3D quantitative myocardial perfusion imaging with hyperpolarized HP001(bis-1,1-(hydroxymethyl)-[1-13C]cyclopropane-d8): Application of gradient echo and balanced SSFP sequences.

PURPOSE: This study aims to show the viability of conducting three-dimensional (3D) myocardial perfusion quantification covering the entire heart using both GRE and bSSFP sequences with hyperpolarized HP001. METHODS: A GRE sequence and a bSSFP sequence, both with a stack-of-spirals readout, were designed and applied to three pigs. The images were reconstructed using 13 $$ {}^{13} $$ C coil sensitivity maps measured in a phantom experiment. Perfusion was quantified using a constrained decomposition method, and the estimated rest/stress perfusion values from 13 $$ {}^{13} $$ C GRE/bSSFP and Dynamic contrast-enhanced MRI (DCE-MRI) were individually analyzed through histograms and the mean perfusion values were compared with reference values obtained from PET( 15 $$ {}^{15} $$ O-water). The Myocardial Perfusion Reserve Index (MPRI) was estimated for 13 $$ {}^{13} $$ C GRE/bSSFP and DCE-MRI and compared with the reference values. RESULTS: Perfusion values, estimated by both DCE and 13 $$ {}^{13} $$ C MRI, were found to be lower than reference values. However, DCE-MRI's estimated perfusion values were closer to the reference values than those obtained from 13 $$ {}^{13} $$ C MRI. In the case of MPRI estimation, the 13 $$ {}^{13} $$ C estimated MPRI values (GRE/bSSFP: 2.3/2.0) more closely align with the literature value (around 3) than the DCE estimated MPRI value (1.6). CONCLUSION: This study demonstrated the feasibility of 3D whole-heart myocardial perfusion quantification using hyperpolarized HP001 with both GRE and bSSFP sequences. The 13 $$ {}^{13} $$ C perfusion measurements underestimated perfusion values compared to the 15 $$ {}^{15} $$ O PET literature value, while the 13 $$ {}^{13} $$ C estimated MPRI value aligned better with the literature. This preliminary result indicates 13 $$ {}^{13} $$ C imaging may more accurately estimate MPRI values compared to DCE-MRI.

Assessment of focal renal ischemia-reperfusion injury in a porcine model using hyperpolarized [1-13 C]pyruvate MRI.

PURPOSE: Ischemic injury in the kidney is a common pathophysiological event associated with both acute kidney injury and chronic kidney disease; however, regional ischemia-reperfusion as seen in thromboembolic renal disease is often undetectable and thus subclinical. Here, we assessed the metabolic alterations following subclinical focal ischemia-reperfusion injury with hyperpolarized [1-13 C]pyruvate MRI in a porcine model. METHODS: Five pigs were subjected to 60 min of focal kidney ischemia. After 90 min of reperfusion, a multiparametric proton MRI protocol was performed on a clinical 3T scanner system. Metabolism was evaluated using 13 C MRI following infusion of hyperpolarized [1-13 C]pyruvate. Ratios of pyruvate to its detectable metabolites (lactate, bicarbonate, and alanine) were used to quantify metabolism. RESULTS: The focal ischemia-reperfusion injury resulted in injured areas with a mean size of 0.971 cm3 (±1.019). Compared with the contralateral kidney, the injured areas demonstrated restricted diffusion (1269 ± 83.59 × 10-6 mm2 /s vs. 1530 ± 52.73 × 10-6 mm2 /s; p = 0.006) and decreased perfusion (158.8 ± 29.4 mL/100 mL/min vs. 274 ± 63.1 mL/100 mL/min; p = 0.014). In the metabolic assessment, the injured areas displayed increased lactate/pyruvate ratios compared with the entire ipsilateral and the contralateral kidney (0.35 ± 0.13 vs. 0.27 ± 0.1 vs. 0.25 ± 0.1; p = 0.0086). Alanine/pyruvate ratio was unaltered, and we were unable to quantify bicarbonate due to low signal. CONCLUSION: MRI with hyperpolarized [1-13 C]pyruvate in a clinical setup is capable of detecting the acute, subtle, focal metabolic changes following ischemia. This may prove to be a valuable future addition to the renal MRI suite.

