PDF file-63KB, Representative 31P spectra of HK-2, UMRC6 and UOK262 cell lines.

PDF file-77KB, Table of metabolite 31P chemical shifts () and T1 relaxation times at 500MHz, measured in living UMRC6 cells within the bioreactor.

PDF file-56KB, Analysis of hyperpolarized dynamics in bioreactors containing perfused HK2, UMRC6 and UOK262 cells at a flow rate of 2.5ml/min.

PurposeTo develop a novel post‐processing pipeline for hyperpolarized (HP) 13C MRSI that integrates tensor denoising and correction to measure pyruvate‐to‐lactate conversion rates (kPL) in patients with liver tumors.MethodsSeven HP 13C MR scans of progressing liver tumors were acquired using a custom 13C surface transmit/receive coil and the echo‐planar spectroscopic imaging (EPSI) data analysis included B0 correction, tensor rank truncation, and zero‐ and first‐order phase corrections to recover metabolite signals that would otherwise be obscured by spectral noise as well as a correction for inhomogeneous transmit () using a map aligned to the coil position for each patient scan. Processed HP data and corrected flip angles were analyzed with an inputless two‐site exchange model to calculate kPL.ResultsDenoising averages SNR increases of pyruvate, lactate, and alanine were 37.4‐, 34.0‐, and 20.1‐fold, respectively, with lactate and alanine dynamics most noticeably recovered and better defined. In agreement with Monte Carlo simulations, over‐flipped regions underestimated kPL and under‐flipped regions overestimated kPL. correction addressed this issue.ConclusionThe new HP 13C EPSI post‐processing pipeline integrated tensor denoising and correction to measure kPL in patients with liver tumors. These technical developments not only recovered metabolite signals in voxels that did not receive the prescribed flip angle, but also increased the extent and accuracy of kPL estimations throughout the tumor and adjacent regions including normal‐appearing tissue and additional lesions.

Purpose The combined hyperpolarized (HP) 13 C pyruvate and urea MRI has provided a simultaneous assessment of glycolytic metabolism and tissue perfusion for improved cancer diagnosis and therapeutic evaluation in preclinical studies. This work aims to translate this dual‐probe HP imaging technique to clinical research. Methods A co‐polarization system was developed where [1‐ 13 C]pyruvic acid (PA) and [ 13 C, 15 N 2 ]urea in water solution were homogeneously mixed and polarized on a 5T SPINlab system. Physical and chemical characterizations and toxicology studies of the combined probe were performed. Simultaneous metabolic and perfusion imaging was performed on a 3T clinical MR scanner by alternatively applying a multi‐slice 2D spiral sequence for [1‐ 13 C]pyruvate and its downstream metabolites and a 3D balanced steady‐state free precession (bSSFP) sequence for [ 13 C, 15 N 2 ]urea. Results The combined PA/urea probe has a glass‐formation ability similar to neat PA and can generate nearly 40% liquid‐state 13 C polarization for both pyruvate and urea in 3‐4 h. A standard operating procedure for routine on‐site production was developed and validated to produce 40 mL injection product of approximately 150 mM pyruvate and 35 mM urea. The toxicology study demonstrated the safety profile of the combined probe. Dynamic metabolite‐specific imaging of [1‐ 13 C]pyruvate, [1‐ 13 C]lactate, [1‐ 13 C]alanine, and [ 13 C, 15 N 2 ]urea was achieved with adequate spatial (2.6 mm × 2.6 mm) and temporal resolution (4.2 s), and urea images showed reduced off‐resonance artifacts due to the J CN coupling. Conclusion The reported technical development and translational studies will lead to the first‐in‐human dual‐agent HP MRI study and mark the clinical translation of the first HP 13 C MRI probe after pyruvate.

