Fast metabolite mapping in the pig heart after injection of hyperpolarized 13C‐pyruvate with low‐flip angle balanced steady‐state free precession imaging

The conversion of hyperpolarized ¹³C pyruvate to metabolic products in the Krebs cycle provides valuable information about the metabolic status and the viability of the myocardium. Therefore, imaging methods must be able to spectrally discriminate different ¹³C metabolites. However, the requirement for spectral selectivity conflicts with the demands for rapid image acquisition and high spatial resolution in cardiac imaging. In this work, the feasibility of a balanced steady state free precession sequence with low flip angles was investigated in the pig heart after injection of hyperpolarized ¹³C₁‐pyruvate. Using cardiac gating, it was possible to acquire ¹³C‐bicarbonate images within a single heartbeat (acquisition time 150 ms) without destroying the substrate signal from the hyperpolarized pyruvate. Therefore, the technique may be useful in dynamic studies of cardiac metabolism. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.     

Investigation of tumor hyperpolarized [1‐13C]‐pyruvate dynamics using time‐resolved multiband RF excitation echo‐planar MRSI

Hyperpolarized [1‐¹³C]‐pyruvate is an exciting new agent for the in vivo study of cellular metabolism and a potential cancer biomarker. The nature of the hyperpolarized signal poses unique challenges because of its short duration and the loss of magnetization with every excitation. In this study, we applied a novel and efficient time‐resolved MR spectroscopic imaging (MRSI) method to investigate in a prostate cancer model the localized temporal dynamics of the uptake of [1‐¹³C]‐pyruvate and its conversion to metabolic products, specifically [1‐¹³C]‐lactate. This hyperpolarized ¹³C method used multiband excitation pulses for efficient use of the magnetization. This study demonstrated that regions of tumor were differentially characterized from normal tissue by the lactate dynamics, where tumors showed later lactate detection and longer lactate duration that was statistically significant (P < 0.001). Compared to late‐pathologic‐stage tumors, early‐ to intermediate‐stage tumors demonstrated significantly (P < 0.01) lower lactate total signal‐to‐noise ratio (SNR), with similar temporal dynamic parameters. Hyperpolarized pyruvate dynamics provided uptake, perfusion, and vascularization information on tumors and normal tissue. Large, heterogeneous tumors demonstrated spatially variable uptake of pyruvate and metabolic conversion that was consistent with cellularity and necrosis identified by histology. The results of this study demonstrated the potential of this new hyperpolarized MR dynamic method for improved cancer detection and characterization. Magn Reson Med 63:582–591, 2010. © 2010 Wiley‐Liss, Inc.     

Magnetization transfer measurements of exchange between hyperpolarized [1‐13C]pyruvate and [1‐13C]lactate in a murine lymphoma

Measurements of the conversion of hyperpolarized [1‐¹³C]pyruvate into lactate, in the reaction catalyzed by lactate dehydrogenase, have shown promise as a metabolic marker for the presence of disease and response to treatment. However, it is unclear whether this represents net flux of label from pyruvate to lactate or exchange of isotope between metabolites that are close to chemical equilibrium. Using saturation and inversion transfer experiments, we show that there is significant exchange of label between lactate and pyruvate in a murine lymphoma in vivo. The rate constants estimated from the magnetization transfer experiments, at specific points during the time course of label exchange, were similar to those obtained by fitting the changes in peak intensities during the entire exchange time course to a kinetic model for two‐site exchange. These magnetization transfer experiments may therefore provide an alternative and more rapid way of estimating flux between pyruvate and lactate to serial measurements of pyruvate and lactate ¹³C peak intensities following injection of hyperpolarized [1‐¹³C]pyruvate. Magn Reson Med 63:872–880, 2010. © 2010 Wiley‐Liss, Inc.     

