Current human brain applications and challenges of dynamic hyperpolarized carbon-13 labeled pyruvate MR metabolic imaging

Abstract

The ability of hyperpolarized carbon-13 MR metabolic imaging to acquire dynamic metabolic information in real time is crucial to gain mechanistic insights into metabolic pathways, which are complementary to anatomic and other functional imaging methods. This review presents the advantages of this emerging functional imaging technology, describes considerations in clinical translations, and summarizes current human brain applications. Despite rapid development in methodologies, significant technological and physiological related challenges continue to impede broader clinical translation.

Keywords: Carbon-13; Hyperpolarized; Lactate; Metabolic imaging; Pyruvate.

Fig. 1

Diagram of observable metabolic pathways using hyperpolarized [1-¹³C]pyruvate (red) and [2-¹³C]pyruvate (green) in the brain metabolism. [1-¹³C] converts to [1-¹³C]lactate via lactate dehydrogenase (LDH), [1-¹³C]alanine via alanine transaminase (ALT) in subcutaneous tissue and muscle outside the brain [43], and ¹³C carbon dioxide (¹³CO₂) via pyruvate dehydrogenase (PDH) within the mitochondria, which is then catalyzed to ¹³C-bicarbonate by carbonic anhydrase (CA). [2-¹³C]pyruvate provides direct measurements of [2-¹³C]lactate, [5-¹³C]glutamate, and other TCA intermediates

Fig. 2

Schematic describing the logistics associated with preparing the ¹³C sample, scanner, and patient. The example of RF coils was from Autry et al. [46]

Fig. 3

Serial k_PL within normal-appearing white matter and anatomic lesions from a patient with IDH mutant glioblastoma over 9 scans spanning 512 days (a). k_PL increased in the lesion when new lesions developed. During time points TP5–TP8, the emergence of a new gadolinium-enhancing lesion with elevated k_PL (red arrows) disappeared following treatment with bevacizumab and subsequent global elevation of k_PL (b). The dynamic data showed that overall lower ¹³C signals after treating with bevacizumab, but the conversion rate to [1-¹³C]lactate was increased (c). Figure adapted from Autry et al. [46]

Fig. 4

Lactate z-scores of new lesions from 11 patients with intracranial metastases. The red circles represent the lesions that progressed at 6 months of post-treatment follow-up or at the time of death, while these open circles are stable or responding lesions. Figure adapted from Lee et al. [63]

Fig. 5

The spectra at 15 s from the start of data acquisition using 2D dynamic EPSI from a 12-year-old patient with DIPG. Whitened singular value decomposition channel sum and tensor rank truncation-image enhancement significantly improved the SNR. Figure adapted from Chen et al. [79]