Medullary Apparent Diffusion Coefficient Research Articles

Effects of semaglutide, empagliflozin and their combination on renal diffusion-weighted MRI and total kidney volume in patients with type 2 diabetes: a post hoc analysis from a 32 week randomised trial.

The apparent diffusion coefficient (ADC) derived from diffusion-weighted MRI (DWI-MRI) has been proposed as a measure of changes in kidney microstructure, including kidney fibrosis. In advanced kidney disease, the kidneys often become atrophic; however, in the initial phase of type 2 diabetes, there is an increase in renal size. Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors both provide protection against progression of kidney disease in diabetes. However, the mechanisms are incompletely understood. To explore this, we examined the effects of semaglutide, empagliflozin and their combination on renal ADC and total kidney volume (TKV). This was a substudy of a randomised clinical trial on the effects of semaglutide and empagliflozin alone or in combination. Eighty patients with type 2 diabetes and high risk of CVD were randomised into four groups (n=20 in each) receiving either tablet placebo, empagliflozin, a combination of semaglutide and tablet placebo (herein referred to as the 'semaglutide' group), or the combination of semaglutide and empagliflozin (referred to as the 'combination-therapy' group). The semaglutide and the combination-therapy group had semaglutide treatment for 16 weeks and then had either tablet placebo or empagliflozin added to the treatment, respectively, for a further 16 weeks; the placebo and empagliflozin groups were treated with the respective monotherapy for 32 weeks. We analysed the effects of treatment on changes in ADC (cortical, medullary and the cortico-medullary difference [ΔADC; medullary ADC subtracted from cortical ADC]), as well as TKV measured by MRI. Both semaglutide and empagliflozin decreased cortical ADC significantly compared with placebo (semaglutide: -0.20×10-3 mm2/s [95% CI -0.30, -0.10], p<0.001; empagliflozin: -0.15×10-3 mm2/s [95% CI -0.26, -0.04], p=0.01). No significant change was observed in the combination-therapy group (-0.05×10-3 mm2/s [95%CI -0.15, 0.05]; p=0.29 vs placebo). The changes in cortical ADC were not associated with changes in GFR, albuminuria, TKV or markers of inflammation. Further, there were no changes in medullary ADC in any of the groups compared with placebo. Only treatment with semaglutide changed ΔADC significantly from placebo, showing a decrease of -0.13×10-3 mm2/s (95% CI -0.22, -0.04; p=0.01). Compared with placebo, TKV decreased by -3% (95% CI -5%, -0.3%; p=0.04), -3% (95% CI -5%, -0.4%; p=0.02) and -5% (95% CI -8%, -2%; p<0.001) in the semaglutide, empagliflozin and combination-therapy group, respectively. The changes in TKV were associated with changes in GFR, albuminuria and HbA1c. In a population with type 2 diabetes and high risk of CVD, semaglutide and empagliflozin significantly reduced cortical ADC compared with placebo, indicating microstructural changes in the kidneys. These changes were not associated with changes in GFR, albuminuria or inflammation. Further, we found a decrease in TKV in all active treatment groups, which was possibly mediated by a reduction in hyperfiltration. Our findings suggest that DWI-MRI may serve as a promising tool for investigating the underlying mechanisms of medical interventions in individuals with type 2 diabetes but may reflect effects not related to fibrosis. European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) 2019-000781-38.

Contralateral renal change in a unilateral ureteral obstruction rat model using intravoxel incoherent motion diffusion-weighted imaging

Objectives Most functional magnetic resonance research has primarily examined alterations in the affected kidney, often neglecting the contralateral kidney. Our study aims to investigate whether imaging parameters accurately depict changes in both the renal cortex and medulla in a unilateral ureteral obstruction rat model, thereby showcasing the utility of intravoxel incoherent motion (IVIM) in evaluating contralateral renal changes. Methods Six rats underwent MR scans and were subsequently sacrificed for baseline histological examination. Following the induction of left ureteral obstruction, 48 rats were scanned, and the histopathological examinations were conducted on days 3, 7, 10, 14, 21, 28, 35, and 42. The apparent diffusion coefficient (ADC), pure molecular diffusion (D), pseudodiffusion (D*), and perfusion fraction (f) values were measured using IVIM. Results On the 10th day of obstruction, both cortical and medullary ADC values differed significantly between the UUO10 group and the sham group (p < 0.01). The cortical D values showed statistically significant differences between UUO3 group and sham group (p < 0.01) but not among UUO groups at other time point. Additionally, the cortical and medullary f values were statistically significant between the UUO21 group and the sham group (p < 0.01). Especially, the cortical f values exhibited significant differences between the UUO21 group and the UUO groups with shorter obstruction time (at time point of 3, 7, 10, 14 day) (p < 0.01). Conclusions Significant hemodynamic alterations were observed in the contralateral kidney following renal obstruction. IVIM accurately captures changes in the unobstructed kidney. Particularly, the cortical f value exhibits the highest potential for assessing contralateral renal modifications.

