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Darwish OI, Koch V, Vogl TJ, Wolf M, Schregel K, Purushotham A, Vilgrain V, Paradis V, Neji R, Sinkus R. MR Elastography Using the Gravitational Transducer. SENSORS (BASEL, SWITZERLAND) 2024; 24:8038. [PMID: 39771774 PMCID: PMC11679839 DOI: 10.3390/s24248038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 12/02/2024] [Accepted: 12/12/2024] [Indexed: 01/11/2025]
Abstract
MR elastography is a non-invasive imaging technique that provides quantitative maps of tissue biomechanical properties, i.e., elasticity and viscosity. Currently, hepatic MR elastography is deployed in the clinic to assess liver fibrosis in MAFLD patients. In addition, research has demonstrated MR elastography's ability to non-invasively assess chronic liver disease and to characterize breast cancer lesions and brain tumors. MR elastography requires efficient mechanical wave generation and penetration, motion-sensitized MRI sequences, and MR elastography inversion algorithms to retrieve the biomechanical properties of the tissue. MR elastography promises to enable non-invasive and versatile assessment of tissue, leading to better diagnosis and staging of several clinical conditions.
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Affiliation(s)
- Omar Isam Darwish
- Research Department of Imaging Physics and Engineering, School of Biomedical Engineering and Imaging Sciences, King’s College London, London WC2R 2LS, UK; (R.N.)
- MR Predevelopment, Siemens Healthineers, 91052 Erlangen, Germany
| | - Vitali Koch
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, 60629 Frankfurt am Main, Germany
| | - Thomas J. Vogl
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, 60629 Frankfurt am Main, Germany
| | - Marcos Wolf
- Centre for Medical Physics and Biomedical Engineering, Medical University of Vienna, 1090 Vienna, Austria
| | - Katharina Schregel
- Department of Neuroradiology, Heidelberg University Hospital, 69120 Heidelberg, Germany
| | - Arnie Purushotham
- School of Cancer & Pharmaceutical Sciences, King’s College London, London WC2R 2LS, UK
| | - Valérie Vilgrain
- INSERM, Centre de Recherche sur l’Inflammation, Universite Paris Cite, 45018 Paris, France
- Department of Radiology, Hospital Beaujon, 92110 Clichy, France
| | - Valérie Paradis
- INSERM, Centre de Recherche sur l’Inflammation, Universite Paris Cite, 45018 Paris, France
- Department of Pathology, Hospital Beaujon, 92110 Clichy, France
| | - Radhouene Neji
- Research Department of Imaging Physics and Engineering, School of Biomedical Engineering and Imaging Sciences, King’s College London, London WC2R 2LS, UK; (R.N.)
| | - Ralph Sinkus
- Research Department of Imaging Physics and Engineering, School of Biomedical Engineering and Imaging Sciences, King’s College London, London WC2R 2LS, UK; (R.N.)
- Laboratory for Vascular Translational Science (LVTS), INSERM U1148, 75877 Paris, France
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Jamshidi MH, Karami A, Keshavarz A, Fatemi A, Ghanavati S. Magnetic Resonance Elastography for Breast Cancer Diagnosis Through the Assessment of Tissue Biomechanical Properties. Health Sci Rep 2024; 7:e70253. [PMID: 39669189 PMCID: PMC11635177 DOI: 10.1002/hsr2.70253] [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: 06/11/2024] [Revised: 11/06/2024] [Accepted: 11/20/2024] [Indexed: 12/14/2024] Open
Abstract
Background and Aim Breast cancer and normal breast tissue exhibit different degrees of stiffness, indicating distinct biomechanical properties. Study results reveal that breast cancer tissue is several times stiffer than normal breast tissue. These variations can serve as indicative factors for imaging purposes. Depicting markers can significantly enhance the process of breast cancer diagnosis and treatment. This article provides a brief review of the biomechanical properties of breast cancer tissue, highlighting the role of the magnetic resonance elastography (MRE) technique in utilizing these properties for diagnosing breast cancer. Methods In breast MRE, low-frequency shear waves are employed to measure breast stiffness. This method not only offers a quantitative diagnosis but also generates an elastogram, determining the stiffness of each area through its colors. Results MRE represents a diagnostic technique with heightened sensitivity, based on depicting the viscoelasticity properties of breast tissue and describing tumors in terms of biomechanical properties. Combining tissue biomechanical properties, such as tissue stiffness, with contrast-enhanced breast Magnetic Resonance Imaging (MRI) leads to tumor diagnosis. The value of MRE in oncological imaging aims at the early detection of tumors and evaluating the prognosis of breast cancer. Conclusion Breast MRE can identify the reduction of interstitial pressure in tumors by detecting changes in tissue stiffness, making it an effective tool for monitoring treatment responses. This technique is safe, repeatable, and highly precise, significantly aiding in patient screening.
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Affiliation(s)
- Mohammad Hossein Jamshidi
- Department of Medical Imaging and Radiation Sciences, School of Allied Medical SciencesAhvaz Jundishapur University of Medical SciencesAhvazIran
| | - Aida Karami
- Department of Medical Imaging and Radiation Sciences, School of Allied Medical SciencesAhvaz Jundishapur University of Medical SciencesAhvazIran
| | - Amirhesam Keshavarz
- Department of Anatomical Science, Faculty of MedicineAhvaz Jundishapur University of Medical SciencesAhvazIran
| | - Ali Fatemi
- Department of PhysicsJackson State UniversityJacksonMississippiUSA
- Department of Radiation OncologyGamma Knife CenterJacksonMississippiUSA
| | - Sepehr Ghanavati
- Department of Medicine, School of MedicineAhvaz Jundishapur University of Medical SciencesAhvazIran
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Meyer T, Castelein J, Schattenfroh J, Sophie Morr A, Vieira da Silva R, Tzschätzsch H, Reiter R, Guo J, Sack I. Magnetic resonance elastography in a nutshell: Tomographic imaging of soft tissue viscoelasticity for detecting and staging disease with a focus on inflammation. PROGRESS IN NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY 2024; 144-145:1-14. [PMID: 39645347 DOI: 10.1016/j.pnmrs.2024.05.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Revised: 05/24/2024] [Accepted: 05/27/2024] [Indexed: 12/09/2024]
Abstract
Magnetic resonance elastography (MRE) is an emerging clinical imaging modality for characterizing the viscoelastic properties of soft biological tissues. MRE shows great promise in the noninvasive diagnosis of various diseases, especially those associated with soft tissue changes involving the extracellular matrix, cell density, or fluid turnover including altered blood perfusion - all hallmarks of inflammation from early events to cancer development. This review covers the fundamental principles of measuring tissue viscoelasticity by MRE, which are based on the stimulation and encoding of shear waves and their conversion into parameter maps of mechanical properties by inverse problem solutions of the wave equation. Technical challenges posed by real-world biological tissue properties such as viscosity, heterogeneity, anisotropy, and nonlinear elastic behavior of tissues are discussed. Applications of MRE measurement in both humans and animal models are presented, with emphasis on the detection, characterization, and staging of diseases related to the cascade of biomechanical property changes from early to chronic inflammation in the liver and brain. Overall, MRE provides valuable insights into the biophysics of soft tissues for imaging-based detection and staging of inflammation-associated tissue changes.
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Affiliation(s)
- Tom Meyer
- Department of Radiology, Charité - Universitätsmedizin Berlin, Germany
| | - Johannes Castelein
- Department of Radiology & Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Netherlands; Department for Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
| | | | - Anna Sophie Morr
- Department of Radiology, Charité - Universitätsmedizin Berlin, Germany
| | - Rafaela Vieira da Silva
- Experimental and Clinical Research Center, a cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité - Universitätsmedizin Berlin, Germany
| | - Heiko Tzschätzsch
- Institute of Medical Informatics, Charité - Universitätsmedizin Berlin, Germany
| | - Rolf Reiter
- Department of Radiology, Charité - Universitätsmedizin Berlin, Germany
| | - Jing Guo
- Department of Radiology, Charité - Universitätsmedizin Berlin, Germany
| | - Ingolf Sack
- Department of Radiology, Charité - Universitätsmedizin Berlin, Germany.
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Vessella T, Xiang S, Xiao C, Stilwell M, Fok J, Shohet J, Rozen E, Zhou HS, Wen Q. DDR2 signaling and mechanosensing orchestrate neuroblastoma cell fate through different transcriptome mechanisms. FEBS Open Bio 2024; 14:867-882. [PMID: 38538106 PMCID: PMC11073507 DOI: 10.1002/2211-5463.13798] [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: 11/12/2023] [Revised: 01/24/2024] [Accepted: 03/18/2024] [Indexed: 05/07/2024] Open
Abstract
The extracellular matrix (ECM) regulates carcinogenesis by interacting with cancer cells via cell surface receptors. Discoidin Domain Receptor 2 (DDR2) is a collagen-activated receptor implicated in cell survival, growth, and differentiation. Dysregulated DDR2 expression has been identified in various cancer types, making it as a promising therapeutic target. Additionally, cancer cells exhibit mechanosensing abilities, detecting changes in ECM stiffness, which is particularly important for carcinogenesis given the observed ECM stiffening in numerous cancer types. Despite these, whether collagen-activated DDR2 signaling and ECM stiffness-induced mechanosensing exert similar effects on cancer cell behavior and whether they operate through analogous mechanisms remain elusive. To address these questions, we performed bulk RNA sequencing (RNA-seq) on human SH-SY5Y neuroblastoma cells cultured on collagen-coated substrates. Our results show that DDR2 downregulation induces significant changes in the cell transcriptome, with changes in expression of 15% of the genome, specifically affecting the genes associated with cell division and differentiation. We validated the RNA-seq results by showing that DDR2 knockdown redirects the cell fate from proliferation to senescence. Like DDR2 knockdown, increasing substrate stiffness diminishes cell proliferation. Surprisingly, RNA-seq indicates that substrate stiffness has no detectable effect on the transcriptome. Furthermore, DDR2 knockdown influences cellular responses to substrate stiffness changes, highlighting a crosstalk between these two ECM-induced signaling pathways. Based on our results, we propose that the ECM could activate DDR2 signaling and mechanosensing in cancer cells to orchestrate their cell fate through distinct mechanisms, with or without involving gene expression, thus providing novel mechanistic insights into cancer progression.
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Affiliation(s)
- Theadora Vessella
- Department of Chemical EngineeringWorcester Polytechnic InstituteMAUSA
| | | | - Cong Xiao
- Nash Family Department of Neuroscience, Friedman Brain InstituteIcahn School of Medicine at Mount SinaiNew YorkNYUSA
- Black Family Stem Cell InstituteIcahn School of Medicine at Mount SinaiNew YorkNYUSA
| | - Madelyn Stilwell
- Department of Biomedical EngineeringWichita State UniversityKSUSA
| | - Jaidyn Fok
- Department of NeurobiologyUniversity of Massachusetts Medical SchoolWorcesterMAUSA
| | - Jason Shohet
- Department of PediatricsUniversity of Massachusetts Medical SchoolWorcesterMAUSA
| | - Esteban Rozen
- Department of PediatricsUniversity of Massachusetts Medical SchoolWorcesterMAUSA
- Crnic Institute Boulder Branch, BioFrontiers InstituteUniversity of Colorado BoulderCOUSA
| | - H. Susan Zhou
- Department of Chemical EngineeringWorcester Polytechnic InstituteMAUSA
| | - Qi Wen
- Department of PhysicsWorcester Polytechnic InstituteMAUSA
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Lee HJ, Cho SB, Lee JK, Kim JS, Oh CH, Kim HJ, Yoon H, Ahn HK, Kim M, Hwang YG, Kwon HY, Hwang MJ. The feasibility of MR elastography with transpelvic vibration for localization of focal prostate lesion. Sci Rep 2024; 14:3864. [PMID: 38366042 PMCID: PMC10873507 DOI: 10.1038/s41598-024-54341-0] [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: 11/16/2023] [Accepted: 02/12/2024] [Indexed: 02/18/2024] Open
Abstract
We aimed to evaluate the feasibility of MR elastography (MRE) using a transpelvic approach. Thirty-one patients who underwent prostate MRE and had a pathological diagnosis were included in this study. MRE was obtained using a passive driver placed at the umbilicus and iliac crests. The shear stiffness, clinical data, and conventional imaging findings of prostate cancer and benign prostatic hyperplasia (BPH) were compared. Inter-reader agreements were evaluated using the intraclass coefficient class (ICC). Prostate MRE was successfully performed for all patients (100% technical success rate). Nineteen cancer and 10 BPH lesions were visualized on MRE. The mean shear stiffness of cancer was significantly higher than that of BPH (5.99 ± 1.46 kPa vs. 4.67 ± 1.54 kPa, p = 0.045). One cancer was detected on MRE but not on conventional sequences. Six tiny cancer lesions were not visualized on MRE. The mean size of cancers that were not detected on MRE was smaller than that of cancers that were visible on MRE (0.8 ± 0.3 cm vs. 2.3 ± 1.8 cm, p = 0.001). The inter-reader agreement for interpreting MRE was excellent (ICC = 0.95). Prostate MRE with transpelvic vibration is feasible without intracavitary actuators. Transpelvic prostate MRE is reliable for detecting focal lesions, including clinically significant prostate cancer and BPH.
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Affiliation(s)
- Hyo Jeong Lee
- Department of Radiology, Ewha Womans University College of Medicine, Seoul, South Korea
| | - Soo Buem Cho
- Department of Radiology, Ewha Womans University College of Medicine, Seoul, South Korea.
| | - Jeong Kyong Lee
- Department of Radiology, Ewha Womans University College of Medicine, Seoul, South Korea
| | - Jin Sil Kim
- Department of Radiology, Ewha Womans University College of Medicine, Seoul, South Korea
| | - Chang Hoon Oh
- Department of Radiology, Ewha Womans University College of Medicine, Seoul, South Korea
| | - Hyun Jin Kim
- Department of Radiology, Ewha Womans University College of Medicine, Seoul, South Korea
| | - Hana Yoon
- Department of Urology, Ewha Womans University College of Medicine, Seoul, South Korea
| | - Hyun Kyu Ahn
- Department of Urology, Ewha Womans University College of Medicine, Seoul, South Korea
| | - Myong Kim
- Department of Urology, Ewha Womans University College of Medicine, Seoul, South Korea
| | - Yeok Gu Hwang
- Department of Orthopedic Surgery, Ewha Womans University College of Medicine, Seoul, South Korea
| | - Hye Young Kwon
- Department of Radiology, Chungnam National University College of Medicine, Daejeon, South Korea
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Wolf M, Darwish O, Neji R, Eder M, Sunder-Plassmann G, Heinz G, Robinson SD, Schmid AI, Moser EV, Sinkus R, Meyerspeer M. Magnetic resonance elastography resolving all gross anatomical segments of the kidney during controlled hydration. Front Physiol 2024; 15:1327407. [PMID: 38384795 PMCID: PMC10880033 DOI: 10.3389/fphys.2024.1327407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Accepted: 01/24/2024] [Indexed: 02/23/2024] Open
Abstract
Introduction: Magnetic resonance elastography (MRE) is a non-invasive method to quantify biomechanical properties of human tissues. It has potential in diagnosis and monitoring of kidney disease, if established in clinical practice. The interplay of flow and volume changes in renal vessels, tubule, urinary collection system and interstitium is complex, but physiological ranges of in vivo viscoelastic properties during fasting and hydration have never been investigated in all gross anatomical segments simultaneously. Method: Ten healthy volunteers underwent two imaging sessions, one following a 12-hour fasting period and the second after a drinking challenge of >10 mL per kg body weight (60-75 min before the second examination). High-resolution renal MRE was performed using a novel driver with rotating eccentric mass placed at the posterior-lateral wall to couple waves (50 Hz) to the kidney. The biomechanical parameters, shear wave speed (cs in m/s), storage modulus (Gd in kPa), loss modulus (Gl in kPa), phase angle ( Υ = 2 π atan G l G d ) and attenuation (α in 1/mm) were derived. Accurate separation of gross anatomical segments was applied in post-processing (whole kidney, cortex, medulla, sinus, vessel). Results: High-quality shear waves coupled into all gross anatomical segments of the kidney (mean shear wave displacement: 163 ± 47 μm, mean contamination of second upper harmonics <23%, curl/divergence: 4.3 ± 0.8). Regardless of the hydration state, median Gd of the cortex and medulla (0.68 ± 0.11 kPa) was significantly higher than that of the sinus and vessels (0.48 ± 0.06 kPa), and consistently, significant differences were found in cs, Υ , and Gl (all p < 0.001). The viscoelastic parameters of cortex and medulla were not significantly different. After hydration sinus exhibited a small but significant reduction in median Gd by -0.02 ± 0.04 kPa (p = 0.01), and, consequently, the cortico-sinusoidal-difference in Gd increased by 0.04 ± 0.07 kPa (p = 0.05). Only upon hydration, the attenuation in vessels became lower (0.084 ± 0.013 1/mm) and differed significantly from the whole kidney (0.095 ± 0.007 1/mm, p = 0.01). Conclusion: High-resolution renal MRE with an innovative driver and well-defined 3D segmentation can resolve all renal segments, especially when including the sinus in the analysis. Even after a prolonged hydration period the approach is sensitive to small hydration-related changes in the sinus and in the cortico-sinusoidal-difference.
