Renal T2 Research Articles

Multiparametric Assessment of Changes in Renal Tissue after Kidney Transplantation with Quantitative MR Relaxometry and Diffusion-Tensor Imaging at 3 T.

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.

Multi-parametric MRI of kidney disease progression for autosomal recessive polycystic kidney disease: mouse model and initial patient results.

Background:Autosomal recessive polycystic kidney disease (ARPKD) is a rare but potentially lethal genetic disorder typically characterized by diffuse renal microcysts. Clinical trials for patients with ARPKD are not currently possible due to the absence of sensitive measures of ARPKD kidney disease progression and/or therapeutic efficacy.Methods:In this study, animal and human MRI scanners were used to obtain quantitative kidney T1 and T2 relaxation time maps for both excised kidneys from bpk and wild type (WT) mice as well as for a pediatric patient with ARPKD and a healthy adult volunteer.Results:Mean kidney T1 and T2 relaxation times showed significant increases with age (p<0.05) as well as significant increases in comparison to WT mice (p<2 × 10−10). Significant or nearly significant linear correlations were observed for mean kidney T1 (p=0.030) and T2 (p=0.054) as a function of total kidney volume, respectively. Initial MRF assessments in a patient with ARPKD showed visible increases in both kidney T1 and T2 in comparison to the healthy volunteer.Conclusions:These preclinical and initial clinical MRI studies suggest that renal T1 and T2 relaxometry may provide an additional outcome measure to assess cystic kidney disease progression in patients with ARPKD.

Probing renal blood volume with magnetic resonance imaging

Damage to the kidney substantially reduces life expectancy. Renal tissue hypoperfusion and hypoxia are key elements in the pathophysiology of acute kidney injury and its progression to chronic kidney disease. In vivo assessment of renal haemodynamics and tissue oxygenation remains a challenge. Blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) is sensitive to changes in the effective transversal relaxation time (T2 *) in vivo, and is non-invasive and indicative of renal tissue oxygenation. However, the renal T2 * to tissue pO2 relationship is not governed exclusively by renal blood oxygenation, but is affected by physiological confounders with alterations in renal blood volume fraction (BVf) being of particular relevance. To decipher this interference probing renal BVf is essential for the pursuit of renal MR oximetry. Superparamagnetic iron oxide nanoparticle (USPIO) preparations can be used as MRI visible blood pool markers for detailing alterations in BVf. This review promotes the opportunities of MRI-based assessment of renal BVf. Following an outline on the specifics of renal oxygenation and perfusion, changes in renal BVf upon interventions and their potential impact on renal T2 * are discussed. We also describe the basic principles of renal BVf assessment using ferumoxytol-enhanced MRI in the equilibrium concentration regimen. We demonstrate that ferumoxytol does not alter control of renal haemodynamics and oxygenation. Preclinical applications of ferumoxytol enhanced renal MRI as well as considerations for its clinical implementation for examining renal BVf changes are provided alongside practical considerations. Finally, we explore the future directions of MRI-based assessment of renal BVf.

Magnetic resonance fingerprinting for simultaneous renal T1 and mapping in a single breath-hold.

To evaluate the use of magnetic resonance fingerprinting (MRF) for simultaneous quantification of and in a single breath-hold in the kidneys. The proposed kidney MRF sequence was based on MRF echo-planar imaging. Thirty-five measurements per slice and overall 4 slices were measured in 15.4seconds. Group matching was performed for in-line quantification of and . Images were acquired in a phantom and 8 healthy volunteers in coronal orientation. To evaluate our approach, region of interests were drawn in the kidneys to calculate mean values and standard deviations of the and times. Precision was calculated across multiple repeated MRF scans. Gaussian filtering is applied on baseline images to improve SNR and match stability. and times acquired with MRF in the phantom showed good agreement with reference measurements and conventional mapping methods with deviations of less than 5% for and less than 10% for . Baseline images in vivo were free of artifacts and relaxation times yielded good agreement with conventional methods and literature (deviation , ). In this feasibility study, the proposed renal MRF sequence resulted in accurate and quantification in a single breath-hold.

