Abstract

Accurate microvascular morphometric information has significant implications in several fields, including the quantification of angiogenesis in cancer research, understanding the immune response for neural prosthetics, and predicting the nature of blood flow as it relates to stroke. We report imaging of the whole mouse brain microvascular system at resolutions sufficient to perform accurate morphometry. Imaging was performed using Knife-Edge Scanning Microscopy (KESM) and is the first example of this technique that can be directly applied to clinical research. We are able to achieve ≈ 0.7μm resolution laterally with 1μm depth resolution using serial sectioning. No alignment was necessary and contrast was sufficient to allow segmentation and measurement of vessels.

Highlights

  • The ability to acquire high-resolution three-dimensional images of microvascular structure has a significant impact in clinical research, in the study of angiogenesis

  • Accurate microvascular morphometric information has significant implications in several fields, including the quantification of angiogenesis in cancer research, understanding the immune response for neural prosthetics, and predicting the nature of blood flow as it relates to stroke

  • We report imaging of the whole mouse brain microvascular system at resolutions sufficient to perform accurate morphometry

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Summary

Introduction

The ability to acquire high-resolution three-dimensional images of microvascular structure has a significant impact in clinical research, in the study of angiogenesis. Angiogenic therapies have shown promise in cancer research, where manipulating microvessel growth can have a direct effect on tumor size and ability to metastasize. The quantification of microvascular structure is important for evaluating angiogenic cancer therapies designed to control blood flow to tumors [1, 2]. Microvascular structure is a major factor in the immune response to neural prosthetics [3]. A strong understanding of microvasculature may provide insights into limiting damage or supressing immune response to neural implants. Microvascular reconstruction can be used to aid in understanding of blood flow as it relates to stroke and vascular disease [4] and in quantifying vascular remodeling in implanted tissue [5]

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