Renal T2 Research Articles

Feasibility and Reproducibility of T2 Mapping Compared with Diffusion-Weighted Imaging in Solid Renal Masses.

Accurate prediction of renal mass subtypes, along with the WHO/ISUP grade and pathological T (pT) stage of clear cell renal cell carcinoma (ccRCC), is crucial for optimal decision making. Our study aimed to investigate the feasibility and reproducibility of motion-robust radial T2 mapping in differentiating lipid-poor angiomyolipoma (MFAML) from RCC and characterizing the WHO/ISUP grade and pT stage of ccRCC. Finally, 92 patients undergoing renal radial T2 mapping and ZOOMit DWI were recruited. The T2 values and apparent diffusion coefficient (ADC) were analyzed. Correlation coefficients were calculated between ADC and T2 values. Notably, ccRCC exhibited higher T2 and ADC values than MFAML (p < 0.05). T2 values were lower in the higher WHO/ISUP grade and pT stage of ccRCC (all p < 0.05). ADC showed no significant difference for pT stage (p = 0.056). T2 values revealed a higher area under the curve (AUC) in evaluating the WHO/ISUP grade compared to ADC (0.936 vs. 0.817, p = 0.027). T2 values moderately positively correlated with ADC (r = 0.675, p < 0.001). In conclusion, quantitative motion-robust radial T2 mapping is feasible for characterizing solid renal masses and could provide additional value for multiparametric imaging in predicting WHO/ISUP grade and pT stage of ccRCC.

Fast and High-Resolution T2 Mapping Based on Echo Merging Plus k-t Undersampling with Reduced Refocusing Flip Angles (TEMPURA) as Methods for Human Renal MRI.

To develop a highly accelerated multi-echo spin-echo method, TEMPURA, for reducing the acquisition time and/or increasing spatial resolution for kidney T2 mapping. TEMPURA merges several adjacent echoes into one k-space by either combining independent echoes or sharing one echo between k-spaces. The combined k-space is reconstructed based on compressed sensing theory. Reduced flip angles are used for the refocusing pulses, and the extended phase graph algorithm is used to correct the effects of indirect echoes. Two sequences were developed: a fast breath-hold sequence; and a high-resolution sequence. The performance was evaluated prospectively on a phantom, 16 healthy subjects, and two patients with different types of renal tumors. The fast TEMPURA method reduced the acquisition time from 3-5 min to one breath-hold (18 s). Phantom measurements showed that fast TEMPURA had a mean absolute percentage error (MAPE) of 8.2%, which was comparable to a standardized respiratory-triggered sequence (7.4%), but much lower than a sequence accelerated by purely k-t undersampling (21.8%). High-resolution TEMPURA reduced the in-plane voxel size from 3 × 3 to 1 × 1 mm2, resulting in improved visualization of the detailed anatomical structure. In vivo T2 measurements demonstrated good agreement (fast: MAPE = 1.3%-2.5%; high-resolution: MAPE = 2.8%-3.3%) and high correlation coefficients (fast: R = 0.85-0.98; high-resolution: 0.82-0.96) with the standardized method, outperforming k-t undersampling alone (MAPE = 3.3-4.5%, R = 0.57-0.59). TEMPURA provides fast and high-resolution renal T2 measurements. It has the potential to improve clinical throughput and delineate intratumoral heterogeneity and tissue habitats at unprecedented spatial resolution.

Improvements in Between-Vendor MRI Harmonization of Renal T2 Mapping using Stimulated Echo Compensation.

T2 mapping is valuable to evaluate pathophysiology in kidney disease. However, variations in T2 relaxation time measurements across MR scanners and vendors may occur requiring additional correction. To harmonize renal T2 measurements between MR vendor platforms, and use an extended-phase-graph-based fitting method ("StimFit") to correct stimulated echoes and reduce between-vendor variations. Prospective. 8 healthy "travelling" volunteers (37.5% female, 32 ± 6 years) imaged on four MRI systems across three vendors at four sites, 10 healthy volunteers (50% female, 32 ± 8 years) scanned multiple times on a given MR scanner for repeatability evaluation. ISMRM/NIST system phantom scanned for evaluation of T2 accuracy. 3T, multiecho spin-echo sequence. T2 images fit using conventional monoexponential fitting and "StimFit." Mean absolute percentage error (MAPE) of phantom measurements with reference T2 values. Average cortex and medulla T2 values compared between MR vendors, with masks obtained from T2-weighted images and T1 maps. Full-width-at-half-maximum (FWHM) T2 distributions to evaluate local homogeneity of measurements. Coefficient of variation (CV), linear mixed-effects model, analysis of variance, student's t-tests, Bland-Altman plots, P-value <0.05 considered statistically significant. In the ISMRM/NIST phantom, "StimFit" reduced the MAPE from 4.9%, 9.1%, 24.4%, and 18.1% for the four sites (three vendors) to 3.3%, 3.0%, 6.6%, and 4.1%, respectively. In vivo, there was a significant difference in kidney T2 measurements between vendors using a monoexponential fit, but not with "StimFit" (P = 0.86 and 0.92, cortex and medulla, respectively). The intervendor CVs of T2 measures were reduced from 8.0% to 2.6% (cortex) and 7.1% to 2.8% (medulla) with StimFit, resulting in no significant differences for the CVs of intravendor repeat acquisitions (P = 0.13 and 0.05). "StimFit" significantly reduced the FWHM of T2 distributions in the cortex and whole kidney. Stimulated-echo correction reduces renal T2 variation across MR vendor platforms. 2 TECHNICAL EFFICACY: Stage 1.

