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Even at 7 T, cardiac 31P 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 31P 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 31P 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 31P spectroscopy at 7 T, improving reproducibility and SNR without the need for a dedicated k‐space sampling strategy. [ABSTRACT FROM AUTHOR]

Purpose: Phosphorous MR spectroscopy (31P‐MRS) forms a powerful, non‐invasive research tool to quantify the energetics of the heart in diverse patient populations. 31P‐MRS is frequently applied alongside other radiological examinations, many of which use various contrast agents that shorten relaxation times of water in conventional proton MR, for a better characterisation of cardiac function, or following prior computed tomography (CT). It is, however, unknown whether these agents confound 31P‐MRS signals, for example, 2,3‐diphosphoglycerate (2,3‐DPG). Methods: In this work, we quantitatively assess the impact of non‐ionic, low osmolar iodinated CT contrast agent (iopamidol/Niopam), gadolinium chelates (linear gadopentetic acid dimeglumine/Magnevist and macrocyclic gadoterate meglumine/Dotarem) and superparamagnetic iron oxide nanoparticles (ferumoxytol/Feraheme) on the nuclear T1 and T2 of 31P metabolites (ie, 2,3‐DPG), and 1H in water in live human blood and saline phantoms at 11.7 T. Results: Addition of all contrast agents led to significant shortening of all relaxation times in both 1H and 31P saline phantoms. On the contrary, the T1 relaxation time of 2,3‐DPG in blood was significantly shortened only by Magnevist (P =.03). Similarly, the only contrast agent that influenced the T2 relaxation times of 2,3‐DPG in blood samples was ferumoxytol (P =.02). Conclusion: Our results show that, unlike conventional proton MR, phosphorus MRS is unconfounded in patients who have had prior CT with contrast, not all gadolinium‐based contrast agents influence 31P‐MRS data in vivo, and that ferumoxytol is a promising contrast agent for the reduction in 31P‐MRS blood‐pool signal. [ABSTRACT FROM AUTHOR]

Purpose: Phosphorus spectroscopy (31P‐MRS) is a proven method to probe cardiac energetics. Studies typically report the phosphocreatine (PCr) to adenosine triphosphate (ATP) ratio. We focus on another 31P signal: inorganic phosphate (Pi), whose chemical shift allows computation of myocardial pH, with Pi/PCr providing additional insight into cardiac energetics. Pi is often obscured by signals from blood 2,3‐diphosphoglycerate (2,3‐DPG). We introduce a method to quantify Pi in 14 min without hindrance from 2,3‐DPG. Methods: Using a 31P stimulated echo acquisition mode (STEAM) sequence at 7 Tesla that inherently suppresses signal from 2,3‐DPG, the Pi peak was cleanly resolved. Resting state UTE‐chemical shift imaging (PCr/ATP) and STEAM 31P‐MRS (Pi/PCr, pH) were undertaken in 23 healthy controls; pH and Pi/PCr were subsequently recorded during dobutamine infusion. Results: We achieved a clean Pi signal both at rest and stress with good 2,3‐DPG suppression. Repeatability coefficient (8 subjects) for Pi/PCr was 0.036 and 0.12 for pH. We report myocardial Pi/PCr and pH at rest and during catecholamine stress in healthy controls. Pi/PCr was maintained during stress (0.098 ± 0.031 [rest] vs. 0.098 ± 0.031 [stress] P =.95); similarly, pH did not change (7.09 ± 0.07 [rest] vs. 7.08 ± 0.11 [stress] P =.81). Feasibility for patient studies was subsequently successfully demonstrated in a patient with cardiomyopathy. Conclusion: We introduced a method that can resolve Pi using 7 Tesla STEAM 31P‐MRS. We demonstrate the stability of Pi/PCr and myocardial pH in volunteers at rest and during catecholamine stress. This protocol is feasible in patients and potentially of use for studying pathological myocardial energetics. [ABSTRACT FROM AUTHOR]

