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

Harmonization of acquisition and analysis protocols is an important step in the validation of BOLD MRI as a renal biomarker. This harmonization initiative provides technical recommendations based on a consensus report with the aim to move towards standardized protocols that facilitate clinical translation and comparison of data across sites. We used a recently published systematic review paper, which included a detailed summary of renal BOLD MRI technical parameters and areas of investigation in its supplementary material, as the starting point in developing the survey questionnaires for seeking consensus. Survey data were collected via the Delphi consensus process from 24 researchers on renal BOLD MRI exam preparation, data acquisition, data analysis, and interpretation. Consensus was defined as ≥ 75% unanimity in response. Among 31 survey questions, 14 achieved consensus resolution, 12 showed clear respondent preference (65-74% agreement), and 5 showed equal (50/50%) split in opinion among respondents. Recommendations for subject preparation, data acquisition, processing and reporting are given based on the survey results and review of the literature. These technical recommendations are aimed towards increased inter-site harmonization, a first step towards standardization of renal BOLD MRI protocols across sites. We expect this to be an iterative process updated dynamically based on progress in the field.

Continuous prospectively navigated multi-echo GRE for improved BOLD imaging of the kidneys.

The objective of this study is to develop improved methods for renal blood oxygenation level dependent (BOLD) imaging. T2* mapping of the kidneys, or renal BOLD imaging, may depict renal oxygen levels and may be valuable as a noninvasive means of following the progression of renal disease. Current renal BOLD data is limited by imaging in a single breath hold, which results in low resolution and low signal-to-noise ratio (SNR). We compare a new free-breathing renal BOLD method with conventional breath-hold BOLD (BH-BOLD). A multi-echo GRE sequence with continuous prospective respiratory navigation and real-time feedback was developed that allows high resolution and high SNR renal BOLD imaging with constant sequence repetition time (TR) during free-breathing BOLD (FB-BOLD). The sequence was evaluated in 10 normal volunteers and compared with conventional BH-BOLD. Scan time for the FB-BOLD sequence was approximately three minutes, compared with 15 seconds for the BH-BOLD sequence. SNR of source images and residual error of T2* fitting were compared between the two methods. The FB-BOLD sequence produced motion-free T2* maps of the kidneys with SNR 1.9 times higher than BH-BOLD images. Residual error of T2* fitting was consistently lower in the right kidney with FB-BOLD (30% less than BH-BOLD) but higher in the left kidney (80% more than BH-BOLD), likely related to placement of the navigator on the right hemidiaphragm. A free-breathing prospectively navigated renal BOLD sequence allows flexible tradeoff between scan time, resolution, and SNR.

Diagnostic Accuracy of Noncontrast MR Angiography Protocols at 3T for the Detection and Characterization of Lower Extremity Peripheral Arterial Disease.

PURPOSE: To compare the diagnostic accuracy of established non-gadolinium (Gd)-enhanced magnetic resonance (MR) angiography protocols with Gd-enhanced MR angiography at 3T for evaluating lower extremity peripheral arterial disease (PAD). MATERIALS AND METHODS: From February 2014 to 2015, 20 patients with PAD and intermittent claudication (16 men; age range, 51-76 y; Fontaine stage II) underwent 3-station (abdominopelvic, thigh, and calf) non-Gd MR angiography and bolus-chase Gd MR angiography protocols performed at 3T (Siemens Tim Trio), including quiescent-interval single-shot (QISS) MR angiography for all 3 stations and a combination of quadruple inversion recovery (QIR) MR angiography for the abdominopelvic station and electrocardiogram-gated fast spin echo (ECG-FSE) MR angiography for the extremities. Two radiologists independently evaluated vessel segments for vascular stenosis, diagnosis confidence, graft presence, and Trans-Atlantic Inter-Society Consensus (TASC) II classification for each station. Diagnostic accuracies and κ agreement were assessed. RESULTS: Of 573 vascular segments imaged, 16.9% (97/573, 19/20 patients) demonstrated hemodynamically significant abnormalities. Reader confidence was sufficient for diagnosis in 98% of segments with Gd MR angiography, 93% with QIR/ECG-FSE, and 95% with QISS. Overall reader confidence was higher with QISS than QIR/ECG-FSE within all 3 stations combined (P < .05). With low-confidence segments treated as misdiagnosis, sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and κ agreement for all 3 stations combined were 81.4/87.2/57.0/95.8/86.2%/0.578 for QIR/ECG-FSE and 75.0/90.6/61.6/94.7/88.0%/0.597 for QISS. Using TASC II criteria to assess severity, QISS and QIR/ECG-FSE had no statistical difference in agreement with Gd MR angiography. CONCLUSIONS: QISS and QIR/ECG-FSE MR angiography protocols demonstrate comparable diagnostic accuracies with high specificity. Either protocol provides an alternative to Gd MR angiography at 3T for patients with PAD.

