MRI-CT图像配准结合纹理分析技术确定保乳术后放疗个体化瘤床靶区的研究

Breast-conserving surgery followed by radiotherapy to the whole breast and boost irradiation to the lumpectomy cavity (LC) is the standard strategy for the early stage breast cancer patients. It is difficult to define the LC accurately using traditional methods, and the uniform standard for the LC delineation has not been formed. Magnetic resonance imaging (MRI) has the superb soft-tissue visualization, and texture analysis based on apparent diffusion coefficient (ADC) maps of diffusion weighted imaging (DWI) are capable of showing the heterogeneity of tumors, which means that parameters extracted from DWI could be used as the delineation guidance of radiotherapeutic target. Our previous study indicates that postoperative MRI (MRI-post) rigid registrated with computed tomographic (CT) substantially improves the visibility and accuracy of LC delineation, but the LC delineated by MRI-post cannot entirely represent the LC. In this study, we plan to present an optimal strategy of LC delineation, hoping to find out a uniform standard for delineate of LC. Detailed protocols are as followed: The enrolled patients undergo preoperative MRI (MRI-pre) examination, and two-/three-dimensional images are reconstructed to acquire three-dimensional ADC parameters of DWI. With the help of the texture analysis and whole mount serial sections which confirm the microscopic extension of tumor, a method for LC delineation was established based on MRI-pre. In order to connect the MRI-pre, pathologic resection volume (PRV), MRI-post and CT, commercial and self-developed software were used to registrate the MRI-pre, MRI-post and CT imaging.

保乳术+术后放疗是早期乳腺癌标准治疗模式，常用的术后瘤床勾画方法存在诸多弊端，尚未形成统一的勾画共识。MRI图像具有较高的软组织对比性，且弥散加权成像（DWI）可通过提取表观弥散系数（ADC）纹理分析，能够比较准确地反应肿瘤异质性以指导靶区勾画。前期研究发现术后MRI与定位CT图像经刚性配准融合有助于瘤床确定，但术后MRI图像勾画的靶区亦不能准确代表瘤床。本研究拟通过术前MRI多序列检查，通过DW-MRI图像获得反映肿瘤二维及三维空间信息的ADC图像纹理参数，结合术后次连续病理大切片技术，确定乳腺肿瘤亚临床浸润范围，建立基于术前MRI临床靶区勾画方法；通过商用及自研软件将术前、术后MRI图像与保乳术后放疗CT定位图像进行刚性/形变配准，使肿瘤术前MRI→病理切除体积→术后MRI→定位CT有机串联起来，最终建立保乳术后放疗瘤床靶区的最佳勾画策略，有望解决瘤床勾画缺乏准确性及标准性的问题。

保乳术后放疗存在一些难以解决的技术瓶颈，比如瘤床靶区勾画无统一标准、部分患者术后放疗获益不明确、治疗靶区过大带来的毒副反应等，新辅助放疗已成为早期乳腺癌研究前沿之一。在当今免疫治疗时代，放疗与免疫治疗的结合在很多肿瘤中获得良好的疗效。国内外尚无乳腺新辅助放疗联合免疫治疗的临床试验。项目组在资助期间进行了以下几方面的研究：.靶区勾画研究：本项目建立了保乳术后放疗基于术前MRI临床靶区勾画方法，建立了基于多序列MRI和聚类算法的乳腺癌肿瘤区域映射模型，解决了目前乳腺癌临床勾画缺乏规范的问题。构建了基于Gabor特征的乳腺癌MR图像分类识别模型，进一步印证了MRI纹理分析对乳腺浸润性导管癌级别的鉴别诊断价值。通过MRI图像纹理分析预测新辅助疗效。采用次连续病理大切片技术，明确乳腺肿瘤亚临床浸润范围极其影响因素，指导大体肿瘤靶区（GTV） 边界外扩形成准确代表肿瘤位置和大小的临床靶区（CTV），构建MRI和病理三维重建模型。将肿瘤术前MRI→病理切除体积→定位CT有机串联起来，建立了保乳术后放疗瘤床靶区的最佳勾画策略。.基础探索：从基础出发研究内皮抑素调节免疫微环境改善早期三阴性乳腺癌新辅助放射免疫的疗效机制。建立 三阴性乳腺癌（TNBC） 细胞株的动物模型，同步联合PD-1单抗免疫治疗，筛选早期乳腺癌放疗的最佳放疗剂量分割模式和精准靶区勾画方法，建立早期乳腺癌新辅助放疗免疫策略。.临床转化：开展早期三阴性乳腺癌新辅助大分割放疗联合化疗及免疫治疗的临床研究，探索乳腺癌治疗的新模式，评价新辅助放疗联合化疗及免疫治疗在早期三阴性乳腺癌的疗效及安全性。.总之该项目建立了保乳术后放疗瘤床靶区的最佳勾画策略，从基础出发探索早期乳腺癌新辅助放疗免疫策略，临床转化开展早期三阴性乳腺癌新辅助大分割放疗联合化疗及免疫治疗的临床研究，评估其疗效及安全性，为乳腺癌治疗提供了新的方向。