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Affiliation(s)
- Marcos Wolf
- High Field MR Center, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
| | - Omar Darwish
- School of Biomedical Engineering and Imaging Sciences, King’s College London, London, United Kingdom
- MR Research Collaborations, Siemens Healthcare Limited, Frimley, United Kingdom
| | - Radhouene Neji
- School of Biomedical Engineering and Imaging Sciences, King’s College London, London, United Kingdom
| | - Michael Eder
- Department of Medicine III, Division of Nephrology and Dialysis, General Hospital and Medical University of Vienna, Vienna, Austria
| | - Gere Sunder-Plassmann
- Department of Medicine III, Division of Nephrology and Dialysis, General Hospital and Medical University of Vienna, Vienna, Austria
| | - Gertraud Heinz
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum St. Pölten, Sankt Pölten, Austria
| | - Simon Daniel Robinson
- High Field MR Centre, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria
- Centre of Advanced Imaging, University of Queensland, Brisbane, QLD, Australia
| | - Albrecht Ingo Schmid
- High Field MR Center, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
| | - Ewald V. Moser
- High Field MR Center, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
| | - Ralph Sinkus
- Institut National de La Santé et de La Recherche Médicale, U1148, Laboratory for Vascular Translational Science, Paris, France
| | - Martin Meyerspeer
- High Field MR Center, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
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Mei Y, Feng X, Jin Y, Kang R, Wang X, Zhao D, Ghosh S, Neu CP, Avril S. Cell nucleus elastography with the adjoint-based inverse solver. COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE 2023; 242:107827. [PMID: 37801883 DOI: 10.1016/j.cmpb.2023.107827] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 09/09/2023] [Accepted: 09/22/2023] [Indexed: 10/08/2023]
Abstract
BACKGROUND AND OBJECTIVES The mechanics of the nucleus depends on cellular structures and architecture, and impact a number of diseases. Nuclear mechanics is yet rather complex due to heterogeneous distribution of dense heterochromatin and loose euchromatin domains, giving rise to spatially variable stiffness properties. METHODS In this study, we propose to use the adjoint-based inverse solver to identify for the first time the nonhomogeneous elastic property distribution of the nucleus. Inputs of the inverse solver are deformation fields measured with microscopic imaging in contracting cardiomyocytes. RESULTS The feasibility of the proposed method is first demonstrated using simulated data. Results indicate accurate identification of the assumed heterochromatin region, with a maximum relative error of less than 5%. We also investigate the influence of unknown Poisson's ratio on the reconstruction and find that variations of the Poisson's ratio in the range [0.3-0.5] result in uncertainties of less than 15% in the identified stiffness. Finally, we apply the inverse solver on actual deformation fields acquired within the nuclei of two cardiomyocytes. The obtained results are in good agreement with the density maps obtained from microscopy images. CONCLUSIONS Overall, the proposed approach shows great potential for nuclear elastography, with promising value for emerging fields of mechanobiology and mechanogenetics.
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Affiliation(s)
- Yue Mei
- State Key Laboratory of Structural Analysis, Optimization and CAE Software for Industrial Equipment, Department of Engineering Mechanics, Dalian University of Technology, Dalian 116023, China; International Research Center for Computational Mechanics, Dalian University of Technology, Dalian 116023, China; Ningbo Institute of Dalian University of Technology, No. 26 Yucai Road, Jiangbei District, Ningbo 315016, China
| | - Xuan Feng
- State Key Laboratory of Structural Analysis, Optimization and CAE Software for Industrial Equipment, Department of Engineering Mechanics, Dalian University of Technology, Dalian 116023, China; International Research Center for Computational Mechanics, Dalian University of Technology, Dalian 116023, China
| | - Yun Jin
- State Key Laboratory of Structural Analysis, Optimization and CAE Software for Industrial Equipment, Department of Engineering Mechanics, Dalian University of Technology, Dalian 116023, China; International Research Center for Computational Mechanics, Dalian University of Technology, Dalian 116023, China
| | - Rongyao Kang
- State Key Laboratory of Structural Analysis, Optimization and CAE Software for Industrial Equipment, Department of Engineering Mechanics, Dalian University of Technology, Dalian 116023, China; International Research Center for Computational Mechanics, Dalian University of Technology, Dalian 116023, China
| | - XinYu Wang
- State Key Laboratory of Structural Analysis, Optimization and CAE Software for Industrial Equipment, Department of Engineering Mechanics, Dalian University of Technology, Dalian 116023, China; International Research Center for Computational Mechanics, Dalian University of Technology, Dalian 116023, China
| | - Dongmei Zhao
- State Key Laboratory of Structural Analysis, Optimization and CAE Software for Industrial Equipment, Department of Engineering Mechanics, Dalian University of Technology, Dalian 116023, China; International Research Center for Computational Mechanics, Dalian University of Technology, Dalian 116023, China
| | - Soham Ghosh
- Department of Mechanical Engineering, Colorado State University, Fort Collins, CO, United States of America
| | - Corey P Neu
- Paul M. Rady Department of Mechanical Engineering, University of Colorado Boulder, Boulder, CO, United States of America; Biomedical Engineering Program, University of Colorado Boulder, Boulder, CO, United States of America; BioFrontiers Institute, University of Colorado Boulder, Boulder, CO, United States of America
| | - Stephane Avril
- Mines Saint-Étienne, Univ Jean Monnet, INSERM, U 1059 Sainbiose, F - 42023, Saint-Étienne, France.
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Abstract
ABSTRACT The mechanical traits of cancer include abnormally high solid stress as well as drastic and spatially heterogeneous changes in intrinsic mechanical tissue properties. Whereas solid stress elicits mechanosensory signals promoting tumor progression, mechanical heterogeneity is conducive to cell unjamming and metastatic spread. This reductionist view of tumorigenesis and malignant transformation provides a generalized framework for understanding the physical principles of tumor aggressiveness and harnessing them as novel in vivo imaging markers. Magnetic resonance elastography is an emerging imaging technology for depicting the viscoelastic properties of biological soft tissues and clinically characterizing tumors in terms of their biomechanical properties. This review article presents recent technical developments, basic results, and clinical applications of magnetic resonance elastography in patients with malignant tumors.
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Affiliation(s)
- Jing Guo
- From the Department of Radiology
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Patras L, Paul D, Matei IR. Weaving the nest: extracellular matrix roles in pre-metastatic niche formation. Front Oncol 2023; 13:1163786. [PMID: 37350937 PMCID: PMC10282420 DOI: 10.3389/fonc.2023.1163786] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2023] [Accepted: 05/15/2023] [Indexed: 06/24/2023] Open
Abstract
The discovery that primary tumors condition distant organ sites of future metastasis for seeding by disseminating tumor cells through a process described as the pre-metastatic niche (PMN) formation revolutionized our understanding of cancer progression and opened new avenues for therapeutic interventions. Given the inherent inefficiency of metastasis, PMN generation is crucial to ensure the survival of rare tumor cells in the otherwise hostile environments of metastatic organs. Early on, it was recognized that preparing the "soil" of the distal organ to support the outgrowth of metastatic cells is the initiating event in PMN development, achieved through the remodeling of the organ's extracellular matrix (ECM). Remote restructuring of ECM at future sites of metastasis under the influence of primary tumor-secreted factors is an iterative process orchestrated through the crosstalk between resident stromal cells, such as fibroblasts, epithelial and endothelial cells, and recruited innate immune cells. In this review, we will explore the ECM changes, cellular effectors, and the mechanisms of ECM remodeling throughout PMN progression, as well as its impact on shaping the PMN and ultimately promoting metastasis. Moreover, we highlight the clinical and translational implications of PMN ECM changes and opportunities for therapeutically targeting the ECM to hinder PMN formation.
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Affiliation(s)
- Laura Patras
- Children’s Cancer and Blood Foundation Laboratories, Department of Pediatrics, Division of Hematology/Oncology, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, United States
- Department of Molecular Biology and Biotechnology, Center of Systems Biology, Biodiversity and Bioresources, Faculty of Biology and Geology, Babes-Bolyai University, Cluj-Napoca, Romania
| | - Doru Paul
- Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medicine, New York, NY, United States
| | - Irina R. Matei
- Children’s Cancer and Blood Foundation Laboratories, Department of Pediatrics, Division of Hematology/Oncology, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, United States
- Department of Molecular Biology and Biotechnology, Center of Systems Biology, Biodiversity and Bioresources, Faculty of Biology and Geology, Babes-Bolyai University, Cluj-Napoca, Romania
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10
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Sievers J, Mahajan V, Welzel PB, Werner C, Taubenberger A. Precision Hydrogels for the Study of Cancer Cell Mechanobiology. Adv Healthc Mater 2023; 12:e2202514. [PMID: 36826799 PMCID: PMC11468035 DOI: 10.1002/adhm.202202514] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 01/23/2023] [Indexed: 02/25/2023]
Abstract
Cancer progression is associated with extensive remodeling of the tumor microenvironment (TME), resulting in alterations of biochemical and biophysical cues that affect both cancer and stromal cells. In particular, the mechanical characteristics of the TME extracellular matrix undergo significant changes. Bioengineered polymer hydrogels can be instrumental to systematically explore how mechanically changed microenvironments impact cancer cell behavior, including proliferation, survival, drug resistance, and invasion. This article reviews studies that have explored the impact of different mechanical cues of the cells' 3D microenvironment on cancer cell behavior using hydrogel-based in vitro models. In particular, advanced engineering strategies are highlighted for tailored hydrogel matrices recapitulating the TME's micrometer- and sub-micrometer-scale architectural and mechanical features, while accounting for its intrinsically heterogenic and dynamic nature. It is anticipated that such precision hydrogel systems will further the understanding of cancer mechanobiology.
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Affiliation(s)
- Jana Sievers
- Max Bergmann Center of Biomaterials DresdenLeibniz Institute for Polymer Research DresdenHohe Str. 601069DresdenGermany
| | - Vaibhav Mahajan
- Center for Molecular and Cellular Bioengineering (CMCB)BIOTECTU Dresden01307DresdenGermany
| | - Petra B. Welzel
- Max Bergmann Center of Biomaterials DresdenLeibniz Institute for Polymer Research DresdenHohe Str. 601069DresdenGermany
| | - Carsten Werner
- Max Bergmann Center of Biomaterials DresdenLeibniz Institute for Polymer Research DresdenHohe Str. 601069DresdenGermany
- Center of Regenerative Therapies Dresden and Cluster of Excellence Physics of LifeTU Dresden01062DresdenGermany
| | - Anna Taubenberger
- Max Bergmann Center of Biomaterials DresdenLeibniz Institute for Polymer Research DresdenHohe Str. 601069DresdenGermany
- Center for Molecular and Cellular Bioengineering (CMCB)BIOTECTU Dresden01307DresdenGermany
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11
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Teixeira AM, Martins P. A review of bioengineering techniques applied to breast tissue: Mechanical properties, tissue engineering and finite element analysis. Front Bioeng Biotechnol 2023; 11:1161815. [PMID: 37077233 PMCID: PMC10106631 DOI: 10.3389/fbioe.2023.1161815] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Accepted: 03/14/2023] [Indexed: 04/05/2023] Open
Abstract
Female breast cancer was the most prevalent cancer worldwide in 2020, according to the Global Cancer Observatory. As a prophylactic measure or as a treatment, mastectomy and lumpectomy are often performed at women. Following these surgeries, women normally do a breast reconstruction to minimize the impact on their physical appearance and, hence, on their mental health, associated with self-image issues. Nowadays, breast reconstruction is based on autologous tissues or implants, which both have disadvantages, such as volume loss over time or capsular contracture, respectively. Tissue engineering and regenerative medicine can bring better solutions and overcome these current limitations. Even though more knowledge needs to be acquired, the combination of biomaterial scaffolds and autologous cells appears to be a promising approach for breast reconstruction. With the growth and improvement of additive manufacturing, three dimensional (3D) printing has been demonstrating a lot of potential to produce complex scaffolds with high resolution. Natural and synthetic materials have been studied in this context and seeded mainly with adipose derived stem cells (ADSCs) since they have a high capability of differentiation. The scaffold must mimic the environment of the extracellular matrix (ECM) of the native tissue, being a structural support for cells to adhere, proliferate and migrate. Hydrogels (e.g., gelatin, alginate, collagen, and fibrin) have been a biomaterial widely studied for this purpose since their matrix resembles the natural ECM of the native tissues. A powerful tool that can be used in parallel with experimental techniques is finite element (FE) modeling, which can aid the measurement of mechanical properties of either breast tissues or scaffolds. FE models may help in the simulation of the whole breast or scaffold under different conditions, predicting what might happen in real life. Therefore, this review gives an overall summary concerning the human breast, specifically its mechanical properties using experimental and FE analysis, and the tissue engineering approaches to regenerate this particular tissue, along with FE models.
