Brain Tumor Imaging: Quantitative MRI and 1H MRS

描述（由申请人提供）：在美国，癌症在疾病死亡原因中排名第二。在34岁以下的儿童和成年人中，脑肿瘤是导致癌症相关死亡的第二大原因，并且影响到所有年龄段的成年人。原发性恶性脑瘤与第三高的癌症相关死亡率以及不成比例的残疾和发病率有关。脑肿瘤的准确诊断和分级是决定预后和治疗的关键。本提案的健康相关重点是通过开发基于综合磁共振成像（MRI）的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。我们认为，全面的、定量的、结构的和非解剖的MRI和质子磁共振光谱（1H MRS）可以提供肿瘤恶性的替代标记物，允许对脑肿瘤进行准确的术前分级，并可能提供超越组织病理表型的独立预后信息。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，这可以通过灌注MRI （pMRI）方法定量和无创地测量。本提案的总体目标是应用一种全面、定量的MRI方法，以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，确定生存结果的替代标记物，并帮助开发新的治疗方法。申请人的直接目标是通过在脑肿瘤基础生物学、生物统计学和临床研究设计方面的分阶段和精心设计的多学科教学培训，获得成为一名独立临床研究者所需的知识和技能，专注于以患者为导向的研究。在优化pMRI和多维1H mrs的方法中，具体目标1是开发一种基于成像的系统，通过使用综合MRI方法对胶质瘤进行分级，并确定那些最能预测肿瘤恶性的MR变量。具体目标2是通过直接关联来自同一解剖位置的活检样本的成像和组织学结果，验证肿瘤血管生成和血管通透性的MRI测量与组织学标记。特异性目的3是通过参与辅助化疗临床试验的新诊断恶性胶质瘤患者接受外束放射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.