ABSTRACT
Purpose@#With advancing endovascular technology and increasing interest in minimally invasive intra-arterial therapies such as stem cell and chemotherapy for cerebral disease, the establishment of a translational model with cerebral circulation accessible to microcatheters is needed. We report our experience catheterizing canine cerebral circulation with microcatheters, present high-resolution angiographic images of the canine vascular anatomy, describe arterial branch flow patterns and provide measurements of canine arterial conduits. @*Materials and Methods@#Angiograms were performed on 10 intact purpose-bred hounds. Angiography, measurements of arterial conduits and catheterization information for intracranial arterial branches were obtained. @*Results@#Selective and superselective cerebral angiography was successful in all subjects. Relevant arterial mean diameters include the femoral (4.64 mm), aorta (9.38 mm), external carotid (3.65 mm), internal carotid arteries (1.6 mm), vertebrobasilar system and Circle of Willis branches. Catheterization of the Circle of Willis was achieved via the posterior circulation in all subjects tested (n=3) and the use of flow directed microcatheters resulted in reduced arterial tree deformation and improved superselection of intracranial vessels. Catheterization of the intracranial circulation was attempted but not achieved via the internal carotid artery (n=7) due to its tortuosity and subsequent catheter related vasospasm. @*Conclusion@#The canine cerebral vasculature is posterior circulation dominant. Anterior circulation angiography is achievable via the internal carotid artery, but direct cerebral arterial access is best achieved via the posterior circulation using flow-directed microcatheters. It is feasible to deliver intra-arterial therapies to selective vascular territories within the canine cerebral circulation, thus making it a viable animal model for testing novel intra-arterial cerebral treatments.
ABSTRACT
Extensive research in this decade has led to detailed understanding of genetic changes underlying human cancers. Two major tumorigenic events are mutation and amplification of oncogenes and inactivation of tumor suppressor genes. These events then trigger a series of signal transduction cascades, activating expression of downstream genes that control various cellular activities including cell cycle progression, DNA synthesis, programmed cell death, DNA repair, and cell migration. Investigations of these molecular pathways has led to the identification of many targets for therapeutic intervention. Knowledge of the expression patterns and functions of all human genes wil l provide a frame work for future molecular, genetic medicine. During the past ten years, the human genome project has generated an enormous amount of sequencing information, and sequencing of the entire human genome may be completed by the year 2003 (1,2). One can envision that this will irreversibly transform the methodology of medical research and the practice of medicine. The search for new genes, which currently consumes the effort of many talented scientists, will become past history. Additionally, studying one gene at a time will be replaced by studying large number of genes simultaneously(3). Reductionistic approaches to human disease will be replaced by systemic approach. As a prelude to this revolution, tools used for parallel analysis of gene expression in the format of ordered gene arrays have been developed and are under continued expansion. In this technical tip, we will introduce the Atlas Human cDNA Expression Array system developed by Clontech Laboratories, Inc.(4). With this technology, a conventional laboratory can profile the expression of 588 human genes simultaneously in one simple experiment without the using of expensive equipment. We will demonstrate the profiling of 588 genes in a human glioblastoma cell line to exemplify the utility of this technique.