|
1
|
Miranda J, Key Wakate Teruya A, Leão Filho H, Lahan-Martins D, Tamura Sttefano Guimarães C, de Paula Reis Guimarães V, Ide Yamauchi F, Blasbalg R, Velloni FG. Diffuse and focal liver fat: advanced imaging techniques and diagnostic insights. Abdom Radiol (NY) 2024; 49:4437-4462. [PMID: 38896247 DOI: 10.1007/s00261-024-04407-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 05/21/2024] [Accepted: 05/22/2024] [Indexed: 06/21/2024]
Abstract
The fatty liver disease represents a complex, multifaceted challenge, requiring a multidisciplinary approach for effective management and research. This article uses conventional and advanced imaging techniques to explore the etiology, imaging patterns, and quantification methods of hepatic steatosis. Particular emphasis is placed on the challenges and advancements in the imaging diagnostics of fatty liver disease. Techniques such as ultrasound, CT, MRI, and elastography are indispensable for providing deep insights into the liver's fat content. These modalities not only distinguish between diffuse and focal steatosis but also help identify accompanying conditions, such as inflammation and fibrosis, which are critical for accurate diagnosis and management.
Collapse
Affiliation(s)
- Joao Miranda
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA.
- Department of Radiology, University of São Paulo, R. Dr. Ovídio Pires de Campos, 75-Cerqueira César, São Paulo, SP, 05403-010, Brazil.
| | - Alexandre Key Wakate Teruya
- Department of Radiology, Diagnósticos da América SA (DASA), Av Juruá 434, Alphaville Industrial, Barueri, São Paulo, SP, 06455-010, Brazil
| | - Hilton Leão Filho
- Department of Radiology, Diagnósticos da América SA (DASA), Av Juruá 434, Alphaville Industrial, Barueri, São Paulo, SP, 06455-010, Brazil
| | - Daniel Lahan-Martins
- Department of Radiology, Diagnósticos da América SA (DASA), Av Juruá 434, Alphaville Industrial, Barueri, São Paulo, SP, 06455-010, Brazil
- Departament of Radiology-FCM, State University of Campinas (UNICAMP), R. Tessália Vieira de Camargo, 126 Cidade Universitária, Campinas, SP, 13083-887, Brazil
| | - Cássia Tamura Sttefano Guimarães
- Department of Radiology, Diagnósticos da América SA (DASA), Av Juruá 434, Alphaville Industrial, Barueri, São Paulo, SP, 06455-010, Brazil
| | - Vivianne de Paula Reis Guimarães
- Department of Radiology, Diagnósticos da América SA (DASA), Av Juruá 434, Alphaville Industrial, Barueri, São Paulo, SP, 06455-010, Brazil
| | - Fernando Ide Yamauchi
- Department of Radiology, Diagnósticos da América SA (DASA), Av Juruá 434, Alphaville Industrial, Barueri, São Paulo, SP, 06455-010, Brazil
| | - Roberto Blasbalg
- Department of Radiology, Diagnósticos da América SA (DASA), Av Juruá 434, Alphaville Industrial, Barueri, São Paulo, SP, 06455-010, Brazil
| | - Fernanda Garozzo Velloni
- Department of Radiology, Diagnósticos da América SA (DASA), Av Juruá 434, Alphaville Industrial, Barueri, São Paulo, SP, 06455-010, Brazil
| |
Collapse
|
|
2
|
Liu J, Wang Z, Yu D, Yang Y, Li Z, Wang X, Yang Y, Cheng C, Zou C, Gan J. Comparative analysis of hepatic fat quantification across 5 T, 3 T and 1.5 T: A study on consistency and feasibility. Eur J Radiol 2024; 180:111709. [PMID: 39222564 DOI: 10.1016/j.ejrad.2024.111709] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2024] [Revised: 08/01/2024] [Accepted: 08/27/2024] [Indexed: 09/04/2024]
Abstract
OBJECTIVES Magnetic resonance imaging (MRI) is a critical noninvasive technique for evaluating liver steatosis, with efficient and precise fat quantification being essential for diagnosing liver diseases. This study leverages 5 T ultra-high-field MRI to demonstrate the clinical significance of liver fat quantification, and explores the consistency and accuracy of the Proton Density Fat Fraction (PDFF) in the liver across different magnetic field strengths and measurement methodologies. METHODS The study involved phantoms with lipid contents ranging from 0 % to 30 % and 35 participants (21 females, 14 males; average age 30.17 ± 13.98 years, body mass index 25.84 ± 4.76, waist-hip ratio 0.84 ± 0.09). PDFF measurements were conducted using chemical shift encoded (CSE) MRI at 5 T, 3 T, and 1.5 T, alongside magnetic resonance spectroscopy (MRS) at 5 T and 1.5 T for both liver and phantoms, analyzed using jMRUI software. The MRS-derived PDFF values served as the reference standard. Repeatability of 5 T MRI measurements was assessed through correlation analysis, while accuracy was evaluated using linear regression analysis against the reference standards. RESULTS The CSE-PDFF measurements at 5 T demonstrated strong consistency with those at 3 T and 1.5 T, showing high intraclass correlation coefficients (ICC) of 0.988 and 0.980, respectively (all p < 0.001). There was also significant consistency across ROIs within liver lobes, with ICC values ranging from 0.975 to 0.986 (all p < 0.001). MRS-PDFF measurements for both phantoms and liver at 5 T and 1.5 T exhibited substantial agreement, with ICC values of 0.996 and 0.980, respectively (all p < 0.001). Particularly, ICC values for ROIs in the liver ranged from 0.963 to 0.990 (all p < 0.001). Despite overall agreement, statistically significant differences were noted in specific ROIs within the liver lobes (p = 0.004 and 0.012). The CSE and MRS PDFF measurements at 5 T displayed strong consistency, with an ICC of 0.988 (p < 0.001), and significant agreement was also found between 5 T CSE and 1.5 T MRS PDFF measurements, with an ICC of 0.978 (p < 0.001). Agreement was significant within the ROIs of the liver lobes on the same platform at 5 T, with ICC values ranging from 0.986 to 0.991 (all p < 0.001). CONCLUSION PDFF measurements at 5 T MR imaging exhibited both accuracy and repeatability, indicating that 5 T imaging provides reliable quantification of liver fat content and shows substantial potential for clinical diagnostic applications.
Collapse
Affiliation(s)
- Jianxian Liu
- Department of Radiology, Shandong Provincial Third Hospital: Shandong University Affiliated Shandong Provincial Third Hospital, Jinan 250031, China
| | - Zhensong Wang
- Department of Radiology, Shandong Provincial Third Hospital: Shandong University Affiliated Shandong Provincial Third Hospital, Jinan 250031, China
| | - Dan Yu
- United Imaging Research Institute of Intelligent Imaging, Beijing 100089, China
| | - Yanxing Yang
- Shanghai United Imaging Healthcare Co., Shanghai 201807, China
| | - Zhengyi Li
- Department of Radiology, Shandong Provincial Third Hospital: Shandong University Affiliated Shandong Provincial Third Hospital, Jinan 250031, China
| | - Xin Wang
- Department of Radiology, Shandong Provincial Third Hospital: Shandong University Affiliated Shandong Provincial Third Hospital, Jinan 250031, China
| | - Yuxin Yang
- United Imaging Research Institute of Intelligent Imaging, Beijing 100089, China
| | - Chuanli Cheng
- Paul C. Lauterbur Research Center for Biomedical Imaging, Chinese Academy of Sciences Shenzhen Institutes of Advanced Technology, Shenzhen 518055, China
| | - Chao Zou
- Paul C. Lauterbur Research Center for Biomedical Imaging, Chinese Academy of Sciences Shenzhen Institutes of Advanced Technology, Shenzhen 518055, China
| | - Jie Gan
- Department of Radiology, Shandong Provincial Third Hospital: Shandong University Affiliated Shandong Provincial Third Hospital, Jinan 250031, China.
| |
Collapse
|
|
3
|
Honecker J, Prokopchuk O, Seeliger C, Hauner H, Junker D, Karampinos DC, Ruschke S. Feasibility of omega-3 fatty acid fraction mapping using chemical shift encoding-based imaging at 3 T. NMR IN BIOMEDICINE 2024; 37:e5181. [PMID: 38830747 DOI: 10.1002/nbm.5181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 04/21/2024] [Accepted: 05/06/2024] [Indexed: 06/05/2024]
Abstract
PURPOSE The aim of this work is to develop an ω-3 fatty acid fraction mapping method at 3 T based on a chemical shift encoding model, to assess its performance in a phantom and in vitro study, and to further demonstrate its feasibility in vivo. METHODS A signal model was heuristically derived based on spectral appearance and theoretical considerations of the corresponding molecular structures to differentiate between ω-3 and non-ω-3 fatty acid substituents in triacylglycerols in addition to the number of double bonds (ndb), the number of methylene-interrupted double bonds (nmidb), and the mean fatty acid chain length (CL). First, the signal model was validated using single-voxel spectroscopy and a time-interleaved multi-echo gradient-echo (TIMGRE) sequence in gas chromatography-mass spectrometry (GC-MS)-calibrated oil phantoms. Second, the TIMGRE-based method was validated in vitro in 21 adipose tissue samples with corresponding GC-MS measurements. Third, an in vivo feasibility study was performed for the TIMGRE-based method in the gluteal region of two healthy volunteers. Phantom and in vitro data was analyzed using a Bland-Altman analysis. RESULTS Compared with GC-MS, MRS showed in the phantom study significant correlations in estimating the ω-3 fraction (p < 0.001), ndb (p < 0.001), nmidb (p < 0.001), and CL (p = 0.001); MRI showed in the phantom study significant correlations (all p < 0.001) for the ω-3 fraction, ndb, and nmidb, but no correlation for CL. Also in the in vitro study, significant correlations (all p < 0.001) between MRI and GC-MS were observed for the ω-3 fraction, ndb, and nmidb, but not for CL. An exemplary ROI measurement in vivo in the gluteal subcutaneous adipose tissue yielded (mean ± standard deviation) 0.8% ± 1.9% ω-3 fraction. CONCLUSION The present study demonstrated strong correlations between gradient-echo imaging-based ω-3 fatty acid fraction mapping and GC-MS in the phantom and in vitro study. Furthermore, feasibility was demonstrated for characterizing adipose tissue in vivo.
Collapse
Affiliation(s)
- Julius Honecker
- Else Kröner Fresenius Center for Nutritional Medicine, ZIEL-Institute for Food and Health, Technical University of Munich, Freising, Germany
| | - Olga Prokopchuk
- Department of Surgery, Klinikum rechts der Isar, School of Medicine and Health, Technical University of Munich, Munich, Germany
| | - Claudine Seeliger
- Else Kröner Fresenius Center for Nutritional Medicine, ZIEL-Institute for Food and Health, Technical University of Munich, Freising, Germany
| | - Hans Hauner
- Else Kröner Fresenius Center for Nutritional Medicine, ZIEL-Institute for Food and Health, Technical University of Munich, Freising, Germany
- Institute of Nutritional Medicine, School of Medicine and Health, Technical University of Munich, Munich, Germany
| | - Daniela Junker
- Department of Diagnostic and Interventional Radiology, Klinikum rechts der Isar, School of Medicine and Health, Technical University of Munich, Munich, Germany
| | - Dimitrios C Karampinos
- Department of Diagnostic and Interventional Radiology, Klinikum rechts der Isar, School of Medicine and Health, Technical University of Munich, Munich, Germany
| | - Stefan Ruschke
- Department of Diagnostic and Interventional Radiology, Klinikum rechts der Isar, School of Medicine and Health, Technical University of Munich, Munich, Germany
| |
Collapse
|
|
4
|
Hui SCN, Murali-Manohar S, Zöllner HJ, Hupfeld KE, Davies-Jenkins CW, Gudmundson AT, Song Y, Yedavalli V, Wisnowski JL, Gagoski B, Oeltzschner G, Edden RAE. Integrated Short-TE and Hadamard-edited Multi-Sequence (ISTHMUS) for advanced MRS. J Neurosci Methods 2024; 409:110206. [PMID: 38942238 PMCID: PMC11286357 DOI: 10.1016/j.jneumeth.2024.110206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Revised: 05/20/2024] [Accepted: 06/21/2024] [Indexed: 06/30/2024]
Abstract
BACKGROUND To examine data quality and reproducibility using ISTHMUS, which has been implemented as the standardized MR spectroscopy sequence for the multi-site Healthy Brain and Child Development (HBCD) study. METHODS ISTHMUS is the consecutive acquisition of short-TE PRESS (32 transients) and long-TE HERCULES (224 transients) data with dual-TE water reference scans. Voxels were positioned in the centrum semiovale, dorsal anterior cingulate cortex, posterior cingulate cortex and bilateral thalamus regions. After acquisition, ISTHMUS data were separated into the PRESS and HERCULES portions for analysis and modeled separately using Osprey. In vivo experiments were performed in 10 healthy volunteers (6 female; 29.5±6.6 years). Each volunteer underwent two scans on the same day. Differences in metabolite measurements were examined. T2 correction based on the dual-TE water integrals were compared with: 1) T2 correction based on the default white matter and gray matter T2 reference values in Osprey and 2) shorter WM and GM T2 values from recent literature. RESULTS No significant difference in linewidth was observed between PRESS and HERCULES. Bilateral thalamus spectra had produced significantly higher (p<0.001) linewidth compared to the other three regions. Linewidth measurements were similar between scans, with scan-to-scan differences under 1 Hz for most subjects. Paired t-tests indicated a significant difference only in PRESS NAAG between the two thalamus scans (p=0.002). T2 correction based on shorter T2 values showed better agreement to the dual-TE water integral ratio. CONCLUSIONS ISTHMUS facilitated data acquisition and post-processing and reduced operator workload to eliminate potential human error.
Collapse
Affiliation(s)
- Steve C N Hui
- Developing Brain Institute, Children's National Hospital, Washington, D.C., USA; Department of Radiology, The George Washington University School of Medicine and Health Sciences, Washington, D.C., USA; Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, D.C., USA
| | - Saipavitra Murali-Manohar
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA
| | - Helge J Zöllner
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA
| | - Kathleen E Hupfeld
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA
| | - Christopher W Davies-Jenkins
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA
| | - Aaron T Gudmundson
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA
| | - Yulu Song
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA
| | - Vivek Yedavalli
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA
| | - Jessica L Wisnowski
- Department of Radiology, Children's Hospital Los Angeles, Los Angeles, CA, USA; Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, CA, USA
| | - Borjan Gagoski
- Fetal Neonatal Neuroimaging and Developmental Science Center, Boston Children's Hospital, Boston, MA, USA; Department of Radiology, Harvard Medical School, Boston, MA, USA
| | - Georg Oeltzschner
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA
| | - Richard A E Edden
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA.
| |
Collapse
|
|
5
|
Jonuscheit M, Uhlemeyer C, Korzekwa B, Schouwink M, Öner-Sieben S, Ensenauer R, Roden M, Belgardt BF, Schrauwen-Hinderling VB. Post mortem analysis of hepatic volume and lipid content by magnetic resonance imaging and spectroscopy in fixed murine neonates. NMR IN BIOMEDICINE 2024; 37:e5140. [PMID: 38556731 DOI: 10.1002/nbm.5140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 01/31/2024] [Accepted: 02/14/2024] [Indexed: 04/02/2024]
Abstract
Maternal obesity and hyperglycemia are linked to an elevated risk for obesity, diabetes, and steatotic liver disease in the adult offspring. To establish and validate a noninvasive workflow for perinatal metabolic phenotyping, fixed neonates of common mouse strains were analyzed postmortem via magnetic resonance imaging (MRI)/magnetic resonance spectroscopy (MRS) to assess liver volume and hepatic lipid (HL) content. The key advantage of nondestructive MRI/MRS analysis is the possibility of further tissue analyses, such as immunohistochemistry, RNA extraction, and even proteomics, maximizing the data that can be gained per individual and therefore facilitating comprehensive correlation analyses. This study employed an MRI and 1H-MRS workflow to measure liver volume and HL content in 65 paraformaldehyde-fixed murine neonates at 11.7 T. Liver volume was obtained using semiautomatic segmentation of MRI acquired by a RARE sequence with 0.5-mm slice thickness. HL content was measured by a STEAM sequence, applied with and without water suppression. T1 and T2 relaxation times of lipids and water were measured for respective correction of signal intensity. The HL content, given as CH2/(CH2 + H2O), was calculated, and the intrasession repeatability of the method was tested. The established workflow yielded robust results with a variation of ~3% in repeated measurements for HL content determination. HL content measurements were further validated by correlation analysis with biochemically assessed triglyceride contents (R2 = 0.795) that were measured in littermates. In addition, image quality also allowed quantification of subcutaneous adipose tissue and stomach diameter. The highest HL content was measured in C57Bl/6N (4.2%) and the largest liver volume and stomach diameter in CBA (53.1 mm3 and 6.73 mm) and NMRI (51.4 mm3 and 5.96 mm) neonates, which also had the most subcutaneous adipose tissue. The observed effects were independent of sex and litter size. In conclusion, we have successfully tested and validated a robust MRI/MRS workflow that allows assessment of morphology and HL content and further enables paraformaldehyde-fixed tissue-compatible subsequent analyses in murine neonates.
