Assessing the optimal preparation strategy to minimize the variability of cardiac pyruvate dehydrogenase flux measurements with hyperpolarized MRS

Abstract

Hyperpolarized [1‐13C] pyruvate MRS can measure cardiac pyruvate dehydrogenase (PDH) flux in vivo through 13C‐label incorporation into bicarbonate. Using this technology, substrate availability as well as pathology have been shown to modulate PDH flux. Clinical protocols attempt to standardize PDH flux with oral glucose loading prior to scanning, while rodents in preclinical studies are usually scanned in the fed state. We aimed to establish which strategy was optimal to maximize PDH flux and minimize its variability in both control and Type II diabetic rats, without affecting the pathological variation being assessed. We found similar variances in the bicarbonate to pyruvate ratio, reflecting PDH flux, in fed and fasted/glucose‐loaded animals, which showed no statistically significant differences. Furthermore, fasting/glucose loading did not alter the low PDH flux seen in Type II diabetic rats. Overall this suggests that preclinical cardiac hyperpolarized magnetic resonance studies could be performed either in the fed or in the fasted/glucose‐loaded state. Centres planning to start new clinical studies with cardiac hyperpolarized magnetic resonance in man may find it beneficial to run small proof‐of‐concept trials to determine whether metabolic standardizations by oral or intravenous glucose load are beneficial compared with scanning patients in the fed state.

Detection of increased pyruvate dehydrogenase flux in the human heart during adenosine stress test using hyperpolarized [1-13C]pyruvate cardiovascular magnetic resonance imaging

“…Participants were fasted for 8 to 15 h and oral glucose loading was used to maximize PDH flux and standardize metabolic conditions in both the rest and stress study [ 16 , 20 , 21 ]. Adenosine is a validated and widely used pharmacological stress test in cardiac imaging [ 10 , 22 , 23 ].…”

Regional quantification of cardiac metabolism with hyperpolarized [1 -13C]-pyruvate MRI evaluated in an oral glucose challenge

“…For subject preparation, most prior studies suggesting imaging in a fed state to allow for PDH measurements by increasing 13 C-bicarbonate SNR, with animal model studies showing increased conversion to lactate, alanine, and bicarbonate in a fed state 33 . Interestingly, similar performance in terms of sensitivity, repeatability, and measurement of pathologic variations was measured when imaging in fed state created by a carbohydrate rich meal versus an oral glucose load 34 . However, in HCM, imaging in the fasting state may be useful to demonstrate metabolic remodeling in hypertrophied myocardium.…”

Regional quantification of cardiac metabolism with hyperpolarized [1-13C]-pyruvate CMR evaluated in an oral glucose challenge

“…For subject preparation, most prior studies suggesting imaging in a fed state to allow for PDH measurements by increasing 13 C-bicarbonate SNR, with animal model studies showing increased conversion to lactate, alanine, and bicarbonate in a fed state [ 33 ]. Interestingly, similar performance in terms of sensitivity, repeatability, and measurement of pathologic variations was measured when imaging in fed state created by a carbohydrate rich meal versus an oral glucose load [ 34 ]. However, in HCM, imaging in the fasting state may be useful to demonstrate metabolic remodeling in hypertrophied myocardium.…”