Purpose: Hyperpolarized imaging experiments have conflicting requirements of high spatial, temporal, and spectral resolution. Spectral‐spatial RF excitation has been shown to form an attractive magnetization‐efficient method for hyperpolarized imaging, but the optimum readout strategy is not yet known. Methods: In this work, we propose a novel 3D hybrid‐shot spiral sequence which features two constant density regions that permit the retrospective reconstruction of either high spatial or high temporal resolution images post hoc, (adaptive spatiotemporal imaging) allowing greater flexibility in acquisition and reconstruction. Results: We have implemented this sequence, both via simulation and on a preclinical scanner, to demonstrate its feasibility, in both a 1H phantom and with hyperpolarized 13C pyruvate in vivo. Conclusions: This sequence forms an attractive method for acquiring hyperpolarized imaging datasets, providing adaptive spatiotemporal imaging to ameliorate the conflict of spatial and temporal resolution, with significant potential for clinical translation. [ABSTRACT FROM AUTHOR]

Hyperpolarized (HP) 13C MRI provides the means to monitor lactate metabolism noninvasively in tumours. Since 13C‐lactate signal levels obtained from HP 13C imaging depend on multiple factors, such as the rate of 13C substrate delivery via the vasculature, the expression level of monocarboxylate transporters (MCTs) and lactate dehydrogenase (LDH), and the local lactate pool size, the interpretation of HP 13C metabolic images remains challenging. In this study, ex vivo tissue extract measurements (i.e., NMR isotopomer analysis, western blot analysis) derived from an MDA‐MB‐231 xenograft model in nude rats were used to test for correlations between the in vivo 13C data and the ex vivo measures. The lactate‐to‐pyruvate ratio from HP 13C MRI was strongly correlated with [1‐ 13C]lactate concentration measured from the extracts using NMR (R = 0.69, p< 0.05), as well as negatively correlated with tumour wet weight (R = − 0.60, p< 0.05). In this tumour model, both MCT1 and MCT4 expressions were positively correlated with wet weight (ρ = 0.78 and 0.93, respectively, p< 0.01). Lactate pool size and the lactate‐to‐pyruvate ratio were not significantly correlated. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the feasibility of performing large FOV hyperpolarized 13C metabolic imaging using simultaneous multislice excitation. Methods: A spectral‐spatial multislice excitation pulse was constructed by cosine modulation and incorporated into a 13C spiral imaging sequence. Phantom and in vivo pig experiments were performed to test the feasibility of simultaneous multislice data acquisition and image reconstruction. In vivo cardiac‐gated images of hyperpolarized pyruvate, bicarbonate, and lactate were obtained at 1 × 1 × 1 cm3 resolution over a 48 × 48 × 24 cm3 FOV with 2‐fold acceleration in the slice direction. Sensitivity encoding was used for image reconstruction with both autocalibrated and numerically calculated coil sensitivities. Results: Simultaneous multislice images obtained with 2‐fold acceleration were comparable to reference unaccelerated images. Retained SNR figures greater than 80% were achieved over the part of the image containing the heart. Conclusion: This method is anticipated to enable large FOV imaging studies using hyperpolarized 13C substrates, with an aim toward whole‐body exams that have to date been out of reach. [ABSTRACT FROM AUTHOR]

Purpose: For 13C echo‐planar imaging (EPI) with spectral‐spatial excitation, main field inhomogeneity can result in reduced flip angle and spatial artifacts. A hybrid time‐resolved pulse sequence, multi‐echo spectral‐spatial EPI, is proposed combining broader spectral‐spatial passbands for greater off‐resonance tolerance with a multi‐echo acquisition to separate signals from potentially co‐excited resonances. Methods: The performance of the imaging sequence and the reconstruction pipeline were evaluated for 1H imaging using a series of increasingly dilute 1,4‐dioxane solutions and for 13C imaging using an ethylene glycol phantom. Hyperpolarized [1‐13C]pyruvate was administered to two healthy rats. Multi‐echo data of the rat kidneys were acquired to test realistic cases of off‐resonance. Results: Analysis of separated images of water and 1,4‐dioxane following multi‐echo signal decomposition showed water‐to‐dioxane 1H signal ratios that were in agreement with the independent measurements by 1H spectroscopy for all four concentrations of 1,4‐dioxane. The 13C signal ratio of two co‐excited resonances of ethylene glycol was accurately recovered after correction for the spectral profile of the redesigned spectral‐spatial pulse. In vivo, successful separation of lactate and pyruvate‐hydrate signals was achieved for all except the early time points during which signal variations exceeded the temporal resolution of the multi‐echo acquisition. Conclusion: Improved tolerance to off‐resonance in the new 13C data acquisition pipeline was demonstrated in vitro and in vivo. Magn Reson Med 80:925–934, 2018. © 2018 International Society for Magnetic Resonance in Medicine. [ABSTRACT FROM AUTHOR]

