Imaging oxygen metabolism with hyperpolarized magnetic resonance: a novel approach for the examination of cardiac and renal function

Abstract

Every tissue in the body critically depends on meeting its energetic demands with sufficient oxygen supply. Oxygen supply/demand imbalances underlie the diseases that inflict the greatest socio-economic burden globally. The purpose of this review is to examine how hyperpolarized contrast media, used in combination with MR data acquisition methods, may advance our ability to assess oxygen metabolism non-invasively and thus improve management of clinical disease. We first introduce the concept of hyperpolarization and how hyperpolarized contrast media have been practically implemented to achieve translational and clinical research. We will then analyse how incorporating hyperpolarized contrast media could enable realization of unmet technical needs in clinical practice. We will focus on imaging cardiac and renal oxygen metabolism, as both organs have unique physiological demands to satisfy their requirements for tissue oxygenation, their dysfunction plays a fundamental role in society’s most prevalent diseases, and each organ presents unique imaging challenges. It is our aim that this review attracts a multi-disciplinary audience and sparks collaborations that utilize an exciting, emergent technology to advance our ability to treat patients adversely affected by an oxygen supply/demand mismatch.

Effects of anesthesia on renal function and metabolism in rats assessed by hyperpolarized MRI

“…A multitude of different anesthetics and anesthesia procedures are used throughout the literature, potentially affecting the acquired bio‐chemical information and thus imposing constraints on the comparability of studies performed under different circumstances. This is particularly true with the advancement of the metabolic imaging methods, such as hyperpolarized MRI and spectroscopy, which enable in vivo metabolic examinations in real time, and as such, are inherently sensitive to metabolic disturbances imposed by the anesthesia . Furthermore, some anesthetics have been shown to even protect animals against various conditions, such as renal ischemia‐reperfusion injury, during the investigations.…”

Probing the cardiac malate–aspartate shuttle non‐invasively using hyperpolarized [1,2‐13C2]pyruvate

“…27 However, the very strength of hyperpolarized 13 C MR -its ability to measure fluxes through these targeted enzymatic pathways non-invasively -also necessitates careful interpretation of the data generated based on the physiological context in which they are acquired. 28,29 For example, the metabolites detectable from TCA cycle-mediated oxidation of [2-13 C]pyruvate are the result of several metabolic steps. In the instance of the [5-13 C]glutamate signal, the amplitude could be modulated by changes to the rates of PDH flux and TCA cycle flux.…”

Paracrine potential of adipose stromal vascular fraction cells to recover hypoxia‐induced loss of cardiomyocyte function

“…Although the limitation given by the use of a 2D model, this confirms the importance of oxygen imbalances in the generation/maintenance of CM hibernating phenotype (Canty & Suzuki, 2012;Schroeder & Laustsen, 2017), and reminds that possible future cell therapies targeting chronic ischemic conditions may be conceived to promote also beneficial effects to the microvascular reperfusion (Canty & Suzuki, 2012). In fact, the crucial role of oxygen levels was highlighted by attempting to recover CM at ultra-low oxygen tensions.…”

“…(c) Quantification of percentage of CM (trop-I-positive cells) following culture of further 5 days in either ambient or ultra-low oxygen concentration in either SVF-conditioned media or control medium (CTR). Ultra-low oxygen tension levels were applied to facilitate the use of neonatal rat CM, which are known to be more resistant to harsh hypoxic environments due to their early-differentiated status (Schroeder & Laustsen, 2017). CM: cardiomyocytes; DAPI: 4′,6diamidino-2-phenylindole; SVF: stromal vascular fraction [Color figure can be viewed at wileyonlinelibrary.com] re-established upon removal of blood clot (known as ischemia-reperfusion injury), low-perfused areas characterized by microvascular dysfunction (typical of chronic cardiac ischemia conditions) are long-term hypoxic or quasi-anoxic environments, characterized by oxygen imbalances, which affect CM healthy functionality (Schroeder & Laustsen, 2017).…”