Ana Gabriela Salvio

Experience and BCC subtypes as determinants of MAL-PDT response: Preliminary results of a national Brazilian project

Non-melanoma skin cancer is the most prevalent cancer type in Brazil and worldwide. Photodynamic therapy (PDT) is a noninvasive technique with excellent cosmetic outcome and good curative results, when used for the initial stages of skin cancer. A Brazilian program was established to determine the efficacy of methyl aminolevulinate (MAL)-PDT, using Brazilian device and drug. The equipment is a dual device that combines the photodiagnosis, based on widefield fluorescence, and the treatment at 630nm. A protocol was defined for the treatment of basal cell carcinoma with 20% MAL cream application. The program also involves the training of the medical teams at different Brazilian regions, and with distinct facilities and previous PDT education. In this report we present the partial results of 27 centers with 366 treated BCC lesions in 294 patients. A complete response (CR) was observed in 76.5% (280/366). The better response was observed for superficial BCC, with CR 160 lesions (80.4%), when compared with nodular or pigmented BCC. Experienced centers presented CR of 85.8% and 90.6% for superficial and nodular BCC respectively. A high influence of the previous doctor experience on the CR values was observed, especially due to a better tumor selection.

Fluorescence guided PDT for optimization of the outcome of skin cancer treatment

The photodynamic therapy (PDT) is an alternative technique that can be indicated for superficial basal cell carcinoma (sBCC), Bowen’s disease and actinic keratosis with high efficiency. The objective of this study is to present the importance of fluorescence imaging for PDT guidance and monitoring in real time. Confirming that the lesion is well prepared and the photosensitizer shows a homogenous distribution, the outcome after few PDT sessions will be positive and the recurrence should be lower. Our proposition in this study is use the widefield fluorescence imaging to evaluate the PDT protocol in situ and in real time for each lesion. This evaluation procedure is performed in two steps: first with the monitoring of the production of protoporphyrin IX (PpIX) induced by methyl aminolevulinate (MAL), an derivative of 5-aminolevulinic acid (ALA) and second with the detection of PpIX photobleaching after illumination. The fluorescence images provide information correlated with distinct clinical features and with the treatment outcome. Eight BCC lesions are presented and discussed in this study. Different fluorescence patterns of PpIX production and photobleaching could be correlated with the treatment response. The presented results show the potential of using widefield fluorescence imaging as a guidance tool to customized PDT.

Portable fluorescence lifetime spectroscopy system for in-situ interrogation of biological tissues

Abstract. Fluorescence spectroscopy and lifetime techniques are potential methods for optical diagnosis and characterization of biological tissues with an in-situ, fast, and noninvasive interrogation. Several diseases may be diagnosed due to differences in the fluorescence spectra of targeted fluorophores, when, these spectra are similar, considering steady-state fluorescence, others may be detected by monitoring their fluorescence lifetime. Despite this complementarity, most of the current fluorescence lifetime systems are not robust and portable, and not being feasible for clinical applications. We describe the assembly of a fluorescence lifetime spectroscopy system in a suitcase, its characterization, and validation with clinical measurements of skin lesions. The assembled system is all encased and robust, maintaining its mechanical, electrical, and optical stability during transportation, and is feasible for clinical measurements. The instrument response function measured was about 300 ps, and the system is properly calibrated. At the clinical study, the system showed to be reliable, and the achieved spectroscopy results support its potential use as an auxiliary tool for skin diagnostics.

Discrimination of benign-versus-malignant skin lesions by thermographic images using support vector machine classifier

Skin cancer is the cancer type with the highest incidence in the world. Its diagnosis requires a specialist physician, with expertise in skin diagnostics. Thermography is a noninvasive technique based on the detection of infrared emission that is completely safe to humans. In this study, thermal images of clinically similar lesions were registered and analyzed aiming to provide a noninvasive diagnostic information for discrimination of: basal cell carcinoma versus intradermal nevus, squamous cell carcinoma versus actinic keratosis, and melanoma versus pigmented seborrheic keratosis. Thermal images were analyzed using a MATLAB® routine to evaluate statistical, histogram, and filtering metrics of each image, and a support vector machine classifier was used to discriminate the lesions based on those metrics values. Actinic keratoses and squamous cell carcinoma showed distinct average temperatures, whereas the other pairs of lesions presented similar temperatures. Nevertheless, the benign lesions showed higher definition of borders detection than malignant lesions, as a general rule. The results showed that support vector machine classifier has great ability for discrimination of clinically similar lesions based on their thermal images, suggesting that the thermography can be used as an auxiliary tool for the diagnosis of skin malignant lesions.Skin cancer is the cancer type with the highest incidence in the world. Its diagnosis requires a specialist physician, with expertise in skin diagnostics. Thermography is a noninvasive technique based on the detection of infrared emission that is completely safe to humans. In this study, thermal images of clinically similar lesions were registered and analyzed aiming to provide a noninvasive diagnostic information for discrimination of: basal cell carcinoma versus intradermal nevus, squamous cell carcinoma versus actinic keratosis, and melanoma versus pigmented seborrheic keratosis. Thermal images were analyzed using a MATLAB® routine to evaluate statistical, histogram, and filtering metrics of each image, and a support vector machine classifier was used to discriminate the lesions based on those metrics values. Actinic keratoses and squamous cell carcinoma showed distinct average temperatures, whereas the other pairs of lesions presented similar temperatures. Nevertheless, the benign lesions showed highe...

A Quantitative Study of In Vivo Protoporphyrin IX Fluorescence Build Up During Occlusive Treatment Phases

BACKGROUND Topical photodynamic therapy (PDT) is a non-invasive light based therapy used to treat non-melanoma skin cancer (NMSC) and dysplasia. During PDT, the light sensitive molecule protoporphyrin IX (PpIX) is activated, resulting in the production of singlet oxygen, which subsequently leads to cell death. PpIX is metabolised from a topically applied pro-drug and the strong fluorescence signal associated with PpIX can be utilised as an indicator of the amount of PpIX present within the tumour tissue. In this work we measure the build up PpIX during the occlusive treatment phase and investigate how the PpIX production rate is affected by different lesion and patient characteristics. METHODS Fluorescence measurements were used to investigate the build up of PpIX within the tumour tissue during the 3h long occlusive treatment prior to irradiation. The study included in vivo measurements of 38 lesions from 38 individual patients. Actinic keratosis (AK) and basal cell carcinoma (BCC) were the lesion types included in this study. The resulting data from the study was analysed using generalised linear mixed effects models. RESULTS It was found that the surface fluorescence signal linearly increased with occlusive treatment time. The predictive models suggest that there is a significant difference in PpIX production between lesion location, however no significant difference is demonstrated between different lesion types, gender and skin type. CONCLUSIONS The study extends and supports previous knowledge of PpIX production during the occlusive treatment phase.

Asymmetry and irregularity border as discrimination factor between melanocytic lesions

Image processing tools have been widely used in systems supporting medical diagnosis. The use of mobile devices for the diagnosis of melanoma can assist doctors and improve their diagnosis of a melanocytic lesion. This study proposes a method of image analysis for melanoma discrimination from other types of melanocytic lesions, such as regular and atypical nevi. The process is based on extracting features related with asymmetry and border irregularity. It were collected 104 images, from medical database of two years. The images were obtained with standard digital cameras without lighting and scale control. Metrics relating to the characteristics of shape, asymmetry and curvature of the contour were extracted from segmented images. Linear Discriminant Analysis was performed for dimensionality reduction and data visualization. Segmentation results showed good efficiency in the process, with approximately 88:5% accuracy. Validation results presents sensibility and specificity 85% and 70% for melanoma detection, respectively.

Thermographic diagnostics to discriminate skin lesions: a clinical study

Cancer is responsible for about 13% of all causes of death in the world. Over 7 million people die annually of this disease. In most cases, the survival rates are greater when diagnosed in early stages. It is known that tumor lesions present a different temperature compared with the normal tissues. Some studies have been performed in an attempt to establish new diagnosis methods, targeting this temperature difference. In this study, we aim to investigate the use of a handheld thermographic camera to discriminate skin lesions. The patients presenting Basal Cell Carcinoma, Squamous Cell Carcinoma, Actinic Keratosis, Pigmented Seborrheic Keratosis, Melanoma or Intradermal Nevus lesions have been investigated at the Skin Departament of Amaral Carvalho Hospital. Patients are selected by a dermatologist, and the lesion images are recorded using an infrared camera. The images are evaluated taken into account the temperature level, and differences into lesion areas, borders, and between altered and normal skin. The present results show that thermography may be an important tool for aiding in the clinical diagnostics of superficial skin lesions.

New Device for PpIX Fluorescence Imaging and Non-melanoma Skin Cancer Treatment

Non melanoma skin cancer (NMSC) is the most frequent worldwide, and it is necessary the development of new technologies with successful results. We are presenting our National Program for the Photodynamic Therapy of NMSC.

Fluorescence Monitoring of Haematoporphyrin Derivatives for Photodynamic Diagnosis

In vitro and in vivo tests were performed to investigate marked fluorescence diagnosis of basal cell carcinoma. Results showed improved differentiation between normal and lesion tissues. Excitation light showed to be limiting factor for diagnosis.