In vivo hyperpolarization transfer in a clinical MRI scanner.

PURPOSE: The purpose of this study was to investigate the feasibility of in vivo 13 C->1 H hyperpolarization transfer, which has significant potential advantages for detecting the distribution and metabolism of hyperpolarized 13 C probes in a clinical MRI scanner. METHODS: A standalone pulsed 13 C RF transmit channel was developed for operation in conjunction with the standard 1 H channel of a clinical 3T MRI scanner. Pulse sequences for 13 C power calibration and polarization transfer were programmed on the external hardware and integrated with a customized water-suppressed 1 H MRS acquisition running in parallel on the scanner. The newly developed RF system was tested in both phantom and in vivo polarization transfer experiments in 1 JCH -coupled systems: phantom experiments in thermally polarized and hyperpolarized [2-13 C]glycerol, and 1 H detection of [2-13 C]lactate generated from hyperpolarized [2-13 C]pyruvate in rat liver in vivo. RESULTS: Operation of the custom pulsed 13 C RF channel resulted in effective 13 C->1 H hyperpolarization transfer, as confirmed by the characteristic antiphase appearance of 1 H-detected, 1 JCH -coupled doublets. In conjunction with a pulse sequence providing 190-fold water suppression in vivo, 1 H detection of hyperpolarized [2-13 C]lactate generated in vivo was achieved in a rat liver slice. CONCLUSION: The results show clear feasibility for effective 13 C->1 H hyperpolarization transfer in a clinical MRI scanner with customized heteronuclear RF system.

Sensitivity enhancement for detection of hyperpolarized 13 C MRI probes with 1 H spin coupling introduced by enzymatic transformation in vivo.

PURPOSE: Although 1 H spin coupling is generally avoided in probes for hyperpolarized (HP) 13 C MRI, enzymatic transformations of biological interest can introduce large 13 C-1 H couplings in vivo. The purpose of this study was to develop and investigate the application of 1 H decoupling for enhancing the sensitivity for detection of affected HP 13 C metabolic products. METHODS: A standalone 1 H decoupler system and custom concentric 13 C/1 H paddle coil setup were integrated with a clinical 3T MRI scanner for in vivo 13 C MR studies using HP [2-13 C]dihydroxyacetone, a novel sensor of hepatic energy status. Major 13 C-1 H coupling JCH = ∼150 Hz) is introduced after adenosine triphosphate-dependent enzymatic transformation of HP [2-13 C]dihydroxyacetone to [2-13 C]glycerol-3-phosphate in vivo. Application of WALTZ-16 1 H decoupling for elimination of large 13 C-1 H couplings was first tested in thermally polarized glycerol phantoms and then for in vivo HP MR studies in three rats, scanned both with and without decoupling. RESULTS: As configured, 1 H-decoupled 13 C MR of thermally polarized glycerol and the HP metabolic product [2-13 C]glycerol-3-phosphate was achieved at forward power of approximately 15 W. High-quality 3-s dynamic in vivo HP 13 C MR scans were acquired with decoupling duty cycle of 5%. Application of 1 H decoupling resulted in sensitivity enhancement of 1.7-fold for detection of metabolic conversion of [2-13 C]dihydroxyacetone to HP [2-13 C]glycerol-3-phosphate in vivo. CONCLUSIONS: Application of 1 H decoupling provides significant sensitivity enhancement for detection of HP 13 C metabolic products with large 1 H spin couplings, and is therefore expected to be useful for preclinical and potentially clinical HP 13 C MR studies. Magn Reson Med 80:36-41, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Chemical shift separation with controlled aliasing for hyperpolarized (13) C metabolic imaging.

PURPOSE: A chemical shift separation technique for hyperpolarized (13) C metabolic imaging with high spatial and temporal resolution was developed. Specifically, a fast three-dimensional pulse sequence and a reconstruction method were implemented to acquire signals from multiple (13) C species simultaneously with subsequent separation into individual images. THEORY AND METHODS: A stack of flyback echo-planar imaging readouts and a set of multiband excitation radiofrequency pulses were designed to spatially modulate aliasing patterns of the acquired metabolite images, which translated the chemical shift separation problem into parallel imaging reconstruction problem. An eight-channel coil array was used for data acquisition and a parallel imaging method based on nonlinear inversion was developed to separate the aliased images. RESULTS: Simultaneous acquisitions of pyruvate and lactate in a phantom study and in vivo rat experiments were performed. The results demonstrated successful separation of the metabolite distributions into individual images having high spatial resolution. CONCLUSION: This method demonstrated the ability to provide accelerated metabolite imaging in hyperpolarized (13) C MR using multichannel coils, tailored readout, and specialized RF pulses.