Early assessment of acute kidney injury in severe acute pancreatitis with multimodal DWI: an animal model.

To evaluate the feasibility of multimodal diffusion-weighted imaging (DWI) for detecting the occurrence and severity of acute kidney injury (AKI) caused by severe acute pancreatitis (SAP) in rats. SAP was induced in thirty rats by the retrograde injection of 5.0% sodium taurocholate through the biliopancreatic duct. Six rats underwent MRI of the kidneys 24h before and 2, 4, 6, and 8h after this AKI model was generated. Conventional and functional MRI sequences were used, including intravoxel incoherent motion imaging (IVIM), diffusion tensor imaging (DTI), and diffusion kurtosis imaging (DTI). The main DWI parameters and histological results were analyzed. The fast apparent diffusion coefficient (ADC) of the renal cortex was significantly reduced at 2h, as was the fractional anisotropy (FA) value of the renal cortex on DTI. The mean kurtosis (MK) values for the renal cortex and medulla gradually increased after model generation. The renal histopathological score was negatively correlated with the medullary slow ADC, fast ADC, and perfusion scores for both the renal cortex and medulla, as were the ADC and FA values of the renal medulla in DTI, whereas the MK values of the cortex and medulla were positively correlated (r = 0.733, 0.812). Thus, the cortical fast ADC, medullary MK, FADTI, and slow ADC were optimal parameters for diagnosing AKI. Of these parameters, cortical fast ADC had the highest diagnostic efficacy (AUC = 0.950). The fast ADC of the renal cortex is the core indicator of early AKI, and the medullary MK value might serve as a sensitive biomarker for grading renal injury in SAP rats. The multimodal parameters of renal IVIM, DTI, and DKI are potential beneficial for the early diagnosis and severity grading of renal injury in SAP patients. • The multimodal parameters of renal DWI, including IVIM, DTI, and DKI, may be valuable for the noninvasive detection of early AKI and the severity grading of renal injury in SAP rats. • Cortical fast ADC, medullary MK, FA, and slow ADC are optimal parameters for early diagnosis of AKI, and cortical fast ADC has the highest diagnostic efficacy. • Medullary fast ADC, MK, and FA as well as cortical MK are useful for predicting the severity grade of AKI, and the renal medullary MK value exhibits the strongest correlation with pathological scores.

Assessment of renal allograft rejection with diffusion tensor imaging.

To investigate the value of DTI in differentiation of renal allograft rejection from well-functioning stable allograft, using fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values. In this prospective study, 22 transplant recipients with well-functioning stable allograft (group A) and 20 patients with renal allograft rejection (group B + C) were recruited over a period of 19 months from January 2018 to July 2019. DTI-MRI was performed in all the patients, and FA and ADC values were measured in cortical and medullary regions of the transplanted kidney. On biopsy, graft rejection was classified as acute (group B) (n = 7) and chronic graft rejection (group C) (n = 13) based on the BANNF scoring system. Statistical analysis was performed using STATA v.14.0. Statistically significant difference between group A and group B + C was noted for cortical (p < 0.001), and medullary (p = 0.003) FA values, and cortical (p = 0.020), and medullary (p = 0.046) ADC values. Cortical(p < 0.001) and Medullary(p = 0.020) FA values showed statistically significant difference between group A and group C, and cortical FA value(p = 0.012) also showed statistically significant difference between group B and group C. AUC (to differentiate between renal allograft rejection and well-functioning stable allograft) for cortical, and medullary FA values and cortical and medullary ADC values were 0.853(p < 0.001), 0.757(p = 0.004), 0.709(p = 0.021) and 0.736(p = 0.009), respectively. DTI is a promising functional MRI technique for the non-invasive assessment of renal allograft function. Diffusion parameters, such as FA and ADC values, can be useful in the differentiation of renal allograft rejection from well-functioning stable allograft.

