Photodynamic therapy (PDT) dosimetry, including light dose, photosensitizer dose and tissue oxygen, has been a research focus in PDT. In this work, we present a three-dimensional (3D) quantification of protoporphyrin IX (PpIX) using combined spatial frequency domain imaging (SFDI) and diffuse fluorescence tomography (DFT). The SFDI maps both the distributions of tissue absorption and scattering properties at three wavelengths and accordingly provides the optical background for DFT and extracts the tissue oxygenation for assessing the therapeutic outcomes, while DFT dynamically monitors the 3D distribution of PpIX dose from measured fluorescence signals for the procedure optimization. A pilot in vivo application in tumor nude models showed that the proposed SFDI/DFT is able to dynamically trace changes in the PpIX concentration and tissue oxygen during the treatment, rendering it a potentially powerful tool for PDT to improve clinical efficacy.Photodynamic therapy (PDT) dosimetry, including light dose, photosensitizer dose and tissue oxygen, has been a research focus in PDT. In this work, we present a three-dimensional (3D) quantification of protoporphyrin IX (PpIX) using combined spatial frequency domain imaging (SFDI) and diffuse fluorescence tomography (DFT). The SFDI maps both the distributions of tissue absorption and scattering properties at three wavelengths and accordingly provides the optical background for DFT and extracts the tissue oxygenation for assessing the therapeutic outcomes, while DFT dynamically monitors the 3D distribution of PpIX dose from measured fluorescence signals for the procedure optimization. A pilot in vivo application in tumor nude models showed that the proposed SFDI/DFT is able to dynamically trace changes in the PpIX concentration and tissue oxygen during the treatment, rendering it a potentially powerful tool for PDT to improve clinical efficacy.

基于动态扩散荧光层析成像(DFT)的荧光剂药代动力学参数(渗透率等),可为判断不同生物组织体的生理过程和病理信息提供参考。自适应扩展卡尔曼滤波(AEKF)作为一种动态分析方法,具有精确的建模和多参数在线估计等优势。基于DFT系统对吲哚菁绿(ICG)在健康小鼠肝脏和荷瘤小鼠皮下移植瘤组织中的代谢过程进行了测量,然后采用DFT重建技术获得了ICG的时间序列荧光层析图像,在此基础上结合二室模型和AEKF方法得到了ICG的时间序列渗透率参数层析图像。对比两种实验结果可知,肿瘤中ICG的渗透率参数Kpe、Kep均较健康小鼠肝脏中的小。时间序列荧光层析图像显示,AEKF方法能有效获得复杂生物体实时、稳定的ICG药代动力学参数。

为实现小动物吲哚菁绿(ICG)药代动力学成像, 设计了一套高灵敏度扩散荧光层析成像系统。该系统采用了基于离散光纤耦合光子计数采集的仿计算机断层成像扫描方式, 在保障高灵敏度和大动态范围测量的前提下, 可有效提高系统的空间采样分辨率; 同时采用了基于光开关切换四通道串-并混和的测量模式, 兼顾了测量时间分辨率和系统性价比之间的平衡。为验证实验系统的有效性, 设计了可模拟小动物体内ICG代谢规律的动态仿体, 并结合实验室开发的荧光剂药代动力学直接重建算法, 实现了ICG代谢速率的重建。实验结果表明, 该系统具有较高的空间分辨率、灵敏度和量化性。