High-resolution tomographic imaging of microvessels

Abstract

Cancer belongs to the primary diseases these days. Although different successful treatments including surgery, chemical, pharmacological, and radiation therapies are established, the aggressive proliferation of cancerous cells and the related formation of blood vessels has to be better understood to develop more powerful strategies against the different kinds of cancer. Angiogenesis is one of the crucial steps for the survival and metastasis formation of malignant tumors. Although therapeutic strategies attempting to inhibit these processes are being developed, the biological regulation is still unclear. This study concentrates on the three-dimensional morphology of vessels formed in a mouse tumor xenograft model post mortem. Synchrotron radiation-based micro computed tomography (SRµCT) could provide the necessary information that is essential for validating the simulations. Using mouse and human brain tissue, the different approaches to extract the vessel tree from SRµCT data are discussed. These approaches include corrosion casting, the application of contrast agents such as barium sulfate, tissue embedding, all of them regarded as materials science based. Alternatively, phase contrast tomography was used, which gave rise to promising results but still not reaches the spatial resolution to uncover the smallest capillaries.

High-Resolution Imaging of Kidney Vascular Corrosion Casts with Nano-CT

“…To acquire larger volumes of 3D data from corrosion casts, tomographic X-ray scanning of casts with Micro-CT has been employed~Bentley et al., 2002;Sled et al, 2004;Marxen et al, 2004;Rennie et al, 2007;Muller et al, 2008;Wagner & Hossler, 2008;Mondy et al, 2009;Folarin et al, 2010!. However, due to limited resolution of the Micro-CT systems, the true submicron resolution of Nano-CT systems is preferred for detailed studies of the smallest capillary structures.…”

Visualization of tumor vessels using synchrotron radiation-based micro computed tomography

“…Healthy and cancerous tissue can be straightforwardly differentiated, since the fast grown tumor tissue exhibits a much higher density of capillaries than the surrounding healthy vascular structure. In several regions, however, the opposite behavior has been observed [2]. The explanation lies most probably in the necrosis of the inner part of the tumor.…”

“…First, already in alive mouse the tumor becomes dark red in the advanced stages indicating extended regions of blood coagulation. Second, the applied pressure for the injection of the barium sulfate suspension generates leakage as experimentally found at several sites of the tumor tissue [2] and demonstrated in Fig. 1a.…”

“…To understand the formation of cancerous tissue, the vascular network of tumors should be uncovered down to the capillary level. Standard synchrotron radiation-based micro computed tomography (SRμCT) in absorption contrast mode provides the necessary micrometer resolution [1] even for centimeter-sized tumors [2]. The visualization of a vessel tree, however, also requires sufficient contrast.…”

“…So, the successful application of absorption contrast tomography requires dedicated tissue preparation procedures including embedding [3] and erosion casting [4]. The more common procedure is the use of staining materials such as the incorporation of barium sulfate into the vessels [1,2,5]. The present study is based on the injection of a barium sulfate suspension with a grain size of 0.5 to 1 m and a concentration of 80 g/l via the left ventricle of the heart of mice under anesthesia using a peristaltic pump.…”