Evaluation of Kidney Injury Using Arterial Spin Labeling and Blood Oxygen Level-Dependent MRI: An Experimental Study in Rats With Carbon Tetrachloride-Induced Liver Cirrhosis.

Serum creatinine (Scr) may be not suited to timely and accurately reflect kidney injury related to chronic liver disease. Currently, the ability of arterial spin labeling (ASL) and blood oxygen level-dependent (BOLD) sequences to evaluate renal blood flow (RBF) and blood oxygen in chronic liver disease remains to be verified. To investigate the value of ASL and BOLD imaging in evaluating hemodynamics and oxygenation changes during kidney injury in an animal model of chronic liver disease. Prospective. Chronic liver disease model was established by subcutaneous injection of carbon tetrachloride. Forty-three male Sprague-Dawley rats (8 weeks) were divided into a pathological group (0, 2, 4, 6, 8, 12 weeks, each group: N = 6) and a continuous-scanning group (N = 7). 3-T, ASL, BOLD, and T2W. Regions of interest in the cortex (CO), outer stripe of the outer medulla (OSOM), and inner stripe of the outer medulla (ISOM) are manually delineated. The RBF and T2* values at each time point (0, 2, 4, 6, 8, 12 weeks) are measured and compared. Hematoxylin-eosin score (HE Score, damage area scoring method), alpha-smooth muscle actin (α-SMA), hypoxia-inducible factor-1alpha (HIF-1α), peritubular capillar (PTC) density, Scr, and neutrophil gelatinase-associated lipocalin were harvested. Analysis of variance, Spearman correlation analysis, Kruskal-Wallis tests, and receiver operating characteristic analysis with the area under the curve (AUC). A P-value <0.05 was considered statistically significant. Renal RBF and T2* values of CO, OSOM, and ISOM were significantly different from baseline. Both RBF and T2* were significantly correlated with HE Score, α-SMA, HIF-1α, and PTC density (|r| = 0.406-0.853). RBF demonstrated superior diagnostic capability in identifying severe kidney injury in this model of chronic liver disease (AUC = 0.964). Imaging by ASL and BOLD may detect renal hemodynamics and oxygenation changes related to chronic liver disease early. 5 TECHNICAL EFFICACY: Stage 2.

T1 mapping combined with arterial spin labeling MRI to identify renal injury in patients with liver cirrhosis.

We investigated the capability and imaging criteria of T1 mapping and arterial spin labeling (ASL) MRI to identify renal injury in patients with liver cirrhosis. We recruited 27 patients with cirrhosis and normal renal function (cirrhosis-NR), 10 with cirrhosis and renal dysfunction (cirrhosis-RD) and 23 normal controls (NCs). All participants were examined via renal T1 mapping and ASL imaging. Renal blood flow (RBF) derived from ASL was measured from the renal cortex, and T1 values were measured from the renal parenchyma (cortex and medulla). MRI parameters were compared between groups. Diagnostic performances for detecting renal impairment were statistically analyzed. Cortical T1 (cT1) and medullary T1 (mT1) were significantly lower in the NCs than in the cirrhosis-NR group. The cortical RBF showed no significant changes between the NCs and cirrhosis-NR group but was markedly decreased in the cirrhosis-RD group. The areas under the curve (AUCs) for discriminating cirrhosis-NR from NCs were 0.883 and 0.826 by cT1 and mT1, respectively. Cortical RBF identified cirrhosis-RD with AUC of 0.978, and correlated with serum creatinine (r = -0.334) and the estimated glomerular filtration rate (r = 0.483). A classification and regression tree based on cortical RBF and cT1 achieved 85% accuracy in detecting renal impairment in the cirrhosis. Renal T1 values might be sensitive predictors of early renal impairment in patients with cirrhosis-NR. RBF enabled quantifying renal perfusion impairment in patients with cirrhosis-RD. The diagnostic algorithm based on cortical RBF and T1 values allowed detecting renal injury during cirrhosis.