A cryogenic 14-channel 13 C receiver array for 3T human head imaging.

PURPOSE: This article presents a novel 14-channel receive-only array for 13 C human head imaging at 3 T that explores the SNR gain by operating at cryogenic temperature cooled by liquid nitrogen. METHODS: Cryostats are developed to evaluate single-coil bench SNR performance and cool the 14-channel array with liquid nitrogen while having enough thermal insulation between the coils and the sample. The temperature distribution for the coil array is measured. Circuits are adapted to the -189°C environment and implemented in the 14-channel array. 13 C images are acquired with the array at cryogenic and room temperature in a 3T scanner. RESULTS: Compared with room temperature, the array at cryogenic temperature provides 27%-168% SNR improvement over all voxels and 47% SNR improvement near the image center. The measurements show a decrease of the element noise correlation at cryogenic temperature. CONCLUSION: It is demonstrated that higher SNR can be achieved by cryogenically cooling the 14-channel array. A cryogenic array suitable for clinical imaging can be further developed on the array proposed. The cryogenic coil array is most likely suited for scenarios in which high SNR deep in a head and decent SNR on the periphery are required.

The effects of methylene blue during and after cardiac arrest in a porcine model; a randomized, blinded, placebo-controlled study.

PURPOSE: To evaluate the effect of methylene blue administered as a bolus on return of spontaneous circulation (ROSC), lactate levels, vasopressor requirements, and markers of neurological injury in a clinically relevant pig model of cardiac arrest. MATERIALS AND METHODS: 40 anesthetized pigs were subjected to acute myocardial infarction and 7 min of untreated cardiac arrest. Animals were randomized into three groups: one group received saline only (controls), one group received 2 mg/kg methylene blue and saline (MB + saline), and one group received two doses of 2 mg/kg methylene blue (MB + MB). The first intervention was given after the 3rd rhythm analysis, while the second dose was administered one hour after achieving ROSC. Animals underwent intensive care and observation for six hours, followed by cerebral magnetic resonance imaging (MRI). The primary outcome for this study was development in lactate levels after cardiac arrest. Categorical data were compared using Fisher's exact test and pointwise data were analyzed using one-way analysis of variance (ANOVA) or equivalent non-parametric test. Continuous data collected over time were analyzed using a linear mixed effects model. A value of p < .05 was considered statistically significant. RESULTS: Lactate levels increased in all groups after cardiac arrest and resuscitation, however lactate levels in the MB + MB group decreased significantly faster compared with the control group (p = .007) and the MB + saline group (p = .02). The proportion of animals achieving initial ROSC was similar across groups: 11/13 (85%) in the control group, 10/13 (77%) in the MB + saline group, and 12/14 (86%) in the MB + MB group (p = .81). Time to ROSC did not differ between groups (p = .67). There was no significant difference in accumulated norepinephrine dose between groups (p = .15). Cerebral glycerol levels were significantly lower in the MB + MB group after resuscitation compared with control group (p = .03). However, MRI data revealed no difference in apparent diffusion coefficient, cerebral blood flow, or dynamic contrast enhanced MR perfusion between groups. CONCLUSION: Treatment with a bolus of methylene blue during cardiac arrest and after resuscitation did not significantly improve hemodynamic function. A bolus of methylene blue did not yield the neuroprotective effects that have previously been described in animals receiving methylene blue as an infusion.

The number of glomeruli and pyruvate metabolism is not strongly coupled in the healthy rat kidney.

PURPOSE: The number of glomeruli is different in men and women, as they also present different prevalence and progression of chronic kidney disease. A recent study has demonstrated a potential difference in renal metabolism between sexes, and a potential explanation could be the differences in glomeruli number. This study investigates the potential correlation between glomerular number and pyruvate metabolism in healthy kidneys. METHODS: This study is an experimental study with rats (N = 12). We used cationized-ferritin MRI to visualize and count glomeruli and hyperpolarized [1-13 C]pyruvate to map the metabolism. Dynamic contrast-enhanced MRI was used to analyze kidney hemodynamics using gadolinium tracer. RESULTS: Data showed no or subtle correlation between the number of glomeruli and the pyruvate metabolism. Minor differences were observed in the number of glomeruli (female = 24,509 vs. male = 26 350; p = .16), renal plasma flow (female = 606.6 vs. male= 455.7 ml/min/100 g; p = .18), and volume of distribution (female = 87.44 vs. male = 76.61 ml/100 ml; p = .54) between sexes. Mean transit time was significantly prolonged in males compared with females (female = 8.868 s vs. male = 10.63 s; p = .04). CONCLUSION: No strong statistically significant correlation between the number of glomeruli and the pyruvate metabolism was found in healthy rat kidneys.

Remodeling after myocardial infarction and effects of heart failure treatment investigated by hyperpolarized [1-13 C]pyruvate magnetic resonance spectroscopy.

PURPOSE: Hyperpolarized [1-13 C]pyruvate MRS can measure cardiac metabolism in vivo. We investigated whether [1-13 C]pyruvate MRS could predict left ventricular remodeling following myocardial infarction (MI), long-term left ventricular effects of heart failure medication, and could identify responders to treatment. METHODS: Thirty-five rats were scanned with hyperpolarized [1-13 C]pyruvate MRS 3 days after MI or sham surgery. The animals were re-examined after 30 days of therapy with ß-blockers and ACE-inhibitors (active group, n = 12), placebo treatment (placebo group, n = 13) or no treatment (sham group, n = 10). Furthermore, heart tissue mitochondrial respiratory capacity was assessed by high-resolution respirometry. Metabolic results were compared between groups, over time and correlated to functional MR data at each time point. RESULTS: At 30 ± 0.5 days post MI, left ventricular ejection fraction (LVEF) differed between groups (sham, 77% ± 1%; placebo, 52% ± 3%; active, 63% ± 2%, P < .001). Cardiac metabolism, measured by both hyperpolarized [1-13 C]pyruvate MRS and respirometry, neither differed between groups nor between baseline and follow-up. Three days post MI, low bicarbonate + CO2 /pyruvate ratio was associated with low LVEF. At follow-up, in the active group, a poor recovery of LVEF was associated with high bicarbonate + CO2 /pyruvate ratio, as measured by hyperpolarized MRS. CONCLUSION: In a rat model of moderate heart failure, medical treatment improved function, but did not on average influence [1-13 C]pyruvate flux as measured by MRS; however, responders to heart failure medication had reduced capacity for carbohydrate metabolism.

Concentration-dependent effects of dichloroacetate in type 2 diabetic hearts assessed by hyperpolarized [1-13 C]-pyruvate magnetic resonance imaging.

Personalized medicine or individualized therapy promises a paradigm shift in healthcare. This is particularly true in complex and multifactorial diseases such as diabetes and the multitude of related pathophysiological complications. Diabetic cardiomyopathy represents an emerging condition that could be effectively treated if better diagnostic and, in particular, better therapeutic monitoring tools were available. In this study, we investigate the ability to differentiate low and high doses of metabolically targeted therapy in an obese type 2 diabetic rat model. Low-dose dichloroacetate (DCA) treatment was associated with increased lactate production, while no or little change was seen in bicarbonate production. High-dose DCA treatment was associated with a significant metabolic switch towards increased bicarbonate production. These findings support further studies using hyperpolarized [1-13 C]-pyruvate magnetic resonance imaging to differentiate treatment effects and thus allow for personalized titration of therapeutics.

Development of a human heart-sized perfusion system for metabolic imaging studies using hyperpolarized [1-13 C]pyruvate MRI.

