Smartphone-based dual radiometric fluorescence and white-light imager for quantification of protoporphyrin IX in skin

基于智能手机的双辐射荧光和白光成像仪用于量化皮肤中的原卟啉 IX

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作者:Alberto J Ruiz, Richard Allen, Mia K Giallorenzi, Kimberley S Samkoe, M Shane Chapman, Brian W Pogue

Aim

We aim to develop a smartphone-based imager for performing simultaneous radiometric fluorescence (FL) and white light (WL) imaging to study the baseline levels, accumulation, and photobleaching of PpIX in skin. Approach: A smartphone-based dual FL and WL imager (sDUO) is introduced alongside new radiometric calibration

Conclusions

The phantom, pre-clinical, and clinical measurements demonstrated the capability of the sDUO to provide quantitative measurements of PpIX FL. The results demonstrate the use of the sDUO for the quantification of PpIX accumulation and photobleaching in a clinical setting, with implications for improving the diagnosis and treatment of various skin conditions.

Results

The sDUO alongside the developed methods provided radiometric FL measurements (nW/cm2nW/cm2<math><mrow><mi>nW</mi><mo>/</mo><msup><mrow><mi>cm</mi></mrow><mrow><mn>2</mn></mrow></msup></mrow></math>) with a demonstrated sub nanomolar PpIX sensitivity in 1% intralipid phantoms. Patients undergoing PDT treatment of actinic keratosis (AK) lesions were imaged, capturing the increase and subsequent decrease in FL associated with the incubation and irradiation timepoints of lamp-based PDT. Furthermore, the clinical measurements showed mechanistic differences in new daylight-based treatment modalities alongside the selective accumulation of PpIX within AK lesions. The use of the radiometric calibration enabled the reporting of detected PpIX FL in units of nW/cm2nW/cm2<math><mrow><mi>nW</mi><mo>/</mo><msup><mi>cm</mi><mn>2</mn></msup></mrow></math> with the use of liquid phantom measurements allowing for the estimation of in-vivo molar concentrations of skin PpIX. Conclusions: The phantom, pre-clinical, and clinical measurements demonstrated the capability of the sDUO to provide quantitative measurements of PpIX FL. The results demonstrate the use of the sDUO for the quantification of PpIX accumulation and photobleaching in a clinical setting, with implications for improving the diagnosis and treatment of various skin conditions.

Significance

The quantification of protoporphyrin IX (PpIX) in skin can be used to study photodynamic therapy (PDT) treatments, understand porphyrin mechanisms, and enhance preoperative mapping of non-melanoma skin cancers. Aim: We aim to develop a smartphone-based imager for performing simultaneous radiometric fluorescence (FL) and white light (WL) imaging to study the baseline levels, accumulation, and photobleaching of PpIX in skin. Approach: A smartphone-based dual FL and WL imager (sDUO) is introduced alongside new radiometric calibration methods for providing SI-units of measurements in both pre-clinical and clinical settings. These radiometric measurements and corresponding PpIX concentration estimations are applied to clinical measurements to understand mechanistic differences between PDT treatments, accumulation differences between normal tissue and actinic keratosis lesions, and the correlation of photosensitizer concentrations to treatment outcomes. Results: The sDUO alongside the developed methods provided radiometric FL measurements (nW/cm2nW/cm2<math><mrow><mi>nW</mi><mo>/</mo><msup><mrow><mi>cm</mi></mrow><mrow><mn>2</mn></mrow></msup></mrow></math>) with a demonstrated sub nanomolar PpIX sensitivity in 1% intralipid phantoms. Patients undergoing PDT treatment of actinic keratosis (AK) lesions were imaged, capturing the increase and subsequent decrease in FL associated with the incubation and irradiation timepoints of lamp-based PDT. Furthermore, the clinical measurements showed mechanistic differences in new daylight-based treatment modalities alongside the selective accumulation of PpIX within AK lesions. The use of the radiometric calibration enabled the reporting of detected PpIX FL in units of nW/cm2nW/cm2<math><mrow><mi>nW</mi><mo>/</mo><msup><mi>cm</mi><mn>2</mn></msup></mrow></math> with the use of liquid phantom measurements allowing for the estimation of in-vivo molar concentrations of skin PpIX. Conclusions: The phantom, pre-clinical, and clinical measurements demonstrated the capability of the sDUO to provide quantitative measurements of PpIX FL. The results demonstrate the use of the sDUO for the quantification of PpIX accumulation and photobleaching in a clinical setting, with implications for improving the diagnosis and treatment of various skin conditions.

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