Collapse
Affiliation(s)
- Marc Jonuscheit
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- German Center for Diabetes Research (DZD e.V.), München-Neuherberg, Germany
| | - Celina Uhlemeyer
- German Center for Diabetes Research (DZD e.V.), München-Neuherberg, Germany
- Institute for Vascular and Islet Cell Biology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Benedict Korzekwa
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- German Center for Diabetes Research (DZD e.V.), München-Neuherberg, Germany
| | - Marten Schouwink
- University Children's Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Soner Öner-Sieben
- Institute of Child Nutrition, Max Rubner-Institut, Federal Research Institute of Nutrition and Food, Karlsruhe, Germany
| | - Regina Ensenauer
- Institute of Child Nutrition, Max Rubner-Institut, Federal Research Institute of Nutrition and Food, Karlsruhe, Germany
| | - Michael Roden
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- German Center for Diabetes Research (DZD e.V.), München-Neuherberg, Germany
- Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Bengt-Frederik Belgardt
- German Center for Diabetes Research (DZD e.V.), München-Neuherberg, Germany
- Institute for Vascular and Islet Cell Biology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Vera B Schrauwen-Hinderling
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- German Center for Diabetes Research (DZD e.V.), München-Neuherberg, Germany
- Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
| |
Collapse
|
|
6
|
Li W, Wang W, Zhang M, Chen Q, Li S. Associations of marrow fat fraction with MR imaging based trabecular bone microarchitecture in first-time diagnosed type 1 diabetes mellitus. Front Endocrinol (Lausanne) 2024; 15:1287591. [PMID: 38774224 PMCID: PMC11106440 DOI: 10.3389/fendo.2024.1287591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Accepted: 04/24/2024] [Indexed: 05/24/2024] Open
Abstract
Purpose To determine whether there are alterations in marrow fat content in individuals first-time diagnosed with type 1 diabetes mellitus (T1DM) and to explore the associations between marrow fat fraction and MRI-based findings in trabecular bone microarchitecture. Method A case-control study was conducted, involving adults with first-time diagnosed T1DM (n=35) and age- and sex-matched healthy adults (n=46). Dual-energy X-ray absorptiometry and 3 Tesla-MRI of the proximal tibia were performed to assess trabecular microarchitecture and vertebral marrow fat fraction. Multiple linear regression analysis was used to test the associations of marrow fat fraction with trabecular microarchitecture and bone density while adjusting for potential confounding factors. Results In individuals first-time diagnosed with T1DM, the marrow fat fraction was significantly higher (p < 0.001) compared to healthy controls. T1DM patients also exhibited higher trabecular separation [median (IQR): 2.19 (1.70, 2.68) vs 1.81 (1.62, 2.10), p < 0.001], lower trabecular volume [0.45 (0.30, 0.56) vs 0.53 (0.38, 0.60), p = 0.013], and lower trabecular number [0.37 (0.26, 0.44) vs 0.41 (0.32, 0.47), p = 0.020] compared to controls. However, bone density was similar between the two groups (p = 0.815). In individuals with T1DM, there was an inverse association between marrow fat fraction and trabecular volume (r = -0.69, p < 0.001) as well as trabecular number (r = -0.55, p < 0.001), and a positive association with trabecular separation (r = 0.75, p < 0.001). Marrow fat fraction was independently associated with total trabecular volume (standardized β = -0.21), trabecular number (β = -0.12), and trabecular separation (β = 0.57) of the proximal tibia after adjusting for various factors including age, gender, body mass index, physical activity, smoking status, alcohol consumption, blood glucose, plasma glycated hemoglobin, lipid profile, and bone turnover biomarkers. Conclusions Individuals first-time diagnosed with T1DM experience expansion of marrow adiposity, and elevated marrow fat content is associated with MRI-based trabecular microstructure.
Collapse
Affiliation(s)
- Wei Li
- Department of Radiology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, China
| | - Wei Wang
- Department of Radiology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, China
| | - Minlan Zhang
- Department of Laboratory Medicine, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, China
| | - Qi Chen
- Department of Radiology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, China
| | - Shaojun Li
- Department of Radiology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, China
| |
Collapse
|
|
7
|
Hui SC, Murali-Manohar S, Zöllner HJ, Hupfeld KE, Davies-Jenkins CW, Gudmundson AT, Song Y, Yedavalli V, Wisnowski JL, Gagoski B, Oeltzschner G, Edden RA. Integrated Short-TE and Hadamard-edited Multi-Sequence (ISTHMUS) for Advanced MRS. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.02.15.580516. [PMID: 38659947 PMCID: PMC11042202 DOI: 10.1101/2024.02.15.580516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/26/2024]
Abstract
Background To examine data quality and reproducibility using ISTHMUS, which has been implemented as the standardized MR spectroscopy sequence for the multi-site Healthy Brain and Child Development (HBCD) study. Methods ISTHMUS is the consecutive acquisition of short-TE PRESS (32 transients) and long-TE HERCULES (224 transients) data with dual-TE water reference scans. Voxels were positioned in the centrum semiovale, dorsal anterior cingulate cortex, posterior cingulate cortex and bilateral thalamus regions. After acquisition, ISTHMUS data were separated into the PRESS and HERCULES portions for analysis and modeled separately using Osprey. In vivo experiments were performed in 10 healthy volunteers (6 female; 29.5±6.6 years). Each volunteer underwent two scans on the same day. Differences in metabolite measurements were examined. T2 correction based on the dual-TE water integrals were compared with: 1) T2 correction based the default white matter and gray matter T2 reference values in Osprey; 2) shorter WM and GM T2 values from recent literature; and 3) reduced CSF fractions. Results No significant difference in linewidth was observed between PRESS and HERCULES. Bilateral thalamus spectra had produced significantly higher (p<0.001) linewidth compared to the other three regions. Linewidth measurements were similar between scans, with scan-to-scan differences under 1 Hz for most subjects. Paired t-tests indicated a significant difference only in PRESS NAAG between the two thalamus scans (p=0.002). T2 correction based on shorter T2 values showed better agreement to the dual-TE water integral ratio. Conclusions ISTHMUS facilitated and standardized acquisition and post-processing and reduced operator workload to eliminate potential human error.
Collapse
Affiliation(s)
- Steve C.N. Hui
- Developing Brain Institute, Children’s National Hospital, Washington, D.C. USA
- Departments of Radiology, The George Washington University School of Medicine and Health Sciences, Washington, D.C. USA
- Departments of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, D.C. USA
| | - Saipavitra Murali-Manohar
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA
| | - Helge J. Zöllner
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA
| | - Kathleen E. Hupfeld
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA
| | - Christopher W. Davies-Jenkins
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA
| | - Aaron T. Gudmundson
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA
| | - Yulu Song
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA
| | - Vivek Yedavalli
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA
| | - Jessica L Wisnowski
- Department of Radiology, Children’s Hospital Los Angeles, Los Angeles, CA, USA
- Department of Pediatrics, Children’s Hospital Los Angeles, Los Angeles, CA, USA
| | - Borjan Gagoski
- Fetal Neonatal Neuroimaging and Developmental Science Center, Boston Children’s Hospital, Boston, MA, USA
- Department of Radiology, Harvard Medical School, Boston, MA, USA
| | - Georg Oeltzschner
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA
| | - Richard A.E. Edden
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA
| |
Collapse
|
|
8
|
Tan AA, Demirtas D, Hizarcioglu-Gulsen H, Karakaya J, Isiyel E, Ozen H, Oguz B, Haliloglu M, Ozcan HN. Liver magnetic resonance elastography and fat fraction in pediatric patients with cystic fibrosis versus healthy children. Pediatr Radiol 2024; 54:250-259. [PMID: 38133654 DOI: 10.1007/s00247-023-05832-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 12/05/2023] [Accepted: 12/06/2023] [Indexed: 12/23/2023]
Abstract
BACKGROUND Liver involvement is an important cause of morbidity and mortality in patients with cystic fibrosis (CF). While liver biopsy is the gold standard for demonstrating involvement, its invasiveness prompts a search for noninvasive alternatives. OBJECTIVE To evaluate liver involvement in pediatric patients with CF (versus healthy controls) using magnetic resonance (MR) elastography/spectroscopy and to correlate the imaging findings with clinical/laboratory characteristics. MATERIALS AND METHODS This was a single-center, prospective cross-sectional study conducted between April 2020 and March 2022 in patients with CF versus healthy controls. Patients with CF were divided into two subgroups: those with CF-related liver disease and those without. MR images were acquired on a 1.5-tesla machine. Kilopascal (kPa) values were derived from processing MR elastography images. MR spectroscopy was used to measure liver fat fraction, as an indication of hepatosteatosis. Groups were compared using either the Student's t test or the Mann‒Whitney U test. The chi-square test or Fisher's exact test were used to compare qualitative variables. RESULTS Fifty-one patients with CF (12 ± 3.3 years, 32 boys) and 24 healthy volunteers (11.1 ± 2.4 years, 15 boys) were included in the study. Median liver stiffness (P=0.003) and fat fraction (P=0.03) were higher in the CF patients than in the controls. Median liver stiffness values were higher in CF patients with CF-related liver disease than in those without CF-related liver disease (P=0.002). Liver stiffness values of CF patients with high alanine aminotransferase (ALT), high gamma-glutamyl transferase, and thrombocytopenia were found to be higher than those without (P=0.004, P<0.001, P<0.001, respectively). Only the high ALT group showed a high fat fraction (P=0.002). CONCLUSIONS Patients with CF had higher liver stiffness than the control group, and patients with CF-related liver disease had higher liver stiffness than both the CF patients without CF-related liver disease and the control group. Patients with CF had a higher fat fraction than the control group. Noninvasive assessment of liver involvement using MR elastography/spectroscopy can support the diagnosis of CF-related liver disease and the follow-up of patients with CF.
Collapse
Affiliation(s)
- Aziz Anil Tan
- Department of Radiology, Hacettepe University School of Medicine, Ankara, Turkey
| | - Duygu Demirtas
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hacettepe University School of Medicine, Ankara, Turkey
| | - Hayriye Hizarcioglu-Gulsen
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hacettepe University School of Medicine, Ankara, Turkey
| | - Jale Karakaya
- Department of Biostatistics, Hacettepe University School of Medicine, Ankara, Turkey
| | - Emel Isiyel
- Department of Pediatrics, Hacettepe University School of Medicine, Ankara, Turkey
| | - Hasan Ozen
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hacettepe University School of Medicine, Ankara, Turkey
| | - Berna Oguz
- Department of Radiology, Division of Pediatric Radiology, Hacettepe University School of Medicine, Sihhiye, 06100, Ankara, Turkey
| | - Mithat Haliloglu
- Department of Radiology, Division of Pediatric Radiology, Hacettepe University School of Medicine, Sihhiye, 06100, Ankara, Turkey
| | - H Nursun Ozcan
- Department of Radiology, Division of Pediatric Radiology, Hacettepe University School of Medicine, Sihhiye, 06100, Ankara, Turkey.
| |
Collapse
|
|
9
|
Wu PH, Joseph G, Saeed I, Pirmoazen AM, Kenny K, Kim TY, Schafer AL, Schwartz AV, Li X, Link TM, Kazakia GJ. Bone Marrow Adiposity Alterations in Type 2 Diabetes Are Sex-Specific and Associated with Serum Lipid Levels. J Bone Miner Res 2023; 38:1877-1884. [PMID: 37904318 PMCID: PMC10842815 DOI: 10.1002/jbmr.4931] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Revised: 09/26/2023] [Accepted: 10/26/2023] [Indexed: 11/01/2023]
Abstract
Type 2 diabetes (T2D) has negative effects on skeletal health. A proposed mechanism of diabetic bone disease connects hyperlipidemia to increased bone marrow adiposity and decreased bone quality. Previous research on Type 1 diabetes reported positive associations between serum lipid levels and marrow adiposity, but no data exist for T2D. In addition, marrow adiposity is sex-dependent in healthy populations, but sex has not been addressed adequately in previous reports of marrow adiposity in T2D. The purpose of this study was to quantify associations of marrow adiposity and composition with T2D status, serum lipid levels, and sex. T2D patients and normoglycemic controls (n = 39/37) were included. Single-voxel magnetic resonance spectroscopy (MRS) was performed at the spine and tibia. Quantitative MRS outcomes of marrow adiposity and composition were calculated. Linear regression models were used to compare MRS outcomes among groups and to evaluate associations of MRS outcomes with serum lipid levels. All analyses were performed on sex-stratified subgroups. Total, unsaturated, and saturated fat content at the spine were lower in T2D participants compared to controls in age-adjusted models; these differences were significant in men but not in women. In our study cohort, total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were lower in T2D participants compared to controls. Adjustment for LDL, HDL, and statin use attenuated the association of T2D status with unsaturated fat but not saturated fat in men. Further analysis confirmed significant associations between serum lipid levels and MRS outcomes. Specifically, we found a positive association between LDL cholesterol and total marrow fat in the male T2D group and a negative association between HDL and total marrow fat in the female T2D group. In conclusion, our results suggest that marrow adiposity and composition are associated with lipid levels as well as T2D status, and these relationships are sex-specific. © 2023 American Society for Bone and Mineral Research (ASBMR).
Collapse
Affiliation(s)
- Po-hung Wu
- Department of Radiology and Biomedical Imaging, University of California - San Francisco, 185 Berry St, Suite 350, San Francisco, CA, USA 94107
| | - Gabby Joseph
- Department of Radiology and Biomedical Imaging, University of California - San Francisco, 185 Berry St, Suite 350, San Francisco, CA, USA 94107
| | - Isra Saeed
- Department of Radiology and Biomedical Imaging, University of California - San Francisco, 185 Berry St, Suite 350, San Francisco, CA, USA 94107
| | - Amir M. Pirmoazen
- Department of Radiology and Biomedical Imaging, University of California - San Francisco, 185 Berry St, Suite 350, San Francisco, CA, USA 94107
| | - Katie Kenny
- Department of Radiology and Biomedical Imaging, University of California - San Francisco, 185 Berry St, Suite 350, San Francisco, CA, USA 94107
- Department of Bioengineering, University of California – Berkeley, 306 Stanley Hall MC #1762, Berkeley, CA, USA 94720
| | - Tiffany Y. Kim
- Department of Medicine, University of California - San Francisco, 4150 Clement St., San Francisco CA, USA 94121
- San Francisco VA Health Care System, 4150 Clement St., San Francisco CA, USA 94121, Tel: (415) 221-4810
| | - Anne L. Schafer
- Department of Medicine, University of California - San Francisco, 4150 Clement St., San Francisco CA, USA 94121
- Department of Epidemiology and Biostatistics, University of California - San Francisco 550 16th. Street, San Francisco, CA, USA 94158
- San Francisco VA Health Care System, 4150 Clement St., San Francisco CA, USA 94121, Tel: (415) 221-4810
| | - Ann V. Schwartz
- Department of Epidemiology and Biostatistics, University of California - San Francisco 550 16th. Street, San Francisco, CA, USA 94158
| | - Xiaojuan Li
- Department of Biomedical Engineering, Program for Advanced Musculoskeletal Imaging (PAMI), Cleveland Clinic, Lerner Research Institute, 9500 Euclid Avenue, Cleveland, Ohio, USA 44195
| | - Thomas M. Link
- Department of Radiology and Biomedical Imaging, University of California - San Francisco, 185 Berry St, Suite 350, San Francisco, CA, USA 94107
| | - Galateia J. Kazakia
- Department of Radiology and Biomedical Imaging, University of California - San Francisco, 185 Berry St, Suite 350, San Francisco, CA, USA 94107
| |
Collapse
|
|
10
|
Buitinga M, Veeraiah P, Haans F, Schrauwen-Hinderling VB. Ectopic lipid deposition in muscle and liver, quantified by proton magnetic resonance spectroscopy. Obesity (Silver Spring) 2023; 31:2447-2459. [PMID: 37667838 DOI: 10.1002/oby.23865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 05/09/2023] [Accepted: 05/09/2023] [Indexed: 09/06/2023]
Abstract
Advances in the development of noninvasive imaging techniques have spurred investigations into ectopic lipid deposition in the liver and muscle and its implications in the development of metabolic diseases such as type 2 diabetes. Computed tomography and ultrasound have been applied in the past, though magnetic resonance-based methods are currently considered the gold standard as they allow more accurate quantitative detection of ectopic lipid stores. This review focuses on methodological considerations of magnetic resonance-based methods to image hepatic and muscle fat fractions, and it emphasizes anatomical and morphological aspects and how these may influence data acquisition, analysis, and interpretation.
Collapse
Affiliation(s)
- Mijke Buitinga
- Department of Radiology and Nuclear Medicine, Maastricht University Medical Center+, Maastricht, The Netherlands
- Department of Nutrition and Movement Sciences (NUTRIM), Maastricht University, Maastricht, The Netherlands
| | - Pandichelvam Veeraiah
- Department of Radiology and Nuclear Medicine, Maastricht University Medical Center+, Maastricht, The Netherlands
- Scannexus (Ultra-High Field Imaging Center), Maastricht, The Netherlands
- Faculty of Health Medicine and Life Sciences (FHML), Maastricht, The Netherlands
| | - Florian Haans
- Department of Radiology and Nuclear Medicine, Maastricht University Medical Center+, Maastricht, The Netherlands
| | - Vera B Schrauwen-Hinderling
- Department of Radiology and Nuclear Medicine, Maastricht University Medical Center+, Maastricht, The Netherlands
- Department of Nutrition and Movement Sciences (NUTRIM), Maastricht University, Maastricht, The Netherlands
- Institute for Clinical Diabetology, German Diabetes Center and Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
| |
Collapse
|
|
11
|
Bawden SJ, Hoad C, Kaye P, Stephenson M, Dolman G, James MW, Wilkes E, Austin A, Guha IN, Francis S, Gowland P, Aithal GP. Comparing magnetic resonance liver fat fraction measurements with histology in fibrosis: the difference between proton density fat fraction and tissue mass fat fraction. MAGMA (NEW YORK, N.Y.) 2023; 36:553-563. [PMID: 36538248 PMCID: PMC10468948 DOI: 10.1007/s10334-022-01052-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 11/22/2022] [Accepted: 11/23/2022] [Indexed: 06/17/2023]
Abstract
OBJECTIVE Magnetic resonance spectroscopy (MRS) provides a powerful method of measuring fat fraction. However, previous studies have shown that MRS results give lower values compared with visual estimates from biopsies in fibrotic livers. This study investigated these discrepancies and considered whether a tissue water content correction, as assessed by MRI relaxometry, could provide better agreement. MATERIALS AND METHODS 110 patients were scanned in a 1.5 T Philips scanner and biopsies were obtained. Multiple echo MRS (30 × 30 × 30 mm volume) was used to determine Proton Density Fat Fraction (PDFF). Biopsies were assessed by visual assessment for fibrosis and steatosis grading. Digital image analysis (DIA) was also used to quantify fat fraction within tissue samples. T1 relaxation times were then used to estimate tissue water content to correct PDFF for confounding factors. RESULTS PDFF values across the four visually assessed steatosis grades were significantly less in the higher fibrosis group (F3-F4) compared to the lower fibrosis group (F0-F2). The slope of the linear regression of PDFF vs DIA fat fraction was ~ 1 in the low fibrosis group and 0.77 in the high fibrosis group. Correcting for water content based on T1 increased the gradient but it did not reach unity. DISCUSSION In fibrotic livers, PDFF underestimated fat fraction compared to DIA methods. Values were improved by applying a water content correction, but fat fractions were still underestimated.
