Utilizing magnetization transfer imaging to investigate tissue remodeling in a murine model of autosomal dominant polycystic kidney disease

Kline, Timothy L.; Irazabal, María V.; Ebrahimi, Behzad; Hopp, Katharina; Udoji, Kelly N.; Warner, Joshua D.; Korfiatis, Panagiotis; Mishra, Prasanna K.; Macura, Slobodan; Venkatesh, Sudhakar K.; Lerman, Lilach O.; Harris, Peter C.; Torres, Vicente E.; King, Bernard F.; Erickson, Bradley J.

doi:10.1002/mrm.25701

Cited by 35 publications

(29 citation statements)

References 30 publications

(38 reference statements)

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“…5 These include blood oxygenation level dependent (BOLD) MRI, diffusion-weighted MRI (DWI), magnetic resonance elastography (MRE) and magnetization transfer (MT) imaging . [13][14][15][16][17][18][19][20] Each of these techniques has limitations, although each has shown potential for detecting renal fibrosis. BOLD MRI is not a specific measure of renal fibrosis because transverse relaxation time T 2 * could be affected by multiple processes such as tubular cell apoptosis, decreased oxygen consumption, reduced oxygen delivery, renal blood flow and tubular function.…”

Section: Introductionmentioning

confidence: 99%

Noninvasive quantitative magnetization transfer MRI reveals tubulointerstitial fibrosis in murine kidney

Wang

Zhang

et al. 2019

NMR in Biomedicine

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Excessive tissue scarring, or fibrosis, is a critical contributor to end stage renal disease, but current clinical tests are not sufficient for assessing renal fibrosis. Quantitative magnetization transfer (qMT) MRI provides indirect information about the macromolecular composition of tissues. We evaluated measurements of the pool size ratio (PSR, the ratio of immobilized macromolecular to free water protons) obtained by qMT as a biomarker of tubulointerstitial fibrosis in a well‐established murine model with progressive renal disease. MR images were acquired from 16‐week‐old fibrotic hHB‐EGFTg/Tg mice and normal wild‐type (WT) mice (N = 12) at 7 T. QMT parameters were derived using a two‐pool five‐parameter fitting model. A normal range of PSR values in the cortex and outer stripe of outer medulla (CR + OSOM) was determined by averaging across voxels within WT kidneys (mean ± 2SD). Regions in diseased mice whose PSR values exceeded the normal range above a threshold value (tPSR) were identified and measured. The spatial distribution of fibrosis was confirmed using picrosirius red stains. Compared with normal WT mice, scattered clusters of high PSR regions were observed in the OSOM of hHB‐EGFTg/Tg mouse kidneys. Moderate increases in mean PSR (mPSR) of CR + OSOM regions were observed across fibrotic kidneys. The abnormally high PSR regions (% area) detected by the tPSR were significantly increased in hHB‐EGFTg/Tg mice, and were highly correlated with regions of fibrosis detected by histological fibrosis indices measured from picrosirius red staining. Renal tubulointerstitial fibrosis in OSOM can thus be assessed by qMT MRI using an appropriate analysis of PSR. This technique may be used as an imaging biomarker for chronic kidney diseases.

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Section: Introductionmentioning

confidence: 99%

Noninvasive quantitative magnetization transfer MRI reveals tubulointerstitial fibrosis in murine kidney

