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Alterations of Renal Function in Patients with Diabetic Kidney Disease: A BOLD and DTI Study. COMPUTATIONAL INTELLIGENCE AND NEUROSCIENCE 2022; 2022:6844102. [PMID: 36210998 PMCID: PMC9546653 DOI: 10.1155/2022/6844102] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 08/17/2022] [Accepted: 08/23/2022] [Indexed: 11/17/2022]
Abstract
Objectives Our study aims to determine the patterns of renal oxygenation changes and microstructural changes by BOLD and DTI with deteriorating kidney function in patients with diabetic kidney disease (DKD). Methods Seventy-two patients with type 2 diabetes mellitus (DM) and twenty healthy controls (HCs) underwent laboratory examinations, and renal BOLD and DTI images were obtained on a 3T-MRI machine. R2∗, fractional anisotropy (FA), and average diffusion coefficient (ADC) values were evaluated. DM patients were divided into three subgroups (Group-DI/DII/DIII, based on urinary albumin-creatinine ratio (UACR)) and a nondiabetic kidney disease group (Group-NDKD). D-value and MCR of R2∗ and FA were proposed to evaluate the differentiation between medulla and cortex of the individual kidney among HCs and three subgroups for reducing individual differences. Comparisons were made between NDKD and kidney function-matched DKD patients. Correlations between MRI parameters and renal clinical indices were analyzed. Results Compared with Group-HC/DI, medullary R2∗ and FA values were significantly different in Group-DII/III. The D-value of R2∗ and FA in Group-III were significantly smaller than that in Group-HC. However, only MCR of R2∗ in Group-III was significantly smaller than that in HCs. Medullary R2∗ and FA were negatively associated with serum creatinine (SCr) and cystatin C (Cys C) and positively associated with eGFR. Conclusions With renal function declining, BOLD and DTI could capture alterations including the first rising and then falling medullary R2∗, continuously declining medullary FA, and apparent cortex-medullary differentiation in DKD patients. The MRI parameters showed renal changes accompanied by varying degrees of albuminuria, sharing common involvement in DKD and NDKD patients, but it was hard to distinguish between them. BOLD seemed more sensitive than DTI in identifying renal cortex-medullary differentiation.
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Zhao Q, Ridout RP, Shen J, Wang N. Effects of Angular Resolution and b Value on Diffusion Tensor Imaging in Knee Joint. Cartilage 2021; 13:295S-303S. [PMID: 33843284 PMCID: PMC8804734 DOI: 10.1177/19476035211007909] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
OBJECTIVE To investigate the influences of the diffusion gradient directions (angular resolution) and the strength of the diffusion gradient (b value) on diffusion tensor imaging (DTI) metrics and tractography of various connective tissues in knee joint. DESIGN Two rat knee joints were scanned on a preclinical 9.4-T system using a 3-dimensional diffusion-weighted spin echo pulse sequence. One protocol with b value of 500, 1500, and 2500 s/mm2 were acquired separately using 43 diffusion gradient directions. The other protocol with b value of 1000 s/mm2 was performed using 147 diffusion gradient directions. The in-plane resolution was 45 µm isotropic. Fractional anisotropy (FA) and mean diffusivity (MD) were compared at different angular resolution. Tractography was quantitatively evaluated at different b values and angular resolutions in cartilage, ligament, meniscus, and growth plate. RESULTS The ligament showed higher FA value compared with growth plate and cartilage. The FA values were largely overestimated at the angular resolution of 6. Compared with FA, MD showed less sensitivity to the angular resolution. The fiber tracking was failed at low angular resolution (6 diffusion gradient directions) or high b value (2500 s/mm2). The quantitative measurements of tract length and track volume were strongly dependent on angular resolution and b value. CONCLUSIONS To obtain consistent DTI outputs and tractography in knee joint, the scan may require a proper b value (ranging from 500 to 1500 s/mm2) and sufficient angular resolution (>14) with signal-to-noise ratio >10.
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Affiliation(s)
- Qi Zhao
- School of Psychology, Shanghai
University of Sport, Shanghai, China
| | - Rees P. Ridout
- Pratt School of Engineering, Duke
University, Durham, NC, USA
| | - Jikai Shen
- Pratt School of Engineering, Duke
University, Durham, NC, USA
| | - Nian Wang
- Department of Radiology, Duke
University School of Medicine, Durham, NC, USA,Department of Radiology and Imaging
Sciences, Indiana University School of Medicine, Indianapolis, IN, USA,Nian Wang, Department of Radiology and
Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN 46202,
USA.
