Research: Analysis of Spatially Complex Structures

Figure 1: (A) Projection of MPLSM images. (B) Projection as in A, with superimposed skeleton shown in blue. (C) Ball-and-stick representation of vascular network showing superimposed diameters. (D) Generalized cylinder representation of vascular network.

Abnormal vasculature is a hallmark of many human diseases, and of solid tumor or lesion development, in particular. Blood vessels in tumors do not follow the hierarchic branching pattern of most normal vascular networks. The normal equilibrium between vascular growth and cellular demands in tumors results in avascular, hypoxic voids of multiple sizes. When quantified with fractal measures such as fractal dimension, minimum path length (a measure of tortuosity) and lacunarity, the size and number of such voids correspond to invasion percolation, a stochastic process in which a network expands around randomly distributed obstacles.

Such approaches have revealed the extent of abnormality in tumor vascular networks, the effect on nutrient and drug delivery and the process of vessel normalization during different therapies. Significantly, tumor and vascular growth can also be simulated with statistical growth models, providing insights into tumor morphology and function that are important for understanding the transport of nutrients in tumors, and for the design and delivery of blood-borne treatments.

Furthermore, the functional integrity of the brain microvascular network is crucial for the maintenance of energy metabolism and furnishing oxygen and nutrients to the brain parenchyma. Considering that the microvascular network can be severely altered in neurodegenerative disorders, it becomes important to assess quantitatively and dynamically potential disease or aging-related alterations in the brain microvascular bed in animal models.

Recent technology permits in vitro and in vivo approaches to these issues. Although relatively difficult, live imaging of the microvasculature following injection of a fluorescent dye in the peripheral circulation is feasible. We have recently applied our imaging and 3D reconstruction protocols successfully to such microvascular networks. This will make it possible to observe and quantify changes in blood vessels and blood flow dynamics in physiological conditions as well as in models of human diseases.