Getting the phase consistent: The importance of phase description in balanced steady-state free precession MRI of multi-compartment systems.

PURPOSE: Determine the correct mathematical phase description for balanced steady-state free precession (bSSFP) signals in multi-compartment systems. THEORY AND METHODS: Based on published bSSFP signal models, different phase descriptions can be formulated: one predicting the presence and the other predicting the absence of destructive interference effects in multi-compartment systems. Numerical simulations of bSSFP signals of water and acetone were performed to evaluate the predictions of these different phase descriptions. For experimental validation, bSSFP profiles were measured at 3T using phase-cycled bSSFP acquisitions performed in a phantom containing mixtures of water and acetone, which replicates a system with two signal components. Localized single voxel MRS was performed at 7T to determine the relative chemical shift of the acetone-water mixtures. RESULTS: Based on the choice of phase description, the simulated bSSFP profiles of water-acetone mixtures varied significantly, either displaying or lacking destructive interference effects, as predicted theoretically. In phantom experiments, destructive interference was consistently observed in the measured bSSFP profiles of water-acetone mixtures, supporting the theoretical description that predicts such interference effects. The connection between the choice of phase description and predicted observation enables unambiguous experimental identification of the correct phase description for multi-compartment bSSFP profiles, which is consistent with the Bloch equations. CONCLUSION: The study emphasizes that consistent phase descriptions are crucial for accurately describing multi-compartment bSSFP signals, as incorrect phase descriptions result in erroneous predictions.

Fat-free noncontrast whole-heart CMR with fast and power-optimized off-resonant water excitation pulses.

BACKGROUND: Cardiovascular MRI (CMR) faces challenges due to the interference of bright fat signals in visualizing structures like coronary arteries. Effective fat suppression is crucial, especially when using whole-heart CMR techniques. Conventional methods often fall short due to rapid fat signal recovery, leading to residual fat content hindering visualization. Water-selective off-resonant radiofrequency (RF) pulses have been proposed but come with tradeoffs between pulse duration, which increases scan time, and increased RF energy deposit, which limits their applicability due to specific absorption rate (SAR) constraints. The study introduces a lipid-insensitive binomial off-resonant (LIBOR) RF pulse, which addresses concerns about SAR and scan time, and aims to provide a comprehensive quantitative comparison with published off-resonant RF pulses for CMR at 3T. METHODS: A short (1ms) LIBOR pulse, with reduced RF power requirements, was developed and implemented in a free-breathing respiratory-self-navigated 3D radial whole-heart CMR sequence at 3T. A binomial off-resonant rectangular (BORR) pulse with matched duration, as well as previously published lipid-insensitive binomial off-resonant excitation (LIBRE) pulses (1ms and 2.2ms), were implemented and optimized for fat suppression in numerical simulations and validated in volunteers (n=3). Whole-heart CMR was performed in volunteers(n=10) with all four pulses. The signal-to-noise ratio (SNR) of ventricular blood, skeletal muscle, myocardium, and subcutaneous fat and the coronary vessel detection rates and sharpness were compared. RESULTS: Experimental results validated numerical findings and near homogeneous fat suppression was achieved with all four pulses. Comparing the short RF pulses (1ms), LIBOR reduced the RF power nearly two-fold compared with LIBRE, and three-fold compared with BORR, and LIBOR significantly decreased overall fat SNR from cardiac scans, compared to LIBRE and BORR. The reduction in RF pulse duration (from 2.2ms to 1ms) shortened the whole-heart acquisition from 8.5min to 7min. No significant differences in coronary arteries detection and sharpness were found when comparing all four pulses. CONCLUSION: LIBOR pulses enabled whole-heart CMR under 7minutes at 3T, with large volume fat signal suppression, while reducing RF power compared with LIBRE and BORR pulses. LIBOR is an excellent candidate to address SAR problems encountered in CMR sequences where fat suppression remains challenging and short RF pulses are required. AVAILABILITY OF DATA AND MATERIALS: An online repository containing the anonymized human MRI raw data, as well as RF pulse shapes used in this study is publicly available at: https://zenodo.org/records/8338079(PART 1: KNEE V1-V3, HEART V1-V5) https://zenodo.org/records/10715769 (PART 2: HEART V6-V10) Matlab code to 1) simulate the different RF pulses within a GRE sequence and 2) to read and display the anonymized raw data is available from: https://github.com/QIS-MRI/LIBOR_LIBRE_BORR_SimulationCode The compiled research sequence can be requested through the Teamplay platform of Siemens Healthineers.

Trajectory correction enables free-running chemical shift encoded imaging for accurate cardiac proton-density fat fraction quantification at 3T.

