NOVEL METHODOLGY FOR MEASURING REGIONAL MYOCARDIAL EFFICIENCY

Objectives: Cardiac efficiency is an important measure for evaluating the state of most cardiomyopathies because a common feature is the inherent inefficiency of the heart in using oxygen to metabolize energetic substrates for the production of external work. Cardiac efficiency is usually measured as overall heart work (stroke volume × pressure) divided by oxygen consumption. Overall assessment of heart work is relatively straightforward by estimating the area contained within the pressure volume-loop. Only knowledge of stroke volume (i.e. LV end-diastolic and end-systolic volumes) and end-systolic LV pressure is required. In order to determine efficiency, measures of oxygen consumption by ¹¹C-acetate PET is then combined with measures of cardiac output and arterial pressure to define an overall work-metabolic index. Our approach differs from this global measure in that we seek to measure efficiency of tissue regions equal to the size of the resolution of the PET scanner. The Work (stress x strain) accomplished by a volume of tissue is divided by the chemical energy expended by the tissue region measured with PET using ¹¹C-acetate to obtain oxygen utilization (MVO₂) , and to obtain cardiac efficiency (=Work/MVO₂).

Methods: Our methodology is demonstrated by performing a simultaneous PET/MRI cardiac patient study 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 finite element (FE) biomechanical model of the heart was constructed by utilizing deformable image registration to alter the Dassault Systèmes FE Living Heart model to fit the geometry given in the cardiac MRI cine data. The passive material properties of the model were optimized to reproduce end-diastolic deformations using the FE analysis package Abaqus. The new patient specific FE cardiac model was transformed back into PET/MRI format providing 17 polar regional stresses and strains. To estimate regional Myocardial Equivalent 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 = T_{von M-sys} ε_p-sys HR/ 𝛾; (Newton-m g^-1 min^-1), where T_{von M-sys}is the systolic von Mises stress, ε_p-sys is the principal component of the systolic strain tensor, HR is the heart rate, and 𝛾; is the specific mass (1.055 g/cm³) of the tissue region. 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. The wash-in K₁ was used to calculate blood flow and k₂ was used to calculate oxygen consumption using the expression MVO₂=135(k₂)-0.96 (ml/100gm/min) assuming 1 ml oxygen = 21 joules or 21 Newton-m. 3) Cardiac Efficiency = MEMW/MVO₂ was then calculated for the 17 tissue regions.

Results: Transaxial images of ¹¹C-acetate 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 provided an oxygen consumption MVO₂ range of 10 to 25 ml/100gm/min or 210 to 525 joules/100gm/min (assuming 1 ml oxygen = 21 joules = 21 Newton-m). Five central slices of the MRI cine data provided measures of strains and stresses for a cardiac work MEMW range of 0.1 to 1 joules/gm/min and a Cardiac Efficiency range of 2 to 20 %.

Conclusions: Cardiac efficiency of specific tissue regions is obtained using a FE biomechanical model of the heart to calculate work and kinetic modelling of dynamic ¹¹C-acetate data to calculate oxygen consumption. The calculation of myocardial efficiency in patients provides a wealth of diagnostic information of functional analysis as well as biochemical and physiological characterization of inhomogeneity of cardiac efficiency.