional magnetic resonance imaging and diffusion magnetic resonance imaging, have been used to detect and monitor concussion-related brain abnormalities in research settings, their clinical utility remains limited. In this narrative review, we have performed a comprehensive search of the available literature regarding emotional regulation, adolescent concussion, and advanced neuroimaging techniques in electronic databases (PubMed, Scopus, and Google Scholar). We highlight clinical evidence showing the heightened susceptibility of adolescents to experiencing emotional dysregulation symptoms following a concussion. Furthermore, we describe and provide empirical support for widely used magnetic resonance imaging modalities (i.e., functional and diffusion imaging), which are utilized to detect abnormalities in circuits responsible for emotional regulation. Additionally, we assess how these abnormalities relate to the emotional dysregulation symptoms often reported by adolescents post-injury. Yet, it remains to be determined if a progression of concussion-related abnormalities exists, especially in brain regions that undergo significant developmental changes during adolescence. We conclude that neuroimaging techniques hold potential as clinically useful tools for predicting and, ultimately, monitoring the treatment response to emotional dysregulation in adolescents following a concussion.
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Affiliation(s)
- João Paulo Lima Santos
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; (M.J.-R.); (A.V.)
| | - Meilin Jia-Richards
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; (M.J.-R.); (A.V.)
| | - Anthony P. Kontos
- Department of Orthopaedic Surgery, UPMC Sports Concussion Program, University of Pittsburgh, Pittsburgh, PA 15213, USA; (A.P.K.); (M.W.C.)
| | - Michael W. Collins
- Department of Orthopaedic Surgery, UPMC Sports Concussion Program, University of Pittsburgh, Pittsburgh, PA 15213, USA; (A.P.K.); (M.W.C.)
| | - Amelia Versace
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; (M.J.-R.); (A.V.)
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17
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Grant M, Liu J, Wintermark M, Bagci U, Douglas D. Current State of Diffusion-Weighted Imaging and Diffusion Tensor Imaging for Traumatic Brain Injury Prognostication. Neuroimaging Clin N Am 2023; 33:279-297. [PMID: 36965946 DOI: 10.1016/j.nic.2023.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/27/2023]
Abstract
Advanced imaging techniques are needed to assist in providing a prognosis for patients with traumatic brain injury (TBI), particularly mild TBI (mTBI). Diffusion tensor imaging (DTI) is one promising advanced imaging technique, but has shown variable results in patients with TBI and is not without limitations, especially when considering individual patients. Efforts to resolve these limitations are being explored and include developing advanced diffusion techniques, creating a normative database, improving study design, and testing machine learning algorithms. This article will review the fundamentals of DTI, providing an overview of the current state of its utility in evaluating and providing prognosis in patients with TBI.
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Affiliation(s)
- Matthew Grant
- Department of Radiology, Stanford University, 453 Quarry Road, Palo Alto, CA 94304, USA; Department of Radiology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd, Bethesda, MD 20814, USA; Department of Radiology, Landstuhl Regional Medical Center, Dr Hitzelberger Straße, 66849 Landstuhl, Germany.
| | - JiaJing Liu
- Department of Radiology, Stanford University, 453 Quarry Road, Palo Alto, CA 94304, USA
| | - Max Wintermark
- Department of Radiology, Stanford University, 453 Quarry Road, Palo Alto, CA 94304, USA; Neuroradiology Department, The University of Texas Anderson Cancer Center, 1400 Pressler Street, Unit 1482, Houston, TX 77030, USA
| | - Ulas Bagci
- Radiology and Biomedical Engineering Department, Northwestern University, 737 North Michigan Drive, Suite 1600, Chicago, IL 60611, USA; Department of Computer Science, University of Central Florida, 4328 Scorpius Street, Orlando, Florida, 32816
| | - David Douglas
- Department of Radiology, Stanford University, 453 Quarry Road, Palo Alto, CA 94304, USA; Department of Radiology, 96th Medical Group, Eglin Air Force Base, 307 Boatner Road, Eglin Air Force Base, Florida 32542, USA
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18
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Christensen BA, Clark B, Muir AM, Allen WD, Corbin EM, Jaggi T, Alder N, Clawson A, Farrer TJ, Bigler ED, Larson MJ. Interhemispheric transfer time and concussion in adolescents: A longitudinal study using response time and event-related potential measures. Front Hum Neurosci 2023; 17:1161156. [PMID: 37056961 PMCID: PMC10086259 DOI: 10.3389/fnhum.2023.1161156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Accepted: 03/07/2023] [Indexed: 03/30/2023] Open
Abstract
IntroductionConcussion in children and adolescents is a public health concern with higher concussion incidence than adults and increased susceptibility to axonal injury. The corpus callosum is a vulnerable location of concussion-related white matter damage that can be associated with short- and long-term effects of concussion. Interhemispheric transfer time (IHTT) of visual information across the corpus callosum can be used as a direct measure of corpus callosum functioning that may be impacted by adolescent concussion with slower IHTT relative to matched controls. Longitudinal studies and studies testing physiological measures of IHTT following concussion in adolescents are lacking.MethodsWe used the N1 and P1 components of the scalp-recorded brain event-related potential (ERP) to measure IHTT in 20 adolescents (ages 12–19 years old) with confirmed concussion and 16 neurologically-healthy control participants within 3 weeks of concussion (subacute stage) and approximately 10 months after injury (longitudinal).ResultsSeparate two-group (concussion, control) by two-time (3 weeks, 10 months) repeated measures ANOVAs on difference response times and IHTT latencies of the P1 and N1 components showed no significant differences by group (ps ≥ 0.25) nor by time (ps ≥ 0.64), with no significant interactions (ps ≥ 0.15).DiscussionResults from the current sample suggest that measures of IHTT may not be strongly influenced at 3 weeks or longitudinally following adolescent concussion using the current IHTT paradigm.
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Affiliation(s)
- Benjamin A. Christensen
- Neuroscience Center, Brigham Young University, Provo, UT, United States
- Department of Psychology, Brigham Young University, Provo, UT, United States
| | - Bradley Clark
- Neuroscience Center, Brigham Young University, Provo, UT, United States
| | - Alexandra M. Muir
- Department of Psychology, Brigham Young University, Provo, UT, United States
| | - Whitney D. Allen
- Department of Psychology, Brigham Young University, Provo, UT, United States
| | - Erin M. Corbin
- Neuroscience Center, Brigham Young University, Provo, UT, United States
| | - Tyshae Jaggi
- Pacific Northwest University of Health Sciences, Yakima, WA, United States
| | - Nathan Alder
- University of Utah School of Medicine, Salt Lake City, UT, United States
| | - Ann Clawson
- Children’s National Hospital, Washington, DC, United States
| | - Thomas J. Farrer
- Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, United States
| | - Erin D. Bigler
- Neuroscience Center, Brigham Young University, Provo, UT, United States
- Department of Psychology, Brigham Young University, Provo, UT, United States
- Departments of Psychiatry and Neurology, University of Utah, Salt Lake City, UT, United States
| | - Michael J. Larson
- Neuroscience Center, Brigham Young University, Provo, UT, United States
- Department of Psychology, Brigham Young University, Provo, UT, United States
- *Correspondence: Michael J. Larson,
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19
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Moro F, Lisi I, Tolomeo D, Vegliante G, Pascente R, Mazzone E, Hussain R, Micotti E, Dallmeier J, Pischiutta F, Bianchi E, Chiesa R, Wang KK, Zanier ER. Acute Blood Levels of Neurofilament Light Indicate One-Year White Matter Pathology and Functional Impairment in Repetitive Mild Traumatic Brain Injured Mice. J Neurotrauma 2023. [PMID: 36576018 DOI: 10.1089/neu.2022.0252] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Mild traumatic brain injury (mTBI) mostly causes transient symptoms, but repeated (r)mTBI can lead to neurodegenerative processes. Diagnostic tools to evaluate the presence of ongoing occult neuropathology are lacking. In a mouse model of rmTBI, we investigated MRI and plasma biomarkers of brain damage before chronic functional impairment arose. Anesthetized adult male and female C57BL/6J mice were subjected to rmTBI or a sham procedure. Sensorimotor deficits were evaluated up to 12 months post-injury in SNAP and Neuroscore tests. Cognitive function was assessed in the novel object recognition test at six and 12 months. Diffusion tensor imaging (DTI) and structural magnetic resonance imaging (MRI) were performed at six and 12 months to examine white matter and structural damage. Plasma levels of neurofilament light (NfL) were assessed longitudinally up to 12 months. Brain histopathology was performed at 12 months. Independent groups of mice were used to examine the effects of 2-, 7- and 14-days inter-injury intervals on acute plasma NfL levels and on hyperactivity. Twelve months after an acute transient impairment, sensorimotor functions declined again in rmTBI mice (p < 0.001 vs sham), but not earlier. Similarly, rmTBI mice showed memory impairment at 12 (p < 0.01 vs sham) but not at 6 months. White matter damage examined by DTI was evident in rmTBI mice at both six and 12 months (p < 0.001 vs sham). This was associated with callosal atrophy (p < 0.001 vs sham) evaluated by structural MRI. Plasma NfL at one week was elevated in rmTBI (p < 0.001 vs sham), and its level correlated with callosal atrophy at 12 months (Pearson r = 0.72, p < 0.01). Histopathology showed thinning of the corpus callosum and marked astrogliosis in rmTBI mice. The NfL levels were higher in mice subjected to short (2 days) compared with longer (7 and 14 days) inter-injury intervals (p < 0.05), and this correlated with hyperactivity in mice (Pearson r = 0.50; p < 0.05). These findings show that rmTBI causes white matter pathology detectable by MRI before chronic functional impairment. Early quantification of plasma NfL correlates with the degree of white matter atrophy one year after rmTBI and can serve to monitor the brain's susceptibility to a second mTBI, supporting its potential clinical application to guide the return to practice in sport-related TBI.
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Affiliation(s)
- Federico Moro
- Department of Acute Brain Injury, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
| | - Ilaria Lisi
- Department of Acute Brain Injury, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
| | - Daniele Tolomeo
- Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
| | - Gloria Vegliante
- Department of Acute Brain Injury, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
| | - Rosaria Pascente
- Department of Acute Brain Injury, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
| | - Edoardo Mazzone
- Department of Acute Brain Injury, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
| | - Riaz Hussain
- Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
| | - Edoardo Micotti
- Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
| | - Julian Dallmeier
- Department of Acute Brain Injury, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.,University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Francesca Pischiutta
- Department of Acute Brain Injury, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
| | - Elisa Bianchi
- Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
| | - Roberto Chiesa
- Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
| | - Kevin K Wang
- Program for Neurotrauma, Neuroproteomics & Biomarkers Research, Departments of Emergency Medicine, Psychiatry, Neuroscience and Chemistry, University of Florida, Gainesville, Florida, USA.,Brain Rehabilitation Research Center, Malcom Randall VA Medical Center, North Florida/South Georgia Veterans Health System, Gainesville, Florida, USA
| | - Elisa R Zanier
- Department of Acute Brain Injury, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
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20
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Ouyang Z, Zhang N, Li M, Hong T, Ouyang T, Meng W. A meta-analysis of the role of diffusion tensor imaging in cervical spinal cord compression. J Neuroimaging 2023. [PMID: 36914383 DOI: 10.1111/jon.13093] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 02/08/2023] [Accepted: 02/08/2023] [Indexed: 03/14/2023] Open
Abstract
BACKGROUND AND PURPOSE At present, the role of diffusion tensor imaging (DTI) remains controversial. This study aimed to confirm the role of DTI by comparing the differences in fractional anisotropy (FA) values between patients with cervical spinal cord compression (CSCC) and healthy individuals. METHODS A systematic and comprehensive literature search was conducted using the Web of Science, Embase, PubMed, and Cochrane Library databases to compare the mean FA values of patients with CSCC and healthy controls across all compression levels in the cervical spinal cord. Essential data from the literature, such as demographic information, imaging parameters, and DTI analysis method, were extracted. Fixed- or random-effect models based on I2 heterogeneity were applied to the pooled and subgroup analyses. RESULTS Ten studies containing 445 patients and 197 healthy volunteers were eligible. The pooled results demonstrated a decrease in mean FA values across all compression levels in the experiment group compared to those in healthy controls (standardized mean difference = -1.54; 95% confidence interval = [-1.95, -1.14]; p < .001). Meta-regression revealed that the scanner field strength and DTI analysis method had a significant effect on heterogeneity. CONCLUSIONS Our results show that FA values in the spinal cord decline in patients with CSCC, thus confirming the crucial role of DTI in CSCC.