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3
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Morozov D, Parvin N, Charlton JR, Bennett KM. Mapping kidney tubule diameter ex vivo by diffusion MRI. Am J Physiol Renal Physiol 2021; 320:F934-F946. [PMID: 33719573 DOI: 10.1152/ajprenal.00369.2020] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Tubular pathologies are a common feature of kidney disease. Current metrics to assess kidney health, in vivo or in transplant, are generally based on urinary or serum biomarkers and pathological findings from kidney biopsies. Biopsies, usually taken from the kidney cortex, are invasive and prone to sampling error. Tools to directly and noninvasively measure tubular pathology could provide a new approach to assess kidney health. This study used diffusion magnetic resonance imaging (dMRI) as a noninvasive tool to measure the size of the tubular lumen in ex vivo, perfused kidneys. We first used Monte Carlo simulations to demonstrate that dMRI is sensitive to restricted tissue water diffusion at the scale of the kidney tubule. We applied dMRI and biophysical modeling to examine the distribution of tubular diameters in ex vivo, fixed kidneys from mice, rats, and a human donor. The biophysical model to fit the dMRI signal was based on a superposition of freely diffusing water and water diffusing inside infinitely long cylinders of different diameters. Tubular diameters measured by dMRI were within 10% of those measured by histology within the same tissue. Finally, we applied dMRI to investigate kidney pathology in a mouse model of folic-acid-induced acute kidney injury. dMRI detected heterogeneity in the distribution of tubules within the kidney cortex of mice with acute kidney injury compared with control mice. We conclude that dMRI can be used to measure the distribution of tubule diameters in the kidney cortex ex vivo and that dMRI may provide a new noninvasive biomarker of tubular pathology.NEW & NOTEWORTHY Tubular pathologies are a common feature of kidney disease. Current metrics to assess kidney health, in vivo or in transplant, are generally based on urinary or serum biomarkers and pathological findings from kidney biopsies. Diffusion MRI can be used to measure the distribution of tubule diameters in the kidney cortex ex vivo and may provide a new noninvasive biomarker of tubular pathology.
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Affiliation(s)
- Darya Morozov
- Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri
| | - Neda Parvin
- Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri
| | | | - Kevin M Bennett
- Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri
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Lim RP, Lim JC, Teruel JR, Botterill E, Seah JM, Farquharson S, Ekinci EI, Sigmund EE. Geometric Distortion Correction of Renal Diffusion Tensor Imaging Using the Reversed Gradient Method. J Comput Assist Tomogr 2021; 45:218-223. [PMID: 33661149 PMCID: PMC8194095 DOI: 10.1097/rct.0000000000001124] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
ABSTRACT Renal echo planar diffusion tensor imaging (DTI) has clinical potential but suffers from geometric distortion. We evaluated feasibility of reversed gradient distortion correction in 10 diabetic patients and 6 volunteers. Renal area, apparent diffusion coefficient, fractional anisotropy, and tensor eigenvalues were measured on uncorrected and distortion-corrected DTI. Corrected DTI correlated better than uncorrected DTI (r = 0.904 vs 0.840, P = 0.002) with reference anatomic T2-weighted imaging, with no significant difference in DTI metrics.
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Affiliation(s)
- Ruth P. Lim
- Austin Health, Radiology and Surgery, The University of Melbourne, Melbourne, Australia
- Department of Medicine, Radiology and Surgery, The University of Melbourne, Melbourne, Australia
| | - Jeremy C. Lim
- Austin Health, Radiology and Surgery, The University of Melbourne, Melbourne, Australia
| | - Jose R. Teruel
- Department of Radiation Oncology, NYU Langone Health, New York, NY
| | - Elissa Botterill
- Austin Health, Radiology and Surgery, The University of Melbourne, Melbourne, Australia
| | - Jas-mine Seah
- Austin Health, Radiology and Surgery, The University of Melbourne, Melbourne, Australia
| | - Shawna Farquharson
- The Florey Institute of Neuroscience and Mental Health, Melbourne, Australia
| | - Elif I. Ekinci
- Austin Health, Radiology and Surgery, The University of Melbourne, Melbourne, Australia
- Department of Medicine, Radiology and Surgery, The University of Melbourne, Melbourne, Australia
| | - Eric E. Sigmund
- Department of Radiology, NYU Langone Medical Center, New York, NY
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Hu X, Kuang M, Peng B, Yang Y, Lin W, Li W, Wu Y. Diffusion Tensor Imaging in Rat Models of Preclinical Diabetic Nephropathy: A Preliminary Study. Front Endocrinol (Lausanne) 2021; 12:701116. [PMID: 34512547 PMCID: PMC8429902 DOI: 10.3389/fendo.2021.701116] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Accepted: 08/10/2021] [Indexed: 01/12/2023] Open
Abstract
PURPOSE This study aimed to investigate the value of diffusion tensor imaging to assess renal injury in a rat model of preclinical diabetic nephropathy. METHODS Twenty-eight male Sprague Dawley rats were divided into two groups: the normal control (NC) group of 10 rats and the diabetic nephropathy (DN) group of 18 rats. Eight weeks after diabetes induction by streptozotocin, 3.0-T magnetic resonance (MR) imaging (b = 0 and 600 s/mm2, 15 diffusion directions) using a 32-channel knee coil was performed. After MR imaging, we measured serum creatinine, and collected double kidney tissues for pathology. The apparent diffusion coefficients(ADC) and fractional anisotropy(FA) values of the renal cortex and medulla were calculated for all kidneys. Physiological parameters, laboratory parameters, and imaging results were compared between the two groups. RESULTS All DN group animals developed hyperglycemia, polyuria, and emaciation. Serum creatinine was not significantly different between the groups (P > 0.05). Urinary albumin at 2, 4, and 8 weeks was higher in the DN group than in the NC group but <20 µg/min (P < 0.05). Pathologically, renal damage in the DN rats was observed. The ADC value was significantly increased in DN animals in the cortex (1.75×10-3mm2/s),medulla(1.53×10-3mm2/s)compared with NC group(cortex, 1.52×10-3mm2/s; medulla,1.35×10-3mm2/s). The FA value was significantly reduced in DN animals in the cortex (0.21),medulla(0.25)compared with NC group(cortex,0.26;medulla,0.3). CONCLUSIONS Increased apparent diffusion coefficients and decreased fractional anisotropy values on diffusion tensor imaging were associated with preclinical DN. Diffusion tensor imaging may be useful in early, non-invasive, quantitative detection, and therapy monitoring of DN.
