Safety and efficacy of (+)-epicatechin in subjects with Friedreich's ataxia: A phase II, open-label, prospective study.

BACKGROUND: (+)-Epicatechin (EPI) induces mitochondrial biogenesis and antioxidant metabolism in muscle fibers and neurons. We aimed to evaluate safety and efficacy of (+)-EPI in pediatric subjects with Friedreich's ataxia (FRDA). METHODS: This was a phase II, open-label, baseline-controlled single-center trial including 10 participants ages 10 to 22 with confirmed FA diagnosis. (+)-EPI was administered orally at 75 mg/d for 24 weeks, with escalation to 150 mg/d at 12 weeks for subjects not showing improvement of neuromuscular, neurological or cardiac endpoints. Neurological endpoints were change from baseline in Friedreich's Ataxia Rating Scale (FARS) and 8-m timed walk. Cardiac endpoints were changes from baseline in left ventricular (LV) structure and function by cardiac magnetic resonance imaging (MRI) and echocardiogram, changes in cardiac electrophysiology, and changes in biomarkers for heart failure and hypertrophy. RESULTS: Mean FARS/modified (m)FARS scores showed nonstatistically significant improvement by both group and individual analysis. FARS/mFARS scores improved in 5/9 subjects (56%), 8-m walk in 3/9 (33%), 9-peg hole test in 6/10 (60%). LV mass index by cardiac MRI was significantly reduced at 12 weeks (P = .045), and was improved in 7/10 (70%) subjects at 24 weeks. Mean LV ejection fraction was increased at 24 weeks (P = .008) compared to baseline. Mean maximal septal thickness by echocardiography was increased at 24 weeks (P = .031). There were no serious adverse events. CONCLUSION: (+)-EPI was well tolerated over 24 weeks at up to 150 mg/d. Improvement was observed in cardiac structure and function in subset of subjects with FRDA without statistically significant improvement in primary neurological outcomes. SYNOPSIS: A (+)-epicatechin showed improvement of cardiac function, nonsignificant reduction of FARS/mFARS scores, and sustained significant upregulation of muscle-regeneration biomarker follistatin.

In a Phase 1a escalating clinical trial, autologous mesenchymal stem cell infusion for renovascular disease increases blood flow and the glomerular filtration rate while reducing inflammatory biomarkers and blood pressure.

Atherosclerotic renovascular disease (ARVD) reduces tissue perfusion and eventually leads to loss of kidney function with limited therapeutic options. Here we describe results of Phase 1a escalating dose clinical trial of autologous mesenchymal stem cell infusion for ARVD. Thirty-nine patients with ARVD were studied on two occasions separated by three months. Autologous adipose-derived mesenchymal stem cells were infused through the renal artery in 21 patients at three different dose levels (1, 2.5 and 5.0 × 105 cells/kg) in seven patients each. We measured renal blood flow, glomerular filtration rate (GFR) (iothalamate and estimated GFR), renal vein cytokine levels, blood pressure, and tissue oxygenation before and three months after stem cell delivery. These indices were compared to those of 18 patients with ARVD matched for age, kidney function and blood pressure receiving medical therapy alone that underwent an identical study protocol. Cultured mesenchymal stem cells were also studied in vitro. For the entire stem cell treated-cohort, mean renal blood flow in the treated stenotic kidney significantly increased after stem cell infusion from (164 to 190 ml/min). Hypoxia, renal vein inflammatory cytokines, and angiogenic biomarkers significantly decreased following stem cell infusion. Mean systolic blood pressure significantly fell (144 to 136 mmHg) and the mean two-kidney GFR (Iothalamate) modestly but significantly increased from (53 to 56 ml/min). Changes in GFR and blood pressure were largest in the high dose stem cell treated individuals. No such changes were observed in the cohort receiving medical treatment alone. Thus, our data demonstrate the potential for autologous mesenchymal stem cell to increase blood flow, GFR and attenuate inflammatory injury in post-stenotic kidneys. The observation that some effects are dose-dependent and related to in-vitro properties of mesenchymal stem cell may direct efforts to maximize potential therapeutic efficacy.

