Erratum: "A comprehensive mathematical model of microscopic dose deposition in photodynamic therapy" [Med. Phys. 34, 282-293 (2007)].
Erratum: "A comprehensive mathematical model of microscopic dose deposition in photodynamic therapy" [Med. Phys. 34, 282-293 (2007)].
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勘误：“光动力疗法中微观剂量沉积的综合数学模型”[Med。
DOI：
10.1118/1.2959704
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发表时间：
2008
期刊：
影响因子：
3.8
通讯作者：
Foster,ThomasH
中科院分区：
文献类型：
--
作者：
Wang,KenKang-Hsin;Mitra,Soumya;Foster,ThomasH
我们建立了一个完整的理论模型来严格描述体内光动力治疗(PDT)过程中氧的消耗和运输的时空动态以及微观光动力学剂量沉积。以前发表的模型已经得到了改进，将灌流的血管视为依赖于时间的来源，并通过Hill方程将血管内的浓度与组织内的浓度联系起来。与时间相关的光化学消耗速率包括感光剂的光漂白效应和实验确定的最初不均匀的光敏剂分布。在毛细血管和周围组织中提供了轴向传输。用自敏化单线态氧介导的漂白机制和血管内给药后测量到的初始不均匀分布的Meso-四羟基苯基氯来验证该模型的能力。通过数值求解毛细血管和邻近组织中的二维扩散-反应方程，得到了浓度的时间演化分布。利用实验建立的生理和光物理参数，该数学模型可以计算血管内血红蛋白饱和度的动态变化、光漂白引起的不可逆敏化剂降解以及不同照射条件下敏化剂浓度和剂量沉积的微观分布。模拟显示，光动力剂量沉积中和在光动力剂量沉积中的严重轴向梯度响应于广泛的临床相关治疗参数。因此，与以前的基于Krogh圆柱体的模型不同，该模型假设血管中的浓度恒定，该新模型识别了在血管轴段末端附近存在耗竭和最小限度的反应沉积的条件，并表明治疗限制耗竭是在低至这些计算还表明，光敏剂的毛细管间非均质性对光动力剂量的分布有重要影响。这一更严格的数学模型可以与实验可观察到的体积平均量进行比较，例如通过漂白和漂白造成的增感剂荧光的损失，这些都没有包括在以前的分析中。此外，它还确立了此类测量的一些内在局限性。具体地说，我们的模拟表明，光漂白和光漂白的组织测量必然对光动力剂量沉积的微观异质性不敏感，而对毛细管间距敏感。因为肿瘤毛细血管间距离的先验知识通常是不可获得的，所以这些测量必须谨慎地解释。我们预计，该模型将做出有用的剂量学预测，为最佳治疗条件提供信息，并改进当前的临床方案。
We have developed a comprehensive theoretical model for rigorously describing the spatial and temporal dynamics of oxygen consumption and transport and microscopic photodynamic dose deposition during photodynamic therapy (PDT)in vivo. Previously published models have been improved by considering perfused vessels as a time‐dependent source and linking the concentration in the vessel to that within the tissue through the Hill equation. The time‐dependent photochemical consumption rate incorporates sensitizer photobleaching effects and an experimentally determined initially nonuniform photosensitizer distribution. The axial transport of is provided for in the capillaries and in the surrounding tissue. A self‐sensitized singlet oxygen ‐mediated bleaching mechanism and the measured, initially nonuniform distribution ofmeso‐tetrahydroxyphenyl chlorin at after intravascular administration were used to demonstrate the capabilities of the model. Time‐evolved distributions of concentration were obtained by numerically solving two‐dimensional diffusion‐with‐reaction equations both in the capillary and the adjacent tissue. Using experimentally established physiological and photophysical parameters, the mathematical model allows computation of the dynamic variation of hemoglobin‐ saturation within the vessels, irreversible sensitizer degradation due to photobleaching, and the microscopic distributions of , sensitizer concentration, and dose deposition under various irradiation conditions. The simulations reveal severe axial gradients in and in photodynamic dose deposition in response to a wide range of clinically relevant treatment parameters. Thus, unlike former Krogh cylinder‐based models, which assume a constant concentration at the vessel, this new model identifies conditions in which depletion and minimal deposition of reacting exist near the end of axial segments of vessels and shows that treatment‐limiting depletion is induced at fluence rates as low as . These calculations also demonstrate that intercapillary heterogeneity of photosensitizer contributes significantly to the distribution of photodynamic dose. This more rigorous mathematical model enables comparison with experimentally observable, volume‐averaged quantities such as and the loss of sensitizer fluorescence through bleaching that have not been included in previous analyses. Further, it establishes some of the intrinsic limitations of such measurements. Specifically, our simulations demonstrate that tissue measurements of and of photobleaching are necessarily insensitive to microscopic heterogeneity of photodynamic dose deposition and are sensitive to intercapillary spacing. Because prior knowledge of intercapillary distances in tumors is generally unavailable, these measurements must be interpreted with caution. We anticipate that this model will make useful dosimetry predictions that should inform optimal treatment conditions and improve current clinical protocols.