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Affiliation(s)
- Xiaoyan Hu
- Department of Radiology, Chengdu First People’s Hospital, Chengdu, China
| | - Min Kuang
- Department of Radiology, Chengdu Second People’s Hospital, Chengdu, China
| | - Bo Peng
- Department of Radiology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yang Yang
- Department of Radiology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Wei Lin
- Department of Radiology, Chengdu First People’s Hospital, Chengdu, China
| | - Wenbo Li
- Department of Radiology, Chengdu First People’s Hospital, Chengdu, China
| | - Yinghua Wu
- Sichuan General Practitioner Training Center, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- *Correspondence: Yinghua Wu,
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Nery F, Szczepankiewicz F, Kerkelä L, Hall MG, Kaden E, Gordon I, Thomas DL, Clark CA. In vivo demonstration of microscopic anisotropy in the human kidney using multidimensional diffusion MRI. Magn Reson Med 2019; 82:2160-2168. [PMID: 31243814 PMCID: PMC6988820 DOI: 10.1002/mrm.27869] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2019] [Revised: 04/26/2019] [Accepted: 05/25/2019] [Indexed: 12/23/2022]
Abstract
PURPOSE To demonstrate the feasibility of multidimensional diffusion MRI to probe and quantify microscopic fractional anisotropy (µFA) in human kidneys in vivo. METHODS Linear tensor encoded (LTE) and spherical tensor encoded (STE) renal diffusion MRI scans were performed in 10 healthy volunteers. Respiratory triggering and image registration were used to minimize motion artefacts during the acquisition. Kidney cortex-medulla were semi-automatically segmented based on fractional anisotropy (FA) values. A model-free analysis of LTE and STE signal dependence on b-value in the renal cortex and medulla was performed. Subsequently, µFA was estimated using a single-shell approach. Finally, a comparison of conventional FA and µFA is shown. RESULTS The hallmark effect of µFA (divergence of LTE and STE signal with increasing b-value) was observed in all subjects. A statistically significant difference between LTE and STE signal was found in the cortex and medulla, starting from b = 750 s/mm2 and b = 500 s/mm2 , respectively. This difference was maximal at the highest b-value sampled (b = 1000 s/mm2 ) which suggests that relatively high b-values are required for µFA mapping in the kidney compared to conventional FA. Cortical and medullary µFA were, respectively, 0.53 ± 0.09 and 0.65 ± 0.05, both respectively higher than conventional FA (0.19 ± 0.02 and 0.40 ± 0.02). CONCLUSION The feasibility of combining LTE and STE diffusion MRI to probe and quantify µFA in human kidneys is demonstrated for the first time. By doing so, we show that novel microstructure information-not accessible by conventional diffusion encoding-can be probed by multidimensional diffusion MRI. We also identify relevant technical limitations that warrant further development of the technique for body MRI.
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Affiliation(s)
- Fabio Nery
- Developmental Imaging and Biophysics Section, UCL Great Ormond Street Institute of Child Health, London, United Kingdom
| | - Filip Szczepankiewicz
- Department of Radiology, Brigham and Women’s Hospital, Boston, Massachusetts
- Harvard Medical School, Boston, Massachusetts
- Medical Radiation Physics, Clinical Sciences, Lund, Lund University, Lund, Sweden
| | - Leevi Kerkelä
- Developmental Imaging and Biophysics Section, UCL Great Ormond Street Institute of Child Health, London, United Kingdom
| | - Matt G. Hall
- Developmental Imaging and Biophysics Section, UCL Great Ormond Street Institute of Child Health, London, United Kingdom
- National Physical Laboratory, Teddington, United Kingdom
| | - Enrico Kaden
- Centre for Medical Image Computing, University College London, London, United Kingdom
| | - Isky Gordon
- Developmental Imaging and Biophysics Section, UCL Great Ormond Street Institute of Child Health, London, United Kingdom
| | - David L. Thomas
- Leonard Wolfson Experimental Neurology Centre, UCL Queen Square Institute of Neurology, London, United Kingdom
- Department of Brain Repair and Rehabilitation, UCL Queen Square Institute of Neurology, London, United Kingdom
| | - Chris A. Clark
- Developmental Imaging and Biophysics Section, UCL Great Ormond Street Institute of Child Health, London, United Kingdom
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7
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Ljimani A, Caroli A, Laustsen C, Francis S, Mendichovszky IA, Bane O, Nery F, Sharma K, Pohlmann A, Dekkers IA, Vallee JP, Derlin K, Notohamiprodjo M, Lim RP, Palmucci S, Serai SD, Periquito J, Wang ZJ, Froeling M, Thoeny HC, Prasad P, Schneider M, Niendorf T, Pullens P, Sourbron S, Sigmund EE. Consensus-based technical recommendations for clinical translation of renal diffusion-weighted MRI. MAGNETIC RESONANCE MATERIALS IN PHYSICS BIOLOGY AND MEDICINE 2019; 33:177-195. [PMID: 31676990 PMCID: PMC7021760 DOI: 10.1007/s10334-019-00790-y] [Citation(s) in RCA: 64] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/06/2019] [Revised: 10/17/2019] [Accepted: 10/19/2019] [Indexed: 12/13/2022]
Abstract
Objectives Standardization is an important milestone in the validation of DWI-based parameters as imaging biomarkers for renal disease. Here, we propose technical recommendations on three variants of renal DWI, monoexponential DWI, IVIM and DTI, as well as associated MRI biomarkers (ADC, D, D*, f, FA and MD) to aid ongoing international efforts on methodological harmonization. Materials and methods Reported DWI biomarkers from 194 prior renal DWI studies were extracted and Pearson correlations between diffusion biomarkers and protocol parameters were computed. Based on the literature review, surveys were designed for the consensus building. Survey data were collected via Delphi consensus process on renal DWI preparation, acquisition, analysis, and reporting. Consensus was defined as ≥ 75% agreement. Results Correlations were observed between reported diffusion biomarkers and protocol parameters. Out of 87 survey questions, 57 achieved consensus resolution, while many of the remaining questions were resolved by preference (65–74% agreement). Summary of the literature and survey data as well as recommendations for the preparation, acquisition, processing and reporting of renal DWI were provided. Discussion The consensus-based technical recommendations for renal DWI aim to facilitate inter-site harmonization and increase clinical impact of the technique on a larger scale by setting a framework for acquisition protocols for future renal DWI studies. We anticipate an iterative process with continuous updating of the recommendations according to progress in the field. Electronic supplementary material The online version of this article (10.1007/s10334-019-00790-y) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Alexandra Ljimani
- Department of Diagnostic and Interventional Radiology, Medical Faculty, University Dusseldorf, Moorenstr. 5, 40225, Düsseldorf, Germany.
