面向非黑色素瘤皮肤癌光动力治疗在体测评的动态SFD-DOT/FMT方法

Non-melanoma skin cancer (NMSC) is one of the most common skin malignancies, with its incidence being increasing year by year in our country. Photodynamic therapy (PDT) of NMSC not only has a series of advantages, such as good therapeutic effect, noninvasiveness and skin aesthetics maintaining, but also has good synergism with other methods. The bottleneck affecting effect of NMSC-PDT is how to achieve accuracy and personalization of the light and photosensitizer doses according to the individual differences of patients. The effective solution to this issue is to developing in vivo assessment methodologies for real-time dose adjustment and process optimization..This proposal is based on the potential advantages of spatial frequency domain (SFD) imaging in the in-vivo assessment of NMSC-PDT, and studies in depth its relevant key scientific problems in theory, technology and application. Firstly, the dynamic measurement method and system for SFD imaging with potential clinical application are explored, where the lock-in photon counting detection and single-pixel imaging modality are combined to achieve the high sensitivity and multi-wavelength parallelization required by the dynamics and practicability of the application; Secondly, a quantitative methodology for SFD imaging is developed based on diffuse optical/fluorescence tomography (DOT/FMT) theory, which reconstructs the light flux and photosensitizer concentration images within tissues, respectively. Finally, a pilot research on the SFD-DOT/FMT application in in-vivo assessment of NMSC-PDT, including small-animal-based validations, ALA-PDT modeling based light dose optimization and clinical trials etc. This project not only provides an efficient method for the precision of NMSC-PDT, but also provides an important evaluation tool for the development of new photosensitizers.

非黑色素皮肤癌(NMSC)是常见的皮肤恶性肿瘤之一，发病率在我国呈逐年上升趋势。与传统手术治疗相比，NMSC的光动力疗法(PDT)不但具有治疗效果好、无创和保持皮肤美观性等一系列优势，而且和其它方法有良好的协同性。影响NMSC-PDT效果的瓶颈在如何根据病人的个体化差异精准化剂量，有效的解决方案是通过发展NMSC-PDT在体评测进行实时剂量调整和优化。.本申请利用空间频率域(SFD)成像在NMSC-PDT在体测评上的技术优势，针对其理论、技术和应用上存在的关键科学问题开展深入研究：探索建立具有临床应用潜力的多波长、高灵敏SFD成像动态测量系统；发展基于扩散光/荧光层析(DOT/FMT)理论的SFD成像定量方法；研究SFD-DOT/FMT在NMSC-PDT在体测评中的应用。本项目不仅为NMSC-PDT的精准化提供在体测评有效方法，也可为新型光敏剂研制提供重要的评估工具。

基于5-氨基酮戊酸(5-ALA)的光动力治疗(PDT)方法用于具有治疗效果好，创伤小、毒性低，协同性好等一系列优势，在非黑色素瘤皮肤癌(NMSC)治疗领域获得广泛应用，而建立PDT在体剂量学和测评方法，以实现个性化和精准化光动力治疗中的剂量控制与优化已经成为亟待解决的临床问题。本项目面向NMSC-PDT在体测评及精准化治疗所需解决的宽场、快速、多波长成像测量系统、具有深度分辨能力的组织光剂量和光敏剂剂量三维分布定量方法以及个性化、精准化治疗光剂量投照等三个关键科学问题开展研究。项目以单像素空间频域成像(SP-SFD)方法为中心，有效建立了一个理论严谨、实用高效的NMSC-PDT在体测评系统和方法体系，并通过离体组织和活体小动物测评实验验证了所发展的系统和方法的可行性、定量性和临床适用性等性能。.在测量系统方面，建立了具有临床应用潜力的NMSC-PDT在体测评SP-SFD成像系统，该系统整合了超高灵敏度的锁相光子计数技术和多波长并行化的压缩感知技术，并实现了组织轮廓在线获取与矫正功能，可实现多波长宽场快速成像，满足了NMSC-PDT在体测评所要求的高灵敏度、准确性和动态性；在算法理论方面，建立了面向复杂组织的空间调制光传播模型，发展了三维光学和荧光图像反演理论和技术(SFD-DOT/FMT)，实现了NMSC-PDT在体测评对光剂量学和光敏剂剂量学定量性和动态性的要求；在评测方法方面，在做发展的SFD-DOT/FMT光剂量学和光敏剂剂量学的基础上，开展了基于荷瘤小动物模型的5-ALA-PDT在体测评预临床实验，验证了所发展系统和方法的临床可行性与适用性，并初步探索了精准化ALA-PDT单态氧阈值评定模型的构建。.本研究的成果的不但为探索个性化、精准化的NMSC-PDT光剂量的投放方法和过程优化方案提供新的手段，还可为新型光敏剂创制提供重要的评估工具。