Dynamic hyperpolarized carbon-13 MR metabolic imaging of nonhuman primate brain.

PURPOSE: To investigate hyperpolarized (13) C metabolic imaging methods in the primate brain that can be translated into future clinical trials for patients with brain cancer. METHODS: (13) C coils and pulse sequences designed for use in humans were tested in phantoms. Dynamic (13) C data were obtained from a healthy cynomolgus monkey brain using the optimized (13) C coils and pulse sequences. The metabolite kinetics were estimated from two-dimensional localized (13) C dynamic imaging data from the nonhuman primate brain. RESULTS: Pyruvate and lactate signal were observed in both the brain and the surrounding tissues with the maximum signal-to-noise ratio of 218 and 29 for pyruvate and lactate, respectively. Apparent rate constants for the conversion of pyruvate to lactate and the ratio of lactate to pyruvate showed a difference between brain and surrounding tissues. CONCLUSION: The feasibility of using hyperpolarized [1-(13) C]-pyruvate for assessing in vivo metabolism in a healthy nonhuman primate brain was demonstrated using a hyperpolarized (13) C imaging experimental setup designed for studying patients with brain tumors. The kinetics of the metabolite conversion suggests that this approach may be useful in future studies of human neuropathology.

Combined parallel and partial fourier MR reconstruction for accelerated 8-channel hyperpolarized carbon-13 in vivo magnetic resonance Spectroscopic imaging (MRSI).

PURPOSE: To implement and evaluate combined parallel magnetic resonance imaging (MRI) and partial Fourier acquisition and reconstruction for rapid hyperpolarized carbon-13 ((13) C) spectroscopic imaging. Short acquisition times mitigate hyperpolarized signal losses that occur due to T1 decay, metabolism, and radiofrequency (RF) saturation. Human applications additionally require rapid imaging to permit breath-holding and to minimize the effects of physiologic motion. MATERIALS AND METHODS: Numerical simulations were employed to validate and characterize the reconstruction. In vivo MR spectroscopic images were obtained from a rat following injection of hyperpolarized (13) C pyruvate using an 8-channel array of carbon-tuned receive elements. RESULTS: For small spectroscopic matrix sizes, combined parallel imaging and partial Fourier undersampling resulted primarily in decreased spatial resolution, with relatively less visible spatial aliasing. Parallel reconstruction qualitatively restored lost image detail, although some pixel spectra had persistent numerical error. With this technique, a 30 × 10 × 16 matrix of 4800 3D MR spectroscopy imaging voxels from a whole rat with isotropic 8 mm(3) resolution was acquired within 11 seconds. CONCLUSION: Parallel MRI and partial Fourier acquisitions can provide the shorter imaging times and wider spatial coverage that will be necessary as hyperpolarized (13) C techniques move toward human clinical applications.

A quantum description of radiation damping and the free induction signal in magnetic resonance.

We apply the methods of cavity quantum electrodynamics (CQED), to obtain a microscopic and fully quantum-mechanical picture of radiation damping in magnetic resonance, and the nascent formation of the free induction signal. Numerical solution of the Tavis-Cummings model - i.e., multiple spins 1∕2 coupled to a lossless single-mode cavity - shows in fine detail the transfer of Zeeman energy, via spin coherence, to excite the cavity - represented here by a quantized LC resonator. The case of a single spin is also solved analytically. Although the motion of the Bloch vector is non-classical, we nonetheless show that the quantum mechanical Rabi nutation frequency (as enhanced by cavity coupling and stimulated emission) gives realistic estimates of macroscopic signal strength and the radiation damping constant in nuclear magnetic resonance. We also show how to introduce dissipation: cavity losses by means of a master equation, and relaxation by the phenomenological method of Bloch. The failure to obtain the full Bloch equations (unless semi-classical conditions are imposed on the cavity) is discussed in light of similar issues arising in CQED (and in earlier work in magnetic resonance as well), as are certain problems relative to quantization of the electromagnetic near-field.

Simultaneous investigation of cardiac pyruvate dehydrogenase flux, Krebs cycle metabolism and pH, using hyperpolarized [1,2-(13)C2]pyruvate in vivo.

