Compartment-based reconstruction of 3D acquisition-weighted 31 P cardiac magnetic resonance spectroscopic imaging at 7 T: A reproducibility study.

Even at 7 T, cardiac 31 P magnetic resonance spectroscopic imaging (MRSI) is fundamentally limited by low signal-to-noise ratio (SNR), leading to long scan times and poor temporal and spatial resolutions. Compartment-based reconstruction algorithms such as magnetic resonance spectroscopy with linear algebraic modeling (SLAM) and spectral localization by imaging (SLIM) may improve SNR or reduce scan time without changes to acquisition. Here, we compare the repeatability and SNR performance of these compartment-based methods, applied to three different acquisition schemes at 7 T. Twelve healthy volunteers were scanned twice. Each scan session consisted of a 6.5-min 3D acquisition-weighted (AW) cardiac 31 P phase encode-based MRSI acquisition and two 6.5-min truncated k-space acquisitions with increased averaging (4 × 4 × 4 central k-space phase encodes and fractional SLAM [fSLAM] optimized k-space phase encodes). Spectra were reconstructed using (i) AW Fourier reconstruction; (ii) AW SLAM; (iii) AW SLIM; (iv) 4 × 4 × 4 SLAM; (v) 4 × 4 × 4 SLIM; and (vi) fSLAM acquisition-reconstruction combinations. The phosphocreatine-to-adenosine triphosphate (PCr/ATP) ratio, the PCr SNR, and spatial response functions were computed, in addition to coefficients of reproducibility and variability. Using the compartment-based reconstruction algorithms with the AW 31 P acquisition resulted in a significant increase in SNR compared with previously published Fourier-based MRSI reconstruction methods while maintaining the measured PCr/ATP ratio and improving interscan reproducibility. The alternative acquisition strategies with truncated k-space performed no better than the common AW approach. Compartment-based spectroscopy approaches provide an attractive reconstruction method for cardiac 31 P spectroscopy at 7 T, improving reproducibility and SNR without the need for a dedicated k-space sampling strategy.

Myocardial ATP depletion detected noninvasively predicts sudden cardiac death risk in patients with heart failure.

BACKGROUNDSudden cardiac death (SCD) remains a worldwide public health problem in need of better noninvasive predictive tools. Current guidelines for primary preventive SCD therapies, such as implantable cardioverter defibrillators (ICDs), are based on left ventricular ejection fraction (LVEF), but these guidelines are imprecise: fewer than 5% of ICDs deliver lifesaving therapy per year. Impaired cardiac metabolism and ATP depletion cause arrhythmias in experimental models, but to our knowledge a link between arrhythmias and cardiac energetic abnormalities in people has not been explored, nor has the potential for metabolically predicting clinical SCD risk.METHODSWe prospectively measured myocardial energy metabolism noninvasively with phosphorus magnetic resonance spectroscopy in patients with no history of significant arrhythmias prior to scheduled ICD implantation for primary prevention in the setting of reduced LVEF (≤35%).RESULTSBy 2 different analyses, low myocardial ATP significantly predicted the composite of subsequent appropriate ICD firings for life-threatening arrhythmias and cardiac death over approximately 10 years. Life-threatening arrhythmia risk was approximately 3-fold higher in patients with low ATP and independent of established risk factors, including LVEF. In patients with normal ATP, rates of appropriate ICD firings were several-fold lower than reported rates of ICD complications and inappropriate firings.CONCLUSIONTo the best of our knowledge, these are the first data linking in vivo myocardial ATP depletion and subsequent significant arrhythmic events in people, suggesting an energetic component to clinical life-threatening ventricular arrhythmogenesis. The findings support investigation of metabolic strategies that limit ATP loss to treat or prevent life-threatening cardiac arrhythmias and herald noninvasive metabolic imaging as a complementary SCD risk stratification tool.TRIAL REGISTRATIONClinicalTrials.gov NCT00181233.FUNDINGThis work was supported by the DW Reynolds Foundation, the NIH (grants HL61912, HL056882, HL103812, HL132181, HL140034), and Russell H. Morgan and Clarence Doodeman endowments at Johns Hopkins.

Mitochondrial Creatine Kinase Attenuates Pathologic Remodeling in Heart Failure.

BACKGROUND: Abnormalities in cardiac energy metabolism occur in heart failure (HF) and contribute to contractile dysfunction, but their role, if any, in HF-related pathologic remodeling is much less established. CK (creatine kinase), the primary muscle energy reserve reaction which rapidly provides ATP at the myofibrils and regenerates mitochondrial ADP, is down-regulated in experimental and human HF. We tested the hypotheses that pathologic remodeling in human HF is related to impaired cardiac CK energy metabolism and that rescuing CK attenuates maladaptive hypertrophy in experimental HF. METHODS: First, in 27 HF patients and 14 healthy subjects, we measured cardiac energetics and left ventricular remodeling using noninvasive magnetic resonance 31P spectroscopy and magnetic resonance imaging, respectively. Second, we tested the impact of metabolic rescue with cardiac-specific overexpression of either Ckmyofib (myofibrillar CK) or Ckmito (mitochondrial CK) on HF-related maladaptive hypertrophy in mice. RESULTS: In people, pathologic left ventricular hypertrophy and dilatation correlate closely with reduced myocardial ATP levels and rates of ATP synthesis through CK. In mice, transverse aortic constriction-induced left ventricular hypertrophy and dilatation are attenuated by overexpression of CKmito, but not by overexpression of CKmyofib. CKmito overexpression also attenuates hypertrophy after chronic isoproterenol stimulation. CKmito lowers mitochondrial reactive oxygen species, tissue reactive oxygen species levels, and upregulates antioxidants and their promoters. When the CK capacity of CKmito-overexpressing mice is limited by creatine substrate depletion, the protection against pathologic remodeling is lost, suggesting the ADP regenerating capacity of the CKmito reaction rather than CK protein per se is critical in limiting adverse HF remodeling. CONCLUSIONS: In the failing human heart, pathologic hypertrophy and adverse remodeling are closely related to deficits in ATP levels and in the CK energy reserve reaction. CKmito, sitting at the intersection of cardiac energetics and redox balance, plays a crucial role in attenuating pathologic remodeling in HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00181259.

Rapid, B1 -insensitive, dual-band quasi-adiabatic saturation transfer with optimal control for complete quantification of myocardial ATP flux.

PURPOSE: Phosphorus saturation-transfer experiments can quantify metabolic fluxes noninvasively. Typically, the forward flux through the creatine kinase reaction is investigated by observing the decrease in phosphocreatine (PCr) after saturation of γ-ATP. The quantification of total ATP utilization is currently underexplored, as it requires simultaneous saturation of inorganic phosphate ( Pi ) and PCr. This is challenging, as currently available saturation pulses reduce the already-low γ-ATP signal present. METHODS: Using a hybrid optimal-control and Shinnar-Le Roux method, a quasi-adiabatic RF pulse was designed for the dual saturation of PCr and Pi to enable determination of total ATP utilization. The pulses were evaluated in Bloch equation simulations, compared with a conventional hard-cosine DANTE saturation sequence, before being applied to perfused rat hearts at 11.7 T. RESULTS: The quasi-adiabatic pulse was insensitive to a >2.5-fold variation in B1 , producing equivalent saturation with a 53% reduction in delivered pulse power and a 33-fold reduction in spillover at the minimum effective B1 . This enabled the complete quantification of the synthesis and degradation fluxes for ATP in 30-45 minutes in the perfused rat heart. While the net synthesis flux (4.24 ± 0.8 mM/s, SEM) was not significantly different from degradation flux (6.88 ± 2 mM/s, P = .06) and both measures are consistent with prior work, nonlinear error analysis highlights uncertainties in the Pi -to-ATP measurement that may explain a trend suggesting a possible imbalance. CONCLUSIONS: This work demonstrates a novel quasi-adiabatic dual-saturation RF pulse with significantly improved performance that can be used to measure ATP turnover in the heart in vivo.

Real-Time High-Resolution MRI Endoscopy at up to 10 Frames per Second.

Objective. Atherosclerosis is a leading cause of mortality and morbidity. Optical endoscopy, ultrasound, and X-ray offer minimally invasive imaging assessments but have limited sensitivity for characterizing disease and therapeutic response. Magnetic resonance imaging (MRI) endoscopy is a newer idea employing tiny catheter-mounted detectors connected to the MRI scanner. It can see through vessel walls and provide soft-tissue sensitivity, but its slow imaging speed limits practical applications. Our goal is high-resolution MRI endoscopy with real-time imaging speeds comparable to existing modalities. Methods. Intravascular (3 mm) transmit-receive MRI endoscopes were fabricated for highly undersampled radial-projection MRI in a clinical 3-tesla MRI scanner. Iterative nonlinear reconstruction was accelerated using graphics processor units connected via a single ethernet cable to achieve true real-time endoscopy visualization at the scanner. MRI endoscopy was performed at 6-10 frames/sec and 200-300 µm resolution in human arterial specimens and porcine vessels ex vivo and in vivo and compared with fully sampled 0.3 frames/sec and three-dimensional reference scans using mutual information (MI) and structural similarity (3-SSIM) indices. Results. High-speed MRI endoscopy at 6-10 frames/sec was consistent with fully sampled MRI endoscopy and histology, with feasibility demonstrated in vivo in a large animal model. A 20-30-fold speed-up vs. 0.3 frames/sec reference scans came at a cost of ~7% in MI and ~45% in 3-SSIM, with reduced motion sensitivity. Conclusion. High-resolution MRI endoscopy can now be performed at frame rates comparable to those of X-ray and optical endoscopy and could provide an alternative to existing modalities, with MRI's advantages of soft-tissue sensitivity and lack of ionizing radiation.

Exercise intolerance and rapid skeletal muscle energetic decline in human age-associated frailty.

BACKGROUNDPhysical frailty in older individuals is characterized by subjective symptoms of fatigue and exercise intolerance (EI). Objective abnormalities in skeletal muscle (SM) mitochondrial high-energy phosphate (HEP) metabolism contribute to EI in inherited myopathies; however, their presence or link to EI in the frail older adult is unknown.METHODSHere, we studied 3 groups of ambulatory, community-dwelling adults with no history of significant coronary disease: frail older (FO) individuals (81 ± 2.7 years, mean ± SEM), nonfrail older (NFO) individuals (79 ± 2.0 years), and healthy middle-aged individuals, who served as controls (CONT, 51 ± 2.1 years). Lower extremity SM HEP levels and mitochondrial function were measured with 31P magnetic resonance (MR) techniques during graded multistage plantar flexion exercise (PFE). EI was quantified by a 6-minute walk (6MW) and peak oxygen consumption during cardiopulmonary testing (peak VO2).RESULTSDuring graded exercise, FO, NFO, and CONT individuals all fatigued at similar SM HEP levels, as measured by 31P-MR. However, FO individuals fatigued fastest, with several-fold higher rates of PFE-induced HEP decline that correlated closely with shorter exercise duration in the MR scanner and with 6MW distance and lower peak oxygen consumption on cardiopulmonary testing (P < 0.001 for all). SM mitochondrial oxidative capacity was lower in older individuals and correlated with rapid HEP decline but less closely with EI.CONCLUSIONSeveral-fold faster SM energetic decline during exercise occurs in FO individuals and correlates closely with multiple measures of EI. Rapid energetic decline represents an objective, functional measure of SM metabolic changes and a potential new target for mitigating frailty-associated physical limitations.FUNDINGThis work was supported by NIH R21 AG045634, R01 AG063661, R01 HL61912, the Johns Hopkins University Claude D. Pepper Older Americans Independence Center P30AG021334, and the Clarence Doodeman Endowment in Cardiology at Johns Hopkins.

High-resolution intravascular MRI-guided perivascular ultrasound ablation.

PURPOSE: To develop and test in animal studies ex vivo and in vivo, an intravascular (IV) MRI-guided high-intensity focused ultrasound (HIFU) ablation method for targeting perivascular pathology with minimal injury to the vessel wall. METHODS: IV-MRI antennas were combined with 2- to 4-mm diameter water-cooled IV-ultrasound ablation catheters for IV-MRI on a 3T clinical MRI scanner. A software interface was developed for monitoring thermal dose with real-time MRI thermometry, and an MRI-guided ablation protocol developed by repeat testing on muscle and liver tissue ex vivo. MRI thermal dose was measured as cumulative equivalent minutes at 43°C (CEM43 ). The IV-MRI IV-HIFU protocol was then tested by targeting perivascular ablations from the inferior vena cava of 2 pigs in vivo. Thermal dose and lesions were compared by gross and histological examination. RESULTS: Ex vivo experiments yielded a 6-min ablation protocol with the IV-ultrasound catheter coolant at 3-4°C, a 30 mL/min flow rate, and 7 W ablation power. In 8 experiments, 5- to 10-mm thick thermal lesions of area 0.5-2 cm2 were produced that spared 1- to 2-mm margins of tissue abutting the catheters. The radial depths, areas, and preserved margins of ablation lesions measured from gross histology were highly correlated (r ≥ 0.79) with those measured from the CEM43 = 340 necrosis threshold determined by MRI thermometry. The psoas muscle was successfully targeted in the 2 live pigs, with the resulting ablations controlled under IV-MRI guidance. CONCLUSION: IV-MRI-guided, IV-HIFU has potential as a precision treatment option that could preserve critical blood vessel wall during ablation of nonresectable perivascular tumors or other pathologies.

Neural-network classification of cardiac disease from 31P cardiovascular magnetic resonance spectroscopy measures of creatine kinase energy metabolism.

BACKGROUND: The heart's energy demand per gram of tissue is the body's highest and creatine kinase (CK) metabolism, its primary energy reserve, is compromised in common heart diseases. Here, neural-network analysis is used to test whether noninvasive phosphorus (31P) cardiovascular magnetic resonance spectroscopy (CMRS) measurements of cardiac adenosine triphosphate (ATP) energy, phosphocreatine (PCr), the first-order CK reaction rate kf, and the rate of ATP synthesis through CK (CK flux), can predict specific human heart disease and clinical severity. METHODS: The data comprised the extant 178 complete sets of PCr and ATP concentrations, kf, and CK flux data from human CMRS studies performed on clinical 1.5 and 3 Tesla scanners. Healthy subjects and patients with nonischemic cardiomyopathy, dilated (DCM) or hypertrophic disease, New York Heart Association (NYHA) class I-IV heart failure (HF), or with anterior myocardial infarction are included. Three-layer neural-networks were created to classify disease and to differentiate DCM, hypertrophy and clinical NYHA class in HF patients using leave-one-out training. Network performance was assessed using 'confusion matrices' and 'area-under-the-curve' (AUC) analyses of 'receiver operating curves'. Possible methodological bias and network imbalance were tested by segregating 1.5 and 3 Tesla data, and by data augmentation by random interpolation of nearest neighbors, respectively. RESULTS: The network differentiated healthy, HF and non-HF cardiac disease with an overall accuracy of 84% and AUC > 90% for each category using the four CK metabolic parameters, alone. HF patients with DCM, hypertrophy, and different NYHA severity were differentiated with ~ 80% overall accuracy independent of CMRS methodology. CONCLUSIONS: While sample-size was limited in some sub-classes, a neural network classifier applied to noninvasive cardiac 31P CMRS data, could serve as a metabolic biomarker for common disease types and HF severity with clinically-relevant accuracy. Moreover, the network's ability to individually classify disease and HF severity using CK metabolism alone, implies an intimate relationship between CK metabolism and disease, with subtle underlying phenotypic differences that enable their differentiation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00181259.

Fast 3D chemical exchange saturation transfer imaging with variably-accelerated sensitivity encoding (vSENSE).