A phase I study of the VEGFR kinase inhibitor vatalanib in combination with the mTOR inhibitor, everolimus, in patients with advanced solid tumors.

Purpose Combining small-molecule inhibitors of different targets was shown to be synergistic in preclinical studies. Testing this concept in clinical trials is, however, daunting due to challenges in toxicity management and efficacy assessment. This study attempted to evaluate the safety and efficacy of vatalanib plus everolimus in patients with advanced solid tumors and explore the utility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) studies as a predictive biomarker. Patients and Methods This single-center, phase I trial containing 70 evaluable patients consisted of a dose escalation proportion based on the traditional "3 + 3" design (cohort IA and IB) and a dose expansion proportion (cohort IIA and IIB). Toxicity was evaluated using the Common Terminology Criteria of Adverse Events. Antitumor activity was assessed using the Modified Response Evaluation Criteria in Solid Tumors. Results The maximum tolerated doses were determined to be vatalanib 1250 mg once daily or 750 mg twice daily in combination with everolimus 10 mg once daily. No treatment-related death occurred. The most common toxicities were hypertriglyceridemia, hypercholesterolemia, fatigue, vomiting, nausea and diarrhea. There was no complete response. Nine patients (12.9%) had partial response (PR) and 41 (58.6%) had stable disease (SD). Significant antitumor activity was observed in neuroendocrine tumors with a disease-control rate (PR + SD) of 66.7% and other tumor types including renal cancer, melanoma, and non-small-cell lung cancer. Conclusions The combination of vatalanib and everolimus demonstrated reasonable toxicity and clinical activity. Future studies combining targeted therapies and incorporating biomarker analysis are warranted based on this phase I trial.

Tissue hypoxia, inflammation, and loss of glomerular filtration rate in human atherosclerotic renovascular disease.

The relationships between renal blood flow (RBF), tissue oxygenation, and inflammatory injury in atherosclerotic renovascular disease (ARVD) are poorly understood. We sought to correlate RBF and tissue hypoxia with glomerular filtration rate (GFR) in 48 kidneys from patients with ARVD stratified by single kidney iothalamate GFR (sGFR). Oxygenation was assessed by blood oxygenation level dependent magnetic resonance imaging (BOLD MRI), which provides an index for the levels of deoxyhemoglobin within a defined volume of tissue (R2*). sGFR correlated with RBF and with the severity of vascular stenosis as estimated by duplex velocities. Higher cortical R2* and fractional hypoxia and higher levels of renal vein neutrophil-gelatinase-associated-lipocalin (NGAL) and monocyte-chemoattractant protein-1 (MCP-1) were observed at lower GFR, with an abrupt inflection below 20 ml/min. Renal vein MCP-1 levels correlated with cortical R2* and with fractional hypoxia. Correlations between cortical R2* and RBF in the highest sGFR stratum (mean sGFR 51 ± 12 ml/min; R = -0.8) were degraded in the lowest sGFR stratum (mean sGFR 8 ± 3 ml/min; R = -0.1). Changes in fractional hypoxia after furosemide were also absent in the lowest sGFR stratum. These data demonstrate relative stability of renal oxygenation with moderate reductions in RBF and GFR but identify a transition to overt hypoxia and inflammatory cytokine release with severely reduced GFR. Tissue oxygenation and RBF were less correlated in the setting of reduced sGFR, consistent with variable oxygen consumption or a shift to alternative mechanisms of tissue injury. Identifying transitions in tissue oxygenation may facilitate targeted therapy in ARVD.

Time-resolved contrast-enhanced MR angiography with single-echo Dixon fat suppression.

PURPOSE: Dixon-based fat suppression has recently gained interest for dynamic contrast-enhanced MRI, but multi-echo techniques require longer scan times and reduce temporal resolution compared to single-echo alternatives without fat suppression. The purpose of this work is to demonstrate accelerated single-echo Dixon imaging with high spatial and temporal resolution. THEORY AND METHODS: Real-valued water and fat images can be obtained from a single measurement if the shared initial phase and that due to ΔB0 are assumed known a priori. An expression for simultaneous sensitivity encoding (SENSE) unfolding and fat-water separation is derived for the general undersampling case, and simplified under the special case of uniform Cartesian undersampling. In vivo experiments were performed in extremities and brain with SENSE acceleration factors of up to R = 8. RESULTS: Single-echo Dixon reconstruction of highly undersampled data was successfully demonstrated. Dynamic contrast-enhanced water and fat images provided high spatial and temporal resolution dynamic images with image update times shorter than previous single-echo Dixon work. CONCLUSION: Time-resolved contrast-enhanced MRI with single-echo Dixon fat suppression shows high image quality, improved vessel delineation, and reduced sensitivity to motion when compared to time-subtraction methods.

Cardiac MR elastography using reduced-FOV, single-shot, spin-echo EPI.

PURPOSE: To implement a reduced field of view (rFOV) technique for cardiac MR elastography (MRE) and to demonstrate the improvement in image quality of both magnitude images and post-processed MRE stiffness maps compared to the conventional full field of view (full-FOV) acquisition. METHODS: With Institutional Review Board approval, 17 healthy volunteers underwent both full-FOV and rFOV cardiac MRE scans using 140-Hz vibrations. Two cardiac radiologists blindly compared the magnitude images and stiffness maps and graded the images based on several image quality attributes using a 5-point ordinal scale. Fisher's combined probability test was performed to assess the overall evaluation. The octahedral shear strain-based signal-to-noise ratio (OSS-SNR) and median stiffness over the left ventricular myocardium were also compared. RESULTS: One volunteer was excluded because of an inconsistent imaging resolution during the exam. In the remaining 16 volunteers (9 males, 7 females), the rFOV scans outperformed the full-FOV scans in terms of subjective image quality and ghosting artifacts in the magnitude images and stiffness maps, as well as the overall preference. The quantitative measurements showed that rFOV had significantly higher OSS-SNR (median: 1.4 [95% confidence interval (CI): 1.2-1.5] vs. 2.1 [95% CI: 1.8-2.4]), P < 0.05) compared to full-FOV. Although no significant change was found in the median myocardial stiffness between the 2 scans, we observed a decrease in the stiffness variation within the myocardium from 2.1 kPa (95% CI: [1.9, 2.3]) to 1.9 kPa (95% CI: [1.7, 2.0]) for full-FOV and rFOV, respectively (P < 0.05) in a subgroup of 7 subjects with ghosting present in the myocardium. CONCLUSION: This pilot volunteer study demonstrated that rFOV cardiac MRE has the capability to reduce ghosting and to improve image quality in both MRE magnitude images and stiffness maps. Magn Reson Med 80:231-238, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Autologous Mesenchymal Stem Cells Increase Cortical Perfusion in Renovascular Disease.

