A Diffusion-Based MRI Method to Detect Glioma Invasion

描述（由申请人提供）：肿瘤细胞的侵袭是手术切除和局部放射治疗未能显著改善胶质瘤患者预后的主要原因。没有非侵入性的方法来检测入侵的程度，因此无法用治疗靶向这些区域。拟议研究的总体目标是开发和验证一种基于扩散的MRI（磁共振成像）方法用于检测胶质瘤侵袭。我们的方法是使用多个扩散加权（b值）采集MR信号，并对数据进行拉伸指数分析，这是一种我们称为“alpha“DWI的新方法。三个度量，异质性指数（“alpha”），分布扩散系数DDC，和亚体素扩散率E（1/D^n）的n阶矩，推导出。拉伸指数可能优于其他扩散模型，因为它允许人们估计子体素而不是水扩散速率的体素间分布，并且避免对扩散分量的数量进行假设。在大鼠脑肿瘤模型中获得的初步结果表明？DWI图像，其在空间上对应于肿瘤浸润区域，如荧光标记的肿瘤细胞的存在所指示的。另外的结果表明，这种技术的入侵肿瘤细胞的灵敏度可以优化与扩散定时参数的正确选择。尽管很有前途，但只有当它能够提供针对入侵肿瘤细胞的特定信息，并且不被其他病理过程（例如水肿或辐射效应）的存在所混淆时，这项技术才被证明是可行的，这两种病理过程通常存在于未经治疗和经过治疗的胶质瘤患者中。为了测试我们方法的可行性，将在接种稳定表达DSred-C6胶质瘤细胞的大鼠脑肿瘤模型和脑肿瘤患者中进行研究。在论证了可行性之后，未来的提案将结合联合收割机？DWI和灌注MRI方法，这也是我们实验室正在开发的，用于全面评估脑肿瘤的侵袭，血管生成，生长和复发。这种全面的脑肿瘤成像方法将大大改善脑肿瘤患者的治疗和预后。

DESCRIPTION (provided by applicant): Invasion of tumor cells is a primary reason for the failure of surgical excision and focal radiation therapy to significantly improve the prognosis for patients with gliomas. No non-invasive method exists to detect the extent of invasion, thus the inability to target such areas with therapy. The overall goal of the proposed research is to develop and validate a diffusion-based MRI (magnetic resonance imaging) approach for the detection of glioma invasion. Our approach is to acquire MR signal using multiple diffusion-weightings (bvalues) and apply a stretched exponential analysis of the data, a new approach that we refer to as "alpha"DWI. Three metrics, the heterogeneity index ("alpha"), the distributed diffusion coefficient DDC, and the nth moments of the sub-voxel diffusion rates E(1/D^n), are derived. The stretched-exponential may be preferred to other models of diffusion because it allows one to estimate the sub-voxel rather than the inter-voxel distribution of water diffusion rates, and avoids making assumptions about the number of diffusion components. Preliminary results obtained in a rat brain tumor model demonstrate changes on ?DWI images, which correspond spatially to areas of tumor invasion as indicated by the presence of fluorescence-labeled tumor cells. Additional results suggest that the sensitivity of this technique to invading tumor cells may be optimized with the correct choice of diffusion timing parameters. Though promising, this technique will only prove feasible if it can provide information specific for invading tumor cells that is not confounded by the presence of other pathologic processes such as edema or radiation effects, both of which are commonly present in untreated and treated glioma patients. To test the feasibility of our approach, studies will be performed in rat brain tumor models, inoculated with stably expressing DSred-C6 glioma cells, and in patients with brain tumors. After feasibility is demonstrated, a future proposal will combine ?DWI and perfusion MRI methods, which are also being developed in our laboratory, for the comprehensive evaluation of brain tumor invasion, angiogenesis, growth and recurrence. This comprehensive approach to brain tumor imaging should dramatically improve the treatment and prognosis for patients with brain tumors.