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

BACKGROUND: 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. PURPOSE: 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. STUDY TYPE: Prospective. SUBJECTS: 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. FIELD STRENGTH/SEQUENCE: 3T, multiecho spin-echo sequence. ASSESSMENT: 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. STATISTICAL TESTS: 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. RESULTS: 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. DATA CONCLUSION: Stimulated-echo correction reduces renal T2 variation across MR vendor platforms. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Randomized trial comparing standard versus thermocontrolled haemodialysis using intradialytic cardiac, brain and renal magnetic resonance imaging.

BACKGROUND: Ischaemic end-organ damage during haemodialysis (HD) is a significant problem that may be ameliorated by intradialytic cooling. A randomised trial was performed to compare standard HD (SHD; dialysate temperature 37°C) and programmed cooling of the dialysate [thermocontrolled HD (TCHD)] using multiparametric magnetic resonance imaging (MRI) to assess structural, functional and blood flow changes in the heart, brain and kidneys. METHODS: Prevalent HD patients were randomly allocated to receive either SHD or TCHD for 2 weeks before undergoing serial MRI at four time points: pre-, during (30 min and 180 min) and post-dialysis. MRI measures include cardiac index, myocardial strain, longitudinal relaxation time (T1), myocardial perfusion, internal carotid and basilar artery flow, grey matter perfusion and total kidney volume. Participants then crossed to the other modality to repeat the study protocol. RESULTS: Eleven participants completed the study. Separation in blood temperature between TCHD (-0.1 ± 0.3°C) and SHD (+0.3 ± 0.2°C; P = .022) was observed, although there was no difference in tympanic temperature changes between arms. There were significant intradialytic reductions in cardiac index, cardiac contractility (left ventricular strain), left carotid and basilar artery blood flow velocities, total kidney volume, longitudinal relaxation time (T1) of the renal cortex and transverse relaxation rate (T2*) of the renal cortex and medulla, but no differences between arms. Pre-dialysis T1 of the myocardium and left ventricular wall mass index were lower after 2 weeks of TCHD compared with SHD [1266 ms (interquartile range 1250-1291) versus 1311 ± 58 ms, P = .02; 66 ± 22 g/m2 versus 72 ± 23 g/m2, P = .004]. CONCLUSIONS: HD adversely affects cardiac function, reduces carotid and basilar artery blood flow and total kidney volume, but mild dialysate cooling using a biofeedback module did not result in differences in intradialytic MRI measures compared with SHD.

Automated renal segmentation in healthy and chronic kidney disease subjects using a convolutional neural network.

PURPOSE: Total kidney volume (TKV) is an important measure in renal disease detection and monitoring. We developed a fully automated method to segment the kidneys from T2 -weighted MRI to calculate TKV of healthy control (HC) and chronic kidney disease (CKD) patients. METHODS: This automated method uses machine learning, specifically a 2D convolutional neural network (CNN), to accurately segment the left and right kidneys from T2 -weighted MRI data. The data set consisted of 30 HC subjects and 30 CKD patients. The model was trained on 50 manually defined HC and CKD kidney segmentations. The model was subsequently evaluated on 50 test data sets, comprising data from 5 HCs and 5 CKD patients each scanned 5 times in a scan session to enable comparison of the precision of the CNN and manual segmentation of kidneys. RESULTS: The unseen test data processed by the 2D CNN had a mean Dice score of 0.93 ± 0.01. The difference between manual and automatically computed TKV was 1.2 ± 16.2 mL with a mean surface distance of 0.65 ± 0.21 mm. The variance in TKV measurements from repeat acquisitions on the same subject was significantly lower using the automated method compared to manual segmentation of the kidneys. CONCLUSION: The 2D CNN method provides fully automated segmentation of the left and right kidney and calculation of TKV in <10 s on a standard office computer, allowing high data throughput and is a freely available executable.

