Biophysical Models of the Cardiovascular System - Systems Biology: Networks, Models, and Applications - page 280

direction being oriented predominantly in the base-apex direction
on the epicardial and endocardial surfaces, and rotating to a circum-
ferential direction in the midwall. These early studies of transmural
variation of inclination angle were restricted to a small number of
measurement sites. Nielsen et al. [78] overcame this limitation by using
a custom-built histological apparatus to measure fiber orientation at
up to ~14,000 points throughout the myocardium, with a resolution
of ~500, 2500, and 5000

m in the radial, longitudinal, and circumferen-
tial directions, respectively. This work led to the first complete
reconstruction of ventricular geometry and fiber inclination angle—an
achievement that has had significant impact on the cardiac mechanics
and electrophysiology communities.
Despite this important advance, present histological methods
suffer from the disadvantage that they require many weeks to even
months for reconstruction of a single heart. As a consequence, only
small numbers of canine and rabbit hearts have been reconstructed.
The complete ventricular fiber organization of the human heart has
never been reconstructed and modeled. Full reconstruction of ventric-
ular fiber organization in diseased hearts has never been performed.
The use of DTMRI to measure cardiac geometry and fiber orienta-
tion solves many of these problems. 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 [79,80]. Several studies have now confirmed that the
principal eigenvector of the diffusion tensor measured at each imag-
ing voxel is locally aligned with the long axis of cardiac fibers [81-83].
Use of DTMRI for reconstruction of cardiac fiber orientation provides
several advantages over traditional histological methods:

µ

1. DTMRI yields estimates of the absolute orientation of cardiac
fibers, whereas histological methods yield estimates of only
fiber inclination angle (defined as the angle formed by project-
ing fiber orientation onto the epicardial tangent plane, and
computing the angle between this projection and a circumfer-
entially oriented epicardial tangent plane vector).
2. DTMRI performed using formalin-fixed tissue (a) yields high-
resolution images of the cardiac boundaries, thus enabling pre-
cise reconstruction of ventricular geometry using image
segmentation software, and (b) eliminates flow artifacts pres-
ent in perfused heart, enabling longer imaging times, increased
signal-to-noise ratio, and improved spatial resolution.
3. DTMRI provides estimates of fiber orientation at more than
several orders of magnitude more points than is possible with
histological methods.