Evaluation of Radiographic Contrast-Induced Nephropathy by Functional Diffusion Weighted Imaging.

Contrast-induced nephropathy (CIN) resembles an important complication of radiographic contrast medium (XCM) displayed by a rise in creatinine levels 48–72 h after XCM administration. The purpose of the current study was to evaluate microstructural renal changes due to CIN in high-risk patients by diffusion weighted (DWI) and diffusion tensor imaging (DTI). Fifteen patients (five CIN and ten non-CIN) scheduled for cardiological intervention were included in the study. All patients were investigated pre- and post-intervention on a clinical 3T scanner. After anatomical imaging, renal DWI was performed by a paracoronal echo-planar-imaging sequence. Renal clinical routine serum parameters and advanced urinary injury markers were determined to monitor renal function. We observed a drop in cortical and medullar apparent diffusion coefficient (ADC) and fractional anisotropy (FA) before and after XCM administration in the CIN group. In contrast, the non-CIN group differed only in medullary ADC. The decrease of ADC and FA was apparent even before serum parameters of the kidney changed. In conclusion, DWI/DTI may be a useful tool for monitoring high-risk CIN patients as part of multi-modality based clinical protocol. Further studies, including advanced analysis of the diffusion signal, may improve the identification of patients at risk for CIN.

Assessment of chronic allograft injury in renal transplantation using diffusional kurtosis imaging

BackgroundChronic allograft injury (CAI) is a significant reason for which many grafts were lost. The study was conducted to assess the usefulness of diffusional kurtosis imaging (DKI) technology in the non-invasive assessment of CAI.MethodsBetween February 2019 and October 2019, 110 renal allograft recipients were included to analyze relevant DKI parameters. According to estimated glomerular filtration rate (eGFR) (mL/min/ 1.73 m2) level, they were divided to 3 groups: group 1, eGFR ≥ 60 (n = 10); group 2, eGFR 30–60 (n = 69); group 3, eGFR < 30 (n = 31). We performed DKI on a clinical 3T magnetic resonance imaging system. We measured the area of interest to determine the mean kurtosis (MK), mean diffusivity (MD), and apparent diffusion coefficient (ADC) of the renal cortex and medulla. We performed a Pearson correlation analysis to determine the relationship between eGFR and the DKI parameters. We used the receiver operating characteristic curve to estimate the predicted values of DKI parameters in the CAI evaluation. We randomly selected five patients from group 2 for biopsy to confirm CAI.ResultsWith the increase of creatinine, ADC, and MD of the cortex and medulla decrease, MK of the cortex and medulla gradually increase. Among the three different eGFR groups, significant differences were found in cortical and medullary MK (P = 0.039, P < 0.001, P < 0.001, respectively). Cortical and medullary ADC and MD are negatively correlated with eGFR (r = − 0.49, − 0.44, − 0.57, − 0.57, respectively; P < 0.001), while cortical and medullary MK are positively correlated with eGFR (r = 0.42, 0.38; P < 0.001). When 0.491 was set as the cutoff value, MK's CAI assessment showed 87% sensitivity and 100% specificity. All five patients randomly selected for biopsy from the second group confirmed glomerulosclerosis and tubular atrophy/interstitial fibrosis.ConclusionThe DKI technique is related to eGFR as allograft injury progresses and is expected to become a potential non-invasive method for evaluating CAI.

Diffusion Tensor Imaging in early prediction of renal fibrosis in patients with renal disease: Functional and histopathological correlations.

Renal fibrosis (RF) is a well-known marker of chronic kidney disease (CKD) progression. However, renal biopsy is an available tool for evaluation of RF, non-invasive tools are needed not only to detect but also to monitor the progression of fibrosis. The aim of this study is to evaluate the role of diffusion tensor imaging (DTI) in the assessment of renal dysfunction and RF in patients with renal disease. Fifty-six patients with renal disorders and 22 healthy controls were recruited. All participants underwent DTI. Renal biopsy was performed for all patients. Mean renal medullary and cortical fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were compared between patients and healthy controls and correlated to serum creatinine (SCr), estimated glomerular filtration rate (eGFR), 24-h urinary protein (24h-UPRO) and renal histopathological scores. Cortical FA values were significantly higher (P=.001), while cortical ADC values were significantly lower in the patients' group (P=.002). Cortical FA values positively correlated to SCr (P=.006) and negatively correlated to eGFR (P=.03), while cortical ADC negatively correlated to percentage of sclerotic glomeruli, atrophic tubules and interstitial fibrosis (P=.001 for all variables). Medullary ADC negatively correlated to tubular atrophy (P=.02). The diagnostic performance of DTI for detecting RF was supported by ROC curve. Multiple linear regression analysis revealed that the mean cortex ADC was significantly decreased by 0.199mg/dL for patients with >50% glomerulosclerosis in renal biopsy. DTI appears to represent a valuable tool for the non-invasive assessment of renal dysfunction and renal fibrosis.