PURPOSE: To extend the variably-accelerated sensitivity encoding (vSENSE) method from 2D to 3D for fast chemical exchange saturation transfer (CEST) imaging, and prospectively implement it for clinical MRI. METHODS: The CEST scans were acquired from 7 normal volunteers and 15 brain tumor patients using a 3T clinical scanner. The 2D and 3D "artifact suppression" (AS) vSENSE algorithms were applied to generate sensitivity maps from a first scan acquired with conventional SENSE-accelerated 2D and 3D CEST data. The AS sensitivity maps were then applied to reconstruct the other CEST frames at higher acceleration factors. Both retrospective and prospective acceleration in phase-encoding and slice-encoding dimensions were implemented. RESULTS: Applying the 2D AS vSENSE algorithm to a 2-fold undersampled 3.5-ppm CEST frame halved the scan time of conventional SENSE, while generating essentially identical reconstruction errors (p ≈ 1.0). The 3D AS vSENSE algorithm permitted prospective acceleration by up to 8-fold, in total, from phase-encoding and slice-encoding directions for individual source CEST images, and an overall speed-up in scan time of 5-fold. The resulting vSENSE-accelerated amide proton transfer-weighted images agreed with conventional 2-fold-accelerated SENSE CEST results in brain tumor patients and healthy volunteers. Importantly, the vSENSE method eliminated unfolding artifacts in the slice-encoding direction that compromised conventional SENSE CEST scans. CONCLUSION: The vSENSE method can be extended to 3D CEST imaging to provide higher acceleration factors than conventional SENSE without compromising accuracy.

The relative age effect in European elite soccer: A practical guide to Poisson regression modelling.

Many disciplines of scholarship are interested in the Relative Age Effect (RAE), whereby age-banding confers advantages on older members of the cohort over younger ones. Most research does not test this relationship in a manner consistent with theory (which requires a decline in frequency across the cohort year), instead resorting to non-parametric, non-directional approaches. In this article, the authors address this disconnect, provide an overview of the benefits associated with Poisson regression modelling, and two managerially useful measures for quantifying RAE bias, namely the Indices of Discrimination and Wastage. In a tutorial-like exposition, applications and extensions of this approach are illustrated using data on professional soccer players competing in the top two tiers of the "Big Five" European football leagues in the search to identify paragon clubs, leagues, and countries from which others may learn to mitigate this form of age-discrimination in the talent identification process. As with OLS regression, Poisson regression may include more than one independent variable. In this way we test competing explanations of RAE; control for unwanted sources of covariation; model interaction effects (that different clubs and countries may not all be subject to RAE to the same degree); and test for non-monotonic versions of RAE suggested in the literature.

Cardiac work is related to creatine kinase energy supply in human heart failure: a cardiovascular magnetic resonance spectroscopy study.

BACKGROUND: It has been hypothesized that the supply of chemical energy may be insufficient to fuel normal mechanical pump function in heart failure (HF). The creatine kinase (CK) reaction serves as the heart's primary energy reserve, and the supply of adenosine triphosphate (ATP flux) it provides is reduced in human HF. However, the relationship between the CK energy supply and the mechanical energy expended has never been quantified in the human heart. This study tests whether reduced CK energy supply is associated with reduced mechanical work in HF patients. METHODS: Cardiac mechanical work and CK flux in W/kg, and mechanical efficiency were measured noninvasively at rest using cardiac pressure-volume loops, magnetic resonance imaging and phosphorus spectroscopy in 14 healthy subjects and 27 patients with mild-to-moderate HF. RESULTS: In HF, the resting CK flux (126 ± 46 vs. 179 ± 50 W/kg, p < 0.002), the average (6.8 ± 3.1 vs. 10.1 ± 1.5 W/kg, p  <0.001) and the peak (32 ± 14 vs. 48 ± 8 W/kg, p < 0.001) cardiac mechanical work-rates, as well as the cardiac mechanical efficiency (53% ± 16 vs. 79% ± 3, p < 0.001), were all reduced by a third compared to healthy subjects. In addition, cardiac CK flux correlated with the resting peak and average mechanical power (p < 0.01), and with mechanical efficiency (p = 0.002). CONCLUSION: These first noninvasive findings showing that cardiac mechanical work and efficiency in mild-to-moderate human HF decrease proportionately with CK ATP energy supply, are consistent with the energy deprivation hypothesis of HF. CK energy supply exceeds mechanical work at rest but lies within a range that may be limiting with moderate activity, and thus presents a promising target for HF treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00181259 .