(13)C MR spectroscopy studies performed on hearts ex vivo and in vivo following perfusion of prepolarized [1-(13)C]pyruvate have shown that changes in pyruvate dehydrogenase (PDH) flux may be monitored non-invasively. However, to allow investigation of Krebs cycle metabolism, the (13)C label must be placed on the C2 position of pyruvate. Thus, the utilization of either C1 or C2 labeled prepolarized pyruvate as a tracer can only afford a partial view of cardiac pyruvate metabolism in health and disease. If the prepolarized pyruvate molecules were labeled at both C1 and C2 positions, then it would be possible to observe the downstream metabolites that were the results of both PDH flux ((13)CO(2) and H(13)CO(3)(-)) and Krebs cycle flux ([5-(13)C]glutamate) with a single dose of the agent. Cardiac pH could also be monitored in the same experiment, but adequate SNR of the (13)CO(2) resonance may be difficult to obtain in vivo. Using an interleaved selective RF pulse acquisition scheme to improve (13)CO(2) detection, the feasibility of using dual-labeled hyperpolarized [1,2-(13)C(2)]pyruvate as a substrate for dynamic cardiac metabolic MRS studies to allow simultaneous investigation of PDH flux, Krebs cycle flux and pH, was demonstrated in vivo.

Detection of inflammatory arthritis by using hyperpolarized 13C-pyruvate with MR imaging and spectroscopy.

PURPOSE: To examine the feasibility of using magnetic resonance (MR) spectroscopy with hyperpolarized carbon 13 ((13)C)-labeled pyruvate to detect inflammation. MATERIALS AND METHODS: The animal care and use committee approved all work with animals. Arthritis was induced in the right hind paw of six rats; the left hind paw served as an internal control. The lactate dehydrogenase-catalyzed conversion of pyruvate to lactate was measured in inflamed and control paws by using (13)C MR spectroscopy. Clinical and histologic data were obtained to confirm the presence and severity of arthritis. Hyperpolarized (13)C-pyruvate was intravenously injected into the rats before simultaneous imaging of both paws with (13)C MR spectroscopy. The Wilcoxon signed rank test was used to test for differences in metabolites between the control and arthritic paws. RESULTS: All animals showed findings of inflammation in the affected paws and no signs of arthritis in the control paws at both visible inspection (clinical index of 3 for arthritic paws and 0 for control paws) and histologic examination (histologic score of 3-5 for arthritic paws and 0 for control paws). Analysis of the spectroscopic profiles of (13)C-pyruvate and converted (13)C-lactate showed an increase in the amount of (13)C-lactate in inflamed paws (median lactate-to-pyruvate ratio, 0.50; mean lactate-to-pyruvate ratio ± standard deviation, 0.52 ± 0.16) versus control paws (median lactate-to-pyruvate ratio, 0.27; mean lactate-to-pyruvate ratio, 0.32 ± 0.11) (P < .03). The ratio of (13)C-lactate to total (13)C was also significantly increased in inflamed paws compared with control paws (P < .03). CONCLUSION: These results suggest that alterations in the conversion of pyruvate to lactate as detected with (13)C-MR spectroscopy may be indicative of the presence of inflammatory arthritis.

Dynamic and high-resolution metabolic imaging of hyperpolarized [1-13C]-pyruvate in the rat brain using a high-performance gradient insert.

Fast chemical shift imaging (CSI) techniques are advantageous in metabolic imaging of hyperpolarized compounds due to the limited duration of the signal amplification. At the same time, reducing the acquisition time in hyperpolarized imaging does not necessarily lead to the conventional penalty in signal-to-noise ratio that occurs in imaging at thermal equilibrium polarization levels. Here a high-performance gradient insert was used in combination with undersampled spiral CSI to increase either the imaging speed or the spatial resolution of hyperpolarized (13)C metabolic imaging on a clinical 3T MR scanner. Both a single-shot sequence with a total acquisition time of 125 ms and a three-shot sequence with a nominal in-plane resolution of 1.5 mm were implemented. The k-space trajectories were measured and then used during image reconstruction. The technique was applied to metabolic imaging of the rat brain in vivo after the injection of hyperpolarized [1-(13)C]-pyruvate. Dynamic imaging afforded the measurement of region-of-interest-specific time courses of pyruvate and its metabolic products, while imaging at high spatial resolution was used to better characterize the spatial distribution of the metabolite signals.

Quantification of in vivo metabolic kinetics of hyperpolarized pyruvate in rat kidneys using dynamic 13C MRSI.