Diffusion tensor imaging in renal artery stenosis: a preliminary report.

To investigate the diffusion properties in the kidneys affected by renal artery stenosis (RAS) using diffusion tensor imaging (DTI). In this prospective study, 35 patients with RAS and 15 patients without renal abnormalities were enrolled and examined using DTI. Cortical and medullary regions of interest (ROIs) were located to obtain the corresponding values of the apparent diffusion coefficient (ADC) and fractional anisotropy (FA). The cortical and medullary ADC and FA were compared in the kidney affected by variable degrees of stenosis (RAS 50-75% and >75%) vs controls, using the one-way ANOVA and Student's t-test. The Spearman correlation test was used to correlate the mean ADC and FA values in the cortex and medulla with the estimate glomerular filtration rate (eGFR). For the controls, the ADC value was significantly (p = 0.03) higher in the cortex than in the medulla; the FA value was significantly (p = 0.001) higher in the medulla than in the cortex. Compared with the controls, a significant reduction in the cortical ADC was present with a RAS of 50-75% and >75% (p = 0.001 and 0.041, respectively); a significant reduction in the medullary FA was verified only for RAS >75% (p = 0.023). The Spearman correlation test did not show a statistically significant correlation between the cortical and medullary ADC and FA, and the eGFR. The alterations of the diffusional parameters caused by RAS can be detected by DTI and could be useful in the diagnostic evaluation of these patients. 1. Magnetic resonance DTI could provide useful information about renal involvement in RAS.2. Magnetic resonance DTI allows non-invasive repeatable evaluation of the renal parenchyma, without contrast media.

P0289MULTI-PARAMETRIC RENAL MAGNETIC RESONANCE IMAGING IN EARLY KIDNEY TRANSPLANTATION

Abstract Background and Aims Existing methods of investigating renal transplant dysfunction do not provide reliable information regarding diagnosis nor prognosis. Multi-parametric magnetic resonance imaging (MRI) may provide novel biomarkers for evaluation of transplant dysfunction. We aim to determine how MRI parameters change over the first year of transplantation, and how these relate to future renal function. Method Patients receiving a kidney transplant attended for study visits at 6, 26 and 52 weeks post operatively, comprising measurement of clinical and biochemical parameters, together with research multi-parametric MRI. Imaging measurements comprised kidney volume, arterial spin labelling (ASL) perfusion, T1 relaxation time, T2*, apparent diffusion coefficient (ADC) and fractional anisotropy (FA). Imaging was performed at 3.0 Tesla using a Siemens MAGNETOM Prisma system. Regions of interest were drawn in whole kidney (WK), cortex (Cx) and medulla (Md) (figure 1). Results 20 patients were included: 16 were male, with age 55.5±12.8 years, baseline eGFR 54.0±23.6 ml/min/1.73m2, and blood pressure 146/80 ± 15/15 mmHg. 14 received deceased, and 6 received live, donor transplants. Patients were all managed with tacrolimus, mycophenolate and low dose prednisolone, following induction therapy with either basiliximab or anti-thymocyte globulin. 6 week ADC was 1.69±0.14 in WK, 1.65±0.08 in Cx, and 1.67±0.10 ×10-3 mm2/s in Md. FA was 0.19±0.04 in WK, 0.14 ± 0.04 in Cx and 0.22 ± 0.10 in Md. T2* was 57.6±9.4 in WK, 63.9±8.7 in Cx and 45.0±8.0 ms in Md. Over the 3 visits there was reduction in FA (p=0.008) and medullary T2* (p&amp;lt;0.001). There was no significant change over 12 months in any other MRI parameter. Over 1 year the median change in eGFR was -2ml/min/1.73m2. There was correlation between baseline eGFR and the following variables: volume (r=0.29, p=0.04), whole kidney ADC (r=0.36, p=0.01), cortical ADC (r=0.46, p=0.001), representative cortex ADC (r=0.48, p&amp;lt;0.001) and medullary ADC (r=0.29, p=0.04). There was no correlation between eGFR and other imaging biomarkers. There was correlation between baseline whole kidney ADC (r=0.54, p=0.02), cortical ADC (r=0.49, p=0.03), and renal function at 12 months. Conclusion Diffusion weighted MRI measurements correlate with eGFR and may allow improved prognostication regarding future renal function. Certain MRI parameters including FA and R2* vary depending on time point of transplantation which may reflect changes in transplant microstructure in the early postoperative period. Multi-parametric MRI provides a novel method of evaluating renal transplants non-invasively and may allow more accurate prediction of future transplant function than existing biochemical measures.

