Ethan P M LaRochelle1, Kayla Marra2, Robert E LeBlanc3, M Shane Chapman4, Edward V Maytin5, Brian W Pogue6. 1. Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA. Electronic address: ethan.phillip.m.larochelle.th@dartmouth.edu. 2. Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA. 3. Department Pathology & Laboratory Medicine, Geisel School of Medicine, Dartmouth College, Lebanon, NH 03756, USA. 4. Department of Surgery, Geisel School of Medicine, Dartmouth College, Lebanon, NH 03756, USA. 5. Department of Biomedical Engineering, Cleveland Clinic, Cleveland, OH 44195, USA. 6. Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA; Department of Surgery, Geisel School of Medicine, Dartmouth College, Lebanon, NH 03756, USA.
Abstract
BACKGROUND: Daylight-activated PDT has seen increased support in recent years as a treatment method for actinic keratosis and other non-melanoma skin cancers. The inherent variability observed in broad-spectrum light used in this methodology makes it difficult to plan and monitor light dose, or compare to lamp light doses. METHODS: The present study expands on the commonly used PpIX-weighted effective surface irradiance metric by introducing a Monte Carlo method for estimating effective fluence rates into depths of the skin. The fluence rates are compared between multiple broadband and narrowband sources that have been reported in previous studies, and an effective total fluence for various treatment times is reported. A dynamic estimate of PpIX concentration produced during pro-drug incubation and treatment is used with the fluence estimates to calculate a photodynamic dose. RESULTS: Even when there is up to a 5x reduction between the effective surface irradiance of the broadband light sources, the effective fluence below 250 μm depth is predicted to be relatively equivalent. An effective threshold fluence value (0. 70Jeff/cm2) is introduced based on a meta-analysis of previously published ALA-PpIX induced cell death. This was combined with a threshold PpIX concentration (50 nM) to define a threshold photodynamic dose of 0.035 u M Jeff/cm2. CONCLUSIONS: The threshold was used to generate lookup tables to prescribe minimal treatment times to achieve depth-dependent cytotoxic effect based on incubation times and irradiance values for each light source.
BACKGROUND: Daylight-activated PDT has seen increased support in recent years as a treatment method for actinic keratosis and other non-melanoma skin cancers. The inherent variability observed in broad-spectrum light used in this methodology makes it difficult to plan and monitor light dose, or compare to lamp light doses. METHODS: The present study expands on the commonly used PpIX-weighted effective surface irradiance metric by introducing a Monte Carlo method for estimating effective fluence rates into depths of the skin. The fluence rates are compared between multiple broadband and narrowband sources that have been reported in previous studies, and an effective total fluence for various treatment times is reported. A dynamic estimate of PpIX concentration produced during pro-drug incubation and treatment is used with the fluence estimates to calculate a photodynamic dose. RESULTS: Even when there is up to a 5x reduction between the effective surface irradiance of the broadband light sources, the effective fluence below 250 μm depth is predicted to be relatively equivalent. An effective threshold fluence value (0. 70Jeff/cm2) is introduced based on a meta-analysis of previously published ALA-PpIX induced cell death. This was combined with a threshold PpIX concentration (50 nM) to define a threshold photodynamic dose of 0.035 u M Jeff/cm2. CONCLUSIONS: The threshold was used to generate lookup tables to prescribe minimal treatment times to achieve depth-dependent cytotoxic effect based on incubation times and irradiance values for each light source.
Authors: Ethan P M LaRochelle; Michael Shane Chapman; Edward V Maytin; Tayyaba Hasan; Brian W Pogue Journal: Photochem Photobiol Date: 2019-10-21 Impact factor: 3.421