Association between native T1 mapping of the kidney and renal fibrosis in patients with IgA nephropathy

IntroductionIgA nephropathy (IgAN) is the commonest global cause of glomerulonephritis. Extent of fibrosis, tubular atrophy and glomerulosclerosis predict renal function decline. Extent of renal fibrosis is assessed with renal biopsy which is invasive and prone to sampling error. We assessed the utility of non-contrast native T1 mapping of the kidney in patients with IgAN for assessment of renal fibrosis.MethodsRenal native T1 mapping was undertaken in 20 patients with IgAN and 10 healthy subjects. Ten IgAN patients had a second scan to assess test-retest reproducibility of the technique. Native T1 times were compared to markers of disease severity including degree of fibrosis, eGFR, rate of eGFR decline and proteinuria.ResultsAll patients tolerated the MRI scan and analysable quality T1 maps were acquired in at least one kidney in all subjects. Cortical T1 times were significantly longer in patients with IgAN than healthy subjects (1540 ms ± 110 ms versus 1446 ± 88 ms, p = 0.038). There was excellent test-retest reproducibility of the technique, with Coefficient-of-variability of axial and coronal T1 mapping analysis being 2.9 and 3.7% respectively. T1 correlated with eGFR and proteinuria (r = − 0.444, p = 0.016; r = 0.533, p = 0.003 respectively).Patients with an eGFR decline > 2 ml/min/year had increased T1 times compared to those with a decline < 2 ml/min/year (1615 ± 135 ms versus 1516 ± 87 ms, p = 0.068), and T1 time was also higher in patients with a histological ‘T’-score of > 0, compared to those with a ‘T’-score of 0 (1575 ± 106 ms versus 1496 ± 105 ms, p = 0.131), though not to significance.ConclusionsCortical native T1 time is significantly increased in patients with IgAN compared to healthy subjects and correlates with markers of renal disease. Reproducibility of renal T1 mapping is excellent. This study highlights the potential utility of native T1 mapping in IgAN and other progressive nephropathies, and larger prospective studies are warranted.

Is Magnetic Resonance Imaging Detection of Kidney Iron Deposition Increased in Haptoglobin 2-2 Genotype Carriers with Type 1 Diabetes?

Haptoglobin's (Hp) main role is to bind free hemoglobin (Hb), reducing its oxidative potential. The Hp-Hb complex formed is cleared from the circulation by macrophage receptor CD163. In diabetes, impaired Hp 2-2-Hb CD163 clearance and abnormal glomerular permeability allow the large Hp 2-2-Hb complex to cross the barrier, where its redox active iron leads to cellular toxicity. Although Hp 2-2 predicts renal function decline, whether renal iron deposition differs by Hp is unknown. We used renal quantitative T2* magnetic resonance imaging to estimate iron level in the cortex and medullar of type 1 diabetes (T1D) adults [15 Hp 1-1 and 15 Hp 2-2 carriers of similar age (53 years), duration (45 years), and gender]. Total kidney iron level was estimated as the sum of the cortex and medullar iron. Albuminuria was defined as urinary albumin to creatinine ratio >30 mg/g in two of three samples. Total kidney iron did not differ by gender or Hp but was higher in those with albuminuria (p = 0.05), an association confined to Hp 2-2 carriers (p = 0.04 vs. p = 0.51 in Hp 1-1). These data lead to the hypothesis that kidney iron deposition is increased among Hp 2-2 carriers with albuminuria in T1D. Antioxid. Redox Signal. 29, 735-741.

Multi-organ assessment of compensated cirrhosis patients using quantitative magnetic resonance imaging

Advancing liver disease results in deleterious changes in a number of critical organs. The ability to measure structure, blood flow and tissue perfusion within multiple organs in a single scan has implications for determining the balance of benefit vs. harm for therapies. Our aim was to establish the feasibility of magnetic resonance imaging (MRI) to assess changes in Compensated Cirrhosis (CC), and relate this to disease severity and future liver-related outcomes (LROs). A total of 60 patients with CC, 40 healthy volunteers and 7 patients with decompensated cirrhosis were recruited. In a single scan session, MRI measures comprised phase-contrast MRI vessel blood flow, arterial spin labelling tissue perfusion, T1 longitudinal relaxation time, heart rate, cardiac index, and volume assessment of the liver, spleen and kidneys. We explored the association between MRI parameters and disease severity, analysing differences in baseline MRI parameters in the 11 (18%) patients with CC who experienced future LROs. In the liver, compositional changes were reflected by increased T1 in progressive disease (p <0.001) and an increase in liver volume in CC (p = 0.006), with associated progressive reduction in liver (p <0.001) and splenic (p <0.001) perfusion. A significant reduction in renal cortex T1 and increase in cardiac index and superior mesenteric arterial blood flow was seen with increasing disease severity. Baseline liver T1 (p = 0.01), liver perfusion (p <0.01), and renal cortex T1 (p <0.01) were significantly different in patients with CC who subsequently developed negative LROs. MRI enables the contemporaneous assessment of organs in liver cirrhosis in a single scan without the requirement for a contrast agent. MRI parameters of liver T1, renal T1, hepatic and splenic perfusion, and superior mesenteric arterial blood flow were related to the risk of LROs. This study assesses the changes to structure, blood flow and perfusion that occur in the key organs (liver, spleen and kidney) associated with severe liver disease (Compensated Cirrhosis), using magnetic resonance imaging. The magnetic resonance imaging measures which changed with disease severity and were related to negative liver-related clinical outcomes are described.

