Purpose Calibration of hyperpolarized 13C‐MRI is limited by the low signal from endogenous carbon‐containing molecules and consequently requires 13C‐enriched external phantoms. This study investigated the feasibility of using either 23Na‐MRI or 1H‐MRI to calibrate the 13C excitation. Methods Commercial 13C‐coils were used to estimate the transmit gain and center frequency for 13C and 23Na resonances. Simulations of the transmit B1 profile of a Helmholtz loop were performed. Noise correlation was measured for both nuclei. A retrospective analysis of human data assessing the use of the 1H resonance to predict [1‐13C]pyruvate center frequency was also performed. In vivo experiments were undertaken in the lower limbs of 6 pigs following injection of hyperpolarized 13C‐pyruvate. Results The difference in center frequencies and transmit gain between tissue 23Na and [1‐13C]pyruvate was reproducible, with a mean scale factor of 1.05179 ± 0.00001 and 10.4 ± 0.2 dB, respectively. Utilizing the 1H water peak, it was possible to retrospectively predict the 13C‐pyruvate center frequency with a standard deviation of only 11 Hz sufficient for spectral–spatial excitation‐based studies. Conclusion We demonstrate the feasibility of using the 23Na and 1H resonances to calibrate the 13C transmit B1 using commercially available 13C‐coils. The method provides a simple approach for in vivo calibration and could improve clinical workflow.

Hyperpolarised MRI with Dynamic Nuclear Polarisation overcomes the fundamental thermodynamic limitations of conventional magnetic resonance, and is translating to human studies with several early-phase clinical trials in progress including early reports that demonstrate the utility of the technique to observe lactate production in human brain cancer patients. Owing to the fundamental coupling of metabolism and tissue function, metabolic neuroimaging with hyperpolarised [1-13C]pyruvate has the potential to be revolutionary in numerous neurological disorders (e.g. brain tumour, ischemic stroke, and multiple sclerosis). Through the use of [1-13C]pyruvate and ethyl-[1-13C]pyruvate in naïve brain, a rodent model of metastasis to the brain, or porcine brain subjected to mannitol osmotic shock, we show that pyruvate transport across the blood-brain barrier of anaesthetised animals is rate-limiting. We show through use of a well-characterised rat model of brain metastasis that the appearance of hyperpolarized [1-13C]lactate production corresponds to the point of blood-brain barrier breakdown in the disease. With the more lipophilic ethyl-[1-13C]pyruvate, we observe pyruvate production endogenously throughout the entire brain and lactate production only in the region of disease. In the in vivo porcine brain we show that mannitol shock permeabilises the blood-brain barrier sufficiently for a dramatic 90-fold increase in pyruvate transport and conversion to lactate in the brain, which is otherwise not resolvable. This suggests that earlier reports of whole-brain metabolism in anaesthetised animals may be confounded by partial volume effects and not informative enough for translational studies. Issues relating to pyruvate transport and partial volume effects must therefore be considered in pre-clinical studies investigating neuro-metabolism in anaesthetised animals, and we additionally note that these same techniques may provide a distinct biomarker of blood-brain barrier permeability in future studies.

