Superficial radially resolved fluorescence and 3D photochemical time-dependent model for photodynamic therapy

Photodynamic therapy (PDT) dosimetric tools are crucial for treatment planning and noninvasive monitoring by means of fluorescence. Present approaches consider usually a 1D problem, a simple photochemical process, or a spatially homogeneous photosensitizer. In this work, a radially resolved superficial photosensitizer fluorescence and 3D photochemical time-dependent PDT model are presented. The model provides a time-dependent estimation of tissue fluorescence and the photosensitizer and singlet oxygen 3D concentrations. The model is applied to a basal cell carcinoma treated by Metvix topical photosensitizer protocol. The analysis shows the potentiality in treatment planning and monitoring. The fluorescence results are in agreement with previous measurements

Analysis of laser surgery in non-melanoma skin cancer for optimal tissue removal

Laser surgery is a commonly used technique for tissue ablation or the resection of malignant tumors. It presents advantages over conventional non-optical ablation techniques, like a scalpel or electrosurgery, such as the increased precision of the resected volume, minimization of scars and shorter recovery periods. Laser surgery is employed in medical branches such as ophthalmology or dermatology. The application of laser surgery requires the optimal adjustment of laser beam parameters, taking into account the particular patient and lesion. In this work we present a predictive tool for tissue resection in biological tissue after laser surgery, which allows an a priori knowledge of the tissue ablation volume, area and depth. The model employs a Monte Carlo 3D approach for optical propagation and a rate equation for plasma-induced ablation. The tool takes into account characteristics of the specific lesion to be ablated, mainly the geometric, optical and ablation properties. It also considers the parameters of the laser beam, such as the radius, spatial profile, pulse width, total delivered energy or wavelength. The predictive tool is applied to dermatology tumor resection, particularly to different types of non-melanoma skin cancer tumors: basocellular carcinoma, squamous cell carcinoma and infiltrative carcinoma. The ablation volume, area and depth are calculated for healthy skin and for each type of tumor as a function of the laser beam parameters. The tool could be used for laser surgery planning before the clinical application. The laser parameters could be adjusted for optimal resection volume, by personalizing the process to the particular patient and lesion.This work has been partially supported by the project MAT2012-38664-C02-01 of the Spanish Ministery of Economy and Competitiveness and by The San Cándido Foundatio

Influence of the human skin tumor type in photodynamic therapy analysed by a predictive model

Photodynamic Therapy (PDT) modeling allows the prediction of the treatment results depending on the lesion properties, the photosensitizer distribution, or the optical source characteristics. We employ a predictive PDT model and apply it to different skin tumors. It takes into account optical radiation distribution, a nonhomogeneous topical photosensitizer spatial temporal distribution, and the time-dependent photochemical interaction. The predicted singlet oxygen molecular concentrations with varying optical irradiance are compared and could be directly related with the necrosis area. The results show a strong dependence on the particular lesion. This suggests the need to design optimal PDT treatment protocols adapted to the specific patient and lesion

Analysis of superficial fluorescence patterns in nonmelanoma skin cancer during photodynamic therapy by a dosimetric tool

In this work the superficial fluorescence patterns in different nonmelanoma skin cancers and their photodynamic treatment response are analysed by a fluorescence based dosimetric model. Results show differences of even more than 50% in the fluorescence patterns as photodynamic therapy progresses depending on the malignant tissue type. They demonstrate the great relevance of the biological media as an additional dosimetric factor and contribute to the development of a future customized therapy with the assistance of dosimetric tools to interpret the fluorescence images obtained during the treatment monitoring and the differential photodiagnosis.This work has been partially supported by the project MAT2012-38664-C02-01 of the Spanish Ministery of Economy and Competitiveness and by San Cándido Foundation

FDTD-based Transcranial Magnetic Stimulation model applied to specific neurodegenerative disorders

Non-invasive treatment of neurodegenerative diseases is particularly challenging in Western countries, where the population age is increasing. In this work, magnetic propagation in human head is modelled by Finite-Difference Time-Domain (FDTD) method, taking into account specific characteristics of Transcranial Magnetic Stimulation (TMS) in neurodegenerative diseases. It uses a realistic high-resolution three-dimensional human head mesh. The numerical method is applied to the analysis of magnetic radiation distribution in the brain using two realistic magnetic source models: a circular coil and a figure-8 coil commonly employed in TMS. The complete model was applied to the study of magnetic stimulation in Alzheimer and Parkinson Diseases (AD, PD). The results show the electrical field distribution when magnetic stimulation is supplied to those brain areas of specific interest for each particular disease. Thereby the current approach entails a high potential for the establishment of the current underdeveloped TMS dosimetry in its emerging application to AD and PD

Comparative numerical analysis of magnetic and optical radiation propagation in adult human head

In this work, magnetic and optical propagation in human head are modeled by FDTD and Monte Carlo methods. Both of them use a realistic high-resolution three-dimensional human head mesh. The numerical methods are applied to the analysis of magnetic and optical radiation distribution in the brain using different sources. The results show the characteristics of both types of stimulation, and highlight the spatial selectivity achieved by optical sources, which entails a high potential for illuminating specific brain regions. The presented approach can be applied for predictive purposes in magnetic stimulation techniques and in the emerging field of optical brain stimulation

Predictive model for Photodynamic Therapy with gold nanoparticles as vehicle for the photosensitizer delivery

Photodynamic Therapy offers multiple advantages to treat nonmelanoma skin cancer compared to conventional treatment techniques such as surgery, radiotherapy or chemotherapy. Among these advantages are particularly relevant its noninvasive nature, the use of non ionizing radiation and its high selectivity. However the therapeutic efficiency of the current clinical protocol is not complete in all the patients and depends on the type of pathology. Emerging strategies to overcome its current shortcomings include the use of nanostructures that can act as carriers for conventional photosensitizers and improve the treatment selectivity and provide a controlled release of the photoactive agent. In this work, a model for photodynamic therapy combined with gold nanocarriers for a photosensitizer commonly used in dermatology is presented and applied to a basal cell carcinoma in order to predict the cytotoxic agent spatial and temporal evolution.This work has been partially supported by the project MAT2012-38664-C02-01 of the Spanish Ministery of Economy and Competitivenss and by San Cándido Foundatio

Singlet oxygen prediction in gold nanoparticles-assisted PDT applied to a squamous cell carcinoma in the esophagus

A predictive model for PDT singlet oxygen production in esophageal squamous cell carcinomas with gold nanoparticles is proposed. Differences enhance the ