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.

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.

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.

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.

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.

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.

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.

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 .

Chemical exchange saturation transfer (CEST) imaging with fast variably-accelerated sensitivity encoding (vSENSE).

PURPOSE: The widespread clinical use of chemical exchange saturation transfer (CEST) imaging is hampered by relatively long scan times due to its requirement that multiple saturation-offset image frames be acquired. Here, a novel variably-accelerated sensitivity encoding (vSENSE) method is proposed that provides faster CEST acquisition than conventional SENSE. THEORY AND METHODS: The vSENSE method fully samples one CEST saturation frame, then undersamples the other frames variably. The fully-sampled frame, in conjunction with newly proposed incoherence absorption and artifact suppression strategies, improves the accuracy of sensitivity maps and permits higher acceleration factors for the other undersampled frames than regular SENSE. vSENSE is validated in a phantom, a normal volunteer and eight brain tumor patients at 3 Tesla. RESULTS: vSENSE with an acceleration factor of four generated a 3-6 times smaller error on average than conventional SENSE (P ≤ 0.02), with acceleration factors of 2-4, as compared with full k-space reconstruction. vSENSE permitted four-fold acceleration for amide proton transfer-weighted images, while regular SENSE could only provide a factor of two. When conventional SENSE is used with vSENSE's variable undersampling pattern, erroneous (∼9%) z-spectra result. CONCLUSION: The vSENSE method enabled twice the acceleration and generated more accurate images than conventional SENSE. Magn Reson Med 77:2225-2238, 2017. © 2016 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.

Radiofrequency Ablation, MR Thermometry, and High-Spatial-Resolution MR Parametric Imaging with a Single, Minimally Invasive Device.

Purpose To develop and demonstrate in vitro and in vivo a single interventional magnetic resonance (MR)-active device that integrates the functions of precise identification of a tissue site with the delivery of radiofrequency (RF) energy for ablation, high-spatial-resolution thermal mapping to monitor thermal dose, and quantitative MR imaging relaxometry to document ablation-induced tissue changes for characterizing ablated tissue. Materials and Methods All animal studies were approved by the institutional animal care and use committee. A loopless MR imaging antenna composed of a tuned microcable either 0.8 or 2.2 mm in diameter with an extended central conductor was switched between a 3-T MR imaging unit and an RF power source to monitor and perform RF ablation in bovine muscle and human artery samples in vitro and in rabbits in vivo. High-spatial-resolution (250-300-µm) proton resonance frequency shift MR thermometry was interleaved with ablations. Quantitative spin-lattice (T1) and spin-spin (T2) relaxation time MR imaging mapping was performed before and after ablation. These maps were compared with findings from gross tissue examination of the region of ablated tissue after MR imaging. Results High-spatial-resolution MR imaging afforded temperature mapping in less than 8 seconds for monitoring ablation temperatures in excess of 85°C delivered by the same device. This produced irreversible thermal injury and necrosis. Quantitative MR imaging relaxation time maps demonstrated up to a twofold variation in mean regional T1 and T2 after ablation versus before ablation. Conclusion A simple, integrated, minimally invasive interventional probe that provides image-guided therapy delivery, thermal mapping of dose, and detection of ablation-associated MR imaging parametric changes was developed and demonstrated. With this single-device approach, coupling-related safety concerns associated with multiple conductor approaches were avoided. © RSNA, 2016 Online supplemental material is available for this article.

Highly accelerated chemical exchange saturation transfer (CEST) measurements with linear algebraic modeling.

PURPOSE: In clinical studies, compartmental average chemical exchange saturation transfer (CEST) measurements rather than voxel-by-voxel CEST images may suffice for evaluating its diagnostic value. A recently developed method-spectroscopy with linear algebraic modeling, or SLAM-could directly provide compartmental measures with dramatically reduced scan time and optimal signal-to-noise ratios. Here, we test whether SLAM can be adapted to significantly accelerate CEST acquisitions. THEORY AND METHODS: Conventional anatomical images and raw CEST image k-space data were acquired from seven brain tumor patients. SLAM was applied to the CEST data using acceleration factors of R = 1-45, after segmenting compartments from co-registered images. SLAM-CEST measures were compared with average values from the identical compartments obtained by conventional Fourier transform (FT) CEST. RESULTS: SLAM generated compartmental average CEST z-spectra that were indistinguishable from conventional FT-CEST for R ≤ 45. SLAM-CEST z-spectra at ±3.5 ppm were highly correlated with FT-CEST measures (r(2) ≥ 0.98 for R ≤ 9; r ≥ 0.995 for R ≤ 45). The average error of SLAM-CEST versus FT-CEST measures was ≤10% for R ≤ 45, in acquisitions requiring as few as a single k-space phase-encoding step. CONCLUSION: Applied to patients with brain tumors, SLAM-CEST can yield results that are quantitatively equivalent to conventional CEST up to 45 times faster, which could prove enabling in clinical settings where scan time is limiting. Magn Reson Med 76:136-144, 2016. © 2015 Wiley Periodicals, Inc.

Sodium MRI in human heart: a review.

This paper offers a critical review of the properties, methods and potential clinical application of sodium ((23)Na) MRI in human heart. Because the tissue sodium concentration (TSC) in heart is about ~40 µmol/g wet weight, and the (23)Na gyromagnetic ratio and sensitivity are respectively about one-quarter and one-11th of that of hydrogen ((1)H), the signal-to-noise ratio of (23)Na MRI in the heart is about one-6000th of that of conventional cardiac (1)H MRI. In addition, as a quadrupolar nucleus, (23)Na exhibits ultra-short and multi-component relaxation behavior (T1 ~ 30 ms; T2 ~ 0.5-4 ms and 12-20 ms), which requires fast, specialized, ultra-short echo-time MRI sequences, especially for quantifying TSC. Cardiac (23)Na MRI studies from 1.5 to 7 T measure a volume-weighted sum of intra- and extra-cellular components present at cytosolic concentrations of 10-15 mM and 135-150 mM in healthy tissue, respectively, at a spatial resolution of about 0.1-1 ml in 10 min or so. Currently, intra- and extra-cellular sodium cannot be unambiguously resolved without the use of potentially toxic shift reagents. Nevertheless, increases in TSC attributable to an influx of intra-cellular sodium and/or increased extra-cellular volume have been demonstrated in human myocardial infarction consistent with prior animal studies, and arguably might also be seen in future studies of ischemia and cardiomyopathies--especially those involving defects in sodium transport. While technical implementation remains a hurdle, a central question for clinical use is whether cardiac (23)Na MRI can deliver useful information unobtainable by other more convenient methods, including (1)H MRI.

Acceleration and motion-correction techniques for high-resolution intravascular MRI.

PURPOSE: High-resolution intravascular (IV) MRI is susceptible to degradation from physiological motion and requires high frame-rates for true endoscopy. Traditional cardiac-gating techniques compromise efficiency by reducing the effective scan rate. Here we test whether compressed sensing (CS) reconstruction and ungated motion-compensation using projection shifting, could provide faster motion-suppressed, IVMRI. THEORY AND METHODS: CS reconstruction is developed for undersampled Cartesian and radial imaging using a new IVMRI-specific cost function to effectively increase imaging speed. A new motion correction method is presented wherein individual IVMRI projections are shifted based on the IVMRI detector's intrinsic amplitude and phase properties. The methods are tested at 3 Tesla (T) in fruit, human vessel specimens, and a rabbit aorta in vivo. Images are compared using structural-similarity and "spokal variation" indices. RESULTS: Although some residual artifacts persisted, CS acceleration and radial motion compensation strategies reduced motion artifact in vitro and in vivo, allowing effective accelerations of up to eight-fold at 200-300 µm resolution. CONCLUSION: The 3T IVMRI detectors are well-suited to CS and motion correction strategies based on their intrinsic radially-sparse sensitivity profiles and high signal-to-noise ratios.

Minimizing lipid signal bleed in brain (1) H chemical shift imaging by post-acquisition grid shifting.

PURPOSE: Low spatial resolution in conventional 1H brain chemical shifting imaging (CSI) studies causes partial volume error (PVE) or signal "bleed" that is especially deleterious to voxels near the scalp. The standard spatial apodization approach adversely affects spatial resolution. Here, a novel automated post-processing strategy of partial volume correction employing grid shifting ("PANGS") is presented, which minimizes residual PVE without compromising spatial resolution. METHODS: PANGS shifts the locations of the reconstruction coordinates in a designated region of image space-the scalp, to match the tissue "centers-of-mass" instead of the geometric centers of each voxel, by iteratively minimizing the PVE from the scalp into outside voxels. PANGS' performance was evaluated by numerical simulation, and in 3 Tesla 1H CSI human studies employing outer volume suppression and long echo times. RESULTS: PANGS reduced lipid contamination of cortical spectra by up to 86% (54% on average). Metabolite maps exhibited significantly less lipid artifact than conventional and spatially-filtered CSI. All methods generated quantitatively identical spectral peak areas from central brain locations, but spatial filtering increased spectral linewidths and reduced spatial resolution. CONCLUSION: PANGS significantly reduces lipid artifacts in 1H brain CSI spectra and metabolite maps, and improves metabolite detection in cortical regions without compromising resolution.

On the theoretical limits of detecting cyclic changes in cardiac high-energy phosphates and creatine kinase reaction kinetics using in vivo ³¹P MRS.

