Effects of Semaglutide on Muscle Structure and Function in the SLIM LIVER Study.

BACKGROUND: Semaglutide, a GLP-1 receptor agonist, is highly effective for decreasing weight. Concomitant loss of muscle mass often accompanies weight loss and may have consequences on muscle function. METHODS: This is a secondary analysis from the SLIM LIVER (ACTG A5371) study, a single-arm study of semaglutide in people with HIV (PWH) with metabolic dysfunction-associated steatotic liver disorder (MASLD). Participants received subcutaneous semaglutide for 24 weeks (titrated to 1 mg/week by week 4). Psoas volume and fat fraction were assessed from liver magnetic resonance imaging and physical function by 10-time chair rise test and 4m gait speed. Mean change from baseline to week 24 was estimated with linear regression modeling. RESULTS: 51 PWH enrolled; muscle measures were available from 46 participants. The mean age was 50 (standard deviation [SD] 11) years and BMI 35.5 (5.6) kg/m2, 43% were women, 33% Black, and 39% Hispanic/Latino. Psoas muscle volume decreased by 9.3% (95% confidence interval [CI]: -13.4, -5.2; p<0.001) over 24 weeks but psoas muscle fat did not significantly change (-0.42%, CI: -1.00, 0.17; p=0.16). Chair rise and gait speed had non-significant improvements of 1.27 seconds (CI: -2.7, 0.10) and 0.05 m/sec (CI: -0.01, 0.10), respectively (both p>0.07). The prevalence of slow gait speed (< 1 m/sec) decreased from 63% to 46% (p=0.029). CONCLUSIONS: In PWH receiving low-dose semaglutide for MASLD, despite decreased psoas muscle volume, there was no significant change in physical function. This suggests that function was maintained despite significant loss of muscle concomitant with weight loss.

High frame rate cardiac cine MRI for the evaluation of diastolic function and its direct correlation with echocardiography.

BACKGROUND: Breath-hold cine MR is the method of choice for evaluating left ventricular (LV) systolic function; however, the evaluation of diastolic function remains in the domain of high frame rate echocardiography. Thus, a cine MR technique for simultaneously evaluating LV systolic and diastolic function would be clinically valuable. PURPOSE: To test the feasibility of extracting indices that characterize LV diastolic function from high frame rate cine MR. STUDY TYPE: Single center, prospective. POPULATION: Asymptomatic volunteers (N = 24; age 45.8 ± 12.3 years). FIELD STRENGTH/SEQUENCE: High frame rate (70 fps) cine MR and phase-contrast MR during free breathing were acquired at 1.5T. ASSESSMENT: The following MR-based LV filling metrics were extracted from LV volume changes during the cardiac cycle: 1) the volume-rate ratio, REFP /RLFP (ratio of the peak LV filling rate during the early filling period [EFP] to that during the late filling period [LFP]); and 2) the volume ratio, VEFP /VLFP (the ratio of cumulative LV volume change between the EFP and LFP). These metrics were then compared with traditional transmitral blood flow-based MR and echocardiographic indices. The effect of temporal resolution on these metrics was also evaluated. STATISTICAL TESTS: Bland-Altman and linear regression analyses were used to evaluate the performance of the proposed metrics against traditional indices of diastolic function. RESULTS: The REFP /RLFP and VEFP /VLFP correlated well with E/AQ-flow (r 2 = 0.66 and 0.54, respectively) and E/Aecho (r 2 = 0.58 and 0.49, respectively). Systolic indices remained robust (<3% error) for frame rates ≥20 fps. Although the proposed VEFP /VLFP was robust (<5% error) up to 25 fps, the proposed volume-rate diastolic function metrics were less reliable (>8% error) for frame rates below 35 fps. DATA CONCLUSION: In asymptomatic volunteers, cardiac cine MR images acquired at frame rates >35 fps can be used to extract LV diastolic function indices from the temporal changes in LV volume. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2019;50:1571-1582.

Evaluation of Cell Therapy on Exercise Performance and Limb Perfusion in Peripheral Artery Disease: The CCTRN PACE Trial (Patients With Intermittent Claudication Injected With ALDH Bright Cells).

BACKGROUND: Atherosclerotic peripheral artery disease affects 8% to 12% of Americans >65 years of age and is associated with a major decline in functional status, increased myocardial infarction and stroke rates, and increased risk of ischemic amputation. Current treatment strategies for claudication have limitations. PACE (Patients With Intermittent Claudication Injected With ALDH Bright Cells) is a National Heart, Lung, and Blood Institute-sponsored, randomized, double-blind, placebo-controlled, phase 2 exploratory clinical trial designed to assess the safety and efficacy of autologous bone marrow-derived aldehyde dehydrogenase bright (ALDHbr) cells in patients with peripheral artery disease and to explore associated claudication physiological mechanisms. METHODS: All participants, randomized 1:1 to receive ALDHbr cells or placebo, underwent bone marrow aspiration and isolation of ALDHbr cells, followed by 10 injections into the thigh and calf of the index leg. The coprimary end points were change from baseline to 6 months in peak walking time (PWT), collateral count, peak hyperemic popliteal flow, and capillary perfusion measured by magnetic resonance imaging, as well as safety. RESULTS: A total of 82 patients with claudication and infrainguinal peripheral artery disease were randomized at 9 sites, of whom 78 had analyzable data (57 male, 21 female patients; mean age, 66±9 years). The mean±SEM differences in the change over 6 months between study groups for PWT (0.9±0.8 minutes; 95% confidence interval [CI] -0.6 to 2.5; P=0.238), collateral count (0.9±0.6 arteries; 95% CI, -0.2 to 2.1; P=0.116), peak hyperemic popliteal flow (0.0±0.4 mL/s; 95% CI, -0.8 to 0.8; P=0.978), and capillary perfusion (-0.2±0.6%; 95% CI, -1.3 to 0.9; P=0.752) were not significant. In addition, there were no significant differences for the secondary end points, including quality-of-life measures. There were no adverse safety outcomes. Correlative relationships between magnetic resonance imaging measures and PWT were not significant. A post hoc exploratory analysis suggested that ALDHbr cell administration might be associated with an increase in the number of collateral arteries (1.5±0.7; 95% CI, 0.1-2.9; P=0.047) in participants with completely occluded femoral arteries. CONCLUSIONS: ALDHbr cell administration did not improve PWT or magnetic resonance outcomes, and the changes in PWT were not associated with the anatomic or physiological magnetic resonance imaging end points. Future peripheral artery disease cell therapy investigational trial design may be informed by new anatomic and perfusion insights. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01774097.

Tissue characterization of uterine fibroids with an intravoxel incoherent motion model: The need for T2 correction.

BACKGROUND: Diminished signal intensity of uterine fibroids in T2 -weighted images is routinely used as a qualitative marker of fibroid hypoperfusion. However, quantitative classification of fibroid perfusion with intravoxel incoherent motion (IVIM) model-based metrics is not yet clinically accepted. PURPOSE: To investigate the influence of T2 correction on the estimation of IVIM model parameters for characterizing uterine fibroid tissue. STUDY TYPE: Prospective. POPULATION: Fourteen women with 41 fibroids (12 Type I and 29 Type II, per Funaki classification) underwent diffusion-weighted imaging and T2 mapping. FIELD STRENGTH: Diffusion-weighted images (b values: 0, 20, 40, 60, 100, 200, 400, 600, 800, 1000 s/mm2 ) and T2 maps were obtained at 1.5T. ASSESSMENT: The effect of uterine fibroid T2 variation on IVIM model parameters (diffusion coefficient, perfusion coefficient, and perfusion volume fraction) were numerically modeled and experimentally evaluated without (D, D*, f) and with (Dc , D c * , fc ) T2 correction. The relationship of T2 with D and the T2 -corrected perfusion volume fraction (fc ) was also examined. STATISTICAL TEST: D-values and f-values estimated with and without T2 correction were compared by using a two-tailed Student's t-test. RESULTS: Type II fibroids had higher D and f than Type I fibroids, but the differences were not significant (Type I vs. Type II, D: 0.83 ± 0.20 vs. 0.80 ± 0.25 mm2 /s, P = 0.78; f: 23.64 ± 4.87% vs. 25.27 ± 7.46%, P = 0.49). For Type I and Type II fibroids, fc was lower than f, and fc of Type II fibroids was significantly higher than that of Type I fibroids (Type I vs. Type II, fc : 7.80 ± 1.88% vs. 11.82 ± 4.13%, P = 0.003). Both D and fc exponentially increased with the increase of fibroid T2 as functions: D c ( T 2 ) = - 1.52 × 10 - 3 ⋅ e - 3.42 T 2 290 + 1.84 × 10 - 3 and f c ( T 2 ) = - 0.2336 ⋅ e - 3.217 T 2 290 + 0.2269 , respectively. D asymptotically approached 1.79 × 10-3 mm2 /s, and fc approached 21.74%. DATA CONCLUSION: T2 correction is important when using IVIM-based models to characterize uterine fibroid tissue. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;48:994-1001.

