Focus Session
SCMR 22nd Annual Scientific Sessions
Andrew Apps, MD
Clinical Research Training Fellow
Oxford Centre for Clinical Magnetic Resonance Research
Jack Miller, PhD
Physicist
Oxford Centre for Clinical Magnetic Resonance Research
Justin Lau, PhD
Physicist
Oxford Centre for Clinical Magnetic Resonance Research
Mark Peterzan
Clinical Research Training Fellow
Oxford Centre for Clinical Magnetic Resonance Research
Andrew Lewis, PhD
Clinical Research Fellow
University of Oxford Centre for Clinical Magnetic Resonance
Claire Trumper, BSc
Clinical Pharmacist
Oxford Centre for Clinical Magnetic Resonance Research
Michael Dodd, PhD
Postdoctoral Research Fellow
Oxford Centre for Clinical Magnetic Resonance Research
Angus Lau, PhD
Physicist
University of Toronto
Oliver Rider, PhD
Associate Professor of Cardiovascular Medicine
University of Oxford
Stefan Neubauer, MD
Director, Oxford Centre for Clinical Magnetic Resonance Research
University of Oxford
Damian Tyler, PhD
Professor
University of Oxford
Background:
Hyperpolarized MR opens the door to the real time in-vivo metabolic imaging of a number of metabolic pathways, depending on the choice of 13C substrate used. The transition from the fasted to fed state is characterised by a shift in energy substrate utilisation towards glucose and away from fatty acids, mediated in part by the activation of Pyruvate Dehydrogenase (PDH) which catalyses the decarboxylation of pyruvate. Metabolic flexibility of fuel substrate is lost in diabetes, which is characterised by blunted cardiac PDH flux. We aimed to investigate the ability of Hyperpolarized MR to characterise such physiological and pathological changes by assessing the substrate switching that occurs during the fasted to fed transition in healthy and type II diabetic subjects.
Methods:
Five Type 2 diabetics (age 53+/-4, BMI 31+/-6, HbA1c 6.8+/-.7%, left ventricular ejection fraction (LVEF) 57+/-5%)), and four controls (age 50+/-12, BMI 22+/-2, LVEF 59+/-3%) received 1H CINE imaging for functional assessment and 13C MR spectroscopy for assessment of PDH flux in the fasted state. Five (3Controls, 2Diabetics) then went on to receive successful repeat 13C imaging 45-60 minutes after a 70g oral glucose load (Rapilose®) Hyperpolarized [1-13C]pyruvate (SpinLab, GE healthcare, 0.4ml/kg) was injected via a Medrad syringe, following which an ECG gated 13C, slice selective spectroscopy sequence ran for four minutes (FA100, BW5Khz, TR500ms). All patients received echocardiography.
Results:
Hyperpolarized injections were well tolerated in all subjects. One minute of the acquired spectra were summed, beginning from the first appearance of pyruvate within the LV. Baseline cardiac and demographic data, and enzymatic pyruvate metabolism data are shown in figure 1. Summed spectra from a control and diabetic participant are shown in figure 2. H13CO3-/Pyr ratios for all successful injections are shown in figure 3, alongside the time course of H13CO3- production for a control and diabetic participant. A two way-ANOVA run on paired data sets (N=3 controls, N=2 diabetics) demonstrated diabetes significantly reduced PDH flux (df =1, p<0.05). Within healthy controls, PDH flux increased after feeding, but not significantly so (0.0077 vs 0.0111; p=0.56, unpaired t-test).
Conclusion:
Using hyperpolarized 13C MRS, for the first time in humans we demonstrated the impaired cardiac PDH flux that characterises diabetes. The power of this technology to measure real time, in-vivo metabolism is shown. Defining the hallmark metabolic consequences of various cardiac diseases may potentially offer unparalleled diagnostic and even therapeutic opportunities.