High-resolution DT-MRI for differentiation of malignant glioma from radiation nec

描述(由申请人提供)： 脑肿瘤的标准治疗方法包括最大限度的手术切除、放射治疗和化疗。然而，即使有了这些干预措施，这些肿瘤也普遍是致命的，通常在几个月内。以Gd为基础的造影剂MRI是目前评估脑肿瘤的临床标准。然而，Gd增强，尽管它描绘了血脑屏障(BBB)的破坏，但并不是肿瘤增殖的特异性。Gd增强MRI的局限性在于：(I)许多低级别甚至一些高级别胶质瘤(10%的多形性胶质母细胞瘤和20%-30%的间变性星形细胞瘤)没有Gd增强，以及(Ii)将复发肿瘤与其他导致血脑屏障功能障碍的原因(如治疗导致的坏死)分开是极其困难的。此外，最近越来越多的人担心Gd暴露的长期安全性。扩散核磁共振可以在相当于细胞尺寸的范围内非侵入性地提供关于组织微结构和微动力学的信息。这项建议的目的是利用大鼠胶质瘤和放射性坏死模型，在近细胞水平上证明这些独特的扩散模式和肿瘤微观结构可以区分复发肿瘤和辐射效应。具体目的是：(1)利用4.7T的高分辨率DTI，确定与体内大鼠脑胶质瘤模型相关的水扩散模式。(2)明确正常大鼠尾壳核局灶性照射后与组织学证实的放射性坏死灶相关的水扩散模式。(3)评价4.7T高分辨DTI对体内增生性肿瘤和放射性损伤的鉴别能力。在人类脑肿瘤的治疗中，肿瘤复发和放射损伤的鉴别仍然是一个诊断难题。如果我们的目标实现，高分辨率DTI的独特能力将显著提高MRI对脑癌的无创性诊断准确性。公共卫生相关性：这项建议的目标是证明在近细胞水平上独特的扩散模式和相关的肿瘤微结构可以使用大鼠脑胶质瘤和放射性坏死模型区分复发肿瘤和辐射效应。如果我们的目标实现，高分辨率扩散张量磁共振成像的独特能力可以显著提高MRI对脑肿瘤的无创性诊断准确率。

DESCRIPTION (provided by applicant): Standard therapies for brain tumors include maximal surgical resection, radiation therapy, and chemotherapy. However, even with these interventions, these tumors are universally fatal, often within months. MRI with gadolinium (Gd)-based contrast agents is the current clinical standard for evaluating brain tumors. However, Gd enhancement, although it depicts the disruption of the blood brain barrier (BBB), is not specific for tumor proliferation. Gd-enhanced MRI is limited in that (i) many low-grade and even some high-grade gliomas (10% of glioblastoma multiforme and 20-30% of anaplastic astrocytoma) demonstrate no Gd-enhancement, and (ii) separating recurrent tumor from other causes of BBB dysfunction, such as treatment-induced necrosis, is extremely difficult. In addition, there has recently been increasing concern about the long-term safety of Gd exposure. Diffusion NMR can provide information noninvasively about tissue microstructure and microdynamics at a scale comparable to cell dimensions. The goal of this proposal is to demonstrate that these unique diffusion patterns and tumor microstructures at the near-cellular level can distinguish between recurrent tumors and radiation effects using the rat glioma and radiation necrosis models. The specific aims are: (1) To define the water diffusion patterns associated with rat glioma models in vivo, using high-resolution DTI at 4.7T. (2) To define water diffusion patterns associated with histologically confirmed radiation-induced necrosis after focal radiation to the caudate-putamen in healthy rats. (3) To assess the ability of high-resolution DTI at 4.7T to distinguish between proliferating tumor and radiation-induced injury in vivo. Differentiation of tumor recurrence from radiation injury remains a diagnostic dilemma in the management of human brain tumors. If our goal is achieved, the unique capability of high-resolution DTI could significantly enhance the diagnostic accuracy of MRI for brain cancer noninvasively. PUBLIC HEALTH RELEVANCE: The goal of this proposal is to demonstrate the possibility that unique diffusion patterns and related tumor microstructures at the near-cellular level can distinguish between recurrent tumors and radiation effects using the rat glioma and radiation necrosis models. If our goal is achieved, the unique capability of high-resolution diffusion tensor MRI could significantly enhance the diagnostic accuracy of MRI for brain cancer noninvasively.