Hyperpolarized 13C spectroscopy and an NMR‐compatible bioreactor system for the investigation of real‐time cellular metabolism

The purpose of this study was to combine a three‐dimensional NMR‐compatible bioreactor with hyperpolarized ¹³C NMR spectroscopy in order to probe cellular metabolism in real time. JM1 (immortalized rat hepatoma) cells were cultured in a three‐dimensional NMR‐compatible fluidized bioreactor. ³¹P spectra were acquired before and after each injection of hyperpolarized [1‐¹³C] pyruvate and subsequent ¹³C spectroscopy at 11.7 T. ¹H and two‐dimensional ¹H‐¹H‐total correlation spectroscopy spectra were acquired from extracts of cells grown in uniformly labeled ¹³C‐glucose, on a 16.4 T, to determine ¹³C fractional enrichment and distribution of ¹³C label. JM1 cells were found to have a high rate of aerobic glycolysis in both two‐dimensional culture and in the bioreactor, with 85% of the ¹³C label from uniformly labeled ¹³C‐glucose being present as either lactate or alanine after 23 h. Flux measurements of pyruvate through lactate dehydrogenase and alanine aminotransferase in the bioreactor system were 12.18 ± 0.49 nmols/sec/10⁸ cells and 2.39 ± 0.30 nmols/sec/10⁸ cells, respectively, were reproducible in the same bioreactor, and were not significantly different over the course of 2 days. Although this preliminary study involved immortalized cells, this combination of technologies can be extended to the real‐time metabolic exploration of primary benign and cancerous cells and tissues prior to and after therapy. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Fast dynamic 3D MR spectroscopic imaging with compressed sensing and multiband excitation pulses for hyperpolarized 13C studies

Hyperpolarized ¹³C MR spectroscopic imaging can detect not only the uptake of the pre‐polarized molecule but also its metabolic products in vivo, thus providing a powerful new method to study cellular metabolism. Imaging the dynamic perfusion and conversion of these metabolites provides additional tissue information but requires methods for efficient hyperpolarization usage and rapid acquisitions. In this work, we have developed a time‐resolved 3D MR spectroscopic imaging method for acquiring hyperpolarized ¹³C data by combining compressed sensing methods for acceleration and multiband excitation pulses to efficiently use the magnetization. This method achieved a 2 sec temporal resolution with full volumetric coverage of a mouse, and metabolites were observed for up to 60 sec following injection of hyperpolarized [1‐¹³C]‐pyruvate. The compressed sensing acquisition used random phase encode gradient blips to create a novel random undersampling pattern tailored to dynamic MR spectroscopic imaging with sampling incoherency in four (time, frequency, and two spatial) dimensions. The reconstruction was also tailored to dynamic MR spectroscopic imaging by applying a temporal wavelet sparsifying transform to exploit the inherent temporal sparsity. Customized multiband excitation pulses were designed with a lower flip angle for the [1‐¹³C]‐pyruvate substrate given its higher concentration than its metabolic products ([1‐¹³C]‐lactate and [1‐¹³C]‐alanine), thus using less hyperpolarization per excitation. This approach has enabled the monitoring of perfusion and uptake of the pyruvate, and the conversion dynamics to lactate and alanine throughout a volume with high spatial and temporal resolution. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.     

The effect of hyperpolarized tracer concentration on myocardial uptake and metabolism

Hyperpolarized ¹³C‐labeled substrates directly provide a source of magnetic resonance (MR) signal to observe the substrates' real‐time uptake and enzymatic conversion. The aim of this study was to optimize the concentration of hyperpolarized [1‐¹³C]pyruvate infused as a metabolic tracer, by observing the mitochondrial conversion of pyruvate to H¹³CO₃^? in heart tissue. Hyperpolarized pyruvate was infused into rats at concentrations between 20 mM and 80 mM and the relationships between [1‐¹³C]lactate, [1‐¹³C]alanine, and H¹³CO₃^? production and the infused pyruvate concentration were investigated. H¹³CO₃^? production reached saturation above 40 mM infused pyruvate concentration, indicating that hyperpolarized MR experiments performed at this concentration maximize the H¹³CO₃^? signal with minimal alterations to in vivo substrate composition. Additionally, the linear dependence of alanine production on pyruvate concentration confirmed that hyperpolarized MR methods in the heart reveal enzyme activity, rather than cellular uptake. H¹³CO₃^? production demonstrated evidence of sigmoidal enzyme kinetics, a reflection of the allosteric nature of the pyruvate dehydrogenase (PDH) enzyme complex. This protocol could be useful to optimize the infused concentration of other hyperpolarized metabolites in different organs, to ensure adequate MR signal with minimum metabolic perturbation. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Metabolite kinetics in C6 rat glioma model using magnetic resonance spectroscopic imaging of hyperpolarized [1‐13C]pyruvate