Wang

Zhang

et al. 2019

NMR in Biomedicine

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“…MTI has been applied to detect microstructural disruptions in the brain (15, 16), lungs (17), intestines (18–20), and rectal cancer (21). Recently, MTI was applied for the evaluation of nephropathy, including unilateral ureteral obstruction (22) and polycystic kidney disease (23). However, the utility of MTI for detection of renal fibrosis cannot be easily evaluated in these two models due to concomitant accumulation of fluids, which is unlikely to be present in RAS.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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Purpose To test the utility of magnetization transfer imaging (MTI) in detection and monitoring the progression of renal fibrosis in mice with unilateral renal artery stenosis (RAS). Materials and Methods This prospective study was approved by the Institutional Animal Care and Use Committee. RAS (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 post-surgery. Following a 16.4T MRI exam, magnetization transfer ratio (MTR) 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 histology and hydroxyproline assay. The Wilcoxon rank-sum or signed-rank test was used for statistical comparisons between or within groups, and Pearson’s and Spearman’s rank correlation to compare fibrosis measured in-vivo and ex-vivo. Results In the stenotic kidney, the median MTR showed progressive increases from baseline to 6 weeks post-surgery (by 13.7% [P=0.0006] and 21.3% [P=0.0005] in cortex and medulla, respectively), which were accompanied by a progressive loss in renal volume, perfusion, blood flow, and oxygenation. The 6-week MTR map showed good correlation with fibrosis measured ex-vivo (Pearson’s r=0.9038 and Spearman’s ρ=0.8107, P=0.0002 vs. trichrome staining; r=0.9540 and ρ=0.8821, P<0.0001 vs. Sirius red staining; r=0.8429 and ρ=0.7607, P=0.001 vs. hydroxyproline assay). Conclusion MT successfully measured and longitudinally monitored the progression of renal fibrosis in mice with unilateral RAS.

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“…These techniques could provide a deeper understanding of the composition of an ADPKD patient's renal tissue. For example, magnetization transfer imaging (MTI) has been shown to identify fibrotic tissue within kidneys 18-20 , perfusion imaging (e.g., arterial spin labeling) can identify reduced perfusion territories 21 , and blood oxygen level dependent (BOLD) imaging reflects regional renal oxygenation status 22-24 . Other techniques such as measurement of renal blood flow 25-27 , magnetic resonance elastography (to measure tissue stiffness) 28 , sodium imaging 29 , diffusion weighted imaging (DWI) 30 with intra-voxel incoherent motion (IVIM) processing 31 , and chemical exchange saturation transfer imaging 32 are additional imaging techniques currently being explored which could show utility in ADPKD management.…”

Section: Introductionmentioning

confidence: 99%

Image texture features predict renal function decline in patients with autosomal dominant polycystic kidney disease

Kline

Korfiatis

Edwards

et al. 2017

Kidney International

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Magnetic resonance imaging (MRI) examinations provide high-resolution information about the anatomic structure of the kidneys and are used to measure total kidney volume (TKV) in patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD). Height adjusted TKV (HtTKV) has become the gold-standard imaging biomarker for ADPKD progression at early stages of the disease when estimated glomerular filtration rate (eGFR) is still normal. However, HtTKV does not take advantage of the wealth of information provided by MRI. Here we tested whether image texture features provide additional insights into the ADPKD kidney that may be used as complementary information to existing biomarkers. A retrospective cohort of 122 patients from The Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP study) was identified who had T2-weighted MRIs, and eGFR values over 70 mL/min/1.73m2 at the time of their baseline scan. We computed nine distinct image texture features for each patient. The ability of each feature to predict subsequent progression to CKD stage 3A, 3B, and 30% reduction in eGFR at eight-year follow up was assessed. A multiple linear regression model was developed incorporating age, baseline eGFR, HtTKV, and three image texture features identified by stability feature selection (Entropy, Correlation, and Energy). Including texture in a multiple linear regression model (predicting percent change in eGFR) improved Pearson correlation coefficient from -0.51 (using age, eGFR, and HtTKV) to -0.70 (adding texture). Thus, texture analysis offers an approach to refine ADPKD prognosis and should be further explored for its utility in individualized clinical decision making and outcome prediction.

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Utilizing magnetization transfer imaging to investigate tissue remodeling in a murine model of autosomal dominant polycystic kidney disease

Cited by 35 publications

References 30 publications

Noninvasive quantitative magnetization transfer MRI reveals tubulointerstitial fibrosis in murine kidney

Noninvasive quantitative magnetization transfer MRI reveals tubulointerstitial fibrosis in murine kidney

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

Image texture features predict renal function decline in patients with autosomal dominant polycystic kidney disease

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