PURPOSE: Increasing worldwide demand for cardiac transplantation has spurred new developments to increase the donor pool. Normothermic preservation of heart grafts for transplantation is an emerging strategy to improve the utilization of marginal grafts. Hyperpolarized MR using metabolic tracers such as [1-13 C]pyruvate, provide a novel means of investigating metabolic status without the use of ionizing radiation. We demonstrate the use of this methodology to examine ex vivo perfused porcine heart grafts. METHODS: Hearts from three 40-kg Danish domestic pigs were harvested and subsequently perfused in Langendorff mode under normothermic conditions, using an MR-compatible perfusion system adapted to the heart. Proton MRI and hyperpolarized [1-13 C]pyruvate were used to investigate and quantify the functional and metabolic status of the grafts. RESULTS: Hearts were perfused with whole blood for 120 min, using a dynamic contrast-enhanced perfusion experiment to verify successful myocardial perfusion. Hyperpolarized [1-13 C]pyruvate MRI was used to assess the metabolic state of the myocardium. Functional assessment was performed using CINE imaging and ventricular pressure data. High lactate and modest alanine levels were observed in the hyperpolarized experiment. The functional assessment produced reduced functional parameters. This suggests an altered functional and metabolic profile compared with corresponding in vivo values. CONCLUSION: We investigated the metabolic and functional status of machine-perfused porcine hearts. Utilizing hyperpolarized methodology to acquire detailed myocardial metabolic information-in combination with already established MR methods for cardiac investigation-provides a powerful tool to aid the progress of donor heart preservation.

Hyperpolarized pyruvate to measure the influence of PKM2 activation on glucose metabolism in the healthy kidney.

The purpose of the current study was to investigate if hyperpolarized [1-13 C]pyruvate can inform us on the metabolic consequences for the kidney glucose metabolism upon treatment with the pyruvate kinase M2 (PKM2) activator TEPP-46, which has shown promise as a novel therapeutic target for diabetic nephropathy. A healthy male Wistar rat model was employed to study the conversion of [1-13 C]pyruvate to [1-13 C]lactate in the kidney 2 and 4 h after treatment with TEPP-46. All rats were scanned with hyperpolarized [1-13 C]pyruvate kidney MR and vital parameters and blood samples were taken after scanning. The PKM2 activator TEPP-46 increases the glycolytic activity in the kidneys, leading to an increased lactate production, as seen by hyperpolarized pyruvate-to-lactate conversion. The results are supported by an increase in blood lactate, a decreased blood glucose level and an increased pyruvate kinase (PK) activity. The metabolic changes observed in both kidneys following treatment with TEPP-46 are largely independent of renal function and could as such represent a new and extremely sensitive metabolic readout for future drugs targeting PKM2. These results warrant further studies in disease models to evaluate if [1-13 C]pyruvate-to-[1-13 C]lactate conversion can predict treatment outcome.

Hyperpolarized [1-13 C]pyruvate combined with the hyperinsulinaemic euglycaemic and hypoglycaemic clamp technique in skeletal muscle in a large animal model.

