Dual‐phase imaging of cardiac metabolism using hyperpolarized pyruvate

Abstract

Purpose: Previous cardiac imaging studies using hyperpolarized (HP) [1- 13 C] pyruvate were acquired at end-diastole (ED). Little is known about the interaction between cardiac cycle and metabolite content in the myocardium. In this study, we compared images of HP pyruvate and products at end-systole (ES) and ED.Methods: A dual-phase 13 C MRI sequence was implemented to acquire two sequential HP images within a single cardiac cycle at ES and ED during successive R-R intervals in an interleaved manner. Each healthy volunteer (N = 3) received two injections of HP [1-13 C]pyruvate for the dual-phase imaging on the shortaxis and the vertical long-axis planes. Spatial distribution of HP 13 C metabolites at each cardiac phase was correlated to multiphase 1 H MRI to confirm the mechanical changes. Ratios of myocardial HP metabolites were compared between ES and ED. Segmental analysis was performed on the midcavity short-axis plane. Results:In addition to mechanical changes, metabolic profiles of the heart detected by HP [1-13 C]pyruvate differed between ES and ED. The myocardial signal of [ 13 C]bicarbonate relative to [1-13 C]lactate was significantly smaller at ED than the ratio at ES (p < .05), particularly in mid-anterior and mid-inferoseptal segments. The distinct metabolic profiles in the myocardium likely reflect the technical aspects of the imaging approach such as the coronary flow in addition to the cyclical changes in metabolism. Conclusion:The study demonstrates that metabolic profiles of the heart, measured by HP [1-13 C]pyruvate, are affected by the cardiac cycle in which that the data are acquired.

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

“…Previous human heart studies with HP 13 C MRI have performed crucial demonstrations of feasibility 8 , improvements to pulse sequence and reconstruction methods 9,10 , the effect of cardiac cycle on metabolic imaging 11 , the effect of adenosine stress tests 12 , the effect of fasting and fed states 14 , and patient studies investigating the effects of chemotherapy in breast cancer 13 , type 2 diabetes mellitus 14 , and post-myocardial infarction 15 . Several prior studies have included imaging acquisitions 8–12,15 , ratiometric methods 11,13,14 and pharmacokinetic modeling 12 . The major unique contribution of this work is to perform regional quantification of metabolism, including comparing ratiometric and pharmacokinetic modeling, with the fed/fasted volunteer studies demonstrating experimental changes in metabolism.…”

“…These results demonstrate the ability of HP 13 C MRI to quantify regional cardiac metabolism, and the initial methods and kinetic rates reported will improve the design and interpretation of future studies. Previous human heart studies with HP 13 C MRI have performed crucial demonstrations of feasibility 8 , improvements to pulse sequence and reconstruction methods 9,10 , the effect of cardiac cycle on metabolic imaging 11 , the effect of adenosine stress tests 12 , the effect of fasting and fed states 14 , and patient studies investigating the effects of chemotherapy in breast cancer 13 , type 2 diabetes mellitus 14 , and post-myocardial infarction 15 .…”

“…Several prior studies have included imaging acquisitions [8][9][10][11][12]15 , ratiometric methods 11,13,14 and pharmacokinetic modeling 12 . The major unique contribution of this work is to perform regional quantification of metabolism, including comparing ratiometric and pharmacokinetic modeling, with the fed/fasted volunteer studies demonstrating experimental changes in metabolism.…”

“…In parallel, the pyruvate solution was drawn into a syringe (Medrad Inc, Warrendale, PA, USA) through a 0.2 μm sterile filter (ZenPure, Manassas, VA, USA) and transported into the scanner for injection. The delay between dissolution and injection averaged 66.4 s, with a range of 63.4 to 73.1 s. A 0.43 mL/kg dose of an approximately 250 mM hyperpolarized[1][2][3][4][5][6][7][8][9][10][11][12][13]…”

Current methods for hyperpolarized [1‐13C]pyruvate MRI human studies

“…To cope with the periodic cardiac motion, most human heart studies to date used gating to the diastolic window, the longest cardiac cycle interval, which has reduced motion. 2,22,28,30,35,36,38,45,52 The duration of the diastolic window limits the available data sampling time, making cardiac acquisitions the most time-constrained of the HP 13 C MRI applications. The most common acquisition approach is metabolite-specific imaging with spiral k-space trajectories.…”