Experimental MRI Monitoring of Renal Blood Volume Fraction Variations En Route to Renal Magnetic Resonance Oximetry.

Diagnosis of early-stage acute kidney injury (AKI) will benefit from a timely identification of local tissue hypoxia. Renal tissue hypoxia is an early feature in AKI pathophysiology, and renal oxygenation is increasingly being assessed through T2*-weighted magnetic resonance imaging (MRI). However, changes in renal blood volume fraction (BVf) confound renal T2*. The aim of this study was to assess the feasibility of intravascular contrast-enhanced MRI for monitoring renal BVf during physiological interventions that are concomitant with variations in BVf and to explore the possibility of correcting renal T2* for BVf variations. A dose-dependent study of the contrast agent ferumoxytol was performed in rats. BVf was monitored throughout short-term occlusion of the renal vein, which is known to markedly change renal blood partial pressure of O2 and BVf. BVf calculated from MRI measurements was used to estimate oxygen saturation of hemoglobin (SO2). BVf and SO2 were benchmarked against cortical data derived from near-infrared spectroscopy. As estimated from magnetic resonance parametric maps of T2 and T2*, BVf was shown to increase, whereas SO2 was shown to decline during venous occlusion (VO). This observation could be quantitatively reproduced in test–retest scenarios. Changes in BVf and SO2 were in good agreement with data obtained from near-infrared spectroscopy. Our findings provide motivation to advance multiparametric MRI for studying AKIs, with the ultimate goal of translating MRI-based renal BVf mapping into clinical practice en route noninvasive renal magnetic resonance oximetry as a method of assessing AKI and progression to chronic damage.

Multiparametric Renal Magnetic Resonance Imaging: Validation, Interventions, and Alterations in Chronic Kidney Disease.

Background: This paper outlines a multiparametric renal MRI acquisition and analysis protocol to allow non-invasive assessment of hemodynamics (renal artery blood flow and perfusion), oxygenation (BOLD T2*), and microstructure (diffusion, T1 mapping).Methods: We use our multiparametric renal MRI protocol to provide (1) a comprehensive set of MRI parameters [renal artery and vein blood flow, perfusion, T1, T2*, diffusion (ADC, D, D*, fp), and total kidney volume] in a large cohort of healthy participants (127 participants with mean age of 41 ± 19 years) and show the MR field strength (1.5 T vs. 3 T) dependence of T1 and T2* relaxation times; (2) the repeatability of multiparametric MRI measures in 11 healthy participants; (3) changes in MRI measures in response to hypercapnic and hyperoxic modulations in six healthy participants; and (4) pilot data showing the application of the multiparametric protocol in 11 patients with Chronic Kidney Disease (CKD).Results: Baseline measures were in-line with literature values, and as expected, T1-values were longer at 3 T compared with 1.5 T, with increased T1 corticomedullary differentiation at 3 T. Conversely, T2* was longer at 1.5 T. Inter-scan coefficients of variation (CoVs) of T1 mapping and ADC were very good at <2.9%. Intra class correlations (ICCs) were high for cortex perfusion (0.801), cortex and medulla T1 (0.848 and 0.997 using SE-EPI), and renal artery flow (0.844). In response to hypercapnia, a decrease in cortex T2* was observed, whilst no significant effect of hyperoxia on T2* was found. In CKD patients, renal artery and vein blood flow, and renal perfusion was lower than for healthy participants. Renal cortex and medulla T1 was significantly higher in CKD patients compared to healthy participants, with corticomedullary T1 differentiation reduced in CKD patients compared to healthy participants. No significant difference was found in renal T2*.Conclusions: Multiparametric MRI is a powerful technique for the assessment of changes in structure, hemodynamics, and oxygenation in a single scan session. This protocol provides the potential to assess the pathophysiological mechanisms in various etiologies of renal disease, and to assess the efficacy of drug treatments.

