Brain Tumor Imaging: Quantitative MRI and 1H MRS

描述（由申请人提供）：癌症在美国是第二大死亡原因。脑肿瘤是儿童和34岁以下成人癌症相关死亡的第二大原因，并且影响所有年龄段的成人。原发性恶性脑肿瘤与第三高的癌症相关死亡率和不成比例的残疾和发病率水平相关。脑肿瘤的准确诊断和分级是决定预后和治疗的关键。该提案的健康相关重点是通过开发基于磁共振（MR）成像（MRI）的综合分级系统来评估肿瘤行为和预后，从而降低脑肿瘤患者的发病率和死亡率。我们建议，全面的，定量的，结构和非解剖MRI和质子磁共振波谱（1H MRS）可以提供肿瘤恶性程度的替代标记物，允许准确的术前分级的脑肿瘤，并可能提供独立的预后信息以上和超越组织病理学表型。我们的中心假设是，原发性脑肿瘤的恶性生物学行为和侵袭性生长阶段的早期阶段与肿瘤血管生成有关，这可以通过使用灌注MRI（pMRI）方法进行定量和非侵入性测量。该提案的总体目标是应用一种全面的定量MRI方法，该方法将增强当前的诊断和肿瘤分级方法，提供治疗失败的早期证据，确定生存结局的替代标志物，并有助于开发新的治疗方法。申请人的直接目标是获得所需的知识和技能，成为一个独立的临床医生，研究者专注于以患者为导向的研究，通过分阶段和精心设计的，多学科的，教学式的培训，在脑肿瘤的基础生物学，生物统计学和临床研究设计，以及优化pMRI和多维1H MRS的方法。具体目标1是开发成像-通过使用综合MRI方法对神经胶质瘤进行分级，并确定最能预测肿瘤恶性程度的MR变量。具体目标2是通过直接关联从相同解剖位置获得的活检样本的成像和组织学结果，验证具有组织学标志物的肿瘤血管生成和血管通透性的MRI测量。具体目标3是通过在新诊断的恶性胶质瘤患者接受外射束放射治疗的同时参与辅助化疗的临床试验，使用治疗前后灌注和代谢MRI变量的变化来预测治疗反应和无进展生存期。

DESCRIPTION (provided by applicant): Cancer ranks second as the cause of death from disease in the United States. Brain tumors rank second as the cause of cancer-related deaths in children and adults younger than 34 years old, and they affect adults of all ages. Primary malignant brain tumors are associated with the third highest cancer-related mortality rate and a disproportionate level of disability and morbidity. Accurate diagnosis and grading of brain tumors is critical to determining prognosis and therapy. The health related focus of this proposal is to reduce morbidity and mortality rates for patients with brain tumors through the development of a comprehensive magnetic resonance (MR) imaging (MRI)-based grading system that assesses tumor behavior and prognosis. We propose that comprehensive, quantitative, structural and non-anatomic MRI and proton MR spectroscopy (1H MRS) can provide surrogate markers of tumor malignancy permitting accurate preoperative grading of brain tumors, and potentially can offer independent prognostic information above and beyond the histopathologic phenotype. Our central hypothesis is that the malignant biologic behavior of primary brain tumors and the early stages of an aggressive growth phase are related to tumor angiogenesis, which can be measured quantitatively and non-invasively by using perfusion MRI (pMRI) methods. The overarching goal of this proposal is to apply a comprehensive, quantitative MRI method that will augment current methods of diagnosis and tumor grading, provide earlier evidence of treatment failure, identify surrogate markers of survival outcome, and aid in the development of novel therapies. The applicant's immediate goal is to acquire the knowledge and skills required to become an independent clinician-investigator focused on patient-oriented research through phased and well-designed, multidisciplinary, didactic training in the basic biology of brain tumors, in biostatistics and clinical study design, and in methods of optimizing pMRI and multidimensional 1H MRS. Specific Aim 1 is to develop an imaging-based system for grading gliomas by using comprehensive MRI methods and to identify those MR variables that best predict tumor malignancy. Specific Aim 2 is to validate MRI measurements of tumor angiogenesis and vascular permeability with histologic markers by directly correlating imaging and histologic results from biopsy samples obtained from the same anatomic location. Specific Aim 3 is to predict treatment response and progression-free survival by using changes in perfusion and metabolic MRI variables before and after therapy in patients with newly diagnosed malignant glioma undergoing external-beam radiation therapy while participating in a clinical trial of adjuvant chemotherapy.