Collapse
Affiliation(s)
- Stephen James Bawden
- Nottingham Digestive Diseases Centre, NIHR Nottingham Biomedical Research Centre at the Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, NG7 2RD, UK.
- Sir Peter Mansfield Imaging Centre, SPMIC, University Park, Physics and Astronomy, University of Nottingham, Nottingham, UK.
| | - Caroline Hoad
- Nottingham Digestive Diseases Centre, NIHR Nottingham Biomedical Research Centre at the Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, NG7 2RD, UK
| | - Philip Kaye
- Nottingham Digestive Diseases Centre, NIHR Nottingham Biomedical Research Centre at the Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, NG7 2RD, UK
- Department of Cellular Pathology, Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - Mary Stephenson
- Clinical Imaging Research Centre (CIRC), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
| | - Grace Dolman
- Nottingham Digestive Diseases Centre, NIHR Nottingham Biomedical Research Centre at the Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, NG7 2RD, UK
| | - Martin W James
- Nottingham Digestive Diseases Centre, NIHR Nottingham Biomedical Research Centre at the Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, NG7 2RD, UK
| | - Emilie Wilkes
- Nottingham Digestive Diseases Centre, NIHR Nottingham Biomedical Research Centre at the Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, NG7 2RD, UK
| | | | - Indra Neil Guha
- Nottingham Digestive Diseases Centre, NIHR Nottingham Biomedical Research Centre at the Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, NG7 2RD, UK
| | - Susan Francis
- Sir Peter Mansfield Imaging Centre, SPMIC, University Park, Physics and Astronomy, University of Nottingham, Nottingham, UK
| | - Penny Gowland
- Sir Peter Mansfield Imaging Centre, SPMIC, University Park, Physics and Astronomy, University of Nottingham, Nottingham, UK
| | - Guruprasad P Aithal
- Nottingham Digestive Diseases Centre, NIHR Nottingham Biomedical Research Centre at the Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, NG7 2RD, UK
| |
Collapse
|
|
12
|
Paavilainen E, Niinikoski H, Parkkola R, Koskensalo K, Nikkinen H, Veijola R, Vääräsmäki M, Loo BM, Tossavainen P, Rönnemaa T, Tertti K. Metformin versus insulin for gestational diabetes: Adiposity variables and adipocytokines in offspring at age of 9 years. Diabetes Res Clin Pract 2023:110780. [PMID: 37331522 DOI: 10.1016/j.diabres.2023.110780] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 05/30/2023] [Accepted: 06/13/2023] [Indexed: 06/20/2023]
Abstract
AIMS To compare body composition, visceral adiposity, adipocytokines, and low-grade inflammation markers in prepubertal offspring of mothers who were treated with metformin or insulin for gestational diabetes mellitus (GDM). METHODS 172 offspring of 311 mothers randomized to receive metformin (n=82) or insulin (n=90) for GDMwere studied at 9 years of age (follow-up rate 55%). Measurements included anthropometrics, adipocytokines, markers of the low-grade inflammation, abdominal magnetic resonance imaging (MRI), magnetic liver spectrometry (MRS), and whole body dual-energy X-ray absorptiometry (DXA). RESULTS Serum markers of low-grade inflammation, visceral adipose tissue volume, total fat percentage, and liver fat percentage were similar between the study groups. Serum adiponectin concentration was higher in children in the metformin group compared to insulin group (median 10.37 vs 9.50 µg/ml, p = 0.016). This difference between groups was observed in boys only (median 12.13 vs 7.50 µg/ml, p<0.001). Leptin/adiponectin-ratio was lower in boys in the metformin group than in the insulin group (median 0.30 vs 0.75; p = 0.016). CONCLUSIONS Maternal metformin treatment for GDM had no effects on adiposity, body composition, liver fat, or inflammation markers in prepubertal offspring compared to maternal insulin treatment but was associated with higher adiponectin concentration and lower leptin/adiponectin-ratio in boys.
Collapse
Affiliation(s)
- Elisa Paavilainen
- Department of Pediatrics and Adolescent Medicine, University of Turku and Turku University Hospital, Turku, Finland.
| | - Harri Niinikoski
- Department of Pediatrics and Adolescent Medicine, University of Turku and Turku University Hospital, Turku, Finland
| | - Riitta Parkkola
- Department of Radiology, University of Turku and Turku University Hospital, Turku, Finland
| | - Kalle Koskensalo
- Department of Medical Physics, Turku University Hospital, Turku, Finland
| | - Hilkka Nikkinen
- Department of Obstetrics and Gynecology, Research Unit of Clinical Medicine, University of Oulu and Oulu University Hospital, Oulu, Finland
| | - Riitta Veijola
- Department of Pediatrics, Research Unit of Clinical Medicine, Medical Research Center, University of Oulu and Oulu University Hospital, Oulu, Finland
| | - Marja Vääräsmäki
- Department of Obstetrics and Gynecology, Research Unit of Clinical Medicine, University of Oulu and Oulu University Hospital, Oulu, Finland
| | - Britt-Marie Loo
- Joint Clinical Biochemistry Laboratory of University of Turku and Turku University Hospital, Turku, Finland
| | - Päivi Tossavainen
- Department of Pediatrics, Research Unit of Clinical Medicine, Medical Research Center, University of Oulu and Oulu University Hospital, Oulu, Finland
| | - Tapani Rönnemaa
- Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland
| | - Kristiina Tertti
- Department of Obstetrics and Gynecology, University of Turku and Turku University Hospital, Turku, Finland
| |
Collapse
|
|
13
|
Jang W, Song JS. Non-Invasive Imaging Methods to Evaluate Non-Alcoholic Fatty Liver Disease with Fat Quantification: A Review. Diagnostics (Basel) 2023; 13:diagnostics13111852. [PMID: 37296703 DOI: 10.3390/diagnostics13111852] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2023] [Revised: 05/17/2023] [Accepted: 05/23/2023] [Indexed: 06/12/2023] Open
Abstract
Hepatic steatosis without specific causes (e.g., viral infection, alcohol abuse, etc.) is called non-alcoholic fatty liver disease (NAFLD), which ranges from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH), fibrosis, and NASH-related cirrhosis. Despite the usefulness of the standard grading system, liver biopsy has several limitations. In addition, patient acceptability and intra- and inter-observer reproducibility are also concerns. Due to the prevalence of NAFLD and limitations of liver biopsies, non-invasive imaging methods such as ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI) that can reliably diagnose hepatic steatosis have developed rapidly. US is widely available and radiation-free but cannot examine the entire liver. CT is readily available and helpful for detection and risk classification, significantly when analyzed using artificial intelligence; however, it exposes users to radiation. Although expensive and time-consuming, MRI can measure liver fat percentage with magnetic resonance imaging proton density fat fraction (MRI-PDFF). Specifically, chemical shift-encoded (CSE)-MRI is the best imaging indicator for early liver fat detection. The purpose of this review is to provide an overview of each imaging modality with an emphasis on the recent progress and current status of liver fat quantification.
Collapse
Affiliation(s)
- Weon Jang
- Department of Radiology, Jeonbuk National University Medical School and Hospital, 20 Geonji-ro, Deokjin-gu, Jeonju 54907, Jeonbuk, Republic of Korea
- Research Institute of Clinical Medicine, Jeonbuk National University, Jeonju 54907, Jeonbuk, Republic of Korea
- Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju 54907, Jeonbuk, Republic of Korea
| | - Ji Soo Song
- Department of Radiology, Jeonbuk National University Medical School and Hospital, 20 Geonji-ro, Deokjin-gu, Jeonju 54907, Jeonbuk, Republic of Korea
- Research Institute of Clinical Medicine, Jeonbuk National University, Jeonju 54907, Jeonbuk, Republic of Korea
- Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju 54907, Jeonbuk, Republic of Korea
| |
Collapse
|
|
14
|
Fortier V, Levesque IR. MR-oximetry with fat DESPOT. Magn Reson Imaging 2023; 97:112-121. [PMID: 36608912 DOI: 10.1016/j.mri.2022.12.023] [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: 09/27/2022] [Revised: 12/23/2022] [Accepted: 12/31/2022] [Indexed: 01/07/2023]
Abstract
PURPOSE The R1 relaxation rate of fat is a promising marker of tissue oxygenation. Existing techniques to map fat R1 in MR-oximetry offer limited spatial coverage, require long scan times, or pulse sequences that are not readily available on clinical scanners. This work addresses these limitations with a 3D voxel-wise fat R1 mapping technique for MR-oximetry based on a variable flip angle (VFA) approach at 3 T. METHODS Varying levels of dissolved oxygen (O2) were generated in a phantom consisting of vials of safflower oil emulsion, used to approximate human fat. Joint voxel-wise mapping of fat and water R1 was performed with a two-compartment VFA model fitted to multi-echo gradient-echo magnitude data acquired at four flip angles, referred to as Fat DESPOT. Global R1 was also calculated. Variations of fat, water, and global R1 were investigated as a function of the partial pressure of O2 (pO2). Inversion-prepared stimulated echo magnetic resonance spectroscopy was used as the reference technique for R1 measurements. RESULTS Fat R1 from Fat DESPOT was more sensitive than water R1 and global R1 to variations in pO2, consistent with previous studies performed with different R1 mapping techniques. Fat R1 sensitivity to pO2 variations with Fat DESPOT (median O2 relaxivity r1, O2 = 1.57× 10-3 s-1 mmHg-1) was comparable to spectroscopy-based measurements for methylene, the main fat resonance (median r1, O2= 1.80 × 10-3 s-1 mmHg-1). CONCLUSION Fat and water R1 can be measured on a voxel-wise basis using a two-component fit to multi-echo 3D VFA magnitude data in a clinically acceptable scan time. Fat and water R1 measured with Fat DESPOT were sensitive to variations in pO2. These observations suggest an approach to 3D in vivo MR oximetry.
Collapse
Affiliation(s)
- Véronique Fortier
- Medical Physics Unit, McGill University, Montréal, QC, Canada; Biomedical Engineering, McGill University, Montréal, QC, Canada; Medical Imaging, McGill University Health Centre, Montréal, QC, Canada; Department of Diagnostic Radiology, McGill University, Montréal, QC, Canada; Gerald Bronfman Department of Oncology, McGill University, Montréal, QC, Canada.
| | - Ives R Levesque
- Medical Physics Unit, McGill University, Montréal, QC, Canada; Biomedical Engineering, McGill University, Montréal, QC, Canada; Gerald Bronfman Department of Oncology, McGill University, Montréal, QC, Canada; Research Institute of the McGill University Health Centre, Montréal, QC, Canada
| |
Collapse
|
|
15
|
Ringe KI, Yoon JH. Strategies and Techniques for Liver Magnetic Resonance Imaging: New and Pending Applications for Routine Clinical Practice. Korean J Radiol 2023; 24:180-189. [PMID: 36788770 PMCID: PMC9971842 DOI: 10.3348/kjr.2022.0838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 12/11/2022] [Accepted: 12/22/2022] [Indexed: 02/16/2023] Open
Affiliation(s)
- Kristina I. Ringe
- Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany
| | - Jeong Hee Yoon
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
| |
Collapse
|
|
16
|
Hui SC, Gong T, Zöllner HJ, Hupfeld KE, Gudmundson AT, Murali-Manohar S, Davies-Jenkins CW, Song Y, Chen Y, Oeltzschner G, Wang G, Edden RAE. sLASER and PRESS Perform Similarly at Revealing Metabolite-Age Correlations. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.01.18.524597. [PMID: 36711794 PMCID: PMC9882274 DOI: 10.1101/2023.01.18.524597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Purpose To compare the respective ability of PRESS and sLASER to reveal biological relationships, using age as a validation covariate. Methods MRS data were acquired from 102 healthy volunteers using PRESS and sLASER in centrum semiovale (CSO) and posterior cingulate cortex (PCC) regions. Acquisition parameters included TR/TE 2000/30 ms; 96 transients; 2048 datapoints sampled at 2 kHz.Spectra were analyzed using Osprey. Signal-to-noise ratio (SNR), full-width-half-maximum linewidth of tCr, and metabolite concentrations were extracted. A linear model was used to compare SNR and linewidth. Paired t-tests were used to assess differences in metabolite measurements between PRESS and sLASER. Correlations were used to evaluate the relationship between PRESS and sLASER metabolite estimates, as well as the strength of each metabolite-age relationship. Coefficients of variation were calculated to assess inter-subject variability in each metabolite measurement. Results SNR and linewidth were significantly higher (p<0.05) for sLASER than PRESS. Paired t-tests showed significant differences between PRESS and sLASER in most metabolite measurements. Metabolite measures were significantly correlated (p<0.05) for most metabolites between the two methods except GABA, Gln and Lac in CSO and GSH, Lac and NAAG in PCC. Metabolite-age relationships were consistently identified using both PRESS and sLASER. Similar CVs were observed for most metabolites. Conclusion The study results suggest strong agreement between PRESS and sLASER in identifying relationships between brain metabolites and age in CSO and PCC data acquired at 3T. sLASER is technically desirable due to the reduced chemical shift displacement artifact; however, PRESS performed similarly in 'good' brain regions at clinical field strength.
Collapse
Affiliation(s)
- Steve C.N. Hui
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA
| | - Tao Gong
- Department of Radiology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Helge J. Zöllner
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA
| | - Kathleen E. Hupfeld
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA
| | - Aaron T. Gudmundson
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA
| | - Saipavitra Murali-Manohar
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA
| | - Christopher W. Davies-Jenkins
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA
| | - Yulu Song
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA
| | - Yufan Chen
- Department of Radiology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Georg Oeltzschner
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA
| | - Guangbin Wang
- Department of Radiology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Richard A. E. Edden
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA
| |
Collapse
|
|
17
|
Roberts NT, Tamada D, Muslu Y, Hernando D, Reeder SB. Confounder-corrected T 1 mapping in the liver through simultaneous estimation of T 1 , PDFF, R 2 * , and B 1 + in a single breath-hold acquisition. Magn Reson Med 2023; 89:2186-2203. [PMID: 36656152 PMCID: PMC10139739 DOI: 10.1002/mrm.29590] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 12/23/2022] [Accepted: 01/01/2023] [Indexed: 01/20/2023]
Abstract
PURPOSE Quantitative volumetric T1 mapping in the liver has the potential to aid in the detection, diagnosis, and quantification of liver fibrosis, inflammation, and spatially resolved liver function. However, accurate measurement of hepatic T1 is confounded by the presence of fat and inhomogeneous B 1 + $$ {B}_1^{+} $$ excitation. Furthermore, scan time constraints related to respiratory motion require tradeoffs of reduced volumetric coverage and/or increased acquisition time. This work presents a novel 3D acquisition and estimation method for confounder-corrected T1 measurement over the entire liver within a single breath-hold through simultaneous estimation of T1 , fat and B 1 + $$ {B}_1^{+} $$ . THEORY AND METHODS The proposed method combines chemical shift encoded MRI and variable flip angle MRI with a B 1 + $$ {B}_1^{+} $$ mapping technique to enable confounder-corrected T1 mapping. The method was evaluated theoretically and demonstrated in both phantom and in vivo acquisitions at 1.5 and 3.0T. At 1.5T, the method was evaluated both pre- and post- contrast enhancement in healthy volunteers. RESULTS The proposed method demonstrated excellent linear agreement with reference inversion-recovery spin-echo based T1 in phantom acquisitions at both 1.5 and 3.0T, with minimal bias (5.2 and 45 ms, respectively) over T1 ranging from 200-1200 ms. In vivo results were in general agreement with reference saturation-recovery based 2D T1 maps (SMART1 Map, GE Healthcare). CONCLUSION The proposed 3D T1 mapping method accounts for fat and B 1 + $$ {B}_1^{+} $$ confounders through simultaneous estimation of T1 , B 1 + $$ {B}_1^{+} $$ , PDFF and R 2 * $$ {R}_2^{\ast } $$ . It demonstrates strong linear agreement with reference T1 measurements, with low bias and high precision, and can achieve full liver coverage in a single breath-hold.