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Affiliation(s)
| | - Pedro Martins
- UBS, INEGI, LAETA, Porto, Portugal
- I3A, Universidad de Zaragoza, Zaragoza, Spain
- *Correspondence: Pedro Martins,
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Fakhouri FS, Joseph M, Ballinger M, Shukla V, Weimar D, Novak C, Ghadiali S, Kolipaka A. Magnetic Resonance Elastography (MRE) of Bleomycin-Induced Pulmonary Fibrosis in an Animal Model. Invest Radiol 2023; 58:299-306. [PMID: 36730906 PMCID: PMC10023269 DOI: 10.1097/rli.0000000000000935] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Idiopathic pulmonary fibrosis is responsible for 40,000 deaths annually in the United States. A hallmark of idiopathic pulmonary fibrosis is elevated collagen deposition, which alters lung stiffness. Clinically relevant ways to measure changes in lung stiffness during pulmonary fibrosis are not available, and new noninvasive imaging methods are needed to measure changes in lung mechanical properties. OBJECTIVES Magnetic resonance elastography (MRE) is an in vivo magnetic resonance imaging technique proven to detect changes in shear stiffness in different organs. This study used MRE, histology, and bronchoalveolar lavage (BAL) to study changes in the mechanical and structural properties of the lungs after bleomycin-induced pulmonary fibrosis in pigs. MATERIALS AND METHODS Pulmonary fibrosis was induced in 9 Yorkshire pigs by intratracheal instillation of 2 doses of bleomycin into the right lung only. Magnetic resonance elastography scans were performed at baseline and week 4 and week 8 postsurgery in a 1.5 T magnetic resonance imaging scanner using a spin-echo echo planar imaging sequence to measure changes in lung shear stiffness. At the time of each scan, a BAL was performed. After the final scan, whole lung tissue was removed and analyzed for histological changes. RESULTS Mean MRE-derived stiffness measurements at baseline, week 4, and week 8 for the control (left) lungs were 1.02 ± 0.27 kPa, 0.86 ± 0.29 kPa, and 0.68 ± 0.20 kPa, respectively. The ratio of the shear stiffness in the injured (right) lung to the uninjured control (left) lung at baseline, week 4, and week 8 was 0.98 ± 0.23, 1.52 ± 0.41, and 1.64 ± 0.40, respectively. High-dose animals showed increased protein in BAL fluid, elevated inflammation observed by the presence of patchy filtrates, and enhanced collagen and α-smooth muscle actin staining on histological sections. Low-dose animals and the control (left) lungs of high-dose animals did not show significant histopathological changes. CONCLUSION This study demonstrated that MRE can be used to detect changes in lung stiffness in pigs after bleomycin challenge.
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Affiliation(s)
- Faisal S. Fakhouri
- Department of Biomedical Engineering, The Ohio State University, Columbus, OH, 43210, USA
- Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA
- Department of Biomedical Technology, King Saud University, Riyadh, 12372, KSA
| | - Matthew Joseph
- Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, 43210, USA
| | - Megan Ballinger
- Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, 43210, USA
- Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA
| | - Vasudha Shukla
- Department of Biomedical Engineering, The Ohio State University, Columbus, OH, 43210, USA
| | - David Weimar
- Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, 43210, USA
- Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA
| | - Caymen Novak
- Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, 43210, USA
- Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA
| | - Samir Ghadiali
- Department of Biomedical Engineering, The Ohio State University, Columbus, OH, 43210, USA
- Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA
| | - Arunark Kolipaka
- Department of Biomedical Engineering, The Ohio State University, Columbus, OH, 43210, USA
- Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA
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Multi-frequency shear modulus measurements discriminate tumorous from healthy tissues. J Mech Behav Biomed Mater 2023; 140:105721. [PMID: 36791572 DOI: 10.1016/j.jmbbm.2023.105721] [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: 07/19/2022] [Revised: 02/07/2023] [Accepted: 02/08/2023] [Indexed: 02/11/2023]
Abstract
As far as their mechanical properties are concerned, cancerous lesions can be confused with healthy surrounding tissues in elastography protocols if only the magnitude of moduli is considered. We show that the frequency dependence of the tissue's mechanical properties allows for discriminating the tumor from other tissues, obtaining a good contrast even when healthy and tumor tissues have shear moduli of comparable magnitude. We measured the shear modulus G*(ω) of xenograft subcutaneous tumors developed in mice using breast human cancer cells, compared with that of fat, skin and muscle harvested from the same mice. As the absolute shear modulus |G*(ω)| of tumors increases by 42% (from 5.2 to 7.4 kPa) between 0.25 and 63 Hz, it varies over the same frequency range by 77% (from 0.53 to 0.94 kPa) for the fat, by 103% (from 3.4 to 6.9 kPa) for the skin and by 120% (from 4.4 to 9.7 kPa) for the muscle. These measurements fit well to the fractional model G*(ω)=K(iω)n, yielding a coefficient K and a power-law exponent n for each sample. Tumor, skin and muscle have comparable K parameter values, that of fat being significantly lower; the p-values given by a Mann-Whitney test are above 0.14 when comparing tumor, skin and muscle between themselves, but below 0.001 when comparing fat with tumor, skin or muscle. With regards the n parameter, tumor and fat are comparable, with p-values above 0.43, whereas tumor differs from both skin and muscle, with p-values below 0.001. Tumor tissues thus significantly differs from fat, skin and muscle on account of either the K or the n parameter, i.e. of either the magnitude or the frequency-dependence of the shear modulus.
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Kabir IE, Caban-Rivera DA, Ormachea J, Parker KJ, Johnson CL, Doyley MM. Reverberant magnetic resonance elastographic imaging using a single mechanical driver. Phys Med Biol 2023; 68:055015. [PMID: 36780698 PMCID: PMC9969521 DOI: 10.1088/1361-6560/acbbb7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 01/31/2023] [Accepted: 02/13/2023] [Indexed: 02/15/2023]
Abstract
Reverberant elastography provides fast and robust estimates of shear modulus; however, its reliance on multiple mechanical drivers hampers clinical utility. In this work, we hypothesize that for constrained organs such as the brain, reverberant elastography can produce accurate magnetic resonance elastograms with a single mechanical driver. To corroborate this hypothesis, we performed studies on healthy volunteers (n= 3); and a constrained calibrated brain phantom containing spherical inclusions with diameters ranging from 4-18 mm. In both studies (i.e. phantom and clinical), imaging was performed at frequencies of 50 and 70 Hz. We used the accuracy and contrast-to-noise ratio performance metrics to evaluate reverberant elastograms relative to those computed using the established subzone inversion method. Errors incurred in reverberant elastograms varied from 1.3% to 16.6% when imaging at 50 Hz and 3.1% and 16.8% when imaging at 70 Hz. In contrast, errors incurred in subzone elastograms ranged from 1.9% to 13% at 50 Hz and 3.6% to 14.9% at 70 Hz. The contrast-to-noise ratio of reverberant elastograms ranged from 63.1 to 73 dB compared to 65 to 66.2 dB for subzone elastograms. The average global brain shear modulus estimated from reverberant and subzone elastograms was 2.36 ± 0.07 kPa and 2.38 ± 0.11 kPa, respectively, when imaging at 50 Hz and 2.70 ± 0.20 kPa and 2.89 ± 0.60 kPa respectively, when imaging at 70 Hz. The results of this investigation demonstrate that reverberant elastography can produce accurate, high-quality elastograms of the brain with a single mechanical driver.
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Affiliation(s)
- Irteza Enan Kabir
- University of Rochester, Hajim School of Engineering and Applied Sciences 1467, Rochester, NY, United States of America
| | - Diego A Caban-Rivera
- University of Delaware, Department of Biomedical Engineering 19716, Newark, DE, United States of America
| | - Juvenal Ormachea
- Verasonics, Inc., 11335 NE 122nd Way, Suite 100 98034 Kirkland, WA, United States of America
| | - Kevin J Parker
- University of Rochester, Hajim School of Engineering and Applied Sciences 1467, Rochester, NY, United States of America
| | - Curtis L Johnson
- University of Delaware, Department of Biomedical Engineering 19716, Newark, DE, United States of America
| | - Marvin M Doyley
- University of Rochester, Hajim School of Engineering and Applied Sciences 1467, Rochester, NY, United States of America
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Pancreatic Cancer Presents Distinct Nanomechanical Properties During Progression. Ann Biomed Eng 2023:10.1007/s10439-023-03168-3. [PMID: 36813931 DOI: 10.1007/s10439-023-03168-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Accepted: 02/11/2023] [Indexed: 02/24/2023]
Abstract
Cancer progression is closely related to changes in the structure and mechanical properties of the tumor microenvironment (TME). In many solid tumors, including pancreatic cancer, the interplay among the different components of the TME leads to a desmoplastic reaction mainly due to collagen overproduction. Desmoplasia is responsible for the stiffening of the tumor, poses a major barrier to effective drug delivery and has been associated with poor prognosis. The understanding of the involved mechanisms in desmoplasia and the identification of nanomechanical and collagen-based properties that characterize the state of a particular tumor can lead to the development of novel diagnostic and prognostic biomarkers. In this study, in vitro experiments were conducted using two human pancreatic cell lines. Morphological and cytoskeleton characteristics, cells' stiffness and invasive properties were assessed using optical and atomic force microscopy techniques and cell spheroid invasion assay. Subsequently, the two cell lines were used to develop orthotopic pancreatic tumor models. Tissue biopsies were collected at different times of tumor growth for the study of the nanomechanical and collagen-based optical properties of the tissue using Atomic Force Microscopy (AFM) and picrosirius red polarization microscopy, respectively. The results from the in vitro experiments demonstrated that the more invasive cells are softer and present a more elongated shape with more oriented F-actin stress fibers. Furthermore, ex vivo studies of orthotopic tumor biopsies on MIAPaCa-2 and BxPC-3 murine tumor models highlighted that pancreatic cancer presents distinct nanomechanical and collagen-based optical properties relevant to cancer progression. The stiffness spectrums (in terms of Young's modulus values) showed that the higher elasticity distributions were increasing during cancer progression mainly due desmoplasia (collagen overproduction), while a lower elasticity peak was evident - due to cancer cells softening - on both tumor models. Optical microscopy studies highlighted that collagen content increases while collagen fibers tend to form align patterns. Consequently, during cancer progression nanomechanical and collagen-based optical properties alter in relation to changes in collagen content. Therefore, they have the potential to be used as novel biomarkers for assessing and monitoring tumor progression and treatment outcomes.
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Jugé L, Foley P, Hatt A, Yeung J, Bilston LE. Ex vivo bovine liver nonlinear viscoelastic properties: MR elastography and rheological measurements. J Mech Behav Biomed Mater 2023; 138:105638. [PMID: 36623403 DOI: 10.1016/j.jmbbm.2022.105638] [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: 10/04/2022] [Revised: 11/28/2022] [Accepted: 12/19/2022] [Indexed: 12/29/2022]
Abstract
INTRODUCTION Knowledge of the nonlinear viscoelastic properties of the liver is important, but the complex tissue behavior outside the linear viscoelastic regime has impeded their characterization, particularly in vivo. Combining static compression with magnetic resonance (MR) elastography has the potential to be a useful imaging method for assessing large deformation mechanical properties of soft tissues in vivo. However, this remains to be verified. Therefore this study aims first to determine whether MR elastography can measure the nonlinear mechanical properties of ex vivo bovine liver tissue under varying levels of uniform and focal preloads (up to 30%), and second to compare MR elastography-derived complex shear modulus with standard rheological measurements. METHOD Nine fresh bovine livers were collected from a local abattoir, and experiments were conducted within 12hr of death. Two cubic samples (∼10 × 10 × 10 cm3) were dissected from each liver and imaged using MR elastography (60 Hz) under 4 levels of uniform and focal preload (1, 10, 20, and 30% of sample width) to investigate the relationship between MR elastography-derived complex shear modulus (G∗) and the maximum principal Right Cauchy Green Strain (C11). Three tissue samples from each of the same 9 livers underwent oscillatory rheometry under the same 4 preloads (1, 10, 20, and 30% strain). MR elastography-derived complex shear modulus (G∗) from the uniform preload was validated against rheometry by fitting the frequency dependence of G∗ with a power-law and extrapolating rheometry-derived G∗ to 60 Hz. RESULTS MR elastography-derived G∗ increased with increasing compressive large deformation strain, and followed a power-law curve (G∗ = 1.73 × C11-0.38, R2 = 0.96). Similarly, rheometry-derived G∗ at 1 Hz, increasing from 0.66 ± 1.03 kPa (1% strain) to 1.84 ± 1.65 kPa (30% strain, RM one-way ANOVA, P < 0.001), and the frequency dependence of G∗ followed a power-law with the exponent decreasing from 0.13 to 0.06 with increasing preload. MR elastography-derived G∗ was 1.4-3.1 times higher than the extrapolated rheometry-derived G∗ at 60 Hz, but the strain dependence was consistent between rheometry and MR elastography measurements. CONCLUSIONS This study demonstrates that MR elastography can detect changes in ex vivo bovine liver complex shear modulus due to either uniform or focal preload and therefore can be a useful technique to characterize nonlinear viscoelastic properties of soft tissue, provided that strains applied to the tissue can be quantified. Although MR elastography could reliably characterize the strain dependence of the ex vivo bovine liver, MR elastography overestimated the complex shear modulus of the tissue compared to rheological measurements, particularly at lower preload (<10%). That is likely to be important in clinical hepatic MR elastography diagnosis studies if preload is not carefully considered. A limitation is the absence of overlapping frequency between rheometry and MR elastography for formal validation.
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Affiliation(s)
- Lauriane Jugé
- Neuroscience Research Australia, PO Box 1165, Randwick NSW 2031, Australia; University of New South Wales, Faculty of Medicine & Health, UNSW Sydney, 18 High St, Kensington NSW 2052, Australia
| | - Patrick Foley
- Neuroscience Research Australia, PO Box 1165, Randwick NSW 2031, Australia
| | - Alice Hatt
- Neuroscience Research Australia, PO Box 1165, Randwick NSW 2031, Australia
| | - Jade Yeung
- Neuroscience Research Australia, PO Box 1165, Randwick NSW 2031, Australia
| | - Lynne E Bilston
- Neuroscience Research Australia, PO Box 1165, Randwick NSW 2031, Australia; University of New South Wales, Faculty of Medicine & Health, UNSW Sydney, 18 High St, Kensington NSW 2052, Australia.
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Liu L, Bongers A, Bilston LE, Jugé L. The combined use of DTI and MR elastography for monitoring microstructural changes in the developing brain of a neurodevelopmental disorder model: Poly (I:C)-induced maternal immune-activated rats. PLoS One 2023; 18:e0280498. [PMID: 36638122 PMCID: PMC9838869 DOI: 10.1371/journal.pone.0280498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Accepted: 01/03/2023] [Indexed: 01/14/2023] Open
Abstract
Early neuropathology mechanisms in neurodevelopmental disorders are partially understood because routine anatomical magnetic resonance imaging (MRI) cannot detect subtle brain microstructural changes in vivo during postnatal development. Therefore, we investigated the potential value of magnetic resonance elastography (MRE) and diffusion tensor imaging (DTI) in a rat model of neurodevelopmental disorder induced by maternal immune activation. We studied 12 offspring of mothers injected with polyriboinosinic-polyribocytidylic acid (poly (I:C), 4 mg/kg) on gestational day 15, plus 8 controls. T2-weighted anatomical MR images, MRE (800 Hz) and DTI (30 gradient directions, b = 765.8 s/mm2, 5 images, b = 0 s/mm2) were collected when the rats were 4 and 10 weeks old, and results were compared with histological analysis performed at week 10. Ventricles were ~1.4 fold larger from week 4 in poly (I:C) rats than in controls. No other morphological abnormalities were detected in poly(I:C) rats. At week 4, larger ventricles were correlated with lower external capsule fractional anisotropy and internal capsule radial diffusion (Pearson, r = -0.53, 95% confidence intervals (CI) [-0.79 to -0.12], and r = -0.45, 95% CI [-0.74 to -0.01], respectively). The mean and radial diffusion of the corpus callosum, the mean and axial diffusion of the internal capsule and the radial diffusion properties in the external capsule increased with age for poly (I:C) rats only (Sidak's comparison, P<0.05). Cortical stiffness did not increase with age in poly (I:C) rats, in contrast with controls (Sidak's comparison, P = 0.005). These temporal variations probably reflected abnormal myelin content, decreased cell density and microglia activation observed at week 10 after histological assessment. To conclude, MRE and DTI allow monitoring of abnormal brain microstructural changes in poly (I:C) rats from week 4 after birth. This suggests that both imaging techniques have the potential to be used as complementary imaging tools to routine anatomical imaging to assist with the early diagnosis of neurodevelopmental disorders and provide new insights into neuropathology.
