Hyperpolarization MRI: Preclinical Models and Potential Applications in Neuroradiology

Abstract

Hyperpolarization is a novel technology that can dramatically increase signal to noise in magnetic resonance. The method is being applied to small injectable endogenous molecules, which can be used to monitor transient in vivo metabolic events, in real time. The emergence of hyperpolarized C-labeled probes, specifically C pyruvate, has enabled monitoring of core cellular metabolic events. Neuro-oncological applications have been demonstrated in preclinical models. Many more applications of this technology are envisioned, with transformative potential in magnetic resonance imaging.

FIGURE 1

Pyruvate metabolic fates diagram. Isotopically labeling pyruvate at the first carbon position permits detection of lactate (anaerobic metabolism) and bicarbonate (aerobic metabolism), as well as alanine some TCA intermediates. Isotopically labeling pyruvate at the second carbon position permits detection of additional TCA cycle intermediates. Reproduced with permission from Chem Soc Rev 2014; 43:1627–1659.

FIGURE 2

Pyruvate metabolism in preclinical animal model. Hyperpolarized [1-¹³C] pyruvate is preferentially metabolized to lactate in the anesthesized rat brain. Metabolic maps of lactate, alanine, and pyruvate are shown in the top row. The left lower panel shows ¹H anatomic imaging. The right lower panel shows the source magnetic resonance spectroscopic imaging (MRSI), with individual resonances corresponding to pyruvate and its metabolic product, lacatate. Reproduced with permission from Magn Reson Med 2010; 63:1137–1143.

FIGURE 3

Hyperpolarized pyruvate metabolism in the nonhuman primate brain. Pyruvate (black arrow) and its metabolic product lactate resonance (grey arrow) are detected. Top panel: ¹H anatomic image with overlayed MRSI grid. Bottom panel: corresponding MRSI. Reproduced with permission from Magn Reson Med 2014; 71:19–25.

FIGURE 4

Hyperpolarized pyruvate in assessment of treatment response. Hyperpolarized [1-¹³C] pyruvate to lacate metabolism decreases following temozolamide treatment in a rat xenograft glioma model. The left, middle, and right columns show the changes at days 0, 1, 2 following 100 mg/kg temozolomide treatment. The top row shows contrast-enhanced images, with overlayed MRSI grid. The middle row shows corresponding spectra. The bottom row shows the corresponding metabolite maps. Reproduced with permission from J Magn Reson Imaging 2011; 33:1284–1290.

FIGURE 5

Monitoring oxidative potential in the brain. The oxidized metabolic precursor dehydroascorbate (DHA) is rapidly reduced to Vitamin C in the anesthetized rat brain, indicating high reductive potential of the brain. Left image: ¹H anatomic imaging; middle image: DHA metabolite map; right image: Vitamin C metabolite map; left most panel: representative spectrum with Vitamin C and DHA resonances. Reproduced with permission from Proc Natl Acad Sci U S A 2011; 108: 18606–18611.