Collapse
Affiliation(s)
- Nathan T Roberts
- Department of Radiology, University of Wisconsin - Madison, Madison, Wisconsin, USA.,Department of Electrical and Computer Engineering, University of Wisconsin - Madison, Madison, Wisconsin, USA
| | - Daiki Tamada
- Department of Radiology, University of Wisconsin - Madison, Madison, Wisconsin, USA
| | - Yavuz Muslu
- Department of Radiology, University of Wisconsin - Madison, Madison, Wisconsin, USA.,Department of Biomedical Engineering, University of Wisconsin - Madison, Madison, Wisconsin, USA
| | - Diego Hernando
- Department of Radiology, University of Wisconsin - Madison, Madison, Wisconsin, USA.,Department of Electrical and Computer Engineering, University of Wisconsin - Madison, Madison, Wisconsin, USA.,Department of Biomedical Engineering, University of Wisconsin - Madison, Madison, Wisconsin, USA.,Department of Medical Physics, University of Wisconsin - Madison, Madison, Wisconsin, USA
| | - Scott B Reeder
- Department of Radiology, University of Wisconsin - Madison, Madison, Wisconsin, USA.,Department of Biomedical Engineering, University of Wisconsin - Madison, Madison, Wisconsin, USA.,Department of Medical Physics, University of Wisconsin - Madison, Madison, Wisconsin, USA.,Department of Medicine, University of Wisconsin - Madison, Madison, Wisconsin, USA.,Department of Emergency Medicine, University of Wisconsin - Madison, Madison, Wisconsin, USA
| |
Collapse
|
|
18
|
Li YW, Jiao Y, Chen N, Gao Q, Chen YK, Zhang YF, Wen QP, Zhang ZM. How to select the quantitative magnetic resonance technique for subjects with fatty liver: A systematic review. World J Clin Cases 2022; 10:8906-8921. [PMID: 36157636 PMCID: PMC9477046 DOI: 10.12998/wjcc.v10.i25.8906] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 05/25/2022] [Accepted: 07/22/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Early quantitative assessment of liver fat content is essential for patients with fatty liver disease. Mounting evidence has shown that magnetic resonance (MR) technique has high accuracy in the quantitative analysis of fatty liver, and is suitable for monitoring the therapeutic effect on fatty liver. However, many packaging methods and postprocessing functions have puzzled radiologists in clinical applications. Therefore, selecting a quantitative MR imaging technique for patients with fatty liver disease remains challenging.
AIM To provide information for the proper selection of commonly used quantitative MR techniques to quantify fatty liver.
METHODS We completed a systematic literature review of quantitative MR techniques for detecting fatty liver, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. Studies were retrieved from PubMed, Embase, and Cochrane Library databases, and their quality was assessed using the Quality Assessment of Diagnostic Studies criteria. The Reference Citation Analysis database (https://www.referencecitationanalysis.com) was used to analyze citation of articles which were included in this review.
RESULTS Forty studies were included for spectroscopy, two-point Dixon imaging, and multiple-point Dixon imaging comparing liver biopsy to other imaging methods. The advantages and disadvantages of each of the three techniques and their clinical diagnostic performances were analyzed.
CONCLUSION The proton density fat fraction derived from multiple-point Dixon imaging is a noninvasive method for accurate quantitative measurement of hepatic fat content in the diagnosis and monitoring of fatty liver progression.
Collapse
Affiliation(s)
- You-Wei Li
- Department of Radiology, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, China
| | - Yang Jiao
- Department of Rehabilitation Psychology, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, China
| | - Na Chen
- Department of Otorhinolaryngology, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, China
| | - Qiang Gao
- Department of Gastroenterology and Hepatology, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, China
| | - Yu-Kun Chen
- Department of Radiology, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, China
| | - Yuan-Fang Zhang
- Department of Radiology, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, China
| | - Qi-Ping Wen
- Department of Radiology, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, China
| | - Zong-Ming Zhang
- Department of General Surgery, Beijing Electric Power Hospital, State Grid Corporation of China, Capital Medical University, Beijing 100073, China
| |
Collapse
|
|
19
|
Martel D, Saxena A, Belmont HM, Honig S, Chang G. Fatty Acid Composition of Proximal Femur Bone Marrow Adipose Tissue in Subjects With Systemic Lupus Erythematous Using 3 T Magnetic Resonance Spectroscopy. J Magn Reson Imaging 2022; 56:618-624. [PMID: 34964533 PMCID: PMC10023192 DOI: 10.1002/jmri.28038] [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: 09/20/2021] [Revised: 12/09/2021] [Accepted: 12/10/2021] [Indexed: 11/08/2022] Open
Abstract
BACKGROUND Systemic lupus erythematosus (SLE) is a chronic, inflammatory disease with common musculoskeletal manifestations, notably reductions in bone quality. Bone marrow adipose tissue composition and quantity has been previously linked to bone quality and may play a role in SLE pathophysiology but has not been thoroughly studied. PURPOSE To use magnetic resonance spectroscopy (MRS) to investigate bone marrow adipose tissue quantity and composition in proximal femur subregions of untreated SLE patients compared to controls and treated patients. STUDY TYPE Prospective. SUBJECTS A total of 64 female subjects: 28 SLE, 15 glucocorticoid (GC)-treated SLE and 21 matched controls. FIELD STRENGTH/SEQUENCE Stimulated echo acquisition mode (STEAM) sequence at 3 T. ASSESSMENT MRS was performed at multiple echo times in the femoral neck and trochanter regions and fatty acids (FA) composition was computed. STATISTICAL TESTS Intergroup comparisons were carried out using ANOVA. A P value < 0.05 was considered statistically significant. RESULTS SLE patients had significantly higher saturated FA compared to controls in both the femoral neck (+0.12) and trochanter (+0.11), significantly lower monounsaturated FA in the trochanter compared to controls (-0.05), and significantly lower polyunsaturated FA in the femoral neck compared to both controls (-0.07) and SLE patients on GC therapy (-0.05). DATA CONCLUSION SLE patients have altered proximal femur marrow fat metabolism, which may reflect a manifestation of, or play a role in, the altered inflammatory response of these patients. EVIDENCE LEVEL 2 TECHNICAL EFFICACY: Stage 2.
Collapse
Affiliation(s)
- Dimitri Martel
- New York Langone Health, Department of Radiology, New York, New York, USA
| | - Amit Saxena
- New York Langone Health, Division of Rheumatology, Hospital for Joint Diseases, New York, New York, USA
| | - Howard Michael Belmont
- New York Langone Health, Division of Rheumatology, Hospital for Joint Diseases, New York, New York, USA
| | - Stephen Honig
- New York Langone Health, Osteoporosis Center, Hospital for Joint Diseases, New York, New York, USA
| | - Gregory Chang
- New York Langone Health, Department of Radiology, New York, New York, USA
| |
Collapse
|
|
20
|
Yoshimaru D. [6. Methods of Abdominal MR Spectroscopy and Future Prospects]. Nihon Hoshasen Gijutsu Gakkai Zasshi 2022; 78:213-218. [PMID: 35185101 DOI: 10.6009/jjrt.780214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
|
|
21
|
Fortier V, Levesque IR. Longitudinal relaxation in fat-water mixtures and its dependence on fat content at 3 T. NMR IN BIOMEDICINE 2022; 35:e4629. [PMID: 34636097 DOI: 10.1002/nbm.4629] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 08/27/2021] [Accepted: 09/14/2021] [Indexed: 06/13/2023]
Abstract
Longitudinal (T1 ) relaxation of triglyceride molecules and water is of interest for fat-water separation and fat quantification. A better understanding of T1 relaxation could benefit modeling for applications in fat quantification and relaxation mapping. This work investigated T1 relaxation of spectral resonances of triglyceride molecules and water in liquid fat-water mixtures and its dependence on the fat fraction. Dairy cream and a safflower oil emulsion were used. These were diluted with distilled water to produce a variety of fat mass fractions (4.4% to 35% in dairy cream and 6.3% to 52.3% in safflower oil emulsion). T1 was measured at room temperature at 3 T using an inversion recovery STimulated Echo Acquisition Mode (STEAM) MR spectroscopy method with a series of inversion times. T1 variations as a function of fat fraction were investigated for various resonances. A two-component model was developed to describe the relaxation in a fat-water mixture as a function of the fat fraction. The T1 of water and of all fat resonances studied in this work decreased as the fat fraction increased. The relative variation in T1 was different for each fat resonance. The T1 of the methylene resonance showed the least variation as a function of the fat fraction. The proposed two-component model closely fits the observed T1 variations. In conclusion, this work clarifies how the T1 of major and minor fat resonances and of the water resonance varies as a function of the fat fraction in fat-water mixtures. Knowledge of these variations could serve modeling, analysis of MRI measurements in fat-water mixtures, and phantom preparation.
Collapse
Affiliation(s)
- Véronique Fortier
- Medical Physics Unit, McGill University, Montréal, QC, Canada
- Biomedical Engineering, McGill University, Montréal, QC, Canada
| | - Ives R Levesque
- Medical Physics Unit, McGill University, Montréal, QC, Canada
- Biomedical Engineering, McGill University, Montréal, QC, Canada
- Research Institute of the McGill University Health Centre, Montréal, QC, Canada
- Gerald Bronfman Department of Oncology, McGill University, Montréal, Canada
| |
Collapse
|
|
22
|
Ruschke S, Karampinos DC. Single-voxel short-TR multi-TI multi-TE STEAM MRS for water-fat relaxometry. Magn Reson Med 2022; 87:2587-2599. [PMID: 35014731 DOI: 10.1002/mrm.29157] [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: 10/18/2021] [Revised: 12/20/2021] [Accepted: 12/23/2021] [Indexed: 11/09/2022]
Abstract
PURPOSE To propose a short-TR multi-TI multi-TE (SHORTIE, ['shȯr-tē]) STEAM single-voxel MRS acquisition scheme for the simultaneous assessment of T1 relaxation, T2 relaxation, and the proton density fat fraction at reduced scan times when compared with conventional long-TR multi-TI STEAM and long-TR multi-TE STEAM single-voxel MRS. METHODS Theoretical analysis for multi-TI (TI = 10, 100, 500, 1500 ms; scan time = 2:43 minutes), multi-TE (TE = 12, 15, 20, 25 ms; scan time = 2:24 minutes), and SHORTIE STEAM (all TI and TE combinations; scan time = 2:52 minutes) was carried out including Cramér-Rao lower bound and parameter estimation efficiency analysis for T1 (150-2000 ms) and T2 (5-150 ms) relaxation. The SHORTIE STEAM acquisition was compared with multi-TI STEAM and multi-TE STEAM in water-fat phantoms and in a human in vivo study of the adipose tissue depot in the supraclavicular fossa in 7 volunteers at 3 T. RESULTS Cramér-Rao lower bound analysis revealed similar to increased variances for T1 and T2 estimators for SHORTIE STEAM. Parameter efficiency analysis demonstrated superior performance of SHORTIE, particularly for shorter T1 and T2 when compared with multi-TI STEAM and multi-TE STEAM. For the phantom data, linear regression and Bland-Altmann analysis yielded a slope/intercept/mean difference of 1.07/-15.40/-17.18 for T1 (in ms; r = 0.999), 0.93/+1.32/+1.09 for T2 (in ms; r = 0.995), and 0.98/-0.04/+0.78 for the fat fraction (in percent; r = 0.999); and for the in vivo data 1.08/+1.77/-62.2 for T1 (r = 0.994), 0.88/+6.69/-1.55 for T2 (r = 0.884), and 0.56/+34.40/-0.46 for the fat fraction (r = 0.673), respectively. CONCLUSION The SHORTIE STEAM acquisition allows shorter scan times for the simultaneous probing of relaxation properties and spectral content in the water-fat environment when compared with combined long-TR multi-TI, and long-TR multi-TE STEAM.
Collapse
Affiliation(s)
- Stefan Ruschke
- Department of Diagnostic and Interventional Radiology, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Dimitrios C Karampinos
- Department of Diagnostic and Interventional Radiology, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.,Munich Institute of Biomedical Engineering, Technical University of Munich, Garching, Germany
| |
Collapse
|
|
23
|
Weingärtner S, Desmond KL, Obuchowski NA, Baessler B, Zhang Y, Biondetti E, Ma D, Golay X, Boss MA, Gunter JL, Keenan KE, Hernando D. Development, validation, qualification, and dissemination of quantitative MR methods: Overview and recommendations by the ISMRM quantitative MR study group. Magn Reson Med 2021; 87:1184-1206. [PMID: 34825741 DOI: 10.1002/mrm.29084] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 10/20/2021] [Accepted: 10/27/2021] [Indexed: 12/26/2022]
Abstract
On behalf of the International Society for Magnetic Resonance in Medicine (ISMRM) Quantitative MR Study Group, this article provides an overview of considerations for the development, validation, qualification, and dissemination of quantitative MR (qMR) methods. This process is framed in terms of two central technical performance properties, i.e., bias and precision. Although qMR is confounded by undesired effects, methods with low bias and high precision can be iteratively developed and validated. For illustration, two distinct qMR methods are discussed throughout the manuscript: quantification of liver proton-density fat fraction, and cardiac T1 . These examples demonstrate the expansion of qMR methods from research centers toward widespread clinical dissemination. The overall goal of this article is to provide trainees, researchers, and clinicians with essential guidelines for the development and validation of qMR methods, as well as an understanding of necessary steps and potential pitfalls for the dissemination of quantitative MR in research and in the clinic.
Collapse
Affiliation(s)
- Sebastian Weingärtner
- Department of Imaging Physics, Delft University of Technology, Delft, The Netherlands
| | - Kimberly L Desmond
- Brain Health Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.,Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
| | - Nancy A Obuchowski
- Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, USA
| | - Bettina Baessler
- Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich, Switzerland
| | - Yuxin Zhang
- Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin, USA.,Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Emma Biondetti
- Department of Neuroscience, Imaging and Clinical Sciences, D'Annunzio University of Chieti and Pescara, Chieti, Italy
| | - Dan Ma
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, USA
| | - Xavier Golay
- Brain Repair & Rehabilitation, Institute of Neurology, University College London, United Kingdom.,Gold Standard Phantoms Limited, Rochester, United Kingdom
| | - Michael A Boss
- Center for Research and Innovation, American College of Radiology, Philadelphia, Pennsylvania, USA
| | | | - Kathryn E Keenan
- National Institute of Standards and Technology, Boulder, Colorado, USA
| | - Diego Hernando
- Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin, USA.,Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | | |
Collapse
|
|
24
|
Starekova J, Hernando D, Pickhardt PJ, Reeder SB. Quantification of Liver Fat Content with CT and MRI: State of the Art. Radiology 2021; 301:250-262. [PMID: 34546125 PMCID: PMC8574059 DOI: 10.1148/radiol.2021204288] [Citation(s) in RCA: 132] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 04/19/2021] [Accepted: 04/26/2021] [Indexed: 12/13/2022]
Abstract
Hepatic steatosis is defined as pathologically elevated liver fat content and has many underlying causes. Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, with an increasing prevalence among adults and children. Abnormal liver fat accumulation has serious consequences, including cirrhosis, liver failure, and hepatocellular carcinoma. In addition, hepatic steatosis is increasingly recognized as an independent risk factor for the metabolic syndrome, type 2 diabetes, and, most important, cardiovascular mortality. During the past 2 decades, noninvasive imaging-based methods for the evaluation of hepatic steatosis have been developed and disseminated. Chemical shift-encoded MRI is now established as the most accurate and precise method for liver fat quantification. CT is important for the detection and quantification of incidental steatosis and may play an increasingly prominent role in risk stratification, particularly with the emergence of CT-based screening and artificial intelligence. Quantitative imaging methods are increasingly used for diagnostic work-up and management of steatosis, including treatment monitoring. The purpose of this state-of-the-art review is to provide an overview of recent progress and current state of the art for liver fat quantification using CT and MRI, as well as important practical considerations related to clinical implementation.
Collapse
Affiliation(s)
- Jitka Starekova
- From the Departments of Radiology (J.S., D.H., P.J.P., S.B.R.),
Medical Physics (D.H., S.B.R.), Biomedical Engineering (S.B.R.), Medicine
(S.B.R.), and Emergency Medicine (S.B.R.), University of Wisconsin, 1111
Highland Ave, Madison, WI 53705
| | - Diego Hernando
- From the Departments of Radiology (J.S., D.H., P.J.P., S.B.R.),
Medical Physics (D.H., S.B.R.), Biomedical Engineering (S.B.R.), Medicine
(S.B.R.), and Emergency Medicine (S.B.R.), University of Wisconsin, 1111
Highland Ave, Madison, WI 53705
| | - Perry J. Pickhardt
- From the Departments of Radiology (J.S., D.H., P.J.P., S.B.R.),
Medical Physics (D.H., S.B.R.), Biomedical Engineering (S.B.R.), Medicine
(S.B.R.), and Emergency Medicine (S.B.R.), University of Wisconsin, 1111
Highland Ave, Madison, WI 53705
| | - Scott B. Reeder
- From the Departments of Radiology (J.S., D.H., P.J.P., S.B.R.),
Medical Physics (D.H., S.B.R.), Biomedical Engineering (S.B.R.), Medicine
(S.B.R.), and Emergency Medicine (S.B.R.), University of Wisconsin, 1111
Highland Ave, Madison, WI 53705
| |
Collapse
|
|
25
|
Al-Awadi A, Grove J, Taylor M, Valdes A, Vijay A, Bawden S, Gowland P, Aithal G. Effects of an isoenergetic low Glycaemic Index (GI) diet on liver fat accumulation and gut microbiota composition in patients with non-alcoholic fatty liver disease (NAFLD): a study protocol of an efficacy mechanism evaluation. BMJ Open 2021; 11:e045802. [PMID: 34620653 PMCID: PMC8499287 DOI: 10.1136/bmjopen-2020-045802] [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] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
INTRODUCTION A Low Glycaemic Index (LGI) diet is a proposed lifestyle intervention in non-alcoholic fatty liver diseases (NAFLD) which is designed to reduce circulating blood glucose levels, hepatic glucose influx, insulin resistance and de novo lipogenesis. A significant reduction in liver fat content through following a 1-week LGI diet has been reported in healthy volunteers. Changes in dietary fat and carbohydrates have also been shown to alter gut microbiota composition and lead to hepatic steatosis through the gut-liver axis. There are no available trials examining the effects of an LGI diet on liver fat accumulation in patients with NAFLD; nor has the impact of consuming an LGI diet on gut microbiota composition been studied in this population. The aim of this trial is to investigate the effects of LGI diet consumption on liver fat content and its effects on gut microbiota composition in participants with NAFLD compared with a High Glycaemic Index (HGI) control diet. METHODS AND ANALYSIS A 2×2 cross-over randomised mechanistic dietary trial will allocate 16 participants with NAFLD to a 2-week either HGI or LGI diet followed by a 4-week wash-out period and then the LGI or HGI diet, alternative to that followed in the first 2 weeks. Baseline and postintervention (four visits) outcome measures will be collected to assess liver fat content (using MRI/S and controlled attenuation parameter-FibroScan), gut microbiota composition (using 16S RNA analysis) and blood biomarkers including glycaemic, insulinaemic, liver, lipid and haematological profiles, gut hormones levels and short-chain fatty acids. ETHICS AND DISSEMINATION Study protocol has been approved by the ethics committees of The University of Nottingham and East Midlands Nottingham-2 Research Ethics Committee (REC reference 19/EM/0291). Data from this trial will be used as part of a Philosophy Doctorate thesis. Publications will be in peer-reviewed journals. TRIAL REGISTRATION NUMBER NCT04415632.