Magnetic Resonance Imaging of the Fibrotic Kidney.

Magnetic resonance imaging (MRI) has been used for many years for anatomic evaluation of the kidney. Recently developed methods attempt to go beyond anatomy to give information about the health and function of the kidneys. Several methods, including diffusion-weighted MRI, renal blood oxygen level-dependent MRI, renal MR elastography, and renal susceptibility imaging, show promise for providing unique insight into kidney function and severity of fibrosis. However, substantial limitations in accuracy and practicality limit the immediate clinical application of each method. Further development and improvement are necessary to achieve the ideal of a noninvasive image-based measure of renal fibrosis. Our brief review provides a short explanation of these emerging MRI methods and outlines the promising initial results obtained with each as well as current limitations and barriers to clinical implementation.

T2* Measurement bias due to concomitant gradient fields.

PURPOSE: 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. THEORY AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Optimization of saturation-recovery dynamic contrast-enhanced MRI acquisition protocol: monte carlo simulation approach demonstrated with gadolinium MR renography.

Dynamic contrast-enhanced (DCE) MRI is widely used for the measurement of tissue perfusion and to assess organ function. MR renography, which is acquired using a DCE sequence, can measure renal perfusion, filtration and concentrating ability. Optimization of the DCE acquisition protocol is important for the minimization of the error propagation from the acquired signals to the estimated parameters, thus improving the precision of the parameters. Critical to the optimization of contrast-enhanced T1 -weighted protocols is the balance of the T1 -shortening effect across the range of gadolinium (Gd) contrast concentration in the tissue of interest. In this study, we demonstrate a Monte Carlo simulation approach for the optimization of DCE MRI, in which a saturation-recovery T1 -weighted gradient echo sequence is simulated and the impact of injected dose (D) and time delay (TD, for saturation recovery) is tested. The results show that high D and/or high TD cause saturation of the peak arterial signals and lead to an overestimation of renal plasma flow (RPF) and glomerular filtration rate (GFR). However, the use of low TD (e.g. 100 ms) and low D leads to similar errors in RPF and GFR, because of the Rician bias in the pre-contrast arterial signals. Our patient study including 22 human subjects compared TD values of 100 and 300 ms after the injection of 4 mL of Gd contrast for MR renography. At TD = 100 ms, we computed an RPF value of 157.2 ± 51.7 mL/min and a GFR of 33.3 ± 11.6 mL/min. These results were all significantly higher than the parameter estimates at TD = 300 ms: RPF = 143.4 ± 48.8 mL/min (p = 0.0006) and GFR = 30.2 ± 11.5 mL/min (p = 0.0015). In conclusion, appropriate optimization of the DCE MRI protocol using simulation can effectively improve the precision and, potentially, the accuracy of the measured parameters. Copyright © 2016 John Wiley & Sons, Ltd.

Synchronous Radial 1H and 23Na Dual-Nuclear MRI on a Clinical MRI System, Equipped With a Broadband Transmit Channel.

The purpose of this work was to synchronously acquire proton (1H) and sodium (23Na) image data on a 3T clinical MRI system within the same sequence, without internal modification of the clinical hardware, and to demonstrate synchronous acquisition with 1H/23Na-GRE imaging with Cartesian and radial k-space sampling. Synchronous dual-nuclear imaging was implemented by: mixing down the 1H signal so that both the 23Na and 1H signal were acquired at 23Na frequency by the conventional MRI system; interleaving 1H/23Na transmit pulses in both Cartesian and radial sequences; and using phase stabilization on the 1H signal to remove mixing effects. The synchronous 1H/23Na setup obtained images in half the time necessary to sequentially acquire the same 1H and 23Na images with the given setup and parameters. Dual-nuclear hardware and sequence modifications were used to acquire 23Na images within the same sequence as 1H images, without increases to the 1H acquisition time. This work demonstrates a viable technique to acquire 23Na image data without increasing 1H acquisition time using minor additional custom hardware, without requiring modification of a commercial scanner with multinuclear capability.