BACKGROUND: Metabolic diseases can negatively alter epicardial fat accumulation and composition, which can be probed using quantitative cardiac chemical shift encoded (CSE) cardiovascular magnetic resonance (CMR) by mapping proton-density fat fraction (PDFF). To obtain motion-resolved high-resolution PDFF maps, we proposed a free-running cardiac CSE-CMR framework at 3T. To employ faster bipolar readout gradients, a correction for gradient imperfections was added using the gradient impulse response function (GIRF) and evaluated on intermediate images and PDFF quantification. METHODS: Ten minutes free-running cardiac 3D radial CSE-CMR acquisitions were compared in vitro and in vivo at 3T. Monopolar and bipolar readout gradient schemes provided 8 echoes (TE1/ΔTE = 1.16/1.96 ms) and 13 echoes (TE1/ΔTE = 1.12/1.07 ms), respectively. Bipolar-gradient free-running cardiac fat and water images and PDFF maps were reconstructed with or without GIRF correction. PDFF values were evaluated in silico, in vitro on a fat/water phantom, and in vivo in 10 healthy volunteers and 3 diabetic patients. RESULTS: In monopolar mode, fat-water swaps were demonstrated in silico and confirmed in vitro. Using bipolar readout gradients, PDFF quantification was reliable and accurate with GIRF correction with a mean bias of 0.03% in silico and 0.36% in vitro while it suffered from artifacts without correction, leading to a PDFF bias of 4.9% in vitro and swaps in vivo. Using bipolar readout gradients, in vivo PDFF of epicardial adipose tissue was significantly lower compared to subcutaneous fat (80.4 ± 7.1% vs 92.5 ± 4.3%, P < 0.0001). CONCLUSIONS: Aiming for an accurate PDFF quantification, high-resolution free-running cardiac CSE-MRI imaging proved to benefit from bipolar echoes with k-space trajectory correction at 3T. This free-breathing acquisition framework enables to investigate epicardial adipose tissue PDFF in metabolic diseases.

Combined free-running four-dimensional anatomical and flow magnetic resonance imaging with native contrast using Synchronization of Neighboring Acquisitions by Physiological Signals.

BACKGROUND: Four-dimensional (4D) flow magnetic resonance imaging (MRI) often relies on the injection of gadolinium- or iron-oxide-based contrast agents to improve vessel delineation. In this work, a novel technique is developed to acquire and reconstruct 4D flow data with excellent dynamic visualization of blood vessels but without the need for contrast injection. Synchronization of Neighboring Acquisitions by Physiological Signals (SyNAPS) uses pilot tone (PT) navigation to retrospectively synchronize the reconstruction of two free-running three-dimensional radial acquisitions, to create co-registered anatomy and flow images. METHODS: Thirteen volunteers and two Marfan syndrome patients were scanned without contrast agent using one free-running fast interrupted steady-state (FISS) sequence and one free-running phase-contrast MRI (PC-MRI) sequence. PT signals spanning the two sequences were recorded for retrospective respiratory motion correction and cardiac binning. The magnitude and phase images reconstructed, respectively, from FISS and PC-MRI, were synchronized to create SyNAPS 4D flow datasets. Conventional two-dimensional (2D) flow data were acquired for reference in ascending (AAo) and descending aorta (DAo). The blood-to-myocardium contrast ratio, dynamic vessel area, net volume, and peak flow were used to compare SyNAPS 4D flow with Native 4D flow (without FISS information) and 2D flow. A score of 0-4 was given to each dataset by two blinded experts regarding the feasibility of performing vessel delineation. RESULTS: Blood-to-myocardium contrast ratio for SyNAPS 4D flow magnitude images (1.5 ± 0.3) was significantly higher than for Native 4D flow (0.7 ± 0.1, p < 0.01) and was comparable to 2D flow (2.3 ± 0.9, p = 0.02). Image quality scores of SyNAPS 4D flow from the experts (M.P.: 1.9 ± 0.3, E.T.: 2.5 ± 0.5) were overall significantly higher than the scores from Native 4D flow (M.P.: 1.6 ± 0.6, p = 0.03, E.T.: 0.8 ± 0.4, p < 0.01) but still significantly lower than the scores from the reference 2D flow datasets (M.P.: 2.8 ± 0.4, p < 0.01, E.T.: 3.5 ± 0.7, p < 0.01). The Pearson correlation coefficient between the dynamic vessel area measured on SyNAPS 4D flow and that from 2D flow was 0.69 ± 0.24 for the AAo and 0.83 ± 0.10 for the DAo, whereas the Pearson correlation between Native 4D flow and 2D flow measurements was 0.12 ± 0.48 for the AAo and 0.08 ± 0.39 for the DAo. Linear correlations between SyNAPS 4D flow and 2D flow measurements of net volume (r2 = 0.83) and peak flow (r2 = 0.87) were larger than the correlations between Native 4D flow and 2D flow measurements of net volume (r2 = 0.79) and peak flow (r2 = 0.76). CONCLUSION: The feasibility and utility of SyNAPS were demonstrated for joint whole-heart anatomical and flow MRI without requiring electrocardiography gating, respiratory navigators, or contrast agents. Using SyNAPS, a high-contrast anatomical imaging sequence can be used to improve 4D flow measurements that often suffer from poor delineation of vessel boundaries in the absence of contrast agents.