Adenosine triphosphate (ATP) is absolutely required to fuel normal cyclic contractions of the heart. The creatine kinase (CK) reaction is a major energy reserve reaction that rapidly converts creatine phosphate (PCr) to ATP during the cardiac cycle and at times of stress and ischemia, but is significantly impaired in conditions such as hypertrophy and heart failure. Because the magnitudes of possible in vivo cyclic changes in cardiac high-energy phosphates (HEPs) during the cardiac cycle are not well known from previous work, this study uses mathematical modeling to assess whether, and to what extent, cyclic variations in HEPs and in the rate of ATP synthesis through CK (CK flux) could exist in the human heart, and whether they could be measured with current in vivo (31)P MRS methods. Multi-site exchange models incorporating enzymatic rate equations were used to study the cyclic dynamics of the CK reaction, and Bloch equations were used to simulate (31)P MRS saturation transfer measurements of the CK reaction. The simulations show that short-term buffering of ATP by CK requires temporal variations over the cardiac cycle in the CK reaction velocities modeled by enzymatic rate equations. The maximum variation in HEPs in the normal human heart beating at 60 min(-1) was approximately 0.4 mM and proportional to the velocity of ATP hydrolysis. Such HEP variations are at or below the current limits of detection by in vivo (31)P MRS methods. Bloch equation simulations show that (31)P MRS saturation transfer estimates the time-averaged, pseudo-first-order forward rate constant, k(f,ap)', of the CK reaction, and that periodic short-term fluctuations in kf ' and CK flux are not likely to be detectable in human studies employing current in vivo (31)P MRS methods.

Two repetition time saturation transfer (TwiST) with spill-over correction to measure creatine kinase reaction rates in human hearts.

BACKGROUND: Phosphorus saturation transfer (ST) magnetic resonance spectroscopy can measure the rate of ATP generated from phosphocreatine (PCr) via creatine kinase (CK) in the human heart. Recently, the triple-repetition time ST (TRiST) method was introduced to measure the CK pseudo-first-order rate constant kf in three acquisitions. In TRiST, the longitudinal relaxation time of PCr while γ-ATP is saturated, T1`, is measured for each subject, but suffers from low SNR because the PCr signal is reduced due to exchange with saturated γ-ATP, and the short repetition time of one of the acquisitions. Here, a two-repetition time ST (TwiST) method is presented. In TwiST, the acquisition with γ-ATP saturation and short repetition time is dropped. Instead of measuring T1`, an intrinsic relaxation time T1 for PCr, T1 (intrinsic), is assumed. The objective was to validate TwiST measurements of CK kinetics in healthy subjects and patients with heart failure (HF). METHODS: Bloch equation simulations that included the effect of spillover irradiation on PCr were used to derive formulae for T1 (intrinsic) and kf measured by both TRiST and TwiST methods. Spillover was quantified from an unsaturated PCr measurement used in the current protocol for determining PCr and ATP concentrations. Cardiac TRiST and TwiST data were acquired at 3 T from 12 healthy and 17 HF patients. RESULTS: Simulations showed that both kf measured by TwiST and T1 (intrinsic) require spill-over corrections. In human heart at 3 T, the spill-over corrected T1 (intrinsic) = 8.4 ± 1.4 s (mean ± SD) independent of study group. TwiST and TRiST kf measurements were the same, but TwiST was 9 min faster. Spill-over corrected TwiST kf was 0.33 ± 0.08 s(-1) vs. 0.20 ± 0.06 s(-1) in healthy vs HF hearts, respectively (p < 0.0001). CONCLUSION: TwiST was validated against TRiST in the human heart at 3 T, generating the same results 9 min faster. TwiST detected significant reductions in CK kf in HF compared to healthy subjects, consistent with prior 1.5 T studies using different methodology.

7 Tesla MRI with a transmit/receive loopless antenna and B1-insensitive selective excitation.

PURPOSE: Use of external coils with internal detectors or conductors is challenging at 7 Tesla (T) due to radiofrequency (RF) field (B1 ) penetration, B1 -inhomogeneity, mutual coupling, and potential local RF heating. The present study tests whether the near-quadratic gains in signal-to-noise ratio and field-of-view with field-strength previously reported for internal loopless antennae at 7T can suffice to perform MRI with an interventional transmit/receive antenna without using any external coils. METHODS: External coils were replaced by semi-rigid or biocompatible transmit/receive loopless antennae requiring only a few Watts of peak RF power. Slice selection was provided by spatially selective B1 -insensitive composite RF pulses that compensate for the antenna's intrinsically nonuniform B1 -field. Power was adjusted to maintain local temperature rise ≤1°C. Fruit, intravascular MRI of diseased human vessels in vitro, and MRI of rabbit aorta in vivo are demonstrated. RESULTS: Scout MRI with the transmit/receive antennae yielded a ≤10 cm cylindrical field-of-view, enabling subsequent targeted localization at ∼100 µm resolution in 10-50 s and/or 50 µm MRI in ∼2 min in vitro, and 100-300 µm MRI of the rabbit aorta in vivo. CONCLUSION: A simple, low-power, one-device approach to interventional MRI at 7T offers the potential of truly high-resolution MRI, while avoiding issues with external coil excitation and interactions at 7T.