Value of MRI T2* in quantification of visceral iron deposition in patients with β-thalassemia major

Objective To explore the value of MRI T2*quantification of visceral iron deposition in patients with β-thalassemia major. Methods A total of one hundred and two patients with β-thalassemia major were retrospectively analyzed. They underwent genetic testing and the cardiac and (or) abdominal MRI scanning. Among them, 47 patients underwent splenectomy operation, 95 patients underwent cardiac MRI scanning, 102 underwent abdominal MRI scanning for their livers, pancreases and kidneys, and 55 underwent splenic MRI scanning. The T2* values of the hearts, livers, pancreases and kidneys were measured, meanwhile the liver iron concentrations (LIC) were measured. The levels of serum ferritin (SF) patients were measured in 81 patients. The Spearman rank correlation was employed to analyze the relationship between SF, LIC, age and each organs T2* values. Independent sample t test (normal distribution) or the Mann-Whitney U test (non-normal distribution) were used to compare the hepatic, cardiac, renal and splenic T2* values differences between patients with splenectomy and those without. Results Serum ferritin were highly positively correlated with LIC, moderately correlatied with age, moderately negatively correlated with hepatic and pancreatic T2* values, with r values of 0.833, 0.537, -0.623 and -0.403, respectively (P 0.05). The hepatic and pancreatic T2* values were reduced (P 0.05). Conclusions The patients with β-thalassemia major have prone to suffer from excessive iron deposition in the heart and abdominal organs. The technology of MRI quantification of T2* values could reflect the body iron overload. Key words: Beta-thalassemia; Magnetic resonance imaging; Iron overload

Renal Iron Load in Sickle Cell Anemia Patients - a Brazilian Study

Background and Objectives: Sickle cell anemia (SCA) is characterized by chronic haemolysis and frequent painful vaso-occlusive episodes, eventually leading to multiple organ damage, including the kidneys. Chronic haemolysis is frequent in SCA patients receiving regular transfusions. Not all renal disease in patients with SCA is due to sickle cell nephropathy (SCN), but the incidence of renal failure increases as patient survival improves. Since Magnetic Resonance Image can provide a unique evaluation of the abdomen in a single exam, the aim of this study was to assess renal iron deposits in patients with SCA, correlating these values with transfusion burden, liver and heart T2* and blood LDH levels.Material and methods: Twenty patients with SCA older than 20 years of age and transfusion burden were studied in a 1.5T scanner (Avanto, Siemens Medical Systems, Erlangen, Germany) using T2* technique and compared to age- and sex-matched normal controls. For liver T2* analysis, regions of interest (ROI) were manually drawn in the liver, using Viewing software (Leonardo - Siemens) avoiding all major visible vessels. For heart T2* analysis, a full-thickness ROI was manually defined in the interventricular septum (routinely chosen to avoid T2* artifacts from the cardiac veins, liver, and lungs). For renal T2* analysis, ROI were manually drawn in the cortex, using Viewing software (Leonardo - Siemens) avoiding the medullary region. All parameters are presented as mean ± standard deviation. Spearman’s rank test was used to assess the correlation between renal T2* and blood LDH levels. The Ethics Committee for Research approved this trial.Results: Mean renal T2* was significantly lower (p < 0.001) in the SCA patients [16.4 ± 11.8 ms] compared with healthy controls (47.9 ± 11.1 ms). However there was no correlation between renal T2* and heart (p = 0.500) and liver T2* (p= 0.578). Median liver and myocardial T2* in this population was 3.96 ± 3.58 ms and 36.87 ± 8.06 ms. Cortico-medullary signal differences in renal iron loading were observed. Low signal intensity in the cortex relative to the medulla was observed in thirteen patients (65%). SCA patients who showed no cortico-medullary difference in signal intensity had a mean T2* of 30.9 ± 6.5 ms, which was significantly lower (p < 0.001) than that of the group of patients showing a hypointense cortical signal (8.6 ± 2.8 ms). We investigated the relationship between cortico-medullary differences and haemolysis using LDH values as a marker of haemolysis. Renal T2* showed a significant correlation with LDH values. Mean LDH values were significantly different between patients with and without cortico-medullary differences (p = 0.004), being 470.6 ± 123.1 IU/L for those with no cortico-medullary differences, and 1313.0 ± 788.6 IU/L for those with hypointense cortex. The seven highest LDH values in this cohort of 20 patients corresponded to seven patients with cortico-medullary signal intensity differences. Conclusion: Our study in SCA shows that iron deposition in the kidney is not related to systemic iron overload, but to haemolysis. There appears to be a clear localization of iron deposition within the kidney, with the deposits being found in the cortex and not in the medulla, as found by T1 and T2-weighted MRI. Our results suggest that haemolysis is a major determinant of renal iron load in SCA patiests. DisclosuresNo relevant conflicts of interest to declare.

