Hyperpolarized MRI - An Update and Future Perspectives.

In recent years, hyperpolarized 13C magnetic resonance spectroscopic (MRS) imaging has emerged as a complementary metabolic imaging approach. Hyperpolarization via dissolution dynamic nuclear polarization is a technique that enhances the MR signal of 13C-enriched molecules by a factor of > 104, enabling detection downstream metabolites in a variety of intracellular metabolic pathways. The aim of the present review is to provide the reader with an update on hyperpolarized 13C MRS imaging and to assess the future clinical potential of the technology. Several carbon-based probes have been used in hyperpolarized studies. However, the first and most widely used 13C-probe in clinical studies is [1-13C]pyruvate. In this probe, the enrichment of 13C is performed at the first carbon position as the only modification. Hyperpolarized [1-13C]pyruvate MRS imaging can detect intracellular production of [1-13C]lactate and 13C-bicarbonate non-invasively and in real time without the use of ionizing radiation. Thus, by probing the balance between oxidative and glycolytic metabolism, hyperpolarized [1-13C]pyruvate MRS imaging can image the Warburg effect in malignant tumors and detect the hallmarks of ischemia or viability in the myocardium. An increasing number of clinical studies have demonstrated that clinical hyperpolarized 13C MRS imaging is not only possible, but also it provides metabolic information that was previously inaccessible by non-invasive techniques. Although the technology is still in its infancy and several technical improvements are warranted, it is of paramount importance that nuclear medicine physicians gain knowledge of the possibilities and pitfalls of the technique. Hyperpolarized 13C MRS imaging may become an integrated feature in combined metabolic imaging of the future.

Organ-specific responses during brain death: increased aerobic metabolism in the liver and anaerobic metabolism with decreased perfusion in the kidneys.

Hepatic and renal energy status prior to transplantation correlates with graft survival. However, effects of brain death (BD) on organ-specific energy status are largely unknown. We studied metabolism, perfusion, oxygen consumption, and mitochondrial function in the liver and kidneys following BD. BD was induced in mechanically-ventilated rats, inflating an epidurally-placed Fogarty-catheter, with sham-operated rats as controls. A 9.4T-preclinical MRI system measured hourly oxygen availability (BOLD-related R2*) and perfusion (T1-weighted). After 4 hrs, tissue was collected, mitochondria isolated and assessed with high-resolution respirometry. Quantitative proteomics, qPCR, and biochemistry was performed on stored tissue/plasma. Following BD, the liver increased glycolytic gene expression (Pfk-1) with decreased glycogen stores, while the kidneys increased anaerobic- (Ldha) and decreased gluconeogenic-related gene expression (Pck-1). Hepatic oxygen consumption increased, while renal perfusion decreased. ATP levels dropped in both organs while mitochondrial respiration and complex I/ATP synthase activity were unaffected. In conclusion, the liver responds to increased metabolic demands during BD, enhancing aerobic metabolism with functional mitochondria. The kidneys shift towards anaerobic energy production while renal perfusion decreases. Our findings highlight the need for an organ-specific approach to assess and optimise graft quality prior to transplantation, to optimise hepatic metabolic conditions and improve renal perfusion while supporting cellular detoxification.