Biomedical Engineering Reference
In-Depth Information
inform modeling and modeling suggests new experiments. However, modeling
of cardiac ventricular conduction has to a large extent lacked this interplay.
While it is now possible to measure electrical activation of the epicardium at
relatively high spatial resolution, the difficulty of measuring the geometry and
fiber structure of hearts that have been electrically mapped has limited our abil-
ity to relate ventricular structure to conduction via quantitative models. As de-
scribed in the following sections, we are approaching this problem by: (a)
mapping ventricular activation using high-density epicardial electrode arrays;
(b) measuring and modeling ventricular geometry and fiber orientation at high
spatial resolution using diffusion tensor magnetic resonance imaging (DTMRI);
(c) constructing computational models of the imaged hearts; and (d) comparing
simulated conduction properties with those measured experimentally in the same
heart. This is one approach to "closing the loop" between experiment and model-
ing at the whole-heart level.
3.1. Mapping of Epicardial Conduction in Canine Hearts
We have recently performed electrical mapping studies in which epicardial
conduction in response to various current stimuli has been measured using elec-
trode arrays consisting of a nylon mesh with 256 electrodes and electrode spac-
ing of ~5 mm sewn around its surface. Bipolar epicardial twisted-pair pacing
electrodes were sewn onto the right atrium (RA) and the right-ventricular (RV)
free-wall. Four to ten glass beads filled with gadolinium-DTPA (~5 mM) were
attached to the sock as localization markers, and responses to different pacing
protocols we recorded. Figure 5A shows an example of measurement of activa-
tion time (color bar, in msec) measured in response to an RV stimulus pulse
applied at the epicardial locations marked in red. After all electrical recordings
are obtained, the animal is euthanized with a bolus of potassium chloride, and
the heart is then scanned with high-resolution T1-weighted imaging in order to
locate the gadolinium-DTPA filled beads in scanner coordinates. The heart is
then excised, sock electrode locations are determined using a 3D digitizer (Mi-
croScribe 3DLX), and the heart is formalin-fixed in preparation for DTMRI.
3.2. Measuring the Fiber Structure of the Cardiac Ventricles Using DTMRI
DTMRI is based on the principle that proton diffusion in the presence of a
magnetic field gradient causes signal attenuation, and that measurement of this
attenuation in several different directions can be used to estimate a diffusion
tensor at each image voxel (60,61). Several studies have now confirmed that the
principal eigenvector of the diffusion tensor is locally aligned with the long axis
of cardiac fibers (62-64).