Validity of diffusion-weighted magnetic resonance imaging in the evaluation of acute pyelonephritis in comparison with contrast-enhanced computed tomography.

PurposeApplications of diffusion-weighted magnetic resonance imaging outside the brain have gained increasing importance in recent years, and recent studies have shown the usage of diffusion-weighted (DW) imaging in diagnosing pyelonephritis based on renal cortical and medullary apparent diffusion coefficient (ADC) values. The aim of this study was to assess the validity of DW magnetic resonance (MR) imaging in comparison with contrast-enhanced computed tomography (CECT) in diagnosing pyelonephritis.Material and methodsA cross-sectional observational study was conducted for a period of six months in a tertiary hospital in Coimbatore. All patients with clinical and laboratory diagnosis of acute pyelonephritis, who were referred for radiological imaging (CECT), were taken into the study. Out of 112 patients with a clinical and laboratorial diagnosis of acute pyelonephritis (APN), who underwent both DW MR and CECT, diagnosis of APN was made in 100 patients based on CECT, while in 12 cases the investigation (CECT) was negative. Finally, these 100 patients were included in the study. The validity of DW MR imaging in diagnosing APN was assessed by deriving sensitivity, specificity, and positive and negative predictive value in comparison with CECT findings.ResultsThe validity report of DW MR imaging in the detection of APN showed a very high sensitivity (96-100%) and specificity (86-90%) and very low false positives (6-10%) and negatives (< 5%), and it also showed that in the areas of affected renal parenchyma ADC values were consistently lower compared to unaffected renal parenchyma.ConclusionBased on the generated hypothesis, DW MR imaging of the kidneys seems to be highly sensitive and specific for the detection of focal or diffuse infections within the kidney in comparison with CECT.

Multiparametric magnetic resonance imaging shows promising results to assess renal transplant dysfunction with fibrosis

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/1.73m2), and 12 with chronic dysfunction/established fibrosis (eGFR mean 30.1 ml/min/1.73m2), 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 R2*) and T1 quantification. True diffusion D, pseudodiffusion D*, perfusion fraction PF, apparent diffusion coefficient (ADC), fractional anisotropy (FA), R2* and T1 were calculated for cortex and medulla. ΔT1 was calculated as (100x(T1 Cortex-T1 Medulla)/T1 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 ΔT1 were all significantly decreased, while cortical T1 was significantly elevated in fibrotic allografts. Cortical T1 showed positive correlation to the Banff fibrosis and tubular atrophy scores. The combination of ΔT1 and cortical ADC had excellent cross-validated diagnostic performance for detection of chronic dysfunction with fibrosis. Cortical ADC and T1 had good performance for predicting eGFR decline at 18 months (4 or more ml/min/1.73m2/year). Thus, the combination of cortical ADC and T1 measurements shows promising results for the non-invasive assessment of renal allograft histology and outcomes.

Non-invasive evaluation of renal structure and function of healthy individuals with multiparametric MRI: Effects of sex and age