Two-center clinical validation and quantitative assessment of respiratory triggered retrospectively cardiac gated balanced-SSFP cine cardiovascular magnetic resonance imaging in adults.

BACKGROUND: Breath-hold (BH) requirement remains the limiting factor on the spatio-temporal resolution and coverage of the cine balanced steady-state free precession (bSSFP) cardiovascular magnetic resonance (CMR) imaging. In this prospective two-center clinical trial, we validated the performance of a respiratory triggered (RT) bSSFP cine sequence for evaluation of biventricular function. METHODS: Our study included 23 asymptomatic healthy subjects and 60 consecutive patients from Institute A (n = 39) and Institute B (n = 21) referred for a clinically indicated CMR study. We implemented a RT sequence with a respiratory synchronized drive to steady state (SS) of bSSFP signal, before the commencement of image data acquisition with prospective cardiac arrhythmia rejection and retrospectively cardiac gated reconstruction in real-time. Left (LV) and right (RV) ventricular function and LV mass were evaluated by using RT-bSSFP and conventional BH-bSSFP sequences with one cardiac cycle for SS preparation keeping all the imaging parameters identical. The performance of the sequences was evaluated by using quantitative and semi-quantitative metrics. RESULTS: Global LV and RV functional parameters and LV mass obtained from the RT-bSSFP and BH-bSSFP sequences were in good agreement. Quantitative metrics designed to capture fluctuation in SS signal intensity showed no significant difference between sequences. In addition, blood-to-myocardial contrast was nearly identical between sequences. The combined clinical score for image quality was excellent or good for 100% of cases with the BH-bSSFP and 83% of cases with the RT-bSSFP sequence. The de facto image acquisition time for RT-bSSFP was statistically significantly longer than that for conventional BH-bSSFP (7.9 ± 3.4 min vs. 5.1 ± 2.6 min). CONCLUSIONS: Cine RT-bSSFP is an alternative for evaluating global biventricular function with contrast and spatio-temporal resolutions that are similar to those attained by using the BH-bSSFP sequence, albeit with a modest time penalty and a small reduction in image quality.

Baseline assessment and comparison of arterial anatomy, hyperemic flow, and skeletal muscle perfusion in peripheral artery disease: The Cardiovascular Cell Therapy Research Network "Patients with Intermittent Claudication Injected with ALDH Bright Cells" (CCTRN PACE) study.

BACKGROUND: Peripheral artery disease (PAD) is important to public health as a major contributor to cardiovascular morbidity and mortality. Recent developments in magnetic resonance imaging (MRI) techniques permit improved assessment of PAD anatomy and physiology, and may serve as surrogate end points after proangiogenic therapies. METHODS: The PACE study is a randomized, double-blind, placebo-controlled clinical trial designed to assess the physiologic impact and potential clinical efficacy of autologous bone marrow-derived ALDHbr stem cells. The primary MRI end points of the study are as follows: (1) total collateral count, (2) calf muscle plasma volume (a measure of capillary perfusion) by dynamic contrast-enhanced MRI, and (3) peak hyperemic popliteal flow by phase-contrast MRI (PC-MRI). RESULTS: The interreader and intrareader and test-retest results demonstrated good-to-excellent reproducibility (interclass correlation coefficient range 0.61-0.98) for all magnetic resonance measures. The PAD participants (n=82) had lower capillary perfusion measured by calf muscle plasma volume (3.8% vs 5.6%) and peak hyperemic popliteal flow (4.1 vs 13.5mL/s) as compared with the healthy participants (n=16), with a significant level of collateralization. CONCLUSIONS: Reproducibility of the MRI primary end points in PACE was very good to excellent. The PAD participants exhibited decreased calf muscle capillary perfusion as well as arterial flow reserve when compared with healthy participants. The MRI tools used in PACE may advance PAD science by enabling accurate measurement of PAD microvascular anatomy and perfusion before and after stem cell or other PAD therapies.

Short-Term Repeatability of Magnetic Resonance Elastography at 3.0T: Effects of Motion-Encoding Gradient Direction, Slice Position, and Meal Ingestion.

PURPOSE: Magnetic resonance elastography (MRE) can estimate liver stiffness (LS) noninvasively. We prospectively assessed whether motion-encoding gradient (MEG) direction, slice position, or high-caloric food intake affects the repeatability of MRE measurements of LS. MATERIALS AND METHODS: Twenty healthy volunteers (8 women, 12 men; age, 48 ± 12 years) were imaged in a 3.0T scanner at four timepoints: twice after overnight fasting (B1 , B2 ) and twice after consuming a 1050-calorie standardized meal (A1 , A2 ; after 30 and 60 min, respectively). Each session comprised sequential MRE acquisitions in which MEG was applied in three orthogonal directions with three slices positioned over the liver for each. Between sessions, the participants were repositioned to assess test-retest reproducibility. RESULTS: The LS measurements before/after food intake were 3.36 ± 1.31 kPa/3.22 ± 1.03 kPa, 2.04 ± 0.33 kPa/2.27 ± 0.38 kPa, and 2.47 ± 0.50 kPa/2.64 ± 0.76 kPa for MEG superimposed along the anterior-posterior (AP), foot-head (FH), and right-left (RL) directions, respectively. Before and after food intake, LS estimates were lower and more reproducible (<10% coefficient of variation) when the MEG was in the FH direction, not the AP or RL direction. Liver stiffness estimates were significantly elevated after meal consumption when the MEG was in the FH direction (P < 0.05 for B1 vs. A1 , B1 vs. A2 , B2 vs. A1 , and B2 vs. A2 ). CONCLUSION: MRE estimates of LS were highly reproducible, particularly when MEG was applied in the FH direction, suggesting that this method could be used for long-term monitoring of antifibrotic therapy without repeated biopsies. High-caloric food intake resulted in slightly elevated LS on MRE.

4D Contrast-enhanced MR Angiography with the Keyhole Technique in Children: Technique and Clinical Applications.

Unlike in adults, contrast agent-enhanced magnetic resonance (MR) angiography in the pediatric population raises unique challenges such as faster heart rates, more rapid arteriovenous transit, smaller structures, smaller volumes of contrast agent used, and more complex disease processes. A need exists for a rapid contrast-enhanced MR angiographic technique that can separate the arterial and venous phases of contrast enhancement in sedated pediatric patients breathing freely during the course of an examination. In time-resolved contrast-enhanced MR angiography with the keyhole method (four-dimensional [4D] contrast-enhanced MR angiography), various spatial and temporal frequency undersampling schemes are used to substantially reduce the time of acquisition without markedly compromising spatial resolution. The keyhole method can be briefly described as an undersampling approach in which only a small region of the k-space (keyhole) around the center is repeatedly sampled while the periphery is sampled only once during acquisition. This method provides a wide range of options that can be used to overcome conventional limitations of contrast-enhanced MR angiography in children and opens the door for several new pediatric applications, including evaluation of congenital heart disease in neonates and infants, thoracic and extremity vascular pathologic conditions, high-flow vascular malformations, systemic vein thrombosis, and pediatric portal hypertension. This review provides a technical overview of 4D contrast-enhanced MR angiography, outlines its advantages and pitfalls in the pediatric population, and also describes various applications in children, including modifications of the technique needed for each application.