SPARCQ: A new approach for fat fraction mapping using asymmetries in the phase-cycled balanced SSFP signal profile.

PURPOSE: To develop SPARCQ (Signal Profile Asymmetries for Rapid Compartment Quantification), a novel approach to quantify fat fraction (FF) using asymmetries in the phase-cycled balanced SSFP (bSSFP) profile. METHODS: SPARCQ uses phase-cycling to obtain bSSFP frequency profiles, which display asymmetries in the presence of fat and water at certain TRs. For each voxel, the measured signal profile is decomposed into a weighted sum of simulated profiles via multi-compartment dictionary matching. Each dictionary entry represents a single-compartment bSSFP profile with a specific off-resonance frequency and relaxation time ratio. Using the results of dictionary matching, the fractions of the different off-resonance components are extracted for each voxel, generating quantitative maps of water and FF and banding-artifact-free images for the entire image volume. SPARCQ was validated using simulations, experiments in a water-fat phantom and in knees of healthy volunteers. Experimental results were compared with reference proton density FFs obtained with 1 H-MRS (phantoms) and with multiecho gradient-echo MRI (phantoms and volunteers). SPARCQ repeatability was evaluated in six scan-rescan experiments. RESULTS: Simulations showed that FF quantification is accurate and robust for SNRs greater than 20. Phantom experiments demonstrated good agreement between SPARCQ and gold standard FFs. In volunteers, banding-artifact-free quantitative maps and water-fat-separated images obtained with SPARCQ and ME-GRE demonstrated the expected contrast between fatty and non-fatty tissues. The coefficient of repeatability of SPARCQ FF was 0.0512. CONCLUSION: SPARCQ demonstrates potential for fat quantification using asymmetries in bSSFP profiles and may be a promising alternative to conventional FF quantification techniques.

Motion-resolved fat-fraction mapping with whole-heart free-running multiecho GRE and pilot tone.

PURPOSE: To develop a free-running 3D radial whole-heart multiecho gradient echo (ME-GRE) framework for cardiac- and respiratory-motion-resolved fat fraction (FF) quantification. METHODS: (NTE = 8) readouts optimized for water-fat separation and quantification were integrated within a continuous non-electrocardiogram-triggered free-breathing 3D radial GRE acquisition. Motion resolution was achieved with pilot tone (PT) navigation, and the extracted cardiac and respiratory signals were compared to those obtained with self-gating (SG). After extra-dimensional golden-angle radial sparse parallel-based image reconstruction, FF, R2 *, and B0 maps, as well as fat and water images were generated with a maximum-likelihood fitting algorithm. The framework was tested in a fat-water phantom and in 10 healthy volunteers at 1.5 T using NTE = 4 and NTE = 8 echoes. The separated images and maps were compared with a standard free-breathing electrocardiogram (ECG)-triggered acquisition. RESULTS: The method was validated in vivo, and physiological motion was resolved over all collected echoes. Across volunteers, PT provided respiratory and cardiac signals in agreement (r = 0.91 and r = 0.72) with SG of the first echo, and a higher correlation to the ECG (0.1% of missed triggers for PT vs. 5.9% for SG). The framework enabled pericardial fat imaging and quantification throughout the cardiac cycle, revealing a decrease in FF at end-systole by 11.4% ± 3.1% across volunteers (p < 0.0001). Motion-resolved end-diastolic 3D FF maps showed good correlation with ECG-triggered measurements (FF bias of -1.06%). A significant difference in free-running FF measured with NTE = 4 and NTE = 8 was found (p < 0.0001 in sub-cutaneous fat and p < 0.01 in pericardial fat). CONCLUSION: Free-running fat fraction mapping was validated at 1.5 T, enabling ME-GRE-based fat quantification with NTE = 8 echoes in 6:15 min.

Predictive value of cardiac magnetic resonance right ventricular longitudinal strain in patients with suspected myocarditis.