| | - Anna Caroli
- Department of Biomedical Engineering, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy
| | - Christoffer Laustsen
- MR Research Centre, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Susan Francis
- Sir Peter Mansfield Imaging Centre, University Park, University of Nottingham, Nottingham, NG7 2RD, UK
| | | | - Octavia Bane
- Translational and Molecular Imaging Institute and Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Fabio Nery
- Developmental Imaging and Biophysics Section, UCL Great Ormond Street Institute of Child Health, London, UK
| | - Kanishka Sharma
- Imaging Biomarkers Group, Department of Biomedical Imaging Sciences, University of Leeds, Leeds, UK
| | - Andreas Pohlmann
- Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrueck Center for Molecular Medicine in the Helmholtz Association, 13125, Berlin, Germany
| | - Ilona A Dekkers
- Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
| | - Jean-Paul Vallee
- Department of Diagnostic, Geneva University Hospital and University of Geneva, 1211, Geneva-14, Switzerland
| | - Katja Derlin
- Department of Radiology, Hannover Medical School, Hannover, Germany
| | - Mike Notohamiprodjo
- Die Radiologie, Munich, Germany.,Department of Radiology, University Hospital Tuebingen, Tübingen, Germany
| | - Ruth P Lim
- Department of Radiology, Austin Health, The University of Melbourne, Melbourne, Australia
| | - Stefano Palmucci
- Department of Medical Surgical Sciences and Advanced Technologies, Radiology I Unit, University Hospital "Policlinico-Vittorio Emanuele", University of Catania, Catania, Italy
| | - Suraj D Serai
- Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Joao Periquito
- Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrueck Center for Molecular Medicine in the Helmholtz Association, 13125, Berlin, Germany
| | - Zhen Jane Wang
- Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA
| | - Martijn Froeling
- Department of Radiology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Harriet C Thoeny
- Department of Radiology, Hôpital Cantonal Fribourgois (HFR), University of Fribourg, 1708, Fribourg, Switzerland
| | - Pottumarthi Prasad
- Department of Radiology, Center for Advanced Imaging, NorthShore University Health System, Evanston, IL, USA
| | - Moritz Schneider
- Department of Radiology, University Hospital, LMU Munich, Munich, Germany.,Comprehensive Pneumology Center, German Center for Lung Research, Munich, Germany
| | - Thoralf Niendorf
- Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrueck Center for Molecular Medicine in the Helmholtz Association, 13125, Berlin, Germany
| | - Pim Pullens
- Ghent Institute for Functional and Metabolic Imaging, Ghent University, Ghent, Belgium.,Department of Radiology, University Hospital Ghent, Ghent, Belgium
| | - Steven Sourbron
- Imaging Biomarkers Group, Department of Biomedical Imaging Sciences, University of Leeds, Leeds, UK
| | - Eric E Sigmund
- Department of Radiology, Center for Biomedical Imaging (CBI), Center for Advanced Imaging Innovation and Research (CAI2R), NYU Langone Health, New York, NY, USA
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Diffusion Tensor Imaging of the Kidney: Design and Evaluation of a Reliable Processing Pipeline. Sci Rep 2019; 9:12789. [PMID: 31484949 PMCID: PMC6726597 DOI: 10.1038/s41598-019-49170-5] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Accepted: 08/15/2019] [Indexed: 12/14/2022] Open
Abstract
Diffusion tensor imaging (DTI) is particularly suitable for kidney studies due to tubules, collector ducts and blood vessels in the medulla that produce spatially restricted diffusion of water molecules, thus reflecting the high grade of anisotropy detectable by DTI. Kidney DTI is still a challenging technique where the off-resonance susceptibility artefacts and subject motion can severely affect the reproducibility of results. The aim of this study is to design a reliable processing pipeline by assessing different image processing approaches in terms of reproducibility and image artefacts correction. The results of four different processing pipelines (eddy: correction of eddy-currents and motion between DTI volume; eddy-s2v: eddy and within DTI volume motion correction; topup: eddy and geometric distortion correction; topup-s2v: topup and within DTI volume motion correction) are compared in terms of reproducibility by test-retest analysis in 14 healthy subjects. Within-subject coefficient of variation (wsCV) and intra-class correlation coefficient (ICC) are measured to assess the reproducibility and Dice similarity index is evaluated for the spatial alignment between DTI and anatomical images. Topup-s2v pipeline provides highest reproducibility (wsCV = 0.053, ICC = 0.814) and best correction of image distortion (Dice = 0.83). This study definitely provides a recipe for data processing, enabling for a clinical suitability of kidney DTI.