With signal-to-noise ratio enhancements on the order of 10,000-fold, hyperpolarized MRSI of metabolically active substrates allows the study of both the injected substrate and downstream metabolic products in vivo. Although hyperpolarized [1-(13)C]pyruvate, in particular, has been used to demonstrate metabolic activities in various animal models, robust quantification and metabolic modeling remain important areas of investigation. Enzyme saturation effects are routinely seen with commonly used doses of hyperpolarized [1-(13)C]pyruvate; however, most metrics proposed to date, including metabolite ratios, time-to-peak of metabolic products and single exchange rate constants, fail to capture these saturation effects. In addition, the widely used small-flip-angle excitation approach does not correctly model the inflow of fresh downstream metabolites generated proximal to the target slice, which is often a significant factor in vivo. In this work, we developed an efficient quantification framework employing a spiral-based dynamic spectroscopic imaging approach. The approach overcomes the aforementioned limitations and demonstrates that the in vivo (13)C labeling of lactate and alanine after a bolus injection of [1-(13)C]pyruvate is well approximated by saturatable kinetics, which can be mathematically modeled using a Michaelis-Menten-like formulation, with the resulting estimated apparent maximal reaction velocity V(max) and apparent Michaelis constant K(M) being unbiased with respect to critical experimental parameters, including the substrate dose, bolus shape and duration. Although the proposed saturatable model has a similar mathematical formulation to the original Michaelis-Menten kinetics, it is conceptually different. In this study, we focus on the (13)C labeling of lactate and alanine and do not differentiate the labeling mechanism (net flux or isotopic exchange) or the respective contribution of various factors (organ perfusion rate, substrate transport kinetics, enzyme activities and the size of the unlabeled lactate and alanine pools) to the labeling process.

Combination of two fat saturation pulses improves detectability of glucose signals in carbon-13 MR spectroscopy.

In order to improve the fat suppression performance of in vivo (13)C-MRS operating at 3.0 Tesla, a phantom model study was conducted using a combination of two fat suppression techniques; a set of pulses for frequency (chemical shift) selective suppression (CHESS), and spatial saturation (SAT). By optimizing the slab thickness for SAT and the irradiation bandwidth for CHESS, the signals of the -(13)CH(3) peak at 49 ppm and the -(13)CH(2)- peak at 26 ppm simulating fat components were suppressed to 5% and 19%, respectively. Combination of these two fat suppression pulses achieved a 53% increase of the height ratio of the glucose C1ß peak compared with the sum of all other peaks, indicating better sensitivity for glucose signal detection. This method will be applicable for in vivo (13)C-MRS by additional adjustment with the in vivo relaxation times of the metabolites.

Metabolic imaging in the anesthetized rat brain using hyperpolarized [1-13C] pyruvate and [1-13C] ethyl pyruvate.

Formulation, polarization, and dissolution conditions were developed to obtain a stable hyperpolarized solution of [1-(13)C]-ethyl pyruvate. A maximum tolerated concentration and injection rate were determined, and (13)C spectroscopic imaging was used to compare the uptake of hyperpolarized [1-(13)C]-ethyl pyruvate relative to hyperpolarized [1-(13)C]-pyruvate into anesthetized rat brain. Hyperpolarized [1-(13)C]-ethyl pyruvate and [1-(13)C]-pyruvate metabolic imaging in normal brain is demonstrated and quantified in this feasibility and range-finding study.

T(2) relaxation times of (13)C metabolites in a rat hepatocellular carcinoma model measured in vivo using (13)C-MRS of hyperpolarized [1-(13)C]pyruvate.

A single-voxel Carr-Purcell-Meibloom-Gill sequence was developed to measure localized T(2) relaxation times of (13)C-labeled metabolites in vivo for the first time. Following hyperpolarized [1-(13)C]pyruvate injections, pyruvate and its metabolic products, alanine and lactate, were observed in the liver of five rats with hepatocellular carcinoma and five healthy control rats. The T(2) relaxation times of alanine and lactate were both significantly longer in HCC tumors than in normal livers (p < 0.002). The HCC tumors also showed significantly higher alanine signal relative to the total (13)C signal than normal livers (p < 0.006). The intra- and inter-subject variations of the alanine T(2) relaxation time were 11% and 13%, respectively. The intra- and inter-subject variations of the lactate T(2) relaxation time were 6% and 7%, respectively. The intra-subject variability of alanine to total carbon ratio was 16% and the inter-subject variability 28%. The intra-subject variability of lactate to total carbon ratio was 14% and the inter-subject variability 20%. The study results show that the signal level and relaxivity of [1-(13)C]alanine may be promising biomarkers for HCC tumors. Its diagnostic values in HCC staging and treatment monitoring are yet to be explored.

