David J. Niles

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.

Hyperpolarized Helium-3 MRI of Exercise-Induced Bronchoconstriction During Challenge and Therapy

To investigate the utility of hyperpolarized He‐3 MRI for detecting regional lung ventilated volume (VV) changes in response to exercise challenge and leukotriene inhibitor montelukast, human subjects with exercise induced bronchoconstriction (EIB) were recruited. This condition is described by airway constriction following exercise leading to reduced forced expiratory volume in 1 second (FEV1) coinciding with ventilation defects on hyperpolarized He‐3 MRI.

Exercise-induced bronchoconstriction: reproducibility of hyperpolarized 3He MR imaging.

PURPOSE To quantitatively evaluate interday, interreader, and intersite agreement of readers of hyperpolarized helium 3 (HPHe) MR images in patients with exercise-induced bronchoconstriction. MATERIALS AND METHODS This HIPAA-compliant, institutional review board approved study included 13 patients with exercise-induced bronchoconstriction. On two separate days, HPHe MR imaging of the lungs was performed at baseline, immediately after a 10-minute exercise challenge (postchallenge), and 45 minutes after exercise (recovery). Patients were imaged at two sites, six at site A and seven at site B. Images were analyzed independently by multiple readers at each site. Lung volume, ventilation defect volume, ventilated volume, and the number of defects were measured quantitatively, and the location of defects was evaluated qualitatively at site A. Interday and interreader agreement were evaluated by using the intraclass correlation coefficient (ICC), and intersite agreement was evaluated by using a modified Bland-Altman analysis. RESULTS The ICC between days for ventilation defect volume, ventilated volume, and number of defects was at least 0.74 at both sites. The ICC for lung volume was greater at site B (0.83-0.86) than at site A (0.60-0.65). Defects seen in the same location in the lung on both days included 19.7% of those seen on baseline images and 29.2% and 18.6% of defects on postchallenge and recovery images, respectively. Interreader ICC for each measurement was at least 0.82 for each site. Analysis of intersite agreement showed biases of 612 mL for lung volume, -60.7 mL for ventilation defect volume, 2.91% for ventilated volume, and -6.56 for number of defects. CONCLUSION The reported measures of reproducibility of HPHe MR imaging may help in the design and interpretation of single- and multicenter studies of patients with exercise-induced bronchoconstriction.

In Vivo Imaging and Spectroscopy of Dynamic Metabolism Using Simultaneous

Hyperpolarized (HP) 13C-labeled pyruvate studies with magnetic resonance (MR) have been used to observe the kinetics of metabolism in vivo. Kinetic modeling to measure metabolic rates in vivo is currently limited because of nonspecific hyperpolarized signals mixing between vascular, extravascular, and intracellular compartments. In this study, simultaneous acquisition of both 1H and 13 C signals after contrast agent injection is used to resolve specific compartments to improve the accuracy of the modeling. We demonstrate a novel technique to provide contrast to the intracellular compartments by sequential injection of HP [1-13C] pyruvate followed by gadolinium-chelate to provide T1-shortening to extra-cellular compartments. A kinetic model that distinguishes the intracellular space and includes the T1-shortening effect of the gadolinium chelate can then be used to directly measure the intracellular 13C kinetics.

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ObjectivesThe aims of this study were to assess renal function in kidney transplant recipients and their respective donors over 2 years using arterial spin labeling (ASL) and blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) and to prospectively evaluate the effect of losartan on functional MRI measures in recipients. Materials and MethodsThe study included 15 matched pairs of renal transplant donors and recipients. Arterial spin labeling and BOLD MRI of the kidneys were performed on donors before transplant surgery (baseline) and on both donors and recipients at 3 months, 1 year, and 2 years after transplant. After 3 months, 7 of the 15 recipients were prescribed 25 to 50 mg/d losartan for the remainder of the study. A linear mixed-effects model was used to evaluate perfusion, R2*, estimated glomerular filtration rate, and fractional excretion of sodium for changes across time or associated with losartan treatment. ResultsIn donors, cortical perfusion in the remaining kidney decreased by 50 ± 19 mL/min per 100 g (11.8%) between baseline and 2 years (P < 0.05), while cortical R2* declined modestly by 0.7 ± 0.3 s−1 (5.6%; P < 0.05). In transplanted kidneys, cortical perfusion decreased markedly by 141 ± 21 mL/min per 100 g (34.2%) between baseline and 2 years (P < 0.001), while medullary R2* declined by 1.5 ± 0.8 s−1 (8.3%; P = 0.06). Single-kidney estimated glomerular filtration rate increased between baseline and 2 years by 17.7 ± 2.7 mL/min per 1.73 m2 (40.3%; P < 0.0001) in donors and to 14.6 ± 4.3 mL/min per 1.73 m2 (33.3%; P < 0.01) in recipients. Cortical perfusion at 1 and 2 years in recipients receiving 25 to 50 mg/d losartan was 62 ± 24 mL/min per 100 g higher than recipients not receiving the drug (P < 0.05). No significant effects of losartan were observed for any other markers of renal function. ConclusionsThe results suggest an important role for noninvasive functional monitoring with ASL and BOLD MRI in kidney transplant recipients and donors, and they indicate a potentially beneficial effect of losartan in recipients.

