Project Details
Description
ABSTRACT
Ascending thoracic aortic aneurysm (ATAA) is a major cardiovascular health problem characterized by
a dilated aorta that may eventually dissect or rupture. ATAA presents a serious challenge in that the surgery is
difficult and dangerous, so aneurysm repair criteria must balance the risk of a dissection and/or rupture with
the risk of surgery. Current surgical guidelines are based on ATAA diameter or growth rate, but up to 60% of
patients with an ATAA experience a dissection before surgical criteria are reached, hence there is a clear need
for additional biomarkers of aneurysm failure. Possible biomarkers fall into broad categories including genetic,
microstructural, geometrical, and biofluids, but it is challenging to obtain enough human data to calculate and
correlate these biomarkers with critical outcomes such as failure. It is likely that a single biomarker is not
sufficient, but composite biomarkers that are not intuitively obvious may be necessary for significant predictions
of patient outcomes. In this proposal we will use a combination of models: 1) a mouse model of ATAA
associated with Marfan Syndrome, 2) a multiscale, multiphysics model of ATAA growth and remodeling, and 3)
virtual patient models derived from real patient imaging data, to determine composite biomarkers that may
predict ATAA growth, progression, and failure. Our first Specific Aim is to use a genetic mouse model of ATAA
associated with Marfan Syndrome to characterize aneurysm progression and failure in previously unachieved
detail, quantifying aortic shape, tissue composition, tissue mechanical properties, and hemodynamics over
time. This level of detail is not possible in human patients and is necessary to validate and test hypotheses on
the growth and remodeling rules in our multiscale, multiphysics model in Specific Aim 2 and to provide an initial
set of biomarkers to evaluate for our virtual patients in Specific Aim 3. Our second Specific Aim is to develop a
novel multiscale, multiphysics computational model of ATAA growth and remodeling to produce results that will
be compared to the mouse data in Specific Aim 1 and used to predict remodeling progression in real and
virtual human patients in Specific Aim 3. In our third Specific Aim, we will use available human ATAA scans
from Marfan Syndrome patients to generate a statistical shape model basis for the ATAA geometry, and we will
use that basis to generate virtual patients, whose TAA course throughout progression and failure will be
created by the model in Specific Aim 2, with parameters determined from published literature and our mouse
data in Specific Aim 1. Both real and virtual patient data will then be used to train a machine learning tool to
relate the composite biomarkers to the remodeling outcomes and predict failure risk. This plan synthesizes
multiple recent advances and supplements them with new ideas to produce a computer system capable of
making useful failure predictions for ATAA.
Status | Active |
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Effective start/end date | 7/1/22 → 6/30/24 |
Funding
- National Heart, Lung, and Blood Institute: $623,800.00
- National Heart, Lung, and Blood Institute: $600,449.00
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