NEW FINDINGS: What is the central question of this study? Is it possible to combine the hyperpolarized magnetic resonance technique and the hyperinsulinaemic clamp method in order to evaluate skeletal muscle metabolism in a large animal model? What is the main finding and its importance? The logistical set-up is possible, and we found substantial increments in glucose infusion rates representing skeletal muscle glucose uptake but no differences in ratios of [1-13 C]lactate to [1-13 C]pyruvate, [1-13 C]alanine to [1-13 C]pyruvate, and 13 C-bicarbonate to [1-13 C]pyruvate, implying that the hyperpolarization technique might not be optimal for detecting effects of insulin in skeletal muscle of anaesthetized animals, which is of significance for future studies. ABSTRACT: In skeletal muscle, glucose metabolism is tightly regulated by the reciprocal relationship between insulin and adrenaline, with pyruvate being at the intersection of both pathways. Hyperpolarized magnetic resonance (hMR) is a new approach to gain insights into these pathways, and human trials involving hMR and skeletal muscle metabolism are imminent. We aimed to combine the hyperinsulinaemic clamp technique and hMR in a large animal model resembling human physiology. Fifteen anaesthetized pigs were randomized to saline (control group), hyperinsulinaemic euglycaemic clamp technique (HE group) or hyperinsulinaemic hypoglycaemic clamp technique (HH group). Skeletal muscle metabolism was evaluated by hyperpolarized [1-13 C]pyruvate injection and hMR at baseline and after intervention. The glucose infusion rate per kilogram increased by a statistically significant amount in the HE and HH groups (P < 0.001). Hyperpolarized magnetic resonance showed no statistically significant changes in metabolite ratios: [1-13 C]lactate to [1-13 C]pyruvate in the HH group versus control group (P = 0.19); and 13 C-bicarbonate to [1-13 C]pyruvate ratio in the HE group versus the control group (P = 0.12). We found evidence of profound increments in glucose infusion rates representing skeletal muscle glucose uptake, but interestingly, no signs of significant changes in aerobic and anaerobic metabolism using hMR. These results imply that hyperpolarized [1-13 C]pyruvate might not be optimally suited to detect effects of insulin in anaesthetized resting skeletal muscle, which is of significance for future studies.

Di-chromatic interpolation of magnetic resonance metabolic images.

OBJECTIVE: Magnetic resonance imaging with hyperpolarized contrast agents can provide unprecedented in vivo measurements of metabolism, but yields images that are lower resolution than that achieved with proton anatomical imaging. In order to spatially localize the metabolic activity, the metabolic image must be interpolated to the size of the proton image. The most common methods for choosing the unknown values rely exclusively on values of the original uninterpolated image. METHODS: In this work, we present an alternative method that uses the higher-resolution proton image to provide additional spatial structure. The interpolated image is the result of a convex optimization algorithm which is solved with the fast iterative shrinkage threshold algorithm (FISTA). RESULTS: Results are shown with images of hyperpolarized pyruvate, lactate, and bicarbonate using data of the heart and brain from healthy human volunteers, a healthy porcine heart, and a human with prostate cancer.

Autonomous cryogenic RF receive coil for 13 C imaging of rodents at 3 T.

PURPOSE: To develop an autonomous, in-bore, MR-compatible cryostat cooled with liquid nitrogen that provides full-day operation, and to demonstrate that the theoretical signal-to-noise benefit can be achieved for 13 C imaging at 3 T (32.13 MHz). METHODS: The cryogenic setup uses a vacuum-insulated fiberglass cryostat, which indirectly cools a cold finger where the RF coil is attached. The cryostat was evacuated before use and had a reservoir of liquid nitrogen for full-day operation. A 30 × 40 mm2 copper coil was mounted inside the cryostat with a 3-mm distance to the sample. Two examples of in vivo experiments of rat brain metabolism after a hyperpolarized [1-13 C]pyruvate injection are reported. RESULTS: A coil Q-factor ratio of Q88K /Q290K = 550/280 was obtained, and the theoretical SNR enhancement was verified with MR measurements. We achieved a coil temperature of 88 K and a preamplifier temperature of 77 K. A 2-fold overall SNR enhancement was achieved, compared with the best case at room temperature. The thermal performance of the coil was adequate for in vivo experiments, with an autonomy of 5 hours consuming 6 L of LN2 , extendable to over 12 hours by LN2 refilling. CONCLUSION: Cryogenic surface coils can be highly beneficial for 13 C imaging, provided that the coil-to-sample distance remains short. An autonomous, in-bore cryostat was developed that achieved the theoretical improvement in SNR.

Graft assessment of the ex vivo perfused porcine kidney using hyperpolarized [1-13 C]pyruvate.

