Hyperpolarized 13C MRI: A novel approach for probing cerebral metabolism in health and neurological disease

Abstract

Cerebral metabolism is tightly regulated and fundamental for healthy neurological function. There is increasing evidence that alterations in this metabolism may be a precursor and early biomarker of later stage disease processes. Proton magnetic resonance spectroscopy (¹H-MRS) is a powerful tool to non-invasively assess tissue metabolites and has many applications for studying the normal and diseased brain. However, the technique has limitations including low spatial and temporal resolution, difficulties in discriminating overlapping peaks, and challenges in assessing metabolic flux rather than steady-state concentrations. Hyperpolarized carbon-13 magnetic resonance imaging is an emerging clinical technique that may overcome some of these spatial and temporal limitations, providing novel insights into neurometabolism in both health and in pathological processes such as glioma, stroke and multiple sclerosis. This review will explore the growing body of pre-clinical data that demonstrates a potential role for the technique in assessing metabolism in the central nervous system. There are now a number of clinical studies being undertaken in this area and this review will present the emerging clinical data as well as the potential future applications of hyperpolarized ¹³C magnetic resonance imaging in the brain, in both clinical and pre-clinical studies.

Keywords: MRI; hyperpolarization; metabolism; neuro-oncology; neurology.

Figure 1.

A sterile fluid path for clinical studies. The fluid path contains pyruvate (in sample vial), water for injection (dissolution syringe), and a neutralization medium (held in the receiver vessel). The filter on the receiver vessel removes the electron paramagnetic agent (EPA) prior to quality control (QC). Figure adapted from Park et al.

Figure 2.

The clinical “SPINlab” hyperpolariser system exterior (a) and interior (b). The Quality Control (QC) unit is shown on the right of each image, and the hyperpolarizer on the left. The system is sited next to a clinical scanner with a hatch in the wall for the delivery of the hyperpolarized sample; this will be placed into a syringe driver and injected into the patient.

Figure 3.

Metabolic imaging of the porcine brain. Imaging of the naïve porcine brain following injection of hyperpolarized ¹³C-pyruvate. (a) ¹³C-pyruvate signal is demonstrated in the vasculature. However, no ¹³C-lactate signal (b) is seen in the brain parenchyma and therefore no significant metabolism is demonstrated on the kinetic rate constant map (c) (k_PL in s⁻¹; calculated only in the brain region). After the introduction of mannitol, both ¹³C-pyruvate (d) and ¹³C-lactate (e) are seen in the brain parenchyma as demonstrated on the calculated kinetic rate constant map (f). Figure adapted from Miller et al.

Figure 4.

¹³C imaging demonstrating metabolite distribution in the healthy human brain. Example summed images from the brain of a healthy volunteer demonstrating ¹³C-pyruvate, ¹³C-lactate, and ¹³C-bicarbonate signal from three axial slices: superior, central and inferior. The T₁-weighted images have also been shown, as have the quantitative maps of the exchange of pyruvate to lactate (k_PL in s⁻¹).

Figure 5.

Resolution of ¹³C imaging of the normal human brain. (a) Proton anatomical imaging. IDEAL spiral Chemical Shift Images (CSI) are shown at the acquired spatial resolution to demonstrate the difference in SNR between: (b) pyruvate; (c) lactate; and (d) bicarbonate. ¹³C images are normalized to the metabolite peak signal in the slice. Imaging parameters: field of view = 240 mm, matrix size = 40 × 40, slice thickness = 30 mm. Adapted from Grist et al.