Hyperpolarized MRI of Human Prostate Cancer Reveals Increased Lactate with Tumor Grade Driven by Monocarboxylate Transporter 1.

Metabolic imaging using hyperpolarized magnetic resonance can increase the sensitivity of MRI, though its ability to inform on relevant changes to biochemistry in humans remains unclear. In this work, we image pyruvate metabolism in patients, assessing the reproducibility of delivery and conversion in the setting of primary prostate cancer. We show that the time to max of pyruvate does not vary significantly within patients undergoing two separate injections or across patients. Furthermore, we show that lactate increases with Gleason grade. RNA sequencing data demonstrate a significant increase in the predominant pyruvate uptake transporter, monocarboxylate transporter 1. Increased protein expression was also observed in regions of high lactate signal, implicating it as the driver of lactate signal in vivo. Targeted DNA sequencing for actionable mutations revealed the highest lactate occurred in patients with PTEN loss. This work identifies a potential link between actionable genomic alterations and metabolic information derived from hyperpolarized pyruvate MRI.

In vivo measurement of ethanol metabolism in the rat liver using magnetic resonance spectroscopy of hyperpolarized [1-13C]pyruvate.

[1-(13)C]pyruvate is a readily polarizable substrate that has been the subject of numerous magnetic resonance spectroscopy (MRS) studies of in vivo metabolism. In this work (13)C-MRS of hyperpolarized [1-(13)C]pyruvate was used to interrogate a metabolic pathway involved in neither aerobic nor anaerobic metabolism. In particular, ethanol consumption leads to altered liver metabolism, which when excessive is associated with adverse medical conditions including fatty liver disease, hepatitis, cirrhosis, and cancer. Here we present a method for noninvasively monitoring this important process in vivo. Following the bolus injection of hyperpolarized [1-(13)C]pyruvate, we demonstrate a significantly increased rat liver lactate production rate with the coadministration of ethanol (P = 0.0016 unpaired t-test). The affect is attributable to increased liver nicotinamide adenine dinucleotide (NADH) associated with ethanol metabolism in combination with NADH's role as a coenzyme in pyruvate-to-lactate conversion. Beyond studies of liver metabolism, this novel in vivo assay of changes in NADH levels makes hyperpolarized [1-(13)C]pyruvate a potentially viable substrate for studying the multiple in vivo metabolic pathways that use NADH (or NAD(+)) as a coenzyme, thus broadening the range of applications that have been discussed in the literature to date.

Application of subsecond spiral chemical shift imaging to real-time multislice metabolic imaging of the rat in vivo after injection of hyperpolarized 13C1-pyruvate.

Dynamic nuclear polarization can create hyperpolarized compounds with MR signal-to-noise ratio enhancements on the order of 10,000-fold. Both exogenous and normally occurring endogenous compounds can be polarized, and their initial concentration and downstream metabolic products can be assessed using MR spectroscopy. Given the transient nature of the hyperpolarized signal enhancement, fast imaging techniques are a critical requirement for real-time metabolic imaging. We report on the development of an ultrafast, multislice, spiral chemical shift imaging sequence, with subsecond acquisition time, achieved on a clinical MR scanner. The technique was used for dynamic metabolic imaging in rats, with measurement of time-resolved spatial distributions of hyperpolarized (13)C(1)-pyruvate and metabolic products (13)C(1)-lactate and (13)C(1)-alanine, with a temporal resolution of as fast as 1 s. Metabolic imaging revealed different signal time courses in liver from kidney. These results demonstrate the feasibility of real-time, hyperpolarized metabolic imaging and highlight its potential in assessing organ-specific kinetic parameters.

Three-frequency RF coil designed for optimized imaging of hyperpolarized, 13C-labeled compounds.

Imaging exams involving hyperpolarized, (13)C-labeled compounds require novel RF coils for efficient signal utilization. While (13)C coils are required for mapping the spatial distribution of the hyperpolarized compounds, imaging/pulsing at different frequencies is also needed for scan setup steps prior to the image acquisition. Imaging/pulsing at the (1)H frequency is typically used for anatomical localization and shimming. Flip angle (FA) calibration, which is difficult or impossible to achieve at the (13)C frequency, can be accurately performed at the (23)Na frequency using the natural abundance signal that exists in any living tissue. We demonstrate here a single RF resonant structure that is capable of operating linearly at the (1)H and (23)Na frequencies for scan setup steps, and in quadrature at the (13)C frequency for imaging. Images at the three resonant frequencies of this coil are presented from an exam involving hyperpolarized (13)C compounds in vivo.

