Biomedical Engineering Reference
In-Depth Information
(a)
(c)
(b)
(d)
Fig. 10.12
Micrographs of
a
normal and
b
bicuspid heart valve leaflets. Collagen fiber architectural
measurements of human explants were used to determine the microstructure and then averaged to
obtain the mean microstructure maps as shown in (
c
). Subsequent statistical analysis shown in (
d
)
on mean fiber directions (
left
) and orientation index (OI) (
right
) shows important differences in the
belly region for the OI but the mean fiber directions are similar in two cases
valve structure. The bicuspid aortic valve (Fig.
10.12
a and b) is the most common
cardiac congenital anomaly and has been found to be a significant risk factor for
developing calcific aortic valve disease. We quantified the structure of human nor-
mal and bicuspid leaflets in the early disease stage. From these individual leaflet
mappings, average fiber structure maps were generated using a novel spline-based
technique to a total of six normal (tricuspid) and six bicuspid human explanted non-
diseased aortic valves. A common template of the simulated heart valve geometry
was used and a spline surface was fitted to this template geometry (RMSD of fitting
<
0.04 mm). The common template allows us to calculate the average fiber structure
of the sampled tricuspid data (Fig.
10.12
c and d), clearly showing the difference in
the fiber microstructure. Interestingly, we found statistically different and consistent
regional structures between the normal and bicuspid valves [
2
]. The regularity in
the observed microstructure was a surprising finding, especially for the pathological
BAV leaflets and is an essential cornerstone of any predictive modeling of the heart
valves.
Ultimately, we would like to connect the organ-scale simulations to evaluate our
understanding of the VIC mechanotransduction. To this end, it would be beneficial
to develop a VIC phenotypic/biosynthetic model linked to organ-level deformations.
For example, in the aortic valve leaflet transvalvular pressures above
5mmHg
predominately result in ECM compaction as the collagen fibers become uncrimped
and taut. From this ECM compaction, significant VIC shape changes have been
observed with increasing pressures. Even a phenomenological model could, thus,
simulate the VIC population with mechanical inputs (quantified by the deforma-
tion of the VIC nuclei) and cytokine activity. It could then be possible to predict
the phenotypic and biosynthetic response of VICs under altered stress conditions.
∼
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