Determination of Optical Properties and Photodynamic Threshold of Lung Tissue for Treatment Planning of In Vivo Lung Perfusion Assisted Photodynamic Therapy

Abstract

BackgroundIsolated lung metastases in sarcoma and colorectal cancer patients are inadequately treated with current standard therapies. In Vivo Lung Perfusion, a novel platform, could overcome limitations to photodynamic therapy treatment volumes by using low cellular perfusate, removing blood, theoretically allowing greater light penetration. To develop personalized photodynamic therapy protocols requires in silico light propagation simulations based on optical properties and maximal permissible photodynamic threshold dose of lung tissue. This study presents quantification of optical properties for two perfusates and the photodynamic threshold for 5-ALA and Chlorin e6. MethodsPorcine and human lungs were placed on Ex Vivo Lung Perfusion, and perfused with acellular solution or blood. Isotropic diffusers were placed within bronchi and on lung surface for light transmission measurements, from which absorption and light scattering properties were calculated at multiple wavelengths. Separately, pigs were injected with 5-ALA or Chlorin e6, and lung tissue was irradiated at increasing doses. Resultant lesion sizes were measured by CT and histology to quantify the photodynamic threshold. ResultsLow cellular perfusate reduced the tissue absorption coefficient significantly, increasing penetration depth of light by 3.3 mm and treatment volumes 3-fold. The photodynamic threshold for lung exposed to 5-ALA was consistent with other malignancies. Chlorin e6 levels were undetectable in lung tissue and did not demonstrate photodynamic-induced necrosis. ConclusionsLight penetration with low cellular perfusate is significantly greater and could enable treatments for diffuse disease. This data aids photodynamic treatment planning and will guide clinical translation of photodynamic therapy protocols in the lung, especially during lung perfusion.