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

BACKGROUND: Multi-parametric magnetic resonance imaging (MRI) provides the potential for a more comprehensive non-invasive assessment of organ structure and function than individual MRI measures, but has not previously been comprehensively evaluated in chronic kidney disease (CKD). METHODS: We performed multi-parametric renal MRI in persons with CKD (n = 22, 61 ± 24 years) who had a renal biopsy and measured glomerular filtration rate (mGFR), and matched healthy volunteers (HV) (n = 22, 61 ± 25 years). Longitudinal relaxation time (T1), diffusion-weighted imaging, renal blood flow (phase contrast MRI), cortical perfusion (arterial spin labelling) and blood-oxygen-level-dependent relaxation rate (R2*) were evaluated. RESULTS: MRI evidenced excellent reproducibility in CKD (coefficient of variation <10%). Significant differences between CKD and HVs included cortical and corticomedullary difference (CMD) in T1, cortical and medullary apparent diffusion coefficient (ADC), renal artery blood flow and cortical perfusion. MRI measures correlated with kidney function in a combined CKD and HV analysis: estimated GFR correlated with cortical T1 (r = -0.68), T1 CMD (r = -0.62), cortical (r = 0.54) and medullary ADC (r = 0.49), renal artery flow (r = 0.78) and cortical perfusion (r = 0.81); log urine protein to creatinine ratio (UPCR) correlated with cortical T1 (r = 0.61), T1 CMD (r = 0.61), cortical (r = -0.45) and medullary ADC (r = -0.49), renal artery flow (r = -0.72) and cortical perfusion (r = -0.58). MRI measures (cortical T1 and ADC, T1 and ADC CMD, cortical perfusion) differed between low/high interstitial fibrosis groups at 30-40% fibrosis threshold. CONCLUSION: Comprehensive multi-parametric MRI is reproducible and correlates well with available measures of renal function and pathology. Larger longitudinal studies are warranted to evaluate its potential to stratify prognosis and response to therapy in CKD.

Consensus-based technical recommendations for clinical translation of renal ASL MRI.

OBJECTIVES: This study aimed at developing technical recommendations for the acquisition, processing and analysis of renal ASL data in the human kidney at 1.5 T and 3 T field strengths that can promote standardization of renal perfusion measurements and facilitate the comparability of results across scanners and in multi-centre clinical studies. METHODS: An international panel of 23 renal ASL experts followed a modified Delphi process, including on-line surveys and two in-person meetings, to formulate a series of consensus statements regarding patient preparation, hardware, acquisition protocol, analysis steps and data reporting. RESULTS: Fifty-nine statements achieved consensus, while agreement could not be reached on two statements related to patient preparation. As a default protocol, the panel recommends pseudo-continuous (PCASL) or flow-sensitive alternating inversion recovery (FAIR) labelling with a single-slice spin-echo EPI readout with background suppression and a simple but robust quantification model. DISCUSSION: This approach is considered robust and reproducible and can provide renal perfusion images of adequate quality and SNR for most applications. If extended kidney coverage is desirable, a 2D multislice readout is recommended. These recommendations are based on current available evidence and expert opinion. Nonetheless they are expected to be updated as more data become available, since the renal ASL literature is rapidly expanding.

Arterial spin labelling MRI to measure renal perfusion: a systematic review and statement paper.

Renal perfusion provides the driving pressure for glomerular filtration and delivers the oxygen and nutrients to fuel solute reabsorption. Renal ischaemia is a major mechanism in acute kidney injury and may promote the progression of chronic kidney disease. Thus, quantifying renal tissue perfusion is critically important for both clinicians and physiologists. Current reference techniques for assessing renal tissue perfusion have significant limitations. Arterial spin labelling (ASL) is a magnetic resonance imaging (MRI) technique that uses magnetic labelling of water in arterial blood as an endogenous tracer to generate maps of absolute regional perfusion without requiring exogenous contrast. The technique holds enormous potential for clinical use but remains restricted to research settings. This statement paper from the PARENCHIMA network briefly outlines the ASL technique and reviews renal perfusion data in 53 studies published in English through January 2018. Renal perfusion by ASL has been validated against reference methods and has good reproducibility. Renal perfusion by ASL reduces with age and excretory function. Technical advancements mean that a renal ASL study can acquire a whole kidney perfusion measurement in less than 5-10 min. The short acquisition time permits combination with other MRI techniques that might inform drug mechanisms and renal physiology. The flexibility of renal ASL has yielded several variants of the technique, but there are limited data comparing these approaches. We make recommendations for acquiring and reporting renal ASL data and outline the knowledge gaps that future research should address.

