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[...]the limited information on conventional imaging approaches is not sufficient to comprehensively assess the treatment response of HCC. Since the liver plays a central role in metabolism and is responsible for most chemical synthesis and degradation in the body, it is usually accompanied by the metabolic reprogramming during hepatocarcinogenesis, disease progression, and HCC recovery. [6] Moreover, to obtain better liver images with high spatial resolution, advanced shimming techniques and abdominal dual-tuned (1H and 13C) coils are essential, which can help to achieve homogeneous B0 field, increase signal-to-noise ratio (SNR), and optimize clinical workflow. According to these unique characteristics, we should expect another small signal peaks after the main peaks,[11] or even a sustained peak of certain metabolite,[12] since the remaining HP 13C substrate and its metabolites produced by the intestines can be brought back to liver through the portal vein. In principle, gadolinium will change the MRI properties and corresponding signals of the tissues and may also affect the hepatic metabolism. [...]Perkons et al[14] suggested performing the HP 13C MRI scanning before contrast enhancement.

Acute myeloblastic leukemia (AML) is one of the most common and life-threatening forms of leukemia. Treatment remains challenging due to its high heterogeneity, drug resistance, and metabolic flexibility. Targeting specific metabolic pathways has emerged as a promising therapeutic approach. The ability to monitor treatment response is crucial for disease management. Here, we utilized hyperpolarized 13 C nuclear magnetic resonance (NMR) spectroscopy to evaluate the therapeutic effects of 2-deoxy-D-glucose (2-DG), a glucose analog known to inhibit glycolysis and induce cell death in leukemic cell lines. Hyperpolarized 13 C NMR spectroscopy, biochemical assays, and respirometry were used to assess the metabolic effects of 2-DG treatment at various concentrations on the AML cell line ML-1 in vitro. Significant metabolic alterations were observed following 2-DG treatment at 2 mM and 5 mM for 24 h, as revealed by multiple analytical approaches. The concentration-dependent effects of 2-DG treatment were clearly detected using hyperpolarized NMR, demonstrating substantial inhibition of glycolytic pathways in ML-1 cells. This study supports the potential of 2-DG for enhancing chemosensitivity in AML treatment and highlights hyperpolarized NMR as a valuable tool for therapy evaluation.

Today, there is a general lack of prognostic biomarkers for development of renal disease and in particular diabetic nephropathy. Increased glycolytic activity, lactate accumulation and altered mitochondrial oxygen utilization are hallmarks of diabetic kidney disease. Fumarate hydratase activity has been linked to mitochondrial dysfunction as well as activation of the hypoxia inducible factor, induction of apoptosis and necrosis. Here, we investigate fumarate hydratase activity in biofluids in combination with the molecular imaging probe, hyperpolarized [1,4- 13 C 2 ]fumarate, to identify the early changes associated with hemodynamics and cell death in a streptozotocin rat model of type 1 diabetes. We found a significantly altered hemodynamic signature of [1,4- 13 C 2 ]fumarate in the diabetic kidneys as well as an systemic increased metabolic conversion of fumarate-to-malate, indicative of increased cell death associated with progression of diabetes, while little to no renal specific conversion was observed. This suggest apoptosis as the main cause of cell death in the diabetic kidney. This is likely resulting from an increased reactive oxygen species production following uncoupling of the electron transport chain at complex II. The mechanism coupling the enzyme leakage and apoptotic phenotype is hypoxia inducible factor independent and seemingly functions as a protective mechanism in the kidney cells.

Acute kidney injury is a major clinical challenge affecting as many as 1 percent of all hospitalized patients. Currently it is not possible to accurately stratify and predict the outcome of the individual patient. Increasing evidence supports metabolic reprogramming as a potential target for new biomarkers. Hyperpolarized [1- 13 C]pyruvate imaging is a promising new tool for evaluating the metabolic status directly in the kidneys. We here investigate the prognostic potential of hyperpolarized [1- 13 C]pyruvate in the setting of acute kidney injury in a rodent model of ischemia reperfusion. A significant correlation was found between the intra-renal metabolic profile 24 hours after reperfusion and 7 days after injury induction, as well as a correlation with the conventional plasma creatinine biomarker of renal function and markers of renal injury. This leads to a possible outcome prediction of renal function and injury development from a metabolic profile measured in vivo . The results support human translation of this new technology to renal patients as all experiements have been performed using clinical MRI equipment.