Currently, no clinical methods reliably predict the development of castration-resistant prostate cancer (CRPC) that occurs almost universally in men undergoing androgen deprivation therapy. Hyperpolarized (HP) 13C magnetic resonance imaging (MRI) could potentially detect the incipient emergence of CRPC based on early metabolic changes. To characterize metabolic shifts occurring upon the transition from androgen-dependent to castration-resistant prostate cancer (PCa), the metabolism of [U-13C]glucose and [U-13C]glutamine was analyzed by nuclear magnetic resonance spectroscopy. Comparison of steady-state metabolite concentrations and fractional enrichment in androgen-dependent LNCaP cells and transgenic adenocarcinoma of the murine prostate (TRAMP) murine tumors versus castration-resistant PC-3 cells and treatment-driven CRPC TRAMP tumors demonstrated that CRPC was associated with upregulation of glycolysis, tricarboxylic acid metabolism of pyruvate; and glutamine, glutaminolysis, and glutathione synthesis. These findings were supported by 13C isotopomer modeling showing increased flux through pyruvate dehydrogenase (PDH) and anaplerosis; enzymatic assays showing increased lactate dehydrogenase, PDH and glutaminase activity; and oxygen consumption measurements demonstrating increased dependence on anaplerotic fuel sources for mitochondrial respiration in CRPC. Consistent with ex vivo metabolomic studies, HP [1-13C]pyruvate distinguished androgen-dependent PCa from CRPC in cell and tumor models based on significantly increased HP [1-13C]lactate.

Determining the aggressiveness of renal cell carcinoma (RCC) noninvasively is a critical part of the diagnostic workup for treating this disease that kills more than 15,000 people annually in the USA. Recently, we have shown that not only the amount of lactate produced, as a consequence of the Warburg effect, but also its efflux out of the cell, is a critical marker of RCC aggressiveness and differentiating RCCs from benign renal tumors. Enzymatic conversions can now be measured in situ with hyperpolarized (HP) 13C magnetic resonance (MR) on a sub‐minute time scale. Using RCC models, we have shown that this technology can interrogate in real time both lactate production and compartmentalization, which are associated with tumor aggressiveness. The dynamic HP MR data have enabled us to robustly characterize parameters that have been elusive to measure directly in intact living cells and murine tumors thus far. Specifically, we were able to measure the same intracellular lactate longitudinal relaxation time in three RCC cell lines of 16.42 s, and lactate efflux rate ranging from 0.14 to 0.8 s−1 in the least to the most aggressive RCC cell lines and correlate it to monocarboxylate transporter isoform 4 expression. We also analyzed dynamic HP lactate and pyruvate data from orthotopic murine RCC tumors using a simplified one‐compartment model, and showed comparable apparent pyruvate to lactate conversion rate (kPL) values with those measured in vitro. This kinetic modeling was then extended to characterize the lactate dynamics in patient‐derived living RCC tissue slices; and even without direct measurement of the extracellular lactate signal the efflux parameter was still assessed and was distinct between the benign renal tumors and RCCs. Across all these preclinical models, the rate parameters of kPL and lactate efflux correlated to cancer aggressiveness, demonstrating the validity of our modeling approach for noninvasive assessment of RCC aggressiveness.

Non-invasive assessment of the biological aggressiveness of prostate cancer (PCa) is needed for men with localized disease. Hyperpolarized (HP) 13C magnetic resonance (MR) spectroscopy is a powerful approach to image metabolism, specifically the conversion of HP [1-13C]pyruvate to [1-13C]lactate, catalyzed by lactate dehydrogenase (LDH). Significant increase in tumor lactate was measured in high-grade PCa relative to benign and low-grade cancer, suggesting that HP 13C MR could distinguish low-risk (Gleason score ≤3 + 4) from high-risk (Gleason score ≥4 + 3) PCa. To test this and the ability of HP 13C MR to detect these metabolic changes, we cultured prostate tissues in an MR-compatible bioreactor under continuous perfusion. 31P spectra demonstrated good viability and dynamic HP 13C-pyruvate MR demonstrated that high-grade PCa had significantly increased lactate efflux compared to low-grade PCa and benign prostate tissue. These metabolic differences are attributed to significantly increased LDHA expression and LDH activity, as well as significantly increased monocarboxylate transporter 4 (MCT4) expression in high- versus low- grade PCa. Moreover, lactate efflux, LDH activity, and MCT4 expression were not different between low-grade PCa and benign prostate tissues, indicating that these metabolic alterations are specific for high-grade disease. These distinctive metabolic alterations can be used to differentiate high-grade PCa from low-grade PCa and benign prostate tissues using clinically translatable HP [1-13C]pyruvate MR.