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Affiliation(s)
- Lucy Liu
- Faculty of Medicine & Health, University of New South Wales, Sydney, New South Wales, Australia
- Neuroscience Research Australia, Sydney, New South Wales, Australia
| | - Andre Bongers
- Biological Resources Imaging Laboratory, University of New South Wales, Sydney, New South Wales, Australia
| | - Lynne E. Bilston
- Faculty of Medicine & Health, University of New South Wales, Sydney, New South Wales, Australia
- Neuroscience Research Australia, Sydney, New South Wales, Australia
| | - Lauriane Jugé
- Faculty of Medicine & Health, University of New South Wales, Sydney, New South Wales, Australia
- Neuroscience Research Australia, Sydney, New South Wales, Australia
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Stylianou A, Mpekris F, Voutouri C, Papoui A, Constantinidou A, Kitiris E, Kailides M, Stylianopoulos T. Nanomechanical properties of solid tumors as treatment monitoring biomarkers. Acta Biomater 2022; 154:324-334. [PMID: 36244596 DOI: 10.1016/j.actbio.2022.10.021] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 10/05/2022] [Accepted: 10/07/2022] [Indexed: 12/14/2022]
Abstract
Many tumors, such as types of sarcoma and breast cancer, stiffen as they grow in a host healthy tissue, while individual cancer cells are becoming softer. Tumor stiffening poses major pathophysiological barriers to the effective delivery of drugs and compromises treatment efficacy. It has been established that normalization of the mechanical properties of a tumor by targeting components of the tumor microenvironment (TME) enhances the delivery of anti-cancer agents and consequently the therapeutic outcome. Consequently, there is an urgent need for the development of biomarkers, which characterize the mechanical state of a particular tumor for the development of personalized treatments or for monitoring therapeutic strategies that target the TME. In this work, Atomic Force Microscopy (AFM) was used to assess human and murine nanomechanical properties from tumor biopsies. In the case of murine tumor models, the nanomechanical properties during tumor progression were measured and a TME normalization drug (tranilast) along with chemotherapy doxorubicin were employed in order to investigate whether AFM has the ability to capture changes in the nanomechanical properties of a tumor during treatment. The nanomechanical data were further correlated with ex vivo characterization of structural components of the TME. The results highlighted that nanomechanical properties alter during cancer progression and AFM measurements are sensitive enough to capture even small alterations during different types of treatments, namely normalization and chemotherapy. The identification of unique AFM-based nanomechanical properties can lead to the development of biomarkers for treatment prediction and monitoring. STATEMENT OF SIGNIFICANCE: Cancer progression is associated with vast remodeling of the tumor microenvironment resulting in changes in the mechanical properties of the tissue. Indeed, many tumors stiffen as they grow and this stiffening compromises treatment efficacy. As a result, a number of treatments target tumor microenvironment in order to normalize its mechanical properties. Consequently, there is an urgent need for the development of innovative tools that can assess the mechanical properties of a particular tumor and monitor tumor progression and treatment outcomes. This work highlights the use of atomic force microscopy (AFM) for assessing the elasticity spectrum of solid tumors at different stages and during treatment. This knowledge is essential for the development of AFM-based nanomechanical biomarkers for treatment prediction and monitoring.
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Affiliation(s)
- Andreas Stylianou
- Cancer Mechanobiology and Applied Biophysics Group, Basic and Translational Cancer Research Center, School of Sciences, European University Cyprus, Cyprus; European University Research Centre Ltd, Nicosia, Cyprus; Cancer Biophysics Laboratory, Department of Mechanical and Manufacturing Engineering, University of Cyprus, Cyprus.
| | - Fotios Mpekris
- Cancer Biophysics Laboratory, Department of Mechanical and Manufacturing Engineering, University of Cyprus, Cyprus
| | - Chrysovalantis Voutouri
- Cancer Biophysics Laboratory, Department of Mechanical and Manufacturing Engineering, University of Cyprus, Cyprus
| | - Antonia Papoui
- Cancer Biophysics Laboratory, Department of Mechanical and Manufacturing Engineering, University of Cyprus, Cyprus
| | - Anastasia Constantinidou
- Medical School, University of Cyprus, Cyprus; Bank of Cyprus Oncology Center, Cyprus; Cyprus Cancer Research Institute, Cyprus
| | | | | | - Triantafyllos Stylianopoulos
- Cancer Biophysics Laboratory, Department of Mechanical and Manufacturing Engineering, University of Cyprus, Cyprus.
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Iglesias M, McGrath DM, Tretyakov MV, Francis ST. Ensemble Kalman inversion for magnetic resonance elastography. Phys Med Biol 2022; 67. [PMID: 36322986 DOI: 10.1088/1361-6560/ac9fa1] [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: 04/08/2022] [Accepted: 11/01/2022] [Indexed: 11/29/2022]
Abstract
Magnetic resonance elastography (MRE) is an MRI-based diagnostic method for measuring mechanical properties of biological tissues. MRE measurements are processed by an inversion algorithm to produce a map of the biomechanical properties. In this paper a new and powerful method (ensemble Kalman inversion with level sets (EKI)) of MRE inversion is proposed and tested. The method has critical advantages: material property variation at disease boundaries can be accurately identified, and uncertainty of the reconstructed material properties can be evaluated by consequence of the probabilistic nature of the method. EKI is tested in 2D and 3D experiments with synthetic MRE data of the human kidney. It is demonstrated that the proposed inversion method is accurate and fast.
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Affiliation(s)
- Marco Iglesias
- School of Mathematical Sciences, University of Nottingham, Nottingham, United Kingdom
| | - Deirdre M McGrath
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, United Kingdom
- Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, United Kingdom
| | - M V Tretyakov
- School of Mathematical Sciences, University of Nottingham, Nottingham, United Kingdom
| | - Susan T Francis
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, United Kingdom
- Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, United Kingdom
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Carlson AL, Carrazco-Carrillo J, Loder A, Elkhadragy L, Schachtschneider KM, Padilla-Benavides T. The Oncopig as an Emerging Model to Investigate Copper Regulation in Cancer. Int J Mol Sci 2022; 23:14012. [PMID: 36430490 PMCID: PMC9697225 DOI: 10.3390/ijms232214012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 11/03/2022] [Accepted: 11/10/2022] [Indexed: 11/16/2022] Open
Abstract
Emerging evidence points to several fundamental contributions that copper (Cu) has to promote the development of human pathologies such as cancer. These recent and increasing identification of the roles of Cu in cancer biology highlights a promising field in the development of novel strategies against cancer. Cu and its network of regulatory proteins are involved in many different contextual aspects of cancer from driving cell signaling, modulating cell cycle progression, establishing the epithelial-mesenchymal transition, and promoting tumor growth and metastasis. Human cancer research in general requires refined models to bridge the gap between basic science research and meaningful clinical trials. Classic studies in cultured cancer cell lines and animal models such as mice and rats often present caveats when extended to humans due to inherent genetic and physiological differences. However, larger animal models such as pigs are emerging as more appropriate tools for translational research as they present more similarities with humans in terms of genetics, anatomical structures, organ sizes, and pathological manifestations of diseases like cancer. These similarities make porcine models well-suited for addressing long standing questions in cancer biology as well as in the arena of novel drug and therapeutic development against human cancers. With the emergent roles of Cu in human health and pathology, the pig presents an emerging and valuable model to further investigate the contributions of this metal to human cancers. The Oncopig Cancer Model is a transgenic swine model that recapitulates human cancer through development of site and cell specific tumors. In this review, we briefly outline the relationship between Cu and cancer, and how the novel Oncopig Cancer Model may be used to provide a better understanding of the mechanisms and causal relationships between Cu and molecular targets involved in cancer.
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Affiliation(s)
- Alyssa L. Carlson
- Department of Molecular Biology and Biochemistry, Wesleyan University, Middletown, CT 06459, USA
| | - Jaime Carrazco-Carrillo
- Department of Molecular Biology and Biochemistry, Wesleyan University, Middletown, CT 06459, USA
| | - Aaron Loder
- Department of Molecular Biology and Biochemistry, Wesleyan University, Middletown, CT 06459, USA
| | - Lobna Elkhadragy
- Department of Radiology, University of Illinois at Chicago, Chicago, IL 60607, USA
| | - Kyle M. Schachtschneider
- Department of Radiology, University of Illinois at Chicago, Chicago, IL 60607, USA
- Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, USA
- National Center for Supercomputing Applications, University of Illinois at Urbana-Champaign, Urbana, IL 61820, USA
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Tardieu M, Salameh N, Souris L, Rousseau D, Jourdain L, Skeif H, Prévot F, de Rochefort L, Ducreux D, Louis B, Garteiser P, Sinkus R, Darrasse L, Poirier-Quinot M, Maître X. Magnetic resonance elastography with guided pressure waves. NMR IN BIOMEDICINE 2022; 35:e4701. [PMID: 35088465 DOI: 10.1002/nbm.4701] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 01/20/2022] [Accepted: 01/21/2022] [Indexed: 06/14/2023]
Abstract
Magnetic resonance elastography aims to non-invasively and remotely characterize the mechanical properties of living tissues. To quantitatively and regionally map the shear viscoelastic moduli in vivo, the technique must achieve proper mechanical excitation throughout the targeted tissues. Although it is straightforward, ante manibus, in close organs such as the liver or the breast, which practitioners clinically palpate already, it is somewhat fortunately highly challenging to trick the natural protective barriers of remote organs such as the brain. So far, mechanical waves have been induced in the latter by shaking the surrounding cranial bones. Here, the skull was circumvented by guiding pressure waves inside the subject's buccal cavity so mechanical waves could propagate from within through the brainstem up to the brain. Repeatable, reproducible and robust displacement fields were recorded in phantoms and in vivo by magnetic resonance elastography with guided pressure waves such that quantitative mechanical outcomes were extracted in the human brain.
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Affiliation(s)
- Marion Tardieu
- Université Paris-Saclay, CEA, CNRS, Inserm, BioMaps, Orsay, France
- Montpellier Cancer Research Institute (IRCM), Inserm U1194, University of Montpellier, Montpellier, France
| | - Najat Salameh
- Université Paris-Saclay, CEA, CNRS, Inserm, BioMaps, Orsay, France
- Center for Adaptable MRI Technology, Department of Biomedical Engineering, University of Basel, Allschwil, Switzerland
| | - Line Souris
- Université Paris-Saclay, CEA, CNRS, Inserm, BioMaps, Orsay, France
| | | | - Laurène Jourdain
- Université Paris-Saclay, CEA, CNRS, Inserm, BioMaps, Orsay, France
| | - Hanadi Skeif
- Université Paris-Saclay, CEA, CNRS, Inserm, BioMaps, Orsay, France
| | - François Prévot
- Université Paris-Saclay, CEA, CNRS, Inserm, BioMaps, Orsay, France
| | - Ludovic de Rochefort
- Université Paris-Saclay, CEA, CNRS, Inserm, BioMaps, Orsay, France
- Aix-Marseille Université, CNRS, CRMBM, Marseille, France
- AP-HM, CHU Timone, Pôle d'Imagerie Médicale, CEMEREM, Marseille, France
| | - Denis Ducreux
- Université Paris-Saclay, CEA, CNRS, Inserm, BioMaps, Orsay, France
| | - Bruno Louis
- Inserm-UPEC UMR955, CNRS EMR7000, Equipe Biomécanique Cellulaire et Respiratoire, Créteil, France
| | - Philippe Garteiser
- Laboratory of Imaging Biomarkers, Center for Research on Inflammation, UMR 1149, Inserm, Université de Paris, Paris, France
| | - Ralph Sinkus
- Imaging Sciences & Biomedical Engineering Division, King's College, London, United Kingdom
| | - Luc Darrasse
- Université Paris-Saclay, CEA, CNRS, Inserm, BioMaps, Orsay, France
| | | | - Xavier Maître
- Université Paris-Saclay, CEA, CNRS, Inserm, BioMaps, Orsay, France
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22
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Patel BK, Pepin K, Brandt KR, Mazza GL, Pockaj BA, Chen J, Zhou Y, Northfelt DW, Anderson K, Kling JM, Vachon CM, Swanson KR, Nikkhah M, Ehman R. Association of breast cancer risk, density, and stiffness: global tissue stiffness on breast MR elastography (MRE). Breast Cancer Res Treat 2022; 194:79-89. [PMID: 35501423 PMCID: PMC9538705 DOI: 10.1007/s10549-022-06607-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 04/05/2022] [Indexed: 11/25/2022]
Abstract
PURPOSE Quantify in vivo biomechanical tissue properties in various breast densities and in average risk and high-risk women using Magnetic Resonance Imaging (MRI)/MRE and examine the association between breast biomechanical properties and cancer risk based on patient demographics and clinical data. METHODS Patients with average risk or high-risk of breast cancer underwent 3.0 T breast MR imaging and elastography. Breast parenchymal enhancement (BPE), density (from most recent mammogram), stiffness, elasticity, and viscosity were recorded. Within each breast density group (non-dense versus dense), stiffness, elasticity, and viscosity were compared across risk groups (average versus high). Separately for stiffness, elasticity, and viscosity, a multivariable logistic regression model was used to evaluate whether the MRE parameter predicted risk status after controlling for clinical factors. RESULTS 50 average risk and 86 high-risk patients were included. Risk groups were similar in age, density, and menopausal status. Among patients with dense breasts, mean stiffness, elasticity, and viscosity were significantly higher in high-risk patients (N = 55) compared to average risk patients (N = 34; all p < 0.001). Stiffness remained a significant predictor of risk status (OR = 4.26, 95% CI [1.96, 9.25]) even after controlling for breast density, BPE, age, and menopausal status. Similar results were seen for elasticity and viscosity. CONCLUSION A structurally based, quantitative biomarker of tissue stiffness obtained from MRE is associated with differences in breast cancer risk in dense breasts. Tissue stiffness could provide a novel prognostic marker to help identify high-risk women with dense breasts who would benefit from increased surveillance and/or risk reduction measures.