BACKGROUND: Recent evidence underlined the importance of right (RV) involvement in suspected myocarditis. We aim to analyze the possible incremental prognostic value from RV global longitudinal strain (GLS) by CMR. METHODS: Patients referred for CMR, meeting clinical criteria for suspected myocarditis and no other cardiomyopathy were enrolled in a dual-center register cohort study. Ejection fraction (EF), GLS and tissue characteristics were assessed in both ventricles to assess their association to first major adverse cardiovascular events (MACE) including hospitalization for heart failure (HF), ventricular tachycardia (VT), recurrent myocarditis and death. RESULTS: Among 659 patients (62.8% male; 48.1 ± 16.1 years), RV GLS was impaired (> - 15.4%) in 144 (21.9%) individuals, of whom 76 (58%), 108 (77.1%), 27 (18.8%) and 40 (32.8%) had impaired right ventricular ejection fraction (RVEF), impaired left ventricular ejection fraction (LVEF), RV late gadolinium enhancement (LGE) or RV edema, respectively. After a median observation time of 3.7 years, 45 (6.8%) patients were hospitalized for HF, 42 (6.4%) patients died, 33 (5%) developed VT and 16 (2.4%) had recurrent myocarditis. Impaired RV GLS was associated with MACE (HR = 1.07, 95% CI 1.04-1.10; p < 0.001), HF hospitalization (HR = 1.17, 95% CI 1.12-1.23; p < 0.001), and death (HR = 1.07, 95% CI 1.02-1.12; p = 0.004), but not with VT and recurrent myocarditis in univariate analysis. RV GLS lost its association with outcomes, when adjusted for RVEF, LVEF, LV GLS and LV LGE extent. CONCLUSION: RV strain is associated with MACE, HF hospitalization and death but has neither independent nor incremental prognostic value after adjustment for RV and LV function and tissue characteristics. Therefore, assessing RV GLS in the setting of myocarditis has only limited value.

A robust broadband fat-suppressing phaser T2 -preparation module for cardiac magnetic resonance imaging at 3T.

PURPOSE: Designing a new T2 -preparation (T2 -Prep) module to simultaneously provide robust fat suppression and efficient T2 preparation without requiring an additional fat-suppression module for T2 -weighted imaging at 3T. METHODS: The tip-down radiofrequency (RF) pulse of an adiabatic T2 -Prep module was replaced by a custom-designed RF-excitation pulse that induces a phase difference between water and fat, resulting in a simultaneous T2 preparation of water signals and the suppression of fat signals at the end of the module (a phaser adiabatic T2 -Prep). Numerical simulations and in vitro and in vivo electrocardiogram (ECG)-triggered navigator-gated acquisitions of the human heart were performed. Blood, myocardium, and fat signal-to-noise ratios and right coronary artery vessel sharpness were compared against previously published adiabatic T2 -Prep approaches. RESULTS: Numerical simulations predicted an increased fat-suppression bandwidth and decreased sensitivity to transmit magnetic field inhomogeneities using the proposed approach while preserving the water T2 -Prep capabilities. This was confirmed by the tissue signals acquired in the phantom and the in vivo images, which show similar blood and myocardium signal-to-noise ratio, contrast-to-noise ratio, and significantly reduced fat signal-to-noise ratio compared with the other methods. As a result, the right coronary artery conspicuity was significantly increased. CONCLUSION: A novel fat-suppressing T2 -Prep method was developed and implemented that showed robust fat suppression and increased vessel sharpness compared with conventional techniques while preserving its T2 -Prep capabilities.

Similarity-driven multi-dimensional binning algorithm (SIMBA) for free-running motion-suppressed whole-heart MRA.

PURPOSE: Whole-heart MRA techniques typically target predetermined motion states, address cardiac and respiratory dynamics independently, and require either complex planning or computationally demanding reconstructions. In contrast, we developed a fast data-driven reconstruction algorithm with minimal physiological assumptions and compatibility with ungated free-running sequences. THEORY AND METHODS: We propose a similarity-driven multi-dimensional binning algorithm (SIMBA) that clusters continuously acquired k-space data to find a motion-consistent subset for whole-heart MRA reconstruction. Free-running 3D radial data sets from 12 non-contrast-enhanced scans of healthy volunteers and six ferumoxytol-enhanced scans of pediatric cardiac patients were reconstructed with non-motion-suppressed regridding of all the acquired data ("All Data"), with SIMBA, and with a previously published free-running framework (FRF) that uses cardiac and respiratory self-gating and compressed sensing. Images were compared for blood-myocardium sharpness and contrast ratio, visibility of coronary artery ostia, and right coronary artery sharpness. RESULTS: Both the 20-second SIMBA reconstruction and FRF provided significantly higher blood-myocardium sharpness than All Data in both patients and volunteers (P < .05). The SIMBA reconstruction provided significantly sharper blood-myocardium interfaces than FRF in volunteers (P < .001) and higher blood-myocardium contrast ratio than All Data and FRF, both in volunteers and patients (P < .05). Significantly more ostia could be visualized with both SIMBA (31 of 36) and FRF (34 of 36) than with All Data (4 of 36) (P < .001). Inferior right coronary artery sharpness using SIMBA versus FRF was observed (volunteers: SIMBA 36.1 ± 8.1%, FRF 40.4 ± 8.9%; patients: SIMBA 35.9 ± 7.7%, FRF 40.3 ± 6.1%, P = not significant). CONCLUSION: The SIMBA technique enabled a fast, data-driven reconstruction of free-running whole-heart MRA with image quality superior to All Data and similar to the more time-consuming FRF reconstruction.

