Age‐associated change in pyruvate metabolism investigated with hyperpolarized ¹³C‐MRI of the human brain

Abstract

In this study, hyperpolarized 13 C MRI (HP-13 C MRI) was used to investigate changes in the uptake and metabolism of pyruvate with age. Hyperpolarized 13 C-pyruvate was administered to healthy aging individuals (N = 35, ages 21-77) and whole-brain spatial distributions of 13 C-lactate and 13 C-bicarbonate production were measured.Linear mixed-effects regressions were performed to compute the regional percentage change per decade, showing a significant reduction in both normalized 13 C-lactate and normalized 13 C-bicarbonate production with age: À7% AE 2% per decade for 13 C-lactate and À9% AE 4% per decade for 13 C-bicarbonate. Certain regions, such as the right medial precentral gyrus, showed greater rates of change while the left caudate nucleus had a flat 13 C-lactate versus age and a slightly increasing 13 C-bicarbonate versus age. The results show that both the production of lactate (visible as 13 C-lactate signal) as well as the consumption of monocarboxylates to make acetyl-CoA (visible as 13 C-bicarbonate signal) decrease with age and that the rate of change varies by brain region.

Hyperpolarized Carbon-13 Magnetic Resonance Imaging: Technical Considerations and Clinical Applications

“…Subsequently, this approach has been applied to various organs and diseases. Table 3 summarizes the clinical applications of HP 13 C-MRI, and Supplementary Table 1 contains the in-depth quantitative results from human studies [ 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 ].…”

“…In patients with mild traumatic brain injury, focal changes at the injured site revealed decreased bicarbonate levels and increased lactate production without apparent anatomical alterations [ 33 ]. Uthayakumar et al [ 35 ] employed HP 13 C-MRI to measure the whole-brain metabolism in individuals of various ages. Their findings showed a 7% decrease in lactate and a 9% decrease in bicarbonate levels per decade, with distinct spatial variations in the rates of change among different brain regions.…”

Task Activation Results in Regional13C-Lactate Signal Increase in the Human Brain

“…The production of 13 C-lactate signal indicates the reduction of 13 C-pyruvate to 13 C-lactate in the cytosol, while 13 C-bicarbonate production indicates the decarboxylation of 13 C-pyruvate into acetyl-CoA on the mitochondrial membrane. HP- 13 C MRI has previously been used to image 13 C-metabolite production in the human brain in healthy and disease states (2, 3, 4, 5, 6, 7).…”

Functional activation of pyruvate dehydrogenase in human brain using hyperpolarized [1‐13C]pyruvate

“…The absence or miniscule amounts of labeled metabolic products specific to pyruvate carboxylase in astrocytes supports that the detected [ 13 C]bicarbonate is predominantly produced from neurons. [9][10][11] Coupling neuronal metabolism with hyperpolarized bicarbonate has not been actively explored in preclinical models because the pyruvate metabolism is heavily impacted by the anesthetic condition [12][13][14] ; therefore, detection of in vivo [ 13 C]bicarbonate production in humans presents exciting opportunities to assess the activation of neuronal metabolism directly.…”