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Affiliation(s)
- Bhavika K Patel
- Diagnostic Radiology, Mayo Clinic, 5777 E. Mayo Blvd., Phoenix, AZ, 85054, USA.
| | - Kay Pepin
- Diagnostic Radiology, Mayo Clinic, Rochester, MN, USA
| | | | - Gina L Mazza
- Department of Biostatistics, Mayo Clinic, Phoenix, AZ, USA
| | | | - Jun Chen
- Diagnostic Radiology, Mayo Clinic, Rochester, MN, USA
| | - Yuxiang Zhou
- Diagnostic Radiology, Mayo Clinic, 5777 E. Mayo Blvd., Phoenix, AZ, 85054, USA
| | | | | | - Juliana M Kling
- Department of Internal Medicine, Mayo Clinic, Phoenix, AZ, USA
| | | | | | - Mehdi Nikkhah
- School of Biological and Health Systems Engineering, Arizona State University, Phoenix, AZ, USA
- Biodesign Virginia G. Piper Center for Personalized Diagnostics, Arizona State University, Tempe, AZ, USA
| | - Richard Ehman
- Diagnostic Radiology, Mayo Clinic, Rochester, MN, USA
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23
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Asp ME, Ho Thanh MT, Germann DA, Carroll RJ, Franceski A, Welch RD, Gopinath A, Patteson AE. Spreading rates of bacterial colonies depend on substrate stiffness and permeability. PNAS NEXUS 2022; 1:pgac025. [PMID: 36712798 PMCID: PMC9802340 DOI: 10.1093/pnasnexus/pgac025] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Revised: 01/25/2022] [Accepted: 03/09/2022] [Indexed: 02/01/2023]
Abstract
The ability of bacteria to colonize and grow on different surfaces is an essential process for biofilm development. Here, we report the use of synthetic hydrogels with tunable stiffness and porosity to assess physical effects of the substrate on biofilm development. Using time-lapse microscopy to track the growth of expanding Serratia marcescens colonies, we find that biofilm colony growth can increase with increasing substrate stiffness, unlike what is found on traditional agar substrates. Using traction force microscopy-based techniques, we find that biofilms exert transient stresses correlated over length scales much larger than a single bacterium, and that the magnitude of these forces also increases with increasing substrate stiffness. Our results are consistent with a model of biofilm development in which the interplay between osmotic pressure arising from the biofilm and the poroelastic response of the underlying substrate controls biofilm growth and morphology.
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Affiliation(s)
- Merrill E Asp
- Physics Department, Syracuse University, Syracuse, NY 13244, USA,BioInspired Institute, Syracuse University, Syracuse, NY 13244, USA
| | - Minh-Tri Ho Thanh
- Physics Department, Syracuse University, Syracuse, NY 13244, USA,BioInspired Institute, Syracuse University, Syracuse, NY 13244, USA
| | - Danielle A Germann
- Physics Department, Syracuse University, Syracuse, NY 13244, USA,BioInspired Institute, Syracuse University, Syracuse, NY 13244, USA
| | - Robert J Carroll
- Physics Department, Syracuse University, Syracuse, NY 13244, USA,BioInspired Institute, Syracuse University, Syracuse, NY 13244, USA
| | - Alana Franceski
- BioInspired Institute, Syracuse University, Syracuse, NY 13244, USA,Biology Department, Syracuse University, Syracuse, NY 13244, USA
| | - Roy D Welch
- BioInspired Institute, Syracuse University, Syracuse, NY 13244, USA,Biology Department, Syracuse University, Syracuse, NY 13244, USA
| | - Arvind Gopinath
- Department of Bioengineering, University of California, Merced, Merced, CA 95343, USA,Health Sciences Research Institute, University of California, Merced, Merced, CA 95343, USA
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24
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Short echo time dual-frequency MR Elastography with Optimal Control RF pulses. Sci Rep 2022; 12:1406. [PMID: 35082303 PMCID: PMC8791955 DOI: 10.1038/s41598-022-05262-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Accepted: 01/03/2022] [Indexed: 01/05/2023] Open
Abstract
Magnetic Resonance Elastography (MRE) quantifies the mechanical properties of tissues, typically applying motion encoding gradients (MEG). Multifrequency results allow better characterizations of tissues using data usually acquired through sequential monofrequency experiments. High frequencies are difficult to reach due to slew rate limitations and low frequencies induce long TEs, yielding magnitude images with low SNR. We propose a novel strategy to perform simultaneous multifrequency MRE in the absence of MEGs: using RF pulses designed via the Optimal Control (OC) theory. Such pulses control the spatial distribution of the MRI magnetization phase so that the resulting transverse magnetization reproduces the phase pattern of an MRE acquisition. The pulse is applied with a constant gradient during the multifrequency mechanical excitation to simultaneously achieve slice selection and motion encoding. The phase offset sampling strategy can be adapted according to the excitation frequencies to reduce the acquisition time. Phantom experiments were run to compare the classical monofrequency MRE to the OC based dual-frequency MRE method and showed excellent agreement between the reconstructed shear storage modulus G′. Our method could be applied to simultaneously acquire low and high frequency components, which are difficult to encode with the classical MEG MRE strategy.
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25
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Fakhouri F, Kannengiesser S, Pfeuffer J, Gokun Y, Kolipaka A. Free-breathing MR elastography of the lungs: An in vivo study. Magn Reson Med 2022; 87:236-248. [PMID: 34463400 PMCID: PMC8616792 DOI: 10.1002/mrm.28986] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 08/04/2021] [Accepted: 08/06/2021] [Indexed: 01/03/2023]
Abstract
PURPOSE Lung stiffness alters with many diseases; therefore, several MR elastography (MRE) studies were performed earlier to investigate the stiffness of the right lung during breathhold at residual volume and total lung capacity. The aims of this study were 1) to estimate shear stiffness of the lungs using MRE under free breathing and demonstrate the measurements' repeatability and reproducibility, and 2) to compare lung stiffness under free breathing to breathhold and as a function of age and gender. METHODS Twenty-five healthy volunteers were scanned on a 1.5 Tesla MRI scanner. Spin-echo dual-density spiral and a spin-echo EPI MRE sequences were used to measure shear stiffness of the lungs during free breathing and breathhold at midpoint of tidal volume, respectively. Concordance correlation coefficient and Bland-Altman analyses were performed to determine the repeatability and reproducibility of the spin-echo dual-density spiral-derived shear stiffness. Repeated measures analyses of variances were used to investigate differences in shear stiffness between spin-echo dual-density spiral and spin-echo EPI, right and left lungs, males and females, and different age groups. RESULTS Free-breathing MRE sequence was highly repeatable and reproducible (concordance correlation coefficient > 0.86 for both lungs). Lung stiffness was significantly lower in breathhold than in free breathing (P < .001), which can be attributed to potential stress relaxation of lung parenchyma or breathhold inconsistencies. However, there was no significant difference between different age groups (P = .08). The left lung showed slightly higher stiffness values than the right lung (P = .14). There is no significant difference in lung stiffness between genders. CONCLUSION This study demonstrated the feasibility of free-breathing lung MRE with excellent repeatability and reproducibility. Stiffness changes with age and during the respiratory cycle. However, gender does not influence lungs stiffness.
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Affiliation(s)
- Faisal Fakhouri
- Department of Biomedical Engineering, The Ohio State University, Columbus, OH, 43210, USA.,Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA
| | | | - Josef Pfeuffer
- MR Application Development, Siemens Healthcare GmbH, Erlangen, Germany
| | - Yevgeniya Gokun
- Department of Biomedical Informatics, Center for Biostatistics, The Ohio State University, Columbus, OH 43210, USA
| | - Arunark Kolipaka
- Department of Biomedical Engineering, The Ohio State University, Columbus, OH, 43210, USA.,Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA
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26
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PCBP1 regulates the transcription and alternative splicing of metastasis‑related genes and pathways in hepatocellular carcinoma. Sci Rep 2021; 11:23356. [PMID: 34857818 PMCID: PMC8640068 DOI: 10.1038/s41598-021-02642-z] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Accepted: 11/03/2021] [Indexed: 02/08/2023] Open
Abstract
PCBP1 is a multifunctional RNA-binding protein (RBP) expressed in most human cells and is involved in posttranscriptional gene regulation. PCBP1 regulates the alternative splicing, translation and RNA stability of many cancer-related genes and has been identified as a potential tumour suppressor gene. PCBP1 inhibits the invasion of hepatocellular carcinoma (HCC) cells, but there are few studies on the specific regulatory target and mechanism of RBPs in HCC, and it is unclear whether PCBP1 plays a role in tumour metastasis as a splicing factor. We analysed the regulation of gene expression by PCBP1 at the transcriptional level. We obtained and analysed PCBP1-knockdown RNA-seq data and eCLIP-seq data of PCBP1 in HepG2 cells and found that PCBP1 widely regulates the alternative splicing and expression of genes enriched in cancer-related pathways, including extracellular matrix, cell adhesion, small molecule metabolic process and apoptosis. We validated five regulated alternative splicing events affected by PCBP1 using RT-qPCR and found that there was a significant difference in the expression of APOC1 and SPHK1 between tumour and normal tissues. In this study, we provided convincing evidence that human PCBP1 profoundly regulates the splicing of genes associated with tumour metastasis. These findings provide new insight into potential markers or therapeutic targets for HCC treatment.
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27
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Chen X, Hughes R, Mullin N, Hawkins RJ, Holen I, Brown NJ, Hobbs JK. Atomic force microscopy reveals the mechanical properties of breast cancer bone metastases. NANOSCALE 2021; 13:18237-18246. [PMID: 34710206 PMCID: PMC8584157 DOI: 10.1039/d1nr03900h] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 10/16/2021] [Indexed: 06/13/2023]
Abstract
Mechanically dependent processes are essential in cancer metastases. However, reliable mechanical characterization of metastatic cancer remains challenging whilst maintaining the tissue complexity and an intact sample. Using atomic force microscopy, we quantified the micro-mechanical properties of relatively intact metastatic breast tumours and their surrounding bone microenvironment isolated from mice, and compared with other breast cancer models both ex vivo and in vitro. A mechanical distribution of extremely low elastic modulus and viscosity was identified on metastatic tumours, which were significantly more compliant than both 2D in vitro cultured cancer cells and subcutaneous tumour explants. The presence of mechanically distinct metastatic tumour did not result in alterations of the mechanical properties of the surrounding microenvironment at meso-scale distances (>200 μm). These findings demonstrate the utility of atomic force microscopy in studies of complex tissues and provide new insights into the mechanical properties of cancer metastases in bone.
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Affiliation(s)
- Xinyue Chen
- Department of Physics and Astronomy, University of Sheffield, S3 7RH, UK.
- Department of Oncology and Metabolism, University of Sheffield, S10 2RX, UK
- The Krebs Institute, University of Sheffield, S10 2TN, UK
| | - Russell Hughes
- Department of Oncology and Metabolism, University of Sheffield, S10 2RX, UK
| | - Nic Mullin
- Department of Physics and Astronomy, University of Sheffield, S3 7RH, UK.
- The Krebs Institute, University of Sheffield, S10 2TN, UK
| | - Rhoda J Hawkins
- Department of Physics and Astronomy, University of Sheffield, S3 7RH, UK.
- The Krebs Institute, University of Sheffield, S10 2TN, UK
| | - Ingunn Holen
- Department of Oncology and Metabolism, University of Sheffield, S10 2RX, UK
| | - Nicola J Brown
- Department of Oncology and Metabolism, University of Sheffield, S10 2RX, UK
| | - Jamie K Hobbs
- Department of Physics and Astronomy, University of Sheffield, S3 7RH, UK.
- The Krebs Institute, University of Sheffield, S10 2TN, UK
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28
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McGrath DM, Bradley CR, Francis ST. In silicoevaluation and optimisation of magnetic resonance elastography of the liver. Phys Med Biol 2021; 66. [PMID: 34678798 DOI: 10.1088/1361-6560/ac3263] [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: 05/12/2021] [Accepted: 10/22/2021] [Indexed: 11/11/2022]
Abstract
Objective.Magnetic resonance elastography (MRE) is widely adopted as a biomarker of liver fibrosis. However,in vivoMRE accuracy is difficult to assess.Approach.Finite element model (FEM) simulation was employed to evaluate liver MRE accuracy and inform methodological optimisation. MRE data was simulated in a 3D FEM of the human torso including the liver, and compared with spin-echo echo-planar imaging MRE acquisitions. The simulated MRE results were compared with the ground truth magnitude of the complex shear modulus (∣G*∣) for varying: (1) ground truth liver ∣G*∣; (2) simulated imaging resolution; (3) added noise; (4) data smoothing. Motion and strain-based signal-to-noise (SNR) metrics were evaluated on the simulated data as a means to select higher-quality voxels for preparation of acquired MRE summary statistics of ∣G*∣.Main results.The simulated MRE accuracy for a given ground truth ∣G*∣ was found to be a function of imaging resolution, motion-SNR and smoothing. At typical imaging resolutions, it was found that due to under-sampling of the MRE wave-field, combined with motion-related noise, the reconstructed simulated ∣G*∣ could contain errors on the scale of the difference between liver fibrosis stages, e.g. 54% error for ground truth ∣G*∣ = 1 kPa. Optimum imaging resolutions were identified for given ground truth ∣G*∣ and motion-SNR levels.Significance.This study provides important knowledge on the accuracy and optimisation of liver MRE. For example, for motion-SNR ≤ 5, to distinguish between liver ∣G*∣ of 2 and 3 kPa (i.e. early-stage liver fibrosis) it was predicted that the optimum isotropic voxel size is 4-6 mm.
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Affiliation(s)
- Deirdre M McGrath
- Sir Peter Mansfield Imaging Centre, University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom.,NIHR Nottingham Biomedical Research Centre, Radiological Sciences, Division of Clinical Neuroscience, Queens Medical Centre, Nottingham, NG7 2UH, United Kingdom
| | - Christopher R Bradley
- Sir Peter Mansfield Imaging Centre, University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom.,NIHR Nottingham Biomedical Research Centre, Radiological Sciences, Division of Clinical Neuroscience, Queens Medical Centre, Nottingham, NG7 2UH, United Kingdom
| | - Susan T Francis
- Sir Peter Mansfield Imaging Centre, University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom.,NIHR Nottingham Biomedical Research Centre, Radiological Sciences, Division of Clinical Neuroscience, Queens Medical Centre, Nottingham, NG7 2UH, United Kingdom
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29
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Babaei B, Fovargue D, Lloyd RA, Miller R, Jugé L, Kaplan M, Sinkus R, Nordsletten DA, Bilston LE. Magnetic Resonance Elastography Reconstruction for Anisotropic Tissues. Med Image Anal 2021; 74:102212. [PMID: 34587584 DOI: 10.1016/j.media.2021.102212] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 06/02/2021] [Accepted: 08/04/2021] [Indexed: 12/19/2022]
Abstract
Elastography has become widely used clinically for characterising changes in soft tissue mechanics that are associated with altered tissue structure and composition. However, some soft tissues, such as muscle, are not isotropic as is assumed in clinical elastography implementations. This limits the ability of these methods to capture changes in anisotropic tissues associated with disease. The objective of this study was to develop and validate a novel elastography reconstruction technique suitable for estimating the linear viscoelastic mechanical properties of transversely isotropic soft tissues. We derived a divergence-free formulation of the governing equations for acoustic wave propagation through a linearly transversely isotropic viscoelastic material, and transformed this into a weak form. This was then implemented into a finite element framework, enabling the analysis of wave input data and tissue structural fibre orientations, in this case based on diffusion tensor imaging. To validate the material constants obtained with this method, numerous in silico phantom experiments were run which encompassed a range of variations in wave input directions, material properties, fibre structure and noise. The method was also tested on ex vivo muscle and in vivo human volunteer calf muscles, and compared with a previous curl-based inversion method. The new method robustly extracted the transversely isotropic shear moduli (G⊥', G∥', G″) from the in silico phantom tests with minimal bias, including in the presence of experimentally realistic levels of noise in either fibre orientation or wave data. This new method performed better than the previous method in the presence of noise. Anisotropy estimates from the ex vivo muscle phantom agreed well with rheological tests. In vivo experiments on human calf muscles were able to detect increases in muscle shear moduli with passive muscle stretch. This new reconstruction method can be applied to quantify tissue mechanical properties of anisotropic soft tissues, such as muscle, in health and disease.