Relative age effect in elite soccer: More early-born players, but no better valued, and no paragon clubs or countries.

The paper analyses two datasets of elite soccer players (top 1000 professionals and UEFA Under-19 Youth League). In both, we find a Relative Age Effect (RAE) for frequency, but not for value. That is, while there are more players born at the start of the competition year, their transfer values are no higher, nor are they given more game time. We use Poisson regression to derive a transparent index of the discrimination present in RAE. Also, because Poisson is valid for small frequency counts, it supports analysis at the disaggregated levels of country and club. From this, we conclude there are no paragon clubs or countries immune to RAE; that is clubs and countries do not differ systematically in the RAE they experience; also, that Poisson regression is a powerful and flexible method of analysing RAE data.

Ultrafast compartmentalized relaxation time mapping with linear algebraic modeling.

PURPOSE: To dramatically accelerate compartmental-average longitudinal (T1 ) and transverse (T2 ) relaxation measurements using the minimal-acquisition linear algebraic modeling (SLAM) method, and to validate it in phantoms and humans. METHODS: Relaxation times were imaged at 3 Tesla in phantoms, in the abdomens of six volunteers, and in six brain tumor patients using standard inversion recovery and multi-spin-echo sequences. k-space was fully sampled to provide reference T1 and T2 measurements, and SLAM was performed using a limited set of phase encodes from central k-space. Anatomical compartments were segmented on scout images post-acquisition, and SLAM reconstruction was implemented using two algorithms. Compartment-average T1 and T2 measurements were determined retroactively from fully sampled data sets, and proactively from SLAM data sets at acceleration factors of up to 16. Values were compared with reference measurements. The compartment's localization properties were analyzed using the discrete spatial response function. RESULTS: At 16-fold acceleration, compartment-average SLAM T1 measurements agreed with the full k-space compartment-average results to within 0.0% ± 0.7%, 1.4% ± 3.4%, and 0.5% ± 2.9% for phantom, abdominal, and brain T1 measurements, respectively. The corresponding T2 measurements agreed within 0.2% ± 1.9%, 0.9% ± 7.9%, and 0.4% ± 5.8%, respectively. CONCLUSION: SLAM can dramatically accelerate relaxation time measurements when compartmental or lesion-average values can suffice, or when standard relaxometry is precluded by scan-time limitations. Magn Reson Med 79:286-297, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

High-resolution and accelerated multi-parametric mapping with automated characterization of vessel disease using intravascular MRI.

BACKGROUND: Atherosclerosis is prevalent in cardiovascular disease, but present imaging modalities have limited capabilities for characterizing lesion stage, progression and response to intervention. This study tests whether intravascular magnetic resonance imaging (IVMRI) measures of relaxation times (T1, T2) and proton density (PD) in a clinical 3 Tesla scanner could characterize vessel disease, and evaluates a practical strategy for accelerated quantification. METHODS: IVMRI was performed in fresh human artery segments and swine vessels in vivo, using fast multi-parametric sequences, 1-2 mm diameter loopless antennae and 200-300 µm resolution. T1, T2 and PD data were used to train a machine learning classifier (support vector machine, SVM) to automatically classify normal vessel, and early or advanced disease, using histology for validation. Disease identification using the SVM was tested with receiver operating characteristic curves. To expedite acquisition of T1, T2 and PD data for vessel characterization, the linear algebraic method ('SLAM') was modified to accommodate the antenna's highly-nonuniform sensitivity, and used to provide average T1, T2 and PD measurements from compartments of normal and pathological tissue segmented from high-resolution images at acceleration factors of R ≤ 18-fold. The results were validated using compartment-average measures derived from the high-resolution scans. RESULTS: The SVM accurately classified ~80% of samples into the three disease classes. The 'area-under-the-curve' was 0.96 for detecting disease in 248 samples, with T1 providing the best discrimination. SLAM T1, T2 and PD measures for R ≤ 10 were indistinguishable from the true means of segmented tissue compartments. CONCLUSION: High-resolution IVMRI measures of T1, T2 and PD with a trained SVM can automatically classify normal, early and advanced atherosclerosis with high sensitivity and specificity. Replacing relaxometric MRI with SLAM yields good estimates of T1, T2 and PD an order-of-magnitude faster to facilitate IVMRI-based characterization of vessel disease.

