Biomedical Engineering Reference
In-Depth Information
a
b
real vasculature
virtual vasculature
inflow (pressures 35...45mmHg)
outflow (pressures 15...25mmHg)
Fig. 3.3 Image reconstruction. We reconstructed the vascular network by applying the following
strategy. 3D multiphoton fluorescence microscopy images ( a ) taken from mouse models in vivo
formed the basis of our geometrical reconstruction. Based on the data, we reconstructed the
vascular graph model that describes the connectivity of the vascular network. ( b ) We assigned
inflow ( red points ) and outflow ( blue points ) nodes at various pressures in order to obtain a
persistent and stable network. The vascular graph is characterised by the spatial coordinates of the
nodes and the connections between them
experimental data. Experimental data defining a vascular network associated with a
tumour were obtained by implanting a tumour construct comprising a central core
of human breast cancer cells surrounded by rat microvessel fragments, embedded in
a collagen matrix into a mouse dorsal window chamber. The cancer cells and rat
microvascular cells express different fluorescent proteins so that, following implan-
tation, the tumour and its vascular network can be visualised.
We used experimental data to reconstruct the vascular graph model, locating
nodes in the vessel centres and connecting them by edges. We embed the vascular
system into healthy tissue and then simulate vessel adaptation until a steady state is
reached. This example provides proof of concept.
Currently in the computational models, the vasculature is embedded in a healthy
tissue into which a small tumour is implanted and its evolution is studied. A
projection of a 3D image set of the tissue is presented on the left-hand side of
Fig. 3.3 , while the virtual reconstruction is shown on the right-hand side. In
Fig. 3.4 , we observe that the tumour expands radially into the surrounding healthy
tissue which it degrades by decreasing the p53 death threshold for normal cells.
Normal cells in the lower left and right corners of the simulation domain (first
column) are exposed to low oxygen (hypoxia), and hence produce VEGF which
induces an angiogenic response in our model. While the new vessel in the lower left
corner is persistent and increases in radius, the vessel in the lower right corner is
pruned back. In this case, pruning occurs because the new blood vessel connects
vessels from the initial network that have similar pressures. In general, the normal
cells are adequately nourished by oxygen as only a few hypoxic cells can be
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