PURPOSE: Normothermic perfusion is an emerging strategy for donor organ preservation and therapy, incited by the high worldwide demand for organs for transplantation. Hyperpolarized MRI and MRS using [1-13 C]pyruvate and other 13 C-labeled molecules pose a novel way to acquire highly detailed information about metabolism and function in a noninvasive manner. This study investigates the use of this methodology as a means to study and monitor the state of ex vivo perfused porcine kidneys, in the context of kidney graft preservation research. METHODS: Kidneys from four 40-kg Danish domestic pigs were perfused ex vivo with whole blood under normothermic conditions, using an MR-compatible perfusion system. Kidneys were investigated using 1 H MRI as well as hyperpolarized [1-13 C]pyruvate MRI and MRS. Using the acquired anatomical, functional and metabolic data, the state of the ex vivo perfused porcine kidney could be quantified. RESULTS: Four kidneys were successfully perfused for 120 minutes and verified using a DCE perfusion experiment. Renal metabolism was examined using hyperpolarized [1-13 C]pyruvate MRI and MRS, and displayed an apparent reduction in pyruvate turnover compared with the usual case in vivo. Perfusion and blood gas parameters were in the normal ex vivo range. CONCLUSION: This study demonstrates the ability to monitor ex vivo graft metabolism and function in a large animal model, resembling human renal physiology. The ability of hyperpolarized MRI and MRS to directly compare the metabolic state of an organ in vivo and ex vivo, in combination with the simple MR implementation of normothermic perfusion, renders this methodology a powerful future tool for graft preservation research.

Three-dimensional accelerated acquisition for hyperpolarized 13 C MR with blipped stack-of-spirals and conjugate-gradient SENSE.

PURPOSE: To test a new parallel imaging strategy for acceleration of hyperpolarized 13 C MR acquisitions based on a 3D blipped stack-of-spirals trajectory and conjugate-gradient SENSE reconstruction with precalibrated sensitivities. METHODS: The blipped stack-of-spirals trajectory was developed for an acceleration factor of 4, based on an undersampled stack-of-spirals with gradient blips during spiral readout. The trajectory was developed with volumetric coverage of a large FOV and with high spatial resolution. High temporal resolution was attained through spectral-spatial excitation and 4 excitations per volume. The blipped stack-of-spirals was evaluated in simulations and phantom experiments. Next, the method was evaluated for kidney and cardiac imaging in 2 separate healthy pigs. RESULTS: Simulation and phantom results showed successful acquisition and reconstruction, but also revealed reconstruction challenges for certain locations and for wide signal sources. For the kidney experiment, the accelerated acquisition showed high similarity to 2 separately acquired fully sampled data sets with matched spatial and temporal resolution, respectively. For the cardiac experiment, the accelerated acquisition proved able to map each metabolite in 3 dimensions within a single cardiac cycle. CONCLUSION: The proposed method demonstrated effective mapping of metabolism in both kidneys and the heart of healthy pigs. Limitations seen in phantom experiments, may be irrelevant for most clinical applications, but should be kept in mind as well as reconstruction challenges related to residual aliasing. All in all, we show that the blipped stack-of-spirals is a relevant parallel imaging method for hyperpolarized human imaging, facilitating better insights into metabolism compared with nonaccelerated acquisition.

The hemodynamic and metabolic effects of spironolactone treatment in acute kidney injury assessed by hyperpolarized MRI.