Pattern and clinical correlates of renal iron deposition in adult beta-thalassemia major patients.

We evaluated pattern and clinical correlates of renal T2* measurements in adult β-thalassemia major (β-TM) patients. Ninety β-TM patients (48 females, 38.15 ± 7.94years), consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia network, underwent T2* magnetic resonance imaging (MRI) for quantification of iron overload (IO) in kidneys, liver, pancreas, and heart. Ten (11.1%) patients showed renal IO (T2* < 31ms). Global kidney T2* values did not show a correlation with gender, age, splenectomy, regular transfusions or chelation starting age, pre-transfusion hemoglobin, and serum ferritin levels. Global kidney T2* values showed an inverse correlation with MRI liver iron concentration (LIC) values (R = - 0.349; p = 0.001) and a positive correlation with global pancreas T2* values (R = 0.212; p = 0.045). Frequency of renal IO was significantly higher in patients with cardiac IO than in patients without cardiac IO (50.0% vs. 6.3%; p = 0.001). A significant inverse association was detected between global kidneys T2* values and lactate dehydrogenase (LDH) (R = - 0.529; p < 0.0001). In multivariate regression analysis, MRI LIC and LDH were the strongest predictors of global kidney T2* values. A MRI LIC > 4.83mg/g dw predicted the presence of renal IO (sensitivity = 90.0%; specificity = 61.2%). Global kidney T2* values were inversely correlated with uric acid (R = - 0.269; p = 0.025). In conclusion, in adult β-TM patients, renal iron deposition is not common and is linked to both hemolysis and total body iron overload.

#4572 EFFECTS OF EMPAGLIFLOZIN ON KIDNEY AND CARDIAC MRI MEASURES IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Abstract Background and Aims EMPA-KIDNEY demonstrated empagliflozin reduced the risk of kidney disease progression or cardiovascular death in patients with CKD at risk of progression, but the mechanisms of benefit are uncertain. MRI was used to assess whether empagliflozin modified the structure and function of the kidneys and heart at around 18 months after randomization. Method Randomized participants from 8 sites in UK and Germany without a contraindication to MRI scanning, were eligible and invited to participate in this substudy. MRI scans were performed using a standardized protocol. Renal T1 mapping (MOLLI 5[3]3 scheme which measures fibrosis and inflammation) was computed by first segmenting MOLLI data using a U-net and then applying the masks to both kidneys. Cardiac MRI included cine steady-state free precession imaging to assess biventricular volumes, mass and function, and T1 mapping to assess myocardial inflammation and fibrosis. The primary outcome was kidney cortical T1 mapping measured by MOLLI. Secondary outcomes included LV ejection fraction, myocardial T1 MOLLI and LV mass index. Differences in MRI measurements between treatment groups were analysed using linear regression adjusted for baseline age, sex, eGFR, UACR and diabetes status. 172 participants were required to provide 90% power at 2p = 0.05 to detect a 50 ms difference in T1. Results 172 participants had an MRI scan around 18 months after randomization. 93 (54%) were allocated empagliflozin and 79 (46%) placebo. Mean (SD) age was 60 (15) years, 26% were female and 23% had diabetes. Mean eGFR was 37 (13) mL/min/1.73m2 and geometric mean (95% CI) UACR was 242 (182-322) mg/g (Table 1). Adjusted mean (SE) cortical T1 mapping by MOLLI was 1623 (10) ms in those allocated empagliflozin versus 1634 (11) ms in those allocated placebo, difference in means (95% CI) −11 (−41 to 18), P = 0.45 (Table 2). Medullary T1 MOLLI scores were similar. Empagliflozin had no significant effect on cardiac MRI measures: difference (95% CI) in LV ejection fraction 1% (−1 to 4); myocardial T1 MOLLI −3 ms (−16 to 10); LV mass index −3 g/m2 (−5 to 0) (Table 2). Conclusion Empagliflozin had no significant effect on MRI-based measures of fibrosis within the kidney cortex or myocardium in people with CKD at risk of progression. There was no effect of treatment on measures of cardiac structure or function. Further MRI measures will be available for presentation by the time of the ERA congress. Funding Boehringer Ingelheim, Eli Lilly and others; Clinicaltrials.gov:NCT03594110.

The Evaluation of Renal Iron Deposition With a 3 Tesla MRI Device in Beta-Thalassemia Major Patients.