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Zhou JY, Wang YC, Zeng CH, Ju SH. Renal Functional MRI and Its Application. J Magn Reson Imaging 2018; 48:863-881. [PMID: 30102436 DOI: 10.1002/jmri.26180] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Accepted: 04/10/2018] [Indexed: 12/11/2022] Open
Abstract
Renal function varies according to the nature and stage of diseases. Renal functional magnetic resonance imaging (fMRI), a technique considered superior to the most common method used to estimate the glomerular filtration rate, allows for noninvasive, accurate measurements of renal structures and functions in both animals and humans. It has become increasingly prevalent in research and clinical applications. In recent years, renal fMRI has developed rapidly with progress in MRI hardware and emerging postprocessing algorithms. Function-related imaging markers can be acquired via renal fMRI, encompassing water molecular diffusion, perfusion, and oxygenation. This review focuses on the progression and challenges of the main renal fMRI methods, including dynamic contrast-enhanced MRI, blood oxygen level-dependent MRI, diffusion-weighted imaging, diffusion tensor imaging, arterial spin labeling, fat fraction imaging, and their recent clinical applications. LEVEL OF EVIDENCE 5 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:863-881.
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Affiliation(s)
- Jia-Ying Zhou
- Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Yuan-Cheng Wang
- Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Chu-Hui Zeng
- Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Sheng-Hong Ju
- Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
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10
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Wu G, Zhao Z, Yao Q, Kong W, Xu J, Zhang J, Liu G, Dai Y. The Study of Clear Cell Renal Cell Carcinoma with MR Diffusion Kurtosis Tensor Imaging and Its Histopathologic Correlation. Acad Radiol 2018; 25:430-438. [PMID: 29198944 DOI: 10.1016/j.acra.2017.10.016] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2017] [Revised: 10/13/2017] [Accepted: 10/20/2017] [Indexed: 12/29/2022]
Abstract
RATIONALE AND OBJECTIVES The objective of this study was to compare the performance of diffusion kurtosis tensor imaging and diffusion-weighted imaging in the characterization of clear cell renal cell carcinoma (ccRCC) and their correlations with tumor histopathology. MATERIALS AND METHODS Ninety-one patients diagnosed with ccRCC who underwent diffusion kurtosis tensor imaging were included in this study. Fractional anisotropy, mean diffusivity, radial diffusivity, axial diffusivity, mean kurtosis (MK), radial kurtosis (Krad), and axial kurtosis (Kax) data were produced. A nuclear grade of 1-4 (G1-4) was assigned for each case based on the Fuhrman grading system, whereas tumor histopathology was characterized by the nuclear-to-cytoplasm ratio, the cell nuclei count, and the cell volume fraction. RESULTS All of the metric values except for Kax and fractional anisotropy could be used to discriminate G1 vs G3, G1 vs G4, G2 vs G3, and G2 vs G4, whereas MK and Kax could be used to discriminate G3 vs G4 (P <0.05). Moreover, the MK and Krad values exhibited better performance in differentiating G2 from G3 (P < 0.04 compared to the other metrics). The nuclear-to-cytoplasm ratio was positively correlated with the MK, Krad, and Kax values (P <0.001) and negatively correlated with the mean diffusivity, radial diffusivity, and axial diffusivity values (P <0.001), whereas the cell volume fraction and the cell nuclei count did not correlate with any metric examined. CONCLUSION The kurtosis metrics were superior to the diffusion metrics in grading ccRCC.
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11
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van Baalen S, Leemans A, Dik P, Lilien MR, ten Haken B, Froeling M. Intravoxel incoherent motion modeling in the kidneys: Comparison of mono-, bi-, and triexponential fit. J Magn Reson Imaging 2017; 46:228-239. [PMID: 27787931 PMCID: PMC5484284 DOI: 10.1002/jmri.25519] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2016] [Accepted: 10/07/2016] [Indexed: 02/03/2023] Open
Abstract
PURPOSE To evaluate if a three-component model correctly describes the diffusion signal in the kidney and whether it can provide complementary anatomical or physiological information about the underlying tissue. MATERIALS AND METHODS Ten healthy volunteers were examined at 3T, with T2 -weighted imaging, diffusion tensor imaging (DTI), and intravoxel incoherent motion (IVIM). Diffusion tensor parameters (mean diffusivity [MD] and fractional anisotropy [FA]) were obtained by iterative weighted linear least squares fitting of the DTI data and mono-, bi-, and triexponential fit parameters (D1 , D2 , D3 , ffast2 , ffast3 , and finterm ) using a nonlinear fit of the IVIM data. Average parameters were calculated for three regions of interest (ROIs) (cortex, medulla, and rest) and from fiber tractography. Goodness of fit was assessed with adjusted R2 ( Radj2) and the Shapiro-Wilk test was used to test residuals for normality. Maps of diffusion parameters were also visually compared. RESULTS Fitting the diffusion signal was feasible for all models. The three-component model was best able to describe fast signal decay at low b values (b < 50), which was most apparent in Radj2 of the ROI containing high diffusion signals (ROIrest ), which was 0.42 ± 0.14, 0.61 ± 0.11, 0.77 ± 0.09, and 0.81 ± 0.08 for DTI, one-, two-, and three-component models, respectively, and in visual comparison of the fitted and measured S0 . None of the models showed significant differences (P > 0.05) between the diffusion constant of the medulla and cortex, whereas the ffast component of the two and three-component models were significantly different (P < 0.001). CONCLUSION Triexponential fitting is feasible for the diffusion signal in the kidney, and provides additional information. LEVEL OF EVIDENCE 2 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:228-239.