Background: Hyperpolarized carbon-13 (HP-C-13)MRI is a non-invasive imaging technique for probing brain metabolism, which may improve clinical cancer surveillance. This work aimed to characterize the consistency of serial HP-C-13 imaging in patients undergoing treatment for brain tumors and determine whether there is evidence of aberrant metabolism in the tumor lesion compared to normal-appearing tissue. Methods: Serial dynamic HP [1-C-13]pyruvate MRI was performed on 3 healthy volunteers (6 total examinations) and 5 patients (21 total examinations) with diffuse infiltrating glioma during their course of treatment, using a frequency-selective echo-planar imaging (EPI) sequence. HP-C-13 imaging at routine clinical timepoints overlapped treatment, including radiotherapy (RT), temozolomide (TMZ) chemotherapy, and anti-angiogenic/investigational agents. Apparent rate constants for [1-C-13]pyruvate conversion to [1-C-13]lactate (k(PL))( )and [C-13] bicarbonate (k(PB)) were simultaneously quantified based on an inputless kinetic model within normal-appearing white matter (NAWM) and anatomic lesions defined from H-1 MRI. The inter/intra-subject consistency of k(PL-)(NAWM) and k(PB-)(NAWM) was measured in terms of the coefficient of variation (CV). Results: When excluding scans following anti-angiogenic therapy, patient values of k(PL-NAWM) and k(PB-NAWM) were 0.020 s(-1) +/- 23.8% and 0.0058 s(-1) +/- 27.7% (mean +/- CV) across 17 HP-C-13 MRIs, with intra-patient serial k(PL-NAWM)/k(PB-NAWM) CVs ranging 6.8-16.6%/10.6-40.7%. In 4/5 patients, these values (0.018 s(-1) +/- 13.4% and 0.0058 s(-1) +/- 24.4%; n = 13) were more similar to those from healthy volunteers (0.018 s(-1) +/- 5.0% and 0.0043 s(-1) +/- 12.6%; n = 6) (mean +/- CV). The anti-angiogenic agent bevacizumab was associated with global elevations in apparent rate constants, with maximum k(PL-NAWM) in 2 patients reaching 0.047 +/- 0.001 and 0.047 +/- 0.003 s(-1) (+/- model error). In 3 patients with progressive disease, anatomic lesions showed elevated k(PL) relative to k(PL-NAWM) of 0.024 +/- 0.001 s(-1) (+/- model error) in the absence of gadolinium enhancement, and 0.032 +/- 0.008, 0.040 +/- 0.003 and 0.041 +/- 0.009 s(-1) with gadolinium enhancement. The lesion k(P)(B) in patients was reduced to unquantifiable values compared to k(PB-NAWM). Conclusion: Serial measures of HP [1-C-13]pyruvate metabolism displayed consistency in the NAWM of healthy volunteers and patients. Both k(PL) and k(P)(B) were globally elevated following bevacizumab treatment, while progressive disease demonstrated elevated k(PL) in gadolinium-enhancing and non-enhancing lesions. Larger prospective studies with homogeneous patient populations are planned to evaluate metabolic changes following treatment.

With the initiation of human hyperpolarized 13C (HP‐13C) trials at multiple sites and the development of improved acquisition methods, there is an imminent need to maximally extract diagnostic information to facilitate clinical interpretation. This study aims to improve human HP‐13C MR spectroscopic imaging through means of Tensor Rank truncation‐Image enhancement (TRI) and optimal receiver combination (ORC).

PurposeTo develop and translate a metabolite‐specific imaging sequence using a symmetric echo planar readout for clinical hyperpolarized (HP) Carbon‐13 (13C) applications.MethodsInitial data were acquired from patients with prostate cancer (N = 3) and high‐grade brain tumors (N = 3) on a 3T scanner. Samples of [1‐13C]pyruvate were polarized for at least 2 h using a 5T SPINlab system operating at 0.8 K. Following injection of the HP substrate, pyruvate, lactate, and bicarbonate (for brain studies) were sequentially excited with a singleband spectral‐spatial RF pulse and signal was rapidly encoded with a single‐shot echo planar readout on a slice‐by‐slice basis. Data were acquired dynamically with a temporal resolution of 2 s for prostate studies and 3 s for brain studies.ResultsHigh pyruvate signal was seen throughout the prostate and brain, with conversion to lactate being shown across studies, whereas bicarbonate production was also detected in the brain. No Nyquist ghost artifacts or obvious geometric distortion from the echo planar readout were observed. The average error in center frequency was 1.2 ± 17.0 and 4.5 ± 1.4 Hz for prostate and brain studies, respectively, below the threshold for spatial shift because of bulk off‐resonance.ConclusionThis study demonstrated the feasibility of symmetric EPI to acquire HP 13C metabolite maps in a clinical setting. As an advance over prior single‐slice dynamic or single time point volumetric spectroscopic imaging approaches, this metabolite‐specific EPI acquisition provided robust whole‐organ coverage for brain and prostate studies while retaining high SNR, spatial resolution, and dynamic temporal resolution.