T2* Measurement bias due to concomitant gradient fields.

To demonstrate that concomitant magnetic fields can cause significant spatially dependent biases in T2* relaxometry measurements with implications for clinical applications such as BOLD and dynamic susceptibility contrast-enhanced MRI. After developing a theoretical framework for intravoxel dephasing and signal loss from concomitant magnetic fields, this framework and the effect of concomitant fields on T2* are validated with phantom experiments and numerical simulation. In lower leg and renal T2* mapping, we quantify measurement bias for imaging protocols with high gradient amplitude multiecho readouts, comparable to those used in clinical applications. Concordance between phantom experiment and numerical simulation validate the theoretical framework. Changes in T2* measured in the lower leg and kidney varied by up to 15% and 35%, respectively, as a result of concomitant gradient effects when compared with the control measurements. Concomitant magnetic fields produced by imaging gradient coils can cause clinically significant T2* mapping errors when high amplitude, long duration gradient waveforms are used. While we have shown that measurement biases can be quite large, modification of imaging parameters can potentially reduce concomitant field-induced measurement errors to acceptable levels. Magn Reson Med 77:1562-1572, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Kidney Transplantation: Multiparametric Functional Magnetic Resonance Imaging for Assessment of Renal Allograft Pathophysiology in Mice.

The aims of this experimental study were to investigate renal allograft pathophysiology by multiparametric functional magnetic resonance imaging (MRI) and to directly correlate MRI parameters with renal histopathology in mouse models of allogenic and isogenic kidney transplantation (ktx). Allograft rejection was induced by transplantation of C57BL/6 (B6) donor kidneys into BALB/c recipients (allogenic ktx). B6 mice that received B6 kidneys served as controls (isogenic ktx). Three weeks after ktx, MRI was performed using a 7-T small-animal scanner. Flow sensitive alternating inversion recovery echoplanar imaging arterial spin labeling, multiecho turbo spin echo, and diffusion-weighted imaging sequences were acquired. Maps of renal perfusion, T2 and T1 relaxation times, and apparent diffusion coefficients were calculated. Histological changes in the kidney were evaluated according to Banff criteria. Renal cell infiltrates and fibrosis were quantified by immunohistochemistry. Differences between groups were assessed using the Mann-Whitney U test, and the correlation of MRI parameters with renal histopathology was determined by Spearman correlation analysis. After allogenic, but not isogenic, ktx, animals developed acute allograft rejection. Allogenic grafts were infiltrated by macrophages and T-lymphocytes and exhibited marked renal fibrosis. Magnetic resonance imaging revealed stronger impairment of renal perfusion (56 ± 7 vs 293 ± 44 mL/[min × 100 g]; P < 0.01) and more pronounced increases in T2 (60.1 ± 2.0 vs 45.7 ± 1.2 milliseconds, P < 0.01) and T1 relaxation times (1938 ± 53 vs 1350 ± 27 milliseconds, P < 0.01) in allogenic than in isogenic kidneys. Apparent diffusion coefficient was reduced to 1.39 ± 0.14 × 10(-3) mm2/s in kidneys with an acute rejection and was 1.83 ± 0.05 × 10(-3) mm2/s in isogenic kidneys without rejection (P < 0.05). Magnetic resonance imaging parameters significantly correlated with the amount of cellular infiltration and renal fibrosis observed histologically. Functional MRI allows detection of acute renal allograft rejection after allogenic ktx in mice. Functional MRI parameters correlate with cell infiltrates and fibrosis. Thus, MRI may be used noninvasively and longitudinally to investigate mechanisms of renal allograft rejection and evaluate novel therapeutic strategies in experimental studies.

