Imaging and Tissue Biomarkers for Improved Management of Patients with Newly Diag

本项目的目标是将代谢和生理MR成像数据整合到临床中， 新诊断的多形性胶质母细胞瘤（GBM）患者的管理。我们目前的研究 提供了强有力的证据，磁共振波谱成像（MRSI），灌注加权 成像（PWI）和扩散加权成像（DWI）产生关于生物学特性的信息。 这类病变的行为可能对临床决策有价值。我们建议探讨 这些成像方法在改善和评价Convection治疗方面的临床影响 生物活性剂的增强递送（CED）。第一个感兴趣的领域是更可靠地 确定手术后残留疾病的位置，以便最终能够指导治疗， 到残留病灶。第二个感兴趣的领域是定义代谢和生理成像 预测患者是否可能从使用CED的治疗中受益的参数。第三区域 是评估CED与随后的辐射相结合所产生的短期变化， 化疗此类病灶治疗的先前研究尚未利用最新技术水平的代谢和 生理成像方法，以选择患者，以识别微观疾病和异质性，或 评估对治疗的反应我们认为，关键是要确定这种做法是否可行， 并获取证据，以帮助决定如何最好地将这些信息纳入 未来的临床试验 特定目标1将通过以下方式提供特定成像和组织特征之间的直接关联： 免疫组织化学和离体核磁共振波谱的图像引导手术样本的患者 新诊断的GBM这将建立体内MR参数与生物学行为之间的联系， 由分子形态学定义。具体目标2将解决以下患者的特征： 参与接受CED的GBM患者的II期临床试验。它将研究 CED前MR参数和随后的成像变化之间的关系，以及比较这些结果 具有相似特征但未接受CED治疗的患者人群。具体目标3 将在GBM患者中进行I期临床试验，该试验将代谢和生理成像结合起来 这些参数已被证明与项目3中获得的结果有关， CED过程以更准确地靶向感兴趣区域。虽然这些初步临床试验的重点是 接受基于常规MR成像的大体全切除术的患者， 将获得广泛的影响，选择和靶向许多其他类型的焦点治疗， 可能改变GBM患者的肿瘤负荷和治疗反应的定义

The objective of this project is to integrate metabolic and physiologic MR imaging data into the clinical management of patients with newly diagnosed glioblastoma multiforme (GBM). Our current studies have provided strong evidence that Magnetic Resonance Spectroscopic Imaging (MRSI), Perfusion Weighted imaging (PWI) and Diffusion Weighted Imaging (DWI) produce information concerning the biological behavior of such lesions that is likely to be valuable for clinical decision making. We propose to explore the clinical impact of these imaging methods with respect to improving and evaluating treatment with Convection Enhanced Delivery (CED) of biologically active agents. The first area that is of interest is to more reliably identify the location of residual disease after surgery so that it will ultimately be possible to direct therapy to to foci of residual disease. The second area of interest is in defining metabolic and physiologic imaging parameters that predict whether the patient is likely to benefit from treatment that uses CED. The third area is in evaluating short-term changes that occur as a result of combining CED with subsequent radiation and chemotherapy. Previous studies of such focal treatments have not utilized state of the art metabolic and physiologic imaging methods to select patients, to identify microscopic disease and heterogeneity or to evaluate response to therapy. We believe that it is critical to determine whether this approach is feasible with regard to CED and to obtain evidence that would help in deciding how to best integrate such information into future clinical trials. Specific Aim 1 will provide direct correlation between specific imaging and tissue characteristics by immunohistochemical and ex-vivo NMR spectroscopy of image guided surgical samples from patients with newly diagnosed GBM. This will establish the link between in vivo MR parameters and biological behavior as defined by molecular morphology. Specific Aim 2 will address the characteristics of patients who are participating in a Phase II clinical trial of GBM patients receiving CED. It will examine the relationship between pre-CED MR parameters and subsequent imaging change, as well as comparing these findings with a population of patients with similar characteristics who have not been treated with CED.Specific Aim 3 will perform a Phase I clinical trial in patients with GBM that integrates the metabolic and physiologic imaging parameters that have been shown relevant with results obtained in Project 3 with regard to improving the CED process to more accurately target regions of interest. While the focus in these initial clinical trials is on patients who have received a gross total resection based on conventional MR imaging, the knowledge that will be gained has broad implications for selecting and targeting many other types of focal therapy and is likely to change the definition of tumor burden and response to therapy for patients with GBM