Atherosclerotic renovascular disease (RVD) reduces renal blood flow (RBF) and GFR and accelerates poststenotic kidney (STK) tissue injury. Preclinical studies indicate that mesenchymal stem cells (MSCs) can stimulate angiogenesis and modify immune function in experimental RVD. We assessed the safety and efficacy of adding intra-arterial autologous adipose-derived MSCs into STK to standardized medical treatment in human subjects without revascularization. The intervention group (n=14) received a single infusion of MSC (1.0 × 105 or 2.5 × 105 cells/kg; n=7 each) plus standardized medical treatment; the medical treatment only group (n=14) included subjects matched for age, kidney function, and stenosis severity. We measured cortical and medullary volumes, perfusion, and RBF using multidetector computed tomography. We assessed tissue oxygenation by blood oxygen level-dependent MRI and GFR by iothalamate clearance. MSC infusions were well tolerated. Three months after infusion, cortical perfusion and RBF rose in the STK (151.8-185.5 ml/min, P=0.01); contralateral kidney RBF increased (212.7-271.8 ml/min, P=0.01); and STK renal hypoxia (percentage of the whole kidney with R2*>30/s) decreased (12.1% [interquartile range, 3.3%-17.8%] to 6.8% [interquartile range, 1.8%-12.9%], P=0.04). No changes in RBF occurred in medical treatment only subjects. Single-kidney GFR remained stable after MSC but fell in the medical treatment only group (-3% versus -24%, P=0.04). This first-in-man dose-escalation study provides evidence of safety of intra-arterial infusion of autologous MSCs in patients with RVD. MSC infusion without main renal artery revascularization associated with increased renal tissue oxygenation and cortical blood flow.

Magnetic Resonance Imaging and Computed Tomography of Cardiac Masses and Pseudomasses in the Atrioventricular Groove.

The atrioventricular (AV) groove constitutes the anatomic space separating the atria and ventricles. The AV groove is often difficult to visualize at echocardiography, and suspected lesions can be further assessed with cardiac computed tomography or magnetic resonance imaging. AV groove lesions may originate from within the AV groove or extend into this space from adjacent structures. The differential diagnosis for AV groove lesions is often wide, but a precise diagnosis can sometimes be made. This pictorial essay illustrates the magnetic resonance imaging and computed tomography appearance of common and uncommon AV groove lesions, and attempts to provide a logical framework for differential diagnosis when confronted with a known or suspected lesion at cross-sectional imaging.

Evaluation of liver stiffness with magnetic resonance elastography in patients with constrictive pericarditis: Preliminary findings.

PURPOSE: To evaluate with magnetic resonance elastography (MRE) whether patients with constrictive pericarditis (CP) have increased hepatic stiffness. CP results in reduced pericardial compliance, ventricular interdependence, and right heart failure. Patients with untreated CP may develop liver fibrosis and ultimately cirrhosis due to chronic venous congestion. Chronic venous congestion ± fibrosis may lead to increased liver stiffness. MATERIALS AND METHODS: Prospectively, patients with suspected CP underwent 2D transthoracic echocardiography, cardiac MRI, and liver MRE. An automated method was used to draw regions of interest (ROIs) on the stiffness maps to calculate the mean liver stiffness in kilopascals (kPa). A t-test with α = 0.05 was performed between stiffness values of patients with positive and negative CP findings based on previously published echocardiography criteria. RESULTS: Nineteen patients met inclusion criteria with a mean ± standard deviation (SD) age of 51 ± 16 years. Nine patients (47%) had CP. Mean liver stiffness trended higher in patients with CP compared to those without CP (4.04 kPa vs. 2.46; P = 0.045). Liver stiffness correlated with MRI septal bounce (P = 0.04), inferior vena cava size (P = 0.003), echo abnormal septal motion (P = 0.04), and echo mitral inflow variation >25% (P = 0.02). Only MRI septal bounce predicted CP by echocardiography (P < 0.001). CONCLUSION: CP was associated with increased liver stiffness. The increased stiffness is most likely secondary to chronic hepatic venous congestion and/or fibrosis. MRE may be useful for noninvasive liver stiffness assessment in CP. J. Magn. Reson. Imaging 2016;44:81-88.

Atherosclerotic renal artery stenosis is associated with elevated cell cycle arrest markers related to reduced renal blood flow and postcontrast hypoxia.