Quantitative T2* magnetic resonance imaging for renal iron overload assessment: normal values by age and sex.

Few studies of renal iron content have been performed with multiecho gradient-echo (ME-GRE) T2* magnetic resonance imaging (MRI). We assessed the feasibility and reproducibility of ME-GRE T2* MRI for measuring regional and global renal T2* values, and established the lower limits of normal in healthy subjects, also correlating the measured values with age and sex. Twenty consecutive healthy subjects (13 men and 7 women, mean age 29.1 ± 7.2 years, range 19-42 years) underwent MRI examinations using a 1.5 T magnet and an ME-GRE T2* sequence. For each kidney, T2* was measured in anterior, posterolateral, and posteromedial renal parenchymal regions. The mean T2* value was calculated as the average of the two kidneys T2* values. For the mean kidney T2* value, the coefficients of variation for intra- and inter-operator reproducibility were 1.76% and 6.23%, respectively. The lower limit of normal for the mean kidney T2* value was 31 ms (median 51.39 ± 10.09). There was no significant difference between left and right kidney T2* values (p = 0.578). No significant correlation was found between T2* values and subjects' age or sex. Renal ME-GRE T2* appears to be a feasible and reproducible technique. The renal T2* values showed no dependence on sex or age.

Identifying Renal Microstructural and Blood Flow Changes in Sickle Cell Disease Using Quantitative MRI Techniques

BACKGROUND: In patients with sickle cell disease (SCD), renal disease is strikingly high, with up to one third of adults developing chronic kidney disease. Renal disease is associated with considerable morbidity and mortality although it has not been as well studied as other SCD-related complications. Studies which could provide insight into clinically silent renal injury are limited. To date, no large studies of functional or structural renal changes have been published, particularly in the context of sickle cell crises. Magnetic Resonance Imaging (MRI) is safe and capable of providing quantitative assessments of disease without ionizing radiation. Clinically available MRI techniques have already been used to assess both acute and chronic kidney disease. This is the first study to evaluate these MRI techniques in SCD renal disease.OBJECTIVE: The objective of this pilot study was to evaluate the capability of quantitative MRI techniques to assess both structural changes and renal blood flow in patients with SCD.METHODS: Pediatric and adult patients were recruited to an IRB approved study from the Sickle Cell Anemia Centers at UH Rainbow Babies & Children’s Hospital and University Hospitals Case Medical Center. Six pediatric patients (age 12-18 years, 1 male, 5 female, eGFR 110-185 mL/min/1.73m2) have been recruited to date. Healthy controls were also recruited. Diffusion (DTI) and Arterial Spin Labeling (ASL) scans were performed to assess medullary microstructure and cortical perfusion (non-contrast), respectively. Apparent Diffusion Coefficient (ADC) and Fractional Anisotropy (FA) maps were calculated using established methods. Mean renal T2* was measured to assess iron burden. A Student’s t-test was performed to compare the mean renal DTI and ASL results between subjects and healthy controls.RESULTS: In the six pediatric subjects, medullary FA values were decreased, suggesting degradation of medullary microstructure. Both cortical ADC and medullary FA were significantly reduced, indicative of microstructural changes in SCD subjects compared to controls. ASL perfusion maps, likewise, showed reduced cortical perfusion for SCD subjects in comparison to controls. Preliminary differences in blood flow and microstructure were seen between SCD subjects on hydroxyurea (HU) and those not on HU. Analysis of the T2* data showed increased renal iron deposition that did not appear to correlate with serum ferritin.CONCLUSIONS: Our results suggest that quantitative diffusion and ASL MRI are sensitive to medullary microstructural and cortical blood flow changes in pediatric patients with SCD. Preliminarily, iron deposition in the kidney appears to relate to chronic hemolysis rather than transfusional iron. These sensitive techniques may be useful in assessing the impact of therapeutic interventions, such as HU, on renal function in children. There may also be utility in assessing the impact of acute hemolysis/sickling on renal microstructure and perfusion. DisclosuresPiccone:Novartis Pharmaceuticals Cooperation: Speakers Bureau.

Measuring renal tissue relaxation times at 7 T.