Radical-free hyperpolarized MRI using endogenously occurring pyruvate analogues and UV-induced nonpersistent radicals.

It was recently demonstrated that nonpersistent radicals can be generated in frozen solutions of metabolites such as pyruvate by irradiation with UV light, enabling radical-free dissolution dynamic nuclear polarization. Although pyruvate is endogenous, the presence of pyruvate may interfere with metabolic processes or the detection of pyruvate as a metabolic product, making it potentially unsuitable as a polarizing agent. Therefore, the aim of the current study was to characterize solutions containing endogenously occurring alternatives to pyruvate as UV-induced nonpersistent radical precursors for in vivo hyperpolarized MRI. The metabolites alpha-ketovalerate (αkV) and alpha-ketobutyrate (αkB) are analogues of pyruvate and were chosen as potential radical precursors. Sample formulations containing αkV and αkB were studied with UV-visible spectroscopy, irradiated with UV light, and their nonpersistent radical yields were quantified with electron spin resonance and compared with pyruvate. The addition of 13 C-labeled substrates to the sample matrix altered the radical yield of the precursors. Using αkB increased the 13 C-labeled glucose liquid-state polarization to 16.3% ± 1.3% compared with 13.3% ± 1.5% obtained with pyruvate, and 8.9% ± 2.1% with αkV. For [1-13 C]butyric acid, polarization levels of 12.1% ± 1.1% for αkV, 12.9% ± 1.7% for αkB, 1.5% ± 0.2% for OX063 and 18.7% ± 0.7% for Finland trityl, were achieved. Hyperpolarized [1-13 C]butyrate metabolism in the heart revealed label incorporation into [1-13 C]acetylcarnitine, [1-13 C]acetoacetate, [1-13 C]butyrylcarnitine, [5-13 C]glutamate and [5-13 C]citrate. This study demonstrates the potential of αkV and αkB as endogenous polarizing agents for in vivo radical-free hyperpolarized MRI. UV-induced, nonpersistent radicals generated in endogenous metabolites enable high polarization without requiring radical filtration, thus simplifying the quality-control tests in clinical applications.

Free-running 5D coronary MR angiography at 1.5T using LIBRE water excitation pulses.

PURPOSE: To implement, optimize, and characterize lipid-insensitive binomial off-resonant RF excitation (LIBRE) pulses for fat-suppressed fully self-gated free-running 5D cardiac MRI. METHODS: Bloch equation simulations were used to optimize LIBRE parameter settings in non-interrupted bSSFP prior to in vitro validation. Thus, optimized LIBRE pulses were subsequently applied to free-running coronary MRA in 20 human adult subjects, where resulting images were quantitatively compared to those obtained with non-fat-suppressing excitation (SP), conventional 1-2-1 water excitation (WE), and a previously published interrupted free-running (IFR) sequence. SAR and scan times were recorded. Respiratory-and-cardiac-motion-resolved images were reconstructed with XD-GRASP, and contrast ratios, coronary artery detection rate, vessel length, and vessel sharpness were computed. RESULTS: The numerically optimized LIBRE parameters were successfully validated in vitro. In vivo, LIBRE had the lowest SAR and a scan time that was similar to that of WE yet 18% shorter than that of IFR. LIBRE improved blood-fat contrast when compared to SP, WE, and IFR, vessel detection relative to SP and IFR, and vessel sharpness when compared to WE and IFR (for example, for the left main and anterior descending coronary artery, 51.5% ± 10.2% [LIBRE] versus 42.1% ± 6.8% [IFR]). Vessel length measurements remained unchanged for all investigated methods. CONCLUSION: LIBRE enabled fully self-gated non-interrupted free-running 5D bSSFP imaging of the heart at 1.5T with suppressed fat signal. Measures of image quality, vessel conspicuity, and scan time compared favorably to those obtained with the more conventional non-interrupted WE and the previously published IFR, while SAR reduction offers added flexibility.