In addition to an increased lactate‐to‐pyruvate ratio, altered metabolism of a malignant glioma can be further characterized by its kinetics. Spatially resolved dynamic data of pyruvate and lactate from C6‐implanted female Sprague–Dawley rat brain were acquired using a spiral chemical shift imaging sequence after a bolus injection of a hyperpolarized [1‐¹³C]pyruvate. Apparent rate constants for the conversion of pyruvate to lactate in three different regions (glioma, normal appearing brain, and vasculature) were estimated based on a two‐site exchange model. The apparent conversion rate constant was 0.018 ± 0.004 s^?1 (mean ± standard deviation, n = 6) for glioma, 0.009 ± 0.003 s^?1 for normal brain, and 0.005 ± 0.001 s^?1 for vasculature, whereas the lactate‐to‐pyruvate ratio, the metabolic marker used to date to identify tumor regions, was 0.36 ± 0.07 (mean ± SD), 0.24 ± 0.07, and 0.12 ± 0.02 for glioma, normal brain, and vasculature, respectively. The data suggest that the apparent conversion rate better differentiate glioma from normal brain (P = 0.001, n = 6) than the lactate‐to‐pyruvate ratio (P = 0.02). Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.     

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 [1‐¹³C]‐ethyl pyruvate. A maximum tolerated concentration and injection rate were determined, and ¹³C spectroscopic imaging was used to compare the uptake of hyperpolarized [1‐¹³C]‐ethyl pyruvate relative to hyperpolarized [1‐¹³C]‐pyruvate into anesthetized rat brain. Hyperpolarized [1‐¹³C]‐ethyl pyruvate and [1‐¹³C]‐pyruvate metabolic imaging in normal brain is demonstrated and quantified in this feasibility and range‐finding study. Magn Reson Med 63:1137–1143, 2010. © 2010 Wiley‐Liss, Inc.     

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 ¹³C₁‐pyruvate and metabolic products ¹³C₁‐lactate and ¹³C₁‐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. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Cardiac metabolism measured noninvasively by hyperpolarized 13C MRI.

Pyruvate is included in the energy production of the heart muscle and is metabolized into lactate, alanine, and CO(2) in equilibrium with HCO(3) (-). The aim of this study was to evaluate the feasibility of using (13)C hyperpolarization enhanced MRI to monitor pyruvate metabolism in the heart during an ischemic episode. The left circumflex artery of pigs (4 months, male, 29-34 kg) was occluded for 15 or 45 min followed by 2 hr of reperfusion. Pigs were examined by (13)C chemical shift imaging following intravenous injection of 1-(13)C pyruvate. (13)C chemical shift MR imaging was used in order to visualize the local concentrations of the metabolites. After a 15-min occlusion (no infarct) the bicarbonate signal level in the affected area was reduced (25-44%) compared with the normal myocardium. Alanine signal level was normal. After a 45-min occlusion (infarction) the bicarbonate signal was almost absent (0.2-11%) and the alanine signal was reduced (27-51%). Due to image-folding artifacts the data obtained for lactate were inconclusive. These studies demonstrate that cardiac metabolic imaging with hyperpolarized 1-(13)C-pyruvate is feasible. The changes in concentrations of the metabolites within a minute after injection can be detected and metabolic maps constructed.     