Background/ObjectivesBrown adipose tissue (BAT) has gained growing interest as a potential target for treatment of obesity. Currently, the most widely used technique/method for in vivo measurements of BAT activity in humans is 18FDG PET/CT. To supplement these investigations novel radiation-free methods are warranted. Deuterium metabolic imaging (DMI) is a novel modality that combines magnetic resonance spectroscopic (MRS) imaging with deuterium-labelled glucose (2H-glucose). This allows for spatio-temporal and metabolic imaging beyond glucose uptake. We aimed to evaluate if DMI could discriminate glucose metabolism in BAT of cold-acclimatised and thermoneutral rats.Subjects/MethodsMale Sprague-Dawley rats were housed in a cold environment (9 °C, n = 10) or at thermoneutrality (30 °C, n = 11) for 1 week. For imaging rats were anaesthetized, received a 2H-glucose (1 M, 1.95 g/kg) bolus and DMI was acquired at baseline followed by 20 min time intervals up to 2 h. Furthermore, Dixon MRI was performed for anatomical determination of the interscapular BAT (iBAT) depot along with dynamic contrast enhanced (DCE) MRI to evaluate perfusion.Results2H-glucose signal was higher in cold-acclimatised rats compared with thermoneutral rats (p ≤ 0.001) indicating an overall increase in glucose uptake and metabolism. This was in line with a lower fat/water threshold, higher perfusion and increased UCP1 mRNA expression in iBAT (ninefold increment) of cold-acclimatised rats compared with thermoneutral rats.ConclusionsWe find that DMI can discriminate cold-acclimatised and thermoneutral BAT in rats. This is the first study to evaluate BAT activity by DMI, which may open up for the use of the non-radioactive DMI method for BAT measurements in humans.

In heart failure, myocardial overload causes vast metabolic changes that impair cardiac energy production and contribute to deterioration of contractile function. However, metabolic therapy is not used in heart failure care. We aimed to investigate the interplay between cardiac function and myocardial carbohydrate metabolism in a large animal heart failure model. Using magnetic resonance spectroscopy with hyperpolarized pyruvate and magnetic resonance imaging at rest and during pharmacological stress, we investigated the in-vivo cardiac pyruvate metabolism and contractility in a porcine model of chronic pulmonary insufficiency causing right ventricular volume overload. To assess if increasing the carbohydrate metabolic reserve improves the contractile reserve, a group of animals were fed dichloroacetate, an activator of pyruvate oxidation. Volume overload caused heart failure with decreased pyruvate dehydrogenase flux and poor ejection fraction reserve. The animals treated with dichloroacetate had a larger contractile response to dobutamine stress than non-treated animals. Further, dichloroacetate prevented myocardial hypertrophy. The in-vivo metabolic data were validated by mitochondrial respirometry, enzyme activity assays and gene expression analyses. Our results show that pyruvate dehydrogenase kinase inhibition improves the contractile reserve and decreases hypertrophy by augmenting carbohydrate metabolism in porcine heart failure. The approach is promising for metabolic heart failure therapy.

Intrarenal backflow (IRB) is known to occur at increased intrarenal pressure (IRP). Irrigation during ureteroscopy increases IRP. Complications such as sepsis is more frequent after prolonged high-pressure ureteroscopy. We evaluated a new method to document and visualize intrarenal backflow as a function of IRP and time in a pig model. Studies were performed on five female pigs. A ureteral catheter was placed in the renal pelvis and connected to a Gadolinium/ saline solution 3 ml/L for irrigation. An occlusion balloon-catheter was left inflated at the uretero-pelvic junction and connected to a pressure monitor. Irrigation was successively regulated to maintain steady IRP levels at 10, 20, 30, 40 and 50 mmHg. MRI of the kidneys was performed at 5-minute intervals. PCR and immunoassay analyses were executed on the harvested kidneys to detect potential changes in inflammatory markers. MRI showed backflow of Gadolinium into the kidney cortex in all cases. The mean time to first visual damage was 15 minutes and the mean registered pressure at first visual damage was 21 mmHg. On the final MRI the mean percentage of IRB affected kidney was 66% after irrigation with a mean maximum pressure of 43 mmHg for a mean duration of 70 minutes. Immunoassay analyses showed increased MCP-1 mRNA expression in the treated kidneys compared to contralateral control kidneys. Gadolinium enhanced MRI provided detailed information about IRB that has not previously been documented. IRB occurs at even very low pressures, and these findings are in conflict with the general consensus that keeping IRP below 30-35 mmHg eliminates the risk of post-operative infection and sepsis. Moreover, the level of IRB was documented to be a function of both IRP and time. The results of this study emphasize the importance of keeping IRP and OR time low during ureteroscopy.

