Abstract:
The coronary circulation is a network of vessels that supplies oxygenated blood to
the myocardium and removes the by-products of metabolism. While this coronary
perfusion is fundamental to maintaining cardiac performance, the heart's mechanical
contraction interferes with blood
ow. Despite several investigations over a prolonged
period, understanding of how mechanical contraction in
uences coronary blood
ow
remains limited.
In part, this limitation exists because we cannot easily measure mechanical activity
and coronary blood
ow in vivo within the heart wall. A practical alternative to direct
measurement is to model the myocardial-vessel interactions mathematically. Focused
on this goal, researchers have developed a variety of mathematical models throughout
the twentieth century. However, a major constraint on model development is the
dearth of detailed data on the vessel anatomy and the myocyte structures within which
it is embedded.
While we possess excellent descriptions of structure at all levels of the coronary vascular
network, we still lack systematic, quantitative data about the three-dimensional
relationship between cardiac muscle cells and the microcirculatory networks that deliver
blood to them. To investigate this relation, the construction of representative,
large scale anatomic models of coronary microcirculation is primary.
Employing recent advancements in tissue clearing and high-throughput imaging,
our group simultaneously acquired myocytes and microcirculation images throughout
the entire short-axis slices of the rat heart. This thesis sought to extract accurate information from these large-scale images and quantitatively assess the anatomical relationship
between cardiomyocytes and coronary microcirculation.
A chunk-based image segmentation pipeline was developed to process large-scale
images and combined with an e cient graph generation technique developed to extract
networks from the segmented images. Next, the dominant orientation of the
myocytes was computed using structure tensor analysis. Finally, the orientation of the
myocytes and microcirculation were compared and statistically analysed throughout
the six short-axis cardiac ventricular slices from the rat, including three normal and
three diseased hearts.
The study identi ed that the microcirculatory vessels were closely aligned with the
myocytes in both the normal and hypertensive hearts. Comparing the diseased and
normal data sets revealed that the microvessels follow the pathophysiologically induced
changes of cardiomyocytes in the event of cardiac remodelling. Additionally, this study
showed that the capillaries which were misaligned with the myocytes were shorter than
the well-aligned capillaries. From analysis on small blocks, the study also found that
the hypertensive hearts had a higher variance of oxygen di usion distance compared
to their normotensive counterparts. Irregular vascular patterns were also observed in
diseased hearts.
To our knowledge, this study is the rst time that such large-scale datasets of
coronary microcirculation and cardiomyocytes have been collected, processed, and statistically
analysed. To achieve this goal, we developed tools and techniques to process
and analyse large-scale microscopy images and created and demonstrated novel methods
to repair vessels networks and register multiple images with no regions of mutual
information. The tools and techniques from this study will serve other medical image
investigations, and the wealth of data from this study will pave the way for numerous
related researches.