Background and objective Beta-thalassemia is the most frequent monogenic disease in the world. In beta-thalassemia major (BTM) patients, blood transfusions for severe anemia usually cause iron overload, leading to increased morbidity and mortality. In this study, we aimed to examine the iron overload in the kidneys of BTM patients with a 3 Tesla (3T) MRIdevice and assess the relationship between iron overload in the liver and heart as well as serum ferritin levels. Methods This was a retrospective study covering the period between November 2014 and March 2015. MRI was performed on 21 patients with BTM who were receiving blood transfusions and chelation therapy. The control group (n=11) included healthy volunteers. A 3TMRI device(Ingenia, Philips, Best, The Netherlands) using a 16-channel phased array SENSE-compatible torso coil was used. Three-point DIXON (mDIXON) sequence and the relaxometry method were employed to measure iron overload. Both kidneys were analyzed via mDIXON sequence for atrophy or variations. Afterward, the images in which renal parenchyma could be distinguished best were selected. Iron deposition was analyzed via the relaxometry method using a unique software (CMR Tools, London, UK). All data were analyzed using IBM SPSS Statistics v.21 (IBM Corp., Armonk, NY). The Kolmogorov-Smirnov test, independent samples t-test, Mann-Whitney U test, and Pearson's and Spearman's rho correlation coefficient were used. A p-value <0.05 was considered statistically significant. Results There was a statistically significant relationship between beta-thalassemia patients who had cardiac iron deposition and those who did not in terms of T2* time (p=0.02). In contrast, there was nosimilar relationship for liver iron deposition (p>0.05). Renal T2* valueswere significantly different between the patient and control groups (p=0.029). T2* times were significantly different between patients who had ferritin levels below2500 ng/ml and those withferritin levels above2500 ng/ml (p=0.042). Conclusion Based on our findings, 3T MRI is a safe and reliable tool for screening iron overload in BTM patients as it makes distinguishing between renal parenchyma and renal sinus much easier and as it is more sensitive to iron deposition.

Impact of surgical management of upper tract urothelial cancer in octogenarians: A population-based study.

Upper tract urothelial carcinoma (UTUC) is an aggressive disease with a high progression rate. The standardmanagement for this disease is nephroureterectomy. Nephron sparing nonradical surgery is an alternative therapeutic approach. In men with limited life expectancy, the potential harm of UTUC progression must be weighed against surgical morbidity and mortality, and thus, more conservative approaches may be selected. This study aims to investigate the comparative benefits of radical and conservative surgical management in patients older than 80 years with localized UTUC. A search was conducted in the Surveillance, Epidemiology, and End Results database for patients older than 80 years who were diagnosed with localized (T1-2N0M0) cancer in the renal pelvis or ureter as the only malignancy from 2004 to 2015. Patients were divided into 3 therapeutic groups: no surgery, local intervention (ie, local tumor excision or segmented ureterectomy), and radical surgery (nephroureterectomy). Demographic and cancer-related parameter data were collected. Logistic regression analysis was conducted to investigate predictors for surgical treatment. Kaplan-Meier curves and Cox regression were used to analyze survival outcomes. Data from 774 patients were analyzed, including 205 in the no-surgery group, 181 in the local intervention group, and 388 in the radical surgery group. Older, African American patients with T1 stage disease were less likely to receive surgical treatment. Among surgically treated patients, renal pelvic tumors, and high-grade and T2 stage disease were associated with radical resection. Surgically treated patients had a longer median overall survival (OS) than in those treated nonsurgically (13, 35, and 47 months in no-surgery, local intervention, and radical surgery groups, respectively; p < 0.001). Although surgically treated patients demonstrated higher 5-year OS (8.8% [no surgery], 23.2% [local intervention], and 23.5% [radical surgery], p < 0.001) and 5-year disease-specific survival (DSS) (41.0%[no surgery], 69.1%[local intervention], and 72.9%[radical surgery]; p < 0.001) than in those treated nonsurgically, no significant differences were found between the local intervention and radical surgery groups (p > 0.05). Based on multivariate Cox regression analysis, surgical treatments, including both nonradical and radical resection, were independently associated with improved OS and DSS after controlling for age, marital status, tumor grade, and radiation status. Patients older than 80 years with localized UTUC who undergo surgery demonstrate longer survival. Radical and nonradical resections seemto have similar OS and DSS outcomes. Thus, when clinically indicated in this population, a more conservative surgical approach may be reasonable.

Variability of noninvasive MRI and biological markers in compensated cirrhosis: insights for assessing disease progression

