Quantitative assessment of renal structural and functional changes in chronic kidney disease using multi-parametric magnetic resonance imaging.
ABSTRACT: BACKGROUND:Multi-parametric magnetic resonance imaging (MRI) provides the potential for a more comprehensive non-invasive assessment of organ structure and function than individual MRI measures, but has not previously been comprehensively evaluated in chronic kidney disease (CKD). METHODS:We performed multi-parametric renal MRI in persons with CKD (n?=?22, 61?±?24 years) who had a renal biopsy and measured glomerular filtration rate (mGFR), and matched healthy volunteers (HV) (n?=?22, 61?±?25 years). Longitudinal relaxation time (T1), diffusion-weighted imaging, renal blood flow (phase contrast MRI), cortical perfusion (arterial spin labelling) and blood-oxygen-level-dependent relaxation rate (R2*) were evaluated. RESULTS:MRI evidenced excellent reproducibility in CKD (coefficient of variation?<10%). Significant differences between CKD and HVs included cortical and corticomedullary difference (CMD) in T1, cortical and medullary apparent diffusion coefficient (ADC), renal artery blood flow and cortical perfusion. MRI measures correlated with kidney function in a combined CKD and HV analysis: estimated GFR correlated with cortical T1 (r = -0.68), T1 CMD (r = -0.62), cortical (r?=?0.54) and medullary ADC (r?=?0.49), renal artery flow (r?=?0.78) and cortical perfusion (r?=?0.81); log urine protein to creatinine ratio (UPCR) correlated with cortical T1 (r?=?0.61), T1 CMD (r?=?0.61), cortical (r = -0.45) and medullary ADC (r = -0.49), renal artery flow (r = -0.72) and cortical perfusion (r = -0.58). MRI measures (cortical T1 and ADC, T1 and ADC CMD, cortical perfusion) differed between low/high interstitial fibrosis groups at 30-40% fibrosis threshold. CONCLUSION:Comprehensive multi-parametric MRI is reproducible and correlates well with available measures of renal function and pathology. Larger longitudinal studies are warranted to evaluate its potential to stratify prognosis and response to therapy in CKD.
Project description:BACKGROUND:Magnetic resonance relaxometry (MRR) offers highly reproducible pixel-wise parametric maps of T1 and T2 relaxation times, reflecting specific tissue properties, while diffusion-tensor imaging (DTI) is a promising technique for the characterization of microstructural changes, depending on the directionality of molecular motion. Both MMR and DTI may be used for non-invasive assessment of parenchymal changes caused by kidney injury or graft dysfunction. METHODS:We examined 46 patients with kidney transplantation and 16 healthy controls, using T1/T2 relaxometry and DTI at 3 T. Twenty-two early transplants and 24 late transplants were included. Seven of the patients had prior renal biopsy (all of them dysfunctional allografts; 6/7 with tubular atrophy and 7/7 with interstitial fibrosis). RESULTS:Compared to healthy controls, T1 and T2 relaxation times in the renal parenchyma were increased after transplantation, with the highest T1/T2 values in early transplants (T1: 1700 ± 53 ms/T2: 83 ± 6 ms compared to T1: 1514 ± 29 ms/T2: 78 ± 4 ms in controls). Medullary and cortical ADC/FA values were decreased in early transplants and highest in controls, with medullary FA values showing the most pronounced difference. Cortical renal T1, mean medullary FA and corticomedullary differentiation (CMD) values correlated best with renal function as measured by eGFR (cortical T1: r = -0.63, p < 0.001; medullary FA: r = 0.67, p < 0.001; FA CMD: r = 0.62, p < 0.001). Mean medullary FA proved to be a significant predictor for tubular atrophy (p < 0.001), while cortical T1 appeared as a significant predictor of interstitial fibrosis (p = 0.003). CONCLUSION:Cortical T1, medullary FA, and FA CMD might serve as new imaging biomarkers of renal function and histopathologic microstructure.