Hyperpolarized 13 C MRI takes advantage of the unprecedented 50 000-fold signal-to-noise ratio enhancement to interrogate cancer metabolism in patients and animals. It can measure the pyruvate-to-lactate conversion rate, kPL , a metabolic biomarker of cancer aggressiveness and progression. Therefore, it is crucial to evaluate kPL reliably. In this study, three sequence components and parameters that modulate kPL estimation were identified and investigated in model simulations and through in vivo animal studies using several specifically designed pulse sequences. These factors included a magnetization spoiling effect due to RF pulses, a crusher gradient-induced flow suppression, and intrinsic image weightings due to relaxation. Simulation showed that the RF-induced magnetization spoiling can be substantially improved using an inputless kPL fitting. In vivo studies found a significantly higher apparent kPL with an additional gradient that leads to flow suppression (kPL,FID-Delay,Crush /kPL,FID-Delay  = 1.37 ± 0.33, P < 0.01, N = 6), which agrees with simulation outcomes (12.5% kPL error with Δv = 40 cm/s), indicating that the gradients predominantly suppressed flowing pyruvate spins. Significantly lower kPL was found using a delayed free induction decay (FID) acquisition versus a minimum-TE version (kPL,FID-Delay /kPL,FID  = 0.67 ± 0.09, P < 0.01, N = 5), and the lactate peak had broader linewidth than pyruvate (Δωlactate /Δωpyruvate  = 1.32 ± 0.07, P < 0.000 01, N = 13). This illustrated that lactate's T2 *, shorter than that of pyruvate, can affect calculated kPL values. We also found that an FID sequence yielded significantly lower kPL versus a double spin-echo sequence that includes spin-echo spoiling, flow suppression from crusher gradients, and more T2 weighting (kPL,DSE /kPL,FID  = 2.40 ± 0.98, P < 0.0001, N = 7). In summary, the pulse sequence, as well as its interaction with pharmacokinetics and the tissue microenvironment, can impact and be optimized for the measurement of kPL . The data acquisition and analysis pipelines can work synergistically to provide more robust and reproducible kPL measures for future preclinical and clinical studies.

Kinetic modeling of the in vivo pyruvate-to-lactate conversion is crucial to investigating aberrant cancer metabolism that demonstrates Warburg effect modifications. Non-invasive detection of alterations to metabolic flux might offer prognostic value and improve the monitoring of response to treatment. In this clinical research project, hyperpolarized [1-13C] pyruvate was intravenously injected in a total of 10 brain tumor patients to measure its rate of conversion to lactate ( kPL ) and bicarbonate ( kPB ) via echo-planar imaging. Our aim was to investigate new methods to provide kPL and kPB maps with whole-brain coverage. The approach was data-driven and addressed two main issues: selecting the optimal model for fitting our data and determining an appropriate goodness-of-fit metric. The statistical analysis suggested that an input-less model had the best agreement with the data. It was also found that selecting voxels based on post-fitting error criteria provided improved precision and wider spatial coverage compared to using signal-to-noise cutoffs alone.

Background Hyperpolarized (HP) 13 C-pyruvate MRI is a stable-isotope molecular imaging modality that provides real-time assessment of the rate of metabolism through glycolytic pathways in human prostate cancer. Heretofore this imaging modality has been successfully utilized in prostate cancer only in localized disease. This pilot clinical study investigated the feasibility and imaging performance of HP 13 C-pyruvate MR metabolic imaging in prostate cancer patients with metastases to the bone and/or viscera. Methods Six patients who had metastatic castration-resistant prostate cancer were recruited. Carbon-13 MR examination were conducted on a clinical 3T MRI following injection of 250 mM hyperpolarized 13 C-pyruvate, where pyruvate-to-lactate conversion rate ( k PL ) was calculated. Paired metastatic tumor biopsy was performed with histopathological and RNA-seq analyses. Results We observed a high rate of glycolytic metabolism in prostate cancer metastases, with a mean k PL value of 0.020 ± 0.006 (s −1 ) and 0.026 ± 0.000 (s −1 ) in bone ( N = 4) and liver ( N = 2) metastases, respectively. Overall, high k PL showed concordance with biopsy-confirmed high-grade prostate cancer including neuroendocrine differentiation in one case. Interval decrease of k PL from 0.026 at baseline to 0.015 (s −1 ) was observed in a liver metastasis 2 months after the initiation of taxane plus platinum chemotherapy. RNA-seq found higher levels of the lactate dehydrogenase isoform A (Ldha,15.7 ± 0.7) expression relative to the dominant isoform of pyruvate dehydrogenase (Pdha1, 12.8 ± 0.9). Conclusions HP 13 C-pyruvate MRI can detect real-time glycolytic metabolism within prostate cancer metastases, and can measure changes in quantitative k PL values following treatment response at early time points. This first feasibility study supports future clinical studies of HP 13 C-pyruvate MRI in the setting of advanced prostate cancer.