BackgroundWe annually monitored stable compensated cirrhosis (CC) patients to evaluate serial variation in blood serum, liver stiffness, and multiparametric magnetic resonance imaging (mpMRI) measures to provide reference change values (RCV) and sample size measures for future studies.MethodsPatients were recruited from a prospectively followed CC cohort, with assessments at baseline and annually over three years. We report on blood markers, transient elastography liver stiffness measures (LSM) and noninvasive mpMRI (volume, T1 mapping, blood flow, perfusion) of the liver, spleen, kidneys, and heart in a stable CC group and a healthy volunteer (HV) group. Coefficient of variation over time (CoVT) and RCV are reported, along with hazard ratio to assess disease progression. Sample size estimates to power future trials of cirrhosis regression on mpMRI are presented.ResultsOf 60 CC patients enrolled, 28 with stable CC were followed longitudinally and compared to 10 HVs. CoVT in mpMRI measures was comparable between CC and HV groups. CoVT of Enhanced Liver Fibrosis score was low (< 5%) compared to Fibrosis-4 index (17.9%) and Aspartate Aminotransferase-to-Platelet-Ratio Index (19.4%). A large CoVT (20.7%) and RCV (48.3%) were observed for LSM. CoVT and RCV were low for liver, spleen, and renal T1 values (CoVT < 5%, RCV < 8%) and volume (CoVT < 10%, RCV < 16%); haemodynamic measures were high (CoVT 12–25%, RCV 16–47%).ConclusionsEvidence of low CoVT and RCV in multiorgan T1 values. RCV and sample size estimates are provided for future longitudinal multiorgan monitoring in CC patients.Trial registrationClinicalTrials.gov identifier: NCT02037867, Registered: 05/01/2013.

Frequency, pattern, and associations of renal iron accumulation in sickle/β-thalassemia patients.

We evaluated frequency, pattern, and associations of renal iron accumulation in sickle/β-thalassemia. Thirty-three sickle/β-thalassemia patients (36.5 ± 14.7years; 13 females), 14 homozygous sickle cell disease (SCD) patients, and 71 thalassemia major (TM) patients, enrolled in the E-MIOT Network, underwent magnetic resonance imaging. Iron overload (IO) was quantified by the T2* technique. Sickle/β-thalassemia patients had a significantly lower frequency of renal IO (T2* < 31ms) than homozygous SCD patients (9.1% vs. 57.1%; P = 0.001), besides having similar hepatic, cardiac and pancreatic IO. Kidney T2* values were comparable between regularly transfused sickle/β-thalassemia and TM patients but were significantly lower in regularly transfused homozygous SCD patients than in the other two groups. In sickle/β-thalassemia patients, global renal T2* values were not associated with age, gender, splenectomy, and presence of regular transfusions or chelation. No correlation was detected between renal T2* values and serum ferritin levels or iron load in the other organs. Global renal T2* values were not associated with serum creatinine levels but showed a significant inverse correlation with serum lactate dehydrogenase (R = - 0.709; P < 0.0001) and indirect bilirubin (R = - 0.462; P = 0.012). Renal IO is not common in sickle/β-thalassemia patients, with a prevalence significantly lower compared to that of homozygous SCD patients, but with a similar underlying mechanism due to the chronic hemolysis.

Assessment of Fasudil on Contrast-Associated Acute Kidney Injury Using Multiparametric Renal MRI.

Aims: To evaluate the utility of fasudil in a rat model of contrast-associated acute kidney injury (CA-AKI) and explore its underlying mechanism through multiparametric renal magnetic resonance imaging (mpMRI). Methods: Experimental rats (n = 72) were grouped as follows: controls (n = 24), CA-AKI (n = 24), or CA-AKI + Fasudil (n = 24). All animals underwent two mpMRI studies (arterial spin labeling, T1 and T2 mapping) at baseline and post iopromide/fasudil injection (Days 1, 3, 7, and 13 respectively). Relative change in renal blood flow (ΔRBF), T1 (ΔT1) and T2 (ΔT2) values were assessed at specified time points. Serum levels of cystatin C (CysC) and interleukin-1β (IL-1β), and urinary neutrophil gelatinase-associated lipocalin (NGAL) concentrations were tested as laboratory biomarkers, in addition to examining renal histology and expression levels of various proteins (Rho-kinase [ROCK], α-smooth muscle actin [α-SMA]), hypoxia-inducible factor-1α (HIF-1α), and transforming growth factor-β1 (TGF-β1) that regulate renal fibrosis and hypoxia. Results: Compared with the control group, serum levels of CysC and IL-1β, and urinary NGAL concentrations were clearly increased from Day 1 to Day 13 in the CA-AKI group (all p < 0.05). There were significant reductions in ΔT2 values on Days 1 and 3, and ΔT1 reductions were significantly more pronounced at all time points (Days 1–13) in the CA-AKI + Fasudil group (vs. CA-AKI) (all p < 0.05). Fasudil treatment lowered expression levels of ROCK-1, and p-MYPT1/MYPT1 proteins induced by iopromide, decreasing TGF-β1 expression and suppressing both extracellular matrix accumulation and α-SMA expression relative to untreated status (all p < 0.05). Fasudil also enhanced PHD2 transcription and inhibition of HIF-1α expression after CA-AKI. Conclusions: In the context of CA-AKI, fasudil appears to reduce renal hypoxia, fibrosis, and dysfunction by activating (Rho/ROCK) or inhibiting (TGF-β1, HIF-1α) certain signaling pathways and reducing α-SMA expression. Multiparametric MRI may be a viable noninvasive tool for monitoring CA-AKI pathophysiology during fasudil therapy.

