Animal patients presented for magnetic resonance (MR!) studies must be anesthetized to limit motion for signal acquisition. Inducing and maintaining general anesthesia can produce profound changes in normal physiology. Depending upon the mechanism of action, anesthetic drugs may precipitate minor to profound changes in cardiovascular, respiratory, hepatic, renal, digestive, and neurologic function. The degree of these effects is influenced by animal species, strain, body temperature, and disease state. Tumor vasculature lacks smooth muscle and cannot autoregulate blood flow. Therefore, systemic effects on cardiac output, blood pressure and systemic vascular resistance will have profound effects upon tumor perfusion. We hypothesize that anesthetizing mice alters physiology sufficiently that the effects of antiangiogenic and anti-vascular drugs are blunted or overridden and the resulting MR investigations of therapeutic response may be confounded. Furthermore, anesthetic protocols can be customized for different imaging tasks (ex: modality, imaging time), and tumor location (ex: SQ, muscle) to allow the reproducible, quantitative imaging of tumor physiology in mouse models of human cancer with minimal perturbation of tumor physiology. We will test this hypothesis by investigating the cardiovascular effects, and resulting effects upon DCE-MRI images, using three commonly used anesthetic protocols: ketamine/xylazine/acepromazine, pentobarbital, and isoflurane, and one customized injectable anesthetic protocol: etomidate/fentanyl/midazolam. These investigations will be accomplished in SCID mice bearing HT-29 colon carcinoma xenografts. Mice will be imaged in three groups: (1) untreated controls that test the physiologic differences between anesthetics and reproducibility within groups, (2) treated with the anti-angiogenic drug PX-478 and (3) treated with the anti-vascular drug Combretastatin-A4P. This investigation is a vital first step in understanding exactly how the anesthetic drugs affect tumor images. It is imperative that the physiologic effects of the anesthetic drugs, and their influence on tumor imaging, be clearly understood so that MRI data may be collected and analyzed properly. We must also be able to clearly define how these relationships change between different strains of mice because there several different strains are used as animal models of human cancer. This will bring us one step closer to true correlation between animal in vivo studies and human application of these imaging techniques in cancer treatment regiments.
| Dalgic, Abdullah; Karakoc, Omer; Karahatay, Serdar et al. (2013) Submandibular triangle masses. J Craniofac Surg 24:e529-31 |