BACKGROUND: Atherosclerotic renal artery stenosis (ARAS) reduces renal blood flow (RBF), ultimately leading to kidney hypoxia and inflammation. Insulin-like growth factor binding protein-7 (IGFBP-7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) are biomarkers of cell cycle arrest, often increased in ischemic conditions and predictive of acute kidney injury (AKI). This study sought to examine the relationships between renal vein levels of IGFBP-7, TIMP-2, reductions in RBF and postcontrast hypoxia as measured by blood oxygen level-dependent (BOLD) magnetic resonance imaging. METHODS: Renal vein levels of IGFBP-7 and TIMP-2 were obtained in an ARAS cohort (n= 29) scheduled for renal artery stenting and essential hypertensive (EH) healthy controls (n = 32). Cortical and medullary RBFs were measured by multidetector computed tomography (CT) immediately before renal artery stenting and 3 months later. BOLD imaging was performed before and 3 months after stenting in all patients, and a subgroup (N = 12) underwent repeat BOLD imaging 24 h after CT/stenting to examine postcontrast/procedure levels of hypoxia. RESULTS: Preintervention IGFBP-7 and TIMP-2 levels were elevated in ARAS compared with EH (18.5 ± 2.0 versus 15.7 ± 1.5 and 97.4 ± 23.1 versus 62.7 ± 9.2 ng/mL, respectively; P< 0.0001); baseline IGFBP-7 correlated inversely with hypoxia developing 24 h after contrast injection (r = -0.73, P< 0.0001) and with prestent cortical blood flow (r = -0.59, P= 0.004). CONCLUSION: These data demonstrate elevated IGFBP-7 and TIMP-2 levels in ARAS as a function of the degree of reduced RBF. Elevated baseline IGFBP-7 levels were associated with protection against postimaging hypoxia, consistent with 'ischemic preconditioning'. Despite contrast injection and stenting, AKI in these high-risk ARAS subjects with elevated IGFBP-7/TIMP-2 was rare and did not affect long-term kidney function.

Magnetic Resonance Imaging of Perirenal Pathology.

The perirenal space can be involved by a variety of neoplastic, inflammatory, infectious, and proliferative disorders. Magnetic resonance imaging is often an ideal technique for identification and staging of lesions arising within the perirenal space, with its superior soft tissue characterization as well as its ability to visualize extension into blood vessels and adjacent organs. This pictorial essay describes the magnetic resonance imaging appearance of a variety of pathologies which can arise from or involve the perirenal space, and provides a framework for categorization and differential diagnosis of these lesions.

Non-invasive detection of liver fibrosis: MR imaging features vs. MR elastography.

PURPOSE: To compare accuracy of morphological features of liver on MRI and liver stiffness with MR elastography (MRE) for detection of significant liver fibrosis and cirrhosis. MATERIALS AND METHODS: In this retrospective study, we evaluated 62 patients who underwent liver MRI with MRE and histological confirmation of liver fibrosis within 6 months. Two radiologists, blinded to histology results, independently evaluated liver parenchyma texture, surface nodularity, signs of volumetric changes, and portal hypertension for presence of significant fibrosis and cirrhosis. Two more readers independently calculated mean liver stiffness values with MRE. Interobserver agreement was evaluated with kappa and intra-class correlation coefficient (ICC) analysis. Diagnostic accuracy was assessed with area under receiver operating characteristic (AUROC) analysis. Comparison of AUROCs of MRI and MRE was performed. RESULTS: Liver fibrosis was present in 37 patients. The interobserver agreement was poor to good (κ = 0.12-0.74) for MRI features and excellent for MRE (ICC 0.97, 95% CI 0.95-0.98). MRI features had 48.5%-87.9% sensitivity, 55.2%-100% specificity, and 71.5%-81.6% accuracy/for detection of significant fibrosis. MRE performed better with 100% sensitivity, 96.5% specificity, and 98.9% accuracy. For the detection of cirrhosis, MRE performed better than MRI features with 88.2% sensitivity (vs. 41.2%-82.3%), 91.1% specificity (vs. 64.4%-95.6%), and 93.5% accuracy (vs. 60.6%-80.5%). Among the MRI features, surface nodularity and overall impression had the best accuracies of 80.3% and 81.6% for detection of significant fibrosis, respectively. For cirrhosis, parenchyma texture and overall impression had the best accuracies of 80.5% and 79.7%, respectively. Overall, MRE had significantly greater AUROC than MRI features for detection of both significant fibrosis (0.98.9 vs 0.71-0.82, P < 0.001) and cirrhosis (0.93.5 vs. 0.61-0.80.5, P < 0.01). CONCLUSION: MRE is superior to MRI for the non-invasive diagnosis of significant liver fibrosis and cirrhosis.