Natively fat-suppressed 5D whole-heart MRI with a radial free-running fast-interrupted steady-state (FISS) sequence at 1.5T and 3T.

PURPOSE: To implement, optimize, and test fast interrupted steady-state (FISS) for natively fat-suppressed free-running 5D whole-heart MRI at 1.5 tesla (T) and 3T. METHODS: FISS was implemented for fully self-gated free-running cardiac- and respiratory-motion-resolved radial imaging of the heart at 1.5T and 3T. Numerical simulations and phantom scans were performed to compare fat suppression characteristics and to determine parameter ranges (number of readouts [NR] per FISS module and TR) for effective fat suppression. Subsequently, free-running FISS data were collected in 10 healthy volunteers and images were reconstructed with compressed sensing. All acquisitions were compared with a continuous balanced steady-state free precession version of the same sequence, and both fat suppression and scan times were analyzed. RESULTS: Simulations demonstrate a variable width and location of suppression bands in FISS that were dependent on TR and NR. For a fat suppression bandwidth of 100 Hz and NR ≤ 8, simulations demonstrated that a TR between 2.2 ms and 3.0 ms is required at 1.5T, whereas a range of 3.0 ms to 3.5 ms applies at 3T. Fat signal increases with NR. These findings were corroborated in phantom experiments. In volunteers, fat SNR was significantly decreased using FISS compared with balanced steady-state free precession (P < 0.05) at both field strengths. After protocol optimization, high-resolution (1.1 mm3 ) 5D whole-heart free-running FISS can be performed with effective fat suppression in under 8 min at 1.5T and 3T at a modest scan time increase compared to balanced steady-state free precession. CONCLUSION: An optimal FISS parameter range was determined enabling natively fat-suppressed 5D whole-heart free-running MRI with a single continuous scan at 1.5T and 3T, demonstrating potential for cardiac imaging and noncontrast angiography.

Detection of myocardial medium-chain fatty acid oxidation and tricarboxylic acid cycle activity with hyperpolarized [1-13 C]octanoate.

Under normal conditions, the heart mainly relies on fatty acid oxidation to meet its energy needs. Changes in myocardial fuel preference are noted in the diseased and failing heart. The magnetic resonance signal enhancement provided by spin hyperpolarization allows the metabolism of substrates labeled with carbon-13 to be followed in real time in vivo. Although the low water solubility of long-chain fatty acids abrogates their hyperpolarization by dissolution dynamic nuclear polarization, medium-chain fatty acids have sufficient solubility to be efficiently polarized and dissolved. In this study, we investigated the applicability of hyperpolarized [1-13 C]octanoate to measure myocardial medium-chain fatty acid metabolism in vivo. Scanning rats infused with a bolus of hyperpolarized [1-13 C]octanoate, the primary metabolite observed in the heart was identified as [1-13 C]acetylcarnitine. Additionally, [5-13 C]glutamate and [5-13 C]citrate could be respectively resolved in seven and five of 31 experiments, demonstrating the incorporation of oxidation products of octanoate into the tricarboxylic acid cycle. A variable drop in blood pressure was observed immediately following the bolus injection, and this drop correlated with a decrease in normalized acetylcarnitine signal (acetylcarnitine/octanoate). Increasing the delay before infusion moderated the decrease in blood pressure, which was attributed to the presence of residual gas bubbles in the octanoate solution. No significant difference in normalized acetylcarnitine signal was apparent between fed and 12-hour fasted rats. Compared with a solution in buffer, the longitudinal relaxation of [1-13 C]octanoate was accelerated ~3-fold in blood and by the addition of serum albumin. These results demonstrate the potential of hyperpolarized [1-13 C]octanoate to probe myocardial medium-chain fatty acid metabolism as well as some of the limitations that may accompany its use.

Simultaneous fat-free isotropic 3D anatomical imaging and T2 mapping of knee cartilage with lipid-insensitive binomial off-resonant RF excitation (LIBRE) pulses.