This study aims to investigate the effects of β-3-hydroxybutyrate (β-3-OHB) infusion on myocardial metabolic flexibility using hyperpolarized [2- 13 C]pyruvate magnetic resonance spectroscopy (MRS) in the pig heart. We hypothesized that β-3-OHB infusion will cause rapid, quantifiable alterations in tricarboxylic acid (TCA) cycle flux as measured non-invasively by 13 C MRS and reflect myocardial work. Five female Danish landrace pigs underwent β-3-OHB infusion during a hyperinsulinemic euglycemic clamp (HEC). Cardiac metabolism and hemodynamics were monitored using hyperpolarized [2- 13 C]pyruvate MRS and cardiac MRI. β-3-OHB infusion during HEC resulted in significant increases in cardiac output over baseline (from 1.9 to 3.8 L/min, p  = 0.0011) and heart rate (from 51 to 85 bpm, p  = 0.0004). Metabolic analysis showed a shift towards increased lactate production and decreased levels of acetyl-carnitine and glutamate during β-3-OHB infusion. Following the termination of the infusion, a normalization of these metabolic markers was observed. These results demonstrate the profound metabolic adaptability of the myocardium to ketone body utilization. The infusion of Na-β-3-OHB significantly alters both the hemodynamics and metabolism of the porcine heart. The observed increase in cardiac output and metabolic shifts towards lactate production suggest that ketone bodies could potentially enhance cardiac function by providing an efficient-energy substrate that, if provided, is preferentially used. This study provides new insights into the metabolic flexibility of the heart and hints at the potential therapeutic benefits of ketone interventions in heart failure treatment.

This review provides a comprehensive assessment of the development of hyperpolarized (HP) carbon-13 metabolic MRI from the early days to the present with a focus on clinical applications. The status and upcoming challenges of translating HP carbon-13 into clinical application are reviewed, along with the complexity, technical advancements, and future directions. The road to clinical application is discussed regarding clinical needs and technological advancements, highlighting the most recent successes of metabolic imaging with hyperpolarized carbon-13 MRI. Given the current state of hyperpolarized carbon-13 MRI, the conclusion of this review is that the workflow for hyperpolarized carbon-13 MRI is the limiting factor.

Background Hyperpolarized (HP) [1- 13 C]pyruvate cardiovascular magnetic resonance (CMR) imaging can visualize the uptake and intracellular conversion of [1- 13 C]pyruvate to either [1- 13 C]lactate or 13 C-bicarbonate depending on the prevailing metabolic state. The aim of the present study was to combine an adenosine stress test with HP [1- 13 C]pyruvate CMR to detect cardiac metabolism in the healthy human heart at rest and during moderate stress. Methods A prospective descriptive study was performed between October 2019 and August 2020. Healthy human subjects underwent cine CMR and HP [1- 13 C]pyruvate CMR at rest and during adenosine stress. HP [1- 13 C]pyruvate CMR images were acquired at the mid-left-ventricle (LV) level. Semi-quantitative assessment of first-pass myocardial [1- 13 C]pyruvate perfusion and metabolism were assessed. Paired t-tests were used to compare mean values at rest and during stress. Results Six healthy subjects (two female), age 29 ± 7 years were studied and no adverse reactions occurred. Myocardial [1- 13 C]pyruvate perfusion was significantly increased during stress with a reduction in time-to-peak from 6.2 ± 2.8 to 2.7 ± 1.3 s, p = 0.02. This higher perfusion was accompanied by an overall increased myocardial uptake and metabolism. The conversion rate constant ( k PL ) for lactate increased from 11 ± 9 *10 –3 to 20 ± 10 * 10 –3  s −1 , p = 0.04. The pyruvate oxidation rate ( k PB ) increased from 4 ± 4 *10 –3 to 12 ± 7 *10 –3  s −1 , p = 0.008. This increase in carbohydrate metabolism was positively correlated with heart rate (R 2  = 0.44, p = 0.02). Conclusions Adenosine stress testing combined with HP [1- 13 C]pyruvate CMR is feasible and well-tolerated in healthy subjects. We observed an increased pyruvate oxidation during cardiac stress. The present study is an important step in the translation of HP [1- 13 C]pyruvate CMR into clinical cardiac imaging. Trial registration EUDRACT, 2018-003533-15. Registered 4th of December 2018, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2018-003533-15