Noninvasive, in vivo determination of uterine fibroid thermal conductivity in MRI-guided high intensity focused ultrasound therapy.

PURPOSE: To estimate the local thermal conductivity of uterine fibroid in vivo at a high temperature range (60-80°C) typically encountered in magnetic resonance imaging-guided high-intensity focused ultrasound (MRgHIFU) surgery. The thermal conductivity of uterine fibroids in vivo is unknown and knowledge about tissue thermal conductivity may aid in effective delivery of thermal energy for ablation. MATERIALS AND METHODS: All subjects (nine women) provided written informed consent to participate in this Institutional Review Board-approved study. A total of 10 fibroids were treated using MRgHIFU surgery with real-time temperature monitoring during both heating and cooling periods. The local thermal conductivity was determined by analyzing the spatiotemporal spread of temperature during the cooling period. RESULTS: The thermal conductivity of MRgHIFU-treated uterine fibroids was 0.47 ± 0.07 W·m(-1) ·K(-1) (range: 0.25∼0.67 W·m(-1) ·K(-1) ) which is slightly lower than the reported value for skeletal muscle at temperatures of <40°C (0.52 to 0.62 W·m(-1) ·K(-1) ). CONCLUSION: It is possible to estimate the thermal conductivity of uterine fibroids in vivo from the spatiotemporal spread of temperature around the HIFU focus during the cooling period.

Clinical validation of free breathing respiratory triggered retrospectively cardiac gated cine balanced steady-state free precession cardiovascular magnetic resonance in sedated children.

BACKGROUND: Cine balanced steady-state free precession (SSFP), the preferred sequence for ventricular function, demands uninterrupted radio frequency (RF) excitation to maintain the steady-state during suspended respiration. This is difficult to accomplish in sedated children. In this work, we validate a respiratory triggered (RT) SSFP sequence that drives the magnetization to steady-state before commencing retrospectively cardiac gated cine acquisition in a sedated pediatric population. METHODS: This prospective study was performed on 20 sedated children with congenital heart disease (8.6 ± 4 yrs). Identical imaging parameters were used for multiple number of signal averages (MN) and RT cine SSFP sequences covering both the ventricles in short-axis (SA) orientation. Image quality assessment and quantitative volumetric analysis was performed on the datasets by two blinded observers. One-sided Wilcoxon signed rank test and Box plot analysis were performed to compare the clinical scores. Bland-Altman (BA) analysis was performed on LV and RV volumes. RESULTS: Scan duration for SA stack using RT-SSFP (3.9 ± 0.8 min) was slightly shorter than MN-SSFP (4.6 ± 0.9 min) acquisitions. The endocardial edge definition was significantly better for RT than MN, blood to myocardial contrast was better for RT than MN without reaching statistical significance, and inter slice alignment was comparable. BA analysis indicates that the variability of volumetric indices between RT and MN is comparable to inter and intra-observer variability reported in the literature. CONCLUSIONS: The free breathing RT-SSFP sequence allows diagnostic images in sedated children with significantly better edge definition when compared to MN-SSFP, without any penalty for total scan time.

Comparison of Low-Dose Higher-Relaxivity and Standard-Dose Lower-Relaxivity Contrast Media for Delayed-Enhancement MRI: A Blinded Randomized Crossover Study.