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Affiliation(s)
- Sophie van Baalen
- MIRA Institute for Biomedical Technology and Technical MedicineUniversity of TwenteEnschedeThe Netherlands
| | - Alexander Leemans
- Image Sciences InstituteUniversity Medical Center UtrechtUtrechtThe Netherlands
| | - Pieter Dik
- Department of Pediatric UrologyWilhelmina Children's Hospital, UMC UtrechtUtrechtThe Netherlands
| | - Marc R. Lilien
- Department of Pediatric NephrologyWilhelmina Children's Hospital, UMC UtrechtUtrechtThe Netherlands
| | - Bennie ten Haken
- MIRA Institute for Biomedical Technology and Technical MedicineUniversity of TwenteEnschedeThe Netherlands
| | - Martijn Froeling
- Department of RadiologyUniversity Medical Center UtrechtUtrechtThe Netherlands
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12
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Wang YT, Li YC, Kong WF, Yin LL, Pu H. Diffusion tensor imaging beyond brains: Applications in abdominal and pelvic organs. World J Meta-Anal 2017; 5:71-79. [DOI: 10.13105/wjma.v5.i3.71] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2016] [Revised: 04/12/2017] [Accepted: 04/24/2017] [Indexed: 02/06/2023] Open
Abstract
Functional magnetic resonance imaging (MRI) provided critical functional information in addition to the anatomic profiles offered by conventional MRI, and has been enormously used in the initial diagnosis and followed evaluation of various diseases. Diffusion tensor imaging (DTI) is a newly developed and advanced technique that measures the diffusion properties including both diffusion motion and its direction in situ, and has been extensively applied in central nerve system with acknowledged success. Technical advances have enabled DTI in abdominal and pelvic organs. Its application is increasing, yet remains less understood. A systematic overview of clinical application of DTI in abdominal and pelvic organs such as liver, pancreas, kidneys, prostate, uterus, etc., is therefore presented. Exploration of techniques with less artifacts and more normative post-processing enabled generally satisfactory image quality and repeatability of measurement. DTI appears to be more valuable in the evaluation of diffused diseases of organs with highly directionally arranged structures, such as the assessment of function impairment of native and transplanted kidneys. However, the utility of DTI to diagnose focal lesions, such as liver mass, pancreatic and prostate tumor, remains limited. Besides, diffusion of different layers of the uterus and the fiber structure disruption can be depicted by DTI. Finally, a discussion of future directions of research is given. The underlying heterogeneous pathologic conditions of certain diseases need to be further differentiated, and it is suggested that DTI parameters might potentially depict certain pathologic characterization such as cell density. Nevertheless, DTI should be better integrated into the current multi-modality evaluation in clinical practice.
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13
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Comparison of Turbo Spin Echo and Echo Planar Imaging for intravoxel incoherent motion and diffusion tensor imaging of the kidney at 3Tesla. Z Med Phys 2017; 27:193-201. [PMID: 28410964 DOI: 10.1016/j.zemedi.2016.12.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2016] [Revised: 07/26/2016] [Accepted: 12/19/2016] [Indexed: 01/09/2023]
Abstract
Echo Planar Imaging (EPI) is most commonly applied to acquire diffusion-weighted MR-images. EPI is able to capture an entire image in very short time, but is prone to distortions and artifacts. In diffusion-weighted EPI of the kidney severe distortions may occur due to intestinal gas. Turbo Spin Echo (TSE) is robust against distortions and artifacts, but needs more time to acquire an entire image compared to EPI. Therefore, TSE is more sensitive to motion during the readout. In this study we compare diffusion-weighted TSE and EPI of the human kidney with regard to intravoxel incoherent motion (IVIM) and diffusion tensor imaging (DTI). Images were acquired with b-values between 0 and 750s/mm2 with TSE and EPI. Distortions were observed with the EPI readout in all volunteers, while the TSE images were virtually distortion-free. Fractional anisotropy of the diffusion tensor was significantly lower for TSE than for EPI. All other parameters of DTI and IVIM were comparable for TSE and EPI. Especially the main diffusion directions yielded by TSE and EPI were similar. The results demonstrate that TSE is a worthwhile distortion-free alternative to EPI for diffusion-weighted imaging of the kidney at 3Tesla.