Clinically, when applying multiparametric magnetic resonance imaging (MRI) examinations in renal diseases, assessment of renal structure and function has to account for age- and sex-related effects. The aim of this study was to investigate the influence of age and sex on multiparametric MRI assessment of renal structure and function in healthy human beings. Studies on 33 healthy volunteers were performed using multiparametric MRI on a 3.0-Tesla MR scanner, including T1-weighted imaging, blood oxygen level-dependent MRI (BOLD MRI), diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI). Our results revealed that the mean renal cortical thickness (RCT), ratio of cortex to parenchyma (CPR), and cortical R2* values were higher in males than in females. The cortical R2* value was higher in older group than in younger group (18.57 ± 0.99 vs 17.53 ± 0.58, p = 0.001); there was no significant difference in medullary R2* between the older and younger groups (38.18 ± 2.96 vs 36.45 ± 2.47, p = 0.077). The parenchymal thickness (PT) and medullary fractional anisotropy (FA) were lower in older group than in younger group (1.547 ± 0.06 vs 1.604 ± 0.05, p = 0.005 and 0.343 ± 0.03 vs 0.371 ± 0.03, p = 0.016, respectively). Pearson’s correlation analysis showed that PT and medullary FA were inversely related with age (r = −0.483, p = 0.004; r = −0.446, p = 0.009) while cortical R2* values was positively related (r = 0.511, p = 0.002, respectively). The medullary apparent diffusion coefficient (ADC) value had a significant association with PT (r = 0.359, p = 0.04). This study indicated that multiparametric renal MRI parameters are age and sex dependent.

SUN-294 FUNCTIONAL MRI IN PREDICTING DIABETIC KIDNEY DISEASE

There are no known studies evaluating functional renal Magnetic Resonance Imaging (MRI) changes in Type 1 Diabetes (T1DM) compared to healthy controls. This is a prospective pilot study with a primary aim to evaluate if multi-parametric MRI can detect renal hypoxia (utilizing BOLD, Blood Oxygen Level Dependent) and structural changes (utilizing diffusion tensor imaging, DTI) in patients with T1DM, comparing patients with different stages of diabetic kidney disease (DKD) to healthy matched controls. 34 T1DM patients with variable degrees of renal impairment and 10 controls with intact renal function were recruited. Following an overnight fast, participants underwent physical examination, blood tests, 24-hour urine collection and functional MRI with controlled water intake. MRI parameters from two independent readers were obtained and analyzed. A value of T2*, from which resonance transverse relaxation rate (R2*) is calculated (1/T2*) is obtained from BOLD images. Functional anisotropy (FA) and apparent diffusion coefficient (ADC) values were obtained from DTI images. To determine measured Glomerular Filtration Rate (mGFR), each patient with T1DM underwent 99m-technetium- diethylene-triamine-penta-acetic acid (99mTc-DTPA) plasma clearance with Brochner-Mortensen correction. Univariate analysis was conducted with Mann-Whitney tests. The median mGFR for participants with T1DM was 105 (77,120) ml/min/1.73m2. 31% had hyperfiltration arbitrarily defined as an mGFR³120ml/ min/1.73m2. Participants with hyperfiltration were younger than the normofiltering group (31.5 years vs. 49.5 years, p=0.006). There were no other significant baseline characteristic differences between the two groups. There were also no significant baseline differences between participants with T1DM and healthy controlsR2* was significantly lower both in the cortex (14.7 [13.7-15.8] vs 15.7 [15.1-16.6], p<0.001) and medulla (24.8 [21.8,28.2] vs 29.3 [24.3,32.4], p<0.001) in participants with diabetes compared to healthy controls, respectively. Medullary FA was higher; while cortical FA was lower in diabetes compared to controls. On the other hand, there were no significant differences in both cortical and medullary ADC in participants with and without diabetes. Univariate comparison of MRI parameters between normofiltration and hyperfiltration showed no significant difference for cortical R2*, cortical FA and medullary FA. There was a marginally higher medullary R2* in the hyperfiltration 25.8(23.3,28.7)(1/s) compared to normofiltration 24.4(21.4,27.9)(1/s) (p=0.01) group. ADC in the cortex 2.61(2.53,2.74) (103mm2/s) vs. 2.40(2.29,2.53) (103mm2/s) (p<0.001) and medulla 2.46(2.34,2.58) vs. 2.27(2.08,2.48) (p=0.02) were also observed to be higher in the hyperfiltration group. A lower R2* in our diabetes cohort reflect higher intra-renal oxygen content in diabetes. Higher medullary R2* suggest that hypoxic changes in hyperfiltration to those without hyperfiltration. FA changes in T1DM compared to controls; as well as ADC changes in hyperfiltration also suggests that renal structural changes in DKD may be detected with functional MRI. Further larger studies are required to evaluate the utility of functional MRI in T1DM and hyperfiltration.

Quantitative assessment of renal structural and functional changes in chronic kidney disease using multi-parametric magnetic resonance imaging.

BackgroundMulti-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).MethodsWe 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.ResultsMRI 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.ConclusionComprehensive 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.

Validation of the corticomedullary difference in magnetic resonance imaging-derived apparent diffusion coefficient for kidney fibrosis detection: a cross-sectional study.

