Tumor NMR Images are Affected by Anesthetic

描述（由申请人提供）： 动物患者接受磁共振（MR！）研究必须被麻醉以限制用于信号采集的运动。诱导和维持全身麻醉会对正常生理产生深刻的变化。根据作用机制，麻醉药物可能引起心血管、呼吸、肝、肾、消化和神经功能的轻微至严重变化。这些影响的程度受动物种类、品系、体温和疾病状态的影响。肿瘤血管系统缺乏平滑肌，不能自动调节血流。因此，对心输出量、血压和全身血管阻力的全身效应将对肿瘤灌注产生深远影响。 我们假设麻醉小鼠充分改变了生理学，使得抗血管生成和抗血管药物的作用减弱或无效，并且由此产生的治疗反应的MR研究可能会混淆。此外，可以针对不同的成像任务（例如：模态、成像时间）和肿瘤位置（例如：SQ、肌肉）定制麻醉方案，以允许在人类癌症小鼠模型中对肿瘤生理学进行可再现的定量成像，同时对肿瘤生理学的干扰最小。 我们将使用三种常用的麻醉方案（氯胺酮/甲苯噻嗪/乙酰丙嗪、戊巴比妥和异氟烷）和一种定制的注射麻醉方案（依托咪酯/芬太尼/咪达唑仑），通过研究心血管效应以及对DCE-MRI图像的影响来检验这一假设。这些研究将在携带HT-29结肠癌异种移植物的SCID小鼠中完成。将小鼠分成三组进行成像：（1）未处理的对照，其测试麻醉剂之间的生理差异和组内的再现性，（2）用抗血管生成药物PX-478处理和（3）用抗血管药物Combretastatin-A4 P处理。 这项研究是准确了解麻醉药物如何影响肿瘤图像的重要第一步。必须清楚地了解麻醉药物的生理作用及其对肿瘤成像的影响，以便正确收集和分析MRI数据。我们还必须能够清楚地定义这些关系如何在不同品系的小鼠之间变化，因为有几种不同的品系被用作人类癌症的动物模型。这将使我们更接近动物体内研究与这些成像技术在癌症治疗方案中的人类应用之间的真正相关性。

DESCRIPTION (provided by applicant): 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.