BACKGROUND: Improved knee cartilage morphological delineation and T2 mapping precision necessitates isotropic 3D high-resolution and efficient fat suppression. PURPOSE: To develop and assess an isotropic 3D lipid-insensitive T2 mapping technique of the knee for improved cartilage delineation and precise measurement of T2 relaxation times. STUDY TYPE: Prospective. PHANTOM/SUBJECTS: Phantoms (n = 6) used in this study were designed to mimic the T1 and T2 relaxation times of cartilage and fat. The study cohort comprised healthy volunteers (n = 7) for morphometry and T2 relaxation time measurements. FIELD STRENGTH/SEQUENCE: A high-resolution isotropic 3D T2 mapping technique that uses sequential T2 -prepared segmented gradient-recalled echo (Iso3DGRE) images and lipid-insensitive binomial off-resonant radiofrequency (RF) excitation (LIBRE) at 3T. ASSESSMENT: Numerical simulations and phantom experiments were performed to optimize the LIBRE pulse. Phantom studies were carried out to test the accuracy of the technique against reference standard spin-echo (SE) T2 mapping. Subsequently, T2 maps with and without LIBRE pulses were acquired in knees of healthy volunteers and the T2 relaxation time values in different cartilage compartments were compared. STATISTICAL TESTS: A two-tailed paired Student's t-test was used to compare the average T2 values and the relative standard deviations (inverse measurement of the precision) obtained with and without LIBRE pulses. RESULTS: A LIBRE pulse of 1 msec suppressed fat with an RF excitation frequency offset of 1560 Hz and optimal RF excitation angle of 35°. These results were corroborated by phantom and knee experiments. Robust and homogeneous fat suppression was obtained (a fat signal-to-noise ratio (SNR) decrease of 86.4 ± 2.4%). In phantoms, T2 values were found in good agreement when comparing LIBRE-Iso3DGRE with SE (slope 0.93 ± 0.04, intercept 0.11 ± 1.6 msec, R2 >0.99). In vivo, LIBRE excitation resulted in more precise T2 estimation (23.7 ± 7.4%) than normal excitation (30.5 ± 9.9%, P < 0.0001). DATA CONCLUSION: Homogeneous LIBRE fat signal suppression was achieved with a total RF pulse duration of 1 msec, allowing for the removal of chemical shift artifacts and resulting in improved cartilage delineation and precise T2 values. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:1275-1284.

Patient respiratory-triggered quantitative T2 mapping in the pancreas.

BACKGROUND: Long acquisition times and motion sensitivity limit T2 mapping in the abdomen. Accelerated mapping at 3 T may allow for quantitative assessment of diffuse pancreatic disease in patients during free-breathing. PURPOSE: To test the feasibility of respiratory-triggered quantitative T2 analysis in the pancreas and correlate T2 -values with age, body mass index, pancreatic location, main pancreatic duct dilatation, and underlying pathology. STUDY TYPE: Retrospective single-center pilot study. POPULATION: Eighty-eight adults. FIELD STRENGTH/SEQUENCE: Ten-fold accelerated multiecho-spin-echo 3 T MRI sequence to quantify T2 at 3 T. ASSESSMENT: Two radiologists independently delineated three regions of interest inside the pancreatic head, body, and tail for each acquisition. Means and standard deviations for T2 values in these regions were determined. T2 -value variation with demographic data, intraparenchymal location, pancreatic duct dilation, and underlying pancreatic disease was assessed. STATISTICAL TESTS: Interreader reliability was determined by calculating the interclass coefficient (ICCs). T2 values were compared for different pancreatic locations by analysis of variance (ANOVA). Interpatient associations between T2 values and demographical, clinical, and radiological data were calculated (ANOVA). RESULTS: The accelerated T2 mapping sequence was successfully performed in all participants (mean acquisition time, 2:48 ± 0:43 min). Low T2 value variability was observed across all patients (intersubject) (head: 60.2 ± 8.3 msec, body: 63.9 ± 11.5 msec, tail: 66.8 ± 16.4 msec). Interreader agreement was good (ICC, 0.82, 95% confidence interval: 0.77-0.86). T2 -values differed significantly depending on age (P < 0.001), location (P < 0.001), main pancreatic duct dilatation (P < 0.001), and diffuse pancreatic disease (P < 0.03). DATA CONCLUSION: The feasibility of accelerated T2 mapping at 3 T in moving abdominal organs was demonstrated in the pancreas, since T2 values were stable and reproducible. In the pancreatic parenchyma, T2 -values were significantly dependent on demographic and clinical parameters. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:410-416.

Noncontrast free-breathing respiratory self-navigated coronary artery cardiovascular magnetic resonance angiography at 3 T using lipid insensitive binomial off-resonant excitation (LIBRE).