Project description:This systematic review, initiated by the European Cooperation in Science and Technology Action Magnetic Resonance Imaging Biomarkers for Chronic Kidney Disease (PARENCHIMA), focuses on potential clinical applications of magnetic resonance imaging in renal non-tumour disease using magnetic resonance relaxometry (MRR), specifically, the measurement of the independent quantitative magnetic resonance relaxation times T1 and T2 at 1.5 and 3Tesla (T), respectively. Healthy subjects show a distinguishable cortico-medullary differentiation (CMD) in T1 and a slight CMD in T2. Increased cortical T1 values, that is, reduced T1 CMD, were reported in acute allograft rejection (AAR) and diminished T1 CMD in chronic allograft rejection. However, ambiguous findings were reported and AAR could not be sufficiently differentiated from acute tubular necrosis and cyclosporine nephrotoxicity. Despite this, one recent quantitative study showed in renal transplants a direct correlation between fibrosis and T1 CMD. Additionally, various renal diseases, including renal transplants, showed a moderate to strong correlation between T1 CMD and renal function. Recent T2 studies observed increased values in renal transplants compared with healthy subjects and in early-stage autosomal dominant polycystic kidney disease (ADPKD), which could improve diagnosis and progression assessment compared with total kidney volume alone in early-stage ADPKD. Renal MRR is suggested to be sensitive to renal perfusion, ischaemia/oxygenation, oedema, fibrosis, hydration and comorbidities, which reduce specificity. Due to the lack of standardization in patient preparation, acquisition protocols and adequate patient selection, no widely accepted reference values are currently available. Therefore this review encourages efforts to optimize and standardize (multi-parametric) protocols to increase specificity and to tap the full potential of renal MRR in future research.
Project description:OBJECTIVE:To assess interobserver reproducibility of different regions of interest (ROIs) on multi-parametric renal MRI using commercially available software. MATERIALS AND METHODS:Healthy volunteers (HV), patients with heart failure (HF) and renal transplant recipients (Tx) were recruited. Localiser scans, T1 mapping and pseudo-continuous arterial spin labelling (pCASL) were performed. HV and Tx also underwent diffusion-weighted imaging to allow calculation of apparent diffusion coefficient (ADC). For T1, pCASL and ADC, ROIs were drawn for whole kidney (WK), cortex (Cx), user-defined representative cortex (rep-Cx) and medulla. Intraclass correlation coefficient (ICC) and coefficient of variation (CoV) were assessed. RESULTS:Forty participants were included (10 HV, 10 HF and 20 Tx). The ICC for renal volume was 0.97 and CoV 6.5%. For T1 and ADC, WK, Cx, and rep-Cx were highly reproducible with ICC???0.76 and CoV?<?5%. However, cortical pCASL results were more variable (ICC?>?0.86, but CoV up to 14.2%). While reproducible, WK values were derived from a wide spread of data (ROI standard deviation 17% to 55% of the mean value for ADC and pCASL, respectively). Renal volume differed between groups (p?<?0.001), while mean cortical T1 values were greater in Tx compared to HV (p?=?0.009) and HF (p?=?0.02). Medullary T1 values were also higher in Tx than HV (p?=?0.03), while medullary pCASL values were significantly lower in Tx compared to HV and HF (p?=?0.03 for both). DISCUSSION:Kidney volume calculated by manually contouring a localiser scan was highly reproducible between observers and detected significant differences across patient groups. For T1, pCASL and ADC, Cx and rep-Cx ROIs are generally reproducible with advantages over WK values.
Project description:Interstitial fibrosis (IF) is the common pathway of chronic kidney injury in various conditions. Magnetic resonance imaging (MRI) may be a promising tool for the noninvasive assessment of IF in renal allografts. Methods:This prospective trial was primarily designed to investigate whether the results of T1-weighted MRI associate with the degree of IF. Thirty-two kidney transplant recipients were subjected to 1.5-Tesla MRI scans shortly before or after routine allograft biopsies. MRI parameters [T1 and T2 relaxation times; apparent diffusion coefficient (ADC)] were assessed for cortical and medullary sections. Results:Advanced IF (Banff ci score >1) was associated with higher cortical T1 (but not T2) values [1451 (median; interquartile range: 1331-1506) versus 1306 (1197-1321) ms in subjects with ci scores ?1; P = 0.011; receiver operating characteristic area under the curve for prediction of ci > 1: 0.76]. In parallel, T1 values were associated with kidney function and proteinuria. There was also a relationship between IF and corticomedullary differences on ADC maps (receiver operating characteristic area under the curve for prediction of ci ? 1: 0.79). Conclusions:Our results support the use of MRI for noninvasive assessment of allograft scarring. Future studies will have to clarify the role of T1 (and ADC) mapping as a surrogate endpoint reflecting the progression of chronic graft damage.