As developments in RF coils and RF management strategies make performing ultra-high-field renal imaging feasible, understanding the relaxation times of the tissue becomes increasingly important for tissue characterization, sequence optimization and quantitative functional renal imaging, such as renal perfusion imaging using arterial spin labeling. By using a magnetization-prepared single-breath-hold fast spin echo imaging method, human renal T1 and T2 imaging studies were successfully performed at 7 T with 11 healthy volunteers (eight males, 45 ± 17 years, and three females, 29 ± 7 years, mean ± standard deviation, S.D.) while addressing challenges of B1 (+) inhomogeneity and short-term specific absorption rate limits. At 7 T, measured renal T1 values for the renal cortex and medulla (mean ± S.D.) from five healthy volunteers who participated in both 3 T and two-session 7 T studies were 1661 ± 68 ms and 2094 ± 67 ms, and T2 values were 108 ± 7 ms and 126 ± 6 ms. For comparison, similar measurements were made at 3 T, where renal cortex and medulla T1 values of 1261 ± 86 ms and 1676 ± 94 ms and T2 values of 121 ± 5 ms and 138 ± 7 ms were obtained. Measurements at 3 T and 7 T were significantly different for both T1 and T2 values in both renal tissues. Reproducibility studies at 7 T demonstrated that T1 and T2 estimations were robust, with group mean percentage differences of less than 4%.

How bold is blood oxygenation level-dependent (BOLD) magnetic resonance imaging of the kidney? Opportunities, challenges and future directions.

Renal tissue hypoperfusion and hypoxia are key elements in the pathophysiology of acute kidney injury and its progression to chronic kidney disease. Yet, in vivo assessment of renal haemodynamics and tissue oxygenation remains a challenge. Many of the established approaches are invasive, hence not applicable in humans. Blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) offers an alternative. BOLD-MRI is non-invasive and indicative of renal tissue oxygenation. Nonetheless, recent (pre-) clinical studies revived the question as to how bold renal BOLD-MRI really is. This review aimed to deliver some answers. It is designed to inspire the renal physiology, nephrology and imaging communities to foster explorations into the assessment of renal oxygenation and haemodynamics by exploiting the powers of MRI. For this purpose, the specifics of renal oxygenation and perfusion are outlined. The fundamentals of BOLD-MRI are summarized. The link between tissue oxygenation and the oxygenation-sensitive MR biomarker T2∗ is outlined. The merits and limitations of renal BOLD-MRI in animal and human studies are surveyed together with their clinical implications. Explorations into detailing the relation between renal T2∗ and renal tissue partial pressure of oxygen (pO2 ) are discussed with a focus on factors confounding the T2∗ vs. tissue pO2 relation. Multi-modality in vivo approaches suitable for detailing the role of the confounding factors that govern T2∗ are considered. A schematic approach describing the link between renal perfusion, oxygenation, tissue compartments and renal T2∗ is proposed. Future directions of MRI assessment of renal oxygenation and perfusion are explored.

Detailing the Relation Between Renal T2* and Renal Tissue pO2 Using an Integrated Approach of Parametric Magnetic Resonance Imaging and Invasive Physiological Measurements

This study was designed to detail the relation between renal T2* and renal tissue pO2 using an integrated approach that combines parametric magnetic resonance imaging (MRI) and quantitative physiological measurements (MR-PHYSIOL). Experiments were performed in 21 male Wistar rats. In vivo modulation of renal hemodynamics and oxygenation was achieved by brief periods of aortic occlusion, hypoxia, and hyperoxia. Renal perfusion pressure (RPP), renal blood flow (RBF), local cortical and medullary tissue pO2, and blood flux were simultaneously recorded together with T2*, T2 mapping, and magnetic resonance-based kidney size measurements (MR-PHYSIOL). Magnetic resonance imaging was carried out on a 9.4-T small-animal magnetic resonance system. Relative changes in the invasive quantitative parameters were correlated with relative changes in the parameters derived from MRI using Spearman analysis and Pearson analysis. Changes in T2* qualitatively reflected tissue pO2 changes induced by the interventions. T2* versus pO2 Spearman rank correlations were significant for all interventions, yet quantitative translation of T2*/pO2 correlations obtained for one intervention to another intervention proved not appropriate. The closest T2*/pO2 correlation was found for hypoxia and recovery. The interlayer comparison revealed closest T2*/pO2 correlations for the outer medulla and showed that extrapolation of results obtained for one renal layer to other renal layers must be made with due caution. For T2* to RBF relation, significant Spearman correlations were deduced for all renal layers and for all interventions. T2*/RBF correlations for the cortex and outer medulla were even superior to those between T2* and tissue pO2. The closest T2*/RBF correlation occurred during hypoxia and recovery. Close correlations were observed between T2* and kidney size during hypoxia and recovery and for occlusion and recovery. In both cases, kidney size correlated well with renal vascular conductance, as did renal vascular conductance with T2*. Our findings indicate that changes in T2* qualitatively mirror changes in renal tissue pO2 but are also associated with confounding factors including vascular volume fraction and tubular volume fraction. Our results demonstrate that MR-PHYSIOL is instrumental to detail the link between renal tissue pO2 and T2* in vivo. Unravelling the link between regional renal T2* and tissue pO2, including the role of the T2* confounding parameters vascular and tubular volume fraction and oxy-hemoglobin dissociation curve, requires further research. These explorations are essential before the quantitative capabilities of parametric MRI can be translated from experimental research to improved clinical understanding of hemodynamics/oxygenation in kidney disorders.