OBJECTIVE: The gadolinium-based MRI contrast agent gadobenate dimeglumine has nearly twice the MR relaxivity of gadopentetate dimeglumine at 1.5 T. The purpose of this study was to determine whether a lower dose (0.1 mmol/kg) of gadobenate dimeglumine can be used to obtain delayed-enhancement MR images comparable to those obtained with a standard dose (0.2 mmol/kg) of gadopentetate dimeglumine. SUBJECTS AND METHODS: In this blinded randomized crossover study, 20 patients with known myocardial infarction underwent two separate delayed-enhancement MRI examinations after receiving 0.1 mmol/kg gadobenate dimeglumine and 0.2 mmol/kg gadopentetate dimeglumine (random administration). The conspicuity of lesion enhancement 5, 10, and 20 minutes after contrast administration was quantified as relative enhancement ratio (RER). RESULTS: With either gadolinium-based contrast agent, damaged myocardium had higher signal intensity than normal remote myocardium (RER > 4) on delayed-enhancement MR images, and the blood RER declined over time after contrast administration. The blood RER was not significantly higher for gadobenate dimeglumine than for gadopentetate dimeglumine at 5 and 10 minutes. Nevertheless, there was a larger reduction in blood RER for gadobenate dimeglumine than for gadopentetate dimeglumine between 5 and 10 minutes and between 10 and 20 minutes. The volumes of enhancement were similar for gadobenate dimeglumine (13.6 ± 8.8 cm(3)) and gadopentetate dimeglumine (13.5 ± 8.9 cm(3)) (p = 0.98). The mean difference in Bland-Altman analysis for delayed-enhancement volume between the agents was 0.1 cm(3). CONCLUSION: Qualitatively and quantitatively, delayed-enhancement MR images of ischemic myocardium obtained with 0.1 mmol/kg gadobenate dimeglumine are comparable to those obtained with 0.2 mmol/kg gadopentetate dimeglumine 5, 10, and 20 minutes after contrast administration.

Volumetric MRI-guided high-intensity focused ultrasound for noninvasive, in vivo determination of tissue thermal conductivity: initial experience in a pig model.

PURPOSE: To estimate the local thermal conductivity of porcine thigh muscle at temperatures required for magnetic resonance imaging (MRI)-guided high-intensity focused ultrasound (MRgHIFU) surgery (60-90°C). MATERIALS AND METHODS: Using MRgHIFU, we performed 40 volumetric ablations in the thigh muscles of four pigs. Thirty-five of the sonications were successful. We used MRI to monitor the resulting temperature increase. We then determined local thermal conductivity by analyzing the spatiotemporal spread of temperature during the cooling period. RESULTS: The thermal conductivity of MRgHIFU-treated porcine thigh muscle fell within a narrow range (0.52 ± 0.05 W/[m*K]), which is within the range reported for porcine thigh muscle at temperatures of <40°C (0.52 to 0.62 W/[m*K]). Thus, there was little change in the thermal conductivity of porcine thigh muscle at temperatures required for MRgHIFU surgery compared to lower temperatures. CONCLUSION: Our MRgHIFU-based approach allowed us to estimate, with good reproducibility, the local thermal conductivity of in vivo deep tissue in real time at temperatures of 60°C to 90°C. Therefore, our method provides a valuable tool for quantifying the influence of thermal conductivity on temperature distribution in tissues and for optimizing thermal dose delivery during thermal ablation with clinical MRgHIFU.

Evaluation of a subject specific dual-transmit approach for improving B1 field homogeneity in cardiovascular magnetic resonance at 3T.

BACKGROUND: Radiofrequency (RF) shading artifacts degrade image quality while performing cardiovascular magnetic resonance (CMR) at higher field strengths. In this article, we sought to evaluate the effect of local RF (B1 field) shimming by using a dual-source-transmit RF system for cardiac cine imaging and to systematically evaluate the effect of subject body type on the B1 field with and without local RF shimming. METHODS: We obtained cardiac images from 37 subjects (including 11 patients) by using dual-transmit 3T CMR. B1 maps with and without subject-specific local RF shimming (exploiting the independent control of transmit amplitude and phase of the 2 RF transmitters) were obtained. Metrics quantifying B1 field homogeneity were calculated and compared with subject body habitus. RESULTS: Local RF shimming across the region encompassed by the heart increased the mean flip angle (µ) in that area (88.5 ± 15.2% vs. 81.2 ± 13.3%; P = 0.0014), reduced the B1 field variation by 42.2 ± 13%, and significantly improved the percentage of voxels closer to µ (39% and 82% more voxels were closer to ± 10% and ± 5% of µ, respectively) when compared with no RF shimming. B1 homogeneity was independent of subject body type (body surface area [BSA], body mass index [BMI] or anterior-posterior/right-left patient width ratio [AP/RL]). Subject specific RF (B1) shimming with a dual-transmit system improved local RF homogeneity across all body types. CONCLUSION: With or without RF shimming, cardiac B1 field homogeneity does not depend on body type, as characterized by BMI, BSA, and AP/RL. For all body types studied, cardiac B1 field homogeneity was significantly improved by performing local RF shimming with 2 independent RF-transmit channels. This finding indicates the need for subject-specific RF shimming.

Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial.

BACKGROUND: Elevated oxidative stress (OxS), mitochondrial dysfunction, and hallmarks of aging are identified as key contributors to aging, but improving/reversing these defects in older adults (OA) is challenging. In prior studies, we identified that deficiency of the intracellular antioxidant glutathione (GSH) could play a role and reported that supplementing GlyNAC (combination of glycine and N-acetylcysteine [NAC]) in aged mice improved GSH deficiency, OxS, mitochondrial fatty-acid oxidation (MFO), and insulin resistance (IR). To test whether GlyNAC supplementation in OA could improve GSH deficiency, OxS, mitochondrial dysfunction, IR, physical function, and aging hallmarks, we conducted a placebo-controlled randomized clinical trial. METHODS: Twenty-four OA and 12 young adults (YA) were studied. OA was randomized to receive either GlyNAC (N = 12) or isonitrogenous alanine placebo (N = 12) for 16-weeks; YA (N = 12) received GlyNAC for 2-weeks. Participants were studied before, after 2-weeks, and after 16-weeks of supplementation to assess GSH concentrations, OxS, MFO, molecular regulators of energy metabolism, inflammation, endothelial function, IR, aging hallmarks, gait speed, muscle strength, 6-minute walk test, body composition, and blood pressure. RESULTS: Compared to YA, OA had GSH deficiency, OxS, mitochondrial dysfunction (with defective molecular regulation), inflammation, endothelial dysfunction, IR, multiple aging hallmarks, impaired physical function, increased waist circumference, and systolic blood pressure. GlyNAC (and not placebo) supplementation in OA improved/corrected these defects. CONCLUSION: GlyNAC supplementation in OA for 16-weeks was safe and well-tolerated. By combining the benefits of glycine, NAC and GSH, GlyNAC is an effective nutritional supplement that improves and reverses multiple age-associated abnormalities to promote health in aging humans. Clinical Trials Registration Number: NCT01870193.

Magnetic resonance imaging-guided volumetric ablation of symptomatic leiomyomata: correlation of imaging with histology.

PURPOSE: To describe the preliminary safety and accuracy of a magnetic resonance (MR) imaging-guided high-intensity-focused ultrasound (HIFU) system employing new technical developments, including ablation control via volumetric thermal feedback, for the treatment of uterine leiomyomata with histopathologic correlation. MATERIALS AND METHODS: In this phase I clinical trial, 11 women underwent MR-guided HIFU ablation (Sonalleve 1.5T; Philips Medical Systems, Vantaa, Finland), followed by hysterectomy within 30 days. Adverse events, imaging findings, and pathologic confirmation of ablation were assessed. The relationship between MR imaging findings, thermal dose estimates, and pathology and HIFU spatial accuracy were assessed using Bland-Altman analyses and intraclass correlations. RESULTS: There were 12 leiomyomata treated. No serious adverse events were observed. Two subjects decided against having hysterectomy and withdrew from the study before surgery. Of 11 women, 9 underwent hysterectomy; all leiomyomata demonstrated treatment in the expected location. A mean ablation volume of 6.92 cm(3) ± 10.7 was observed at histopathologic examination. No significant differences between MR imaging nonperfused volumes, thermal dose estimates, and histopathology ablation volumes were observed (P > .05). Mean misregistration values perpendicular to the ultrasound beam axis were 0.8 mm ± 1.2 in feet-head direction and 0.1 mm ± 1.0 in and left-right direction and -0.7 mm ± 3.1 along the axis. CONCLUSIONS: Safe, accurate ablation of uterine leiomyomata was achieved with an MR-guided HIFU system with novel treatment monitoring capabilities, including ablation control via volumetric thermal feedback.

