Hyperpolarized ¹³C Magnetic Resonance Imaging as a Tool for Imaging Tissue Redox State, Oxidative Stress, Inflammation, and Cellular Metabolism

Abstract

Significance: Magnetic resonance imaging (MRI) with hyperpolarized 13 C-labelled redoxsensitive metabolic tracers can provide non-invasive functional imaging biomarkers reflecting; tissue redox state, oxidative stress, and inflammation, among others. The capability to use endogenous metabolites as 13 C-enriched imaging tracers without structural modification makes hyperpolarized 13 C MRI a promising tool to evaluate redox state in patients with various diseases. Recent Advances:Recent studies have demonstrated the feasibility of in vivo metabolic imaging of 13 C-labelled tracers polarized by parahydrogen-induced polarization techniques, which offer a cost-effective alternative to the more widely-used dissolution dynamic nuclear polarization-based hyperpolarizers.Critical Issues: Although the fluxes of many metabolic pathways reflect the change in tissue redox state, they are not functionally specific. In the present review, we summarize recent challenges in the development of specific 13 C metabolic tracers for biomarkers of redox state, including that for detecting reactive oxygen species.Future Directions: Applications of hyperpolarized 13 C metabolic MRI to evaluate redox state have only just begun to be investigated. The possibility to gain a comprehensive understanding of the correlations between tissue redox potential and metabolism under different pathological conditions by using hyperpolarized 13 C MRI is promoting its interest in the clinical arena, along with its non-invasive biomarkers to evaluate the extent of disease and treatment response.

Parahydrogen-Induced 13C Hyperpolarizer Using a Flow Guide for Magnetic Field Cycling to Evoke 1H-13C Spin Order Transfer Toward Metabolic MRI

“…21-0007). In ex vivo and in vivo experiments, HP [1-13 C]pyruvate solutions were prepared by using the smallest hydrogenation reaction chamber with inner volume of 19.4 cm 3 .…”

“…YPERPOLARIZATION of heteronuclear spins such as 13 C and 15 N is a rapidly developing field of molecular imaging wherein nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) signals can be transiently enhanced more than 10,000 times compared to that at thermal equilibrium level. This enhancement allows for the noninvasive and real-time monitoring of metabolic reactions of 13 C or 15 N labeled tracers in the body [1], [2], [3], [4]. Hyperpolarization-evoking methodologies can be roughly classified into three types: brute force, dynamic nuclear polarization (DNP), and parahydrogen-induced polarization (PHIP) [5].…”

Multinuclear MRI in Drug Discovery

“…In addition, multi-MRS is being used for cardiac studies, the use of 1 H, 13 C and 31 P provides a wealth of metabolic information for accurate diagnosis and treatment [ 54 ]. Hyperpolarized 13 C MRI has the potential to assess tissue redox status, oxidative stress, and inflammation and cellular metabolism [ 55 ]. It also examines the branching points of metabolic pathways to quantify the fate of metabolites in acute lung injury and inflammation [ 56 ].…”

Rapid probing of glucose influx into cancer cell metabolism: using adjuvant and a pH-dependent collection of central metabolites to improve in-cell D-DNP NMR

“…All these prerequisites are met by NMR spectroscopy. In-cell NMR spectroscopy benets from compounded improvements in methodology and instrumentation, including hyperpolarized probe molecules, [5][6][7] improved hardware for enhancing nuclear spin polarization, 8 and cryogenically cooled detection electronics. 9 The objective for in-cell spectroscopy is usually different from metabolite characterization in metabolomics approaches on stable samples, whose pH value and temperature can be chosen for analysis.…”

“…All these prerequisites are met by NMR spectroscopy. In-cell NMR spectroscopy benefits from compounded improvements in methodology and instrumentation, including hyperpolarized probe molecules, 5–7 improved hardware for enhancing nuclear spin polarization, 8 and cryogenically cooled detection electronics. 9…”