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14
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Kjølby B, Khan A, Chuhutin A, Pedersen L, Jensen J, Jakobsen S, Zeidler D, Sangill R, Nyengaard J, Jespersen S, Hansen B. Fast diffusion kurtosis imaging of fibrotic mouse kidneys. NMR IN BIOMEDICINE 2016; 29:1709-1719. [PMID: 27731906 PMCID: PMC5123986 DOI: 10.1002/nbm.3623] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/21/2016] [Revised: 07/25/2016] [Accepted: 08/17/2016] [Indexed: 05/16/2023]
Abstract
Diffusion kurtosis imaging (DKI) is sensitive to tissue microstructure and may therefore be useful in the diagnosis and monitoring of disease in brain and body organs. Generally, diffusion magnetic resonance imaging (dMRI) in the body is challenging because of the heterogeneous body composition, which can cause image artefacts as a result of chemical shifts and susceptibility differences. In addition, the abdomen possesses physiological factors (e.g. breathing, heartbeat, blood flow) which may severely reduce image quality, especially when echo planar imaging is employed, as is typical in dMRI. Collectively, these challenging measurement conditions impede the use and exploration of DKI in the body. This impediment is further exacerbated by the traditionally large amount of data required for DKI and the low signal-to-noise ratio at the b-values needed to effectively probe the kurtosis regime. Recently introduced fast DKI techniques reduce the challenge of DKI in the body by decreasing the data requirement substantially, so that, for example, triggering and breath-hold techniques may be applied for the entire DKI acquisition without causing unfeasible scan times. One common pathological condition for which body DKI may be of immediate clinical value is kidney fibrosis, which causes progressive changes in organ microstructure. With its sensitivity to microstructure, DKI is an obvious candidate for a non-invasive evaluation method. We present preclinical evidence indicating that the rapidly obtainable tensor-derived mean kurtosis ( W̅) distinguishes moderately fibrotic kidneys from healthy controls. The presence and degree of fibrosis are confirmed by histology, which also indicates fibrosis as the main driver behind the DKI differences observed between groups. We therefore conclude that fast kurtosis is a likely candidate for an MRI-based method for the detection and monitoring of renal fibrosis. We provide protocol recommendations for fast renal DKI in humans based on a b-value optimisation performed using data acquired at 3 T in normal human kidney.
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Affiliation(s)
- B.F. Kjølby
- Center of Functionally Integrative Neuroscience (CFIN) and MINDLab, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - A.R. Khan
- Center of Functionally Integrative Neuroscience (CFIN) and MINDLab, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - A. Chuhutin
- Center of Functionally Integrative Neuroscience (CFIN) and MINDLab, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - L. Pedersen
- Research Laboratory for Biochemical Pathology, Aarhus University Hospital, Department of Clinical Medicine, Aarhus, Denmark
| | - J.B. Jensen
- The PET centre, Aarhus University Hospital, Aarhus, Denmark
| | - S. Jakobsen
- The PET centre, Aarhus University Hospital, Aarhus, Denmark
| | - D. Zeidler
- Center of Functionally Integrative Neuroscience (CFIN) and MINDLab, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - R. Sangill
- Center of Functionally Integrative Neuroscience (CFIN) and MINDLab, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - J.R Nyengaard
- Stereology and Electron Microscopy Laboratory, Centre for Stochastic Geometry and Advanced Bioimaging, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - S.N. Jespersen
- Center of Functionally Integrative Neuroscience (CFIN) and MINDLab, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Physics and Astronomy, Aarhus University, Aarhus, Denmark
| | - B. Hansen
- Center of Functionally Integrative Neuroscience (CFIN) and MINDLab, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Corresponding Author: Brian Hansen, CFIN, Aarhus University, Building 10G, 5th Floor, Nørrebrogade 44, DK-8000 Århus C, Denmark,
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15
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Hilbert F, Bock M, Neubauer H, Veldhoen S, Wech T, Bley TA, Köstler H. An intravoxel oriented flow model for diffusion-weighted imaging of the kidney. NMR IN BIOMEDICINE 2016; 29:1403-1413. [PMID: 27488570 DOI: 10.1002/nbm.3584] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/29/2016] [Revised: 06/06/2016] [Accepted: 06/21/2016] [Indexed: 06/06/2023]
Abstract
By combining intravoxel incoherent motion (IVIM) and diffusion tensor imaging (DTI) we introduce a new diffusion model called intravoxel oriented flow (IVOF) that accounts for anisotropy of diffusion and the flow-related signal. An IVOF model using a simplified apparent flow fraction tensor (IVOFf ) is applied to diffusion-weighted imaging of human kidneys. The kidneys of 13 healthy volunteers were examined on a 3 T scanner. Diffusion-weighted images were acquired with six b values between 0 and 800 s/mm(2) and 30 diffusion directions. Diffusivity and flow fraction were calculated for different diffusion models. The Akaike information criterion was used to compare the model fit of the proposed IVOFf model to IVIM and DTI. In the majority of voxels the proposed IVOFf model with a simplified apparent flow fraction tensor performs better than IVIM and DTI. Mean diffusivity is significantly higher in DTI compared with models that account for the flow-related signal. The fractional anisotropy of diffusion is significantly reduced when flow fraction is considered to be anisotropic. Anisotropy of the apparent flow fraction tensor is significantly higher in the renal medulla than in the cortex region. The IVOFf model describes diffusion-weighted data in the human kidney more accurately than IVIM or DTI. The apparent flow fraction in the kidney proved to be anisotropic.