Purpose To provide built-in off-resonance correction in time-resolved, volumetric hyperpolarized 13C metabolic imaging by implementing a novel dual-echo 3D echo-planar imaging (EPI) sequence and reconstruction. Methods A spectral-spatial pulse for single-resonance excitation followed by a dual-echo 3D EPI readout was implemented to provide 64 × 8 × 6 cm3 coverage at 5 × 5 × 5 mm3 nominal resolution. Multiple sources of EPI distortions were encoded using a multi-echo 1H EPI reference scan. Phase maps computed from the reference scans were combined with a bulk 13C frequency offset encoded in the dual-echo [1-13C]pyruvate images to correct geometric distortion and improve spatial registration. The proposed scheme was validated in a phantom study, and in vivo [1-13C]pyruvate and [1-13C]lactate rat images were acquired with intentional transmit frequency deviations to assess the dual-echo 3D EPI sequence. Results The phantom study demonstrated improved spatial registration in off-resonance corrected images. Close agreement was observed between metabolic kidney signal and the underlying anatomy in rat imaging experiments. Relative to a single-echo acquisition, the coherent addition of the two corrected echoes provided the expected increase in signal-to-noise ratio by approximately [ABSTRACT FROM AUTHOR]

Purpose 1H MRI is an established diagnostic method that generally relies on detection of water. Imaging specific macromolecules is normally accomplished only indirectly through the use of paramagnetic tags, which alter the water signal in their vicinity. We demonstrate a new approach in which macromolecular constituents, such as proteins and drug delivery systems, are observed directly and quantitatively in vivo using 1H MRI of 13C-labeled poly(ethylene glycol) (13C-PEG) tags. Methods Molecular imaging of 13C-PEG-labeled species was accomplished by incorporating a modified heteronuclear multiple quantum coherence filter into a gradient echo imaging sequence. We demonstrate the approach by monitoring the real-time distribution of 13C-PEG and 13C-PEGylated albumin injected into the hind leg of a mouse. Results Filtering the 1H PEG signal through the directly coupled 13C nuclei largely eliminates background water and fat signals, thus enabling the imaging of molecules using 1H MRI. Conclusion PEGylation is widely employed to enhance the performance of a multitude of macromolecular therapeutics and drug delivery systems, and 13C-filtered 1H MRI of 13C-PEG thus offers the possibility of imaging and quantitating their distribution in living systems in real time. Magn Reson Med 77:1553-1561, 2017. © 2016 International Society for Magnetic Resonance in Medicine [ABSTRACT FROM AUTHOR]

