Tumor NMR Images are Affected by Anesthetic

描述(由申请人提供)： 动物患者接受磁共振检查(MR！)为了获取信号，必须对研究进行麻醉以限制运动。诱导和维持全身麻醉会对正常生理产生深刻的改变。根据作用机制的不同，麻醉药可能会导致心血管、呼吸、肝脏、肾脏、消化和神经功能的轻微或深刻变化。这些影响的程度受到动物种类、品系、体温和疾病状态的影响。肿瘤血管缺乏平滑的肌肉，不能自动调节血流。因此，全身对心输出量、血压和全身血管阻力的影响将对肿瘤的血流灌注产生深远的影响。 我们假设麻醉小鼠可以充分改变生理学，使抗血管生成和抗血管药物的作用减弱或被覆盖，由此产生的治疗反应的磁共振研究可能会混乱。此外，麻醉方案可以针对不同的成像任务(例如：形态、成像时间)和肿瘤位置(例如：SQ、肌肉)进行定制，以便在对肿瘤生理影响最小的情况下，在人类癌症小鼠模型中对肿瘤生理学进行可重现的定量成像。 我们将使用三种常用的麻醉方案：氯胺酮/赛拉津/乙酰丙嗪、戊巴比妥和异氟烷，以及一种定制的注射麻醉剂方案：依托咪酯/芬太尼/咪达唑仑，通过调查心血管效应和由此对DCE-MRI图像的影响来验证这一假设。这些研究将在携带HT-29结肠癌异种移植瘤的SCID小鼠身上完成。小鼠将被分成三组：(1)未处理的对照组，测试麻醉剂之间的生理差异和组内的重复性；(2)用抗血管生成药物PX-478治疗；(3)用抗血管药物Combretataatin-A4P治疗。 这项研究是准确了解麻醉药如何影响肿瘤图像的关键的第一步。清楚地了解麻醉药物的生理效应及其对肿瘤成像的影响，以便正确地收集和分析MRI数据是非常必要的。我们还必须能够清楚地定义不同品系的小鼠之间的这些关系是如何变化的，因为有几个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和人类在癌症治疗方案中应用这些成像技术之间的真正相关性。

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.