Three-station three-dimensional bolus-chase MR angiography with real-time fluoroscopic tracking.

PURPOSE: To determine the feasibility of using real-time fluoroscopic tracking for bolus-chase magnetic resonance (MR) angiography of peripheral vasculature to image three stations from the aortoiliac bifurcation to the pedal arteries. MATERIALS AND METHODS: This prospective study was institutional review board approved and HIPAA compliant. Eight healthy volunteers (three men; mean age, 48 years; age range, 30-81 years) and 13 patients suspected of having peripheral arterial disease (five men; mean age, 67 years; age range, 47-81 years) were enrolled and provided informed consent. All subjects were imaged with the fluoroscopic tracking MR angiographic protocol. Ten patients also underwent a clinical computed tomographic (CT) angiographic runoff examination. Two readers scored the MR angiographic studies for vessel signal intensity and sharpness and presence of confounding artifacts and venous contamination at 35 arterial segments. Mean aggregate scores were assessed. The paired MR angiographic and CT angiographic studies also were scored for visualization of disease, reader confidence, and overall diagnostic quality and were compared by using a Wilcoxon signed rank test. RESULTS: Real-time fluoroscopic tracking performed well technically in all studies. Vessel segments were scored good to excellent in all but the following categories: For vessel signal intensity and sharpness, the abdominal aorta, iliac arteries, distal plantar arteries, and plantar arch were scored as fair to good; and for presence of confounding artifacts, the abdominal aorta and iliac arteries were scored as fair. The MR angiograms and CT angiograms did not differ significantly in any scoring category (reader 1: P = .50, .39, and .39; reader 2: P = .41, .61, and .33, respectively). CT scores were substantially better in 20% (four of 20) and 25% (five of 20) of the pooled evaluations for the visualization of disease and overall image quality categories, respectively, versus 5% (one of 20) for MR scores in both categories. CONCLUSION: Three-station bolus-chase MR angiography with real-time fluoroscopic tracking provided high-spatial-resolution arteriograms of the peripheral vasculature, enabled precise triggering of table motion, and compared well with CT angiograms.

Balanced steady state-free precession (b-SSFP) imaging for MRCP: techniques and applications.

Balanced steady state-free precession (b-SSFP) pulse sequences have a number of properties which can be useful in magnetic resonance cholangiopancreatography (MRCP), including short acquisition times, high signal-to-noise ratios, and T2/T1 contrast weighting. The utility and versatility of b-SSFP sequences for MRCP imaging are probably underappreciated, and this pictorial essay briefly discusses benefits and limitations of 2D and 3D b-SSFP techniques used in place of or in addition to conventional single-shot fast spin echo or 3D fast spin echo acquisitions and illustrates their appearance in several clinical cases.

Micro-computed tomography and nuclear magnetic resonance imaging for noninvasive, live-mouse cholangiography.