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Affiliation(s)
- Ziqiang Ouyang
- Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.,Department of the First Clinical Medical College, Nanchang University, Jiangxi Province, China
| | - Na Zhang
- Department of Neurology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Meihua Li
- Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Tao Hong
- Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Taohui Ouyang
- Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Wei Meng
- Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, China
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21
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Li KR, Wu AG, Tang Y, He XP, Yu CL, Wu JM, Hu GQ, Yu L. The Key Role of Magnetic Resonance Imaging in the Detection of Neurodegenerative Diseases-Associated Biomarkers: A Review. Mol Neurobiol 2022; 59:5935-5954. [PMID: 35829831 DOI: 10.1007/s12035-022-02944-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Accepted: 06/28/2022] [Indexed: 11/30/2022]
Abstract
Neurodegenerative diseases (NDs), including chronic disease such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis, and acute diseases like traumatic brain injury and ischemic stroke are characterized by progressive degeneration, brain tissue damage and loss of neurons, accompanied by behavioral and cognitive dysfunctions. So far, there are no complete cures for NDs; thus, early and timely diagnoses are essential and beneficial to patients' treatment. Magnetic resonance imaging (MRI) has become one of the advanced medical imaging techniques widely used in the clinical examination of NDs due to its non-invasive diagnostic value. In this review, research published in English in current decade from PubMed electronic database on the use of MRI to detect specific biomarkers of NDs was collected, summarized, and discussed, which provides valuable suggestions for the early diagnosis, prevention, and treatment of NDs in the clinic.
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Affiliation(s)
- Ke-Ru Li
- Department of Human Anatomy, School of Preclinical Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China
- Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, Southwest Medical University, Luzhou, 646000, China
- Department of Radiology, Chongqing University Fuling Hospital, Chongqing, 408000, China
| | - An-Guo Wu
- Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, Southwest Medical University, Luzhou, 646000, China
- School of Pharmacy, Southwest Medical University, Luzhou, 646000, China
| | - Yong Tang
- Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, Southwest Medical University, Luzhou, 646000, China
| | - Xiao-Peng He
- Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Chong-Lin Yu
- Department of Human Anatomy, School of Preclinical Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Jian-Ming Wu
- Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, Southwest Medical University, Luzhou, 646000, China
- School of Pharmacy, Southwest Medical University, Luzhou, 646000, China
| | - Guang-Qiang Hu
- Department of Human Anatomy, School of Preclinical Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China.
| | - Lu Yu
- Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, Southwest Medical University, Luzhou, 646000, China.
- School of Pharmacy, Southwest Medical University, Luzhou, 646000, China.
- Department of Chemistry, School of Preclinical Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China.
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22
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Abdelrahman HAF, Ubukata S, Ueda K, Fujimoto G, Oishi N, Aso T, Murai T. Combining Multiple Indices of Diffusion Tensor Imaging Can Better Differentiate Patients with Traumatic Brain Injury from Healthy Subjects. Neuropsychiatr Dis Treat 2022; 18:1801-1814. [PMID: 36039160 PMCID: PMC9419894 DOI: 10.2147/ndt.s354265] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2021] [Accepted: 07/01/2022] [Indexed: 11/23/2022] Open
Abstract
Aim Diffuse axonal injury (DAI) is one of the most common pathological features of traumatic brain injury (TBI). Diffusion tensor imaging (DTI) indices can be used to identify and quantify white matter microstructural changes following DAI. Recently, many studies have used DTI with various machine learning approaches to predict white matter microstructural changes following TBI. The current study sought to examine whether our classification approach using multiple DTI indices in conjunction with machine learning is a useful tool for diagnosing/classifying TBI patients and healthy controls. Methods Participants were adult patients with chronic TBI (n = 26) with DAI pathology, and age- and sex-matched healthy controls (n = 26). DTI images were obtained from all participants. Tract-based spatial statistics analyses were applied to DTI images. Classification models were built using principal component analysis and support vector machines. Receiver operator characteristic curve analysis and area under the curve were used to assess the classification performance of the different classifiers. Results Tract-based spatial statistics revealed significantly decreased fractional anisotropy, as well as increased mean diffusivity, axial diffusivity, and radial diffusivity in patients with TBI compared with healthy controls (all p-values < 0.01). The principal component analysis and support vector machine-based machine learning classification using combined DTI indices classified patients with TBI and healthy controls with an accuracy of 90.5% with an area under the curve of 93 ± 0.09. Conclusion These results highlight the potential of our approach combining multiple DTI measures to identify patients with TBI.
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Affiliation(s)
| | - Shiho Ubukata
- Kyoto University Graduate School of Medicine-Medical Innovation Center, Kyoto, 606-8507, Japan
| | - Keita Ueda
- Kyoto University Graduate School of Medicine-Department of Psychiatry, Kyoto, 606-8507, Japan
| | - Gaku Fujimoto
- Kyoto University Graduate School of Medicine-Department of Psychiatry, Kyoto, 606-8507, Japan
| | - Naoya Oishi
- Kyoto University Graduate School of Medicine-Medical Innovation Center, Kyoto, 606-8507, Japan
| | - Toshihiko Aso
- Laboratory for Brain Connectomics Imaging, RIKEN Center for Biosystems Dynamics Research, Kobe, 650-0047, Japan
| | - Toshiya Murai
- Kyoto University Graduate School of Medicine-Department of Psychiatry, Kyoto, 606-8507, Japan
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23
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Gharehgazlou A, Jetly R, Rhind SG, Reichelt AC, Da Costa L, Dunkley BT. Cortical Gyrification Morphology in Adult Males with Mild Traumatic Brain Injury. Neurotrauma Rep 2022; 3:299-307. [PMID: 36060456 PMCID: PMC9438439 DOI: 10.1089/neur.2021.0032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
Cortical gyrification, as a specific measure derived from magnetic resonance imaging, remains understudied in mild traumatic brain injury (mTBI). Local gyrification index (lGI) and mean curvature are related measures indexing the patterned folding of the cortex,ml which reflect distinct properties of cortical morphology and geometry. Using both metrics, we examined cortical gyrification morphology in 59 adult males with mTBI (n = 29) versus those without (n = 30) mTBI in the subacute phase of injury (between 2 weeks and 3 months). The effect of IQ on lGI and brain-symptom relations were also examined. General linear models revealed greater lGI in mTBI versus controls in the frontal lobes bilaterally, but reduced lGI in mTBI of the left temporal lobe. An age-related decrease in lGI was found in numerous areas, with no significant group-by-age interaction effects observed. Including other factors (i.e., mTBI severity, symptoms, and IQ) in the lGI model yielded similar results with few exceptions. Mean curvature analyses depicted a significant group-by-age interaction with the absence of significant main effects of group or age. Our results suggest that cortical gyrification morphology is adversely affected by mTBI in both frontal and temporal lobes, which are thought of as highly susceptible regions to mTBI. These findings contribute to understanding the effects of mTBI on neuromorphological properties, such as alterations in cortical gyrification, which reflect underlying microstructural changes (i.e., apoptosis, neuronal number, or white matter alterations). Future studies are needed to infer causal relationships between micro- and macrostructural changes after an mTBI and investigate potential sex differences.
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Affiliation(s)
- Avideh Gharehgazlou
- Neurosciences and Mental Health, The Hospital for Sick Children (SickKids) Research Institute, Toronto, Ontario, Canada
- Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, Ontario, Canada
| | - Rakesh Jetly
- Directorate of Mental Health, Canadian Forces Health Services HQ, Ottawa, Ontario, Canada
- Defence Research and Development Canada–Toronto Research Centre, Toronto, Ontario, Canada
| | - Shawn G. Rhind
- Faculty of Kinesiology and Physical Education, University of Toronto, Toronto, Ontario, Canada
- Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Amy C. Reichelt
- Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia
| | - Leodante Da Costa
- Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Department of Surgery, University of Toronto, Toronto, Ontario, Canada
- Department of Diagnostic Imaging, The Hospital for Sick Children (SickKids) Research Institute, Toronto, Ontario, Canada
| | - Benjamin T. Dunkley
- Neurosciences and Mental Health, The Hospital for Sick Children (SickKids) Research Institute, Toronto, Ontario, Canada
- Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Department of Diagnostic Imaging, The Hospital for Sick Children (SickKids) Research Institute, Toronto, Ontario, Canada
- Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada
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24
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Detection of Chronic Blast-Related Mild Traumatic Brain Injury with Diffusion Tensor Imaging and Support Vector Machines. Diagnostics (Basel) 2022; 12:diagnostics12040987. [PMID: 35454035 PMCID: PMC9030428 DOI: 10.3390/diagnostics12040987] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 04/07/2022] [Accepted: 04/08/2022] [Indexed: 01/13/2023] Open
Abstract
Blast-related mild traumatic brain injury (bmTBI) often leads to long-term sequalae, but diagnostic approaches are lacking due to insufficient knowledge about the predominant pathophysiology. This study aimed to build a diagnostic model for future verification by applying machine-learning based support vector machine (SVM) modeling to diffusion tensor imaging (DTI) datasets to elucidate white-matter features that distinguish bmTBI from healthy controls (HC). Twenty subacute/chronic bmTBI and 19 HC combat-deployed personnel underwent DTI. Clinically relevant features for modeling were selected using tract-based analyses that identified group differences throughout white-matter tracts in five DTI metrics to elucidate the pathogenesis of injury. These features were then analyzed using SVM modeling with cross validation. Tract-based analyses revealed abnormally decreased radial diffusivity (RD), increased fractional anisotropy (FA) and axial/radial diffusivity ratio (AD/RD) in the bmTBI group, mostly in anterior tracts (29 features). SVM models showed that FA of the anterior/superior corona radiata and AD/RD of the corpus callosum and anterior limbs of the internal capsule (5 features) best distinguished bmTBI from HCs with 89% accuracy. This is the first application of SVM to identify prominent features of bmTBI solely based on DTI metrics in well-defined tracts, which if successfully validated could promote targeted treatment interventions.
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25
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Lin JC, Mueller C, Campbell KA, Thannickal HH, Daredia AF, Sheriff S, Maudsley AA, Brunner RC, Younger JW. Investigating whole-brain metabolite abnormalities in the chronic stages of moderate or severe traumatic brain injury. PM R 2022; 14:472-485. [PMID: 33930238 PMCID: PMC9212770 DOI: 10.1002/pmrj.12623] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 04/18/2021] [Accepted: 04/19/2021] [Indexed: 12/30/2022]
Abstract
BACKGROUND Evidence suggests that neurometabolic abnormalities can persist after traumatic brain injury (TBI) and drive clinical symptoms such as fatigue and cognitive disruption. Magnetic resonance spectroscopy has been used to investigate metabolite abnormalities following TBI, but few studies have obtained data beyond the subacute stage or over large brain regions. OBJECTIVE To measure whole-brain metabolites in chronic stages of TBI. DESIGN Observational study. SETTING University. PARTICIPANTS Eleven men with a moderate or severe TBI more than 12 months prior and 10 age-matched healthy controls completed whole-brain spectroscopic imaging. MAIN MEASURES Ratios of N-acetylaspartate (NAA), choline (CHO), and myo-inositol (MI) to creatine (CR) were measured in whole-brain gray and white matter as well as 64 brain regions of interest. Arterial spin labeling (ASL) data were also collected to investigate whether metabolite abnormalities were accompanied by differences in cerebral perfusion. RESULTS There were no differences in metabolite ratios within whole-brain gray and white matter regions of interest (ROIs). Linear regression showed lower NAA/CR in the white matter of the left occipital lobe but higher NAA/CR in the gray matter of the left parietal lobe. Metabolite abnormalities were observed in several brain regions in the TBI group including the corpus callosum, putamen, and posterior cingulate. However, none of the findings survived correction for multiple comparison. There were no differences in cerebral blood flow between patients and controls. CONCLUSION Higher MI/CR may indicate ongoing gliosis, and it has been suggested that low CHO/CR at chronic time points may indicate cell death or lack of healthy turnover and repair. However, with the small sample size of this study, we caution against the over interpretation of our results. None of the findings within ROIs survived correction for multiple comparison. Thus, they may be considered possible avenues for future research in this area.
