PHYSIOLOGIC IMAGING OF HUMAN BRAIN TUMORS

放射成像技术的最新进展提供了详细的 脑肿瘤的大体解剖图;这对 然而，关于临床结果的结构信息有限。 无法直接翻译解剖发现的一个主要原因 静态解剖结构和 肿瘤的动态生物学行为并不简单。 的 肿瘤的病理生物学是许多非解剖因素的函数， 其中之一--细胞分裂--在生理学上至关重要。 细胞 分裂和必需的DNA合成与肿瘤直接相关 生长行为，包括对治疗的反应。 因此，从长远来看， 本研究的目的是开发在体生理成像 与DNA合成和细胞分裂高度相关的技术。 此外，我们将证明这些技术是 胶质瘤的组织病理学分级。 预计这一 生理信息将是解剖成像的补充， 帮助治疗人类脑肿瘤。 将评价三种体内方法与DNA的相关性 原发性和继发性脑肿瘤合成：1）11 C胸苷 通过PET检测掺入DNA，（2葡萄糖利用率， 通过PET 18F脱氧葡萄糖摄取测量，和3） 1H 31 P磁共振波谱（MRS）反映的肿瘤组织。 假设第一种方法是NA合成的直接测量 而后两种方法是细胞分裂的间接反映 因此DNA合成。 对于每种方法，与DNA 通过BUDR掺入、有丝分裂指数和 将进行肿瘤的组织病理学分级。 基于与DNA合成的体内相关性的结果， （1-3年级），最能反映肿瘤细胞分裂的方法 和DNA合成将应用于脑肿瘤患者的术前和术后， 放射治疗 治疗后体内生理成像结果 将与肿瘤生长的3D MR体积测量相关， 以评估其监测急性治疗反应的能力。

Recent advances in radiologic imaging techniques provide detailed pictures of the gross anatomy of brain tumors; the impact of this structural information on clinical outcome, however, has been limited. A major reason for the inability to directly translate anatomic findings into improved treatment is that the relationship between static anatomy and the dynamic biologic behavior of tumors is not straightforward. The pathobiology of a tumor is a function of numerous non-anatomic factors, of which one -- cell division -- is physiologically crucial. Cell division and the requisite DNA synthesis are directly related to tumor growth behavior, including response to treatment. Thus, the long term objective of this research is to develop in vivo physiologic imaging techniques which correlate highly with DNA synthesis and cell division. Furthermore, we will document that these techniques are the histopathologic grade of gliomas. It is anticipated that this physiologic information will be complementary to anatomic imaging in aiding the treatment of human brain tumors. Three in vivo methods will be evaluated for their correlation with DNA synthesis in primary and secondary brain tumors: 1) 11C thymidine incorporation into DNA was detected by PET, (2 glucose utilization as measured by PET 18Fdeoxyglucose uptake, and 3) bioenergetic state of tumor tissue as reflected by 1H31P magnetic resonance spectroscopy (MRS). The first method is postulated to be a direct measure of NA synthesis while the latter two methods are indirect reflections of cell division and therefore DNA synthesis. For each method, correlation with DNA synthesis as measured by BUDR incorporation, mitotic index, and the histopathologic grade of the tumor will be performed. Based on the results of the in vivo correlations with DNA synthesis (Years 1-3), the method or methods which best reflect tumor cell division and DNA synthesis will be applied to brain tumor patients pre and post radiation therapy. Post treatment in vivo physiologic imaging results will be correlated with 3D MR volumetric measurements of tumor growth in order to evaluate their ability to monitor acute treatment response.