A Diffusion-Based MRI Method to Detect Glioma Invasion

描述（申请人提供）：肿瘤细胞的侵袭是手术切除和局灶放射治疗不能显著改善胶质瘤患者预后的主要原因。目前还没有一种非侵入性的方法来检测入侵的程度，因此无法针对这些区域进行治疗。该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）方法来检测胶质瘤的侵袭。我们的方法是使用多个扩散权重（b值）获取MR信号，并对数据进行拉伸指数分析，我们将这种新方法称为“alpha”DWI。导出了三个指标，即异质性指数（alpha）、分布扩散系数DDC和子体素扩散率的n阶矩E（1/D^n）。与其他扩散模型相比，拉伸指数模型可能更受欢迎，因为它允许人们估计水扩散率的子体素分布，而不是体素间分布，并且避免了对扩散分量的数量做出假设。在大鼠脑肿瘤模型中获得的初步结果表明？DWI图像，在空间上对应于肿瘤侵袭区域，如荧光标记的肿瘤细胞的存在。进一步的结果表明，正确选择扩散时间参数可以优化该技术对入侵肿瘤细胞的敏感性。虽然很有希望，但这项技术只有在它能够提供入侵肿瘤细胞的特定信息而不被其他病理过程（如水肿或辐射效应）所混淆的情况下才被证明是可行的，这两种病理过程通常存在于未治疗和治疗的胶质瘤患者中。为了验证我们方法的可行性，研究将在大鼠脑肿瘤模型中进行，接种稳定表达的DSred-C6胶质瘤细胞，并在脑肿瘤患者中进行。可行性论证后，未来的提案将结合？我们实验室正在开发的DWI和灌注MRI方法，可以综合评价脑肿瘤的侵袭、血管生成、生长和复发。这种全面的脑肿瘤成像方法将显著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.