Kidney cortical interstitial fibrosis (IF) is highly predictive of renal prognosis and is currently assessed by the evaluation of a biopsy. Diffusion magnetic resonance imaging (MRI) is a promising tool to evaluate kidney fibrosis via the apparent diffusion coefficient (ADC), but suffers from inter-individual variability. We recently applied a novel MRI protocol to allow calculation of the corticomedullary ADC difference (ΔADC). We here present the validation of ΔADC for fibrosis assessment in a cohort of 164 patients undergoing biopsy and compare it with estimated glomerular filtration rate (eGFR) and other plasmatic parameters for the detection of fibrosis. This monocentric cross-sectional study included 164 patients undergoing renal biopsy at the Nephrology Department of the University Hospital of Geneva between October 2014 and May 2018. Patients underwent diffusion-weighted imaging, and T1 and T2 mappings, within 1 week after biopsy. MRI results were compared with gold standard histology for fibrosis assessment. Absolute cortical ADC or cortical T1 values correlated poorly to IF assessed by the biopsy, whereas ΔADC was highly correlated to IF (r=-0.52, P < 0.001) and eGFR (r = 0.37, P < 0.01), in both native and allograft patients. ΔT1 displayed a lower, but significant, correlation to IF and eGFR, whereas T2 did not correlate to IF nor to eGFR. ΔADC, ΔT1 and eGFR were independently associated with kidney fibrosis, and their combination allowed detection of extensive fibrosis with good specificity. ΔADC is better correlated to IF than absolute cortical or medullary ADC values. ΔADC, ΔT1 and eGFR are independently associated to IF and allow the identification of patients with extensive IF.

Diffusion-MR in kidney transplant recipients: is diuretic stimulation a useful diagnostic tool for improving differentiation between functioning and non-functioning kidneys?

ObjectivesTo evaluate the effects of diuretic stimulation on Diffusion Weighted Imaging (DWI) and Diffusion Tensor Imaging (DTI) techniques in transplanted kidneys. Methods33 transplanted kidney recipients underwent DWI and DTI sequences before and after furosemide. Cortical and medullary Apparent Diffusion Coefficient (ADC) and Fractional Anisotropy (FA) values were calculated in transplanted kidneys. Patients were divided into two groups according to their estimated glomerular rate filtration (Group A ≥ 60 ml/min and Group B < 60 ml/min). Wilcoxon matched pairs signed rank test was applied to compare pre- and post-furosemide values. ADC and FA values were compared between the 2 groups using a Mann-Whitney U test. Receiver Operating Curves (ROC) analysis was performed to predict normal renal function. ResultsWilcoxon test revealed a statistically significant difference for all pre- and post- ADC and FA values in group B. For group A, a significant difference was found comparing pre- and post-medullary ADC and FA values (p = 0.0151 and p = 0.0054).In the comparison between group A and group B, cortical and medullary mean ADC values were significantly different before and after furosemide. With regard to medullary FA values, a significant difference was found between groups before and after diuretic stimulation (p respectively of 0.004 and 0.042). Comparing cortical FA mean values, no statistical difference was observed between groups before and after furosemide.The highest Area Under Curve values were reported for cortical ADC (0.878) and medullary ADC (0.863) before diuretic bolus. ConclusionsIn transplanted kidneys, furosemide did not improve the differentiation between normal and reduced function.

Role of Diffusion Tensor Imaging in renal parenchymal changes.