In this study, a mixture of pyruvic acid and the perfusion agent HP001 was co-polarized for simultaneous assessment of perfusion and metabolism in vivo. The pre-polarized mixture was administered to rats with subcutaneous MDA-MB-231 breast cancer xenografts and imaged using an interleaved sequence with designed spectral-spatial pulses and flyback echo-planar readouts. Voxel-by-voxel signal correlations from 10 animals (15 data sets) were analyzed for tumour, kidney, and muscle regions of interest. The relationship between perfusion and hyperpolarized signal was explored on a voxel-by-voxel basis in various metabolically active tissues, including tumour, healthy kidneys, and skeletal muscle. Positive pairwise correlations between lactate, pyruvate, and HP001 observed in all 10 tumours suggested that substrate delivery was the dominant factor limiting the conversion of pyruvate to lactate in the tumour model used in this study. On the other hand, in cases where conversion is the limiting factor, such as in healthy kidneys, both pyruvate and lactate can act as excellent perfusion markers. In intermediate cases between the two limits, such as in skeletal muscle, some perfusion information may be inferred from the (pyruvate + lactate) signal distribution. Co-administration of pyruvate with a dynamic nuclear polarization (DNP) perfusion agent is an effective approach for distinguishing between slow metabolism and poor perfusion and a practical strategy for lactate signal normalization to account for substrate delivery, especially in cases of rapid pyruvate-to-lactate conversion and in poorly perfused regions with inadequate pyruvate signal-to-noise ratio for reliable determination of the lactate-to-pyruvate ratio. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A calibration-based technique for real-time measurement of pyruvate polarization by partial integral analysis of the doublet from the neighbouring J-coupled carbon is presented. In vitro calibration data relating the C2 and C1 asymmetries to the instantaneous C1 and C2 polarizations, respectively, were acquired in blood. The feasibility of using the in vitro calibration data to determine the instantaneous in vivo C1 and C2 polarizations was demonstrated in the analysis of rat kidney and pig heart spectral data. An approach for incorporating this technique into in vivo protocols is proposed. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

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., (© 2023 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

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 ( P i ) 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 P i 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 B 1 , producing equivalent saturation with a 53% reduction in delivered pulse power and a 33-fold reduction in spillover at the minimum effective B 1 . 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 P i -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., (© 2021 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: Phosphorus spectroscopy ( 31 P-MRS) is a proven method to probe cardiac energetics. Studies typically report the phosphocreatine (PCr) to adenosine triphosphate (ATP) ratio. We focus on another 31 P signal: inorganic phosphate (Pi), whose chemical shift allows computation of myocardial pH, with Pi/PCr providing additional insight into cardiac energetics. Pi is often obscured by signals from blood 2,3-diphosphoglycerate (2,3-DPG). We introduce a method to quantify Pi in 14 min without hindrance from 2,3-DPG., Methods: Using a 31 P stimulated echo acquisition mode (STEAM) sequence at 7 Tesla that inherently suppresses signal from 2,3-DPG, the Pi peak was cleanly resolved. Resting state UTE-chemical shift imaging (PCr/ATP) and STEAM 31 P-MRS (Pi/PCr, pH) were undertaken in 23 healthy controls; pH and Pi/PCr were subsequently recorded during dobutamine infusion., Results: We achieved a clean Pi signal both at rest and stress with good 2,3-DPG suppression. Repeatability coefficient (8 subjects) for Pi/PCr was 0.036 and 0.12 for pH. We report myocardial Pi/PCr and pH at rest and during catecholamine stress in healthy controls. Pi/PCr was maintained during stress (0.098 ± 0.031 [rest] vs. 0.098 ± 0.031 [stress] P = .95); similarly, pH did not change (7.09 ± 0.07 [rest] vs. 7.08 ± 0.11 [stress] P = .81). Feasibility for patient studies was subsequently successfully demonstrated in a patient with cardiomyopathy., Conclusion: We introduced a method that can resolve Pi using 7 Tesla STEAM 31 P-MRS. We demonstrate the stability of Pi/PCr and myocardial pH in volunteers at rest and during catecholamine stress. This protocol is feasible in patients and potentially of use for studying pathological myocardial energetics., (© 2020 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: Hyperpolarized imaging experiments have conflicting requirements of high spatial, temporal, and spectral resolution. Spectral-spatial RF excitation has been shown to form an attractive magnetization-efficient method for hyperpolarized imaging, but the optimum readout strategy is not yet known., Methods: In this work, we propose a novel 3D hybrid-shot spiral sequence which features two constant density regions that permit the retrospective reconstruction of either high spatial or high temporal resolution images post hoc, (adaptive spatiotemporal imaging) allowing greater flexibility in acquisition and reconstruction., Results: We have implemented this sequence, both via simulation and on a preclinical scanner, to demonstrate its feasibility, in both a 1 H phantom and with hyperpolarized 13 C pyruvate in vivo., Conclusions: This sequence forms an attractive method for acquiring hyperpolarized imaging datasets, providing adaptive spatiotemporal imaging to ameliorate the conflict of spatial and temporal resolution, with significant potential for clinical translation., (© 2020 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Hyperpolarized (HP) 13 C MRI provides the means to monitor lactate metabolism noninvasively in tumours. Since 13 C -lactate signal levels obtained from HP 13 C imaging depend on multiple factors, such as the rate of 13 C substrate delivery via the vasculature, the expression level of monocarboxylate transporters (MCTs) and lactate dehydrogenase (LDH), and the local lactate pool size, the interpretation of HP 13 C metabolic images remains challenging. In this study, ex vivo tissue extract measurements (i.e., NMR isotopomer analysis, western blot analysis) derived from an MDA-MB-231 xenograft model in nude rats were used to test for correlations between the in vivo 13 C data and the ex vivo measures. The lactate-to-pyruvate ratio from HP 13 C MRI was strongly correlated with [1- 13 C ]lactate concentration measured from the extracts using NMR (R = 0.69, p < 0.05), as well as negatively correlated with tumour wet weight (R = -  0.60, p < 0.05). In this tumour model, both MCT1 and MCT4 expressions were positively correlated with wet weight ( ρ = 0.78 and 0.93, respectively, p < 0.01). Lactate pool size and the lactate-to-pyruvate ratio were not significantly correlated., (© 2020 John Wiley & Sons, Ltd.)