Background and Motivation: Hyperpolarized (HP) 13C MR spectroscopic imaging (MRSI) enables quantitative monitoring of enzyme-catalyzed metabolism in human subjects. Using HP [1-13C]pyruvate, the rate of conversion of pyruvate to lactate (kPL) via lactate dehydrogenase (LDH) can be computed per voxel in patients with progressing liver metastases. However, 13C surface transmit/receive (T/R) coils do not have a homogeneous B1 excitation profile, resulting in a gradient of decreasing flip angles for voxels increasingly farther away from the coil. In calculating the kPL for each voxel, the nominal flip angle can be corrected based off the coil’s B1 excitation profile. The goal of this project was to develop and test a novel computational framework to improve kPL accuracy using B1+ correction in human studies.

The detection and treatment monitoring of inflammatory states remain challenging in part due to the multifactorial mechanisms of immune activation and spectrum of clinical manifestations. Currently, diagnostic strategies tend to be subjective and limited quantitative tools exist to monitor optimal treatment strategies. Pro-inflammatory M1 polarized macrophages exhibit a distinct metabolic glycolytic phenotype compared to the continuum of M2 polarization states. In the present study, the distinct metabolic phenotypes of resting and activated macrophages were successfully characterized and quantified using hyperpolarized carbon-13 (13C) labeled pyruvate and its metabolic products, i.e. lactate, as a biomarker of resting, disease and treated states. Methods: Mouse macrophage J774A.1 cells were used as a model system in an NMR compatible bioreactor to facilitate dynamic hyperpolarized 13C measurements. The glycolytic metabolism of the cells in the quiescent or resting state were compared with macrophages stimulated by lipopolysaccharide, a classical M1 activator using hyperpolarized 13C labeled pyruvate. Additionally, the activated macrophages were also treated with a non-steroidal anti-inflammatory drug to assess the changes in hyperpolarized lactate signal. The hyperpolarized lactate signals were then correlated using biochemical and molecular assays. Results: We first validated our model system of inflammatory cells by the hallmarks of M1 polarization using steady state metabolic profiling with high resolution NMR in conjunction with nitric oxide Greiss assay, enzyme activity, and mRNA expression. Subsequently, we clearly showed that the cutting edge technology of hyperpolarized 13C NMR can be used to detect elevated lactate levels in M1 polarized macrophages in comparison to control and non-steroidal anti-inflammatory drug treated M2 states. Conclusion: Hyperpolarized 13C lactate has the potential to serve as a biomarker to non-invasively detect and quantify pro-inflammatory state of immune regulatory cells and its response to therapy.