Tumor imaging using hyperpolarized 13C magnetic resonance spectroscopy

Dynamic nuclear polarization is an emerging technique for increasing the sensitivity of magnetic resonance imaging and spectroscopy, particularly for low‐γ nuclei. The technique has been applied recently to a number of ¹³C‐labeled cell metabolites in biological systems: the increase in signal‐to‐noise allows the spatial distribution of an injected molecule to be imaged as well as its metabolic product or products. This review highlights the most significant molecules investigated to date in preclinical cancer models, either in terms of their demonstrated metabolism in vivo or the biological processes that they can probe. In particular, label exchange between hyperpolarized ¹³C‐labeled pyruvate and lactate, catalyzed by lactate dehydrogenase, has been shown to have a number of potential applications. Finally, techniques to image these molecules are also discussed as well as methods that may extend the lifetime of the hyperpolarized signal. Hyperpolarized magnetic resonance imaging and magnetic resonance spectroscopic imaging have shown great promise for the imaging of cancer in preclinical work, both for diagnosis and for monitoring therapy response. If the challenges in translating this technique to human imaging can be overcome, then it has the potential to significantly alter the management of cancer patients. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Detecting response of rat C6 glioma tumors to radiotherapy using hyperpolarized [1‐13C]pyruvate and 13C magnetic resonance spectroscopic imaging

We show here that hyperpolarized [1‐¹³C]pyruvate can be used to detect treatment response in a glioma tumor model; a tumor type where detection of response with ¹⁸fluoro‐2‐deoxyglucose, using positron emission tomography, is limited by the high background signals from normal brain tissue. ¹³C chemical shift images acquired following intravenous injection of hyperpolarized [1‐¹³C]pyruvate into rats with implanted C6 gliomas showed significant labeling of lactate within the tumors but comparatively low levels in surrounding brain.Labeled pyruvate was observed at high levels in blood vessels above the brain and from other major vessels elsewhere but was detected at only low levels in tumor and brain.The ratio of hyperpolarized ¹³C label in tumor lactate compared to the maximum pyruvate signal in the blood vessels was decreased from 0.38 ± 0.16 to 0.23 ± 0.13, (a reduction of 34%) by 72 h following whole brain irradiation with 15 Gy. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.     

Inhibition of carbohydrate oxidation during the first minute of reperfusion after brief ischemia: NMR detection of hyperpolarized 13CO2 and H13CO

Isolated rat hearts were studied by ³¹P NMR and ¹³C NMR. Hyperpolarized [1‐¹³C]pyruvate was supplied to control normoxic hearts and production of [1‐¹³C]lactate, [1‐¹³C]alanine, ¹³CO₂ and H¹³CO was monitored with 1‐s temporal resolution. Hearts were also subjected to 10 min of global ischemia followed by reperfusion. Developed pressure, heart rate, oxygen consumption, [ATP], [phosphocreatine], and pH recovered within 3 min after the ischemic period. During the first 90 s of reperfusion, [1‐¹³C]alanine and [1‐¹³C]lactate appeared rapidly, demonstrating metabolism of pyruvate through two enzymes largely confined to the cytosol, alanine aminotransferase, and lactate dehydrogenase. ¹³CO₂ and H¹³CO were not detected. Late after ischemia and reperfusion, the products of pyruvate dehydrogenase, ¹³CO₂ and H¹³CO were easily detected. Using this multinuclear NMR approach, we established that during the first 90 s of reperfusion PDH flux is essentially zero and recovers within 20 min in reversibly‐injured myocardium. Magn Reson Med 60:1029–1036, 2008. © 2008 Wiley‐Liss, Inc.     

Detection of early response to temozolomide treatment in brain tumors using hyperpolarized 13C MR metabolic imaging

Purpose:

To demonstrate the feasibility of using DNP hyperpolarized [1‐¹³C]‐pyruvate to measure early response to temozolomide (TMZ) therapy using an orthotopic human glioblastoma xenograft model.

Materials and Methods:

Twenty athymic rats with intracranial implantation of human glioblastoma cells were divided into two groups: one group received an oral administration of 100 mg/kg TMZ (n = 10) and the control group received vehicle only (n = 10). ¹³C 3D magnetic resonance spectroscopic imaging (MRSI) data were acquired following injection of 2.5 mL (100 mM) hyperpolarized [1‐¹³C]‐pyruvate using a 3T scanner prior to treatment (day D0), at D1 (days from treatment) or D2.

