Radiation therapy is one of the most successful treatments for malignant tumors. In addition to causing tumor death it also weakens and collapses the rapidly forming vasculature around the tumor. For tumors in the central nervous system (CNS), vasculature damage and radiation-induced activation of astrocytes can cause acute and long-term collateral damage to normal brain tissue.
M. Waleed Gaber, an associate professor at Baylor’s College of Medicine and co-director of the small animal imaging facility at Texas Children’s Hospital, is investigating factors that influence the health of vasculature surrounding CNS tumors to optimize efficacy and safety of anti-cancer therapies. Last year, his team linked tumor necrosis factor-alpha to acute microvascular damage and astrocyte activation around CNS tumors following radiotherapy.
The discovery stemmed from intravital fluorescence microscopy techniques Gaber’s team developed to visualize long-term changes in the health of the same section of cerebral microvasculature in live laboratory mice. “By testing the same vessel or network for the duration of therapy, we reduce variability and enable correlative studies of key markers of vascular health not possible using ex vivo sections,” explains Gaber.
Evaluating leukocyte adhesion to vascular epithelium—a key marker of vascular health—in vivo requires fluorescently labeling the leukocytes’ mitochondria. Over longer time scales, however, standard fluorescence illumination can quickly cause phototoxicity. To solve this problem, Gaber decided to integrate Photometrics CoolSNAP and Cascade II cameras to his fluorescence intravital microscopy system. The high quantum efficiencies (>60% and >90%, respectively) and low noise levels of these cameras enabled low-light, non-cytotoxic imaging of leukocyte trafficking and interactions over longer time periods at 50 to 60 frames per second.
Gaber’s team plans to publish additional data identifying specific receptors expressed after radiotherapy based on imaging receptor-coated fluorescent beads with this system.
This article was published in Vital Signs, a digital magazine supplement to Drug Discovery & Development and Bioscience Technology: Spring, 2010. By following the above link, a video of a mouse brain microvasculature 15 days post radiotherapy can be found.