Psoas Muscle Cross-sectional Area as a Measure of Whole-body Lean Muscle Mass in Maintenance Hemodialysis Patients.

OBJECTIVE: We investigate whether psoas or paraspinous muscle area measured on a single L4-L5 image is a useful measure of whole lean body mass (LBM) compared to dedicated midthigh magnetic resonance imaging (MRI). DESIGN: Observational study. SETTING: Outpatient dialysis units and a research clinic. SUBJECTS: One hundred five adult participants on maintenance hemodialysis. No control group was used. INTERVENTION: Psoas muscle area, paraspinous muscle area, and midthigh muscle area (MTMA) were measured by magnetic resonance imaging. MAIN OUTCOME MEASURE: LBM was measured by dual-energy absorptiometry scan. RESULTS: In separate multivariable linear regression models, psoas, paraspinous, and MTMA were associated with increase in LBM. In separate multivariate logistic regression models, C statistics for diagnosis of sarcopenia (defined as <25th percentile of LBM) were 0.69 for paraspinous muscle area, 0.81 for psoas muscle area, and 0.89 for MTMA. With sarcopenia defined as <10th percentile of LBM, the corresponding C statistics were 0.71, 0.92, and 0.94. CONCLUSIONS: We conclude that psoas muscle area provides a good measure of whole-body muscle mass, better than paraspinous muscle area but slightly inferior to midthigh measurement. Hence, in body composition studies a single axial MR image at the L4-L5 level can be used to provide information on both fat and muscle and may eliminate the need for time-consuming measurement of muscle area in the thigh.

Low Physical Function in Maintenance Hemodialysis Patients Is Independent of Muscle Mass and Comorbidity.

OBJECTIVES: It is unknown whether muscle wasting accounts for impaired physical function in adults on maintenance hemodialysis (MHD). DESIGN: Observational study. SETTING: Outpatient dialysis units and a fall clinic. SUBJECTS: One hundred eight MHD and 122 elderly nonhemodialysis (non-HD) participants. EXPOSURE VARIABLE: Mid-thigh muscle area was measured by magnetic resonance imaging. MAIN OUTCOME MEASURE: Physical function was measured by distance walked in 6 minutes. RESULTS: Compared with non-HD elderly participants, MHD participants were younger (49.2 ± 15.8 vs. 75.3 ± 7.1 years; P < .001) and had higher mid-thigh muscle area (106.2 ± 26.8 vs. 96.1 ± 21.1 cm2; P = .002). However, the distance walked in 6 minutes was lower in MHD participants (322.9 ± 110.4 vs. 409.0 ± 128.3 m; P < .001). In multiple regression analysis adjusted for demographics, comorbid conditions, and mid-thigh muscle area, MHD patients walked significantly less distance (-117 m; 95% confidence interval: -177 to -56 m; P < .001) than the non-HD elderly. CONCLUSIONS: Even when compared with elderly non-HD participants, younger MHD participants have poorer physical function that was not explained by muscle mass or comorbid conditions. We speculate that the uremic milieu may impair muscle function independent of muscle mass. The mechanism of impaired muscle function in uremia needs to be established in future studies.

Measurement of renal tissue oxygenation with blood oxygen level-dependent MRI and oxygen transit modeling.

Blood oxygen level-dependent (BOLD) MRI data of kidney, while indicative of tissue oxygenation level (Po2), is in fact influenced by multiple confounding factors, such as R2, perfusion, oxygen permeability, and hematocrit. We aim to explore the feasibility of extracting tissue Po2 from renal BOLD data. A method of two steps was proposed: first, a Monte Carlo simulation to estimate blood oxygen saturation (SHb) from BOLD signals, and second, an oxygen transit model to convert SHb to tissue Po2. The proposed method was calibrated and validated with 20 pigs (12 before and after furosemide injection) in which BOLD-derived tissue Po2 was compared with microprobe-measured values. The method was then applied to nine healthy human subjects (age: 25.7 ± 3.0 yr) in whom BOLD was performed before and after furosemide. For the 12 pigs before furosemide injection, the proposed model estimated renal tissue Po2 with errors of 2.3 ± 5.2 mmHg (5.8 ± 13.4%) in cortex and -0.1 ± 4.5 mmHg (1.7 ± 18.1%) in medulla, compared with microprobe measurements. After injection of furosemide, the estimation errors were 6.9 ± 3.9 mmHg (14.2 ± 8.4%) for cortex and 2.6 ± 4.0 mmHg (7.7 ± 11.5%) for medulla. In the human subjects, BOLD-derived medullary Po2 increased from 16.0 ± 4.9 mmHg (SHb: 31 ± 11%) at baseline to 26.2 ± 3.1 mmHg (SHb: 53 ± 6%) at 5 min after furosemide injection, while cortical Po2 did not change significantly at ∼58 mmHg (SHb: 92 ± 1%). Our proposed method, validated with a porcine model, appears promising for estimating tissue Po2 from renal BOLD MRI data in human subjects.