Sodium MRI: a new frontier in imaging in nephrology.

PURPOSE OF REVIEW: This review focuses on the recent technological advances in quantitative sodium (Na) MRI to provide a noninvasive measure of tissue viability for use in clinical studies of patients with kidney disease. Na MRI is the only noninvasive imaging technique that allows for the absolute spatial quantification of tissue sodium concentration (TSC), providing assessment of the corticomedullary sodium gradient (CMSG) in the kidney, and allowing measures of TSC in the skin and muscle. RECENT FINDINGS: Na MRI of the kidney has demonstrated the sensitivity to measure the CMSG, providing the normal range in healthy individuals and demonstrating a reduction in CMSG in kidney disease and transplanted kidneys. Studies using Na and H MRI have shown that in humans, skeletal muscle and skin can store sodium without water retention, and that sodium concentrations in muscle and skin increase with advancing age. Recent studies have shown that TSC can be mobilised during haemodialysis, and that skin sodium content links closely to left ventricular mass in patients with chronic kidney disease. SUMMARY: Na MRI is currently a research technique, but with future advances, Na MRI has potential to become a noninvasive renal biomarker and a measure of tissue sodium storage for clinical studies.

Multiparametric Renal Magnetic Resonance Imaging for Prediction and Annual Monitoring of the Progression of Chronic Kidney Disease over Two Years.

BACKGROUND: Multiparametric renal Magnetic Resonance Imaging (MRI) provides a non-invasive method to assess kidney structure and function, but longitudinal studies are limited. METHODS: A total of 22 patients with CKD category G3-4 (estimated glomerular filtration rate (eGFR) 15-59 mL/min/1.73 m2) were recruited. Annual 3T multiparametric renal MRI scans were performed, comprising total kidney volume (TKV), longitudinal relaxation time (T1), apparent diffusion coefficient (ADC), Arterial Spin Labelling, and Blood Oxygen Level Dependent relaxation time (T2*), with 15 patients completing a Year 2 scan. CKD progression over 2 years was defined as eGFR_slope ≥ -5 mL/min/1.73 m2/year. RESULTS: At baseline, T1 was higher (cortex p = 0.05, medulla p = 0.03) and cortex perfusion lower (p = 0.015) in participants with subsequent progression versus stable eGFR. A significant decrease in TKV and ADC and an increase in cortex T1 occurred in progressors at Year 1 and Year 2, with a significant decrease in perfusion in progressors only at Year 2. The only decline in the stable group was a reduction in TKV. There was no significant change in cortex or medulla T2* at Year 1 or Year 2 for progressors or stable participants. CONCLUSION: Lower renal cortex perfusion and higher T1 in the cortex and medulla may predict CKD progression, while renal cortex T1, TKV, and ADC may be useful to monitor progression. This study provides pilot data for future large-scale studies.

A randomized, controlled, double-blind crossover study on the effects of isoeffective and isovolumetric intravenous crystalloid and gelatin on blood volume, and renal and cardiac hemodynamics.