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Affiliation(s)
- Joanne C. Lin
- Department of Psychology, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Christina Mueller
- Department of Psychology, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Kelsey A. Campbell
- Department of Psychology, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | | | - Altamish F. Daredia
- Department of Psychology, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Sulaiman Sheriff
- Department of Radiology, Miller School of Medicine, University of Miami, Miami, Florida, USA
| | - Andrew A. Maudsley
- Department of Radiology, Miller School of Medicine, University of Miami, Miami, Florida, USA
| | - Robert C. Brunner
- Department of Physical Medicine and Rehabilitation, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Jarred W. Younger
- Department of Psychology, University of Alabama at Birmingham, Birmingham, Alabama, USA
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26
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Gard A, Al-Husseini A, Kornaropoulos EN, De Maio A, Tegner Y, Björkman-Burtscher I, Markenroth Bloch K, Nilsson M, Magnusson M, Marklund N. Post-Concussive Vestibular Dysfunction Is Related to Injury to the Inferior Vestibular Nerve. J Neurotrauma 2022; 39:829-840. [PMID: 35171721 PMCID: PMC9225415 DOI: 10.1089/neu.2021.0447] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
Abstract
Symptoms of vestibular dysfunction such as dizziness and vertigo are common after sports-related concussions (SRC) and associated with a worse outcome and a prolonged recovery. Vestibular dysfunction after SRC can be because of an impairment of the peripheral or central neural parts of the vestibular system. The aim of the present study was to establish the cause of vestibular impairment in athletes with SRC who have persisting post-concussive symptoms (PPCS). We recruited 42 participants-21 athletes with previous SRCs and PPCS ≥6 months and 21 healthy athletic age- and sex-matched controls-who underwent symptom rating, a detailed test battery of vestibular function and 7T magnetic resonance imaging with diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) of cerebellar white matter tracts, and T1-weighted imaging for cerebellar volumetrics. Vestibular dysfunction was observed in 13 SRC athletes and three controls (p = 0.001). Athletes with vestibular dysfunction reported more pronounced symptoms on the Dizziness Handicap Inventory (DHI; p < 0.001) and the Hospital Anxiety and Depression Scale (HADS; p < 0.001). No significant differences in DTI metrics were found, while in DKI two metrics were observed in the superior and/or inferior cerebellar tracts. Cerebellar gray and white matter volumes were similar in athletes with SRC and controls. Compared with controls, pathological video head impulse test results (vHIT; p < 0.001) and cervical vestibular evoked myogenic potentials (cVEMP; p = 0.002) were observed in athletes with SRC, indicating peripheral vestibular dysfunction and specifically suggesting injury to the inferior vestibular nerve. In athletes with persisting symptoms after SRC, vestibular dysfunction is associated with injury to the inferior vestibular nerve.
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Affiliation(s)
- Anna Gard
- Department of Clinical Sciences Lund, Lund University, Neurosurgery, Skåne University Hospital, Lund, Sweden
| | - Ali Al-Husseini
- Department of Clinical Sciences Lund, Lund University, Neurosurgery, Skåne University Hospital, Lund, Sweden
| | - Evgenios N. Kornaropoulos
- Department of Clinical Sciences Lund, Diagnostic Radiology, Lund University, Skåne University Hospital, Lund, Sweden
| | - Alessandro De Maio
- Department of Radiological, Oncological and Pathological Sciences. Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
| | - Yelverton Tegner
- Department of Health Sciences, Luleå University of Technology, Luleå, Sweden
| | - Isabella Björkman-Burtscher
- Department of Radiology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | | | - Markus Nilsson
- Department of Clinical Sciences Lund, Diagnostic Radiology, Lund University, Skåne University Hospital, Lund, Sweden
| | - Måns Magnusson
- Department of Clinical Sciences Lund, Otorhinolaryngology, Lund University, Skåne University Hospital, Lund, Sweden
| | - Niklas Marklund
- Department of Clinical Sciences Lund, Lund University, Neurosurgery, Skåne University Hospital, Lund, Sweden
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Diaz-Pacheco V, Vargas-Medrano J, Tran E, Nicolas M, Price D, Patel R, Tonarelli S, Gadad BS. Prognosis and Diagnostic Biomarkers of Mild Traumatic Brain Injury: Current Status and Future Prospects. J Alzheimers Dis 2022; 86:943-959. [PMID: 35147534 DOI: 10.3233/jad-215158] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Mild traumatic brain injury (mTBI) is the most prevalent type of TBI (80-90%). It is characterized by a loss consciousness for less than 30 minutes, post-traumatic amnesia for less than 24 hours, and Glasgow Coma Score of 13-15. Accurately diagnosing mTBIs can be a challenge because the majority of these injuries do not show noticeable or visible changes on neuroimaging studies. Appropriate determination of mTBI is tremendously important because it might lead in some cases to post-concussion syndrome, cognitive impairments including attention, memory, and speed of information processing problems. The scientists have studied different methods to improve mTBI diagnosis and enhanced approaches that would accurately determine the severity of the trauma. The present review focuses on discussing the role of biomarkers as potential key factors in diagnosing mTBI. The present review focuses on 1) protein based peripheral and CNS markers, 2) genetic biomarkers, 3) imaging biomarkers, 4) neurophysiological biomarkers, and 5) the studies and clinical trials in mTBI. Each section provides information and characteristics on different biomarkers for mTBI.
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Affiliation(s)
- Valeria Diaz-Pacheco
- Department of Psychiatry, Paul L. Foster School of Medicine, Texas Tech University Health Science Center, El Paso, TX, USA.,Southwest Brain Bank, Texas Tech University Health Science Center, El Paso, TX, USA
| | - Javier Vargas-Medrano
- Department of Psychiatry, Paul L. Foster School of Medicine, Texas Tech University Health Science Center, El Paso, TX, USA.,Southwest Brain Bank, Texas Tech University Health Science Center, El Paso, TX, USA
| | - Eric Tran
- Paul L. Foster School of Medicine, Texas Tech University Health Science Center, El Paso, TX, USA
| | - Meza Nicolas
- Paul L. Foster School of Medicine, Texas Tech University Health Science Center, El Paso, TX, USA
| | - Diamond Price
- The Chicago School of Professional Psychology, Irvine, CA, USA
| | - Richa Patel
- Department of Psychiatry, Paul L. Foster School of Medicine, Texas Tech University Health Science Center, El Paso, TX, USA
| | - Silvina Tonarelli
- Department of Psychiatry, Paul L. Foster School of Medicine, Texas Tech University Health Science Center, El Paso, TX, USA
| | - Bharathi S Gadad
- Department of Psychiatry, Paul L. Foster School of Medicine, Texas Tech University Health Science Center, El Paso, TX, USA.,Southwest Brain Bank, Texas Tech University Health Science Center, El Paso, TX, USA
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Refined Analysis of Chronic White Matter Changes after Traumatic Brain Injury and Repeated Sports-Related Concussions: Of Use in Targeted Rehabilitative Approaches? J Clin Med 2022; 11:jcm11020358. [PMID: 35054052 PMCID: PMC8780504 DOI: 10.3390/jcm11020358] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 01/03/2022] [Accepted: 01/08/2022] [Indexed: 12/10/2022] Open
Abstract
Traumatic brain injury (TBI) or repeated sport-related concussions (rSRC) may lead to long-term memory impairment. Diffusion tensor imaging (DTI) is helpful to reveal global white matter damage but may underestimate focal abnormalities. We investigated the distribution of post-injury regional white matter changes after TBI and rSRC. Six patients with moderate/severe TBI, and 12 athletes with rSRC were included ≥6 months post-injury, and 10 (age-matched) healthy controls (HC) were analyzed. The Repeatable Battery for the Assessment of Neuropsychological Status was performed at the time of DTI. Major white matter pathways were tracked using q-space diffeomorphic reconstruction and analyzed for global and regional changes with a controlled false discovery rate. TBI patients displayed multiple classic white matter injuries compared with HC (p < 0.01). At the regional white matter analysis, the left frontal aslant tract, anterior thalamic radiation, and the genu of the corpus callosum displayed focal changes in both groups compared with HC but with different trends. Both TBI and rSRC displayed worse memory performance compared with HC (p < 0.05). While global analysis of DTI-based parameters did not reveal common abnormalities in TBI and rSRC, abnormalities to the fronto-thalamic network were observed in both groups using regional analysis of the white matter pathways. These results may be valuable to tailor individualized rehabilitative approaches for post-injury cognitive impairment in both TBI and rSRC patients.
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Smith DR, Caban-Rivera DA, McGarry MD, Williams LT, McIlvain G, Okamoto RJ, Van Houten EE, Bayly PV, Paulsen KD, Johnson CL. Anisotropic mechanical properties in the healthy human brain estimated with multi-excitation transversely isotropic MR elastography. BRAIN MULTIPHYSICS 2022; 3. [DOI: 10.1016/j.brain.2022.100051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022] Open
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30
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Rier L, Zamyadi R, Zhang J, Emami Z, Seedat ZA, Mocanu S, Gascoyne LE, Allen CM, Scadding JW, Furlong PL, Gooding-Williams G, Woolrich MW, Evangelou N, Brookes MJ, Dunkley BT. Mild traumatic brain injury impairs the coordination of intrinsic and motor-related neural dynamics. NEUROIMAGE-CLINICAL 2021; 32:102841. [PMID: 34653838 PMCID: PMC8517919 DOI: 10.1016/j.nicl.2021.102841] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Revised: 09/01/2021] [Accepted: 09/23/2021] [Indexed: 11/23/2022]
Abstract
MTBI is poorly understood and lacks objective diagnostic and prognostic tools. Abnormal neural oscillations are found in subjects with a history of mTBI. We identify transient bursts in MEG data using a Hidden Markov Model. We explain a deficit in beta connectivity and power in terms of transient bursts. Data-driven feature selection identifies symptom-relevant functional connections. Mild traumatic brain injury (mTBI) poses a considerable burden on healthcare systems. Whilst most patients recover quickly, a significant number suffer from sequelae that are not accompanied by measurable structural damage. Understanding the neural underpinnings of these debilitating effects and developing a means to detect injury, would address an important unmet clinical need. It could inform interventions and help predict prognosis. Magnetoencephalography (MEG) affords excellent sensitivity in probing neural function and presents significant promise for assessing mTBI, with abnormal neural oscillations being a potential specific biomarker. However, growing evidence suggests that neural dynamics are (at least in part) driven by transient, pan-spectral bursting and in this paper, we employ this model to investigate mTBI. We applied a Hidden Markov Model to MEG data recorded during resting state and a motor task and show that previous findings of diminished intrinsic beta amplitude in individuals with mTBI are largely due to the reduced beta band spectral content of bursts, and that diminished beta connectivity results from a loss in the temporal coincidence of burst states. In a motor task, mTBI results in diminished burst amplitude, altered modulation of burst probability during movement, and a loss in connectivity in motor networks. These results suggest that, mechanistically, mTBI disrupts the structural framework underlying neural synchrony, which impairs network function. Whilst the damage may be too subtle for structural imaging to see, the functional consequences are detectable and persist after injury. Our work shows that mTBI impairs the dynamic coordination of neural network activity and proposes a potent new method for understanding mTBI.