New magnetic resonance imaging methods in nephrology.

Established as a method to study anatomic changes, such as renal tumors or atherosclerotic vascular disease, magnetic resonance imaging (MRI) to interrogate renal function has only recently begun to come of age. In this review, we briefly introduce some of the most important MRI techniques for renal functional imaging, and then review current findings on their use for diagnosis and monitoring of major kidney diseases. Specific applications include renovascular disease, diabetic nephropathy, renal transplants, renal masses, acute kidney injury, and pediatric anomalies. With this review, we hope to encourage more collaboration between nephrologists and radiologists to accelerate the development and application of modern MRI tools in nephrology clinics.

A 3 T sodium and proton composite array breast coil.

PURPOSE: The objective of this study was to determine whether a sodium phased array would improve sodium breast MRI at 3 T. The secondary objective was to create acceptable proton images with the sodium phased array in place. METHODS: A novel composite array for combined proton/sodium 3 T breast MRI is compared with a coil with a single proton and sodium channel. The composite array consists of a 7-channel sodium receive array, a larger sodium transmit coil, and a 4-channel proton transceive array. The new composite array design utilizes smaller sodium receive loops than typically used in sodium imaging, uses novel decoupling methods between the receive loops and transmit loops, and uses a novel multichannel proton transceive coil. The proton transceive coil reduces coupling between proton and sodium elements by intersecting the constituent loops to reduce their mutual inductance. The coil used for comparison consists of a concentric sodium and proton loop with passive decoupling traps. RESULTS: The composite array coil demonstrates a 2-5× improvement in signal-to-noise ratio for sodium imaging and similar signal-to-noise ratio for proton imaging when compared with a simple single-loop dual resonant design. CONCLUSION: The improved signal-to-noise ratio of the composite array gives breast sodium images of unprecedented quality in reasonable scan times.

Science to practice: Renal hypoxia and fat deposition in diabetic neuropathy--new insights with functional renal MR imaging.

Despite being a valuable tool for evaluation of the kidneys, renal magnetic resonance (MR) imaging in clinical practice has been limited to depiction of anatomy and provides little diagnostic information about the health and function of the kidney in patients with chronic kidney disease (CKD) and diabetic nephropathy. In this issue, Peng et al (1) have used two MR imaging methods that go beyond depiction of anatomy to show renal function: renal blood oxygen level-dependent (BOLD) MR imaging, which shows oxygen levels in the kidney, and chemical shift-selective imaging, which shows the relative content of fat in the kidney parenchyma. In a mouse model of diabetes, Peng et al have shown higher fat and lower oxygen levels in kidneys of mice with diabetes than in those of normal controls. These MR imaging methods may help clarify the role of fat deposition and hypoxia in the progression of CKD. As the factors that contribute to the progression of CKD are better understood, ultimately more widespread clinical use for functional renal MR imaging protocols such as renal BOLD and chemical shift-selective imaging may be found to evaluate the severity of CKD and monitor the efficacy of clinical interventions, altering the course of disease progression.

Simultaneous fat suppression and band reduction with large-angle multiple-acquisition balanced steady-state free precession.

