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Combination of Functional Magnetic Resonance Imaging and Histopathologic Analysis to Evaluate Interstitial Fibrosis in Kidney Allografts.

ABSTRACT: BACKGROUND AND OBJECTIVES:Recent developments indicated that functional magnetic resonance imaging (MRI) could potentially provide noninvasive assessment of kidney interstitial fibrosis in patients with kidney diseases, but direct evidence from histopathology is scarce. We aimed to explore the diagnostic utilities of functional MRI for the evaluation of kidney allograft interstitial fibrosis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:We prospectively examined 103 kidney transplant recipients who underwent for-cause biopsies and 20 biopsy-proven normal subjects with functional MRI. Histomorphometric analyses of interstitial fibrosis and peritubular capillary densities were performed on digitally scanned Masson's trichrome- and CD34-stained slides, respectively. The performances of functional MRI to discriminate interstitial fibrosis were assessed by calculating the area under the curve using receiver-operating characteristic curve. RESULTS:Main pathologic findings in this single-center cohort were representative of common diagnostic entities in the kidney allografts, with rejection (32%) and glomerulonephritides (31%) accounting for the majority of diagnoses. Apparent diffusion coefficient from diffusion-weighted imaging correlated with interstitial fibrosis (?=-0.77; P<0.001). Additionally, decreased arterial spin labelings were accompanied by peritubular capillary density reductions (r=0.77; P<0.001). Blood oxygen level-dependent (BOLD) imaging demonstrated cortical hypoxia with increasing interstitial fibrosis (?=0.61; P<0.001). The area under the curve for the discrimination of ?25% versus >25% interstitial fibrosis and ?50% versus >50% interstitial fibrosis were 0.87 (95% confidence interval [95% CI], 0.79 to 0.93) and 0.88 (95% CI, 0.80 to 0.93) by apparent diffusion coefficient, 0.92 (95% CI, 0.85 to 0.97) and 0.94 (95% CI, 0.87 to 0.98) by arterial spin labeling, 0.81 (95% CI, 0.72 to 0.88) and 0.86 (95% CI, 0.78 to 0.92) by perfusion fraction, 0.79 (95% CI, 0.69 to 0.87) and 0.85 (95% CI, 0.76 to 0.92) by BOLD imaging, respectively. CONCLUSIONS:Functional MRI measurements were strongly correlated with kidney allograft interstitial fibrosis. The performances of functional MRI for discriminating ?50% versus >50% interstitial fibrosis were good to excellent.

SUBMITTER: Wang W

PROVIDER: S-EPMC6730521 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Combination of Functional Magnetic Resonance Imaging and Histopathologic Analysis to Evaluate Interstitial Fibrosis in Kidney Allografts.

Wang Wei W Yu Yuanmeng Y Wen Jiqiu J Zhang Mingchao M Chen Jinsong J Cheng Dongrui D Zhang Longjiang L Liu Zhihong Z

Clinical journal of the American Society of Nephrology : CJASN 20190815 9

<h4>Background and objectives</h4>Recent developments indicated that functional magnetic resonance imaging (MRI) could potentially provide noninvasive assessment of kidney interstitial fibrosis in patients with kidney diseases, but direct evidence from histopathology is scarce. We aimed to explore the diagnostic utilities of functional MRI for the evaluation of kidney allograft interstitial fibrosis.<h4>Design, setting, participants, & measurements</h4>We prospectively examined 103 kidney transp ...[more]

PMID: 31416890

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Project description:BACKGROUND AND OBJECTIVES:Fibrosis is a major cause of kidney allograft injury. Currently, the only means of assessing allograft fibrosis is by biopsy, an invasive procedure that samples <1% of the kidney. We examined whether magnetic resonance elastography, an imaging-based measure of organ stiffness, could noninvasively estimate allograft fibrosis and predict progression of allograft dysfunction. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:Kidney allograft recipients >1 year post-transplant undergoing an allograft biopsy first underwent free-breathing, flow-compensated magnetic resonance elastography on a 3.0-T magnetic resonance imaging scanner. Each patient had serial eGFR measurements after the elastography scan for a follow-up period of up to 1 year. The mean stiffness value of the kidney allograft was compared with both the histopathologic Banff fibrosis score and the rate of eGFR change during the follow-up period. RESULTS:Sixteen patients who underwent magnetic resonance elastography and biopsy were studied (mean age: 54±9 years old). Whole-kidney mean stiffness ranged between 3.5 and 7.3 kPa. Whole-kidney stiffness correlated with biopsy-derived Banff fibrosis score (Spearman rho =0.67; P<0.01). Stiffness was heterogeneously distributed within each kidney, providing a possible explanation for the lack of a stronger stiffness-fibrosis correlation. We also found negative correlations between whole-kidney stiffness and both baseline eGFR (Spearman rho =-0.65; P<0.01) and eGFR change over time (Spearman rho =-0.70; P<0.01). Irrespective of the baseline eGFR, increased kidney stiffness was associated with a greater eGFR decline (regression r2=0.48; P=0.03). CONCLUSIONS:Given the limitations of allograft biopsy, our pilot study suggests the potential for magnetic resonance elastography as a novel noninvasive measure of whole-allograft fibrosis burden that may predict future changes in kidney function. Future studies exploring the utility and accuracy of magnetic resonance elastography are needed.