Evaluation of renal quantitative T2* changes on MRI following administration of ferumoxytol as a T2* contrast agent.

PurposeTo evaluate the time-dependent changes in regional quantitative T2* maps of the kidney following intravenous administration of ferumoxytol.Materials and methodsTwenty-four individuals with normal kidney function underwent T2*-weighted MRI of the kidney before, immediately after, and 48 hours after intravenous administration of ferumoxytol at a dose of 4 mg/kg (group A, n=12) or 6 mg/kg (group B, n=12). T2* values were statistically analyzed using two-tailed paired t-tests.ResultsIn group A, the percentage changes from baseline to immediate post and baseline to 48 hours were 85.3% and 64.2% for the cortex and 90.8% and 64.6% for the medulla, respectively. In group B, the percentage changes from baseline to immediate post and baseline to 48 hours were 85.2% and 73.4% for the cortex and 94.5% and 74% for the medulla, respectively. This difference was significant for both groups (P<0.0001).ConclusionThere is significant and differential uptake of ferumoxytol in the cortex and medulla of physiologically normal kidneys. This differential uptake may offer the ability to interrogate renal cortex and medulla with possible clinical applications in medical renal disease and transplant organ assessment. We propose an organ of interest based dose titration of ferumoxytol to better differentiate circulating from intracellular ferumoxytol particles.

Chronic diuretic therapy attenuates renal BOLD magnetic resonance response to an acute furosemide stimulus.

BackgroundBlood Oxygen Level Dependent (BOLD) magnetic resonance (MR) is a novel imaging tool that detects changes in tissue oxygenation. Increases in renal oxygenation in response to a standard 20 mg intravenous furosemide stimulus have been evaluated to assess kidney viability in patients with renal artery stenosis (RAS). The effect of prior exposure to furosemide on the ability of BOLD MR techniques to evaluate renal function is unknown.This study tested the hypothesis that chronic loop diuretic therapy is associated with attenuated responses in renal tissue oxygenation as measured by BOLD MR with an acute 20 mg intravenous furosemide stimulus in participants undergoing evaluation for RAS.MethodsThirty-eight participants referred for evaluation of RAS were recruited for this study. We examined renal cortical and medullary BOLD signal (T2*) intensities before and after a 20 mg intravenous furosemide stimulus. Additionally, we measured changes in renal artery blood flow using phase contrast techniques.ResultsAfter controlling for covariates age, race, gender, diabetes, glomerular filtration rate, body mass index, and stenosis severity, daily oral furosemide dose was an independent, negative predictor of renal medullary T2* response (p = 0.01) to a standard 20 mg intravenous furosemide stimulus. Stenosis severity and ethnicity were also significant independent predictors of changes in T2* signal intensity in response to an acute furosemide challenge. Changes in renal blood flow in response to acute furosemide administration were correlated with changes in T2* in the renal cortex (r = 0.29, p = 0.03) but not the medulla suggesting changes in renal medullary oxygenation were not due to reduced renal medullary blood flow.ConclusionsChronic furosemide therapy attenuates BOLD MR responses to an acute furosemide stimulus in patients with RAS being evaluated for renal artery revascularization procedures. Thus, patients who are chronically administered loop diuretics may need a different dosing strategy to accurately detect changes in renal oxygenation with BOLD MR in response to a furosemide stimulus.