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Affiliation(s)
- Lukas Rier
- Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, University Park, Nottingham NG7 2RD, UK
| | - Rouzbeh Zamyadi
- Diagnostic Imaging, Hospital for Sick Children, Toronto, Canada
| | - Jing Zhang
- Diagnostic Imaging, Hospital for Sick Children, Toronto, Canada; Neurosciences & Mental Health, Hospital for Sick Children Research Institute, Toronto, Canada
| | - Zahra Emami
- Neurosciences & Mental Health, Hospital for Sick Children Research Institute, Toronto, Canada; Faculty of Medicine, University of Toronto, Toronto, Canada
| | - Zelekha A Seedat
- Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, University Park, Nottingham NG7 2RD, UK
| | - Sergiu Mocanu
- Diagnostic Imaging, Hospital for Sick Children, Toronto, Canada; Neurosciences & Mental Health, Hospital for Sick Children Research Institute, Toronto, Canada
| | - Lauren E Gascoyne
- Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, University Park, Nottingham NG7 2RD, UK
| | - Christopher M Allen
- Mental Health and Clinical Neurosciences Academic Unit, School of Medicine, University of Nottingham, Queen's Medical Centre, Nottingham, UK
| | - John W Scadding
- National Hospital for Neurology and Neurosurgery, London, UK
| | - Paul L Furlong
- Institute of Health and Neurodevelopment, Aston University, Birmingham, UK
| | | | - Mark W Woolrich
- Oxford Centre for Human Brain Activity, Warneford Hospital, University of Oxford, Oxford, UK
| | - Nikos Evangelou
- Mental Health and Clinical Neurosciences Academic Unit, School of Medicine, University of Nottingham, Queen's Medical Centre, Nottingham, UK
| | - Matthew J Brookes
- Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, University Park, Nottingham NG7 2RD, UK
| | - Benjamin T Dunkley
- Diagnostic Imaging, Hospital for Sick Children, Toronto, Canada; Neurosciences & Mental Health, Hospital for Sick Children Research Institute, Toronto, Canada; Medical Imaging, University of Toronto, Toronto, Canada
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The role of diffusion tensor imaging in idiopathic sensorineural hearing loss: is it significant? Pol J Radiol 2021; 86:e474-e480. [PMID: 34567293 PMCID: PMC8449561 DOI: 10.5114/pjr.2021.108372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Accepted: 06/03/2020] [Indexed: 11/27/2022] Open
Abstract
Purpose To assess the role of diffusion tensor imaging metrics in the evaluation of the microstructural integrity of the central auditory tract in patients with idiopathic sensorineural hearing loss (SNHL), and to compare these patients with healthy controls. Material and methods This prospective study, which was conducted upon 30 subjects (21 males, 9 females; age range from 16 to 65 years, mean age 45years) with SNHL proven by audiometric tests. Ten age- and sex-matched healthy volunteers were included as a control group. Patients (n = 30) and volunteers (n = 10) underwent conventional magnetic resonance imaging and diffusion tensor imaging of the brain. Both fractional anisotropy and mean diffusivity (MD) of 3 points along the acoustic tract (inferior colliculus, lateral lemniscus and superior olivary nucleus) were measured bilaterally in all patients and correlated with controls. Results Mean fractional anisotropy (FA) values were reduced bilaterally at the superior olivary nucleus and/or lateral lemniscus and more significantly at the inferior colliculus of subjects with SNHL in comparison to the volunteers. In patients of unilateral SNHL, similar results were obtained in the contralateral side when compared to controls with statistically significant difference at the 3 regions (p = 0.001). No significant changes were noticed in the MD parameters either in patient or control groups. Conclusions The FA value was a valuable non-invasive biomarker in evaluating the subtle microstructural abnormalities of the central auditory tract in idiopathic SNHL and correlated well with hearing impairment.
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Oehr LE, Yang JYM, Chen J, Maller JJ, Seal ML, Anderson JFI. Investigating White Matter Tract Microstructural Changes at Six-Twelve Weeks following Mild Traumatic Brain Injury: A Combined Diffusion Tensor Imaging and Neurite Orientation Dispersion and Density Imaging Study. J Neurotrauma 2021; 38:2255-2263. [PMID: 33307950 DOI: 10.1089/neu.2020.7310] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Using diffusion-weighted imaging (DWI), research has demonstrated changes suggestive of damage to white matter tracts (WMT) following mild traumatic brain injury (mTBI). Yet due to the predominant use of the diffusion tensor imaging (DTI) model, which has numerous well-established limitations, it has not yet been possible to clearly examine the nature of changes to WMT microstructure following mTBI. This study used a second DWI-based technique, neurite orientation dispersion and density imaging (NODDI), in combination with DTI to measure microstructural changes within the corpus callosum, three long association and one projection WMTs at 6-12 weeks following mTBI, compared with matched trauma controls (TC). Between-groups differences were identified across all WMT for the DTI metric fractional anisotropy (FA), and the NODDI metrics orientation dispersion index (ODI) and isotropic volume fraction (ISO). No statistically significant between-groups differences were found for other DTI and NODDI metrics. Our study revealed that reduced FA was accompanied by increased ODI, suggesting that mTBI results in reduced coherence of axonal fiber bundles within the studied WMTs. These between-groups differences in WMT microstructure were found at 6-12 weeks post-injury, which suggests that structural recovery is not yet complete towards end of the typical 3-month recovery period.
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Affiliation(s)
- Lucy E Oehr
- Melbourne School of Psychological Sciences, University of Melbourne, Victoria, Australia
| | - Joseph Yuan-Mou Yang
- Department of Neuroscience Research, Murdoch Childrens Research Institute, Melbourne, Victoria, Australia
- Department of Developmental Imaging, Murdoch Childrens Research Institute, Melbourne, Victoria, Australia
- Department of Neurosurgery, Royal Children's Hospital, Melbourne, Victoria, Australia
- Department of Pediatrics, University of Melbourne, Victoria, Australia
| | - Jian Chen
- Department of Developmental Imaging, Murdoch Childrens Research Institute, Melbourne, Victoria, Australia
| | - Jerome J Maller
- General Electric Healthcare, Melbourne, Victoria, Australia
- Monash Alfred Psychiatry Research Center, Melbourne, Victoria, Australia
| | - Marc L Seal
- Department of Developmental Imaging, Murdoch Childrens Research Institute, Melbourne, Victoria, Australia
| | - Jacqueline F I Anderson
- Melbourne School of Psychological Sciences, University of Melbourne, Victoria, Australia
- Department of Psychology, Alfred Hospital, Melbourne, Victoria, Australia
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Implications of DTI in mild traumatic brain injury for detecting neurological recovery and predicting long-term behavioural outcome in paediatric and young population-a systematic review. Childs Nerv Syst 2021; 37:2475-2486. [PMID: 34128118 DOI: 10.1007/s00381-021-05240-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 06/01/2021] [Indexed: 10/21/2022]
Abstract
PURPOSE This systematic review was done with the aim to answer these three questions: 1) Is there any change in diffusion metrics in MRI-DTI sequences after mild traumatic brain injury in paediatric and young population?, 2) Is there any correlation of these changes in diffusion metrics with severity of post concussion symptoms?, 3) Is the change in diffusion metrics predictive of neurocognitive function or neurological recovery? MATERIAL AND METHODS Eligibility criteria- Mild TBI patients upto 22 years of age, MRI- DTI sequence done post injury, Outcome measurement with follow up at least for onemonth and articles published in English language only. Data sources- PubMed, EMBASE, CINAHL, Scopus and Cochrane RESULTS: Some studies show increased FA and some studies show decrease FA and few showed no change in white matter microstructure in mTBI patients and this depends on the duration of injury. Prediction of PCSs severity on the basis of changes in white matter microstructure showed inconsistent results. Radiological recovery in contrast to clinical recovery, is often delayed ranging from 6 months to 2-3 years. But change in diffusion metrics after mTBI is not definite predictive of neurocognitive outcomes. CONCLUSION Large, properly designed, multicentric studies with appropriate extracranial or orthopedic control and long follow up are needed to establish the use of DTIin mTBI for predicting behavioral outcome.
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34
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Gryffydd L, Mitra B, Wright BJ, Kinsella GJ. Cognitive performance in older adults at three months following mild traumatic brain injury. J Clin Exp Neuropsychol 2021; 43:481-496. [PMID: 34078223 DOI: 10.1080/13803395.2021.1933915] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Introduction: In the context of limited research assessing outcomes following mild traumatic brain injury (mTBI) in older adults, this study evaluated cognitive outcomes through prospective memory, and expected that performance of an older mTBI group (≥65 years) would be lower compared to orthopedic and community controls. The study also explored whether cognitive resources (retrospective memory, executive function) moderated any association between presenting Glasgow Coma Scale (GCS) and prospective memory.Method: At three-months post-injury, a mTBI group (n = 39), an orthopedic control group (n = 63), and a community control group (n = 46) completed a neuropsychological assessment, including (i) prospective memory, using a standardized paper-and-pencil task (Cambridge Prospective Memory Test), an augmented reality task and a naturalistic task, and (ii) standardized measures of retrospective memory (Hopkins Verbal Learning Test) and executive function (Trail Making Test). Group performances were compared, and bootstrapped moderation analyses evaluated the role of cognitive resources in the relationship between GCS and prospective memory outcome.Results: The mTBI group, as compared to community controls, performed significantly lower on the augmented reality task (d = -0.64 to d = -0.79), and there was a small-moderate but non-significant effect (d = -0.45) on the naturalistic task. There were no differences between the mTBI group and orthopedic controls. Retrospective memory was a unique predictor of the augmented reality task (B = 1.83) and moderated the relationship between presenting GCS and the naturalistic task (B = -5.60). Executive function moderated the association between presenting GCS and augmented reality (B = -1.13) and naturalistic task (B = -1.57).Conclusions: At three-months post-mTBI, older adults are at risk of poor cognitive performance; and the relationship between GCS and prospective memory can be moderated by cognitive resources. Further follow-up is indicated to determine whether impairments resolve or persist over time.
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Affiliation(s)
- Lei Gryffydd
- School of Psychology and Public Health, La Trobe University, Melbourne, Australia
| | - Biswadev Mitra
- Emergency and Trauma Centre, The Alfred Hospital, Melbourne, Australia.,School of Public Health and Preventive Medicine, Monash University, Australia.,National Trauma Research Institute, The Alfred Hospital, Melbourne, Australia
| | - Bradley J Wright
- School of Psychology and Public Health, La Trobe University, Melbourne, Australia
| | - Glynda J Kinsella
- School of Psychology and Public Health, La Trobe University, Melbourne, Australia.,Department of Psychology, Caulfield Hospital, Caulfield, Australia
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35
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Liang W, Han B, Hai Y, Yin P, Chen Y, Zou C. Diffusion tensor imaging with fiber tracking provides a valuable quantitative and clinical evaluation for compressed lumbosacral nerve roots: a systematic review and meta-analysis. EUROPEAN SPINE JOURNAL : OFFICIAL PUBLICATION OF THE EUROPEAN SPINE SOCIETY, THE EUROPEAN SPINAL DEFORMITY SOCIETY, AND THE EUROPEAN SECTION OF THE CERVICAL SPINE RESEARCH SOCIETY 2021; 30:818-828. [PMID: 32748258 DOI: 10.1007/s00586-020-06556-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Revised: 07/20/2020] [Accepted: 07/26/2020] [Indexed: 10/23/2022]
Abstract
PURPOSE This study aimed to investigate the diagnostic value of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of the diffusion tensor imaging (DTI) with fiber tracking in patients with compressed lumbosacral nerve roots. METHODS A systematic literature search of databases (PubMed, Embase, Cochrane Library, and Web of Science) was carried out. FA values and ADC values were compared between compressed nerve roots and healthy controls. Pooled and subgroup analyses were performed using fixed or random-effect models based on I2 heterogeneity. RESULTS A total of 262 patients from ten studies with 285 compressed lumbosacral nerve roots and 285 contralateral normal nerve roots were included in the meta-analysis. It was showed in pooled results that FA value was significantly reduced (SMD - 3.03, 95% CI [ - 3.75 to - 2.31], P < 0.001) and ADC value was significantly increased (SMD 2.07, 95% CI [0.92 to 3.22], P < 0.001) in the compressed nerve roots, compared with contralateral normal nerve roots. Subgroup analysis comparing the FA values and ADC values in different nerve root ranges (L2-S1, L4-S1, L5-S1, L5, S1) revealed the different ranges of nerve roots were possible sources of heterogeneity. CONCLUSIONS This study showed that FA value reduction and ADC value increase were valuable indicators of compressed lumbosacral nerve roots. These changes may be related to the neurological symptoms of patients. DTI with fiber tracking can directly visualize and accurately locate the compression zone of nerve roots to help make surgical treatment plans, is more advanced than conventional MRI.