Renal ischemia-reperfusion injury (IRI) is one of the most common types of acute kidney injury. Spironolactone has shown promising kidney protective effects in renal IRI in rats. We investigated the hemodynamic and metabolic effects of spironolactone (100 mg/kg) administered immediately after 40 min unilateral kidney ischemia in rats. Hyperpolarized MRI using co-polarized [1-13 C]pyruvate and [13 C,15 N2 ]urea as well as 1 H dynamic contrast-enhanced (DCE) MRI was performed 24 h after induction of ischemia. We found a significant decrease in renal blood flow (RBF) in the ischemic kidney compared with the contralateral one measured using DCE and [13 C,15 N2 ]urea. The RBF measured using [1-13 C]pyruvate and [13 C,15 N2 ]urea was significantly altered by spironolactone. The RBFs in the ischemic kidney compared with the contralateral kidney were decreased similarly as measured using both [13 C,15 N2 ]urea and [1-13 C]pyruvate in the spironolactone-treated group. Spironolactone treatment increased the perfusion-corrected pyruvate metabolism by 54% in both the ischemic and contralateral kidney. Furthermore, we showed a correlation between vascular permeability using a histological Evans blue analysis and the ratio of the volumes of distribution (VoDs), ie VoD-[13 C,15 N2 ]urea/VoD-[1-13 C]pyruvate. This suggests that [13 C,15 N2 ]urea/[1-13 C]pyruvate VoD ratio may be a novel indicator of renal vascular permeability associated with renal damage in rodents.

Coil profile estimation strategies for parallel imaging with hyperpolarized 13 C MRI.

PURPOSE: To investigate auto- and pre-calibration coil profile estimation for parallel imaging reconstruction of hyperpolarized 13 C MRI volumetric data. METHODS: Parallel imaging reconstruction was studied with 3 different approaches for coil profile estimation: auto-calibration, phantom calibration, and theoretic calibration. Acquisition was performed with a 3D stack-of-spirals sequence with spectral-spatial excitation and Cartesian undersampling. Parallel imaging reconstructions were done with conjugate gradient SENSE and 3D gridding with inhomogeneity correction. The approaches were compared in simulations with different SNR, through phantom experiments, and in an in vivo pig study focused on the kidneys. All imaging was done with a rigid home-built 12-channel 13 C receive coil at 3T. RESULTS: The phantom calibrated and theoretic approaches resulted in the best structural similarities in simulations and demonstrated higher image quality in the phantom experiments compared to the auto-calibrated approach. In vivo mapping of pyruvate uptake and lactate conversion improved for accelerated acquisitions because of a better temporal resolution. From a practical and image quality point of view, use of theoretic coil profiles led to improved results compared to the other approaches. CONCLUSION: The success of the theoretic coil profile estimation demonstrates a negligible effect of load on sensitivity profiles at the carbon frequency at 3T. Through theoretic or phantom calibrated parallel imaging, accelerated 3D volumes could be reconstructed with sufficient sensitivity, temporal, and spatial resolution to map the metabolism of kidneys exemplifying abdominal organs. This approach overcomes a critical step in the clinical translation of parallel imaging in hyperpolarized 13 C MR.

Acute hypertensive stress imaged by cardiac hyperpolarized [1-13 C]pyruvate magnetic resonance.

PURPOSE: Deranged metabolism is now recognized as a key causal factor in a variety of heart diseases, and is being studied extensively. However, invasive methods may alter metabolism, and conventional imaging techniques measure tracer uptake but not downstream metabolism. These challenges may be overcome by hyperpolarized MR, a noninvasive technique currently crossing the threshold into human trials. The aim of this study was to image metabolic changes in the heart in response to endogastric glucose bolus and to acute hypertension. METHODS: Five postprandial pigs were scanned with hyperpolarized [1-13 C]pyruvate cardiac MR at baseline, after oral glucose bolus, and after infusion of angiotensin-II. RESULTS: No effect of glucose bolus was seen using hyperpolarized [1-13 C]pyruvate MR despite changes in circulating substrates. During angiotensin-II infusion, blood pressure increased 179% (P = 0.008) and ejection fraction decreased from 54 ± 2% to 47 ± 6% (P = 0.03) The hemodynamic changes were accompanied by increases in the hyperpolarized [1-13 C]pyruvate MR derived ratios of lactate/alanine (from 0.58 ± 0.13 to 0.78 ± 0.06, P = 0.03) and bicarbonate/alanine (from 0.55 ± 0.12 to 0.91 ± 0.14, P = 0.007). CONCLUSION: Glucose loading did not alter cardiac metabolism, but during acute hypertensive stress, cardiac aerobic, carbohydrate metabolism, and pyruvate-lactate exchange was altered. Hyperpolarized MR allows noninvasive evaluation of acute changes in cardiac metabolism. However, hemodynamics must be taken into account when interpreting the results.