Multiparametric quantitative renal MRI in children and young adults: comparison between healthy individuals and patients with chronic kidney disease

Multiparametric quantitative renal MRI may provide noninvasive radiologic biomarkers of chronic kidney disease (CKD) based on investigations in animal models and adults. We aimed to (1) obtain normative multiparametric quantitative MRI data from the kidneys of healthy children and young adults, (2) compare MRI measurements between healthy control participants and patients with CKD, and (3) determine if MRI measurements correlate with clinical and laboratory data as well as histology. This was a prospective, case-control study of 20 healthy controls and 12 CKD patients who underwent percutaneous renal biopsy ranging from 12 to 23years of age between October 2018 and March 2020. Kidney function was documented and pathology assessed for fibrosis/inflammation. Utilizing a field strength of 1.5T, we examined renal T1, T2, and T2* relaxation mapping, MR elastography (MRE), and diffusion-weighted imaging (DWI). A single analyst made all manual measurements for quantitative MRI pulse sequences. Independent measurements from cortex, medulla, and whole kidney were obtained by drawing regions of interest on single slices from the upper, mid, and lower kidney. A weighted average was calculated for each kidney; if two kidneys, the right and left were averaged. Continuous variables were compared with Mann-Whitney U test; bivariate relationships were assessed using Spearman rank-order correlation. Median estimated glomerular filtration rate (eGFR) was 112.3ml/min/1.73 m2 in controls (n = 20, 10 females) and 55.0ml/min/m2 in CKD patients (n = 12, 2 females) (p < 0.0001). Whole kidney (1333 vs. 1291ms; p = 0.018) and cortical (1212 vs 1137ms; p < 0.0001) T1 values were higher in CKD patients. Cortical T1 values correlated with eGFR (rho = -0.62; p = 0.0003) and cystatin C (rho = 0.58; p = 0.0007). Whole kidney (1.87 vs. 2.02 10-3 mm2/s; p = 0.007), cortical (1.89 vs. 2.04 10-3 mm2/s; p = 0.008), and medullary (1.87 vs. 1.98 10-3 mm2/s; p = 0.0095) DWI apparent diffusion coefficients (ADC) were lower in CKD patients. Whole kidney ADC correlated with eGFR (rho = 0.45; p = 0.012) and cystatin C (rho = -0.46; p = 0.009). Cortical histologic inflammation correlated with DWI ADC (rho = -0.71; p = 0.011). Renal T1 relaxation and DWI ADC measurements differ between pediatric healthy controls and CKD patients, correlate with laboratory markers of CKD, and may have histologic correlates.

Frequency, Pattern, and Associations of Renal Iron Accumulation in Sickle Beta-Thalassemia

▪Background: Chronically transfused homozygous sickle cell disease (HbSS) patients were shown to have higher kidney iron deposition than thalassemia major patients, not associated to total body iron and mainly caused by chronic hemolysis. Kidney iron deposition has not been explored in sickle beta-thalassemia (Sβ-thal), resulting from the inheritance of both sickle cell and beta-thalssemia genes.Aim: This multi center study aimed to study frequency, pattern, and associations of renal iron accumulation in sickle beta-thalassemia.Methods: Thirty-three Sβ-thal patients (36.49±14.72 years; 13 females) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia (E-MIOT) network were considered. Moreover, 20 healthy subjects, 14 HbSS patients and 71 thalassemia major (TM) patients were included as comparison groups. Hepatic, cardiac, pancreatic, and renal iron overload was quantified by the gradient-echo T2* technique. In each kidney T2* was measured in anterior, posterolateral, and posteromedial parenchymal regions and the global T2* value was calculated as the average of the two kidneys T2* values.Results. Global renal T2* were significantly higher in healthy subjects versus both Sβ-thal patients (49.68±10.09 ms vs 43.19±8.07 ms; P=0.013) and HbSS patients (49.68±10.09 ms vs 26.21±17.07 ms; P<0.0001).Sβ-thal patients showed comparable age, sex, frequency of regular transfusion, hematochemical parameters, and hepatic, cardiac and pancreatic iron load than HbSS patients, but they had a significant lower frequency of renal iron overload (global renal T2*<31 ms) (9.1% vs 57.1%; P=0.001).Regularly transfused patients (16 Sβ-thal and 10 HbSS) were compared with TM patients, homogeneous for age and sex, but TM started regular transfusions significantly earlier and they were more frequently chelated. No significant difference was detected in terms of hepatic and cardiac iron levels, but TM patients had significantly lower pancreas T2* values than both the other two groups and significantly higher global renal T2* values than HbSS patients (42.87±9.43 ms vs 24.39±15.74 ms; P=0.001).In Sβ-thal patients no significant difference was detected between T2* values in left and right kidneys, and global renal T2* values were not associated to age, gender, splenectomy, and they were comparable between regularly transfused and non transfused patients.No correlation was detected between renal T2* values and serum ferritin levels or iron load in the other organs.Global renal T2* values were not associated with serum creatinine levels but showed a significant inverse correlation with serum lactate dehydrogenase (Figure 1).Conclusion. Renal iron deposition is not common in Sβ-thal patients, with a prevalence significantly lower compared to that of HbSS patients, but with a similar underlying mechanism due to the chronic hemolysis. [Display omitted] DisclosuresPepe: Bayer S.p.A.: Other: no profit support; Chiesi Farmaceutici S.p.A: Other: no profit support. Maggio: Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene Corp: Membership on an entity's Board of Directors or advisory committees; Bluebird Bio: Membership on an entity's Board of Directors or advisory committees.