BackgroundIntramyocardialhemorrhage (IMH) reflects severe reperfusion injury in acute myocardial infarction. Non-invasive detection of IMH by cardiovascular magnetic resonance (CMR) may serve as a surrogate marker to evaluate the effect of preventive measures to reduce reperfusion injury and hence provide additional prognostic information. We sought to investigate whether IMH could be detected by CMR exploiting the T1 shortening effect of methemoglobin in an experimental model of acute myocardial infarction. The results were compared to T2-weighthed short tau inversion recovery (T2-STIR), and T2*-weighted(T2*W) sequences.Methods and resultsIMH was induced in ten 40 kg pigs by 50-min balloon occlusion of the mid LAD followed by reperfusion. Between 4–9 days (average 4.8) post-injury, the left ventricular myocardium was assessed by T1-weigthed Inversion Recovery(T1W-IR), T2-STIR, and T2*Wsequences. All CMR images were matched to histopathology and compared with the area of IMH. The difference between the size of the IMH area detected on T1W-IR images and pathology was −1.6 ± 11.3% (limits of agreement, -24%–21%), for the T2*W images the difference was −0.1 ± 18.3% (limitsof agreement, -36.8%–36.6%), and for T2-STIR the difference was 8.0 ± 15.5% (limits of agreement, -23%–39%). By T1W IR the diagnostic sensitivity of IMH was 90% and specificity 70%, for T2*W imaging the sensitivity was 70% and specificity 50%, and for T2-STIR sensitivity for imaging IMH was 50% and specificity 60%.ConclusionT1-weigthednon-contrast enhanced CMR detects IMH with high sensitivity and specificity and may become a diagnostic tool for detection of IMH in patients with myocardial infarction.

BackgroundNatural estrogen decline leads to vasomotor symptoms (VMS). Hormone therapy alleviates symptoms but increases cancer risk. Effective treatments against VMS with minimal cancer risks are needed. We investigate the effects of a highly bioavailable aglycone rich Red Clover isoflavone treatment to alleviate existing menopausal VMS, assessed for the first time by 24hour ambulatory skin conductance (SC)Methods and resultsWe conducted a parallel, double blind, randomised control trial of 62 peri-menopausal women aged 40–65, reporting ≥ 5 hot flushes/day and follicle stimulating hormone ≥35 IU/L. Participants received either twice daily treatment with bioavailable RC extract (RCE), providing 34 mg/d isoflavones and probiotics, or masked placebo formulation for 12 weeks. The primary outcome was change in daily hot flush frequency (HFF) from baseline to 12 weeks using 24hr SC. Secondary outcomes were change in SC determined hot flush intensity (HFI), self-reported HFF (rHFF) and hot flush severity (rHFS), blood pressure and plasma lipids. A significant decrease in 24hr HFF (P < 0.01) and HFI (P<0.05) was found when comparing change from baseline to 12 months of the RCE (-4.3 HF/24hr, CI -6.8 to -2.3; -12956 μS s-1, CI -20175 to -5737) with placebo (0.79 HF/24hr, CI -1.56 to 3.15; 515 μS s-1, CI -5465 to 6496). rHFF was also significantly reduced (P <0.05)in the RCE (-2.97 HFs/d, CI -4.77 to -1.17) group compared to placebo (0.036 HFs/d, CI -2.42 to 2.49). Other parameters were non-significant. RCE was well tolerated.ConclusionResults suggest that moderate doses of RCE were more effective and superior to placebo in reducing physiological and self-reported VMS. Findings support that objective physiological symptom assessment methods should be used together with self-report measures in future studies on menopausal VMS.Trial registrationClinicalTrials.gov NCT02028702

Hyperpolarized functional C, N urea MRI can be used to successfully detect changes in the intrarenal urea gradient post-IRI, thereby enabling in vivo monitoring of the intrarenal functional status in the rat kidney. Magn Reson Med 76:1524-1530, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

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 [1‐13C]pyruvate and other 13C‐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 1H MRI as well as hyperpolarized [1‐13C]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 [1‐13C]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.

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- C]pyruvate injections did not alter the blood pressure or ejection fraction over 180 min. Hyperpolarized [1- 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- 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.

PurposeOur aim was to determine the quantitative reproducibility of metabolic breakdown products in the kidney following intravenous injection of hyperpolarized [1‐13C]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.MethodsIn 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 [1‐13C]pyruvate four times within an hour.ResultsThe overall lactate‐to‐pyruvate metabolic profile changed significantly over one hour following an acute sucrose load leading to a significant rise in blood glucose.ConclusionThe 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. Magn Reson Med 74:558–563, 2015. © 2015 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.