IN VIVO MEASURE OF CARDIAC EFFICIENCY USING HYBRID PET/MRI TECHNOLOGY

31 Objectives: A normal heart is approximately 20% efficient as measured by the ratio of mechanical work to oxygen utilization. The heart requires rapid production of ATP resulting in complete turnover of ATP every 10 seconds to maintain cardiac function. In a normal heart this requires oxygen for metabolism of fatty acid (FA) as the primary metabolic substrate, accounting for 50-70% of ATP production from FA β-oxidation. However, in heart failure (HF) there is significant metabolic changes and structural remodeling that leads to reduced cardiac efficiency as exemplified with glucose being the preferred energy source even though FA provides 9 kcal/gram compared to 4 kcal/gram for glucose. This is manifested as an imbalance between oxidative metabolism and cardiac function; and appears to be a key factor of disease progression. Hybrid PET/MRI offers the potential for MRI to measure Work (stress x strain) in a region of myocardial tissue simultaneously with PET to measure oxygen utilization (MVO2) using 11C-acetate, and to study cardiac efficiency (=Work/MVO2) in the etiology of and therapies for HF. Methods: A simultaneous PET/MRI cardiac patient study was performed using the GE PET/MRI 3.0T scanner (GE Healthcare, Milwaukee, WI) at UCSF. A dynamic cardiac PET study began immediately prior to the injection of 15.1 mCi of 11C-acetate acquiring the data for 30 minutes while simultaneously acquiring MRI data from cine pulse sequences. 1) Processing cardiac MRI cine data: A 3D geometry for the FE mechanical model of the heart was constructed by utilizing deformable image registration to alter the Dassault Systemes FE Living Heart model to fit the geometry given in the cardiac MRI cine data. The standard fiber distribution and material properties of the Living Heart model were assumed. The FE model was analyzed using Abaqus to provide regional circumferential stresses and strains for 4 regions (anterior, posterior, septal, and lateral). To estimate regional Myocardial External Minute Work (MEMW), the regional stress values were multiplied by the corresponding regional strain values and by the heart rate and corrected for the specific mass using the equation: MEMW = Tsys ecirc HR/γ (Newton-m g-1 min-1), where Tsysis the systolic stress, ecirc is the circumferential strain, HR is the heart rate, and γ is the specific mass (1.055 g/cm3) of the tissue. 2) Processing dynamic PET data: A 1-tissue compartment model was used to calculate wash-in (K1) and wash-out (k2) rate constants for each tissue region. We did not correct for the 11CO2 contribution in the PET-derived blood activity. The expression MVO2=135(k2)-0.96 (ml/100gm/min) was used to calculate the oxygen consumption assuming 1 ml oxygen = 21 joules or 21 Newton-m. 3) Cardiac Efficiency = MEMW/MVO2 was then calculated for each tissue region. Results: Transaxial images of 11C-acetate uptake show excellent resolution provided by the time-of flight PET camera. From the dynamic 11C-acetate PET data, the global MBF was calculated to be 1.0104 ml/min/gm and the wash-out of 11CO2 to be k2=0.2012 min-1. An oxygen consumption MVO2 of 26.2 ml/100gm/min or 550 joules/100gm/min (assuming 1 ml oxygen = 21 joules = 21 Newton-m) was calculated. Three central slices of the MRI cine data provided measures of strains and stresses for the cardiac efficiency estimates. Conclusions: This preliminary study shows the potential value and feasibility of using a FE mechanical model of the heart to calculate work and kinetic modelling of dynamic 11C-acetate data to calculate oxygen consumption of specific tissue regions. Using PET and MRI together for calculating, evaluating, and studying myocardial efficiency in patients, provides a wealth of diagnostic information from functional analysis as well as biochemical and physiological characterization of inhomogeneity of cardiac efficiency and relationships between myocardial perfusion, structure, and wall dynamics.