BACKGROUND & AIMS: Blood volume expanding properties of colloids are superior to crystalloids. In addition to oncotic/osmotic properties, the electrolyte composition of infusions may have important effects on visceral perfusion, with infusions containing supraphysiological chloride causing hyperchloremic acidosis and decreased renal blood flow. In this non-inferiority study, a validated healthy human subject model was used to compare effects of colloid (4% succinylated gelatin) and crystalloid fluid regimens on blood volume, renal function, and cardiac output. METHODS: Healthy male participants were given infusions over 60 min > 7 days apart in a randomized, crossover manner. Reference arm (A): 1.5 L of Sterofundin ISO, isoeffective arm (B): 0.5 L of 4% Gelaspan®, isovolumetric arm (C): 0.5 L of 4% Gelaspan® and 1 L of Sterofundin ISO (all B. Braun, Melsungen, Germany). Participants were studied over 240 min. Changes in blood volume were calculated from changes in weight and hematocrit. Renal volume, renal artery blood flow (RABF), renal cortex perfusion and diffusion, and cardiac index were measured with magnetic resonance imaging. RESULTS: Ten of 12 males [mean (SE) age 23.9 (0.8) years] recruited, completed the study. Increase in body weight and extracellular fluid volume were significantly less after infusion B than infusions A and C, but changes in blood volume did not significantly differ between infusions. All infusions increased renal volume, with no significant differences between infusions. There was no significant difference in RABF across the infusion time course or between infusion types. Renal cortex perfusion decreased during the infusion (mean 18% decrease from baseline), with no significant difference between infusions. There was a trend for increased renal cortex diffusion (4.2% increase from baseline) for the crystalloid infusion. All infusions led to significant increases in cardiac index. CONCLUSIONS: A smaller volume of colloid (4% succinylated gelatin) was as effective as a larger volume of crystalloid at expanding blood volume, increasing cardiac output and changing renal function. Significantly less interstitial space expansion occurred with the colloid. TRIAL REGISTRATION: The protocol was registered with the European Union Drug Regulating Authorities Clinical Trials Database (https://eudract.ema.europa.eu) (EudraCT No. 2013-003260-32).

Evaluation of 2D Imaging Schemes for Pulsed Arterial Spin Labeling of the Human Kidney Cortex.

A number of imaging readout schemes are proposed for renal arterial spin labeling (ASL) to quantify kidney cortex perfusion, including gradient echo-based methods of balanced fast field echo (bFFE) and gradient-echo echo-planar imaging (GE-EPI), or spin echo-based schemes of spin-echo echo-planar imaging (SE-EPI) and turbo spin-echo (TSE). Here, we compare these two-dimensional (2D) imaging schemes to evaluate the optimal imaging scheme for pulsed ASL (PASL) assessment of human kidney cortex perfusion at 3 T. Ten healthy volunteers with normal renal function were scanned using each 2D multi-slice imaging scheme, in combination with a respiratory triggered flow-sensitive alternating inversion recovery (FAIR) ASL scheme on a 3 T Philips Achieva scanner. All volunteers returned for a second identical scan session within two weeks of the first scan session. Comparisons were made between the imaging schemes in terms of perfusion-weighted image (PWI) signal-to-noise ratio (SNR) and perfusion quantification, temporal SNR (tSNR), spatial coverage, and repeatability. For each imaging scheme, the renal cortex perfusion was calculated (bFFE: 276 ± 29 mL/100g/min, GE-EPI: 222 ± 18 mL/100g/min, SE-EPI: 201 ± 36 mL/100g/min, and TSE: 200 ± 20 mL/100g/min). Perfusion was found to be higher for GE-based readouts when compared with SE-based readouts, with significantly higher measured perfusion for the bFFE readout when compared with all other schemes (p < 0.05), attributed to the greater vascular signal present. Despite the PWI-SNR being significantly lower for SE-EPI when compared with all other schemes (p < 0.05), the SE-EPI readout gave the highest tSNR, and was found to be the most reproducible scheme for the assessment of kidney cortex, with a coefficient of variation (CoV) of 17.2%, whilst minimizing variability of the perfusion-weighted signal across slices for whole-kidney perfusion assessment. For the assessment of kidney cortex perfusion using 2D readout schemes, SE-EPI provides optimal tSNR, minimal variability across slices, and repeatable data acquired in a short scan time with low specific absorption rate.

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.