Ultrafast compartmental relaxation time mapping with linear algebraic modeling.

Image contrast afforded by tissue longitudinal (T1) and transverse (T2) relaxation times is central to the success of modern MRI. Here, a recently-proposed 'spectroscopy with linear algebraic modeling' (SLAM) method is adapted to dramatically accelerate relaxation time imaging at 3 Tesla in phantoms, the abdomens of six volunteers and in six brain tumor patients.. SLAM is validated by omitting up to 15/16ths (94%) of the data acquired retroactively from inversion recovery and multi-echo spin-echo sequences, and proactively applied to accelerate abdominal and brain tumor T1 and T2 measurements by up to 16-fold in humans..

Fast, Reliable 3D Amide Proton Transfer Imaging of Brain Tumors at 3T with Variably-accelerated Sensitivity Encoding (vSENSE).

The clinical use of amide proton transfer (APT) imaging is hindered by long scan times. Accuracy generally limits the use of conventional sensitivity encoding (SENSE) methods in APT, to an acceleration factor of 2. A novel variably-accelerated sensitivity encoding (vSENSE) method can provide more accurate results and therefore substantially higher overall acceleration factors than conventional SENSE. Here, vSENSE is further developed to eliminate the requirement that one fully-sampled APT frame be acquired, and extended to three dimensions (3D). Furthermore, we combine vSENSE with parallel transmit saturation, and apply it proactively to three normal volunteers and eleven patients with brain tumors.

Fatigability, Exercise Intolerance, and Abnormal Skeletal Muscle Energetics in Heart Failure.

BACKGROUND: Among central and peripheral factors contributing to exercise intolerance (EI) in heart failure (HF), the extent to which skeletal muscle (SM) energy metabolic abnormalities occur and contribute to EI and increased fatigability in HF patients with reduced or preserved ejection fraction (HFrEF and HFpEF, respectively) are not known. An energetic plantar flexion exercise fatigability test and magnetic resonance spectroscopy were used to probe the mechanistic in vivo relationships among SM high-energy phosphate concentrations, mitochondrial function, and EI in HFrEF and HFpEF patients and in healthy controls. METHODS AND RESULTS: Resting SM high-energy phosphate concentrations and ATP flux rates were normal in HFrEF and HFpEF patients. Fatigue occurred at similar SM energetic levels in all subjects, consistent with a common SM energetic limit. Importantly, HFrEF New York Heart Association class II-III patients with EI and high fatigability exhibited significantly faster rates of exercise-induced high-energy phosphate decline than did HFrEF patients with low fatigability (New York Heart Association class I), despite similar left ventricular ejection fractions. HFpEF patients exhibited severe EI, the most rapid rates of high-energy phosphate depletion during exercise, and impaired maximal oxidative capacity. CONCLUSIONS: Symptomatic fatigue during plantar flexion exercise occurs at a common energetic limit in all subjects. HFrEF and HFpEF patients with EI and increased fatigability manifest early, rapid exercise-induced declines in SM high-energy phosphates and reduced oxidative capacity compared with healthy and low-fatigability HF patients, suggesting that SM metabolism is a potentially important target for future HF treatment strategies.