Gadolinium-Based Contrast Agents: Updates and Answers to Typical Questions Regarding Gadolinium Use.

Gadolinium-based contrast agents have expanded the diagnostic usefulness and capability of magnetic resonance imaging. Despite their highly favorable safety profile, these agents have been associated with nephrogenic systemic fibrosis in a small number of patients who have advanced kidney disease. Recently, trace amounts of gadolinium deposition in the brain and other organs have been reported after contrast exposure, even in patients with normal renal function. In this review, we provide a brief overview of recent updates and discuss typical clinical situations related to the use of gadolinium-based contrast agents.

Ultrafast Computation of Left Ventricular Ejection Fraction by Using Temporal Intensity Variation in Cine Cardiac Magnetic Resonance.

Cardiac magnetic resonance enables comprehensive cardiac evaluation; however, intense time and labor requirements for data acquisition and processing have discouraged many clinicians from using it. We have developed an alternative image-processing algorithm that requires minimal user interaction: an ultrafast algorithm that computes left ventricular ejection fraction (LVEF) by using temporal intensity variation in cine balanced steady-state free precession (bSSFP) short-axis images, with or without contrast medium. We evaluated the algorithm's performance against an expert observer's analysis for segmenting the LV cavity in 65 study participants (LVEF range, 12%-70%). In 12 instances, contrast medium was administered before cine imaging. Bland-Altman analysis revealed quantitative effects of LV basal, midcavity, and apical morphologic variation on the algorithm's accuracy. Total computation time for the LV stack was <2.5 seconds. The algorithm accurately delineated endocardial boundaries in 1,132 of 1,216 slices (93%). When contours in the extreme basal and apical slices were not adequate, they were replaced with manually drawn contours. The Bland-Altman mean differences were <1.2 mL (0.8%) for end-diastolic volume, <5 mL (6%) for end-systolic volume, and <3% for LVEF. Standard deviation of the difference was ≤4.1% of LV volume for all sections except the midcavity in end-systole (8.3% of end-systolic volume). We conclude that temporal intensity variation-based ultrafast LVEF computation is clinically accurate across a range of LV shapes and wall motions and is suitable for postcontrast cine SSFP imaging. Our algorithm enables real-time processing of cine bSSFP images on a commercial scanner console within 3 seconds in an unobtrusive automated process.

Young athletes: Preventing sudden death by adopting a modern screening approach? A critical review and the opening of a debate.

Preventing sudden cardiac death (SCD) in athletes is a primary duty of sports cardiologists. Current recommendations for detecting high-risk cardiovascular conditions (hr-CVCs) are history and physical examination (H&P)-based. We discuss the effectiveness of H&P-based screening versus more-modern and accurate methods. In this position paper, we review current authoritative statements and suggest a novel alternative: screening MRI (s-MRI), supported by evidence from a preliminary population-based study (completed in 2018), and a prospective, controlled study in military recruits (in development). We present: 1. Literature-Based Comparisons (for diagnosing hr-CVCs): Two recent studies using traditional methods to identify hr-CVCs in >3,000 young athletes are compared with our s-MRI-based study of 5,169 adolescents. 2. Critical Review of Previous Results: The reported incidence of SCD in athletes is presently based on retrospective, observational, and incomplete studies. H&P's screening value seems minimal for structural heart disease, versus echocardiography (which improves diagnosis for high-risk cardiomyopathies) and s-MRI (which also identifies high-risk coronary artery anomalies). Electrocardiography is valuable in screening for potentially high-risk electrophysiological anomalies. 3. Proposed Project : We propose a prospective, controlled study (2 comparable large cohorts: one historical, one prospective) to compare: (1) diagnostic accuracy and resulting mortality-prevention performance of traditional screening methods versus questionnaire/electrocardiography/s-MRI, during 2-month periods of intense, structured exercise (in military recruits, in advanced state of preparation); (2) global costs and cost/efficiency between these two methods. This study should contribute significantly toward a comprehensive understanding of the incidence and causes of exercise-related mortality (including establishing a definition of hr-CVCs) while aiming to reduce mortality.