Hyperpolarized Magnetic Resonance as a Sensitive Detector of Metabolic Function

Abstract

Hyperpolarized magnetic resonance allows for noninvasive measurements of biochemical reactions in vivo. Although this technique provides a unique tool for assaying enzymatic activities in intact organs, the scope of its application is still elusive for the wider scientific community. The purpose of this review is to provide key principles and parameters to guide the researcher interested in adopting this technology to address a biochemical, biomedical, or medical issue. It is presented in the form of a compendium containing the underlying essential physical concepts as well as suggestions to help assess the potential of the technique within the framework of specific research environments. Explicit examples are used to illustrate the power as well as the limitations of hyperpolarized magnetic resonance.

Combined hyperpolarized 13C-pyruvate MRS and 18F-FDG PET (hyperPET) estimates of glycolysis in canine cancer patients

“…Magnetic Resonance Spectroscopy (MRS) can also characterize cancer metabolism [9] and enabled by the development of dissolution Dynamic Nuclear Polarization (d-DNP) [10,11] T MRS has reached clinical accessibility. In particular, 13 C MRS Imaging (MRSI) of prostate cancer using hyperpolarized 13 C-labeled pyruvate as a substrate has been demonstrated in patients [12].…”

“…Accordingly, both 18 F FDG PET and hyperpolarized 13 C-pyruvate MRS are molecular imaging modalities sensitive to glycolysis. However, PET is well-established clinically while hyperpolarized MRS is still at its infancy [11,[13][14][15]. The relation between 18 F FDG PET and hyperpolarized 13 C-pyruvate MRS in cancer has been explored in a limited number of preclinical studies using a sequential setup [13,[16][17][18], focusing on feasibility [17] and treatment effects [13,16,18].…”

“…However, the ratio of lactate generation to 18 F-FDG uptake was found to be significantly higher in sarcoma as compared to carcinoma. The results were found both when lactate generation was estimated as an apparent pyruvate-to-lactate rate constant from dynamic 13 C MRS and as an [1][2][3][4][5][6][7][8][9][10][11][12][13] C]lactate to total 13 C ratio from 13 …”

Direct noninvasive estimation of myocardial tricarboxylic acid cycle flux in vivo using hyperpolarized 13C magnetic resonance

“…The technique provides unique insights into important questions regarding myocardial metabolism, substrate preference, pharmacological intervention, and the ability to differentiate between normal and pathological metabolism [22][23][24][25][26][27][28][29][30][31][32][33]. Pyruvate is by far the most widely used hyperpolarized 13 C substrate and it can be served as a probe for mitochondrial oxidative flux [34]. The entry of the 13 C label into the TCA cycle via acetylCoA is however dependent on the flux through pyruvate dehydrogenase (PDH), an enzyme that is tightly regulated and will hinder the direct assessment of V TCA .…”

Delivering strong 1 H nuclear hyperpolarization levels and long magnetic lifetimes through signal amplification by reversible exchange

“…One route to improve the diagnostic capabilities of MRI involves monitoring in vivo changes in metabolite flux to noninvasively probe human physiology (2). However, for reasons of low sensitivity, MRI detection needs to be coupled with approaches to increase signal strength such as hyperpolarization (3). This process has been exemplified by studies on pyruvate that harness dissolution dynamic nuclear polarization (DNP) (4) to produce the signal strength necessary to track its metabolism (5).…”