Hyperpolarized ¹³ C Metabolic MRI of the Human Heart

Abstract

Rationale:Altered cardiac energetics is known to play an important role in the progression toward heart failure. A noninvasive method for imaging metabolic markers that could be used in longitudinal studies would be useful for understanding therapeutic approaches that target metabolism.Objective:To demonstrate the first hyperpolarized 13C metabolic magnetic resonance imaging of the human heart.Methods and Results:Four healthy subjects underwent conventional proton cardiac magnetic resonance imaging followed by 13C imaging and spectroscopic acquisition immediately after intravenous administration of a 0.1 mmol/kg dose of hyperpolarized [1-13C]pyruvate. All subjects tolerated the procedure well with no adverse effects reported ≤1 month post procedure. The [1-13C]pyruvate signal appeared within the chambers but not within the muscle. Imaging of the downstream metabolites showed 13C-bicarbonate signal mainly confined to the left ventricular myocardium, whereas the [1-13C]lactate signal appeared both within the chambers and in the myocardium. The mean 13C image signal:noise ratio was 115 for [1-13C]pyruvate, 56 for 13C-bicarbonate, and 53 for [1-13C]lactate.Conclusions:These results represent the first 13C images of the human heart. The appearance of 13C-bicarbonate signal after administration of hyperpolarized [1-13C]pyruvate was readily detected in this healthy cohort (n=4). This shows that assessment of pyruvate metabolism in vivo in humans is feasible using current technology.Clinical Trial Registration:URL: https://www.clinicaltrials.gov. Unique identifier: NCT02648009.

Metabolic Studies of Tumor Cells Using [1‐13C] Pyruvate Hyperpolarized by Means of PHIP‐Side Arm Hydrogenation

“…Its transformation into [1‐ 13 C]lactate, [1‐ 13 C]alanine or decarboxylation into 13 CO 2 can be observed within few seconds following to the injection of the HP metabolite in vivo or its administration to cells’ suspension. All these favorable features made HP [1‐ 13 C]pyruvate a quite promising molecular tool that allows to distinguish the metabolism of healthy and diseased tissues in cancer,, heart and brain…”

Increased hyperpolarized [1‐13C] lactate production in a model of joint inflammation is not accompanied by tissue acidosis as assessed using hyperpolarized 13C‐labelled bicarbonate

“…This enormous increase in sensitivity has enabled real‐time imaging of tissue metabolism in vivo following intravenous injection of hyperpolarized 13 C‐labelled substrates,36 including in humans 37, 38. Previous magnetic resonance spectroscopic imaging (MRSI) studies in rats injected with hyperpolarized [1‐ 13 C]pyruvate showed raised lactate‐to‐pyruvate ratios in CFA‐induced inflammation,39 which, considering the relationship observed between lactic acid and acidosis,9, 12, 13 suggested that acidosis must occur in this widely used model.…”

Front Cover: Simulating Non‐linear Chemical and Physical (CAP) Dynamics of Signal Amplification By Reversible Exchange (SABRE) (Chem. Eur. J. 32/2019)

“…In solution, dihydrogen exchanges at ar ate k ex with the transientS ABRE complex IrH 2 S a S e [reaction (3)]. [26] We call this reactiont he "hydrogen exchange".…”

“…The hyperpolarization (HP) of nuclear spins promises to revolutionize medical diagnostics [1][2][3][4][5][6][7][8][9][10] and chemical analysis [11][12][13][14][15] alike. Amongo thers, signal amplification by reversible exchange (SABRE), discovered in 2008, [16] is an up-and-coming technique with unique properties,i ncluding continuous hyperpolarization.…”