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.

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.

Sodium magnetic resonance imaging (MRI) is a powerful, non-invasive technique to assess sodium distribution within the kidney. Here we undertook pre-clinical and clinical studies to quantify the corticomedullary sodium gradient in healthy individuals and in a porcine model of diuresis. The results demonstrated that sodium MRI could detect spatial differences in sodium biodistribution across the kidney. The sodium gradient of the kidney changed significantly after diuresis in the pig model and was independent of blood electrolyte measurements. Thus, rapid sodium MRI can be used to dynamically quantify sodium biodistribution in the porcine and human kidney.

Purpose: X‐nuclei (also called non‐proton MRI) MRI and spectroscopy are limited by the intrinsic low SNR as compared to conventional proton imaging. Clinical translation of x‐nuclei examination warrants the need of a robust and versatile tool improving image quality for diagnostic use. In this work, we compare a novel denoising method with fewer inputs to the current state‐of‐the‐art denoising method.Methods: Denoising approaches were compared on human acquisitions of sodium (²³Na) brain, deuterium (²H) brain, carbon (¹³C) heart and brain, and simulated dynamic hyperpolarized ¹³C brain scans, with and without additional noise. The current state‐of‐the‐art denoising method Global‐local higher order singular value decomposition (GL‐HOSVD) was compared to the few‐input method tensor Marchenko‐Pastur principal component analysis (tMPPCA). Noise‐removal was quantified by residual distributions, and statistical analyses evaluated the differences in mean‐square‐error and Bland–Altman analysis to quantify agreement between original and denoised results of noise‐added data.Results: GL‐HOSVD and tMPPCA showed similar performance for the variety of x‐nuclei data analyzed in this work, with tMPPCA removing ˜5% more noise on average over GL‐HOSVD. The mean ratio between noise‐added and denoising reproducibility coefficients of the Bland–Altman analysis when compared to the original are also similar for the two methods with 3.09 ± 1.03 and 2.83 ± 0.79 for GL‐HOSVD and tMPPCA, respectively.Conclusion: The strength of tMPPCA lies in the few‐input approach, which generalizes well to different data sources. This makes the use of tMPPCA denoising a robust and versatile tool in x‐nuclei imaging improvements and the preferred denoising method.