Abstract
.Significance: While clinical treatment of actinic keratosis by photodynamic therapy (PDT) is widely practiced, there is a well-known variability in response, primarily caused by heterogeneous accumulation of the photosensitizer protoporphyrin IX (PpIX) between patients and between lesions, but measurement of this is rarely done.Aim: Develop a smartphone-based fluorescence imager for simple quantitative photography of the lesions and their PpIX levels that can be used in a new clinical workflow to guide the reliability of aminolevulinic acid (ALA) application for improved lesion clearance.Approach: The smartphone fluorescence imager uses an iPhone and a custom iOS application for image acquisition, a 3D-printed base for measurement standardization, an emission filter for PpIX fluorescence isolation, and a 405-nm LED ring for optical excitation. System performance was tested to ensure measurement reproducibility and the ability to capture photosensitizer accumulation and photobleaching in pre-clinical and clinical settings.Results: PpIX fluorescence signal from tissue-simulating phantoms showed linear sensitivity in the 0.01 to 2.0 μM range. Murine studies with Ameluz® aminolevulinic acid (ALA) gel and initial human testing with Levulan® ALA cream verified that in-vivo imaging was feasible, including that PpIX production over 1 h is easily captured and that photobleaching from the light treatment could be quantified.Conclusions: The presented device is the first quantitative wide-field fluorescence imaging system for PDT dosimetry designed for clinical skin use and for maximal ease of translation into clinical workflow. The results lay the foundation for using the system in clinical studies to establish treatment thresholds for the individualization of PDT treatment.
Highlights
Clinical use of protoporphyrin-IX (PpIX)-based photodynamic therapy (PDT) is widespread for treatment of actinic keratosis (AKs) and increasingly adopted for treatment of nonmelanomaJournal of Biomedical OpticsJune 2020 Vol 25(6)Ruiz et al.: Smartphone fluorescence imager for quantitative dosimetry. . .skin cancers, due to its effectiveness, safety, and cosmetic results.[1]
protoporphyrin IX (PpIX)-based skin PDT involves the topical application of the prodrug aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) to selectively generate the photosensitizer PpIX in the lesion; after incubation, the lesion is commonly irradiated with light where localized cytotoxicity is induced via reactive molecular species.[2]
We present the first quantitative wide-field fluorescence imaging system for PpIX-PDT dosimetry designed for clinical treatment of the skin and for maximal ease in translation into clinical workflow
Summary
Clinical use of protoporphyrin-IX (PpIX)-based photodynamic therapy (PDT) is widespread for treatment of actinic keratosis (AKs) and increasingly adopted for treatment of nonmelanomaJournal of Biomedical OpticsJune 2020 Vol 25(6)Ruiz et al.: Smartphone fluorescence imager for quantitative dosimetry. . .skin cancers, due to its effectiveness, safety, and cosmetic results.[1]. If it was known that there were suboptimal levels of PpIX, there is a range of things that could be done to mitigate this, including increased incubation times, increased skin temperature,[9] reapplication of ALA after curettage,[10] differentiation therapy,[11] and fractionated light treatment.[12] Wide-field imaging of PpIX shows promise in guiding PDT by providing accessible drug production information at the point of care for these treatment enhancements, which may reduce repeat PDT visits or the added cost of future surgical treatments.[4,13]
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