面向早期乳腺癌诊断的锥束相衬XCT/XLCT双模态成像先进方法

The newly developed bimodality imaging technique of fluorescent molecules tomography(FMT)/x-ray computed tomography(XCT) possesses a combined advantage of high sensitivity, excellent specificity, and noninvasive, providing an effective means of exploring the pathogenesis of tumors based on the small-animal model. However, this method has deficiencies in the application of larger size breast tissue imaging: 1) XCT cannot provide sufficient priori structural information of breast tissue for FMT because the XCT image of soft tissue has low contrast; 2) The imaging depth and spatial resolution of FMT is limited because of the scattering effects of the incident laser. In response to these problems, this proposal offers to establish a bimodality imaging technique of phase contrast x-ray computed tomography (XCT)/X-ray luminescence computed tomography (XLCT) with high sensitivity, high contrast and high spatial resolution for in vivo quantitative detection of early breast cancer: 1) To develop a cone-beam phase contrast XCT imaging method for obtaining the high-contrast phase images representing the inner structural information of breast tissue by taking advantage of its phase sensitivity; 2) To overcome the difficulty of insufficient imaging depth and spatial resolution in FMT technique by developing X-ray luminescence computed tomography (XLCT) method with X-ray as the incident excitation light; 3) To establish an accurate image degradation model and effectively compensate the system deterioration from the nonideality of the imaging system; 4) To implement XLCT image reconstruction and information fusion based on the prior phase information provided by phase contrast XCT.

近几年发展的荧光分子层析(FMT)/XCT双模态成像技术，具有高特异性、高灵敏度和无创性等综合优势，提供了小动物模型下探索肿瘤发病机理的有效手段。但是该方法应用于尺寸较大的乳腺组织成像时存在缺欠：XCT对软组织成像对比度低，无法为FMT提供完备的乳腺结构先验信息；FMT因入射激光的散射效应，成像深度和空间分辨率受到限制。针对上述问题，本课题以实现早期乳腺癌在体定量检测为目的，建立高灵敏、高对比度、高空间分辨率的相衬XCT/X射线发光断层成像方法(XLCT)双模态成像方法:1)发展锥束相衬XCT成像方法，利用其相位敏感性，获取表征乳腺组织内部结构信息的高对比度相位信息图像；2)发展以X射线为入射激发光的XLCT，克服FMT方法在成像深度方面的困难；3)建立准确的图像退化模型，有效补偿实际系统非理想性引入的系统恶化效应；4)基于相衬XCT提供的先验相位信息，实现XLCT图像重建及信息融合。

锥束相衬XCT/X射线发光断层成像(XLCT)双模态成像技术，可以克服当前方法成像深度限制以及成像对比度低的问题，在乳腺癌早期检测、诊断等领域具有重要应用价值。本研究在精确建模的基础上实现了一个理论缜密、技术可行的锥束相衬XCT/XLCT双模态图像重建方案，在此基础上探索出有效改善图像重建精度、分辨率和鲁棒性的方法，并开展了相关验证性实验。主要包括：①将基于光纤耦合的多通道光子计数测量技术与扫描、非接触式测量方案相结合，建立了高灵敏、高分辨、高对比度的锥束相衬XCT/XLCT测量系统，可以获得组织体的结构和功能信息，其中XLCT成像扫描时间远少于当前基于EMCCD的单窄束XLCT成像系统；②通过研究系统退化模型与相位抽取结果的相关性，构建了非理想成像系统性能补偿的相衬XCT成像模型，提出时频域联合迭代正则化的相位抽取方法，并发展了基于三维相位抽取的相衬XCT重建方法，提高了相位重建的精度；③构建了XLCT新型扫描机构，并发展了相应的重建方法:基于加权调制和基于宽光束小步长扫描的多光束XLCT重建方法，打破了当前XLCT的成像分辨率，将分辨率提高到传统方法的1.6倍，并兼顾了成像速度。④目前已对所提出的方法和技术进行了仿体、活体小鼠实验，验证了所提方法和技术的可行性和有效性。