The cholangiopathies are a diverse group of biliary tract disorders, many of which lack effective treatment. Murine models are an important tool for studying their pathogenesis, but existing noninvasive methods for assessing biliary disease in vivo are not optimal. Here we report our experience with using micro-computed tomography (microCT) and nuclear magnetic resonance (MR) imaging to develop a technique for live-mouse cholangiography. Using mdr2 knockout (mdr2KO, a model for primary sclerosing cholangitis (PSC)), bile duct-ligated (BDL), and normal mice, we performed in vivo: (1) microCT on a Siemens Inveon PET/CT scanner and (2) MR on a Bruker Avance 16.4 T spectrometer, using Turbo Rapid Acquisition with Relaxation Enhancement, IntraGate Fast Low Angle Shot, and Half-Fourier Acquisition Single-shot Turbo Spin Echo methods. Anesthesia was with 1.5-2.5% isoflurane. Scans were performed with and without contrast agents (iodipamide meglumine (microCT), gadoxetate disodium (MR)). Dissection and liver histology were performed for validation. With microCT, only the gallbladder and extrahepatic bile ducts were visualized despite attempts to optimize timing, route, and dose of contrast. With MR, the gallbladder, extra-, and intrahepatic bile ducts were well-visualized in mdr2KO mice; the cholangiographic appearance was similar to that of PSC (eg, multifocal strictures) and could be improved with contrast administration. In BDL mice, MR revealed cholangiographically distinct progressive dilation of the biliary tree without ductal irregularity. In normal mice, MR allowed visualization of the gallbladder and extrahepatic ducts, but only marginal visualization of the diminutive intrahepatic ducts. One mouse died during microCT and MR imaging, respectively. Both microCT and MR scans could be obtained in ≤20 min. We, therefore, demonstrate that MR cholangiography can be a useful tool for longitudinal studies of the biliary tree in live mice, whereas microCT yields suboptimal duct visualization despite requiring contrast administration. These findings support further development and application of MR cholangiography to the study of mouse models of PSC and other cholangiopathies.

Human renovascular disease: estimating fractional tissue hypoxia to analyze blood oxygen level-dependent MR.

PURPOSE: To test the hypothesis that fractional kidney hypoxia, measured by using blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging, correlates with renal blood flow (RBF), tissue perfusion, and glomerular filtration rate (GFR) in patients with atherosclerotic renal artery stenosis (RAS) better than regionally selected region of interest-based methods. MATERIALS AND METHODS: The study was approved by the institutional review board according to a HIPAA-compliant protocol, with written informed consent. BOLD MR imaging was performed in 40 patients with atherosclerotic RAS (age range, 51-83 years; 22 men, 18 women) and 32 patients with essential hypertension (EH) (age range, 26-85 years; 19 men, 13 women) during sodium intake and renin-angiotensin blockade. Fractional kidney hypoxia (percentage of entire axial image section with R2* above 30 sec(-1)) and conventional regional estimates of cortical and medullary R2* levels were measured. Stenotic and nonstenotic contralateral kidneys were compared for volume, tissue perfusion, and blood flow measured with multidetector computed tomography. Statistical analysis was performed (paired and nonpaired t tests, linear regression analysis). RESULTS: Stenotic RBF was reduced compared with RBF of contralateral kidneys (225.2 mL/min vs 348 mL/min, P = .0003). Medullary perfusion in atherosclerotic RAS patients was lower than in EH patients (1.07 mL/min per milliliter of tissue vs 1.3 mL/min per milliliter of tissue, P = .009). While observer-selected cortical R2* (18.9 sec(-1) [stenosis] vs 18.5 sec(-1) [EH], P = .07) did not differ, fractional kidney hypoxia was higher in stenotic kidneys compared with kidneys with EH (17.4% vs 9.6%, P < .0001) and contralateral kidneys (7.2%, P < .0001). Fractional hypoxia correlated inversely with blood flow (r = -0.34), perfusion (r = -0.3), and GFR (r = -0.32). CONCLUSION: Fractional tissue hypoxia rather than cortical or medullary R2* values used to assess renal BOLD MR imaging demonstrated a direct relationship to chronically reduced blood flow and GFR.

Buildup of image quality in view-shared time-resolved 3D CE-MRA.