Renal MR angiography and perfusion in the pig using hyperpolarized water.

PURPOSE: To study hyperpolarized water as an angiography and perfusion tracer in a large animal model. METHODS: Protons dissolved in deuterium oxide (D2 O) were hyperpolarized in a SPINlab dissolution dynamic nuclear polarization (dDNP) polarizer and subsequently investigated in vivo in a pig model at 3 Tesla (T). Approximately 15 mL of hyperpolarized water was injected in the renal artery by hand over 4-5 s. RESULTS: A liquid state polarization of 5.3 ± 0.9% of 3.8 M protons in 15 mL of deuterium oxide was achieved with a T1 of 24 ± 1 s. This allowed injection through an arterial catheter into the renal artery and subsequently high-contrast imaging of the entire kidney parenchyma over several seconds. The dynamic images allow quantification of tissue perfusion, with a mean cortical perfusion of 504 ± 123 mL/100 mL/min. CONCLUSION: Hyperpolarized water MR imaging was successfully demonstrated as a renal angiography and perfusion method. Quantitative perfusion maps of the kidney were obtained in agreement with literature and control experiments with gadolinium contrast. Magn Reson Med 78:1131-1135, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Imaging porcine cardiac substrate selection modulations by glucose, insulin and potassium intervention: A hyperpolarized [1-13 C]pyruvate study.

Cardiac metabolism has received considerable attention in terms of both diagnostics and prognostics, as well as a novel target for treatment. As human trials involving hyperpolarized magnetic resonance in the heart are imminent, we sought to evaluate the general feasibility of detection of an imposed shift in metabolic substrate utilization during metabolic modulation with glucose-insulin-potassium (GIK) infusion, and thus the limitations associated with this strategy, in a large animal model resembling human physiology. Four [1-13 C]pyruvate injections did not alter the blood pressure or ejection fraction over 180 min. Hyperpolarized [1-13 C]pyruvate conversion showed a generally high reproducibility, with intraclass correlation coefficients between the baseline measurements at 0 and 30 min as follows: lactate to pyruvate, 0.85; alanine to pyruvate, 1.00; bicarbonate to pyruvate, 0.83. This study demonstrates that hyperpolarized [1-13 C]pyruvate imaging is a feasible technique for cardiac studies and shows a generally high reproducibility in fasted large animals. GIK infusion increases the metabolic conversion of pyruvate to its metabolic derivatives lactate, alanine and bicarbonate, but with increased variability.

Acute porcine renal metabolic effect of endogastric soft drink administration assessed with hyperpolarized [1-(13)C]pyruvate.

PURPOSE: Our aim was to determine the quantitative reproducibility of metabolic breakdown products in the kidney following intravenous injection of hyperpolarized [1-(13)C]pyruvate and secondly to investigate the metabolic effect on the pyruvate metabolism of oral sucrose load using dissolution dynamic nuclear polarization. By this technique, metabolic alterations in several different metabolic related diseases and their metabolic treatment responses can be accessed. METHODS: In four healthy pigs the lactate-to-pyruvate, alanine-to-pyruvate and bicarbonate-to-pyruvate ratio was measured following administration of regular cola and consecutive injections of hyperpolarized [1-(13)C]pyruvate four times within an hour. RESULTS: The overall lactate-to-pyruvate metabolic profile changed significantly over one hour following an acute sucrose load leading to a significant rise in blood glucose. CONCLUSION: The reproducibility of hyperpolarized magnetic resonance spectroscopy in the healthy pig kidney demonstrated a repeatability of more than 94% for all metabolites and, furthermore, that the pyruvate to lactate conversion and the blood glucose level is elevated following endogastric sucrose administration.