增强血管靶向光动力效应的时空规律及调控研究

Vascular targeted photodynamic therapy is the most suitable modality for the precise treatment of vascular related diseases, including port wine stain, age-related macular degeneration, and esophageal varices, gastric antral vascular ectasia, radiation gastritis and proctitis. The clinical requirements for the targeted photodynamic precise, intensity and deep are significantly different for each indication, which is strongly depended on the pathological characteristics of treated lesion. For this, the enhancement control of vascular targeted photody-namic effect (VTPE) has been currently considered to be the most effective strategies for enhancing clinical efficiency, and the elucidation of spatiotemporal regularity for VTPE is a key scientific issue for the enhancement control. This project is aimed to investigate the spatiotemporal regularity of VTPE based on the regulation study for photodynamic key factors, which including light, photosensitizer, oxygen and target lesion by using the established optical monitoring platform combined with numerical simulation. In order to improve the safety and efficiency in clinical treatment, the control strategies for enhancing photodynamic precise, intensity and deep of specific targeted lesion will be further developed. The study will provide scientific fundamentals to investigate the spatiotemporal regularity and control of VTPE for tumor targeted and microorganism targeted (virus, bacteria and fungus) photodynamic effect, and a research approach for dramatically improving the precise treatment of PDT will be proposed.

血管靶向光动力疗法已成为精准治疗血管疾病的首选方法，已临床应用于鲜红斑痣、老年眼底黄斑变性、食道静脉曲张、胃粘膜血管扩张症、放射性胃炎和肠炎等疾病的治疗。这些适应证因病变靶点的特性不同，对靶向作用的精度、强度和深度要求不同。因此，针对这些特点进行靶点效应的增强调控已成为提高疗效的最佳途径，而了解血管靶向光动力效应的时空规律是实现调控的关键科学问题。本项目将基于课题组建立的光学监测平台并结合数学仿真方法，研究血管靶向光动力效应的关键因素（光、光敏剂、氧和靶点）相互作用的时空规律，探索建立针对靶点特性的光动力效应（精度、强度和深度）的增强调控方法，以提高治疗的安全性和有效性。本项目还将为研究光动力疗法的另两大应用领域——肿瘤靶向和微生物靶向（病毒、细菌、真菌等）光动力效应的时空规律与调控奠定科学基础，为全面提升光动力疗法在精准治疗方面的水平提供研究方法。

按照项目计划的研究内容，研发了V-PDT时空规律的光学监测平台，发展了针对靶点特性增强V-PDT效应的调控方案，提出了增强V-PDT作用强度、作用精度与作用深度的增强调控方法，动物实验与临床试验验证了优化方案的可行性与有效性。.技术开发：研发了活体单线态氧发光和光敏剂荧光成像新技术，比较研究了单线态氧产量和光敏剂光漂白预测疗效的可行性；发展了高光谱和激光散斑成像新技术，定量检测与研究了光敏剂剂量、光剂量以及氧含量对单线态氧产量和疗效的影响，为增强V-PDT作用精度与作用强度，提供了理论依据；探索了基于图像混合配准与多步深度神经网络法计算血管面积收缩率，进而定量评估V-PDT后的血管损伤，极大地提高了血管损伤定量评估的准确度，有望在V-PDT量效评估中推广应用。.机理探索：结合数学仿真和动物实验定量研究了V-PDT中光、光敏剂、氧等关键要素对单线态氧产量的影响，以及单线态氧在不同类型靶组织中的时空分布特点。通过采用多模光学成像技术，初步建立了光敏剂荧光强度、单线态氧发光强度与血管收缩率之间的量效关系，揭示了V-PDT中单线态氧诱导血管收缩的作用机制。.成果应用：建立了针对不同鲜红斑痣病变的V-PDT方案增强调控方法，18例临床验证均获得较常规V-PDT更显著的治疗效果。减轻了治疗后结痂反应、缩短了避光时间及治疗间隔，有助于在较短治疗周期内达到最佳的治疗效果，减轻了患者的经济负担与治疗后护理成本。.项目执行期间，共发表期刊论文20篇（其中SCI收录14篇，EI收录1篇），发表EI收录会议论文10篇。申请国家发明专利5项，其中获得授权4项；获福建省自然科学奖二等奖1项。