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Affiliation(s)
- Behzad Babaei
- Neuroscience Research Australia, Sydney, NSW, Australia; School of Mechanical and Manufacturing Engineering, University of New South Wales, Sydney, NSW, Australia
| | - Daniel Fovargue
- School of Biomedical Engineering and Imaging Sciences, The Rayne Institute, King's College London, SE1 7EH, London, United Kingdom
| | - Robert A Lloyd
- Neuroscience Research Australia, Sydney, NSW, Australia; Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, Australia
| | - Renee Miller
- School of Biomedical Engineering and Imaging Sciences, The Rayne Institute, King's College London, SE1 7EH, London, United Kingdom
| | - Lauriane Jugé
- School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia
| | - Max Kaplan
- Neuroscience Research Australia, Sydney, NSW, Australia; Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW, Australia
| | - Ralph Sinkus
- School of Biomedical Engineering and Imaging Sciences, The Rayne Institute, King's College London, SE1 7EH, London, United Kingdom
| | - David A Nordsletten
- School of Biomedical Engineering and Imaging Sciences, The Rayne Institute, King's College London, SE1 7EH, London, United Kingdom; Department of Surgery and Biomedical Engineering, University of Michigan, Ann Arbor, MI, United States of America
| | - Lynne E Bilston
- Neuroscience Research Australia, Sydney, NSW, Australia; Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, Australia.
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30
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Kim HY, Jo M, La JA, Choi Y, Cho EC, Kim SH, Jung Y, Kim K, Ryu JH. Detection of Lysyl Oxidase Activity in Tumor Extracellular Matrix Using Peptide-Functionalized Gold Nanoprobes. Cancers (Basel) 2021; 13:cancers13184523. [PMID: 34572752 PMCID: PMC8471099 DOI: 10.3390/cancers13184523] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Revised: 08/20/2021] [Accepted: 09/03/2021] [Indexed: 12/18/2022] Open
Abstract
Simple Summary Although various malignant tumors express high levels of lysyl oxidase (LOX) and though its role in tumor progression is well-defined, there is a lack of sensing techniques to target LOX. This study highlights the application of peptide-functionalized gold nanoprobes for sensing the LOX levels in tumor microenvironments. The gold nanoparticles (AuNPs) in these nanoprobes aggregate upon exposure to LOX, resulting in a red shift of the surface plasmon resonance peak, accompanied by a characteristic color change. This colorimetric assay based on peptide-functionalized AuNP sensitively detects LOX secreted from various cancer cells not only in vitro but also in the tissue extract. In this study, the suggested analytical approach demonstrated high specificity to LOX and did not show any color change in the presence of other enzymes. Abstract High LOX levels in the tumor microenvironment causes the cross-linking of extracellular matrix components and increases the stiffness of tumor tissue. Thus, LOX plays an important role in tumorigenesis and in lowering the tumor response to anticancer drugs. Despite comprehensive efforts to identify the roles of LOX in the tumor microenvironment, sensitive and accurate detection methods have not yet been established. Here, we suggest the use of gold nanoparticles functionalized with LOX-sensitive peptides (LS-AuNPs) that aggregate upon exposure to LOX, resulting in a visual color change. LOX-sensitive peptides (LS-peptides) contain lysine residues that are converted to allysine in the presence of LOX, which is highly reactive and binds to adjacent allysine, resulting in the aggregation of the AuNPs. We demonstrated that the synthesized LS-AuNPs are capable of detecting LOX sensitively, specifically both in vitro and in the tissue extract. Moreover, the suggested LS-AuNP-based assay is more sensitive than commonly employed assays or commercially available kits. Therefore, the LS-AuNPs developed in this study can be used to detect LOX levels and can be further used to predict the stiffness or the anticancer drug resistance of the tumor.
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Affiliation(s)
- Han Young Kim
- Department of Biomedical-Chemical Engineering, The Catholic University of Korea, Bucheon 14662, Gyeonggi-do, Korea;
| | - Mihee Jo
- Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 02792, Korea; (M.J.); (Y.C.); (K.K.)
| | - Ju A La
- Department of Chemical Engineering, Hanyang University, Seoul 04763, Korea; (J.A.L.); (E.C.C.)
| | - Youngjin Choi
- Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 02792, Korea; (M.J.); (Y.C.); (K.K.)
| | - Eun Chul Cho
- Department of Chemical Engineering, Hanyang University, Seoul 04763, Korea; (J.A.L.); (E.C.C.)
| | - Su Hee Kim
- R&D Center, Medifab Ltd., Seoul 08584, Korea;
| | - Youngmee Jung
- Center for Biomaterials, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 02792, Korea;
| | - Kwangmeyung Kim
- Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 02792, Korea; (M.J.); (Y.C.); (K.K.)
| | - Ju Hee Ryu
- Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 02792, Korea; (M.J.); (Y.C.); (K.K.)
- Correspondence: ; Tel.: +82-2-958-5942
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31
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Adebowale K, Gong Z, Hou JC, Wisdom KM, Garbett D, Lee HP, Nam S, Meyer T, Odde DJ, Shenoy VB, Chaudhuri O. Enhanced substrate stress relaxation promotes filopodia-mediated cell migration. NATURE MATERIALS 2021; 20:1290-1299. [PMID: 33875851 PMCID: PMC8390443 DOI: 10.1038/s41563-021-00981-w] [Citation(s) in RCA: 144] [Impact Index Per Article: 36.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Accepted: 03/09/2021] [Indexed: 05/11/2023]
Abstract
Cell migration on two-dimensional substrates is typically characterized by lamellipodia at the leading edge, mature focal adhesions and spread morphologies. These observations result from adherent cell migration studies on stiff, elastic substrates, because most cells do not migrate on soft, elastic substrates. However, many biological tissues are soft and viscoelastic, exhibiting stress relaxation over time in response to a deformation. Here, we have systematically investigated the impact of substrate stress relaxation on cell migration on soft substrates. We observed that cells migrate minimally on substrates with an elastic modulus of 2 kPa that are elastic or exhibit slow stress relaxation, but migrate robustly on 2-kPa substrates that exhibit fast stress relaxation. Strikingly, migrating cells were not spread out and did not extend lamellipodial protrusions, but were instead rounded, with filopodia protrusions extending at the leading edge, and exhibited small nascent adhesions. Computational models of cell migration based on a motor-clutch framework predict the observed impact of substrate stress relaxation on cell migration and filopodia dynamics. Our findings establish substrate stress relaxation as a key requirement for robust cell migration on soft substrates and uncover a mode of two-dimensional cell migration marked by round morphologies, filopodia protrusions and weak adhesions.
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Affiliation(s)
- Kolade Adebowale
- Department of Chemical Engineering, Stanford University, Stanford, CA, USA
- Chemistry, Engineering, and Medicine for Human Health (ChEM-H), Stanford University, Stanford, CA, USA
| | - Ze Gong
- Department of Materials Science and Engineering, University of Pennsylvania, Philadelphia, PA, USA
| | - Jay C Hou
- Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA
| | - Katrina M Wisdom
- Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA
- Department of Mechanical Engineering, Stanford University, Stanford, CA, USA
| | - Damien Garbett
- Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA
| | - Hong-Pyo Lee
- Department of Mechanical Engineering, Stanford University, Stanford, CA, USA
| | - Sungmin Nam
- Department of Mechanical Engineering, Stanford University, Stanford, CA, USA
- John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA
| | - Tobias Meyer
- Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA
- Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY, USA
| | - David J Odde
- Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA
| | - Vivek B Shenoy
- Department of Materials Science and Engineering, University of Pennsylvania, Philadelphia, PA, USA
- Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA
| | - Ovijit Chaudhuri
- Chemistry, Engineering, and Medicine for Human Health (ChEM-H), Stanford University, Stanford, CA, USA.
- Department of Mechanical Engineering, Stanford University, Stanford, CA, USA.
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Ormachea J, Parker KJ. Reverberant shear wave phase gradients for elastography. Phys Med Biol 2021; 66. [PMID: 34359063 DOI: 10.1088/1361-6560/ac1b37] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Accepted: 08/06/2021] [Indexed: 12/19/2022]
Abstract
Reverberant shear wave fields are produced when multiple sources and multiple reflections establish a complex three-dimensional wave field within an organ. The expected values are assumed to be isotropic across all directions and the autocorrelation functions for velocity are expressed in terms of spherical Bessel functions. These results provide the basis for adroit implementations of elastography from imaging systems that can map out the internal velocity or displacement of tissues during reverberant field excitations. By examining the phase distribution of the reverberant field, additional estimators can be derived. In particular, we demonstrate that the reverberantphase gradientis shown to be proportional to the local value of wavenumber. This phase estimator is less sensitive to imperfections in the reverberant field distribution and requires a smaller support window, relative to earlier estimators based on autocorrelation. Applications are shown in simulations, phantoms, andin vivoliver.
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Affiliation(s)
- J Ormachea
- Department of Electrical and Computer Engineering, University of Rochester, 724 Computer Studies Building, PO Box 270231, Rochester, NY 14627, United States of America
| | - K J Parker
- Department of Electrical and Computer Engineering, University of Rochester, 724 Computer Studies Building, PO Box 270231, Rochester, NY 14627, United States of America
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Fiorito M, Fovargue D, Capilnasiu A, Hadjicharalambous M, Nordsletten D, Sinkus R, Lee J. Impact of axisymmetric deformation on MR elastography of a nonlinear tissue-mimicking material and implications in peri-tumour stiffness quantification. PLoS One 2021; 16:e0253804. [PMID: 34242296 PMCID: PMC8270167 DOI: 10.1371/journal.pone.0253804] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Accepted: 06/12/2021] [Indexed: 11/19/2022] Open
Abstract
Solid tumour growth is often associated with the accumulation of mechanical stresses acting on the surrounding host tissue. Due to tissue nonlinearity, the shear modulus of the peri-tumoural region inherits a signature from the tumour expansion which depends on multiple factors, including the soft tissue constitutive behaviour and its stress/strain state. Shear waves used in MR-elastography (MRE) sense the apparent change in shear modulus along their propagation direction, thereby probing the anisotropic stiffness field around the tumour. We developed an analytical framework for a heterogeneous shear modulus distribution using a thick-shelled sphere approximation of the tumour and soft tissue ensemble. A hyperelastic material (plastisol) was identified to validate the proposed theory in a phantom setting. A balloon-catheter connected to a pressure sensor was used to replicate the stress generated from tumour pressure and growth while MRE data were acquired. The shear modulus anisotropy retrieved from the reconstructed elastography data confirmed the analytically predicted patterns at various levels of inflation. An alternative measure, combining the generated deformation and the local wave direction and independent of the reconstruction strategy, was also proposed to correlate the analytical findings with the stretch probed by the waves. Overall, this work demonstrates that MRE in combination with non-linear mechanics, is able to identify the apparent shear modulus variation arising from the strain generated by a growth within tissue, such as an idealised model of tumour. Investigation in real tissue represents the next step to further investigate the implications of endogenous forces in tissue characterisation through MRE.
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Affiliation(s)
- Marco Fiorito
- School of Biomedical Engineering and Imaging Sciences, King’s College London, London, United Kingdom
| | - Daniel Fovargue
- School of Biomedical Engineering and Imaging Sciences, King’s College London, London, United Kingdom
| | - Adela Capilnasiu
- School of Biomedical Engineering and Imaging Sciences, King’s College London, London, United Kingdom
| | | | - David Nordsletten
- School of Biomedical Engineering and Imaging Sciences, King’s College London, London, United Kingdom
- Department of Biomedical Engineering and Cardiac Surgery, University of Michigan, Ann Arbor, Michigan, United States of America
| | - Ralph Sinkus
- School of Biomedical Engineering and Imaging Sciences, King’s College London, London, United Kingdom
- U1148, INSERM, Hôpital Bichat, Paris, France
| | - Jack Lee
- School of Biomedical Engineering and Imaging Sciences, King’s College London, London, United Kingdom
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Lee HK, Kong D, Choi K, Mislati R, Doyley MM. A Robust and Fast Method for 2-D Shear Wave Speed Calculation. IEEE TRANSACTIONS ON ULTRASONICS, FERROELECTRICS, AND FREQUENCY CONTROL 2021; 68:2351-2360. [PMID: 33625981 DOI: 10.1109/tuffc.2021.3061916] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
We developed a new method, called the tangent plane method (TPM), for more efficiently and accurately estimating 2-D shear wave speed (SWS) from any direction of wave propagation. In this technique, we estimate SWS by solving the Eikonal equation because this approach is more robust to noise. To further enhance the performance, we computed the tangent plane of the arrival time surface. To evaluate the approach, we performed simulations and also conducted phantom studies. Simulation studies showed that TPM was more robust to noise than the conventional methods such as 2-D cross correlation (CC) and the distance method. The contrast/CNR for an inclusion (69 kPa; manufacturer provided stiffness) of a phantom is 0.54/4.17, 0.54/1.82, and 0.46/1.22. SWS results [mean and standard deviation (SD)] were 4.41 ± 0.49, 4.62 ± 0.85, and 3.66 ± 0.99 m/s, respectively, while the manufacturer's reported value (mean and range) is 4.81 ± 0.49 m/s. This shows that TPM has the higher CNR and lower SD than other methods. To increase the computation speed, an iterative version of TPM (ITPM) was also developed, which calculated the time-of-flight iteratively. ITPM reduced the computation time to 3.6%, i.e., from 748 to 27 s. In vivo case analysis demonstrated the feasibility of using the conventional ultrasound scanner for the proposed 2-D SWS algorithms.
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Li H, Flé G, Bhatt M, Qu Z, Ghazavi S, Yazdani L, Bosio G, Rafati I, Cloutier G. Viscoelasticity Imaging of Biological Tissues and Single Cells Using Shear Wave Propagation. FRONTIERS IN PHYSICS 2021; 9. [DOI: 10.3389/fphy.2021.666192] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Changes in biomechanical properties of biological soft tissues are often associated with physiological dysfunctions. Since biological soft tissues are hydrated, viscoelasticity is likely suitable to represent its solid-like behavior using elasticity and fluid-like behavior using viscosity. Shear wave elastography is a non-invasive imaging technology invented for clinical applications that has shown promise to characterize various tissue viscoelasticity. It is based on measuring and analyzing velocities and attenuations of propagated shear waves. In this review, principles and technical developments of shear wave elastography for viscoelasticity characterization from organ to cellular levels are presented, and different imaging modalities used to track shear wave propagation are described. At a macroscopic scale, techniques for inducing shear waves using an external mechanical vibration, an acoustic radiation pressure or a Lorentz force are reviewed along with imaging approaches proposed to track shear wave propagation, namely ultrasound, magnetic resonance, optical, and photoacoustic means. Then, approaches for theoretical modeling and tracking of shear waves are detailed. Following it, some examples of applications to characterize the viscoelasticity of various organs are given. At a microscopic scale, a novel cellular shear wave elastography method using an external vibration and optical microscopy is illustrated. Finally, current limitations and future directions in shear wave elastography are presented.
