<p>Cancer and cardiac diseases are the major causes of
morbidity and mortality in the western world. Cardiovascular hemodynamics is
increasingly being used to understand the pathophysiological progression of
these diseases. Advancements in imaging modalities and development of
multiscale numerical models have opened avenues for innovative quantification
of flow metrics that may potentially aid in clinical diagnosis. The motivation
behind this dissertation is to investigate three different physiological flow
phenomena and develop new flow specific parameters as explained in the
following paragraphs.</p>
<p>Drug transport efficacy in treating breast tumors has a
strong correlation with tissue architecture, nanoparticle transport parameters
and hemodynamic metrics that varies from one patient to another. The exact time
interval between nanoparticle introduction and drug release must be accurately
determined to achieve therapeutic efficacy. The first chapter of the current
work implements a numerical model based on mixture theory equations to
investigate effect of varying inter-capillary separation on solute transport in
dual-channel tissues for various solute sizes (0.5-15 nm) and molecular weights
(0.1-70 kDa). The predictive capability of the numerical model is validated by
measurements of dextran transport in an invitro tumor platform containing
multiple blood vessels. The main contribution of this work is in reporting a
unique non-dimensional time at which solute concentration peaks in any location
in the tissue in absence of pharmacokinetics.</p>
<p> The second
chapter focuses on the development of a physics-based metric from color-m-mode
(CMM) echocardiography scans to correctly diagnose different stages of left
ventricle diastolic dysfunction (LVDD). Current practice of diagnosing LVDD
involves calculating a combination of parameters like intraventricular pressure
difference (IVPD) and propagation velocity (Vp) from the CMM scans. The conventional
Vp measurement is based on heuristics. This definition does not utilize the
entire information from the spatio-temporal velocity distribution of the
ventricle filling cycle. The present work challenges the underlying assumption
of the early ventricle filling wave moving with a constant velocity. The
proposed method in this chapter uses wavelets to analyze the early diastolic
ventricle filling wave and introduces a wavelet based peak propagation velocity
(Peak-Vw). Peak-Vw is free of the inherent assumptions of the subjective
selection of an iso-contour in the scan and measuring a slope from it. The
novelty of the Peak-Vw measurement can provide new insights for understanding
the complicated pathophysiology of the left ventricle (LV) diastolic function.</p>
<p>The final focus of this
dissertation is to investigate the evolving hemodynamics of the cardiovascular
system of Japanese medaka while it is growing from embryonic state to larval
stages. Cross-correlation of red blood cell patterns from 2D micro-particle
image velocimetry (µPIV)
images provide measurements of velocity fields in the fish heart and vessels.
Accurate velocity gradient measurements are required to further derive flow
quantities like wall shear stress (WSS), pressure drop across valves and
cardiac strain. </p>
<p>WSS experienced by endocardial
cells and vascular endothelial cells are linked to changes in cardiac specific
gene expressions. Previous studies with other vertebrate models investigating
mechano-genetic correlations were focused on mutating genes or introducing some
perturbation in the blood circulation. In the third chapter of this
dissertation, a baseline longitudinal study tracking the change in
cardiovascular WSS and gene expressions with natural progression of fish age is
presented for the first time. Peak WSS changes with fish age calculated at the
valves located at the ventricle inflow (AVC) and outflow (OFT), at the caudal
artery (CA) showed an inflection trend that coincides with developmental
landmarks of cardiac morphogenesis. Retrograde flow in the medaka heart valve
locations have been documented for the first time. Contrary to intuition, the
caudal and dorsal vessels in the fish tail displayed a reduction in
cross-sectional area with age progression. Identification of these unique
trends in the mechano-genetic tapestry of vertebrates prepares the ground for
future studies that can test the mechano-transduction mechanisms.</p>
<p>The fourth chapter delves deeper
into the flow induced pressure drop (<a>ΔP</a>) across the AVC
and OFT of the ventricle and the peak strain experienced by the ventricle wall
remodeling through fish age progression. Valve regions record the dynamic
variations of ΔP
that may induce WSS fluctuations with age progression. A variation of cardiac
strain with age is the key driver of varying chamber morphology. This is the
first study in teleost species literature that analyzes the endocardial work
(EW) calculated from a ΔP-strain
loop. The increase in EW observed across fish age progression can be directly
related to the heart’s metabolic demand. EW can be used in future studies of
human hearts to distinguish between healthy and diseased ventricles.</p>
<p>Overall, this dissertation provides an in-depth study of
three separate biophysical processes of the vertebrate cardiovascular system
and designs new metrics that have translational clinical potential.</p>
| Identifer | oai:union.ndltd.org:purdue.edu/oai:figshare.com:article/14589501 |
| Date | 14 May 2021 |
| Creators | Sreyashi Chakraborty (10797369) |
| Source Sets | Purdue University |
| Detected Language | English |
| Type | Text, Thesis |
| Rights | CC BY 4.0 |
| Relation | https://figshare.com/articles/thesis/NON-INVASIVE_QUANTIFICATION_OF_CARDIOVASCULAR_FLOW_METRICS_IN_VERTEBRATES/14589501 |
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