Quantification of renal T2 relaxation rate by use of blood oxygen level-dependent magnetic resonance imaging before and after furosemide administration in healthy Beagles.

To assess the feasibility of blood oxygen level-dependent (BOLD) MRI for measurement of the renal T2* relaxation rate (R2*; proxy for renal oxygenation) before and after furosemide administration and to evaluate the reliability and repeatability of those measurements in healthy dogs. 8 healthy adult Beagles (4 males and 4 females). Each dog was anesthetized and underwent BOLD MRI before (baseline) and 3 minutes after administration of furosemide (1 mg/kg, IV) twice, with a 1-week interval between scanning sessions. Mapping software was used to process MRI images and measure R2* and the difference in R2* (ΔR2*) before and after furosemide administration. The intraclass correlation coefficient was calculated to assess measurement reliability, and the coefficient of variation and Bland-Altman method were used to assess measurement repeatability. Mean ± SD baseline R2* in the renal medulla (24.5 ± 3.8 seconds-1) was significantly greater than that in the renal cortex (20.6 ± 2.7 seconds-1). Mean R2* in the renal cortex (18.6 ± 2.6 seconds-1) and medulla (17.8 ± 1.5 seconds-1) decreased significantly after furosemide administration. Mean ΔR2* in the medulla (6.7 ± 2.4 seconds-1) was significantly greater than that in the renal cortex (2.1 ± 0.7 seconds-1). All R2* and ΔR2* values had good or excellent reliability and repeatability, except the cortical ΔR2*, which had poor repeatability. Results suggested that BOLD MRI, when performed before and after furosemide administration, was noninvasive and highly reliable and repeatable for dynamic evaluation of renal oxygenation in healthy dogs.

Noninvasive assessment of kidney dysfunction in children by using blood oxygenation level-dependent MRI and intravoxel incoherent motion diffusion-weighted imaging

ObjectivesTo explore whether multiparametric approach including blood oxygenation level-dependent MRI (BOLD-MRI) and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) can be applied in the assessment of renal function in children with chronic kidney disease (CKD).Materials and methodsThis prospective study included 74 children (CKD stage 1–3, 51; CKD stage 4–5, 12; healthy volunteers, 11) for renal MRI examinations including coronal T2WI, axial T1WI and T2WI, BOLD-MRI, and DWI sequences. We measured the renal cortex and medulla T2*, ADC, Dt, Dp, and fp values on BOLD and DWI images. Appropriate statistical methods were applied for comparing MRI-derived parameters among the three groups and calculating the correlation coefficients between MRI-derived parameters and clinical data. Receiver operating characteristic (ROC) curves were used to assess the diagnostic performance of MRI-derived parameters.ResultsThere were significant differences in cortex T2*, ADC, Dt, fp and medulla T2*, ADC, Dt among the three groups. Cortex T2*, ADC, Dt, fp and medulla T2*, ADC, Dt had a trend: CKD stage 4–5 < CKD stage 1–3 < healthy volunteers. Cortex and medulla T2*, ADC, Dt were significantly correlated with eGFR, serum creatinine (Scr), cystatin C. In addition, cortex T2* and eGFR showed the highest correlation coefficient (r = 0.824, p < 0.001). Cortex Dt and medulla T2* were optimal parameters for differentiating healthy volunteers and CKD stage 1–3 or CKD stage 4–5 and CKD stage 1–3, respectively.ConclusionsBOLD-MRI and IVIM-DWI might be used as a feasible method for noninvasive assessment of renal function in children with CKD.

Application of BOLD-MRI-based radiomics in differentiating malignant from benign renal tumors.