Collapse
Affiliation(s)
- Amina Al-Awadi
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
- National Institute of Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
- Al-Sabah Hospital, Ministry of Health, Civil Service Commission, Kuwait City, Kuwait
| | - Jane Grove
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
- National Institute of Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - Moira Taylor
- School of Life Sciences, University of Nottingham, Nottingham, UK
| | - Ana Valdes
- National Institute of Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
- School of Medicine, University of Nottingham, Nottingham, UK
| | - Amrita Vijay
- School of Medicine, University of Nottingham, Nottingham, UK
| | - Stephen Bawden
- National Institute of Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
- Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, UK
| | - Penny Gowland
- National Institute of Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
- Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, UK
| | - Guruprasad Aithal
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
- National Institute of Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| |
Collapse
|
|
26
|
Simchick G, Zhao R, Hamilton G, Reeder SB, Hernando D. Spectroscopy-based multi-parametric quantification in subjects with liver iron overload at 1.5T and 3T. Magn Reson Med 2021; 87:597-613. [PMID: 34554595 DOI: 10.1002/mrm.29021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 08/13/2021] [Accepted: 09/07/2021] [Indexed: 01/02/2023]
Abstract
PURPOSE To evaluate the precision profile (repeatability and reproducibility) of quantitative STEAM-MRS and to determine the relationships between multiple MR biomarkers of chronic liver disease in subjects with iron overload at both 1.5 Tesla (T) and 3T. METHODS MRS data were acquired in patients with known or suspected liver iron overload. Two STEAM-MRS sequences (multi-TE and multi-TE-TR) were acquired at both 1.5T and 3T (same day), including test-retest acquisition. Each acquisition enabled estimation of R1, R2, and FWHM (each separately for water and fat); and proton density fat fraction. The test-retest repeatability and reproducibility across acquisition modes (multi-TE vs. multi-TE-TR) of the estimates were evaluated using intraclass correlation coefficients, linear regression, and Bland-Altman analyses. Multi-parametric relationships between parameters at each field strength, across field strengths, and with liver iron concentration were also evaluated using linear and nonlinear regression. RESULTS Fifty-six (n = 56) subjects (10 to 73 years, 37 males/19 females) were successfully recruited. Both STEAM-MRS sequences demonstrated good-to-excellent precision (intraclass correlation coefficient ≥ 0.81) for the quantification of R1water , R2water , FWHMwater , and proton density fat fraction at both 1.5T and 3T. Additionally, several moderate (R2 = 0.50 to 0.69) to high (R2 ≥ 0.70) correlations were observed between biomarkers, across field strengths, and with liver iron concentration. CONCLUSIONS Over a broad range of liver iron concentration, STEAM-MRS enables rapid and precise measurement of multiple biomarkers of chronic liver disease. By evaluating the multi-parametric relationships between biomarkers, this work may advance the comprehensive MRS-based assessment of chronic liver disease and may help establish biomarkers of chronic liver disease.
Collapse
Affiliation(s)
- Gregory Simchick
- Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Ruiyang Zhao
- Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin, USA.,Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Gavin Hamilton
- Department of Radiology, University of California, San Diego, California, USA
| | - Scott B Reeder
- Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin, USA.,Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin, USA.,Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA.,Department of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.,Department of Emergency Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Diego Hernando
- Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin, USA.,Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin, USA.,Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA
| |
Collapse
|
|
27
|
McGee KP, Hwang KP, Sullivan DC, Kurhanewicz J, Hu Y, Wang J, Li W, Debbins J, Paulson E, Olsen JR, Hua CH, Warner L, Ma D, Moros E, Tyagi N, Chung C. Magnetic resonance biomarkers in radiation oncology: The report of AAPM Task Group 294. Med Phys 2021; 48:e697-e732. [PMID: 33864283 PMCID: PMC8361924 DOI: 10.1002/mp.14884] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 03/24/2021] [Accepted: 03/28/2021] [Indexed: 12/16/2022] Open
Abstract
A magnetic resonance (MR) biologic marker (biomarker) is a measurable quantitative characteristic that is an indicator of normal biological and pathogenetic processes or a response to therapeutic intervention derived from the MR imaging process. There is significant potential for MR biomarkers to facilitate personalized approaches to cancer care through more precise disease targeting by quantifying normal versus pathologic tissue function as well as toxicity to both radiation and chemotherapy. Both of which have the potential to increase the therapeutic ratio and provide earlier, more accurate monitoring of treatment response. The ongoing integration of MR into routine clinical radiation therapy (RT) planning and the development of MR guided radiation therapy systems is providing new opportunities for MR biomarkers to personalize and improve clinical outcomes. Their appropriate use, however, must be based on knowledge of the physical origin of the biomarker signal, the relationship to the underlying biological processes, and their strengths and limitations. The purpose of this report is to provide an educational resource describing MR biomarkers, the techniques used to quantify them, their strengths and weakness within the context of their application to radiation oncology so as to ensure their appropriate use and application within this field.
Collapse
Affiliation(s)
- Kiaran P McGee
- Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA
| | - Ken-Pin Hwang
- Department of Imaging Physics, Division of Diagnostic Imaging, MD Anderson Cancer Center, University of Texas, Houston, Texas, USA
| | - Daniel C Sullivan
- Department of Radiology, Duke University, Durham, North Carolina, USA
| | - John Kurhanewicz
- Department of Radiology, University of California, San Francisco, California, USA
| | - Yanle Hu
- Department of Radiation Oncology, Mayo Clinic, Scottsdale, Arizona, USA
| | - Jihong Wang
- Department of Radiation Oncology, MD Anderson Cancer Center, University of Texas, Houston, Texas, USA
| | - Wen Li
- Department of Radiation Oncology, University of Arizona, Tucson, Arizona, USA
| | - Josef Debbins
- Department of Radiology, Barrow Neurologic Institute, Phoenix, Arizona, USA
| | - Eric Paulson
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Jeffrey R Olsen
- Department of Radiation Oncology, University of Colorado Denver - Anschutz Medical Campus, Denver, Colorado, USA
| | - Chia-Ho Hua
- Department of Radiation Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
| | | | - Daniel Ma
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA
| | - Eduardo Moros
- Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida, USA
| | - Neelam Tyagi
- Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Caroline Chung
- Department of Radiation Oncology, MD Anderson Cancer Center, University of Texas, Houston, Texas, USA
| |
Collapse
|
|
28
|
Pasanta D, Htun KT, Pan J, Tungjai M, Kaewjaeng S, Kim H, Kaewkhao J, Kothan S. Magnetic Resonance Spectroscopy of Hepatic Fat from Fundamental to Clinical Applications. Diagnostics (Basel) 2021; 11:842. [PMID: 34067193 PMCID: PMC8151733 DOI: 10.3390/diagnostics11050842] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 04/29/2021] [Accepted: 05/06/2021] [Indexed: 02/06/2023] Open
Abstract
The number of individuals suffering from fatty liver is increasing worldwide, leading to interest in the noninvasive study of liver fat. Magnetic resonance spectroscopy (MRS) is a powerful tool that allows direct quantification of metabolites in tissue or areas of interest. MRS has been applied in both research and clinical studies to assess liver fat noninvasively in vivo. MRS has also demonstrated excellent performance in liver fat assessment with high sensitivity and specificity compared to biopsy and other imaging modalities. Because of these qualities, MRS has been generally accepted as the reference standard for the noninvasive measurement of liver steatosis. MRS is an evolving technique with high potential as a diagnostic tool in the clinical setting. This review aims to provide a brief overview of the MRS principle for liver fat assessment and its application, and to summarize the current state of MRS study in comparison to other techniques.
Collapse
Affiliation(s)
- Duanghathai Pasanta
- Center of Radiation Research and Medical Imaging, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (D.P.); (K.T.H.); (J.P.); (M.T.); (S.K.)
| | - Khin Thandar Htun
- Center of Radiation Research and Medical Imaging, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (D.P.); (K.T.H.); (J.P.); (M.T.); (S.K.)
| | - Jie Pan
- Center of Radiation Research and Medical Imaging, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (D.P.); (K.T.H.); (J.P.); (M.T.); (S.K.)
- Shandong Provincial Key Laboratory of Animal Resistant Biology, College of Life Sciences, Shandong Normal University, Jinan 250014, China
| | - Montree Tungjai
- Center of Radiation Research and Medical Imaging, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (D.P.); (K.T.H.); (J.P.); (M.T.); (S.K.)
| | - Siriprapa Kaewjaeng
- Center of Radiation Research and Medical Imaging, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (D.P.); (K.T.H.); (J.P.); (M.T.); (S.K.)
| | - Hongjoo Kim
- Department of Physics, Kyungpook National University, Daegu 41566, Korea;
| | - Jakrapong Kaewkhao
- Center of Excellence in Glass Technology and Materials Science (CEGM), Nakhon Pathom Rajabhat University, Nakhon Pathom 73000, Thailand;
| | - Suchart Kothan
- Center of Radiation Research and Medical Imaging, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (D.P.); (K.T.H.); (J.P.); (M.T.); (S.K.)
| |
Collapse
|
|
29
|
Lu LW, Silvestre MP, Sequeira IR, Plank LD, Foster M, Middleditch N, Acevedo-Fani A, Hollingsworth KG, Poppitt SD. A higher-protein nut-based snack product suppresses glycaemia and decreases glycaemic response to co-ingested carbohydrate in an overweight prediabetic Asian Chinese cohort: the Tū Ora postprandial RCT. J Nutr Sci 2021; 10:e30. [PMID: 34094511 PMCID: PMC8141680 DOI: 10.1017/jns.2021.20] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 03/16/2021] [Accepted: 03/22/2021] [Indexed: 12/27/2022] Open
Abstract
Nut-based products may aid low-glycaemic dietary strategies that are important for diabetes prevention in populations at increased risk of dysglycaemia, such as Asian Chinese. This randomised cross-over trial assessed the postprandial glycaemic response (0-120 min) of a higher-protein nut-based (HP-NB) snack formulation, in bar format (1009 kJ, Nutrient Profiling Score, NPS, -2), when compared with an iso-energetic higher-carbohydrate (CHO) cereal-based bar (HC-CB, 985 kJ, NPS +3). It also assessed the ability to suppress glucose response to a typical CHO-rich food (white bread, WB), when co-ingested. Ten overweight prediabetic Chinese adults (mean, sd: age 47⋅9, 15⋅7 years; BMI 25⋅5, 1⋅6 kg/m2), with total body fat plus ectopic pancreas and liver fat quantified using dual-energy X-ray absorptiometry and magnetic resonance imaging and spectroscopy, received the five meal treatments in random order: HP-NB, HC-CB, HP-NB + WB (50 g available CHO), HC-CB + WB and WB only. Compared with HC-CB, HP-NB induced a significantly lower 30-120 min glucose response (P < 0⋅05), with an approximately 10-fold lower incremental area under the glucose curve (iAUC0-120; P < 0⋅001). HP-NB also attenuated glucose response by approximately 25 % when co-ingested with WB (P < 0⋅05). Half of the cohort had elevated pancreas and/or liver fat, with 13-21 % greater suppression of iAUC0-120 glucose in the low v. high organ fat subgroups across all five treatments. A nut-based snack product may be a healthier alternative to an energy equivalent cereal-based product with evidence of both a lower postprandial glycaemic response and modulation of CHO-induced hyperglycaemia even in high-risk, overweight, pre-diabetic adults.
Collapse
Key Words
- AUC, area under the curve
- BF, body fat
- BMI, body mass index
- CHO, carbohydrate
- DXA, dual-energy X-ray absorptiometry
- Dried fruits
- GI, glycaemic index
- MRI
- MRI, magnetic resonance imaging
- MRS, magnetic resonance spectroscopy
- Nuts
- Postprandial glycaemia
- Prediabetes
- SAT, subcutaneous adipose tissue
- T2D, type 2 diabetes
- VAS, visual analogue scales
- VAT, visceral adipose tissue
- WB, white bread
- iAUC, incremental area under the curve
Collapse
Affiliation(s)
- Louise W. Lu
- Human Nutrition Unit, School of Biological Sciences, University of Auckland, Auckland, New Zealand
- High-Value Nutrition National Science Challenge, Auckland, New Zealand
| | - Marta P. Silvestre
- Human Nutrition Unit, School of Biological Sciences, University of Auckland, Auckland, New Zealand
- High-Value Nutrition National Science Challenge, Auckland, New Zealand
| | - Ivana R. Sequeira
- Human Nutrition Unit, School of Biological Sciences, University of Auckland, Auckland, New Zealand
- High-Value Nutrition National Science Challenge, Auckland, New Zealand
| | - Lindsay D. Plank
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Meika Foster
- Edible Research Ltd, Christchurch, New Zealand
- Department of Medicine, University of Otago, Dunedin, New Zealand
| | - Nikki Middleditch
- High-Value Nutrition National Science Challenge, Auckland, New Zealand
- Riddet Institute, Massey University, Palmerston North, New Zealand
| | - Alejandra Acevedo-Fani
- High-Value Nutrition National Science Challenge, Auckland, New Zealand
- Riddet Institute, Massey University, Palmerston North, New Zealand
| | - Kieren G. Hollingsworth
- Newcastle Magnetic Resonance Centre, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
| | - Sally D. Poppitt
- Human Nutrition Unit, School of Biological Sciences, University of Auckland, Auckland, New Zealand
- High-Value Nutrition National Science Challenge, Auckland, New Zealand
- Riddet Centre of Research Excellence (CoRE) for Food and Nutrition, Palmerston North, New Zealand
- Department of Medicine, University of Auckland, Auckland, New Zealand
| |
Collapse
|
|
30
|
Ruschke S, Syväri J, Dieckmeyer M, Junker D, Makowski MR, Baum T, Karampinos DC. Physiological variation of the vertebral bone marrow water T2 relaxation time. NMR IN BIOMEDICINE 2021; 34:e4439. [PMID: 33205520 DOI: 10.1002/nbm.4439] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Revised: 10/09/2020] [Accepted: 10/14/2020] [Indexed: 06/11/2023]
Abstract
The aim of this study was to investigate physiological variations of the water T2 relaxation time in vertebral bone marrow with respect to age, body mass index (BMI), sex and proton density fat fraction (PDFF) based on single-voxel magnetic resonance spectroscopy (MRS) at 3 T. Multi-TE single-voxel STEAM MRS data of a single lumbar vertebra (L4 or L5) from 260 subjects (160/100 female/male, age: 0.7/37.1/77.7 years, BMI: 13.6/26.2/44.5 kg/m2 [min./median/max.]) with no history of vertebral bone marrow pathologies were retrospectively included. All data were processed using a joint series T2-constrained time domain-based water-fat model. Water T2 and PDFF data were analyzed using (a) Pearson's correlation r and (b) multiple linear regression without interactions of the independent variables. Min./median/max. water T2 and PDFF were 11.2/21.1/42.5 ms and 4.0%/36.8%/82.0%, respectively. Pearson's correlation coefficients were significant (P < .05) for water T2 versus age (r = -0.429/-0.210 female/male) and for water T2 versus PDFF (r = -0.580/-0.546 female/male) for females and males, respectively. Females showed significant higher water T2 values compared with males (P < .001). Multiple linear regression for water T2 without interactions revealed a R2 = 0.407 with PDFF (P < .001) and sex (P < .001) as significant predictors. The current study suggests that under physiological conditions vertebral bone marrow water T2 is negatively correlated with age and PDFF and shows significant differences between females and males. The observed systematic trends are of relevance for the evaluation of T2 values and T2-weighted bone marrow parameters. Further research on the exact mechanisms and drivers of the observed water T2 behavior is required.