Results:

Tumor metabolism as assessed by the ratio of lactate to pyruvate (Lac/Pyr) was significantly altered at D1 for the TMZ‐treated group but tumor volume did not show a reduction until D5 to D7. The percent change in Lac/Pyr from baseline was statistically different between the two groups at D1 and D2 (P < 0.008), while percent tumor volume was not (P > 0.2).

Conclusion:

The results from this study suggest that metabolic imaging with hyperpolarized [1‐¹³C]‐pyruvate may provide a unique tool that clinical neuro‐oncologists can use in the future to monitor tumor response to therapy for patients with brain tumors. J. Magn. Reson. Imaging 2011;33:1284–1290. © 2011 Wiley‐Liss, Inc.     

Detection of radiation‐induced lung injury using hyperpolarized 13C magnetic resonance spectroscopy and imaging

Radiation‐induced lung injury limits radiotherapy of thoracic cancers. Detection of radiation pneumonitis associated with early radiation‐induced lung injury (2–4 weeks postirradiation) may provide an opportunity to adjust treatment, before the onset of acute pneumonitis and/or irreversible fibrosis. In this study, localized magnetic resonance (MR) spectroscopy and imaging of hyperpolarized ¹³C‐pyruvate (pyruvate) and ¹³C‐lactate (lactate) were performed in the thorax and kidney regions of rats 2 weeks following whole‐thorax irradiation (14 Gy). Lactate‐to‐pyruvate signal ratio was observed to increase by 110% (P < 0.01), 57% (P < 0.02), and 107% (P < 0.01), respectively, in the thorax, lung, and heart tissues of the radiated rats compared with healthy age‐matched rats. This was consistent with lung inflammation confirmed using cell micrographs of bronchioalveolar lavage specimens and decreases in arterial oxygen partial pressure (p_aO₂), indicative of hypoxia. No statistically significant difference was observed in either lactate‐to‐pyruvate signal ratios in the kidney region (P = 0.50) between the healthy (0.215 ± 0.100) and radiated cohorts (0.215 ± 0.054) or in blood lactate levels (P = 0.69) in the healthy (1.255 ± 0.247 mmol/L) and the radiated cohorts (1.325 ± 0.214 mmol/L), confirming that the injury is localized to the thorax. This work demonstrates the feasibility of hyperpolarized ¹³C metabolic MR spectroscopy and imaging for detection of early radiation‐induced lung injury. Magn Reson Med 70:601–609, 2013. © 2012 Wiley Periodicals, Inc.     

Methods for metabolic evaluation of prostate cancer cells using proton and 13C HR‐MAS spectroscopy and [3‐13C] pyruvate as a metabolic substrate

Prostate cancer has been shown to undergo unique metabolic changes associated with neoplastic transformation, with associated changes in citrate, alanine, and lactate concentrations. ¹³C high resolution‐magic angle spinning (HR‐MAS) spectroscopy provides an opportunity to simultaneously investigate the metabolic pathways implicated in these changes by using ¹³C‐labeled substrates as metabolic probes. In this work, a method to reproducibly interrogate metabolism in prostate cancer cells in primary culture was developed using HR‐MAS spectroscopy. Optimization of cell culture protocols, labeling parameters, harvesting, storage, and transfer was performed. Using [3‐¹³C] pyruvate as a metabolic probe, ¹H and ¹³C HR‐MAS spectroscopy was used to quantify the net amount and fractional enrichment of several labeled metabolites that evolved in multiple cell samples from each of five different prostate cancers. Average enrichment across all cancers was 32.4 ± 5.4% for [3‐¹³C] alanine, 24.5 ± 5.4% for [4‐¹³C] glutamate, 9.1 ± 2.5% for [3‐¹³C] glutamate, 25.2 ± 5.7% for [3‐¹³C] aspartate, and 4.2 ± 1.0% for [3‐¹³C] lactate. Cell samples from the same parent population demonstrated reproducible fractional enrichments of alanine, glutamate, and aspartate to within 12%, 10%, and 10%, respectively. Furthermore, the cells produced a significant amount of [4‐¹³C] glutamate, which supports the bioenergetic theory for prostate cancer. These methods will allow further characterization of metabolic properties of prostate cancer cells in the future. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

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 ¹³C 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 [1‐¹³C]‐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. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.     

