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Noninvasive Assessment of Renal Fibrosis with Magnetization Transfer MR Imaging: Validation and Evaluation in Murine Renal Artery Stenosis.

ABSTRACT: Purpose To test the utility of magnetization transfer imaging in detecting and monitoring the progression of renal fibrosis in mice with unilateral renal artery stenosis. Materials and Methods This prospective study was approved by the Institutional Animal Care and Use Committee. Renal artery stenosis surgery (n = 10) or sham surgery (n = 5) was performed, and the stenotic and contralateral kidneys were studied longitudinally in vivo at baseline and 2, 4, and 6 weeks after surgery. After a 16.4-T magnetic resonance imaging examination, magnetization transfer ratio was measured as an index of fibrosis (guided by parameters selected in preliminary phantom studies). In addition, renal volume, perfusion, blood flow, and oxygenation were assessed. Fibrosis was subsequently measured ex vivo by means of histologic analysis and hydroxyproline assay. The Wilcoxon rank sum or signed rank test was used for statistical comparisons between or within groups, and Pearson and Spearman rank correlation was used to compare fibrosis measured in vivo and ex vivo. Results In the stenotic kidney, the median magnetization transfer ratio showed progressive increases from baseline to 6 weeks after surgery (increases of 13.7% [P = .0006] and 21.3% [P = .0005] in cortex and medulla, respectively), which were accompanied by a progressive loss in renal volume, perfusion, blood flow, and oxygenation. The 6-week magnetization transfer ratio map showed good correlation with fibrosis measured ex vivo (Pearson r = 0.9038 and Spearman ρ = 0.8107 [P = .0002 vs trichrome staining]; r = 0.9540 and ρ = 0.8821 [P < .0001 vs Sirius red staining]; and r = 0.8429 and ρ = 0.7607 [P = .001 vs hydroxyproline assay]). Conclusion Magnetization transfer imaging was used successfully to measure and longitudinally monitor the progression of renal fibrosis in mice with unilateral renal artery stenosis. ^© RSNA, 2016 Online supplemental material is available for this article.

SUBMITTER: Jiang K

PROVIDER: S-EPMC5359024 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:OBJECTIVES:Renal fibrosis is a useful biomarker for diagnosis and evaluation of therapeutic interventions of renal diseases but often requires invasive testing. Magnetization transfer magnetic resonance imaging (MT-MRI), which evaluates the presence of macromolecules, offers a noninvasive tool to probe renal fibrosis in murine renal artery stenosis (RAS) at 16.4 T. In this study, we aimed to identify appropriate imaging parameters for collagen detection at 3.0 T MRI and to test the utility of MT-MRI in measuring renal fibrosis in a swine model of atherosclerotic RAS (ARAS). MATERIALS AND METHODS:To select the appropriate offset frequency, an MT-MRI study was performed on a phantom containing 0% to 40% collagen I and III with offset frequencies from -1600 to +1600 Hz and other MT parameters empirically set as pulse width at 16 milliseconds and flip angle at 800 degrees. Then selected MT parameters were used in vivo on pigs 12 weeks after sham (n = 8) or RAS (n = 10) surgeries. The ARAS pigs were fed with high-cholesterol diet to induce atherosclerosis. The MT ratio (MTR) was compared with ex vivo renal fibrosis measured using Sirius-red staining. RESULTS:Offset frequencies at 600 and 1000 Hz were selected for collagen detection without direct saturation of free water signal, and subsequently applied in vivo. The ARAS kidneys showed mild cortical and medullary fibrosis by Sirius-red staining. The cortical and medullary MTRs at 600 and 1000 Hz were both increased. Renal fibrosis measured ex vivo showed good linear correlations with MTR at 600 (cortex: Pearson correlation coefficient r = 0.87, P < 0.001; medulla: r = 0.70, P = 0.001) and 1000 Hz (cortex: r = 0.75, P < 0.001; medulla: r = 0.83, P < 0.001). CONCLUSIONS:Magnetization transfer magnetic resonance imaging can noninvasively detect renal fibrosis in the stenotic swine kidney at 3.0 T. Therefore, MT-MRI may potentially be clinically applicable and useful for detection and monitoring of renal pathology in subjects with RAS.

Project description:Purpose To evaluate the role of magnetization transfer (MT) magnetic resonance (MR) imaging for the characterization of intestinal fibrosis compared with contrast material-enhanced and diffusion-weighted MR imaging and its capability for differentiating fibrotic from inflammatory strictures in humans with Crohn disease (CD) by using surgical histopathologic analysis as the reference standard. Materials and Methods Institutional review board approval and informed consent were obtained for this prospective study. Abdominal MT imaging, contrast-enhanced imaging, and diffusion-weighted imaging of 31 consecutive patients with CD were analyzed before elective surgery. The bowel wall MT ratio normalized to skeletal muscle, the apparent diffusion coefficient (ADC), and the percentage of enhancement gain were calculated; region-by-region correlations with the surgical specimen were performed to determine the histologic degree of fibrosis and inflammation. The performance of MT imaging was validated in five new patients. One-way analysis of variance test, Spearman rank correlation, and receiver operating characteristic curve were used for statistical analysis. Results Normalized MT ratios strongly correlated with fibrosis scores (r = 0.769; P = .000) but did not correlate with inflammation scores (r = -0.034; P = .740). Significant differences (F = 49.002; P = .000) in normalized MT ratios were found among nonfibrotic, mildly, moderately, and severely fibrotic walls. The normalized MT ratios of mixed fibrotic and inflammatory bowel walls were significantly higher than those of bowel walls with only inflammation present (t = -8.52; P = .000). A high accuracy of normalized MT ratios was shown with an area under the receiver operating characteristic curve (AUC) of 0.919 (P = .000) for differentiating moderately to severely fibrotic bowel walls from nonfibrotic and mildly fibrotic bowel walls, followed by ADC (AUC, 0.747; P = .001) and the percentage of enhancement gain (AUC, 0.592; P = .209). The sensitivity, specificity, and AUC of MT imaging for diagnosing moderate to severe fibrosis in the validation data set were 80% (12 of 15), 100% (three of three), and 0.9 (P = .033), respectively. Conclusion MT imaging outperforms ADC and contrast-enhanced imaging in detecting and distinguishing varying degrees of bowel fibrosis with or without coexisting inflammation. MT imaging could potentially be used as a method to differentiate fibrotic from inflammatory intestinal strictures in patients with CD. © RSNA, 2018 Online supplemental material is available for this article.

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Noninvasive Assessment of Renal Fibrosis with Magnetization Transfer MR Imaging: Validation and Evaluation in Murine Renal Artery Stenosis.

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