Collapse
Affiliation(s)
- Stefan Ruschke
- Department of Diagnostic and Interventional Radiology, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Jan Syväri
- Department of Diagnostic and Interventional Radiology, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Michael Dieckmeyer
- Department of Diagnostic and Interventional Neuroradiology, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Daniela Junker
- Department of Diagnostic and Interventional Radiology, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Marcus R Makowski
- Department of Diagnostic and Interventional Radiology, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Thomas Baum
- Department of Diagnostic and Interventional Neuroradiology, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Dimitrios C Karampinos
- Department of Diagnostic and Interventional Radiology, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| |
Collapse
|
|
31
|
Fallone CJ, Tessier AG, Field CJ, Yahya A. Resolving the omega-3 methyl resonance with long echo time magnetic resonance spectroscopy in mouse adipose tissue at 9.4 T. NMR IN BIOMEDICINE 2021; 34:e4455. [PMID: 33269481 DOI: 10.1002/nbm.4455] [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: 08/14/2020] [Revised: 10/27/2020] [Accepted: 11/11/2020] [Indexed: 06/12/2023]
Abstract
Tissue omega-3 (ω-3) content is biologically important to disease; however, its quantification with magnetic resonance spectroscopy in vivo is challenging due to its low concentration. In addition, the ω-3 methyl resonance (≈ 0.98 ppm) overlaps that of the non-ω-3 (≈ 0.90 ppm), even at 9.4 T. We demonstrate that a Point-RESolved Spectroscopy (PRESS) sequence with an echo time (TE) of 109 ms resolves the ω-3 and non-ω-3 methyl peaks at 9.4 T. Sequence efficacy was verified on five oils with differing ω-3 fat content; the ω-3 content obtained correlated with that measured using 16.5 T NMR (R2 = 0.97). The PRESS sequence was also applied to measure ω-3 content in visceral adipose tissue of three different groups (all n = 3) of mice, each of which were fed a different 20% w/w fat diet. The fat portion of the diet consisted of low (1.4%), medium (9.0%) or high (16.4%) ω-3 fat. The sequence was also applied to a control mouse fed a standard chow diet (5.6% w/w fat, which was 5.9% ω-3). Gas chromatography (GC) analysis of excised tissue was performed for each mouse. The ω-3 fat content obtained with the PRESS sequence correlated with the GC measures (R2 = 0.96). Apparent T2 times of methyl protons were assessed by obtaining spectra from the oils and another group of four mice (fed the high ω-3 diet) with TE values of 109 and 399 ms. Peak areas were fit to a mono-exponentially decaying function and the apparent T2 values of the ω-3 and non-ω-3 methyl protons were 906 ± 148 and 398 ± 78 ms, respectively, in the oils. In mice, the values were 410 ± 68 and 283 ± 57 ms for ω-3 and non-ω-3 fats, respectively.
Collapse
Affiliation(s)
- Clara J Fallone
- Department of Oncology, University of Alberta, Edmonton, Alberta, Canada
| | - Anthony G Tessier
- Department of Oncology, University of Alberta, Edmonton, Alberta, Canada
- Department of Medical Physics, Cross Cancer Institute, Edmonton, Alberta, Canada
| | - Catherine J Field
- Department of Agricultural, Food, and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada
| | - Atiyah Yahya
- Department of Oncology, University of Alberta, Edmonton, Alberta, Canada
- Department of Medical Physics, Cross Cancer Institute, Edmonton, Alberta, Canada
| |
Collapse
|
|
32
|
Liver fat quantification: where do we stand? Abdom Radiol (NY) 2020; 45:3386-3399. [PMID: 33025153 DOI: 10.1007/s00261-020-02783-1] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 09/09/2020] [Accepted: 09/21/2020] [Indexed: 12/14/2022]
Abstract
Excessive intracellular accumulation of triglycerides in the liver, or hepatic steatosis, is a highly prevalent condition affecting approximately one billion people worldwide. In the absence of secondary cause, the term nonalcoholic fatty liver disease (NAFLD) is used. Hepatic steatosis may progress into nonalcoholic steatohepatitis, the more aggressive form of NAFLD, associated with hepatic complications such as fibrosis, liver failure and hepatocellular carcinoma. Hepatic steatosis is associated with metabolic syndrome, cardiovascular disease and represents an independent risk factor for type 2 diabetes, cardiovascular disease and malignancy. Percutaneous liver biopsy is the current reference standard for NAFLD assessment; however, it is an invasive procedure associated with complications and suffers from high sampling variability, impractical for clinical routine and drug efficiency studies. Therefore, noninvasive imaging methods are increasingly used for the diagnosis and monitoring of NAFLD. Among the methods quantifying liver fat, chemical-shift-encoded MRI (CSE-MRI)-based proton density fat-fraction (PDFF) has shown the most promise. MRI-PDFF is increasingly accepted as quantitative imaging biomarker of liver fat that is transforming daily clinical practice and influencing the development of new treatments for NAFLD. Furthermore, CT is an important imaging method for detection of incidental steatosis, and the practical advantages of quantitative ultrasound hold great promise for the future. Understanding the disease burden of NAFLD and the role of imaging may initiate important interventions aimed at avoiding the hepatic and extrahepatic complications of NAFLD. This article reviews clinical burden of NAFLD, and the role of noninvasive imaging techniques for quantification of liver fat.
Collapse
|
|
33
|
Lawrence EM, Roberts NT, Hernando D, Mao L, Reeder SB. Effect of noise and estimator type on bias for analysis of liver proton density fat fraction. Magn Reson Imaging 2020; 74:244-249. [PMID: 33011211 DOI: 10.1016/j.mri.2020.09.027] [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: 07/01/2020] [Revised: 09/14/2020] [Accepted: 09/29/2020] [Indexed: 10/23/2022]
Abstract
PURPOSE Proton-density fat-fraction (PDFF) is typically measured from PDFF maps by calculating the mean PDFF value within a region of interest (ROI). However, the mean estimator has been shown to result in bias when signal-to-noise ratio (SNR) is low, resulting from a skewed distribution of PDFF noise statistics. Thus, the purpose of this work was to determine the relative performance of three estimation methods (mean, median, maximum likelihood estimators (MLE)) for analysis of liver PDFF maps. METHODS Observational study of adult patients (n = 56) undergoing abdominal MRI. Both 2D-sequential CSE-MRI ('low-SNR') and 3D CSE-MRI ('high-SNR') acquisitions were obtained. Single-voxel MRS formed the independent reference measurement of hepatic PDFF. Intra-class correlation was tested on a subset of 'low-SNR' acquisitions. ROIs were semi-automatically co-registered across all acquisitions. Bland-Altman analysis and intra-class correlation coefficients were used for statistical analysis. A p-value of <0.05 was considered significant. RESULTS For in vivo low-SNR acquisitions, the mean estimator had a larger error than either the median or MLE values (bias ~ -1% absolute PDFF). The intra-class correlation coefficient was significantly greater for median and maximum likelihood estimators (0.992 and 0.993, respectively) compared to the mean estimator (0.973). CONCLUSION Alternative ROI analysis strategies, such as MLE or median estimators, are useful to avoid SNR-related PDFF bias. Median may be the most clinically practical strategy given its ease of calculation.
Collapse
Affiliation(s)
- Edward M Lawrence
- Department of Radiology, University of Wisconsin - Madison, Madison, WI, United States
| | - Nathan T Roberts
- Department of Radiology, University of Wisconsin - Madison, Madison, WI, United States; Electrical and Computer Engineering, University of Wisconsin - Madison, Madison, WI, United States
| | - Diego Hernando
- Department of Radiology, University of Wisconsin - Madison, Madison, WI, United States; Medical Physics, University of Wisconsin - Madison, Madison, WI, United States
| | - Lu Mao
- Biostatistics and Medical Informatics, University of Wisconsin - Madison, Madison, WI, United States
| | - Scott B Reeder
- Department of Radiology, University of Wisconsin - Madison, Madison, WI, United States; Medical Physics, University of Wisconsin - Madison, Madison, WI, United States; Biomedical Engineering, University of Wisconsin - Madison, Madison, WI, United States; Medicine, University of Wisconsin - Madison, Madison, WI, United States; Emergency Medicine, University of Wisconsin - Madison, Madison, WI, United States.
| |
Collapse
|
|
34
|
Chen H, Zeng WK, Shi GZ, Gao M, Wang MZ, Shen J. Liver fat accumulation measured by high-speed T2-corrected multi-echo magnetic resonance spectroscopy can predict risk of cholelithiasis. World J Gastroenterol 2020; 26:4996-5007. [PMID: 32952345 PMCID: PMC7476179 DOI: 10.3748/wjg.v26.i33.4996] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 06/14/2020] [Accepted: 08/01/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Liver fat accumulation is associated with increased cholesterol synthesis and hypersecretion of biliary cholesterol, which may be related to the development of cholelithiasis.
AIM To investigate whether liver fat accumulation measured by high-speed T2-corrected multi-echo magnetic resonance spectroscopy (MRS) is a risk factor for cholelithiasis.
METHODS Forty patients with cholelithiasis and thirty-one healthy controls were retrospectively enrolled. The participants underwent high-speed T2-corrected multi-echo single-voxel MRS of the liver at a 3T MR scanner. The proton density fat fraction (PDFF) and R2 value were calculated. Serum parameters and waist circumference (WC) were recorded. Spearman’s correlation analysis was used to analyze the relationship between PDFF, R2, and WC values. Multivariate logistic regression analysis was carried out to determine the significant predictors of the risk of cholelithiasis. Receiver operating characteristic curve (ROC) analysis was used to evaluate the discriminative performance of significant predictors.
RESULTS Patients with cholelithiasis had higher PDFF, R2, and WC values compared with healthy controls (5.8% ± 4.2% vs 3.3% ± 2.4%, P = 0.001; 50.4 ± 24.8/s vs 38.3 ± 8.8/s, P = 0.034; 85.3 ± 9.0 cm vs 81.0 ± 6.9 cm, P = 0.030; respectively). Liver iron concentration extrapolated from R2 values was significantly higher in the cholelithiasis group (2.21 ± 2.17 mg/g dry tissue vs 1.22 ± 0.49 mg/g dry tissue, P = 0.034) than in the healthy group. PDFF was positively correlated with WC (r = 0.502, P < 0.001) and R2 (r = 0.425, P < 0.001). Multivariate logistic regression analysis showed that only PDFF was an independent risk factor for cholelithiasis (odds ratio = 1.79, 95%CI: 1.22-2.62, P = 0.003). ROC analysis showed that the area under the curve of PDFF was 0.723 for discriminating cholelithiasis from healthy controls, with a sensitivity of 55.0% and specificity of 83.9% when the cut-off value of PDFF was 4.4%.
CONCLUSION PDFF derived from high speed T2-corrected multi-echo MRS can predict the risk of cholelithiasis.
Collapse
Affiliation(s)
- Hong Chen
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong Province, China
| | - Wei-Ke Zeng
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong Province, China
| | - Guang-Zi Shi
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong Province, China
| | - Ming Gao
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong Province, China
| | - Meng-Zhu Wang
- Department of MR Scientific Marketing, Siemens Healthineers, Guangzhou 510120, Guangdong Province, China
| | - Jun Shen
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong Province, China
| |
Collapse
|
|
35
|
Differences in multi-echo chemical shift encoded MRI proton density fat fraction estimation based on multifrequency fat peaks selection in non-alcoholic fatty liver disease patients. Clin Radiol 2020; 75:880.e5-880.e12. [PMID: 32888653 DOI: 10.1016/j.crad.2020.07.031] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Accepted: 07/28/2020] [Indexed: 11/20/2022]
Abstract
AIM To compare the performance of multi-echo chemical-shift-encoded (MECSE) magnetic resonance imaging (MRI) proton density fat fraction (PDFF) estimation, considering three different fat frequency peak combinations, for the quantification of steatosis in patients with non-alcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS The present study was a prospective cross-sectional research of 121 patients with metabolic syndrome and evidence of hepatic steatosis on ultrasound, who underwent a 3 T MRI examination. All patients were studied with a multifrequency MECSE sequence. The PDFF was calculated using six peaks (MECSEp123456), three peaks (MECSEp456), and a single peak (MECSEp5) model. The two simpler fat peak models were compared to the six peaks model, which was considered the reference standard. Linearity was evaluated using linear regression while agreement was described using Bland-Altman analysis. RESULTS The mean age was 47 (±9) years and BMI was 29.9 (±2.9) kg/m2. Steatosis distribution was 15%/31%/54% (S1/S2/S3, respectively). Compared to MECSEp123456, both models provided linear PDFF measurements (R2= 0.99 and 0.97, MECSEp456 and MECSEp5 respectively). Regression slope (0.92; p<0.001) and mean Bland-Altman bias (-1.5%; 95% limits of agreement: -3.19%, 0.22%) indicated minimal underestimation by using PDFF-MECSEp456. Nonetheless, mean differences in PDFF estimations varied from -1.5% (MECSEp456,p=0.006) to -2.2% (MECSEp5,p<0.001) when compared to full six fat frequencies model. CONCLUSION Although simpler spectral fat MECSE analysis shows a linear relationship with the standard six peaks model, their variation in estimated PDFF values introduces a low but clinically significant bias in fat quantification and steatosis grading in NAFLD patients.
Collapse
|
|
36
|
Peterson P, Trinh L, Månsson S. Quantitative 1 H MRI and MRS of fatty acid composition. Magn Reson Med 2020; 85:49-67. [PMID: 32844500 DOI: 10.1002/mrm.28471] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 07/08/2020] [Accepted: 07/20/2020] [Indexed: 12/22/2022]
Abstract
Adipose tissue as well as other depots of fat (triglycerides) are increasingly being recognized as active contributors to the human function and metabolism. In addition to the fat concentration, also the fatty acid chemical composition (FAC) of the triglyceride molecules may play an important part in diseases such as obesity, insulin resistance, hepatic steatosis, osteoporosis, and cancer. MR spectroscopy and chemical-shift-encoded imaging (CSE-MRI) are established methods for non-invasive quantification of fat concentration in tissue. More recently, similar techniques have been developed for assessment also of the FAC in terms of the number of double bonds, the fraction of saturated, monounsaturated, and polyunsaturated fatty acids, or semi-quantitative unsaturation indices. The number of papers focusing on especially CSE-MRI-based techniques has steadily increased during the past few years, introducing a range of acquisition protocols and reconstruction algorithms. However, a number of potential sources of bias have also been identified. Furthermore, the measures used to characterize the FAC using both MRI and MRS differ, making comparisons between different techniques difficult. The aim of this paper is to review MRS- and MRI-based methods for in vivo quantification of the FAC. We describe the chemical composition of triglycerides and discuss various potential FAC measures. Furthermore, we review acquisition and reconstruction methodology and finally, some existing and potential applications are summarized. We conclude that both MRI and MRS provide feasible non-invasive alternatives to the gold standard gas chromatography for in vivo measurements of the FAC. Although both are associated with gas chromatography, future studies are warranted.
Collapse
Affiliation(s)
- Pernilla Peterson
- Medical Radiation Physics, Malmö, Department of Translational Medicine, Lund University, Skåne University Hospital, Malmö, Sweden.,Medical Imaging and Physiology, Skåne University Hospital, Lund, Sweden
| | - Lena Trinh
- Medical Radiation Physics, Malmö, Department of Translational Medicine, Lund University, Skåne University Hospital, Malmö, Sweden
| | - Sven Månsson
- Medical Radiation Physics, Malmö, Department of Translational Medicine, Lund University, Skåne University Hospital, Malmö, Sweden
| |
Collapse
|
|
37
|
Ismail UN, Azlan CA, Khairullah S, Azman RR, Omar NF, Md Shah MN, Yeong CH, Jackson N, Ng KH. Marrow Fat Content and Composition in β-Thalassemia: A Study using 1 H-MRS. J Magn Reson Imaging 2020; 53:190-198. [PMID: 33237616 DOI: 10.1002/jmri.27294] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 07/01/2020] [Accepted: 07/06/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND β-thalassemia is a genetic disease that causes abnormal production of red blood cells (ineffective erythropoiesis, IE). IE is a condition known to change bone marrow composition. PURPOSE To evaluate the effect of IE on the marrow fat content and fat unsaturation levels in the proximal femur using 1 H-MRS. STUDY TYPE Prospective. SUBJECTS Twenty-three subjects were included in this study, seven control and 16 β-thalassemia subjects. FIELD STRENGTH/SEQUENCE 3.0T; stimulated echo acquisition Mode (STEAM); magnetic resonance spectroscopy (MRS) sequence. ASSESSMENT Multiecho MRS scans were performed in four regions of the proximal left femur of each subject, that is, diaphysis, femoral neck, femoral head, and greater trochanter. The examined regions were grouped into red (diaphysis and femoral neck) and yellow marrow regions (femoral head and greater trochanter). STATISTICAL TESTS The Jonckheere-Terpstra test was used to evaluate the impact of increasing disease severity on bone marrow fat fraction (BMFF), marrow conversion index, and fat unsaturation index (UI). Pairwise comparison analysis was performed when a significant trend (P < 0.05) was found. K-means clustering analysis was used to examine the clusters observed when BMFF in the red and yellow regions were studied (diaphysis against greater trochanter). RESULTS BMFF showed a significant decreasing trend with increasing disease severity in both red (TJT = 109.00, z = -4.414, P < 0.05) and yellow marrow regions (TJT = 108.00, z = -4.438, P < 0.05). The opposite trend was observed in UI in both bone marrow regions (red marrow: TJT = 180.5, z = 3.515, P < 0.05; yellow marrow: TJT = 155.0, z = 2.282, P = 0.05). Three distinct forms of marrow adipogenesis were found when plotting BMFF diaphysis against BMFF greater trochanter: 1) normal (centroid: 80.4%, 66.6%), 2) partial disruption (centroid: 51.1%, 16.6%), and 3) total disruption (centroid: 2.6%, 1.6%). DATA CONCLUSION β-thalassemia is associated with decreased marrow fat, and increased marrow fat unsaturation level. LEVEL OF EVIDENCE 2 TECHNICAL EFFICACY STAGE: 3.
