Antenatal architecture and activity of the human heart

Abstract

One contribution of 25 to a Theme Issue 'The virtual physiological human: integrative approaches to computational biomedicine'. We construct the components for a family of computational models of the electrophysiology of the human foetal heart from 60 days gestational age (DGA) to full term. This requires both cell excitation models that reconstruct the myocyte action potentials, and datasets of cardiac geometry and architecture. Fast lowangle shot and diffusion tensor magnetic resonance imaging (DT-MRI) of foetal hearts provides cardiac geometry with voxel resolution of approximately 100 mm. DT-MRI measures the relative diffusion of protons and provides a measure of the average intravoxel myocyte orientation, and the orientation of any higher order orthotropic organization of the tissue. Such orthotropic organization in the adult mammalian heart has been identified with myocardial sheets and cleavage planes between them. During gestation, the architecture of the human ventricular wall changes from being irregular and isotropic at 100 DGA to an anisotropic and orthotropic architecture by 140 DGA, when it has the smooth, approximately 1208 transmural change in myocyte orientation that is characteristic of the adult mammalian ventricle. The DT obtained from DT-MRI provides the conductivity tensor that determines the spread of potential within computational models of cardiac tissue electrophysiology. The foetal electrocardiogram (fECG) can be recorded from approximately 60 DGA, and RR, PR and QT intervals between the P, R, Q and T waves of the fECG can be extracted by averaging from approximately 90 DGA. The RR intervals provide a measure of the pacemaker rate, the QT intervals an index of ventricular action potential duration, and its rate-dependence, and so these intervals constrain and inform models of cell electrophysiology. The parameters of models of adult human sinostrial node and ventricular cells that are based on adult cell electrophysiology and tissue molecular mapping have been modified to construct preliminary models of foetal cell electrophysiology, which reproduce these intervals from fECG recordings. The PR and QR intervals provide an index of conduction times, and hence propagation velocities (approx. 1-10 cm s 21, increasing during gestation) and so inform models of tissue electrophysiology. Although the developing foetal heart is small and the cells are weakly coupled, it can support potentially lethal re-entrant arrhythmia.

Diffusion tensor imaging and histology of developing hearts

“…Previous DTI studies of developing prenatal and postnatal hearts reported different trends (13,(60)(61)(62). Human fetal studies reported progressively increasing FA and nearly no coherent fiber organization in fetal hearts taken at early points of the second trimester compared with term hearts (60,61). A pig DTI study reported increasing FA in mid-gestation hearts that decreased after birth, with clearly detectable and coherent fiber organization at all fetal and term ages (13).…”

Anatomically correct assessment of the orientation of the cardiomyocytes using diffusion tensor imaging

“…It is the combination of the longitudinal and radial orientations that provides the complete anatomical description of the orientation of the cardiomyocytes. 47 In previous investigations, the radial orientation of the cardiomyocytes has been assessed either as the intrusion angle, 8,29,39,40,48 or more often as the transverse angle 12,13,21,22,25,30,32,33,49,50 (Figures 2G and H). Both angles are assessed relative to the epicardial curvature.…”

“…Different investigators have used different reference points when assessing angles. In some studies, the only point of reference used is the left ventricular long axis, shown as e ax in our Figure A . Systolic mural thickening, however, which is the main rearrangement of the myocardium through the cardiac cycle, occurs relative to a radial axis at right angles to the epicardium, shown as e r in Figure B.…”

“…In some studies, the only point of reference used is the left ventricular long axis, shown as e ax in our Figure 2A. 18,32,33 Systolic mural thickening, however, which is the main rearrangement of the myocardium through the cardiac cycle, occurs relative to a radial axis at right angles to the epicardium, shown as e r in Figure 2B. If knowledge of the orientations is to provide the most physiologically relevant information, the angles should also be measured whilst taking account of the epicardial curvature of the ventricular cone.…”

Self-terminating re-entrant cardiac arrhythmias: quantitative characterization

“…The foetal ECG [6,7] was extracted from maternal recordings (non-invasive monitoring of uterine electrical activity) from a Monica AN24 via electrodes placed on the abdomen. Episodes of foetal tachycardia were initially located using Monica software, and then the raw V(t) exported for graphical analysis.…”