Rationale: The recent development of hyperpolarized 13 C magnetic resonance spectroscopy has made it possible to measure cellular metabolism in vivo, in real time., Objective: By comparing participants with and without type 2 diabetes mellitus (T2DM), we report the first case-control study to use this technique to record changes in cardiac metabolism in the healthy and diseased human heart., Methods and Results: Thirteen people with T2DM (glycated hemoglobin, 6.9±1.0%) and 12 age-matched healthy controls underwent assessment of cardiac systolic and diastolic function, myocardial energetics ( 31 P-magnetic resonance spectroscopy), and lipid content ( 1 H-magnetic resonance spectroscopy) in the fasted state. In a subset (5 T2DM, 5 control), hyperpolarized [1- 13 C]pyruvate magnetic resonance spectra were also acquired and in 5 of these participants (3 T2DM, 2 controls), this was successfully repeated 45 minutes after a 75 g oral glucose challenge. Downstream metabolism of [1- 13 C]pyruvate via PDH (pyruvate dehydrogenase, [ 13 C]bicarbonate), lactate dehydrogenase ([1- 13 C]lactate), and alanine transaminase ([1- 13 C]alanine) was assessed. Metabolic flux through cardiac PDH was significantly reduced in the people with T2DM (Fasted: 0.0084±0.0067 [Control] versus 0.0016±0.0014 [T2DM], Fed: 0.0184±0.0109 versus 0.0053±0.0041; P =0.013). In addition, a significant increase in metabolic flux through PDH was observed after the oral glucose challenge ( P <0.001). As is characteristic of diabetes mellitus, impaired myocardial energetics, myocardial lipid content, and diastolic function were also demonstrated in the wider study cohort., Conclusions: This work represents the first demonstration of the ability of hyperpolarized 13 C magnetic resonance spectroscopy to noninvasively assess physiological and pathological changes in cardiac metabolism in the human heart. In doing so, we highlight the potential of the technique to detect and quantify metabolic alterations in the setting of cardiovascular disease.