Collapse
Affiliation(s)
- Umi Nabilah Ismail
- Department of Biomedical Imaging, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Che Ahmad Azlan
- Department of Biomedical Imaging, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Shasha Khairullah
- Haematology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Raja Rizal Azman
- Department of Biomedical Imaging, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Nur Farhayu Omar
- Department of Radiology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia
| | - Mohammad Nazri Md Shah
- Department of Biomedical Imaging, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Chai Hong Yeong
- School of Medicine, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya, Malaysia
| | - Nicholas Jackson
- Red Cell Unit, Department of Haematology, University College Hospital, London, UK
| | - Kwan Hoong Ng
- Department of Biomedical Imaging, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| |
Collapse
|
|
38
|
Syväri J, Ruschke S, Dieckmeyer M, Hauner HH, Junker D, Makowski MR, Baum T, Karampinos DC. Estimating vertebral bone marrow fat unsaturation based on short-TE STEAM MRS. Magn Reson Med 2020; 85:615-626. [PMID: 32783232 DOI: 10.1002/mrm.28453] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 06/09/2020] [Accepted: 07/09/2020] [Indexed: 01/11/2023]
Abstract
PURPOSE To define a metric for the separability between water and olefinic fat peaks that defines a threshold beyond which the extraction of the olefinic fat peak from vertebral bone marrow short-echo time-stimulated echo acquisition mode MRS at 3T is feasible when using a constrained peak fitting based on the triglyceride fat model. METHODS The water and olefinic peak height difference was defined as a metric for quantifying the separability of water and olefinic fat peaks. Fat unsaturation was determined using an unconstrained olefinic peak fitting and a constrained fitting of all fat peaks to the triglyceride model. The agreement between the two peak-fitting methods was used to define a threshold on water and olefinic peak height difference separating two groups (A and B), based on L5 short-echo time-stimulated echo acquisition mode (TE = 11 ms) spectra from 252 subjects measured at 3T. RESULTS A threshold on water and olefinic peak height difference was defined. Group A with a good agreement of the olefinic fat peak between the two peak-fitting methods showed a mean number of double bounds = 2.95 ± 0.21, a mean number of methylene-interrupted double bounds = 0.94 ± 0.16 and also a significantly lower coefficient of variation for all fatty acid composition parameters compared to group B (p < .001). The water and olefinic peak height difference value showed an inverse association with fat fraction. CONCLUSION A threshold of a metric quantifying the separability of the water peak and the olefinic fat peaks was defined for the estimation of the vertebral bone marrow fat unsaturation from short-echo time-stimulated echo acquisition mode MRS. The proposed methodology shows that the assessment of vertebral bone marrow unsaturation is feasible with a short-echo time-stimulated echo acquisition mode MRS in subjects with a higher fat fraction.
Collapse
Affiliation(s)
- Jan Syväri
- Department of Diagnostic and Interventional Radiology, School of Medicine, Technical University of Munich, Munich, Bavaria, Germany
| | - Stefan Ruschke
- Department of Diagnostic and Interventional Radiology, School of Medicine, Technical University of Munich, Munich, Bavaria, Germany
| | - Michael Dieckmeyer
- Department of Diagnostic and Interventional Radiology, School of Medicine, Technical University of Munich, Munich, Bavaria, Germany
| | - Hans H Hauner
- Else Kröner Fresenius Center for Nutritional Medicine, Technical University of Munich, Munich, Bavaria, Germany
| | - Daniela Junker
- Department of Diagnostic and Interventional Radiology, School of Medicine, Technical University of Munich, Munich, Bavaria, Germany
| | - Marcus R Makowski
- Department of Diagnostic and Interventional Radiology, School of Medicine, Technical University of Munich, Munich, Bavaria, Germany
| | - Thomas Baum
- Department of Diagnostic and Interventional Neuroradiology, School of Medicine, Technical University of Munich, Munich, Bavaria, Germany
| | - Dimitrios C Karampinos
- Department of Diagnostic and Interventional Radiology, School of Medicine, Technical University of Munich, Munich, Bavaria, Germany
| |
Collapse
|
|
39
|
Hamilton G, Schlein AN, Wolfson T, Cunha GM, Fowler KJ, Middleton MS, Loomba R, Sirlin CB. The relationship between liver triglyceride composition and proton density fat fraction as assessed by 1 H MRS. NMR IN BIOMEDICINE 2020; 33:e4286. [PMID: 32128921 PMCID: PMC7211117 DOI: 10.1002/nbm.4286] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Revised: 02/11/2020] [Accepted: 02/12/2020] [Indexed: 05/05/2023]
Abstract
The aim of this study was to estimate parameters determining liver triglyceride composition (TC) using 1 H MRS and to assess how TC estimability is affected by proton density fat fraction (PDFF) in adults with nonalcoholic fatty liver disease (NAFLD). In this prospective single-site study, 199 adults with known or suspected NAFLD in whom other causes of liver disease were excluded underwent two 1 H MRS STimulated Echo Acquisition Method (STEAM) sequences at 3 T. A respiratory-gated water-suppressed free breathing sequence (TE 10 ms, 16 signal averages) was used to assess TC in terms of the number of double bonds (ndb) and methylene-interrupted double bonds (nmidb), and a single breath-hold-long TR, multi-TE sequence (TR 3500 ms), which acquired five single average spectra over TE 10-30 ms, was used to estimate liver PDFF. Ndb and nmidb estimability was qualitatively assessed for each case and summarized descriptively. The consistency of ndb and nmidb estimation was examined using ROC analysis. The relationship between ndb and nmidb values and PDFF was presented graphically. Quality-of-fit of ndb and nmidb versus PDFF was evaluated by Pearson-r correlation. A significance level of 0.05 was used. In 263 1 H MRS examinations performed on 199 adult participants, ndb and nmidb were successfully estimated in 7/53 (13.2%) examinations with PDFF < 4%, 13/30 (43.3%) examinations with PDFF between 4% and 7%, 33/41 (80.5%) examinations with PDFF between 7% and 10%, and 124/139 (89.2%) examinations with PDFF > 10% (maximum PDFF 38.1%). Liver TC could be estimated consistently for PDFF > 6.7%. Both ndb and nmidb decreased with increasing PDFF (ndb = 2.83-0.0160·PDFF, r = -0.449, P < 0.0001); nmidb = 0.75-0.0088·PDFF, r = -0.350, P < 0.0001). In a cohort of adults with known or suspected NAFLD, liver TC becomes more saturated as PDFF increases.
Collapse
Affiliation(s)
- Gavin Hamilton
- Liver Imaging Group, Department of Radiology, University of
California San Diego, La Jolla, California, USA
| | - Alex N. Schlein
- Liver Imaging Group, Department of Radiology, University of
California San Diego, La Jolla, California, USA
| | - Tanya Wolfson
- Computational and Applied Statistic Laboratory, San Diego
Supercomputing Center, University of California San Diego, San Diego, California,
USA
| | - Guilherme M. Cunha
- Liver Imaging Group, Department of Radiology, University of
California San Diego, La Jolla, California, USA
| | - Kathryn J. Fowler
- Liver Imaging Group, Department of Radiology, University of
California San Diego, La Jolla, California, USA
| | - Michael S. Middleton
- Liver Imaging Group, Department of Radiology, University of
California San Diego, La Jolla, California, USA
| | - Rohit Loomba
- Division of Epidemiology, Department of Family Medicine and
Public Health, University of California San Diego, La Jolla, California, USA
- NAFLD Research Center, Division of Gastroenterology,
Department of Medicine, University of California San Diego, La Jolla, California,
USA
| | - Claude B. Sirlin
- Liver Imaging Group, Department of Radiology, University of
California San Diego, La Jolla, California, USA
| |
Collapse
|
|
40
|
Alhulail AA, Patterson DA, Xia P, Zhou X, Lin C, Thomas MA, Dydak U, Emir UE. Fat-water separation by fast metabolite cycling magnetic resonance spectroscopic imaging at 3 T: A method to generate separate quantitative distribution maps of musculoskeletal lipid components. Magn Reson Med 2020; 84:1126-1139. [PMID: 32103549 DOI: 10.1002/mrm.28228] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2019] [Revised: 01/03/2020] [Accepted: 02/03/2020] [Indexed: 12/29/2022]
Abstract
PURPOSE To provide a rapid, noninvasive fat-water separation technique that allows producing quantitative maps of particular lipid components. METHODS The calf muscles in 5 healthy adolescents (age 12-16 years; body mass index = 20 ± 3 kg/m2 ) were scanned by two different fat fraction measurement methods. A density-weighted concentric-ring trajectory metabolite-cycling MRSI technique was implemented to collect data with a nominal resolution of 0.25 mL within 3 minutes and 16 seconds. For comparative purposes, the standard Dixon technique was performed. The two techniques were compared using structural similarity analysis. Additionally, the difference in the distribution of each lipid over the adolescent calf muscles was assessed based on the MRSI data. RESULTS The proposed MRSI technique provided individual fat fraction maps for eight musculoskeletal lipid components identified by LCModel analysis (IMC/L [CH3 ], EMCL [CH3 ], IMC/L [CH2 ]n , EMC/L [CH2 ]n , IMC/L [CH2 -CH], EMC/L [CH2 -CH], IMC/L [-CH=CH-], and EMC/L [-CH=CH-]) with mean structural similarity indices of 0.19, 0.04, 0.03, 0.50, 0.45, 0.04, 0.07, and 0.12, respectively, compared with the maps generated by the used Dixon method. Further analysis of voxels with zero structural similarity demonstrated an increased sensitivity of fat fraction lipid maps from the data acquired using this MRSI technique over the standard Dixon technique. The lipid spatial distribution over calf muscles was consistent with previously published findings in adults. CONCLUSION This MRSI technique can be a useful tool when individual lipid fat fraction maps are desired within a clinically acceptable time and with a nominal spatial resolution of 0.25 mL.
Collapse
Affiliation(s)
- Ahmad A Alhulail
- School of Health Sciences, Purdue University, West Lafayette, Indiana.,Department of Radiology and Medical Imaging, Prince Sattam bin Abdulaziz University, Al Kharj, Saudi Arabia
| | - Debra A Patterson
- School of Health Sciences, Purdue University, West Lafayette, Indiana.,Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana
| | - Pingyu Xia
- School of Health Sciences, Purdue University, West Lafayette, Indiana
| | - Xiaopeng Zhou
- School of Health Sciences, Purdue University, West Lafayette, Indiana
| | - Chen Lin
- Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana
| | - M Albert Thomas
- Department of Radiology, University of California Los Angeles, Los Angeles, California
| | - Ulrike Dydak
- School of Health Sciences, Purdue University, West Lafayette, Indiana.,Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana
| | - Uzay E Emir
- School of Health Sciences, Purdue University, West Lafayette, Indiana.,Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana
| |
Collapse
|
|
41
|
Gascho D, Richter H, Karampinos DC, Heimer J, Schaerli S, Thali MJ, Zoelch N. Noninvasive in situ proton MRS in muscle tissue and bone marrow as a novel approach to identify previous freezing in a completely thawed cadaver. NMR IN BIOMEDICINE 2020; 33:e4220. [PMID: 31774230 DOI: 10.1002/nbm.4220] [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: 04/12/2019] [Revised: 10/02/2019] [Accepted: 10/22/2019] [Indexed: 06/10/2023]
Abstract
The temporary or permanent storage of human bodies in freezers following a homicide is a documented method for criminal disposal of human corpses. In these cases, the detection of characteristics which indicate that a thawed cadaver or body part was previously frozen provides crucial information for forensic casework. Previous histological and radiological approaches to detect characteristics of previous freezing are based on the formation of bubble-like gas patterns, which are difficult to distinguish from common postmortem gas formation in the course of decomposition. The objective of this study was to detect changes in the muscle tissue and in the bone marrow after freezing and thawing by means of in situ proton magnetic resonance spectroscopy (1 H-MRS) to provide a noninvasive approach to detect postfreezing alterations in human cadavers. In this experimental study, the hind legs of seven sheep were used as substitutes for human tissue. One hind leg underwent 1 H-MRS before and daily after storage in a deep freezer (-20°C) and complete thawing at room temperature (study group: n = 7). The opposite hind leg was kept at room temperature and was measured daily (control group: n = 7). Spectra and relaxation times were measured using single voxel measurements in the muscle tissue and in the bone marrow. 1 H-MRS revealed several changes in the muscle tissue and in the bone marrow after freezing and thawing. A strongly reduced peak area ratio (<20) between bulk methylene and olefinic and glycerol methine and a reduced T2 relaxation time for bulk methylene (<45 ms) measured in the bone marrow were found to be indicators that a sheep leg was previously frozen and thawed independent of the postmortem interval. Noninvasive in situ 1 H-MRS in the bone marrow potentially provides a new method for detecting previous freezing or extreme cooling in cadavers.
Collapse
Affiliation(s)
- Dominic Gascho
- Department of Forensic Medicine and Imaging, Institute of Forensic Medicine, University of Zurich, Zurich, Switzerland
| | - Henning Richter
- Clinic of Diagnostic Imaging, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland
| | - Dimitrios C Karampinos
- Department of Diagnostic and Interventional Radiology, Technical University of Munich, Munich, Germany
| | - Jakob Heimer
- Department of Forensic Medicine and Imaging, Institute of Forensic Medicine, University of Zurich, Zurich, Switzerland
| | - Sarah Schaerli
- Department of Forensic Medicine and Imaging, Institute of Forensic Medicine, University of Zurich, Zurich, Switzerland
| | - Michael J Thali
- Department of Forensic Medicine and Imaging, Institute of Forensic Medicine, University of Zurich, Zurich, Switzerland
| | - Niklaus Zoelch
- Department of Forensic Medicine and Imaging, Institute of Forensic Medicine, University of Zurich, Zurich, Switzerland
- Hospital of Psychiatry, Department of Psychiatry, Psychotherapy and Psychosomatics, University of Zurich, Zurich, Switzerland
| |
Collapse
|
|
42
|
Abstract
PURPOSE OF REVIEW To provide an overview on recent technical development for quantifying marrow composition using magnetic resonance imaging (MRI) and spectroscopy (MRS) techniques, as well as a summary on recent findings of interrelationship between marrow adipose tissue (MAT) and skeletal health in the context of osteoporosis. RECENT FINDINGS There have been significant technical advances in reliable quantification of marrow composition using MR techniques. Cross-sectional studies have demonstrated a negative correlation between MAT and bone, with trabecular bone associating more strongly with MAT than cortical bone. However, longitudinal studies of MAT and bone are limited. MAT contents and composition have been associated with prevalent vertebral fracture. The evidence between MAT and clinical fracture is more limited, and, to date, no studies have reported on the relationship between MAT and incident fracture. Increasing evidence suggests a dynamic role of marrow fat in skeletal health. Reliable non-invasive quantification of marrow composition will facilitate developing novel treatment strategies for osteoporosis.
Collapse
Affiliation(s)
- Xiaojuan Li
- Department of Biomedical Engineering, Program of Advanced Musculoskeletal Imaging (PAMI), Cleveland Clinic, 9500 Euclid Avenue, ND20, Cleveland, OH, 44195, USA.
| | - Ann V Schwartz
- Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA
| |
Collapse
|
|
43
|
Wang X, Hernando D, Reeder SB. Phase-based T 2 mapping with gradient echo imaging. Magn Reson Med 2019; 84:609-619. [PMID: 31872470 DOI: 10.1002/mrm.28138] [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: 07/06/2019] [Revised: 10/31/2019] [Accepted: 11/27/2019] [Indexed: 12/12/2022]
Abstract
PURPOSE Transverse relaxation time (T2 ) mapping with MRI has a plethora of clinical and research applications. Current T2 mapping techniques are based primarily on spin-echo (SE) relaxometry strategies that rely on the signal magnitude, and often suffer from lengthy acquisition times. In this work, we propose a phase-based T2 mapping technique where T2 information is encoded into the signal phase of rapid gradient echo (GRE) acquisitions. THEORY Bloch equation simulations demonstrate that the phase of GRE acquisitions obtained with a very small inter-repetition RF phase increment has a strong monotonic dependence on T2 , resulting from coherent transverse magnetization. This T2 -dependent phase behavior forms the basis of the proposed T2 mapping technique. To isolate T2 -dependent phase from background phase, at least 2 data sets with different RF phase increments are acquired. The proposed method can also be combined with chemical shift encoded MRI to separate water and fat signals. METHODS The feasibility of the proposed technique was validated in a phantom experiment. In vivo feasibility was demonstrated in the brain, knee, abdomen, and pelvis. Comparisons were made with SE-based T2 mapping, spectroscopy, and T2 values from the literature. RESULTS The proposed method produced accurate T2 maps compared with SE-based T2 mapping in the phantom. Good qualitative agreement was observed in vivo between the proposed method and the reference. T2 measured in various anatomies agreed well with values reported in the literature. CONCLUSION A phase-based T2 mapping technique was developed and its feasibility demonstrated in phantoms and in vivo.