Blood oxygen level dependent magnetic resonance imaging (BOLD-MRI) is a kind of non-invasive MRI technology which reflects the tissue blood oxyen levels. This stuy aims to explore the value of radiomics based on BOLD-MRI in differentiating malignant from benign renal tumors. A total of 141 patients with renal tumors confirmed by pathology were retrospectively analyzed. Seventy-four men and sixty-seven women, aged 26-78 years, with a median age of 56, were included. In all patients, 118 with malignant tumors and 23 with benign tumors were confirmed. All the patients underwent renal T1 weighted imaging (T1WI), T2 weighted imaging (T2WI), and BOLD-MRI scan within 2 weeks before surgery. The patients were randomly assigned into a training group (benign, n=17; malignant, n=83) and a test group (benign, n=6; malignant, n=35). Two radiologists (A and B), who were blind to the pathological results, delineated the regions of interest (ROI) on the maximum axial slices of the tumors. Radiologist B delineated the ROI again at an interval of one month. The intra-class correlation coefficient (ICC) was used to evaluate inter-observer and intra-observer repeatability and ICC>0.75 represented as a good consistency. All the T2* Mapping images and the related ROI files were loaded into the Artificial Intelligence Kit software. A total of 396 texture features, which were calculated based on morphology, histogram, gray level co-occurrence matrix, gray-scale run length matrix, gray-scale area size matrix and gray-scale dependent matrix, were extracted from each ROI. The lowest redundancy and the highest correlation were filtered using minimum redundancy maximum relevance (mRMR) algorithm. Then least absolute shrinkage and selection operator (LASSO) algorithm was used to screened out the most predictive features. Multivariate logistic regression was performed to develop the prediction model after feature selection. The radiomics signature score (Radscore) of each case was calculated. The Wilcoxon test was used to compare the difference in the Radscore between benign and malignant renal tumors in the training and test groups. The diagnostic performance of the model in differentiating malignant from benign renal tumors was evaluated with receiver operating characteristic (ROC) curve and leave group out cross validation. The clinical application value of the model was evaluated by decision curve analysis (DCA). There was significant difference in the age between the patients with benign and those with malignant tumors (t=4.383, P<0.001). There were no significant differences in gender composition and in the largest tumor diameter between the 2 groups (χ2=3.452, P=0.063; t=1.432, P=0.154). The ICC values of all the texture features for the inter-observer repeatability were ranged from 0.71 to 0.87, and the ICC values for the intra-observer repeatability were ranged from 0.76 to 0.91. Thirty features with the lowest redundancy and the highest correlation were screened out. The most predictive 12 features were filtered out. The Radscores of malignant tumors in the training and test groups were higher than those of benign tumors (P<0.001 and P=0.006, respectively). The areas under the ROC curve of the model developed by multivariable logistic regression for differentiating malignant from benign renal tumors in the training and test groups were 0.881 and 0.706, with the accuracy at 82.93% and 79.00%, the sensitivity at 82.86% and 77.11%, and the specificities at 83.33% and 88.24%, respectively. The results of decision curve analysis showed that the net benefit of the radiomics model was higher than that of "all malignant" or "all benign" when the threshold was higher than 0.3. BOLD-MRI-based radiomics can be a reliable non-invasive approach for differentiating renal malignant tumors from benign tumors.

Analysis Protocols for MRI Mapping of Renal T1.

The computation of T1 maps from MR datasets represents an important step toward the precise characterization of kidney disease models in small animals. Here the main strategies to analyze renal T1 mapping datasets derived from small rodents are presented. Suggestions are provided with respect to essential software requirements, and advice is provided as to how dataset completeness and quality may be evaluated. The various fitting models applicable to T1 mapping are presented and discussed. Finally, some methods are proposed for validating the obtained results.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This analysis protocol chapter is complemented by two separate chapters describing the basic concept and experimental procedure.

MRI Mapping of Renal T1: Basic Concept.

In renal MRI, measurement of the T1 relaxation time of water molecules may provide a valuable biomarker for a variety of pathological conditions. Due to its sensitivity to the tissue microenvironment, T1 has gained substantial interest for noninvasive imaging of renal pathology, including inflammation and fibrosis. In this chapter, we will discuss the basic concept of T1 mapping and different T1 measurement techniques and we will provide an overview of emerging preclinical applications of T1 for imaging of kidney disease.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This introduction chapter is complemented by two separate chapters describing the experimental procedure and data analysis.

Experimental Protocols for MRI Mapping of Renal T1.

The water proton longitudinal relaxation time, T1, is a common and useful MR parameter in nephrology research. Here we provide three step-by-step T1-mapping protocols suitable for different types of nephrology research. Firstly, we provide a single-slice 2D saturation recovery protocol suitable for studies of global pathology, where whole-kidney coverage is unnecessary. Secondly, we provide an inversion recovery type imaging protocol that may be optimized for specific kidney disease applications. Finally, we also provide imaging protocol for small animal kidney imaging in a clinical scanner.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This analysis protocol chapter is complemented by two separate chapters describing the basic concept and experimental procedure.