Purpose: To provide built-in off-resonance correction in time-resolved, volumetric hyperpolarized 13 C metabolic imaging by implementing a novel dual-echo 3D echo-planar imaging (EPI) sequence and reconstruction., Methods: A spectral-spatial pulse for single-resonance excitation followed by a dual-echo 3D EPI readout was implemented to provide 64 × 8 × 6 cm 3 coverage at 5 × 5 × 5 mm 3 nominal resolution. Multiple sources of EPI distortions were encoded using a multi-echo 1 H EPI reference scan. Phase maps computed from the reference scans were combined with a bulk 13 C frequency offset encoded in the dual-echo [1- 13 C]pyruvate images to correct geometric distortion and improve spatial registration. The proposed scheme was validated in a phantom study, and in vivo [1- 13 C]pyruvate and [1- 13 C]lactate rat images were acquired with intentional transmit frequency deviations to assess the dual-echo 3D EPI sequence., Results: The phantom study demonstrated improved spatial registration in off-resonance corrected images. Close agreement was observed between metabolic kidney signal and the underlying anatomy in rat imaging experiments. Relative to a single-echo acquisition, the coherent addition of the two corrected echoes provided the expected increase in signal-to-noise ratio by approximately 2., Conclusion: A novel dual-echo 3D EPI acquisition sequence for integrated off-resonance correction in hyperpolarized 13 C imaging was developed and demonstrated. The proposed sequence offers clear advantages over flyback EPI for time-resolved metabolic mapping. Magn Reson Med 79:643-653, 2018. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

This review will highlight recent advances in hyperpolarized 13 C MR spectroscopic imaging, which can be used to noninvasively interrogate tumor metabolism. After providing an overview of MR and hyperpolarization, we will discuss the latest advances in data acquisition techniques. Next, we will shift our focus to hyperpolarized probe design and provide an overview of the latest hyperpolarized 13 C MR spectroscopic imaging probes developed in the last several years., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: 1 H MRI is an established diagnostic method that generally relies on detection of water. Imaging specific macromolecules is normally accomplished only indirectly through the use of paramagnetic tags, which alter the water signal in their vicinity. We demonstrate a new approach in which macromolecular constituents, such as proteins and drug delivery systems, are observed directly and quantitatively in vivo using 1 H MRI of 13 C-labeled poly(ethylene glycol) ( 13 C-PEG) tags., Methods: Molecular imaging of 13 C-PEG-labeled species was accomplished by incorporating a modified heteronuclear multiple quantum coherence filter into a gradient echo imaging sequence. We demonstrate the approach by monitoring the real-time distribution of 13 C-PEG and 13 C-PEGylated albumin injected into the hind leg of a mouse., Results: Filtering the 1 H PEG signal through the directly coupled 13 C nuclei largely eliminates background water and fat signals, thus enabling the imaging of molecules using 1 H MRI., Conclusion: PEGylation is widely employed to enhance the performance of a multitude of macromolecular therapeutics and drug delivery systems, and 13 C-filtered 1 H MRI of 13 C-PEG thus offers the possibility of imaging and quantitating their distribution in living systems in real time. Magn Reson Med 77:1553-1561, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Purpose: To enable large field-of-view, time-resolved volumetric coverage in hyperpolarized 13 C metabolic imaging by implementing a novel data acquisition and image reconstruction method based on the compressed sensing framework., Methods: A spectral-spatial pulse for single-resonance excitation followed by a symmetric echo-planar imaging (EPI) readout was implemented for encoding a 72 × 18 cm 2 field of view at 5 × 5 mm 2 resolution. Random undersampling was achieved with blipped z-gradients during the ramp portion of the echo-planar imaging readout. The sequence and reconstruction were tested with phantom studies and consecutive in vivo hyperpolarized 13 C scans in rats. Retrospectively and prospectively undersampled data were compared on the basis of structural similarity in the reconstructed images and the quantification of the lactate-to-pyruvate ratio in rat kidneys., Results: No artifacts or loss of resolution are evident in the compressed sensing reconstructed images acquired with the proposed sequence. Structural similarity analysis indicate that compressed sensing reconstructions can accurately recover spatial features in the metabolic images evaluated., Conclusion: A novel z-blip acquisition sequence for compressed sensing accelerated hyperpolarized 13 C 3D echo-planar imaging was developed and demonstrated. The close agreement in lactate-to-pyruvate ratios from both retrospectively and prospectively undersampled data from rats shows that metabolic information is preserved with acceleration factors up to 3-fold with the developed method. Magn Reson Med 77:538-546, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Rationale: Altered cardiac energetics is known to play an important role in the progression toward heart failure. A noninvasive method for imaging metabolic markers that could be used in longitudinal studies would be useful for understanding therapeutic approaches that target metabolism., Objective: To demonstrate the first hyperpolarized 13 C metabolic magnetic resonance imaging of the human heart., Methods and Results: Four healthy subjects underwent conventional proton cardiac magnetic resonance imaging followed by 13 C imaging and spectroscopic acquisition immediately after intravenous administration of a 0.1 mmol/kg dose of hyperpolarized [1- 13 C]pyruvate. All subjects tolerated the procedure well with no adverse effects reported ≤1 month post procedure. The [1- 13 C]pyruvate signal appeared within the chambers but not within the muscle. Imaging of the downstream metabolites showed 13 C-bicarbonate signal mainly confined to the left ventricular myocardium, whereas the [1- 13 C]lactate signal appeared both within the chambers and in the myocardium. The mean 13 C image signal:noise ratio was 115 for [1- 13 C]pyruvate, 56 for 13 C-bicarbonate, and 53 for [1- 13 C]lactate., Conclusions: These results represent the first 13 C images of the human heart. The appearance of 13 C-bicarbonate signal after administration of hyperpolarized [1- 13 C]pyruvate was readily detected in this healthy cohort (n=4). This shows that assessment of pyruvate metabolism in vivo in humans is feasible using current technology., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02648009., (© 2016 The Authors.)