Collapse
Affiliation(s)
- Xiaoke Wang
- Department of Radiology, University of Wisconsin, Madison, Wisconsin.,Department of Biomedical Engineering, University of Wisconsin, Madison, Wisconsin
| | - Diego Hernando
- Department of Radiology, University of Wisconsin, Madison, Wisconsin.,Department of Medical Physics, University of Wisconsin, Madison, Wisconsin
| | - Scott B Reeder
- Department of Radiology, University of Wisconsin, Madison, Wisconsin.,Department of Biomedical Engineering, University of Wisconsin, Madison, Wisconsin.,Department of Medical Physics, University of Wisconsin, Madison, Wisconsin.,Department of Medicine, University of Wisconsin, Madison, Wisconsin.,Department of Emergency Medicine, University of Wisconsin, Madison, Wisconsin
| |
Collapse
|
|
44
|
Wang X, Colgan TJ, Hinshaw LA, Roberts NT, Bancroft LCH, Hamilton G, Hernando D, Reeder SB. T 1 -corrected quantitative chemical shift-encoded MRI. Magn Reson Med 2019; 83:2051-2063. [PMID: 31724776 DOI: 10.1002/mrm.28062] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Revised: 09/27/2019] [Accepted: 10/11/2019] [Indexed: 11/06/2022]
Abstract
PURPOSE To develop and validate a T1 -corrected chemical-shift encoded MRI (CSE-MRI) method to improve noise performance and reduce bias for quantification of tissue proton density fat-fraction (PDFF). METHODS A variable flip angle (VFA)-CSE-MRI method using joint-fit reconstruction was developed and implemented. In computer simulations and phantom experiments, sources of bias measured using VFA-CSE-MRI were investigated. The effect of tissue T1 on bias using low flip angle (LFA)-CSE-MRI was also evaluated. The noise performance of VFA-CSE-MRI was compared to LFA-CSE-MRI for liver fat quantification. Finally, a prospective pilot study in patients undergoing gadoxetic acid-enhanced MRI of the liver to evaluate the ability of the proposed method to quantify liver PDFF before and after contrast. RESULTS VFA-CSE-MRI was accurate and insensitive to transmit B1 inhomogeneities in phantom experiments and computer simulations. With high flip angles, phase errors because of RF spoiling required modification of the CSE signal model. For relaxation parameters commonly observed in liver, the joint-fit reconstruction improved the noise performance marginally, compared to LFA-CSE-MRI, but eliminated T1 -related bias. A total of 25 patients were successfully recruited and analyzed for the pilot study. Strong correlation and good agreement between PDFF measured with VFA-CSE-MRI and LFA-CSE-MRI (pre-contrast) was observed before (R2 = 0.97; slope = 0.88, 0.81-0.94 95% confidence interval [CI]; intercept = 1.34, -0.77-1.92 95% CI) and after (R2 = 0.93; slope = 0.88, 0.78-0.98 95% CI; intercept = 1.90, 1.01-2.79 95% CI) contrast. CONCLUSION Joint-fit VFA-CSE-MRI is feasible for T1 -corrected PDFF quantification in liver, is insensitive to B1 inhomogeneities, and can eliminate T1 bias, but with only marginal SNR advantage for T1 values observed in the liver.
Collapse
Affiliation(s)
- Xiaoke Wang
- Department of Radiology, University of Wisconsin, Madison, Wisconsin.,Department of Biomedical Engineering, University of Wisconsin, Madison, Wisconsin
| | - Timothy J Colgan
- Department of Radiology, University of Wisconsin, Madison, Wisconsin
| | - Louis A Hinshaw
- Department of Radiology, University of Wisconsin, Madison, Wisconsin.,Department of Biomedical Engineering, University of Wisconsin, Madison, Wisconsin
| | - Nathan T Roberts
- Department of Radiology, University of Wisconsin, Madison, Wisconsin.,Department of Electrical and Computer Engineering, University of Wisconsin, Madison, Wisconsin
| | | | - Gavin Hamilton
- Liver Imaging Group, Department of Radiology, University of California San Diego, La Jolla, California
| | - Diego Hernando
- Department of Radiology, University of Wisconsin, Madison, Wisconsin.,Department of Medical Physics, University of Wisconsin, Madison, Wisconsin
| | - Scott B Reeder
- Department of Radiology, University of Wisconsin, Madison, Wisconsin.,Department of Biomedical Engineering, University of Wisconsin, Madison, Wisconsin.,Department of Medical Physics, University of Wisconsin, Madison, Wisconsin.,Department of Medicine, University of Wisconsin, Madison, Wisconsin.,Department of Emergency Medicine, University of Wisconsin, Madison, Wisconsin
| |
Collapse
|
|
45
|
Wáng YXJ, Wang X, Wu P, Wang Y, Chen W, Chen H, Li J. Topics on quantitative liver magnetic resonance imaging. Quant Imaging Med Surg 2019; 9:1840-1890. [PMID: 31867237 DOI: 10.21037/qims.2019.09.18] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Liver magnetic resonance imaging (MRI) is subject to continuous technical innovations through advances in hardware, sequence and novel contrast agent development. In order to utilize the abilities of liver MR to its full extent and perform high-quality efficient exams, it is mandatory to use the best imaging protocol, to minimize artifacts and to select the most adequate type of contrast agent. In this article, we review the routine clinical MR techniques applied currently and some latest developments of liver imaging techniques to help radiologists and technologists to better understand how to choose and optimize liver MRI protocols that can be used in clinical practice. This article covers topics on (I) fat signal suppression; (II) diffusion weighted imaging (DWI) and intravoxel incoherent motion (IVIM) analysis; (III) dynamic contrast-enhanced (DCE) MR imaging; (IV) liver fat quantification; (V) liver iron quantification; and (VI) scan speed acceleration.
Collapse
Affiliation(s)
- Yì Xiáng J Wáng
- Department of Imaging and Interventional Radiology, Faculty of Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong SAR, China
| | | | - Peng Wu
- Philips Healthcare (Suzhou) Co., Ltd., Suzhou 215024, China
| | - Yajie Wang
- Center for Biomedical Imaging Research, Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China
| | - Weibo Chen
- Philips Healthcare, Shanghai 200072, China.,Shanghai Key Laboratory of Magnetic Resonance, School of Physics and Electronic Science, East China Normal University, Shanghai 200062, China
| | - Huijun Chen
- Center for Biomedical Imaging Research, Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China
| | - Jianqi Li
- Shanghai Key Laboratory of Magnetic Resonance, School of Physics and Electronic Science, East China Normal University, Shanghai 200062, China
| |
Collapse
|
|
46
|
Landheer K, Schulte RF, Treacy MS, Swanberg KM, Juchem C. Theoretical description of modern1H in Vivo magnetic resonance spectroscopic pulse sequences. J Magn Reson Imaging 2019; 51:1008-1029. [DOI: 10.1002/jmri.26846] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Revised: 06/14/2019] [Accepted: 06/17/2019] [Indexed: 01/20/2023] Open
Affiliation(s)
- Karl Landheer
- Biomedical Engineering, Columbia University Fu Foundation School of Engineering and Applied Science New York New York USA
| | | | - Michael S. Treacy
- Biomedical Engineering, Columbia University Fu Foundation School of Engineering and Applied Science New York New York USA
| | - Kelley M. Swanberg
- Biomedical Engineering, Columbia University Fu Foundation School of Engineering and Applied Science New York New York USA
| | - Christoph Juchem
- Biomedical Engineering, Columbia University Fu Foundation School of Engineering and Applied Science New York New York USA
- Radiology, Columbia University College of Physicians and Surgeons New York New York USA
| |
Collapse
|
|
47
|
Abdelbasset WK, Tantawy SA, Kamel DM, Alqahtani BA, Soliman GS. A randomized controlled trial on the effectiveness of 8-week high-intensity interval exercise on intrahepatic triglycerides, visceral lipids, and health-related quality of life in diabetic obese patients with nonalcoholic fatty liver disease. Medicine (Baltimore) 2019; 98:e14918. [PMID: 30896648 PMCID: PMC6708753 DOI: 10.1097/md.0000000000014918] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Medications are limited for patients with nonalcoholic fatty liver disease (NAFLD). It has been reported that aerobic exercise is effective in reducing the characteristics of NAFLD, although unclear data have ascertained the effects of high-intensity interval aerobic exercise on health-related quality of life (HRQoL) in diabetic obese patients with NAFLD. OBJECTIVES This a randomized controlled trial aimed to ascertain the effectiveness of 8-week high-intensity interval exercise on intrahepatic triglycerides (IHTG), visceral lipids and HRQoL in diabetic obese patients with NAFLD. STUDY DESIGN Between August and December 2017, 32 diabetic obese patients with NAFLD aged 45 to 60 years (21 men and 11 women) were enrolled in this study. They were randomly assigned to 2 groups, 16 patients in each group, high-intensity interval (HII) exercise and control groups. The HII group received a program of HII aerobic exercise for 8 weeks with medications of NAFLD and the control group received only medications without any type of exercise intervention. The test of IHTG, visceral lipids, and HRQoL were recorded at the initial assessment and at the end of the program after 8 weeks. RESULTS There were significant differences between the 2 groups at the end of the study. These study findings exhibited significant improvements in IHTG, VO2peak, visceral lipids, glycohemoglobin, plasma glucose, and all dimensions of HRQoL in the HII group (P <.05), But there was non-significant improvement in any measure in the control group (P >.05) after the 8-week intervention. CONCLUSION Eight-week high-intensity interval aerobic exercise has a beneficial effect on IHTG, visceral lipids, and HRQoL in diabetic obese patients with NAFLD. Effort and awareness should be dedicated to encouraging the active lifestyle among different population, especially diabetic obese patients with NAFLD.
Collapse
Affiliation(s)
- Walid Kamal Abdelbasset
- Department of Physical Therapy and Health Rehabilitation, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Alkharj, Saudi Arabia
- Department of Physical Therapy, Kasr Al-Aini Hospital, Cairo University, Giza, Egypt
| | - Sayed A. Tantawy
- Department of Physiotherapy, College of Medical and Health Sciences, Ahlia University, Manama, Kingdom of Bahrain
- Department of Physiotherapy, Centre of Radiation, Oncology and Nuclear Medicine
| | - Dalia M. Kamel
- Department of Physiotherapy, College of Medical and Health Sciences, Ahlia University, Manama, Kingdom of Bahrain
- Department of Physiotherapy for Women's Health, Faculty of Physical Therapy
| | - Bader A. Alqahtani
- Department of Physical Therapy and Health Rehabilitation, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Alkharj, Saudi Arabia
| | - Gaber S. Soliman
- Department of Physical Therapy for Cardiovascular/Respiratory Disorder and Geriatrics, Faculty of Physical Therapy, Cairo University, Giza, Egypt
- Department of Physical Therapy and Health Rehabilitation, College of Applied Medical Sciences in Al-Qurayyat, Jouf University, Saudi Arabia
| |
Collapse
|
|
48
|
Mozes FE, Tunnicliffe EM, Moolla A, Marjot T, Levick CK, Pavlides M, Robson MD. Mapping tissue water T 1 in the liver using the MOLLI T 1 method in the presence of fat, iron and B 0 inhomogeneity. NMR IN BIOMEDICINE 2019; 32:e4030. [PMID: 30462873 PMCID: PMC6492199 DOI: 10.1002/nbm.4030] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/16/2018] [Revised: 09/11/2018] [Accepted: 09/20/2018] [Indexed: 05/11/2023]
Abstract
Modified Look-Locker inversion recovery (MOLLI) T1 mapping sequences can be useful in cardiac and liver tissue characterization, but determining underlying water T1 is confounded by iron, fat and frequency offsets. This article proposes an algorithm that provides an independent water MOLLI T1 (referred to as on-resonance water T1 ) that would have been measured if a subject had no fat and normal iron, and imaging had been done on resonance. Fifteen NiCl2 -doped agar phantoms with different peanut oil concentrations and 30 adults with various liver diseases, nineteen (63.3%) with liver steatosis, were scanned at 3 T using the shortened MOLLI (shMOLLI) T1 mapping, multiple-echo spoiled gradient-recalled echo and 1 H MR spectroscopy sequences. An algorithm based on Bloch equations was built in MATLAB, and water shMOLLI T1 values of both phantoms and human participants were determined. The quality of the algorithm's result was assessed by Pearson's correlation coefficient between shMOLLI T1 values and spectroscopically determined T1 values of the water, and by linear regression analysis. Correlation between shMOLLI and spectroscopy-based T1 values increased, from r = 0.910 (P < 0.001) to r = 0.998 (P < 0.001) in phantoms and from r = 0.493 (for iron-only correction; P = 0.005) to r = 0.771 (for iron, fat and off-resonance correction; P < 0.001) in patients. Linear regression analysis revealed that the determined water shMOLLI T1 values in patients were independent of fat and iron. It can be concluded that determination of on-resonance water (sh)MOLLI T1 independent of fat, iron and macroscopic field inhomogeneities was possible in phantoms and human subjects.
Collapse
Affiliation(s)
- Ferenc E. Mozes
- The University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), University of Oxford, John Radcliffe HospitalOxfordUK
| | - Elizabeth M. Tunnicliffe
- The University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), University of Oxford, John Radcliffe HospitalOxfordUK
| | - Ahmad Moolla
- The University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), University of Oxford, John Radcliffe HospitalOxfordUK
- Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM)University of Oxford, Churchill HospitalOxfordUK
| | - Thomas Marjot
- Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM)University of Oxford, Churchill HospitalOxfordUK
| | - Christina K. Levick
- The University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), University of Oxford, John Radcliffe HospitalOxfordUK
- Translational Gastroenterology UnitUniversity of Oxford, John Radcliffe HospitalOxfordUK
| | - Michael Pavlides
- The University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), University of Oxford, John Radcliffe HospitalOxfordUK
- Translational Gastroenterology UnitUniversity of Oxford, John Radcliffe HospitalOxfordUK
- Oxford NIHR Biomedical Research CentreOxfordUK
| | - Matthew D. Robson
- The University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), University of Oxford, John Radcliffe HospitalOxfordUK
| |
Collapse
|
|
49
|
Fairgrieve-Park L, Fallone CJ, Yahya A. Long TE PRESS and STEAM for measuring the triglyceride glycerol CH 2 protons at 3 T. NMR IN BIOMEDICINE 2019; 32:e4021. [PMID: 30376203 DOI: 10.1002/nbm.4021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Revised: 08/28/2018] [Accepted: 08/31/2018] [Indexed: 06/08/2023]
Abstract
The glycerol methylene proton resonances (4-4.5 parts per million, ppm), which arise from the triglyceride backbone, are relevant to fat composition assessment and can be measured with proton MRS. The purpose of the presented work is to determine long TE (echo time) point resolved spectroscopy (PRESS) and stimulated echo acquisition mode (STEAM) values at 3 T to resolve the glycerol resonances from that of overlapping water. The response of the glycerol methylene protons of nine edible oils as a function of PRESS and STEAM TE (mixing time, TM = 20 ms) was investigated. In addition, high resolution NMR spectra of the oils were acquired at 16.5 T. Long TE values where J-coupling losses were lowest were selected, namely a TE of 180 ms for PRESS (first echo time 17 ms) and a TE of 100 ms for STEAM (mixing time 20 ms). Oil olefinic (≈5.4 ppm) to glycerol ratios were calculated from the long TE spectra and correlated with 16.5 T ratios. The two techniques yielded olefinic/glycerol ratios that correlated with 16.5 T ratios (R2 = 0.79 for PRESS and 0.90 for STEAM). The efficacy of the sequences in resolving the glycerol resonance from that of water was verified in vivo on tibial bone marrow of four healthy volunteers. In addition, the potential for using the glycerol methylene signal normalized to the methyl signal (≈0.9 ppm) to assess changes in free fatty acid content was demonstrated by measuring differences in spectra acquired from a triglyceride peanut oil phantom and from a phantom composed of a mixture of peanut oil and free fatty acid oleic acid.
Collapse
Affiliation(s)
| | - Clara J Fallone
- Department of Oncology, University of Alberta, Edmonton, Alberta, Canada
| | - Atiyah Yahya
- Department of Oncology, University of Alberta, Edmonton, Alberta, Canada
- Department of Medical Physics, Cross Cancer Institute, Edmonton, Alberta, Canada
| |
Collapse
|
|
50
|
Lee SH, Yoo HJ, Yu SM, Hong SH, Choi JY, Chae HD. Fat Quantification in the Vertebral Body: Comparison of Modified Dixon Technique with Single-Voxel Magnetic Resonance Spectroscopy. Korean J Radiol 2018; 20:126-133. [PMID: 30627028 PMCID: PMC6315074 DOI: 10.3348/kjr.2018.0174] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Accepted: 08/03/2018] [Indexed: 11/15/2022] Open
Abstract
Objective To compare the lumbar vertebral bone marrow fat-signal fractions obtained from six-echo modified Dixon sequence (6-echo m-Dixon) with those from single-voxel magnetic resonance spectroscopy (MRS) in patients with low back pain. Materials and Methods Vertebral bone marrow fat-signal fractions were quantified by 6-echo m-Dixon (repetition time [TR] = 7.2 ms, echo time (TE) = 1.21 ms, echo spacing = 1.1 ms, total imaging time = 50 seconds) and single-voxel MRS measurements in 25 targets (23 normal bone marrows, two focal lesions) from 24 patients. The point-resolved spectroscopy sequence was used for localized single-voxel MRS (TR = 3000 ms, TE = 35 ms, total scan time = 1 minute 42 seconds). A 2 × 2 × 1.5 cm3 voxel was placed within the normal L2 or L3 vertebral body, or other lesions including a compression fracture or metastasis. The bone marrow fat spectrum was characterized on the basis of the magnitude of measurable fat peaks and a priori knowledge of the chemical structure of triglycerides. The imaging-based fat-signal fraction results were then compared to the MRS-based results. Results There was a strong correlation between m-Dixon and MRS-based fat-signal fractions (slope = 0.86, R2 = 0.88, p < 0.001). In Bland-Altman analysis, 92.0% (23/25) of the data points were within the limits of agreement. Bland-Altman plots revealed a slight but systematic error in the m-Dixon based fat-signal fraction, which showed a prevailing overestimation of small fat-signal fractions (< 20%) and underestimation of high fat-signal fractions (> 20%). Conclusion Given its excellent agreement with single-voxel-MRS, 6-echo m-Dixon can be used for visual and quantitative evaluation of vertebral bone marrow fat in daily practice.
Collapse
Affiliation(s)
- Sang Hyup Lee
- Department of Radiology, Seoul National University Hospital, Seoul, Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Hye Jin Yoo
- Department of Radiology, Seoul National University Hospital, Seoul, Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Seung-Man Yu
- Department of Radiological Science, College of Health Science, Gimcheon University, Gimcheon, Korea
| | - Sung Hwan Hong
- Department of Radiology, Seoul National University Hospital, Seoul, Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, Korea.,Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Korea
| | - Ja-Young Choi
- Department of Radiology, Seoul National University Hospital, Seoul, Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Hee Dong Chae
- Department of Radiology, Seoul National University Hospital, Seoul, Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| |
Collapse
|