All ETDs from UAB

Advisory Committee Chair

Andrew E Pollard

Advisory Committee Members

Xun Ai

Silvio H Litovsky

Jack M Rogers

Document Type

Thesis

Date of Award

2012

Degree Name by School

Master of Biomedical Engineering (MBE) School of Engineering

Abstract

The goal of the present study was to identify the microstructural variability in myocyte orientation and in the arrangement of the collagen network to explore the interstitial compartment's contribution to discontinuous propagation. Microstructural data was obtained from healthy rabbit ventricular subepicardium through a sequence of image processing steps. Collagen quantity was measured in successive serial sections using established histological techniques. Binary 2D maps of collagen quantity were obtained from each section as a difference of images acquired under (i) brightfield illumination with a rhodamine filter and (ii) polarized illumination. Images were then registered by x-y translation and rotation to align a set of tissue markers in each section. A realistic 250 x 500 x 260 µm3 3D collagen map was obtained as a stack of the aligned images. To obtain collagen quantities for completion of 3D bidomain simulations, collagen quantity was measured for each 22.7 x 22.7 x 25 µm3 block (n=3146) composing the collagen map. This block size was advantageous as it provided an opportunity to examine conduction with a fine spatial resolution. The principal angle of collagen orientation was calculated and collagen quantity and orientation values were converted to microimpedances for completion of bidomain simulations. Simulations were completed using microimpedances calculated in three ways: (i) assuming homogeneous collagen distribution, (ii) using histologically validated collagen quantity and constant orientation, (iii) using histologically validated collagen quantity and orientation values. Reconstruction of the collagen matrix revealed two primary collagen arrangements: longitudinal strands and punctate architecture. In computer simulations, maximum upstroke velocity significantly increased in punctate regions (paired t-test, p<0.05), while upstroke velocity was maintained in longitudinal regions. This indicates that collagen architecture modulates impulse propagation. Further, reconstructed bipolar surface electrograms with 50 µm spacing revealed increases in interstitial potential amplitude, both in simulations with impedance distributions derived from collagen quantity data alone and derived from collagen quantity and orientation data. This reveals that microstructural heterogeneity is reflected in surface potential recordings even on this small scale.

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Engineering Commons

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