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Dynamic cellular biomechanics in responses to chemotherapeutic drug in hypoxia probed by atomic force spectroscopy. Oncotarget 2021; 12:1165-1177. [PMID: 34136085 PMCID: PMC8202777 DOI: 10.18632/oncotarget.27974] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Accepted: 05/14/2021] [Indexed: 12/11/2022] Open
Abstract
The changes in cellular structure play an important role in cancer cell development, progression, and metastasis. By exploiting single-cell, force spectroscopy methods, we probed biophysical and biomechanical kinetics (stiffness, morphology, roughness, adhesion) of brain, breast, prostate, and pancreatic cancer cells with standard chemotherapeutic drugs in normoxia and hypoxia over 12–24 hours. After exposure to the drugs, we found that brain, breast, and pancreatic cancer cells became approximately 55–75% less stiff, while prostate cancer cells became more stiff, due to either drug-induced disruption or reinforcement of cytoskeletal structure. However, the rate of the stiffness change decreased up to 2-folds in hypoxia, suggesting a correlation between cellular stiffness and drug resistance of cancer cells in hypoxic tumor microenvironment. Also, we observed significant changes in the cell body height, surface roughness, and cytoadhesion of cancer cells after exposure to drugs, which followed the trend of stiffness. Our results show that a degree of chemotherapeutic drug effects on biomechanical and biophysical properties of cancer cells is distinguishable in normoxia and hypoxia, which are correlated with alteration of cytoskeletal structure and integrity during drug-induced apoptotic process.
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Fukui R, Sasaki K, Kawai K, Taira T, Nozawa H, Kaneko M, Murono K, Emoto S, Iida Y, Ishii H, Yokoyama Y, Anzai H, Sonoda H, Ishihara S. Establishing a novel method for assessing elasticity of internal anal sphincter using ultrasonic real-time tissue elastography. ANZ J Surg 2021; 91:E360-E366. [PMID: 33844397 DOI: 10.1111/ans.16760] [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] [Received: 01/05/2021] [Revised: 03/07/2021] [Accepted: 03/08/2021] [Indexed: 11/27/2022]
Abstract
BACKGROUND Evaluating anorectal function using real-time tissue elastography (RTE) has not been reported. A previous study reported that in the internal anal sphincter (IAS) of surgical specimens of patients with rectal cancer who underwent abdominoperineal resection, there was an increased fibrosis trend in those who underwent pre-operative chemoradiotherapy (CRT) compared with non-CRT. We speculated that CRT might have induced sclerosis of the IAS because of fibrosis. Therefore, we aimed to establish a method of quantitating the degree of IAS hardness using RTE on endoanal ultrasonography. METHODS RTE was performed with freehand manual compression under a defined pressure at the middle anal canal. Using the most compressive point in the strain graph, we traced the region of interest in the IAS. The strain histogram showed a frequency distribution of colours according to the degree of strain (numeric scan ranging from 0 to 255; smaller number indicated harder tissue). We defined the mean of the strain histogram as 'elasticity'. Ten patients with locally advanced rectal cancer who underwent pre-operative CRT were prospectively enrolled. We statistically evaluated the correlation between IAS elasticity and maximum resting pressure (MRP) values both at pre- and post-CRT. MRP was examined concurrently with the examination of IAS elasticity. RESULTS Representativity of elasticity measurements was demonstrated. It revealed a trend: IAS elasticity had a moderate inverse correlation with MRP (r = 0.41, P = 0.07), regardless of whether measurements were made before or after CRT. CONCLUSION We established a completely novel method for the assessment of elasticity of the IAS, using RTE on endoanal ultrasonography.
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Affiliation(s)
- Risa Fukui
- Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kazuhito Sasaki
- Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kazushige Kawai
- Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tetsuro Taira
- Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroaki Nozawa
- Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Manabu Kaneko
- Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Koji Murono
- Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Shigenobu Emoto
- Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yuuki Iida
- Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroaki Ishii
- Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yuichiro Yokoyama
- Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroyuki Anzai
- Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hirofumi Sonoda
- Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Soichiro Ishihara
- Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
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Sango Solanas P, Tse Ve Koon K, Ratiney H, Millioz F, Caussy C, Beuf O. Harmonic wideband simultaneous dual-frequency MR Elastography. NMR IN BIOMEDICINE 2021; 34:e4442. [PMID: 33179393 DOI: 10.1002/nbm.4442] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Revised: 10/21/2020] [Accepted: 10/21/2020] [Indexed: 06/11/2023]
Abstract
Magnetic resonance elastography (MRE) is used to non-invasively quantify viscoelastic properties of tissues based on the measurement of propagation characteristics of shear waves. Because some of these viscoelastic parameters show a frequency dependence, multifrequency analysis allows us to measure the wave propagation dispersion, leading to a better characterization of tissue properties. Conventionally, motion encoding gradients (MEGs) oscillating at the same frequency as the mechanical excitation encode motion. Hence, multifrequency data is usually obtained by sequentially repeating monochromatic wave excitations experiments at different frequencies. The result is that the total acquisition time is multiplied by a factor corresponding to the number of repetitions of monofrequency experiments, which is a major limitation of multifrequency MRE. In order to make it more accessible, a novel single-shot harmonic wideband dual-frequency MRE method is proposed. Two superposed shear waves of different frequencies are simultaneously generated and propagate in a sample. Trapezoidal oscillating MEGs are used to encode mechanical vibrations having frequencies that are an odd multiple of the MEG frequency. The number of phase offsets is optimized to reduce the acquisition time. For this purpose, a sampling method not respecting the Shannon theorem is used to produce a controlled temporal aliasing that allows us to encode both frequencies without any additional examination time. Phantom experiments were run to compare conventional monofrequency MRE with the single-shot dual-frequency MRE method and showed excellent agreement between the reconstructed shear storage moduli G'. In addition, dual-frequency MRE yielded an increased signal-to-noise ratio compared with conventional monofrequency MRE acquisitions when encoding the high frequency component. The novel proposed multifrequency MRE method could be applied to simultaneously acquire more than two frequency components, reducing examination time. Further studies are needed to confirm its applicability in preclinical and clinical models.
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Affiliation(s)
- Pilar Sango Solanas
- Univ Lyon, INSA-Lyon, Université Claude Bernard Lyon 1, UJM-Saint Etienne, CNRS, Inserm, CREATIS UMR 5220, U1206, Lyon, France
| | - Kevin Tse Ve Koon
- Univ Lyon, INSA-Lyon, Université Claude Bernard Lyon 1, UJM-Saint Etienne, CNRS, Inserm, CREATIS UMR 5220, U1206, Lyon, France
| | - Helene Ratiney
- Univ Lyon, INSA-Lyon, Université Claude Bernard Lyon 1, UJM-Saint Etienne, CNRS, Inserm, CREATIS UMR 5220, U1206, Lyon, France
| | - Fabien Millioz
- Univ Lyon, INSA-Lyon, Université Claude Bernard Lyon 1, UJM-Saint Etienne, CNRS, Inserm, CREATIS UMR 5220, U1206, Lyon, France
| | - Cyrielle Caussy
- Univ Lyon, CarMen Laboratory, INSERM, INRA, INSA Lyon, Université Claude Bernard Lyon 1, Pierre-Bénite, France
- Hospices Civils de Lyon, Département Endocrinologie, Diabète et Nutrition, Hôpital Lyon Sud, Pierre-Bénite, France
| | - Olivier Beuf
- Univ Lyon, INSA-Lyon, Université Claude Bernard Lyon 1, UJM-Saint Etienne, CNRS, Inserm, CREATIS UMR 5220, U1206, Lyon, France
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Gendin DI, Nayak R, Wang Y, Bayat M, Fazzio RT, Oberai AA, Hall TJ, Barbone PE, Alizad A, Fatemi M. Repeatability of Linear and Nonlinear Elastic Modulus Maps From Repeat Scans in the Breast. IEEE TRANSACTIONS ON MEDICAL IMAGING 2021; 40:748-757. [PMID: 33151880 PMCID: PMC11017922 DOI: 10.1109/tmi.2020.3036032] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Compression elastography allows the precise measurement of large deformations of soft tissue in vivo. From an image sequence showing tissue undergoing large deformation, an inverse problem for both the linear and nonlinear elastic moduli distributions can be solved. As part of a larger clinical study to evaluate nonlinear elastic modulus maps (NEMs) in breast cancer, we evaluate the repeatability of linear and nonlinear modulus maps from repeat measurements. Within the cohort of subjects scanned to date, 20 had repeat scans. These repeated scans were processed to evaluate NEM repeatability. In vivo data were acquired by a custom-built, digitally controlled, uniaxial compression device with force feedback from the pressure-plate. RF-data were acquired using plane-wave imaging, at a frame-rate of 200 Hz, with a ramp-and-hold compressive force of 8N, applied at 8N/sec. A 2D block-matching algorithm was used to obtain sample-level displacement fields which were then tracked at subsample resolution using 2D cross correlation. Linear and nonlinear elasticity parameters in a modified Veronda-Westmann model of tissue elasticity were estimated using an iterative optimization method. For the repeated scans, B-mode images, strain images, and linear and nonlinear elastic modulus maps are measured and compared. Results indicate that when images are acquired in the same region of tissue and sufficiently high strain is used to recover nonlinearity parameters, then the reconstructed modulus maps are consistent.
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40
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Dong H, Jin N, Kannengiesser S, Raterman B, White RD, Kolipaka A. Magnetic resonance elastography for estimating in vivo stiffness of the abdominal aorta using cardiac-gated spin-echo echo-planar imaging: a feasibility study. NMR IN BIOMEDICINE 2021; 34:e4420. [PMID: 33021342 DOI: 10.1002/nbm.4420] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 09/02/2020] [Accepted: 09/10/2020] [Indexed: 06/11/2023]
Abstract
INTRODUCTION Magnetic resonance elastography (MRE)-derived aortic stiffness is a potential biomarker for multiple cardiovascular diseases. Currently, gradient-recalled echo (GRE) MRE is a widely accepted technique to estimate aortic stiffness. However, multi-slice GRE MRE requires multiple breath-holds (BHs), which can be challenging for patients who cannot consistently hold their breath. The aim of this study was to investigate the feasibility of a multi-slice spin-echo echo-planar imaging (SE-EPI) MRE sequence for quantifying in vivo aortic stiffness using a free-breathing (FB) protocol and a single-BH protocol. METHOD On Scanner 1, 25 healthy subjects participated in the validation of FB SE-EPI against FB GRE. On Scanner 2, another 15 healthy subjects were recruited to compare FB SE-EPI with single-BH SE-EPI. Among all volunteers, five participants were studied on both scanners to investigate the inter-scanner reproducibility of FB SE-EPI aortic MRE. Bland-Altman analysis, Lin's concordance correlation coefficient (LCCC) and coefficient of variation (COV) were evaluated. The phase-difference signal-to-noise ratios (PD SNR) were compared. RESULTS Aortic MRE using FB SE-EPI and FB GRE yielded similar stiffnesses (paired t-test, P = 0.19), with LCCC = 0.97. The FB SE-EPI measurements were reproducible (intra-scanner LCCC = 0.96) and highly repeatable (LCCC = 0.99). The FB SE-EPI MRE was also reproducible across different scanners (inter-scanner LCCC = 0.96). Single-BH SE-EPI scans yielded similar stiffness to FB SE-EPI scans (LCCC = 0.99) and demonstrated a low COV of 2.67% across five repeated measurements. CONCLUSION Multi-slice SE-EPI aortic MRE using an FB protocol or a single-BH protocol is reproducible and repeatable with advantage over multi-slice FB GRE in reducing acquisition time. Additionally, FB SE-EPI MRE provides a potential alternative to BH scans for patients who have challenges in holding their breath.
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Affiliation(s)
- Huiming Dong
- Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
- Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio, USA
| | - Ning Jin
- Siemens Medical Solution, Columbus, Ohio, USA
| | | | - Brian Raterman
- Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Richard D White
- Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
- Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio, USA
- Department of Internal Medicine-Division of Cardiology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Arunark Kolipaka
- Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
- Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio, USA
- Department of Internal Medicine-Division of Cardiology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
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Manduca A, Bayly PJ, Ehman RL, Kolipaka A, Royston TJ, Sack I, Sinkus R, Van Beers BE. MR elastography: Principles, guidelines, and terminology. Magn Reson Med 2020; 85:2377-2390. [PMID: 33296103 DOI: 10.1002/mrm.28627] [Citation(s) in RCA: 139] [Impact Index Per Article: 27.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 10/20/2020] [Accepted: 11/09/2020] [Indexed: 12/13/2022]
Abstract
Magnetic resonance elastography (MRE) is a phase contrast-based MRI technique that can measure displacement due to propagating mechanical waves, from which material properties such as shear modulus can be calculated. Magnetic resonance elastography can be thought of as quantitative, noninvasive palpation. It is increasing in clinical importance, has become widespread in the diagnosis and staging of liver fibrosis, and additional clinical applications are being explored. However, publications have reported MRE results using many different parameters, acquisition techniques, processing methods, and varied nomenclature. The diversity of terminology can lead to confusion (particularly among clinicians) about the meaning of and interpretation of MRE results. This paper was written by the MRE Guidelines Committee, a group formalized at the first meeting of the ISMRM MRE Study Group, to clarify and move toward standardization of MRE nomenclature. The purpose of this paper is to (1) explain MRE terminology and concepts to those not familiar with them, (2) define "good practices" for practitioners of MRE, and (3) identify opportunities to standardize terminology, to avoid confusion.
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Affiliation(s)
- Armando Manduca
- Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, USA
| | - Philip J Bayly
- Mechanical Engineering and Materials Science, Washington University in St. Louis, St. Louis, Missouri, USA
| | - Richard L Ehman
- Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, USA
| | - Arunark Kolipaka
- Department of Radiology, Ohio State University, Columbus, Ohio, USA
| | - Thomas J Royston
- Department of Bioengineering, University of Illinois at Chicago, Chicago, Illinois, USA
| | - Ingolf Sack
- Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Ralph Sinkus
- Imaging Sciences & Biomedical Engineering, Kings College London, London, United Kingdom
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Generation of acoustic-Brownian noise in nuclear magnetic resonance under non-equilibrium thermal fluctuations. Sci Rep 2020; 10:21406. [PMID: 33293582 PMCID: PMC7722860 DOI: 10.1038/s41598-020-77206-8] [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] [Received: 06/04/2019] [Accepted: 10/08/2020] [Indexed: 11/20/2022] Open
Abstract
We present an analytical study on generation of acoustic-Brownian noise in nuclear magnetic resonance (NMR) induced as a result of thermal fluctuations of the magnetic moments under non-equilibrium thermal interactions which has not been explored independent of Nyquist–Johnson noise until now. The mechanism of physical coupling between non-equilibrium thermal fluctuations and magnetic moments is illustrated using Lighthill’s formulation on suspension dynamics. We discover that unlike Nyquist–Johnson noise which has a uniform spectral density across a range of frequencies, the spectral dependence of acoustic-Brownian noise decreases with an increase in frequency and resembles Brownian noise associated with a particle in a potential well. The results have applications in the field of image enhancement algorithm as well as noise reduction instrumentation in NMR systems.