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Affiliation(s)
- Weishi Liang
- Department of Orthopedics, Beijing Chao-Yang Hospital, Capital Medical University, GongTiNanLu 8#, Chao-Yang District, Beijing, 100020, China
| | - Bo Han
- Department of Orthopedics, Beijing Chao-Yang Hospital, Capital Medical University, GongTiNanLu 8#, Chao-Yang District, Beijing, 100020, China
| | - Yong Hai
- Department of Orthopedics, Beijing Chao-Yang Hospital, Capital Medical University, GongTiNanLu 8#, Chao-Yang District, Beijing, 100020, China.
| | - Peng Yin
- Department of Orthopedics, Beijing Chao-Yang Hospital, Capital Medical University, GongTiNanLu 8#, Chao-Yang District, Beijing, 100020, China
| | - Yuxiang Chen
- Department of Orthopedics, Beijing Chao-Yang Hospital, Capital Medical University, GongTiNanLu 8#, Chao-Yang District, Beijing, 100020, China
| | - Congying Zou
- Department of Orthopedics, Beijing Chao-Yang Hospital, Capital Medical University, GongTiNanLu 8#, Chao-Yang District, Beijing, 100020, China
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Wiegand TLT, Sollmann N, Bonke EM, Umeasalugo KE, Sobolewski KR, Plesnila N, Shenton ME, Lin AP, Koerte IK. Translational neuroimaging in mild traumatic brain injury. J Neurosci Res 2021; 100:1201-1217. [PMID: 33789358 DOI: 10.1002/jnr.24840] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Revised: 03/09/2021] [Accepted: 03/17/2021] [Indexed: 01/26/2023]
Abstract
Traumatic brain injuries (TBIs) are common with an estimated 27.1 million cases per year. Approximately 80% of TBIs are categorized as mild TBI (mTBI) based on initial symptom presentation. While in most individuals, symptoms resolve within days to weeks, in some, symptoms become chronic. Advanced neuroimaging has the potential to characterize brain morphometric, microstructural, biochemical, and metabolic abnormalities following mTBI. However, translational studies are needed for the interpretation of neuroimaging findings in humans with respect to the underlying pathophysiological processes, and, ultimately, for developing novel and more targeted treatment options. In this review, we introduce the most commonly used animal models for the study of mTBI. We then summarize the neuroimaging findings in humans and animals after mTBI and, wherever applicable, the translational aspects of studies available today. Finally, we highlight the importance of translational approaches and outline future perspectives in the field of translational neuroimaging in mTBI.
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Affiliation(s)
- Tim L T Wiegand
- cBRAIN, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Ludwig-Maximilians-Universität, Munich, Germany
| | - Nico Sollmann
- cBRAIN, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Ludwig-Maximilians-Universität, Munich, Germany
- Department of Diagnostic and Interventional Neuroradiology, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
- TUM-Neuroimaging Center, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
- Department of Diagnostic and Interventional Radiology, University Hospital Ulm, Ulm, Germany
| | - Elena M Bonke
- cBRAIN, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Ludwig-Maximilians-Universität, Munich, Germany
- Graduate School of Systemic Neurosciences, Ludwig-Maximilians-Universität, Munich, Germany
| | - Kosisochukwu E Umeasalugo
- cBRAIN, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Ludwig-Maximilians-Universität, Munich, Germany
- Graduate School of Systemic Neurosciences, Ludwig-Maximilians-Universität, Munich, Germany
- Institute for Stroke and Dementia Research, Ludwig-Maximilians-Universität, Munich, Germany
| | - Kristen R Sobolewski
- Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Center for Clinical Spectroscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Nikolaus Plesnila
- Institute for Stroke and Dementia Research, Ludwig-Maximilians-Universität, Munich, Germany
- Munich Cluster for Systems Neurology (Synergy), Munich, Germany
| | - Martha E Shenton
- Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Alexander P Lin
- Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Center for Clinical Spectroscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Inga K Koerte
- cBRAIN, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Ludwig-Maximilians-Universität, Munich, Germany
- Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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Turner S, Lazarus R, Marion D, Main KL. Molecular and Diffusion Tensor Imaging Biomarkers of Traumatic Brain Injury: Principles for Investigation and Integration. J Neurotrauma 2021; 38:1762-1782. [PMID: 33446015 DOI: 10.1089/neu.2020.7259] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
The last 20 years have seen the advent of new technologies that enhance the diagnosis and prognosis of traumatic brain injury (TBI). There is recognition that TBI affects the brain beyond initial injury, in some cases inciting a progressive neuropathology that leads to chronic impairments. Medical researchers are now searching for biomarkers to detect and monitor this condition. Perhaps the most promising developments are in the biomolecular and neuroimaging domains. Molecular assays can identify proteins indicative of neuronal injury and/or degeneration. Diffusion imaging now allows sensitive evaluations of the brain's cellular microstructure. As the pace of discovery accelerates, it is important to survey the research landscape and identify promising avenues of investigation. In this review, we discuss the potential of molecular and diffusion tensor imaging (DTI) biomarkers in TBI research. Integration of these technologies could advance models of disease prognosis, ultimately improving care. To date, however, few studies have explored relationships between molecular and DTI variables in patients with TBI. Here, we provide a short primer on each technology, review the latest research, and discuss how these biomarkers may be incorporated in future studies.
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Affiliation(s)
- Stephanie Turner
- Defense and Veterans Brain Injury Center, Silver Spring, Maryland, USA.,General Dynamics Information Technology, Falls Church, Virginia, USA
| | - Rachel Lazarus
- Defense and Veterans Brain Injury Center, Silver Spring, Maryland, USA.,General Dynamics Information Technology, Falls Church, Virginia, USA
| | - Donald Marion
- Defense and Veterans Brain Injury Center, Silver Spring, Maryland, USA.,General Dynamics Information Technology, Falls Church, Virginia, USA
| | - Keith L Main
- Defense and Veterans Brain Injury Center, Silver Spring, Maryland, USA.,General Dynamics Information Technology, Falls Church, Virginia, USA
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James SN, Nicholas JM, Lane CA, Parker TD, Lu K, Keshavan A, Buchanan SM, Keuss SE, Murray-Smith H, Wong A, Cash DM, Malone IB, Barnes J, Sudre CH, Coath W, Prosser L, Ourselin S, Modat M, Thomas DL, Cardoso J, Heslegrave A, Zetterberg H, Crutch SJ, Schott JM, Richards M, Fox NC. A population-based study of head injury, cognitive function and pathological markers. Ann Clin Transl Neurol 2021; 8:842-856. [PMID: 33694298 PMCID: PMC8045921 DOI: 10.1002/acn3.51331] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 02/12/2021] [Indexed: 02/01/2023] Open
Abstract
Objective To assess associations between head injury (HI) with loss of consciousness (LOC), ageing and markers of later‐life cerebral pathology; and to explore whether those effects may help explain subtle cognitive deficits in dementia‐free individuals. Methods Participants (n = 502, age = 69–71) from the 1946 British Birth Cohort underwent cognitive testing (subtests of Preclinical Alzheimer Cognitive Composite), 18F‐florbetapir Aβ‐PET and MR imaging. Measures include Aβ‐PET status, brain, hippocampal and white matter hyperintensity (WMH) volumes, normal appearing white matter (NAWM) microstructure, Alzheimer’s disease (AD)‐related cortical thickness, and serum neurofilament light chain (NFL). LOC HI metrics include HI occurring: (i) >15 years prior to the scan (ii) anytime up to age 71. Results Compared to those with no evidence of an LOC HI, only those reporting an LOC HI>15 years prior (16%, n = 80) performed worse on cognitive tests at age 69–71, taking into account premorbid cognition, particularly on the digit‐symbol substitution test (DSST). Smaller brain volume (BV) and adverse NAWM microstructural integrity explained 30% and 16% of the relationship between HI and DSST, respectively. We found no evidence that LOC HI was associated with Aβ load, hippocampal volume, WMH volume, AD‐related cortical thickness or NFL (all p > 0.01). Interpretation Having a LOC HI aged 50’s and younger was linked with lower later‐life cognitive function at age ~70 than expected. This may reflect a damaging but small impact of HI; explained in part by smaller BV and different microstructure pathways but not via pathology related to AD (amyloid, hippocampal volume, AD cortical thickness) or ongoing neurodegeneration (serum NFL).
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Affiliation(s)
- Sarah-Naomi James
- MRC Unit for Lifelong Health and Ageing at UCL, University College London, London, United Kingdom.,Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
| | - Jennifer M Nicholas
- Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom.,Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Christopher A Lane
- Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
| | - Thomas D Parker
- Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
| | - Kirsty Lu
- Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
| | - Ashvini Keshavan
- Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
| | - Sarah M Buchanan
- Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
| | - Sarah E Keuss
- Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
| | - Heidi Murray-Smith
- Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
| | - Andrew Wong
- MRC Unit for Lifelong Health and Ageing at UCL, University College London, London, United Kingdom
| | - David M Cash
- Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
| | - Ian B Malone
- Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
| | - Josephine Barnes
- Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
| | - Carole H Sudre
- MRC Unit for Lifelong Health and Ageing at UCL, University College London, London, United Kingdom.,Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom.,School of Biomedical Engineering and Imaging Sciences, King's College London, Institute of Nuclear Medicine, University College London Hospitals, London, United Kingdom.,Centre for Medical Image Computing, Department of Computer Science, University College London, London, United Kingdom
| | - William Coath
- Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
| | - Lloyd Prosser
- Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
| | - Sebastien Ourselin
- School of Biomedical Engineering and Imaging Sciences, King's College London, Institute of Nuclear Medicine, University College London Hospitals, London, United Kingdom
| | - Marc Modat
- Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom.,School of Biomedical Engineering and Imaging Sciences, King's College London, Institute of Nuclear Medicine, University College London Hospitals, London, United Kingdom
| | - David L Thomas
- Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
| | - Jorge Cardoso
- School of Biomedical Engineering and Imaging Sciences, King's College London, Institute of Nuclear Medicine, University College London Hospitals, London, United Kingdom
| | - Amanda Heslegrave
- UK Dementia Research Institute at UCL, University College London, London, United Kingdom.,Department of Neurodegenerative Disease, UCL Institute of Neurology, London, United Kingdom
| | - Henrik Zetterberg
- UK Dementia Research Institute at UCL, University College London, London, United Kingdom.,Department of Neurodegenerative Disease, UCL Institute of Neurology, London, United Kingdom.,Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.,Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
| | - Sebastian J Crutch
- Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
| | - Jonathan M Schott
- Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
| | - Marcus Richards
- MRC Unit for Lifelong Health and Ageing at UCL, University College London, London, United Kingdom
| | - Nick C Fox
- Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom.,UK Dementia Research Institute at UCL, University College London, London, United Kingdom
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TractLearn: A geodesic learning framework for quantitative analysis of brain bundles. Neuroimage 2021; 233:117927. [PMID: 33689863 DOI: 10.1016/j.neuroimage.2021.117927] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 02/25/2021] [Accepted: 03/01/2021] [Indexed: 12/13/2022] Open
Abstract
Deep learning-based convolutional neural networks have recently proved their efficiency in providing fast segmentation of major brain fascicles structures, based on diffusion-weighted imaging. The quantitative analysis of brain fascicles then relies on metrics either coming from the tractography process itself or from each voxel along the bundle. Statistical detection of abnormal voxels in the context of disease usually relies on univariate and multivariate statistics models, such as the General Linear Model (GLM). Yet in the case of high-dimensional low sample size data, the GLM often implies high standard deviation range in controls due to anatomical variability, despite the commonly used smoothing process. This can lead to difficulties to detect subtle quantitative alterations from a brain bundle at the voxel scale. Here we introduce TractLearn, a unified framework for brain fascicles quantitative analyses by using geodesic learning as a data-driven learning task. TractLearn allows a mapping between the image high-dimensional domain and the reduced latent space of brain fascicles using a Riemannian approach. We illustrate the robustness of this method on a healthy population with test-retest acquisition of multi-shell diffusion MRI data, demonstrating that it is possible to separately study the global effect due to different MRI sessions from the effect of local bundle alterations. We have then tested the efficiency of our algorithm on a sample of 5 age-matched subjects referred with mild traumatic brain injury. Our contributions are to propose: 1/ A manifold approach to capture controls variability as standard reference instead of an atlas approach based on a Euclidean mean. 2/ A tool to detect global variation of voxels' quantitative values, which accounts for voxels' interactions in a structure rather than analyzing voxels independently. 3/ A ready-to-plug algorithm to highlight nonlinear variation of diffusion MRI metrics. With this regard, TractLearn is a ready-to-use algorithm for precision medicine.