BACKGROUND: Robust and homogeneous lipid suppression is mandatory for coronary artery cardiovascular magnetic resonance (CMR) imaging since the coronary arteries are commonly embedded in epicardial fat. However, effective large volume lipid suppression becomes more challenging when performing radial whole-heart coronary artery CMR for respiratory self-navigation and the problem may even be exacerbated at increasing magnetic field strengths. Incomplete fat suppression not only hinders a correct visualization of the coronary vessels and generates image artifacts, but may also affect advanced motion correction methods. The aim of this study was to evaluate a recently reported lipid insensitive CMR method when applied to a noncontrast self-navigated coronary artery CMR acquisitions at 3 T, and to compare it to more conventional fat suppression techniques. METHODS: Lipid insensitive binomial off resonant excitation (LIBRE) radiofrequency excitation pulses were included into a self-navigated 3D radial GRE coronary artery CMR sequence at 3 T. LIBRE was compared against a conventional CHESS fat saturation (FS) and a binomial 1-180°-1 water excitation (WE) pulse. First, fat suppression of all techniques was numerically characterized using Matlab and experimentally validated in phantoms and in legs of human volunteers. Subsequently, free-breathing self-navigated coronary artery CMR was performed using the LIBRE pulse as well as FS and WE in ten healthy subjects. Myocardial, arterial and chest fat signal-to-noise ratios (SNR), as well as coronary vessel conspicuity were quantitatively compared among those scans. RESULTS: The results obtained in the simulations were confirmed by the experimental validations as LIBRE enabled near complete fat suppression for 3D radial imaging in vitro and in vivo. For self-navigated whole-heart coronary artery CMR at 3 T, fat SNR was significantly attenuated using LIBRE compared with conventional FS. LIBRE increased the right coronary artery (RCA) vessel sharpness significantly (37 ± 9% (LIBRE) vs. 29 ± 8% (FS) and 30 ± 8% (WE), both p < 0.05) and led to a significant increase in the measured RCA vessel length to (83 ± 31 mm (LIBRE) vs. 56 ± 12 mm (FS) and 59 ± 27 (WE) p < 0.05). CONCLUSIONS: Applied to a respiratory self-navigated noncontrast 3D radial whole-heart sequence, LIBRE enables robust large volume fat suppression and significantly improves coronary artery image quality at 3 T compared to the use of conventional FS and WE.

Flexible water excitation for fat-free MRI at 3T using lipid insensitive binomial off-resonant RF excitation (LIBRE) pulses.

PURPOSE: To develop a robust and flexible low power water excitation pulse that enables effective fat suppression at high magnetic field strength. METHODS: A water excitation method that uses spatially non-selective pulses was optimized in numerical simulations, and implemented and tested in phantoms and healthy volunteers at 3T. The lipid insensitive binomial off-resonant excitation (LIBRE) pulse comprises two low power rectangular subpulses that have a variable frequency offset, phase offset and duration. The capability and extent of LIBRE fat suppression was quantitatively compared with conventional fat saturation (FS) and water excitation (WE) techniques. RESULTS: LIBRE enables simultaneous water excitation and near complete fat suppression in large volumes at 3T as demonstrated by numerical simulations, and experiments. In phantoms and in human subjects, the frequency responses matched well with those from the numerical simulation. Comparing FS and WE, LIBRE demonstrated an improved robustness to magnetic field inhomogeneities, and a much more effectively suppressed fat signal. This applied for a range of pulse durations and pulses as short as 1.4 ms. CONCLUSION: A flexible water excitation method was developed that shows robust, near complete fat suppression at 3T. Magn Reson Med 79:3007-3017, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Probing cardiac metabolism by hyperpolarized 13C MR using an exclusively endogenous substrate mixture and photo-induced nonpersistent radicals.

PURPOSE: To probe the cardiac metabolism of carbohydrates and short chain fatty acids simultaneously in vivo following the injection of a hyperpolarized 13 C-labeled substrate mixture prepared using photo-induced nonpersistent radicals. METHODS: Droplets of mixed [1-13 C]pyruvic and [1-13 C]butyric acids were frozen into glassy beads in liquid nitrogen. Ethanol addition was investigated as a means to increase the polarization level. The beads were irradiated with ultraviolet light and the radical concentration was measured by ESR spectroscopy. Following dynamic nuclear polarization in a 7T polarizer, the beads were dissolved, and the radical-free hyperpolarized solution was rapidly transferred into an injection pump located inside a 9.4T scanner. The hyperpolarized solution was injected in healthy rats to measure cardiac metabolism in vivo. RESULTS: Ultraviolet irradiation created nonpersistent radicals in a mixture containing 13 C-labeled pyruvic and butyric acids, and enabled the hyperpolarization of both substrates by dynamic nuclear polarization. Ethanol addition increased the radical concentration from 16 to 26 mM. Liquid-state 13 C polarization was 3% inside the pump at the time of injection, and increased to 5% by addition of ethanol to the substrate mixture prior to ultraviolet irradiation. In the rat heart, the in vivo 13 C signals from lactate, alanine, bicarbonate, and acetylcarnitine were detected following the metabolism of the injected substrate mixture. CONCLUSION: Copolarization of two different 13 C-labeled substrates and the detection of their myocardial metabolism in vivo was achieved without using persistent radicals. The absence of radicals in the solution containing the hyperpolarized 13 C-substrates may simplify the translation to clinical use, as no radical filtration is required prior to injection.