Quantification of Total and Intracellular Sodium Concentration in Primary Prostate Cancer and Adjacent Normal Prostate Tissue With Magnetic Resonance Imaging.

OBJECTIVES: The aim of this study was to measure the tissue sodium concentration (TSC) within tumors and normal prostate in prostate cancer patients, using prostatectomy as pathological criterion standard. MATERIALS AND METHODS: Fifteen patients with biopsy-proven, magnetic resonance imaging (MRI) visible, intermediate- or high-risk prostate cancer underwent a dedicated research sodium MRI, before treatment with radical prostatectomy. All participants signed written informed consent for this institutional review board-approved prospective study. 3 T MRI acquired using a dedicated multinuclear clamshell transmit coil and a bespoke dual-tuned H/Na endorectal receive coil, with intracellular-sodium imaging acquired using inversion recovery sequences; a phantom-based calibration enabled quantitative sodium maps. Regions of interest were defined for normal peripheral zone (PZ) and transition zone (TZ) and tumor regions, referenced from histopathology maps. A 1-way analysis of variance compared normal and tumor tissue, using Tukey test for multiple comparisons. RESULTS: Two patients were excluded due to artifact; software error resulted in 1 further intracellular-sodium failure. Fifteen tumors were detected (13 PZ, 2 TZ) in 13 patients: Gleason 3 + 3 (n = 1), 3 + 4 (6), 3 + 5 (2), 4 + 3 (5), 4 + 5 (1). Both mean TSC and intracellular-sodium were significantly higher in normal PZ (39.2 and 17.5 mmol/L, respectively) versus normal TZ (32.9 and 14.7; P < 0.001 and P = 0.02). Mean TSC in PZ tumor (45.0 mmol/L) was significantly higher than both normal PZ and TZ tissue (P < 0.001). Intracellular sodium in PZ tumors (19.9 mmol/L) was significantly higher than normal TZ (P < 0.001) but not normal PZ (P = 0.05). Mean TSC and intracellular-sodium was lower in Gleason ≤3 + 4 tumors (44.4 and 19.5 mmol/L, respectively) versus ≥4 + 3 (45.6 and 20.2), but this was not significant (P = 0.19 and P = 0.29). CONCLUSIONS: Tissue sodium concentration and intracellular sodium concentrations of prostate tumors were quantified, with PZ tumors demonstrating a significantly increased TSC.

Metabolic Imaging of the Human Brain with Hyperpolarized 13C Pyruvate Demonstrates 13C Lactate Production in Brain Tumor Patients.

Hyperpolarized (HP) MRI using [1-13C] pyruvate is a novel method that can characterize energy metabolism in the human brain and brain tumors. Here, we present the first dynamically acquired human brain HP 13C metabolic spectra and spatial metabolite maps in cases of both untreated and recurrent tumors. In vivo production of HP lactate from HP pyruvate by tumors was indicative of altered cancer metabolism, whereas production of HP lactate in the entire brain was likely due to baseline metabolism. We correlated our results with standard clinical brain MRI, MRI DCE perfusion, and in one case FDG PET/CT. Our results suggest that HP 13C pyruvate-to-lactate conversion may be a viable metabolic biomarker for assessing tumor response.Significance: Hyperpolarized pyruvate MRI enables metabolic imaging in the brain and can be a quantitative biomarker for active tumors.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/14/3755/F1.large.jpg Cancer Res; 78(14); 3755-60. ©2018 AACR.

Development and testing of hyperpolarized (13)C MR calibrationless parallel imaging.

A calibrationless parallel imaging technique developed previously for (1)H MRI was modified and tested for hyperpolarized (13)C MRI for applications requiring large FOV and high spatial resolution. The technique was demonstrated with both retrospective and prospective under-sampled data acquired in phantom and in vivo rat studies. A 2-fold acceleration was achieved using a 2D symmetric EPI readout equipped with random blips on the phase encode dimension. Reconstructed images showed excellent qualitative agreement with fully sampled data. Further acceleration can be achieved using acquisition schemes that incorporate multi-dimensional under-sampling.