Project description:BackgroundAlström syndrome (ALMS) is a rare ciliopathy characterised by early onset insulin resistance, obesity, and dyslipidaemia and is a model for diseases that have huge social, health and economic impact. Cardiomyopathy develops in the majority, with high rates of morbidity and mortality, the definitive features of which are coarse replacement fibrosis and diffuse myocardial fibrosis (DIF). The pathogenesis of heart failure is thought to involve fibroblast accumulation and expansion of the extracellular matrix with excess protein deposition, leading to distorted organ architecture and impaired contractile function. Consecutive adults with genetically proven ALMS attending the National Centre for Rare Disease in Birmingham, England were studied. All patients underwent serial CMR, echocardiography and venous blood sampling, with computed tomography coronary angiography (CTCA) performed to assess severity of CAD. The aims of this study were: 1) to evaluate changes over time in DIF by cardiovascular magnetic resonance tissue characterization in ALMS; 2) to examine whether changes in DIF are associated with alteration in systolic or diastolic function; and 3) to evaluate the frequency and severity of coronary artery disease as a confounder for progression of ischaemic versus non-ischaemic fibrosis.ResultsIn total, 30/32 adults (63% male; 67% White British) participated. The median age at first scan was 21.3 years (interquartile range: 19.0-32.6) and participants were followed for a maximum of 67 months. Only 4 patients had significant coronary artery stenosis on post-mortem, invasive coronary angiography or CTCA. Mid short axis myocardial T1 times, myocardial extracellular volume, and left ventricular mass increased significantly over time, by an average of 21.8 ms (95% CI 17.4-26.1; p < 0.001), 1.1 percentage points (0.6-1.6, p < 0.001), and 2.8 g/m2 (1.9-3.7; p < 0.001) per year, respectively. These changes were not associated with significant deterioration in myocardial structure or function.ConclusionsThis is the first comprehensive prospective study demonstrating progression of DIF in ALMS over time, although no structural or functional consequences were noted within a median three and a half years' follow up. Further study is warranted to define whether DIF is a by-stander or the driver to impaired contractile function, heart failure and death.

Project description:Monitoring renal allograft function after transplantation is key for the early detection of allograft impairment, which in turn can contribute to preventing the loss of the allograft. Multiparametric renal MRI (mpMRI) is a promising noninvasive technique to assess and characterize renal physiopathology; however, few studies have employed mpMRI in renal allografts with stable function (maintained function over a long time period). The purposes of the current study were to evaluate the reproducibility of mpMRI in transplant patients and to characterize normal values of the measured parameters, and to estimate the labeling efficiency of Pseudo-Continuous Arterial Spin Labeling (PCASL) in the infrarenal aorta using numerical simulations considering experimental measurements of aortic blood flow profiles. The subjects were 20 transplant patients with stable kidney function, maintained over 1 year. The MRI protocol consisted of PCASL, intravoxel incoherent motion, and T1 inversion recovery. Phase contrast was used to measure aortic blood flow. Renal blood flow (RBF), diffusion coefficient (D), pseudo-diffusion coefficient (D*), flowing fraction ( f ), and T1 maps were calculated and mean values were measured in the cortex and medulla. The labeling efficiency of PCASL was estimated from simulation of Bloch equations. Reproducibility was assessed with the within-subject coefficient of variation, intraclass correlation coefficient, and Bland-Altman analysis. Correlations were evaluated using the Pearson correlation coefficient. The significance level was p less than 0.05. Cortical reproducibility was very good for T1, D, and RBF, moderate for f , and low for D*, while medullary reproducibility was good for T1 and D. Significant correlations in the cortex between RBF and f (r = 0.66), RBF and eGFR (r = 0.64), and D* and eGFR (r = -0.57) were found. Normal values of the measured parameters employing the mpMRI protocol in kidney transplant patients with stable function were characterized and the results showed good reproducibility of the techniques.

Dataset Information

Combination of Functional Magnetic Resonance Imaging and Histopathologic Analysis to Evaluate Interstitial Fibrosis in Kidney Allografts.

Publications

Combination of Functional Magnetic Resonance Imaging and Histopathologic Analysis to Evaluate Interstitial Fibrosis in Kidney Allografts.

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