Context:Diffusion Tensor Imaging (DTI) is a reliable noninvasive tool to assess renal function with medullary Fractional Anisotropy (FA) values showing the most consistent results.Aims:Evaluation of FA, Apparent Diffusion Coefficient (ADC) for detecting diabetic nephropathy (DN) using 1.5-Tesla magnetic resonance imaging (MRI). To determine FA and ADC values in chronic kidney disease (CKD) patients and controls, and comparing these with estimated glomerular filtiration rate (eGFR) and categorizing the stage of CKD.Patients and Methods:Thirty nondiabetic volunteers underwent DTI. The study included 83 diabetics, 30 frank urine proteinuric, 30 micro-albuminuric, 23 normo-albuminuric with only raised blood sugar patients. Patients were stratified by eGFR into groups: eGFR <60 and eGFR>60ml/min. ADC and FA values in cortex and medulla were compared between controls and study groups.Statistical Analysis Used:Analysis of variance and Pearson correlation using SPSS 16 were performed.Results:There was significant difference of FA medulla in controls versus albuminuric and micro-albuminuric versus frank proteinuric patients (P < 0.001). Also, there was significant difference between cortical ADC values between normal, microalbuminuric/proteinuric groups (P = 0.010, P =0.000, respectively). Significant difference between medullary FA values of patients with eGFR >60 and eGFR < 60 versus normal controls (P < 0.001) was noted. With declining renal function from normal to CKD category 5, a negative correlation between medullary FA (r= −0.785, P = 0.001) and ADC cortex values (r= −0.436, P = 0.001) was noted. A strong positive correlation between medullary FA and cortex ADC with eGFR (r = 0.598 and 0.344, respectively) was noted.Conclusion:Medullary FA of diabetics with relatively intact kidney function were significantly lower than those of controls. Hence, drop in medullary FA values can be an indicator of early nephropathy/patients at risk where eGFR is in near normal range. Cortical ADC and medullary FA demonstrated a significant correlation with eGFR with the latter showing a stronger positive correlation.

Prenatal Diagnosis of Renal Failure by Fetal Biparametric Magnetic Resonance Imaging

AbstractCongenital anomalies of the kidneys and urinary tract represent 93% of all prenatally diagnosed malformations. In the reported case, fetal Biparametric MRI (Bp-MRI) by morphologic (T1- and T2-weighted) and functional diffusion-weighted (DW) images allowed both diagnosis of congenital anomalies (e.g., hydrometrocolpos with septate vagina and uterus didelphys), and associated malfunction of kidneys by means of measurement of cortical and medullary apparent diffusion coefficient (ADC) values.

Assessment of renal allograft function early after transplantation with isotropic resolution diffusion tensor imaging.

To investigate the value of diffusion tensor imaging (DTI) and tractography in renal allografts at the early stage after kidney transplantation. This study was approved by the institutional ethical review committee, and written informed consent was obtained. A total of 54 renal allograft recipients 2-3weeks after transplantation and 26 age-matched healthy volunteers underwent renal DTI with a 3.0-T magnetic resonance imaging (MRI) system. Recipients were divided into three groups according to the estimated glomerular filtration rate (eGFR). Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of the cortex and medulla were measured and compared among the groups. Whole-kidney tractography was performed. Correlation of eGFR with diffusion parameters was evaluated. In allografts with stable function, the medullary ADC was higher and the cortical FA was lower (p < 0.001) than in healthy kidneys. The cortical ADC, medullary ADC and FA decreased as the allograft function declined, and with a positive correlation with eGFR (p < 0.001); cortical FA did not. Tractography demonstrated a decrease of tract density in impaired functional allografts. Renal DTI produces reliable results to assess renal allograft function at the early stage after transplantation. • DTI and tractography can evaluate renal allograft function at an early stage • Medullary FA, cortical and medullary ADC can effectively evaluate allograft function • Medullary FA, cortical and medullary ADC are correlated with eGFR in renal allografts • Medullary ADC increased and cortical FA decreased in stable allografts compared to control subjects • Medullary FA, cortical and medullary ADC decreased and allograft function declined.

Assessment of renal fibrosis in chronic kidney disease using diffusion-weighted MRI

To assess the performance of diffusion-weighted magnetic resonance imaging (MRI) for the assessment of renal fibrosis in chronic kidney disease (CKD), with histopathology as a reference standard. Forty patients with CKD and 30 healthy volunteers were recruited for the study. All participants underwent diffusion-weighted MRI. Renal biopsy was performed in 25 patients with CKD. Mean renal medullary and cortical apparent diffusion coefficient (ADC) values were compared between CKD patients and the healthy volunteers. Pearson's correlation coefficient was calculated to investigate the relationship between ADC values, serum creatinine (SCr), estimated glomerular filtration rate (eGFR), 24 h urinary protein (24h-UPRO), and renal histopathological scores. Cortical and medullary ADC values in the CKD group were significantly lower compared to those in the healthy controls. In the CKD group, a significant negative correlation was found between cortical ADC values and SCr/24h-UPRO, and significant positive correlation was found between cortical ADC and eGFR. There was also a significant negative correlation between medullary ADC values and SCr. Both cortical and medullary ADC values were significantly correlated with histopathological fibrosis score. Renal ADC values strongly correlate with histological measures of fibrosis, and have the potential to enhance the non-invasive monitoring of chronic kidney disease.