Project description:Here we assessed the diagnostic value of a quantitative multiparametric magnetic resonance imaging (mpMRI) protocol for evaluation of renal allograft dysfunction with fibrosis. Twenty-seven renal transplant patients, including 15 with stable functional allografts (eGFR mean 71.5 ml/min/1.73m<sup>2</sup>), and 12 with chronic dysfunction/established fibrosis (eGFR mean 30.1 ml/min/1.73m<sup>2</sup>), were enrolled in this prospective single-center study. Sixteen of the patients had renal biopsy (mean 150 days) before the MRI. All patients underwent mpMRI at 1.5T including intravoxel-incoherent motion diffusion-weighted imaging, diffusion tensor imaging, blood oxygen level dependent (BOLD R<sub>2</sub>*) and T<sub>1</sub> quantification. True diffusion D, pseudodiffusion D*, perfusion fraction PF, apparent diffusion coefficient (ADC), fractional anisotropy (FA), R<sub>2</sub>* and T<sub>1</sub> were calculated for cortex and medulla. ?T<sub>1</sub> was calculated as (100x(T<sub>1</sub> Cortex-T<sub>1</sub> Medulla)/T<sub>1</sub> Cortex). Test-retest repeatability and inter-observer reproducibility were assessed in four and ten patients, respectively. mpMRI parameters had substantial test-retest and interobserver repeatability (coefficient of variation under 15%), except for medullary PF and D* (coefficient of variation over 25%). Cortical ADC, D, medullary ADC and ?T<sub>1</sub> were all significantly decreased, while cortical T<sub>1</sub> was significantly elevated in fibrotic allografts. Cortical T<sub>1</sub> showed positive correlation to the Banff fibrosis and tubular atrophy scores. The combination of ?T<sub>1</sub> and cortical ADC had excellent cross-validated diagnostic performance for detection of chronic dysfunction with fibrosis. Cortical ADC and T<sub>1</sub> had good performance for predicting eGFR decline at 18 months (4 or more ml/min/1.73m<sup>2</sup>/year). Thus, the combination of cortical ADC and T<sub>1</sub> measurements shows promising results for the non-invasive assessment of renal allograft histology and outcomes.
Project description:Alterations in renal microperfusion play an important role in the development of acute kidney injury with long-term consequences. Here we used contrast-enhanced ultrasonography as a novel method for depicting intrarenal distribution of blood flow. After infusion of microbubble contrast agent, bubbles were collapsed in the kidney and postbubble destruction refilling was measured in various regions of the kidney. Local perfusion was monitored in vivo at 15, 30, 45, 60 minutes and 24 hours after 28 minutes of bilateral ischemia in 12 mice. High-resolution, pixel-by-pixel analysis was performed on each imaging clip using customized software, yielding parametric perfusion maps of the kidney, representing relative blood volume in each pixel. These perfusion maps revealed that outer medullary perfusion decreased disproportionately to the reduction in the cortical and inner medullary perfusion after ischemia. Outer medullary perfusion was significantly decreased by 69% at 60 minutes postischemia and remained significantly less (40%) than preischemic levels at 24 hours postischemia. Thus, contrast-enhanced ultrasonography with high-resolution parametric perfusion maps can monitor changes in renal microvascular perfusion in space and time in mice. This novel technique can be translated to clinical use in man.
Project description:Experimentally renal tissue hypoxia appears to play an important role in the pathogenesis of chronic kidney disease (CKD) and arterial hypertension (AHT). In this study we measured renal tissue oxygenation and its determinants in humans using blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) under standardized hydration conditions. Four coronal slices were selected, and a multi gradient echo sequence was used to acquire T2* weighted images. The mean cortical and medullary R2* values (?=?1/T2*) were calculated before and after administration of IV furosemide, a low R2* indicating a high tissue oxygenation. We studied 195 subjects (95 CKD, 58 treated AHT, and 42 healthy controls). Mean cortical R2 and medullary R2* were not significantly different between the groups at baseline. In stimulated conditions (furosemide injection), the decrease in R2* was significantly blunted in patients with CKD and AHT. In multivariate linear regression analyses, neither cortical nor medullary R2* were associated with eGFR or blood pressure, but cortical R2* correlated positively with male gender, blood glucose and uric acid levels. In conclusion, our data show that kidney oxygenation is tightly regulated in CKD and hypertensive patients at rest. However, the metabolic response to acute changes in sodium transport is altered in CKD and in AHT, despite preserved renal function in the latter group. This suggests the presence of early renal metabolic alterations in hypertension. The correlations between cortical R2* values, male gender, glycemia and uric acid levels suggest that these factors interfere with the regulation of renal tissue oxygenation.