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Miller LE, Urban JE, Davenport EM, Powers AK, Whitlow CT, Maldjian JA, Stitzel JD. Brain Strain: Computational Model-Based Metrics for Head Impact Exposure and Injury Correlation. Ann Biomed Eng 2021; 49:1083-1096. [PMID: 33258089 PMCID: PMC10032321 DOI: 10.1007/s10439-020-02685-9] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Accepted: 10/20/2020] [Indexed: 12/20/2022]
Abstract
Athletes participating in contact sports are exposed to repetitive subconcussive head impacts that may have long-term neurological consequences. To better understand these impacts and their effects, head impacts are often measured during football to characterize head impact exposure and estimate injury risk. Despite widespread use of kinematic-based metrics, it remains unclear whether any single metric derived from head kinematics is well-correlated with measurable changes in the brain. This shortcoming has motivated the increasing use of finite element (FE)-based metrics, which quantify local brain deformations. Additionally, quantifying cumulative exposure is of increased interest to examine the relationship to brain changes over time. The current study uses the atlas-based brain model (ABM) to predict the strain response to impacts sustained by 116 youth football athletes and proposes 36 new, or derivative, cumulative strain-based metrics that quantify the combined burden of head impacts over the course of a season. The strain-based metrics developed and evaluated for FE modeling and presented in the current study present potential for improved analytics over existing kinematically-based and cumulative metrics. Additionally, the findings highlight the importance of accounting for directional dependence and expand the techniques to explore spatial distribution of the strain response throughout the brain.
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Affiliation(s)
- Logan E Miller
- Department of Biomedical Engineering, Wake Forest School of Medicine, 575 N. Patterson Avenue, Suite 530, Winston-Salem, NC, 27101, USA.
- School of Biomedical Engineering and Sciences, Virginia Tech - Wake Forest University, 575 N. Patterson Avenue, Suite 530, Winston-Salem, NC, 27101, USA.
| | - Jillian E Urban
- Department of Biomedical Engineering, Wake Forest School of Medicine, 575 N. Patterson Avenue, Suite 530, Winston-Salem, NC, 27101, USA
- School of Biomedical Engineering and Sciences, Virginia Tech - Wake Forest University, 575 N. Patterson Avenue, Suite 530, Winston-Salem, NC, 27101, USA
| | - Elizabeth M Davenport
- Department of Radiology, Southwestern Medical School, University of Texas, 5323 Harry Hines Boulevard, Dallas, TX, 75390, USA
| | - Alexander K Powers
- Department of Biomedical Engineering, Wake Forest School of Medicine, 575 N. Patterson Avenue, Suite 530, Winston-Salem, NC, 27101, USA
- Department of Neurosurgery, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157, USA
| | - Christopher T Whitlow
- Department of Biomedical Engineering, Wake Forest School of Medicine, 575 N. Patterson Avenue, Suite 530, Winston-Salem, NC, 27101, USA
- Department of Radiology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157, USA
| | - Joseph A Maldjian
- Department of Radiology, Southwestern Medical School, University of Texas, 5323 Harry Hines Boulevard, Dallas, TX, 75390, USA
| | - Joel D Stitzel
- Department of Biomedical Engineering, Wake Forest School of Medicine, 575 N. Patterson Avenue, Suite 530, Winston-Salem, NC, 27101, USA
- School of Biomedical Engineering and Sciences, Virginia Tech - Wake Forest University, 575 N. Patterson Avenue, Suite 530, Winston-Salem, NC, 27101, USA
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Zane KL, Gfeller JD, Roskos PT, Stout J, Buchanan TW, Malone TM, Bucholz R. Diffusion tensor imaging findings and neuropsychological performance in adults with TBI across the spectrum of severity in the chronic-phase. Brain Inj 2021; 35:536-546. [PMID: 33593218 DOI: 10.1080/02699052.2021.1887521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
PRIMARY OBJECTIVE To examine associations between neuroimaging indicators of cerebral tract integrity and neurocognitive functioning in traumatic brain injury (TBI). RESEARCH DESIGN Between-Groups design with two TBI groups and controls. METHOD AND PROCEDURES Forty-four participants with TBI and 27 matched controls completed diffusion tensor imaging and neuropsychological measures of processing speed, attention, memory, and executive function. Multivariate analyses were conducted to examine group differences in white matter integrity (fractional anisotropy) for 11 regions of interest and cognitive performance among adult males with chronic phase, mild, moderate, or severe TBI. Correlational analyses investigated associations between white matter integrity, brain injury severity, and cognitive status. MAIN OUTCOMES AND RESULTS Participants with moderate or severe TBI exhibited reduced white matter integrity in 8 of 11 ROIs and worse performance on most cognitive measures, relative to control participants. Persons with mild TBI did not differ from controls on white matter integrity values and differed on one measure of processing speed. Significant correlations were found between injury severity ratings and 10 ROIs, most notably between ROIs and measures of processing speed or memory. CONCLUSIONS These findings provide nuanced information regarding white matter connectivity as it relates to neurocognitive abilities across the TBI severity spectrum.
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Affiliation(s)
| | - Jeffrey D Gfeller
- Department of Psychology Saint Louis University, St. Louis, Missouri, USA
| | - P Tyler Roskos
- Department of Physical Medicine and Rehabilitation Beaumont Health, Dearborn, Michigan, USA
| | - Jeff Stout
- National Institute of Mental Health, MEG Core Facility, Bethesda, Maryland, USA
| | - Tony W Buchanan
- Department of Psychology Saint Louis University, St. Louis, Missouri, USA
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Quantitative evaluation of callosal abnormalities in relapsing-remitting multiple sclerosis using diffusion tensor imaging: A systemic review and meta-analysis. Clin Neurol Neurosurg 2021; 201:106442. [DOI: 10.1016/j.clineuro.2020.106442] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Revised: 12/12/2020] [Accepted: 12/14/2020] [Indexed: 01/13/2023]
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Veksler R, Vazana U, Serlin Y, Prager O, Ofer J, Shemen N, Fisher AM, Minaeva O, Hua N, Saar-Ashkenazy R, Benou I, Riklin-Raviv T, Parker E, Mumby G, Kamintsky L, Beyea S, Bowen CV, Shelef I, O'Keeffe E, Campbell M, Kaufer D, Goldstein LE, Friedman A. Slow blood-to-brain transport underlies enduring barrier dysfunction in American football players. Brain 2021; 143:1826-1842. [PMID: 32464655 PMCID: PMC7297017 DOI: 10.1093/brain/awaa140] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Revised: 02/27/2020] [Accepted: 03/11/2020] [Indexed: 12/14/2022] Open
Abstract
Repetitive mild traumatic brain injury in American football players has garnered increasing public attention following reports of chronic traumatic encephalopathy, a progressive tauopathy. While the mechanisms underlying repetitive mild traumatic brain injury-induced neurodegeneration are unknown and antemortem diagnostic tests are not available, neuropathology studies suggest a pathogenic role for microvascular injury, specifically blood–brain barrier dysfunction. Thus, our main objective was to demonstrate the effectiveness of a modified dynamic contrast-enhanced MRI approach we have developed to detect impairments in brain microvascular function. To this end, we scanned 42 adult male amateur American football players and a control group comprising 27 athletes practicing a non-contact sport and 26 non-athletes. MRI scans were also performed in 51 patients with brain pathologies involving the blood–brain barrier, namely malignant brain tumours, ischaemic stroke and haemorrhagic traumatic contusion. Based on data from prolonged scans, we generated maps that visualized the permeability value for each brain voxel. Our permeability maps revealed an increase in slow blood-to-brain transport in a subset of amateur American football players, but not in sex- and age-matched controls. The increase in permeability was region specific (white matter, midbrain peduncles, red nucleus, temporal cortex) and correlated with changes in white matter, which were confirmed by diffusion tensor imaging. Additionally, increased permeability persisted for months, as seen in players who were scanned both on- and off-season. Examination of patients with brain pathologies revealed that slow tracer accumulation characterizes areas surrounding the core of injury, which frequently shows fast blood-to-brain transport. Next, we verified our method in two rodent models: rats and mice subjected to repeated mild closed-head impact injury, and rats with vascular injury inflicted by photothrombosis. In both models, slow blood-to-brain transport was observed, which correlated with neuropathological changes. Lastly, computational simulations and direct imaging of the transport of Evans blue-albumin complex in brains of rats subjected to recurrent seizures or focal cerebrovascular injury suggest that increased cellular transport underlies the observed slow blood-to-brain transport. Taken together, our findings suggest dynamic contrast-enhanced-MRI can be used to diagnose specific microvascular pathology after traumatic brain injury and other brain pathologies.