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Bayat M, Nabavizadeh A, Nayak R, Webb JM, Gregory AV, Meixner DD, Fazzio RT, Insana MF, Alizad A, Fatemi M. Multi-parameter Sub-Hertz Analysis of Viscoelasticity With a Quality Metric for Differentiation of Breast Masses. ULTRASOUND IN MEDICINE & BIOLOGY 2020; 46:3393-3403. [PMID: 32917470 PMCID: PMC7606763 DOI: 10.1016/j.ultrasmedbio.2020.08.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 07/14/2020] [Accepted: 08/04/2020] [Indexed: 05/10/2023]
Abstract
We applied sub-Hertz analysis of viscoelasticity (SAVE) to differentiate breast masses in pre-biopsy patients. Tissue response during external ramp-and-hold stress was ultrasonically detected. Displacements were used to acquire tissue viscoelastic parameters. The fast instantaneous response and slow creep-like deformations were modeled as the response of a linear standard solid from which viscoelastic parameters were estimated. These parameters were used in a multi-variable classification framework to differentiate malignant from benign masses identified by pathology. When employing all viscoelasticity parameters, SAVE resulted in 71.43% accuracy in differentiating lesions. When combined with ultrasound features and lesion size, accuracy was 82.24%. Adding a quality metric based on uniaxial motion increased the accuracy to 81.25%. When all three were combined with SAVE, accuracy was 91.3%. These results confirm the utility of SAVE as a robust ultrasound-based diagnostic tool for non-invasive differentiation of breast masses when used as stand-alone biomarkers or in conjunction with ultrasonic features.
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Affiliation(s)
- Mahdi Bayat
- Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
| | - Alireza Nabavizadeh
- Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
| | - Rohit Nayak
- Department of Radiology, Mayo Clinic College Medicine and Science, Rochester, MN, USA
| | - Jeremy M Webb
- Department of Radiology, Mayo Clinic College Medicine and Science, Rochester, MN, USA
| | - Adriana V Gregory
- Department of Radiology, Mayo Clinic College Medicine and Science, Rochester, MN, USA
| | - Duane D Meixner
- Department of Radiology, Mayo Clinic College Medicine and Science, Rochester, MN, USA
| | - Robert T Fazzio
- Department of Radiology, Mayo Clinic College Medicine and Science, Rochester, MN, USA
| | - Michael F Insana
- Department of Bioengineering, University of Illinois Urbana-Champaign, Champaign, IL, USA
| | - Azra Alizad
- Department of Radiology, Mayo Clinic College Medicine and Science, Rochester, MN, USA
| | - Mostafa Fatemi
- Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.
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Sayed AM, Naser MA, Wahba AA, Eldosoky MAA. Breast Tumor Diagnosis Using Finite-Element Modeling Based on Clinical in vivo Elastographic Data. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2020; 39:2351-2363. [PMID: 32472949 DOI: 10.1002/jum.15344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Revised: 02/21/2020] [Accepted: 04/26/2020] [Indexed: 06/11/2023]
Abstract
OBJECTIVES This study exploited finite-element modeling (FEM) to simulate breast tissue multicompression during ultrasound elastography to classify breast tumors based on their nonlinear biomechanical properties. METHODS Numeric simulations were first calculated by using 3-dimensional (3D) virtual models with an assumed tumor's geometric dimensions but with actual material properties to test and validate the FEM. Further numeric simulations were used to construct 3D models based on in vivo experimental data to verify our models. The models were designed for each individual in vivo case, emphasizing the geometry, position, and biomechanical properties of the breast tissue. At different compression levels, tissue strains were analyzed between the tumors and the background normal tissues to explore their nonlinearity and classify the tumor type. Tumor classification parameters were deduced by using a power-law relationship between the applied compressive forces and strain differences. RESULTS Classification parameters were compared between benign and malignant tumors, for which they were found to be statistically significant in classifying the tumor types (P < .05) by both the validation and verification of FEM. We compared the classification parameters between the in vivo and FEM classifications, for which they were found to be strongly correlated (R = 0.875; P < .001), with no statistical differences between their outcomes (P = .909). CONCLUSIONS Good agreement between the model outcomes and the in vivo diagnostics was reported. The implemented models were validated and verified. The introduced 3D modeling method may augment elastographic methods to preliminary classify breast tumors at an early stage.
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Affiliation(s)
- Ahmed M Sayed
- Biomedical Engineering Department, Faculty of Engineering, Helwan University, Helwan, Egypt
| | - Mohamed A Naser
- Biomedical Engineering Department, Faculty of Engineering, Minia University, Minia, Egypt
| | - Ashraf A Wahba
- Biomedical Engineering Department, Faculty of Engineering, Helwan University, Helwan, Egypt
| | - Mohamed A A Eldosoky
- Biomedical Engineering Department, Faculty of Engineering, Helwan University, Helwan, Egypt
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Mirzaei M, Asif A, Rivaz H. Accurate and Precise Time-Delay Estimation for Ultrasound Elastography With Prebeamformed Channel Data. IEEE TRANSACTIONS ON ULTRASONICS, FERROELECTRICS, AND FREQUENCY CONTROL 2020; 67:1752-1763. [PMID: 32248101 DOI: 10.1109/tuffc.2020.2985060] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Free-hand palpation ultrasound elastography is a noninvasive approach for detecting pathological alteration in tissue. In this method, the tissue is compressed by a handheld probe and displacement of each sample is estimated, a process which is also known as time-delay estimation (TDE). Even with the simplifying assumption that ignores out of plane motion, TDE is an ill-posed problem requiring estimation of axial and lateral displacements for each sample from its intensity. A well-known class of methods for making elastography a well-posed problem is regularized optimization-based methods, which imposes smoothness regularization in the associated cost function. In this article, we propose to utilize channel data that have been compensated for time gain and time delay (introduced by transmission) instead of postbeamformed radio frequency (RF) data in the optimization problem. We name our proposed method Channel data for GLobal Ultrasound Elastography (CGLUE). We analytically derive bias and variances of TDE as functions of data noise for CGLUE and Global Ultrasound Elastography (GLUE) and use the Cauchy-Schwarz inequality to prove that CGLUE provides a TDE with lower bias and variance error. To further illustrate the improved performance of CGLUE, the results of simulation, experimental phantom, and ex-vivo experiments are presented.
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46
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Patel BK, Samreen N, Zhou Y, Chen J, Brandt K, Ehman R, Pepin K. MR Elastography of the Breast: Evolution of Technique, Case Examples, and Future Directions. Clin Breast Cancer 2020; 21:e102-e111. [PMID: 32900617 DOI: 10.1016/j.clbc.2020.08.005] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Revised: 07/20/2020] [Accepted: 08/10/2020] [Indexed: 02/07/2023]
Abstract
Recognizing that breast cancers present as firm, stiff lesions, the foundation of breast magnetic resonance elastography (MRE) is to combine tissue stiffness parameters with sensitive breast MR contrast-enhanced imaging. Breast MRE is a non-ionizing, cross-sectional MR imaging technique that provides for quantitative viscoelastic properties, including tissue stiffness, elasticity, and viscosity, of breast tissues. Currently, the technique continues to evolve as research surrounding the use of MRE in breast tissue is still developing. In the setting of a newly diagnosed cancer, associated desmoplasia, stiffening of the surrounding stroma, and necrosis are known to be prognostic factors that can add diagnostic information to patient treatment algorithms. In fact, mechanical properties of the tissue might also influence breast cancer risk. For these reasons, exploration of breast MRE has great clinical value. In this review, we will: (1) address the evolution of the various MRE techniques; (2) provide a brief overview of the current clinical studies in breast MRE with interspersed case examples; and (3) suggest directions for future research.
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Affiliation(s)
| | | | - Yuxiang Zhou
- Department of Radiology, Mayo Clinic, Phoenix, AZ
| | - Jun Chen
- Department of Radiology, Mayo Clinic, Rochester, MN
| | - Kathy Brandt
- Department of Radiology, Mayo Clinic, Rochester, MN
| | | | - Kay Pepin
- Department of Radiology, Mayo Clinic, Rochester, MN
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47
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Guenthner C, Sethi S, Troelstra M, van Gorkum RJ, Gastl M, Sinkus R, Kozerke S. Unipolar MR elastography: Theory, numerical analysis and implementation. NMR IN BIOMEDICINE 2020; 33:e4138. [PMID: 31664745 PMCID: PMC7003474 DOI: 10.1002/nbm.4138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/06/2018] [Revised: 06/10/2019] [Accepted: 06/14/2019] [Indexed: 06/10/2023]
Abstract
In MR elastography (MRE), zeroth moment balanced motion-encoding gradients (MEGs) are incorporated into MRI sequences to induce a phase shift proportional to the local displacement caused by external actuation. To maximize the signal-to-noise ratio (SNR), fractional encoding is employed, i.e., the MEG duration is reduced below the wave period. Here, gradients encode primarily the velocity of the motion-reducing encoding efficiency. Thus, in GRE-MRE, T2 * decay and motion sensitivity have to be balanced, imposing a lower limit on repetition times (TRs). We propose to use a single trapezoidal gradient, a "unipolar gradient", to directly encode spin displacement. Such gradients cannot be used in conventional sequences as they exhibit a large zeroth moment and dephase magnetization. By time-reversing a spoiled SSFP sequence, the spoiling gradient becomes an efficient unipolar MEG. The proposed "unipolar MRE" technique benefits from this approach in three ways: first, displacement encoding is split over multiple TRs increasing motion sensitivity; second, spoiler and MEG coincide, allowing a reduction in TR; third, motion sensitivity of a typical unipolar lobe is of an order of magnitude higher than a bipolar MEG of equal duration. In this work, motion encoding using unipolar MRE is analyzed using the extended phase graph (EPG) formalism with a periodic motion propagator. As an approximation, the two-transverse TR approximation for diffusion-weighted SSFP is extended to incorporate cyclic motion. A complex encoding efficiency metric is introduced to compare the displacement fields of unipolar and conventional GRE-MRE sequences in both magnitude and phase. The derived theoretical encoding equations are used to characterize the proposed sequence using an extensive parameter study. Unipolar MRE is validated against conventional GRE-MRE in a phantom study showing excellent agreement between measured displacement fields. In addition, unipolar MRE yields significantly increased octahedral shear strain-SNR relative to conventional GRE-MRE and allows for the recovery of high stiffness inclusions, where conventional GRE-MRE fails.
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Affiliation(s)
- Christian Guenthner
- Institute for Biomedical EngineeringUniversity and ETH ZurichZurichSwitzerland
| | - Sweta Sethi
- Division of Research OncologyGuy's and Saint Thomas' NHS Foundation TrustLondonUK
| | - Marian Troelstra
- Division for Imaging Sciences & Biomedical EngineeringKing's College LondonLondonUK
- Department of Radiology and Nuclear MedicineUniversity Medical Center AmsterdamAmsterdamThe Netherlands
| | | | - Mareike Gastl
- Institute for Biomedical EngineeringUniversity and ETH ZurichZurichSwitzerland
| | - Ralph Sinkus
- Division for Imaging Sciences & Biomedical EngineeringKing's College LondonLondonUK
| | - Sebastian Kozerke
- Institute for Biomedical EngineeringUniversity and ETH ZurichZurichSwitzerland
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48
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Broadband Time Domain Diffuse Optical Reflectance Spectroscopy: A Review of Systems, Methods, and Applications. APPLIED SCIENCES-BASEL 2019. [DOI: 10.3390/app9245465] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
This review presents recent developments and a wide overview of broadband time domain diffuse optical spectroscopy (TD-DOS). Various topics including physics of photon migration, advanced instrumentation, methods of analysis, applications covering multiple domains (tissue chromophore, in vivo studies, food, wood, pharmaceutical industry) are elaborated. The key role of standardization and recent studies in that direction are discussed. Towards the end, a brief outlook is presented on the current status and future trends in broadband TD-DOS.
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49
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Liu X, Hubbi B, Zhou X. Spatial coordinate corrected motion tracking for optical coherence elastography. BIOMEDICAL OPTICS EXPRESS 2019; 10:6160-6171. [PMID: 31853392 PMCID: PMC6913417 DOI: 10.1364/boe.10.006160] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 11/03/2019] [Accepted: 11/04/2019] [Indexed: 05/28/2023]
Abstract
We investigate a spatial coordinate correction (SCC) method to track motion with high accuracy for optical coherence elastography (OCE). Through SCC, we refer the displacement field tracked by optical coherence tomography (OCT) in the loaded sample to individual material points defined in a fixed coordinate system. SCC allows OCE to perform spatially and temporally unambiguous tracking of displacement and enables accurate mechanical characterization of biological tissue for cancer diagnosis and tumor margin assessment. In this study, we validated the effectiveness of motion tracking based on SCC using experimental OCE data obtained from ex vivo human breast tissues.
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Affiliation(s)
- Xuan Liu
- Department of Electrical and Computer Engineering, New Jersey Institute of Technology, University Heights, Newark, NJ 07102, USA
| | - Basil Hubbi
- Department of Radiology, New Jersey Medical School, Newark, NJ 07103, USA
| | - Xianlian Zhou
- Department of Biomedical Engineering, New Jersey Institute of Technology, University Heights, Newark, NJ 07102, USA
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Numano T, Habe T, Ito D, Onishi T, Takamoto K, Mizuhara K, Nishijo H, Igarashi K, Ueki T. A new technique for motion encoding gradient-less MR elastography of the psoas major muscle: A gradient-echo type multi-echo sequence. Magn Reson Imaging 2019; 63:85-92. [PMID: 31425804 DOI: 10.1016/j.mri.2019.08.006] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Revised: 07/29/2019] [Accepted: 08/15/2019] [Indexed: 11/29/2022]
Abstract
The present study aimed to develop vibration techniques for magnetic resonance (MR) elastography (MRE) of the psoas major muscle (PM). Seven healthy volunteers were included. MRE was performed with motion-encoding gradient (MEG)-less multi-echo MRE sequence, which allows clinicians to perform MRE using conventional MR imaging. In order to transmit mechanical vibration of the pneumatic type to the PM, a long narrow vibration pad was designed using a 3D printer, and the optimum vibration techniques were verified. The vibration pad was placed under the lower back, with the volunteers in the supine position. The results indicated that the PM vibrated well through the transmitted vibration from the lumbar spine, which suggests that the placement of a narrow vibration pad under the supine body, along the lumbar spine, allows the vibration of the PM. The shear modulus of the PM (n = 7) was 1.23 ± 0.09 kPa (mean ± SEM) on the right side and 1.22 ± 0.15 kPa on the left side, with no significant difference (t-test, P > 0.05). Increased stiffness of the muscle due to continuous local contraction may be an important cause of non-specific low back pain (LBP). The present vibration techniques for MRE of the PM provide a quantitative diagnostic tool for changes in muscle stiffness associated with non-specific LBP.
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Affiliation(s)
- Tomokazu Numano
- Department of Radiological Science, Graduate School of Human Health Science, Tokyo Metropolitan University, Japan; Human Technology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Japan.
| | - Tetsushi Habe
- Department of Radiological Science, Graduate School of Human Health Science, Tokyo Metropolitan University, Japan
| | - Daiki Ito
- Department of Radiological Science, Graduate School of Human Health Science, Tokyo Metropolitan University, Japan; Human Technology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Japan; Office of Radiation Technology, Keio University Hospital, Japan
| | - Takaaki Onishi
- Department of Radiological Science, Graduate School of Human Health Science, Tokyo Metropolitan University, Japan
| | - Koichi Takamoto
- System Emotional Science, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan
| | | | - Hisao Nishijo
- System Emotional Science, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan
| | - Keisuke Igarashi
- Department of Radiological Science, Graduate School of Human Health Science, Tokyo Metropolitan University, Japan
| | - Takamichi Ueki
- Department of Radiological Science, Graduate School of Human Health Science, Tokyo Metropolitan University, Japan
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