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Affiliation(s)
- Fabian Hilbert
- Department of Diagnostic and Interventional Radiology, University of Würzburg, Würzburg, Germany.
| | - Maximilian Bock
- Department of Diagnostic and Interventional Radiology, University of Würzburg, Würzburg, Germany
| | - Henning Neubauer
- Department of Diagnostic and Interventional Radiology, University of Würzburg, Würzburg, Germany
| | - Simon Veldhoen
- Department of Diagnostic and Interventional Radiology, University of Würzburg, Würzburg, Germany
| | - Tobias Wech
- Department of Diagnostic and Interventional Radiology, University of Würzburg, Würzburg, Germany
| | - Thorsten Alexander Bley
- Department of Diagnostic and Interventional Radiology, University of Würzburg, Würzburg, Germany
| | - Herbert Köstler
- Department of Diagnostic and Interventional Radiology, University of Würzburg, Würzburg, Germany
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16
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Ye Q, Chen Z, Zhao Y, Zhang Z, Miao H, Xiao Q, Wang M, Li J. Initial experience of generalized intravoxel incoherent motion imaging and diffusion tensor imaging (GIVIM-DTI) in healthy subjects. J Magn Reson Imaging 2016; 44:732-8. [PMID: 27079733 DOI: 10.1002/jmri.25262] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2016] [Accepted: 03/18/2016] [Indexed: 11/06/2022] Open
Affiliation(s)
- Qiong Ye
- Department of Radiology; The First Affiliated Hospital of Wenzhou Medical University; ZheJiang P.R. China
| | - Zhongwei Chen
- Department of Radiology; The First Affiliated Hospital of Wenzhou Medical University; ZheJiang P.R. China
| | - Youfan Zhao
- Department of Radiology; The First Affiliated Hospital of Wenzhou Medical University; ZheJiang P.R. China
| | - Zhenhua Zhang
- Department of Radiology; The First Affiliated Hospital of Wenzhou Medical University; ZheJiang P.R. China
| | - Haiwei Miao
- Department of Radiology; The First Affiliated Hospital of Wenzhou Medical University; ZheJiang P.R. China
| | - Qinqin Xiao
- Department of Radiology; The First Affiliated Hospital of Wenzhou Medical University; ZheJiang P.R. China
| | - Meihao Wang
- Department of Radiology; The First Affiliated Hospital of Wenzhou Medical University; ZheJiang P.R. China
| | - Jiance Li
- Department of Radiology; The First Affiliated Hospital of Wenzhou Medical University; ZheJiang P.R. China
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17
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Bennett KM. MRI shines (radiofrequency) light on kidney physiology. Am J Physiol Renal Physiol 2016; 310:F41-2. [DOI: 10.1152/ajprenal.00462.2015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Affiliation(s)
- Kevin M. Bennett
- Department of Biology, University of Hawaii at Manoa, Honolulu, Hawaii
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18
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Campbell-Washburn AE, Atkinson D, Nagy Z, Chan RW, Josephs O, Lythgoe MF, Ordidge RJ, Thomas DL. Using the robust principal component analysis algorithm to remove RF spike artifacts from MR images. Magn Reson Med 2015; 75:2517-25. [PMID: 26193125 PMCID: PMC4720596 DOI: 10.1002/mrm.25851] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2015] [Revised: 06/26/2015] [Accepted: 06/29/2015] [Indexed: 11/18/2022]
Abstract
Brief bursts of RF noise during MR data acquisition (“k‐space spikes”) cause disruptive image artifacts, manifesting as stripes overlaid on the image. RF noise is often related to hardware problems, including vibrations during gradient‐heavy sequences, such as diffusion‐weighted imaging. In this study, we present an application of the Robust Principal Component Analysis (RPCA) algorithm to remove spike noise from k‐space. Methods: Corrupted k‐space matrices were decomposed into their low‐rank and sparse components using the RPCA algorithm, such that spikes were contained within the sparse component and artifact‐free k‐space data remained in the low‐rank component. Automated center refilling was applied to keep the peaked central cluster of k‐space from misclassification in the sparse component. Results: This algorithm was demonstrated to effectively remove k‐space spikes from four data types under conditions generating spikes: (i) mouse heart T1 mapping, (ii) mouse heart cine imaging, (iii) human kidney diffusion tensor imaging (DTI) data, and (iv) human brain DTI data. Myocardial T1 values changed by 86.1 ± 171 ms following despiking, and fractional anisotropy values were recovered following despiking of DTI data. Conclusion: The RPCA despiking algorithm will be a valuable postprocessing method for retrospectively removing stripe artifacts without affecting the underlying signal of interest. Magn Reson Med 75:2517–2525, 2016. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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Affiliation(s)
- Adrienne E Campbell-Washburn
- Centre for Advanced Biomedical Imaging, University College London, London, United Kingdom.,Division of Intramural Research, Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - David Atkinson
- Centre for Medical Imaging, University College London, United Kingdom
| | - Zoltan Nagy
- Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology, University College London, London, United Kingdom.,Laboratory for Social and Neural Systems Research (SNS Lab), Department of Economics, University of Zurich, Zurich, Switzerland
| | - Rachel W Chan
- Centre for Medical Imaging, University College London, United Kingdom
| | - Oliver Josephs
- Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology, University College London, London, United Kingdom.,Birkbeck-UCL Centre for Neuroimaging, Birkbeck College, London, United Kingdom
| | - Mark F Lythgoe
- Centre for Advanced Biomedical Imaging, University College London, London, United Kingdom
| | - Roger J Ordidge
- Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Australia
| | - David L Thomas
- Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, University College London, London, United Kingdom
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