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

该项目的目标是将代谢和生理磁共振成像数据整合到临床中。 新诊断的多形性胶质母细胞瘤的处理。我们目前的研究已经 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)产生有关生物的信息 这类病变的行为可能对临床决策有价值。我们建议探讨 这些成像方法对改善和评估对流治疗的临床影响 生物活性物质的强化输送(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，以便最终有可能指导治疗 以残留病为中心。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。第三个领域 是评估CED与随后的辐射相结合而发生的短期变化 化疗。以前对这种局部治疗的研究没有利用最先进的代谢和 生理成像方法选择患者，识别微观疾病和异质性或 评估对治疗的反应。我们认为，确定这一方法是否可行是至关重要的 关于“消除一切形式种族歧视国际公约”，并获得有助于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 影像引导手术标本的免疫组织化学和体外核磁共振波谱研究 新诊断的基底膜。这将在体内磁共振参数和生物行为之间建立联系，如 由分子形态定义的。具体目标2将针对以下患者的特征： 参与接受CED治疗的GBM患者的II期临床试验。它将考察两国关系 CED前MR参数与随后的成像变化之间的关系，以及比较这些发现 具有相似特征但尚未接受CED治疗的患者群体。具体目标3 将对患有GBM的患者进行一期临床试验，该试验整合了代谢和生理成像 已显示与项目3中所取得的关于改进 CED过程，以更准确地瞄准感兴趣的区域。虽然这些初步临床试验的重点是 接受了基于常规磁共振成像的大体全切除的患者，知道 对选择和针对许多其他类型的焦点治疗具有广泛的影响，并且是 可能改变对GBM患者的肿瘤负担和治疗反应的定义

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