Hyperpolarized Carbon 13 MRI: Clinical Applications and Future Directions in Oncology

Abstract

Hyperpolarized carbon 13 MRI (¹³C MRI) is a novel imaging approach that can noninvasively probe tissue metabolism in both normal and pathologic tissues. The process of hyperpolarization increases the signal acquired by several orders of magnitude, allowing injected ¹³C-labeled molecules and their downstream metabolites to be imaged in vivo, thus providing real-time information on kinetics. To date, the most important reaction studied with hyperpolarized ¹³C MRI is exchange of the hyperpolarized ¹³C signal from injected [1-¹³C]pyruvate with the resident tissue lactate pool. Recent preclinical and human studies have shown the role of several biologic factors such as the lactate dehydrogenase enzyme, pyruvate transporter expression, and tissue hypoxia in generating the MRI signal from this reaction. Potential clinical applications of hyperpolarized ¹³C MRI in oncology include using metabolism to stratify tumors by grade, selecting therapeutic pathways based on tumor metabolic profiles, and detecting early treatment response through the imaging of shifts in metabolism that precede tumor structural changes. This review summarizes the foundations of hyperpolarized ¹³C MRI, presents key findings from human cancer studies, and explores the future clinical directions of the technique in oncology. Keywords: Hyperpolarized Carbon 13 MRI, Molecular Imaging, Cancer, Tissue Metabolism © RSNA, 2023.

Keywords: Cancer; Hyperpolarized Carbon 13 MRI; Molecular Imaging; Tissue Metabolism.

Figure 1:

Simplified schematic of the major metabolic pathways that can be investigated with hyperpolarized [1–carbon 13]pyruvate MRI. ALT = alanine transaminase, CA = carbonic anhydrase, CoA = coenzyme A, LDH = lactate dehydrogenase, PDH = pyruvate dehydrogenase, TCA = tricarboxylic acid.

Figure 2:

Hyperpolarized carbon 13 MR images in a patient with glioblastoma that demonstrate heterogeneity in metabolism. (A) Axial contrast-enhanced T1-weighted fast spoiled gradient-echo image through the center of the lesion and (B) overlaid with the pyruvate, (C) lactate, and (D) bicarbonate color maps all summed over the imaging time course. (Reprinted, under a CC BY 4.0 license, from reference .)

Figure 3:

Hyperpolarized [1–carbon 13]pyruvate MR images in a patient with triple-negative breast cancer. (A) Coronal T1-weighted three-dimensional spoiled gradient-echo (SPGR) image. (B) Coronal reformatted dynamic contrast-enhanced (DCE) image at peak enhancement after injection of a gadolinium-based contrast agent. (C) Summed hyperpolarized carbon 13 pyruvate images. (D) Summed hyperpolarized carbon 13 lactate images. (E) Lactate:pyruvate (LAC/PYR) ratio map. (F, G) Dynamic hyperpolarized carbon 13 pyruvate and lactate imaging with a 12-second delay after injection over 15 time points at 4-second intervals. (Reprinted, with permission, from reference .)

Figure 4:

Carbon 13 (¹³C) pyruvate and ¹³C lactate signal intensity summed over all time points superimposed on an axial T1-weighted (T₁^w) image of the largest tumor cross-section for three different grade renal cell carcinomas. The border of the tumor is outlined in blue. ccRCC = clear cell renal cell carcinoma, k_PL = apparent exchange rate constant for lactate dehydrogenase, Lac/Pyr = lactate:pyruvate ratio, WHO/ISUP = World Health Organization/International Society of Urological Pathology. (Reprinted, under a CC BY 4.0 license, from reference .)

Figure 5:

Images in a 64-year-old patient who underwent robot-assisted radical prostatectomy. (A) Postsurgical histopathologic assessment confirmed the diagnosis of adenocarcinoma of the prostate. The red region of interest represents an International Society of Urological Pathology (ISUP) grade 1 lesion in the right peripheral zone, and the black region of interest represents a ISUP grade 3 lesion in the left peripheral zone. (B) T2-weighted MR (T2WI) image demonstrates a single marked area of low signal intensity corresponding to the target lesion in the left peripheral zone (yellow arrow). (C) Apparent diffusion coefficient (ADC) map demonstrates a corresponding focus of markedly restricted diffusion in the left peripheral zone (blue arrow). (D) Dynamic contrast-enhanced (DCE) MR image demonstrates the area of early enhancement in the left peripheral zone (green arrow). (E) Pyruvate signal-to-noise ratio (SNR) map with two areas of high pyruvate signal intensity, with the red and black arrows corresponding to the grade 1 and grade 3 histopathology-confirmed tumor foci, respectively. (F) Lactate SNR map demonstrates high [1–carbon 13]lactate signal intensity in the left peripheral zone lesion. (G) Total carbon SNR map shows higher signal intensity in the left peripheral zone tumor. (H) The apparent exchange rate constant for lactate dehydrogenase (k_PL) map (presented as sec^-1) shows a higher rate of pyruvate-to-lactate conversion in the more aggressive left peripheral zone lesion. (Reprinted, under a CC BY 4.0 license, from reference .)

Figure 6:

Two patients with human epidermal growth factor receptor 2–positive (HER2+) breast cancer (top row) and triple-negative breast cancer (TNBC) (bottom row). (A, F) Hyperpolarized carbon 13 MRI lactate:pyruvate (LAC/PYR) maps for both patients superimposed on hydrogen 1 MR images. (B, G) Diffusion images at baseline. Early follow-up (C, H) hyperpolarized and (D, I) diffusion images. Differences between baseline and follow-up images were significant for tumor volume and diffusivity. (Reprinted, under a CC BY 4.0 license, from reference .)