Brain Tumor Imaging: Quantitative MRI and 1H MRS

描述(申请人提供)：癌症在美国疾病死亡原因中排名第二。在34岁以下的儿童和成人中，脑瘤是与癌症相关的死亡的第二大原因，它们影响到所有年龄段的成年人。原发恶性脑瘤与癌症相关的死亡率位居第三，其致残率和发病率也不成比例。脑肿瘤的准确诊断和分级是决定预后和治疗的关键。这项提案与健康相关的重点是通过开发一种基于磁共振成像(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。我们认为，综合的、定量的、结构的和非解剖的MRI和质子磁共振波谱(1HMRS)可以提供肿瘤恶性程度的替代标记物，使得术前对脑肿瘤进行准确的分级，并有可能在组织病理表型之外提供独立的预后信息。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期的早期阶段与肿瘤血管生成有关，可以使用灌注MRI(PMRI)方法定量和非侵入性地测量肿瘤血管生成。这项建议的总体目标是应用一种全面的、定量的MRI方法，该方法将增强目前的诊断和肿瘤分级方法，提供治疗失败的早期证据，识别生存结果的替代标记物，并帮助开发新的治疗方法。申请人的近期目标是获得所需的知识和技能，成为一名独立的临床研究人员，专注于以患者为中心的研究，通过分阶段和精心设计的、多学科的教学培训，了解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是开发基于成像的系统，通过使用综合的MRI方法对胶质瘤进行分级，并确定最能预测肿瘤恶性程度的MR变量。具体目标2是通过直接将来自同一解剖位置的活检样本的成像和组织学结果相关联，验证MRI测量的肿瘤血管生成和血管渗透性与组织学标志物的相关性。具体目标3是通过使用新诊断的恶性胶质瘤患者在参加辅助化疗的临床试验期间接受外照射治疗的治疗前后血流和代谢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.