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Rapid growth in the field of stem cell research has generated a lot of interest in their therapeutic use, especially in the treatment of neurodegenerative diseases. Specifically, human neural progenitor cells (hNPCs), unique in their capability to differentiate into cells of the neural lineage, have been widely investigated due to their ability to survive, thrive, and migrate toward injured tissues. Still, one of the major roadblocks for clinical applicability arises from the inability to monitor these cells following transplantation. Molecular imaging techniques, such as magnetic resonance imaging (MRI), have been explored to assess hNPC transplant location, migration, and survival. Here we investigated whether inducing hNPCs to overexpress ferritin (hNPCsFer), an iron storage protein, is sufficient to track these cells long term in the rat striatum using MRI. We found that increased hypointensity on MRI images could establish hNPCFer location. Unexpectedly, however, wild-type hNPC transplants were detected in a similar manner, which is likely due to increased iron accumulation following transplantation-induced damage. Hence, we labeled hNPCs with superparamagnetic iron oxide (SPIO) nanoparticles to further increase iron content in an attempt to enhance cell contrast in MRI. SPIO-labeling of hNPCs (hNPCs-SPIO) achieved increased hypointensity, with significantly greater area of decreased T2* compared to hNPCFer (p < 0.0001) and all other controls used. However, none of the techniques could be used to determine graft rejection in vivo, which is imperative for understanding cell behavior following transplantation. We conclude that in order for cell survival to be monitored in preclinical and clinical settings, another molecular imaging technique must be employed, including perhaps multimodal imaging, which would utilize MRI along with another imaging modality.

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To develop a novel imaging technique to reduce the number of excitations and required scan time for hyperpolarized 13C imaging.

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To develop the use of bipolar gradients to suppress partial‐volume and flow‐related artifacts from macrovascular, hyperpolarized spins.

Longitudinal Assessment of Renal Perfusion and Oxygenation in Transplant Donor-Recipient Pairs Using Arterial Spin Labeling and Blood Oxygen Level-Dependent Magnetic Resonance Imaging.

RATIONALE AND OBJECTIVES This study aimed to compare the performance of a semiautomated ventilation defect segmentation approach, adaptive K-means, with manual segmentation of hyperpolarized helium-3 magnetic resonance imaging in subjects with exercise-induced bronchoconstriction (EIB). MATERIALS AND METHODS Six subjects with EIB underwent hyperpolarized helium-3 magnetic resonance imaging and spirometry tests at baseline, post exercise, and recovery over two separate visits. Ventilation defects were analyzed by two methods. First, two independent readers manually segmented ventilation defects. Second, defects were quantified by an adaptive K-means method that corrected for coil sensitivity, applied a vesselness filter to estimate pulmonary vasculature, and segmented defects adaptively based on the overall low-intensity signals in the lungs. These two methods were then compared in four aspects: (1) ventilation defect percent (VDP) measurements, (2) correlation between spirometric measures and measured VDP, (3) regional VDP variations pre- and post exercise challenge, and (4) Dice coefficient for spatial agreement. RESULTS The adaptive K-means method was ~5 times faster, and the measured VDP bias was under 2%. The correlation between predicted forced expiratory volume in 1 second over forced vital capacity and VDP measured by adaptive K-means (ρ = -0.64, P <0.0001) and by the manual method (ρ = -0.63, P <0.0001) yielded almost identical 95% confidence intervals. Neither method of measuring VDP indicated apical/basal or anterior dependence in this small study cohort. CONCLUSIONS Compared to the manual method, the adaptive K-means method provided faster, reproducible, comparable measures of VDP in EIB and may be applied to a variety of lung diseases.

In Vivo Tracking of Human Neural Progenitor Cells in the Rat Brain Using Magnetic Resonance Imaging is Not Enhanced by Ferritin Expression

Real‐time imaging of 13C metabolism in vivo has been enabled by recent advances in hyperpolarization. As a result of the inherently low natural abundance of endogenous 13C nuclei, hyperpolarized 13C images lack structural information that could be used to aid in motion detection and anatomical registration. Motion before or during the 13C acquisition can therefore result in artifacts and misregistration that may obscure measures of metabolism. In this work, we demonstrate a method to simultaneously image both 1H and 13C nuclei using a dual‐nucleus spectral–spatial radiofrequency excitation and a fully coincident readout for rapid multinuclear spectroscopic imaging. With the appropriate multinuclear hardware, and the means to simultaneously excite and receive on both channels, this technique is straightforward to implement requiring little to no increase in scan time. Phantom and in vivo experiments were performed with both Cartesian and spiral trajectories to validate and illustrate the utility of simultaneous acquisitions. Motion compensation of dynamic metabolic measurements acquired during free breathing was demonstrated using motion tracking derived from 1H data. Simultaneous multinuclear imaging provides structural 1H and metabolic 13C images that are correlated both spatially and temporally, and are therefore amenable to joint 1H and 13C analysis and correction of structure–function images. Copyright