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Affiliation(s)
- Ronel Veksler
- Departments of Physiology and Cell Biology, Brain and Cognitive Sciences, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Udi Vazana
- Departments of Physiology and Cell Biology, Brain and Cognitive Sciences, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Yonatan Serlin
- Departments of Physiology and Cell Biology, Brain and Cognitive Sciences, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.,Neurology Residency Training Program, McGill University, Montreal, QC, Canada
| | - Ofer Prager
- Departments of Physiology and Cell Biology, Brain and Cognitive Sciences, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Jonathan Ofer
- Departments of Physiology and Cell Biology, Brain and Cognitive Sciences, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Nofar Shemen
- Departments of Physiology and Cell Biology, Brain and Cognitive Sciences, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Andrew M Fisher
- Molecular Aging and Development Laboratory, Boston University School of Medicine, College of Engineering, Alzheimer's Disease and CTE Center, and Photonics Center, Boston University, Boston, MA, USA
| | - Olga Minaeva
- Molecular Aging and Development Laboratory, Boston University School of Medicine, College of Engineering, Alzheimer's Disease and CTE Center, and Photonics Center, Boston University, Boston, MA, USA
| | - Ning Hua
- Molecular Aging and Development Laboratory, Boston University School of Medicine, College of Engineering, Alzheimer's Disease and CTE Center, and Photonics Center, Boston University, Boston, MA, USA
| | - Rotem Saar-Ashkenazy
- Departments of Physiology and Cell Biology, Brain and Cognitive Sciences, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.,Department of Psychology and the School of Social-work, Ashkelon Academic College, Israel
| | - Itay Benou
- Department of Electrical Engineering, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Tammy Riklin-Raviv
- Department of Electrical Engineering, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Ellen Parker
- Department of Medical Neuroscience, Dalhousie University, Faculty of Medicine, Halifax, NS, Canada
| | - Griffin Mumby
- Department of Medical Neuroscience, Dalhousie University, Faculty of Medicine, Halifax, NS, Canada
| | - Lyna Kamintsky
- Department of Medical Neuroscience, Dalhousie University, Faculty of Medicine, Halifax, NS, Canada
| | - Steven Beyea
- Biomedical Translational Imaging Centre (BIOTIC), IWK Health Centre and QEII Health Sciences Center, Dalhousie University, Halifax, NS, Canada
| | - Chris V Bowen
- Biomedical Translational Imaging Centre (BIOTIC), IWK Health Centre and QEII Health Sciences Center, Dalhousie University, Halifax, NS, Canada
| | - Ilan Shelef
- Department of Medical Imaging, Soroka University Medical Center, Beer-Sheva, Israel
| | - Eoin O'Keeffe
- Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland
| | - Matthew Campbell
- Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland
| | - Daniela Kaufer
- Department of Integrative Biology and the Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA
| | - Lee E Goldstein
- Molecular Aging and Development Laboratory, Boston University School of Medicine, College of Engineering, Alzheimer's Disease and CTE Center, and Photonics Center, Boston University, Boston, MA, USA
| | - Alon Friedman
- Departments of Physiology and Cell Biology, Brain and Cognitive Sciences, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.,Department of Medical Neuroscience, Dalhousie University, Faculty of Medicine, Halifax, NS, Canada
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To XV, Nasrallah FA. A roadmap of brain recovery in a mouse model of concussion: insights from neuroimaging. Acta Neuropathol Commun 2021; 9:2. [PMID: 33407949 PMCID: PMC7789702 DOI: 10.1186/s40478-020-01098-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Accepted: 12/01/2020] [Indexed: 12/17/2022] Open
Abstract
Concussion or mild traumatic brain injury is the most common form of traumatic brain injury with potentially long-term consequences. Current objective diagnosis and treatment options are limited to clinical assessment, cognitive rest, and symptom management, which raises the real danger of concussed patients being released back into activities where subsequent and cumulative injuries may cause disproportionate damages. This study conducted a cross-sectional multi-modal examination investigation of the temporal changes in behavioural and brain changes in a mouse model of concussion using magnetic resonance imaging. Sham and concussed mice were assessed at day 2, day 7, and day 14 post-sham or injury procedures following a single concussion event for motor deficits, psychological symptoms with open field assessment, T2-weighted structural imaging, diffusion tensor imaging (DTI), neurite orientation density dispersion imaging (NODDI), stimulus-evoked and resting-state functional magnetic resonance imaging (fMRI). Overall, a mismatch in the temporal onsets and durations of the behavioural symptoms and structural/functional changes in the brain was seen. Deficits in behaviour persisted until day 7 post-concussion but recovered at day 14 post-concussion. DTI and NODDI changes were most extensive at day 7 and persisted in some regions at day 14 post-concussion. A persistent increase in connectivity was seen at day 2 and day 14 on rsfMRI. Stimulus-invoked fMRI detected increased cortical activation at day 7 and 14 post-concussion. Our results demonstrate the capabilities of advanced MRI in detecting the effects of a single concussive impact in the brain, and highlight a mismatch in the onset and temporal evolution of behaviour, structure, and function after a concussion. These results have significant translational impact in developing methods for the detection of human concussion and the time course of brain recovery.
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Mahan MY, Rafter DJ, Truwit CL, Oswood M, Samadani U. Evaluation of diffusion measurements reveals radial diffusivity indicative of microstructural damage following acute, mild traumatic brain injury. Magn Reson Imaging 2020; 77:137-147. [PMID: 33359428 DOI: 10.1016/j.mri.2020.12.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Revised: 10/25/2020] [Accepted: 12/20/2020] [Indexed: 01/07/2023]
Abstract
PURPOSE Mild TBI, characterized by microstructural damage, often undetectable on conventional imaging techniques, is a pervasive condition that disturbs brain function and can potentially result in long-term deficits. Deciphering the underlying microstructural damage in mild TBI is crucial for establishing a reliable diagnosis and enabling effective therapeutics. Efforts to capture this damage have been extensive, but results have been inconsistent and incomplete. METHODS To that effect, we set out to examine the shape of the diffusion tensor in mild TBI during the acute phase of injury. We inspected diffusivity and geometric measurements describing the diffusion tensor's shape and compared mild TBI (N = 34, 20.4-66.6 yo) measurements with those from healthy control (N = 42, 20.7-67.2 yo) participants using voxelwise tract-based spatial statistics. Subsequently, to explore associations between the diffusion measurements in mild TBI, we performed nonparametric statistics and machine learning techniques. RESULTS Overall, mild TBI displayed a diffuse increase in Dλ2, Dλ3, Dradial, Dmean, and Cspherical, with a diffuse decrease in Afractional, Amode, and Clinear, in addition to no change in Daxial or Cplanar. Most notably, our results provide evidence for Dradial as a potential biomarker for microstructural damage, specifically its main component Dλ2, based on their performance in discriminating between mild TBI and control groups. Afractional was also found to be important for discriminating between groups. CONCLUSION Our results revealed the importance of a diffusion measurement often overlooked, Dradial, in assessing TBI and suggest differentiating diffusion measurements has the potential utility to detect variations in the underlying pathophysiology after injury.
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Affiliation(s)
- Margaret Y Mahan
- Department of Biomedical Informatics and Computational Biology, University of Minnesota, 101 Pleasant St SE, Minneapolis, MN 55455, USA.
| | - Daniel J Rafter
- Department of Biomedical Informatics and Computational Biology, University of Minnesota, 101 Pleasant St SE, Minneapolis, MN 55455, USA
| | - Charles L Truwit
- Diagnostic Imaging, Philips Global, 6655 Wedgwood Rd N #105, Maple Grove, MN 55311, USA; Department of Radiology, Hennepin Healthcare, 701 Park Ave, Minneapolis, MN 55415, USA.
| | - Mark Oswood
- Department of Radiology, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN 55455, USA; Department of Radiology, Hennepin Healthcare, 701 Park Ave, Minneapolis, MN 55415, USA.
| | - Uzma Samadani
- Department of Biomedical Informatics and Computational Biology, University of Minnesota, 101 Pleasant St SE, Minneapolis, MN 55455, USA; Department of Neurosurgery, Minneapolis VA Medical Center, 1 Veterans Drive, Minneapolis, MN 55417, USA.
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Trillingsgaard Naess-Schmidt E, Udby Blicher J, Møller Thastum M, Ulrikka Rask C, Wulff Svendsen S, Schröder A, Høgh Tuborgh A, Østergaard L, Sangill R, Lund T, Nørhøj Jespersen S, Roer Pedersen A, Hansen B, Fristed Eskildsen S, Feldbaek Nielsen J. Microstructural changes in the brain after long-term post-concussion symptoms: A randomized trial. J Neurosci Res 2020; 99:872-886. [PMID: 33319932 DOI: 10.1002/jnr.24773] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Accepted: 11/25/2020] [Indexed: 01/17/2023]
Abstract
A recent randomized controlled trial in young patients with long-term post-concussion symptoms showed that a novel behavioral intervention "Get going After concussIoN" is superior to enhanced usual care in terms of symptom reduction. It is unknown whether these interventional effects are associated with microstructural brain changes. The aim of this study was to examine whether diffusion-weighted MRI indices, which are sensitive to the interactions between cellular structures and water molecules' Brownian motion, respond differently to the interventions of the above-mentioned trial and whether such differences correlate with the improvement of post-concussion symptoms. Twenty-three patients from the intervention group (mean age 22.8, 18 females) and 19 patients from the control group (enhanced usual care) (mean age 23.9, 14 females) were enrolled. The primary outcome measure was the mean kurtosis tensor, which is sensitive to the microscopic complexity of brain tissue. The mean kurtosis tensor was significantly increased in the intervention group (p = 0.003) in the corpus callosum but not in the thalamus (p = 0.78) and the hippocampus (p = 0.34). An increase in mean kurtosis tensor in the corpus callosum tended to be associated with a reduction in symptoms, but this association did not reach significance (p = 0.059). Changes in diffusion tensor imaging metrics did not differ between intervention groups and were not associated with symptoms. The current study found different diffusion-weighted MRI responses from the microscopic cellular structures of the corpus callosum between patients receiving a novel behavioral intervention and patients receiving enhanced usual care. Correlations with improvement of post-concussion symptoms were not evident.
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Affiliation(s)
- Erhard Trillingsgaard Naess-Schmidt
- Hammel Neurorehabilitation Centre and University Research Clinic, Hammel, Denmark.,Department of Clinical Health, Aarhus University, Aarhus, Denmark
| | - Jakob Udby Blicher
- Department of Clinical Medicine, Center of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark
| | - Mille Møller Thastum
- Hammel Neurorehabilitation Centre and University Research Clinic, Hammel, Denmark.,Department of Clinical Health, Aarhus University, Aarhus, Denmark
| | - Charlotte Ulrikka Rask
- Department of Child and Adolescent Psychiatry, Aarhus University Hospital, Aarhus, Denmark
| | - Susanne Wulff Svendsen
- Department of Occupational and Environmental Medicine, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Andreas Schröder
- Research Clinic for Functional Disorders and Psychosomatics, Aarhus University Hospital, Aarhus, Denmark
| | - Astrid Høgh Tuborgh
- Department of Child and Adolescent Psychiatry, Aarhus University Hospital, Aarhus, Denmark
| | - Leif Østergaard
- Department of Clinical Medicine, Center of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark.,Department of Neuroradiology, Aarhus University Hospital, Aarhus, Denmark
| | - Ryan Sangill
- Department of Clinical Medicine, Center of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark
| | - Torben Lund
- Department of Clinical Medicine, Center of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark
| | - Sune Nørhøj Jespersen
- Department of Clinical Medicine, Center of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark.,Department of Physics and Astronomy, Aarhus University, Aarhus, Denmark
| | - Asger Roer Pedersen
- Hammel Neurorehabilitation Centre and University Research Clinic, Hammel, Denmark.,Department of Clinical Health, Aarhus University, Aarhus, Denmark
| | - Brian Hansen
- Department of Clinical Medicine, Center of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark
| | - Simon Fristed Eskildsen
- Department of Clinical Medicine, Center of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark
| | - Jørgen Feldbaek Nielsen
- Hammel Neurorehabilitation Centre and University Research Clinic, Hammel, Denmark.,Department of Clinical Health, Aarhus University, Aarhus, Denmark
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47
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Mohammadian M, Roine T, Hirvonen J, Kurki T, Posti JP, Katila AJ, Takala RSK, Tallus J, Maanpää HR, Frantzén J, Hutchinson PJ, Newcombe VF, Menon DK, Tenovuo O. Alterations in Microstructure and Local Fiber Orientation of White Matter Are Associated with Outcome after Mild Traumatic Brain Injury. J Neurotrauma 2020; 37:2616-2623. [PMID: 32689872 DOI: 10.1089/neu.2020.7081] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
Mild traumatic brain injury (mTBI) can have long-lasting consequences. We investigated white matter (WM) alterations at 6-12 months following mTBI using diffusion tensor imaging (DTI) and assessed if the alterations associate with outcome. Eighty-five patients with mTBI underwent diffusion-weighted magnetic resonance imaging (MRI) on average 8 months post-injury and patients' outcome was assessed at the time of imaging using the Glasgow Outcome Scale-Extended (GOS-E). Additionally, 30 age-matched patients with extracranial orthopedic injuries were used as control subjects. Voxel-wise analysis of the data was performed using a tract-based spatial statistics (TBSS) approach and differences in microstructural metrics between groups were investigated. Further, the susceptibility of the abnormalities to specific fiber orientations was investigated by analyzing the first eigenvector of the diffusion tensor in the voxels with significant differences. We found significantly lower fractional anisotropy (FA) and higher mean diffusivity (MD) and radial diffusivity (RD) in patients with mTBI compared with control subjects, whereas no significant differences were observed in axial diffusivity (AD) between the groups. The differences were present bilaterally in several WM regions and correlated with outcome. Moreover, multiple clusters were found in the principal fiber orientations of the significant voxels in anisotropy, and similar orientation patterns were found for the diffusivity metrics. These directional clusters correlated with patients' functional outcome. Our study showed that mTBI is associated with WM changes at the chronic stage and these alterations occur in several WM regions. In addition, several significant clusters of WM alterations in specific fiber orientations were found and these clusters were associated with outcome.