Time-resolved three-dimensional contrast-enhanced MR angiography often relies on view sharing of peripheral k-space data to enable acquisition of angiograms with both high spatial resolution and a rapid frame rate. It is typically assumed that k-space will be fully sampled during passage of the contrast bolus arterial phase. However, this is not the case when view sharing is incomplete, for example, at the leading edge of an enhancing vessel or if acquisition time is limited as in fluoroscopic tracking for multistation bolus chase MR angiography. Incomplete view sharing will degrade image quality, for example, by reducing vessel signal and sharpness and increasing undersampling artifacts. In this work, the evolution of angiogram quality with view sharing is quantitatively assessed in phantom experiments and in vivo contrast-enhanced MR angiography calf studies. It is demonstrated that there are multiple sets of sequence parameters that can yield a target image update time, but the choice of parameters can profoundly affect how image quality evolves with view sharing. A fundamental tradeoff between vessel signal and sharpness and its relationship to the sequence temporal footprint is investigated and discussed.

Three-dimensional dixon fat-water separated rapid breathheld imaging of myocardial infarction.

PURPOSE: To develop a breathhold three-dimensional (3D) Dixon technique for fat suppressed imaging of myocardial infarction. MATERIALS AND METHODS: A pulse sequence was developed that uses a radial fan-beam k-space segmentation scheme for efficient coverage of k-space, enabling 3D scans in a single breathhold. The sequence uses a dual-echo bipolar readout to enable Dixon fat-water separation for improved visualization of epicardial and pericardial delayed enhancement. The 3D Dixon method was compared with a conventional 2D fast gradient recalled echo (FGRE) -based technique in 25 patients. RESULTS: Pericardial visualization scores and confidence were higher while overall image quality and artifacts were slightly worse for 3D Dixon compared with 2D FGRE. Robust fat suppression was achieved in 21 of 25 cases using the 3D Dixon method. CONCLUSION: A 3D breathhold method for fat-water separated imaging of myocardial delayed enhancement was developed and validated.

Prospective comparison of cartesian acquisition with projection-like reconstruction magnetic resonance angiography with computed tomography angiography for evaluation of below-the-knee runoff.

PURPOSE: To compare prospectively the assessment of stenosis and radiologist confidence in the evaluation of below-the-knee lower extremity runoff vessels between computed tomography (CT) angiography and contrast-enhanced magnetic resonance (MR) angiography in a cohort of 19 clinical patients. MATERIALS AND METHODS: The study was compliant with the Health Insurance Portability and Accountability Act of 1996 and approved by the institutional review board. Imaging was performed in 19 consecutive patients with known or suspected peripheral arterial disease; both CT angiography and a more recently developed MR angiography technique were performed within 24 hours of each other and before any therapeutic intervention. Resulting images were randomized and interpreted in blinded fashion by four board-certified radiologists with expertise in CT angiography and MR angiography. Vasculature of the lower leg was apportioned into 22 segments, 11 for each leg. For each segment, degree of stenosis and confidence of diagnosis were determined using a 3-point scale. Differences between CT angiography and MR angiography were assessed for significance using pooled histograms that were analyzed using the Wilcoxon signed rank test. RESULTS: For assessment of stenosis, there was no difference in CT angiography compared with MR angiography for 20 of 22 segments. For confidence of diagnosis, assessment of popliteal arteries was superior on CT angiography compared with MR angiography (P<.05). Confidence in assessment of both tibioperoneal trunks and the left proximal anterior tibial artery was not significantly different between CT angiography and MR angiography. Confidence in assessment of all other 17 segments was superior with MR angiography compared with CT angiography (P<.02). CONCLUSIONS: MR angiography using the method described here is a promising technique for evaluating lower extremity arterial runoff. MR angiography had an overall superior performance in radiologist confidence compared with CT angiography for imaging runoff vessels below the knee.

Incidental diagnosis of presacral ganglioneuroma in a patient with hematuria.

Ganglioneuromas are benign neuroblastic tumors seen most in pediatric population. The most common locations are mediastinal, retroperitoneal and adrenal regions. Ganglioneuromas rarely occur in presacral space. We present one such case of an incidentally diagnosed presacral ganglioneuroma in an asymptomatic 71-year-old male who initially presented with hematuria.