In this study, a mixture of pyruvic acid and the perfusion agent HP001 was co-polarized for simultaneous assessment of perfusion and metabolism in vivo. The pre-polarized mixture was administered to rats with subcutaneous MDA-MB-231 breast cancer xenografts and imaged using an interleaved sequence with designed spectral-spatial pulses and flyback echo-planar readouts. Voxel-by-voxel signal correlations from 10 animals (15 data sets) were analyzed for tumour, kidney, and muscle regions of interest. The relationship between perfusion and hyperpolarized signal was explored on a voxel-by-voxel basis in various metabolically active tissues, including tumour, healthy kidneys, and skeletal muscle. Positive pairwise correlations between lactate, pyruvate, and HP001 observed in all 10 tumours suggested that substrate delivery was the dominant factor limiting the conversion of pyruvate to lactate in the tumour model used in this study. On the other hand, in cases where conversion is the limiting factor, such as in healthy kidneys, both pyruvate and lactate can act as excellent perfusion markers. In intermediate cases between the two limits, such as in skeletal muscle, some perfusion information may be inferred from the (pyruvate + lactate) signal distribution. Co-administration of pyruvate with a dynamic nuclear polarization (DNP) perfusion agent is an effective approach for distinguishing between slow metabolism and poor perfusion and a practical strategy for lactate signal normalization to account for substrate delivery, especially in cases of rapid pyruvate-to-lactate conversion and in poorly perfused regions with inadequate pyruvate signal-to-noise ratio for reliable determination of the lactate-to-pyruvate ratio. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Purpose: Develop and test an analytic correction method to correct the signal intensity variation caused by the inhomogeneous reception profile of an eight-channel phased array for hyperpolarized (13) C imaging., Theory and Methods: Fiducial markers visible in anatomical images were attached to the individual coils to provide three dimensional localization of the receive hardware with respect to the image frame of reference. The coil locations and dimensions were used to numerically model the reception profile using the Biot-Savart Law. The accuracy of the coil sensitivity estimation was validated with images derived from a homogenous (13) C phantom. Numerical coil sensitivity estimates were used to perform intensity correction of in vivo hyperpolarized (13) C cardiac images in pigs., Results: In comparison to the conventional sum-of-squares reconstruction, improved signal uniformity was observed in the corrected images., Conclusion: The analytical intensity correction scheme was shown to improve the uniformity of multichannel image reconstruction in hyperpolarized [1-(13) C]pyruvate and (13) C-bicarbonate cardiac MRI. The method is independent of the pulse sequence used for (13) C data acquisition, simple to implement and does not require additional scan time, making it an attractive technique for multichannel hyperpolarized (13) C MRI., (© 2015 Wiley Periodicals, Inc.)