Balanced steady-state free precession (bSSFP) MRI is a rapid and signal-to-noise ratio-efficient imaging method, but suffers from characteristic bands of signal loss in regions of large field inhomogeneity. Several methods have been developed to reduce the severity of these banding artifacts, typically involving the acquisition of multiple bSSFP datasets (and the accompanying increase in scan time). Fat suppression with bSSFP is also challenging; most existing methods require an additional increase in scan time, and some are incompatible with bSSFP band-reduction techniques. This work was motivated by the need for both robust fat suppression and band reduction in the presence of field inhomogeneity when using bSSFP for flow-independent peripheral angiography. The large flip angles used in this application to improve vessel conspicuity and contrast lead to specific absorption rate considerations, longer repetition times, and increased severity of banding artifacts. In this work, a novel method that simultaneously suppresses fat and reduces bSSFP banding artifact with the acquisition of only two phase-cycled bSSFP datasets is presented. A weighted sum of the two bSSFP acquisitions is taken on a voxel-by-voxel basis, effectively synthesizing an off-resonance profile at each voxel that puts fat in the stop band while keeping water in the pass band. The technique exploits the near-sinusoidal shape of the bSSFP off-resonance spectrum for many tissues at large (>50°) flip angles.

The Effect of Maximum Tumor Diameter by MRI on Disease Control in Intermediate and High-risk Prostate Cancer Patients Treated With Brachytherapy Boost.

BACKGROUND: Larger maximum tumor diameter (MTD) has been associated with worse prostate cancer (PCa) outcomes. However, the impact of MTD in PCa treated with external beam radiotherapy and brachytherapy boost (EBRT+BB) remains unknown. MATERIALS AND METHODS: Patients with PCa treated with EBRT+BB were identified from an institutional database. Clinical data including MTD, age, androgen deprivation therapy (ADT) use, prostate specific antigen (PSA), International Society of Urologic Pathology (ISUP) group, clinical T-stage, and presence of adverse pathology on imaging were retrospectively collected. Multivariable and univariable cox proportional hazards models for biochemical failure (BF) and distant metastasis (DM) were produced with MTD grouped by receiver operating characteristic (ROC) cut-point. Cumulative hazard functions for BF and DM were compared with log-rank test and stratified by ISUP group. RESULTS: Of 191 patients treated with EBRT+BB, 113 had MTD measurements available. Larger MTD was associated with increased ADT use and seminal vesicle involvement. ROC optimization identified MTD of 24 mm as the optimal cut-point for both BF and DM. MTD was independently associated with both BF (HR 8.61, P = .048, 95% CI 1.02-72.97) and DM (HR 8.55, P = .05, 95% CI 1.00-73.19). In patients with ISUP group 4 to 5 disease, MTD > 24 mm was independently associated with increased risk of DM (HR 10.13, P = .04, 95% CI 1.13-91.12). CONCLUSIONS: This is the first study to evaluate MTD in the setting of EBRT+BB. These results demonstrate that MTD is independently associated with BF and metastasis. This suggests a possible role for MTD in risk assessment models and clinical decision-making for men receiving EBRT+BB.

The Clinical Significance of Maximum Tumor Diameter on MRI in Men Undergoing Radical Prostatectomy or Definitive Radiotherapy for Locoregional Prostate Cancer.

INTRODUCTION: Maximum tumor diameter (MTD) on pretreatment magnetic resonance imaging (MRI) has the potential to further risk stratify for men with prostate cancer (PCa) prior to definitive local therapy. We aim to evaluate the prognostic impact of radiographic maximum tumor diameter (MTD) in men with localized prostate cancer. PATIENTS AND METHODS: From a single-center retrospective cohort of men receiving definitive treatment for PCa (radical prostatectomy [RP] or radiotherapy [RT]) with available pretreatment MRI, we conducted univariable and multivariable Cox proportional-hazards models for progression using clinical variables including age, NCCN risk group, radiographic extracapsular extension (ECE), radiographic seminal vesical invasion (SVI), and MTD. RP and RT cohorts were analyzed separately. Covariates were used in a classification and regression tree (CART) analysis and progression-free survival was estimated with the Kaplan-Meier method and groups were compared using log-rank tests. RESULTS: The cohort included 631 patients (n = 428 RP, n = 203 RT). CART analysis identified 4 prognostic groups for patients treated with RP and 2 prognostic groups in those treated with RT. In the RP cohort, NCCN low/intermediate risk group patients with MTD>=15 mm had significantly worse PFS than those with MTD <= 14 mm, and NCCN high-risk patients with radiographic ECE had significantly worse PFS than those without ECE. In the RT cohort, PFS was significantly worse in the cohort with MTD >= 23 mm than those <= 22 mm. CONCLUSION: Radiographic MTD may be a useful prognostic factor for patients with locoregional prostate cancer. This is the first study to illustrate that the importance of pretreatment tumor size may vary based on treatment modality.