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.
Acute ischemic stroke patients benefit from reperfusion in a short time-window after debut. Later treatment may be indicated if viable brain tissue is demonstrated and this outweighs the inherent risks of late reperfusion. Magnetic resonance imaging (MRI) with hyperpolarized [1-13C]pyruvate is an emerging technology that directly images metabolism. Here, we investigated its potential to detect viable tissue in ischemic stroke. Stroke was induced in pigs by intracerebral injection of endothelin 1. During ischemia, the rate constant of pyruvate-to-lactate conversion, kPL, was 52% larger in penumbra and 85% larger in the infarct compared to the contralateral hemisphere (P = 0.0001). Within the penumbra, the kPL was 50% higher in the regions that later infarcted compared to non-progressing regions (P = 0.026). After reperfusion, measures of pyruvate-to-lactate conversion were slightly decreased in the infarct compared to contralateral. In addition to metabolic imaging, we used hyperpolarized pyruvate for perfusion-weighted imaging. This was consistent with conventional imaging for assessment of infarct size and blood flow. Lastly, we confirmed the translatability of simultaneous assessment of metabolism and perfusion with hyperpolarized MRI in healthy volunteers. In conclusion, hyperpolarized [1-13C]pyruvate may aid penumbral characterization and increase access to reperfusion therapy for late presenting patients.
Chronic kidney disease (CKD) is common and has huge implications for health and mortality. It is aggravated by intrarenal fibrosis, but the assessment of fibrosis is limited to kidney biopsies, which carry a risk of complications and sampling errors. This calls for a noninvasive modality for diagnosing and staging intrarenal fibrosis. The current, exploratory study evaluates a multiparametric MRI protocol including sodium imaging (23Na‐MRI) to determine the opportunities within this modality to assess kidney injury as a surrogate endpoint of fibrosis. The study includes 43 pigs exposed to ischemia–reperfusion injury (IRI) or unilateral ureteral obstruction (UUO), or serving as healthy controls. Fibrosis was determined using gene expression analysis of collagen. The medulla/cortex ratio of 23Na‐MRI decreased in the injured kidney in the IRI pigs, but not in the UUO pigs (p = 0.0180, p = 0.0754). To assess the combination of MRI parameters in estimating fibrosis, we created a linear regression model consisting of the cortical apparent diffusion coefficient, ΔR2*, ΔT1, the 23Na medulla/cortex ratio, and plasma creatinine (R2 = 0.8009, p = 0.0117). The 23Na medulla/cortex ratio only slightly improved the fibrosis prediction model, leaving 23Na‐MRI in an ambiguous place for evaluation of intrarenal fibrosis. Use of multiparametric MRI in combination with plasma creatinine shows potential for the estimation of fibrosis in human kidney disease, but more translational and clinical work is warranted before MRI can contribute to earlier diagnosis and evaluation of treatment for acute kidney injury and CKD.
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 [1‐13C]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 [1‐13C]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 [1‐13C]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.
Kidney disease and its complications represent a huge health concern and economic burden worldwide. 1 Chronic kidney disease (CKD) has a very high prevalence and is associated with high morbidity and mortality. 2 Early stages of CKD are estimated to affect 10% of the world population 3 and can lead to dialysis and eventually
Hyperpolarized 13-carbon metabolic maps from an ex-vivo pig model of human heart transplantation, aimed at assessing the metabolic status of donor myocardium, from the article by .
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