MRI using hyperpolarized (HP) carbon-13 pyruvate is being investigated in clinical trials to provide non-invasive measurements of metabolism for cancer and cardiac imaging. In this project, we applied HP [1-13 C]pyruvate dynamic MRI in prostate cancer to measure the conversion from pyruvate to lactate, which is expected to increase in aggressive cancers. The goal of this work was to develop and test analysis methods for improved quantification of this metabolic conversion. In this work, we compared specialized kinetic modeling methods to estimate the pyruvate-to-lactate conversion rate, kPL , as well as the lactate-to-pyruvate area-under-curve (AUC) ratio. The kinetic modeling included an "inputless" method requiring no assumptions regarding the input function, as well as a method incorporating bolus characteristics in the fitting. These were first evaluated with simulated data designed to match human prostate data, where we examined the expected sensitivity of metabolism quantification to variations in kPL , signal-to-noise ratio (SNR), bolus characteristics, relaxation rates, and B1 variability. They were then applied to 17 prostate cancer patient datasets. The simulations indicated that the inputless method with fixed relaxation rates provided high expected accuracy with no sensitivity to bolus characteristics. The AUC ratio showed an undesired strong sensitivity to bolus variations. Fitting the input function as well did not improve accuracy over the inputless method. In vivo results showed qualitatively accurate kPL maps with inputless fitting. The AUC ratio was sensitive to bolus delivery variations. Fitting with the input function showed high variability in parameter maps. Overall, we found the inputless kPL fitting method to be a simple, robust approach for quantification of metabolic conversion following HP [1-13 C]pyruvate injection in human prostate cancer studies. This study also provided initial ranges of HP [1-13 C]pyruvate parameters (SNR, kPL , bolus characteristics) in the human prostate.

PurposeThe purpose of this study was to develop a new 3D dynamic carbon‐13 compressed sensing echoplanar spectroscopic imaging (EPSI) MR sequence and test it in phantoms, animal models, and then in prostate cancer patients to image the metabolic conversion of hyperpolarized [1‐13C]pyruvate to [1‐13C]lactate with whole gland coverage at high spatial and temporal resolution.MethodsA 3D dynamic compressed sensing (CS)‐EPSI sequence with spectral–spatial excitation was designed to meet the required spatial coverage, time and spatial resolution, and RF limitations of the 3T MR scanner for its clinical translation for prostate cancer patient imaging. After phantom testing, animal studies were performed in rats and transgenic mice with prostate cancers. For patient studies, a GE SPINlab polarizer (GE Healthcare, Waukesha, WI) was used to produce hyperpolarized sterile GMP [1‐13C]pyruvate. 3D dynamic 13C CS‐EPSI data were acquired starting 5 s after injection throughout the gland with a spatial resolution of 0.5 cm3, 18 time frames, 2‐s temporal resolution, and 36 s total acquisition time.ResultsThrough preclinical testing, the 3D CS‐EPSI sequence developed in this project was shown to provide the desired spectral, temporal, and spatial 5D HP 13C MR data. In human studies, the 3D dynamic HP CS‐EPSI approach provided first‐ever simultaneously volumetric and dynamic images of the LDH‐catalyzed conversion of [1‐13C]pyruvate to [1‐13C]lactate in a biopsy‐proven prostate cancer patient with full gland coverage.ConclusionThe results demonstrate the feasibility to characterize prostate cancer metabolism in animals, and now patients using this new 3D dynamic HP MR technique to measure kPL, the kinetic rate constant of [1‐13C]pyruvate to [1‐13C]lactate conversion.

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

PurposeHyperpolarized carbon‐13 (13C) metabolic imaging is a noninvasive imaging modality for evaluating real‐time metabolism. The purpose of this study was to develop and implement experimental strategies for using [1‐13C]pyruvate to probe in vivo metabolism for patients with brain tumors and other neurological diseases.MethodsThe 13C radiofrequency coils and pulse sequences were tested in a phantom and were performed using a 3 Tesla whole‐body scanner. Samples of [1‐13C]pyruvate were polarized using a SPINlab system. Dynamic 13C data were acquired from 8 patients previously diagnosed with brain tumors, who had received treatment and were being followed with serial magnetic resonance scans.ResultsThe phantom studies produced good‐quality spectra with a reduction in signal intensity in the center attributed to the reception profiles of the 13C receive coils. Dynamic data obtained from a 3‐cm slice through a patient's brain following injection with [1‐13C]pyruvate showed the anticipated arrival of the agent, its conversion to lactate and bicarbonate, and subsequent reduction in signal intensity. A similar temporal pattern was observed in 2D dynamic patient studies, with signals corresponding to pyruvate, lactate, and bicarbonate being in normal appearing brain, but only pyruvate and lactate being detected in regions corresponding to the anatomical lesion. Physiological monitoring and follow‐up confirmed that there were no adverse events associated with the injection.ConclusionThis study has presented the first application of hyperpolarized 13C metabolic imaging in patients with brain tumor and demonstrated the safety and feasibility of using hyperpolarized [1‐13C]pyruvate to evaluate in vivo brain metabolism. Magn Reson Med 80:864–873, 2018. © 2018 International Society for Magnetic Resonance in Medicine.