Evaluation of heterogeneous metabolic profile in an orthotopic human glioblastoma xenograft model using compressed sensing hyperpolarized 3D 13C magnetic resonance spectroscopic imaging

High resolution compressed sensing hyperpolarized ¹³C magnetic resonance spectroscopic imaging was applied in orthotopic human glioblastoma xenografts for quantitative assessment of spatial variations in ¹³C metabolic profiles and comparison with histopathology. A new compressed sensing sampling design with a factor of 3.72 acceleration was implemented to enable a factor of 4 increase in spatial resolution. Compressed sensing 3D ¹³C magnetic resonance spectroscopic imaging data were acquired from a phantom and 10 tumor‐bearing rats following injection of hyperpolarized [1‐¹³C]‐pyruvate using a 3T scanner. The ¹³C metabolic profiles were compared with hematoxylin and eosin staining and carbonic anhydrase 9 staining. The high‐resolution compressed sensing ¹³C magnetic resonance spectroscopic imaging data enabled the differentiation of distinct ¹³C metabolite patterns within abnormal tissues with high specificity in similar scan times compared to the fully sampled method. The results from pathology confirmed the different characteristics of ¹³C metabolic profiles between viable, non‐necrotic, nonhypoxic tumor, and necrotic, hypoxic tissue. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Kinetic modeling of hyperpolarized 13C pyruvate metabolism in tumors using a measured arterial input function

Mathematical models are required to estimate kinetic parameters of [1‐¹³C] pyruvate‐lactate interconversion from magnetic resonance spectroscopy data. One‐ or two‐way exchange models utilizing a hypothetical approximation to the true arterial input function (AIF), (e.g. an ideal ‘box‐car’ function) have been used previously. We present a method for direct measurement of the AIF in the rat. The hyperpolarized [1‐¹³C] pyruvate signal was measured in arterial blood as it was continuously withdrawn through a small chamber. The measured signal was corrected for T₁ relaxation of pyruvate, RF pulses and dispersion of blood in the chamber to allow for the estimation of the direct AIF. Using direct AIF, rather than the commonly used box‐car AIF, provided realistic estimates of the rate constant of conversion of pyruvate to lactate, k_pl, the rate constant of conversion of lactate to pyruvate k_lp, the clearance rate constant of pyruvate from blood to tissue, K_ip, and the relaxation rate of lactate T_1la. Since no lactate signal was present in blood, it was possible to use a simple precursor‐product relationship, with the tumor tissue pyruvate time‐course as the input for the lactate time‐course. This provided a robust estimate of k_pl, similar to that obtained using a directly measured AIF. Magn Reson Med, 70:943–953, 2013. © 2012 Wiley Periodicals, Inc.     

In vivo 13 carbon metabolic imaging at 3T with hyperpolarized 13C-1-pyruvate.

We present for the first time dynamic spectra and spectroscopic images acquired in normal rats at 3T following the injection of (13)C-1-pyruvate that was hyperpolarized by the dynamic nuclear polarization (DNP) method. Spectroscopic sampling was optimized for signal-to-noise ratio (SNR) and for spectral resolution of (13)C-1-pyruvate and its metabolic products (13)C-1-alanine, (13)C-1-lactate, and (13)C-bicarbonate. Dynamic spectra in rats were collected with a temporal resolution of 3 s from a 90-mm axial slab using a dual (1)H-(13)C quadrature birdcage coil to observe the combined effects of metabolism, flow, and T(1) relaxation. In separate experiments, spectroscopic imaging data were obtained during a 17-s acquisition of a 20-mm axial slice centered on the rat kidney region to provide information on the spatial distribution of the metabolites. Conversion of pyruvate to lactate, alanine, and bicarbonate occurred within a minute of injection. Alanine was observed primarily in skeletal muscle and liver, while pyruvate, lactate, and bicarbonate concentrations were relatively high in the vasculature and kidneys. In contrast to earlier work at 1.5 T, bicarbonate was routinely observed in skeletal muscle as well as the kidney and vasculature.