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Affiliation(s)
- Mehrbod Mohammadian
- Department of Clinical Neurosciences, Intensive Care, Emergency Care and Pain Medicine, University of Turku, Turku, Finland.,Turku Brain Injury Center, Intensive Care Medicine and Pain Management, Turku University Hospital, Turku, Finland
| | - Timo Roine
- Turku Brain and Mind Center, Intensive Care, Emergency Care and Pain Medicine, University of Turku, Turku, Finland.,Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Espoo, Finland
| | - Jussi Hirvonen
- Department of Radiology, Intensive Care, Emergency Care and Pain Medicine, University of Turku, Turku, Finland
| | - Timo Kurki
- Department of Clinical Neurosciences, Intensive Care, Emergency Care and Pain Medicine, University of Turku, Turku, Finland.,Turku Brain Injury Center, Intensive Care Medicine and Pain Management, Turku University Hospital, Turku, Finland.,Department of Radiology, Intensive Care, Emergency Care and Pain Medicine, University of Turku, Turku, Finland
| | - Jussi P Posti
- Department of Clinical Neurosciences, Intensive Care, Emergency Care and Pain Medicine, University of Turku, Turku, Finland.,Turku Brain Injury Center, Intensive Care Medicine and Pain Management, Turku University Hospital, Turku, Finland.,Department of Neurosurgery, Division of Clinical Neurosciences, Intensive Care Medicine and Pain Management, Turku University Hospital, Turku, Finland
| | - Ari J Katila
- Perioperative Services, Intensive Care Medicine and Pain Management, Turku University Hospital, Turku, Finland.,Anesthesiology, Intensive Care, Emergency Care and Pain Medicine, University of Turku, Turku, Finland
| | - Riikka S K Takala
- Perioperative Services, Intensive Care Medicine and Pain Management, Turku University Hospital, Turku, Finland.,Anesthesiology, Intensive Care, Emergency Care and Pain Medicine, University of Turku, Turku, Finland
| | - Jussi Tallus
- Department of Clinical Neurosciences, Intensive Care, Emergency Care and Pain Medicine, University of Turku, Turku, Finland.,Turku Brain Injury Center, Intensive Care Medicine and Pain Management, Turku University Hospital, Turku, Finland
| | - Henna-Riikka Maanpää
- Turku Brain Injury Center, Intensive Care Medicine and Pain Management, Turku University Hospital, Turku, Finland.,Department of Neurosurgery, Division of Clinical Neurosciences, Intensive Care Medicine and Pain Management, Turku University Hospital, Turku, Finland
| | - Janek Frantzén
- Department of Clinical Neurosciences, Intensive Care, Emergency Care and Pain Medicine, University of Turku, Turku, Finland.,Department of Neurosurgery, Division of Clinical Neurosciences, Intensive Care Medicine and Pain Management, Turku University Hospital, Turku, Finland
| | - Peter J Hutchinson
- Department of Clinical Neurosciences, Neurosurgery Unit, Addenbrooke's Hospital, Cambridge, United Kingdom
| | | | - David K Menon
- Division of Anesthesia, Addenbrooke's Hospital, Cambridge, United Kingdom
| | - Olli Tenovuo
- Department of Clinical Neurosciences, Intensive Care, Emergency Care and Pain Medicine, University of Turku, Turku, Finland.,Turku Brain Injury Center, Intensive Care Medicine and Pain Management, Turku University Hospital, Turku, Finland
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48
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Kawata K, Steinfeldt JA, Huibregtse ME, Nowak MK, Macy JT, Kercher K, Rettke DJ, Shin A, Chen Z, Ejima K, Newman SD, Cheng H. Association Between Proteomic Blood Biomarkers and DTI/NODDI Metrics in Adolescent Football Players: A Pilot Study. Front Neurol 2020; 11:581781. [PMID: 33304306 PMCID: PMC7701105 DOI: 10.3389/fneur.2020.581781] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Accepted: 10/08/2020] [Indexed: 12/11/2022] Open
Abstract
While neuroimaging and blood biomarker have been two of the most active areas of research in the neurotrauma community, these fields rarely intersect to delineate subconcussive brain injury. The aim of the study was to examine the association between diffusion MRI techniques [diffusion tensor imaging (DTI) and neurite orientation/dispersion density imaging (NODDI)] and brain-injury blood biomarker levels [tau, neurofilament-light (NfL), glial-fibrillary-acidic-protein (GFAP)] in high-school football players at their baseline, aiming to detect cumulative neuronal damage from prior seasons. Twenty-five football players were enrolled in the study. MRI measures and blood samples were obtained during preseason data collection. The whole-brain, tract-based spatial statistics was conducted for six diffusion metrics: fractional anisotropy (FA), mean diffusivity (MD), axial/radial diffusivity (AD, RD), neurite density index (NDI), and orientation dispersion index (ODI). Five players were ineligible for MRIs, and three serum samples were excluded due to hemolysis, resulting in 17 completed set of diffusion metrics and blood biomarker levels for association analysis. Our permutation-based regression model revealed that serum tau levels were significantly associated with MD and NDI in various axonal tracts; specifically, elevated serum tau levels correlated to elevated MD (p = 0.0044) and reduced NDI (p = 0.016) in the corpus callosum and surrounding white matter tracts (e.g., longitudinal fasciculus). Additionally, there was a negative association between NfL and ODI in the focal area of the longitudinal fasciculus. Our data suggest that high school football players may develop axonal microstructural abnormality in the corpus callosum and surrounding white matter tracts, such as longitudinal fasciculus. A future study is warranted to determine the longitudinal multimodal relationship in response to repetitive exposure to sports-related head impacts.
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Affiliation(s)
- Keisuke Kawata
- Department of Kinesiology, School of Public Health-Bloomington, Indiana University, Bloomington, IN, United States
- Program in Neuroscience, College of Arts and Sciences, Indiana University, Bloomington, IN, United States
| | - Jesse A. Steinfeldt
- Department of Counseling and Educational Psychology, School of Education, Indiana University, Bloomington, IN, United States
| | - Megan E. Huibregtse
- Department of Kinesiology, School of Public Health-Bloomington, Indiana University, Bloomington, IN, United States
| | - Madeleine K. Nowak
- Department of Kinesiology, School of Public Health-Bloomington, Indiana University, Bloomington, IN, United States
| | - Jonathan T. Macy
- Department of Applied Health Science, School of Public Health-Bloomington, Indiana University, Bloomington, IN, United States
| | - Kyle Kercher
- Department of Applied Health Science, School of Public Health-Bloomington, Indiana University, Bloomington, IN, United States
| | - Devin J. Rettke
- Department of Kinesiology, School of Public Health-Bloomington, Indiana University, Bloomington, IN, United States
| | - Andrea Shin
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, United States
| | - Zhongxue Chen
- Department of Epidemiology and Biostatistics, School of Public Health-Bloomington, Indiana University, Bloomington, IN, United States
| | - Keisuke Ejima
- Department of Epidemiology and Biostatistics, School of Public Health-Bloomington, Indiana University, Bloomington, IN, United States
| | - Sharlene D. Newman
- Department of Psychological and Brain Sciences, College of Arts and Sciences, Indiana University, Bloomington, IN, United States
- Alabama Life Research Institute, University of Alabama, Tuscaloosa, AL, United States
| | - Hu Cheng
- Program in Neuroscience, College of Arts and Sciences, Indiana University, Bloomington, IN, United States
- Department of Psychological and Brain Sciences, College of Arts and Sciences, Indiana University, Bloomington, IN, United States
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49
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Mahan MY, Samadani U. Editorial. Lessons from the failure of diffusion tensor imaging to differentiate concussed from nonconcussed NFL players. J Neurosurg 2020; 133:1059-1062. [PMID: 31491767 DOI: 10.3171/2019.5.jns19892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
| | - Uzma Samadani
- Departments of1Bioinformatics and Computational Biology
- 2Neurosurgery, and
- 3Neuroscience, University of Minnesota, Minneapolis, Minnesota
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50
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Diekfuss JA, Yuan W, Barber Foss KD, Dudley JA, DiCesare CA, Reddington DL, Zhong W, Nissen KS, Shafer JL, Leach JL, Bonnette S, Logan K, Epstein JN, Clark J, Altaye M, Myer GD. The effects of internal jugular vein compression for modulating and preserving white matter following a season of American tackle football: A prospective longitudinal evaluation of differential head impact exposure. J Neurosci Res 2020; 99:423-445. [PMID: 32981154 DOI: 10.1002/jnr.24727] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 08/27/2020] [Indexed: 01/17/2023]
Abstract
The purpose of this clinical trial was to examine whether internal jugular vein compression (JVC)-using an externally worn neck collar-modulated the relationships between differential head impact exposure levels and pre- to postseason changes in diffusion tensor imaging (DTI)-derived diffusivity and anisotropy metrics of white matter following a season of American tackle football. Male high-school athletes (n = 284) were prospectively assigned to a non-collar group or a collar group. Magnetic resonance imaging data were collected from participants pre- and postseason and head impact exposure was monitored by accelerometers during every practice and game throughout the competitive season. Athletes' accumulated head impact exposure was systematically thresholded based on the frequency of impacts of progressively higher magnitudes (10 g intervals between 20 to 150 g) and modeled with pre- to postseason changes in DTI measures of white matter as a function of JVC neck collar wear. The findings revealed that the JVC neck collar modulated the relationships between greater high-magnitude head impact exposure (110 to 140 g) and longitudinal changes to white matter, with each group showing associations that varied in directionality. Results also revealed that the JVC neck collar group partially preserved longitudinal changes in DTI metrics. Collectively, these data indicate that a JVC neck collar can provide a mechanistic response to the diffusion and anisotropic properties of brain white matter following the highly diverse exposure to repetitive head impacts in American tackle football. Clinicaltrials.gov: NCT# 04068883.
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Affiliation(s)
- Jed A Diekfuss
- The SPORT Center, Division of Sports Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Weihong Yuan
- Pediatric Neuroimaging Research Consortium, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.,Departments of Pediatrics and Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Kim D Barber Foss
- The SPORT Center, Division of Sports Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Jonathan A Dudley
- Pediatric Neuroimaging Research Consortium, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Christopher A DiCesare
- The SPORT Center, Division of Sports Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Danielle L Reddington
- The SPORT Center, Division of Sports Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Wen Zhong
- The SPORT Center, Division of Sports Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.,Departments of Pediatrics and Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Katharine S Nissen
- The SPORT Center, Division of Sports Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Jessica L Shafer
- The SPORT Center, Division of Sports Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - James L Leach
- Division of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Scott Bonnette
- The SPORT Center, Division of Sports Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Kelsey Logan
- The SPORT Center, Division of Sports Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Jeffery N Epstein
- Departments of Pediatrics and Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA.,Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's Medical Center, Cincinnati, OH, USA
| | - Joseph Clark
- Departments of Pediatrics and Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Mekibib Altaye
- Departments of Pediatrics and Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA.,Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Gregory D Myer
- The SPORT Center, Division of Sports Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.,Departments of Pediatrics and Orthopaedic Surgery, University of Cincinnati, Cincinnati, OH, USA.,The Micheli Center for Sports Injury Prevention, Waltham, MA, USA
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