Project description:The purpose was to characterize acute kidney injury (AKI) in C57BL/6 (B6)- and 129/Sv (Sv)-mice by noninvasive measurement of renal perfusion and tissue edema using functional MRI.Different severities of AKI were induced in B6- and Sv-mice by renal ischemia reperfusion injury (IRI). Unilateral clamping of the renal pedicle for 35 min (moderate AKI) or 45 min (severe AKI) was done. MRI (7-Tesla) was performed 1, 7 and 28 days after surgery using a flow alternating inversion recovery (FAIR) arterial spin labeling (ASL) sequence. Maps of perfusion and T1-relaxation time were calculated. Relative MRI-parameters of the IRI kidney compared to the contralateral not-clipped kidney were compared between AKI severities and between mouse strains using unpaired t-tests. In addition, fibrosis was assessed by Masson Trichrome and collagen IV staining.After moderate AKI relative perfusion impairment was significantly higher in B6- than in Sv-mice at d7 (55±7% vs. 82±8%, p<0.05) and d28 (76±7% vs. 102±3%, p<0.01). T1-values increased in the early phase after AKI in both mouse strains. T1-increase was more severe after prolonged ischemia times of 45 min compared to 35 min in both mouse strains, measured in the renal cortex and outer stripe of outer medulla. Kidney volume loss (compared to the contralateral kidney) occurred already after 7 days but proceeded markedly towards 4 weeks in severe AKI. Early renal perfusion impairment was predictive for later kidney volume loss. The progression to chronic kidney disease (CKD) in the severe AKI model was similar in both mouse strains as revealed by histology.Quantification of renal perfusion and tissue edema by functional MRI allows characterization of strain differences upon AKI. Renal perfusion impairment was stronger in B6- compared to Sv-animals following moderate AKI. Prolonged ischemia times were associated with more severe perfusion impairment and edema formation in the early phase and progression to CKD within 4 weeks of observation.
Project description:BACKGROUND:Renal flow abnormalities are believed to play a central role in the pathogenesis of nephropathy and in primary and secondary hypertension, but are difficult to measure in humans. Handgrip exercise is known to reduce renal arterial flow (RAF) by means of increased renal sympathetic nerve activity. METHODS:To monitor medullary and cortical oxygenation under handgrip exercise-reduced perfusion, we used contrast- and radiation-free magnetic resonance imaging (MRI) to measure regional changes in renal perfusion and blood oxygenation in ten healthy normotensive individuals during handgrip exercise. We used phase-contrast MRI to measure RAF, arterial spin labeling to measure perfusion, and both changes in transverse relaxation time (T2*) and dynamic blood oxygenation level-dependent imaging to measure blood oxygenation. RESULTS:Handgrip exercise induced a significant decrease in RAF. In the renal medulla, this was accompanied by an increase of oxygenation (reflected by an increase in T2*) despite a significant drop in medullary perfusion; the renal cortex showed a significant decrease in both perfusion and oxygenation. We also found a significant correlation (R 2=0.8) between resting systolic BP and the decrease in RAF during handgrip exercise. CONCLUSIONS:Renal MRI measurements in response to handgrip exercise were consistent with a sympathetically mediated decrease in RAF. In the renal medulla, oxygenation increased despite a reduction in perfusion, which we interpreted as the result of decreased GFR and a subsequently reduced reabsorptive workload. Our results further indicate that the renal flow response's sensitivity to sympathetic activation is correlated with resting BP, even within a normotensive range.
Project description:Interstitial fibrosis and hypoxia accelerate the progression of CKD, but clinical tools to quantitate these factors in patients are lacking. Here, we evaluated the use of two magnetic resonance imaging (MRI) techniques, diffusion-weighted (DW)-MRI and blood oxygen level-dependent (BOLD)-MRI, to assess kidney fibrosis and hypoxia of the cortex in 142 patients with either diabetic nephropathy (n = 43), CKD without diabetes (n = 76), or acute kidney injury (AKI) (n = 23). Apparent diffusion coefficient (ADC) values of DW-MRI correlated with estimated glomerular filtration rates (eGFR) in the diabetic nephropathy and CKD groups (r(2) = 0.56 and r(2) = 0.46, respectively). Although the T2* values of BOLD-MRI and eGFR displayed good correlation in the CKD group (r(2) = 0.38), we did not observe a significant correlation between these values in the diabetic nephropathy group, suggesting that factors other than tubulointerstitial alteration determine the degree of hypoxia in the renal cortex. In the AKI group, neither the T2* nor ADC values correlated with eGFR. Renal biopsies from patients with CKD demonstrated that the T2* and ADC MRI values correlated with renal pathology. Taken together, ADC and T2* values appear to serve as accurate indices for evaluating renal tubulointerstitial alterations and parenchymal hypoxia, respectively, in the cortex. Functional MRI can thus contribute to multilateral, noninvasive, in vivo assessment of kidney function.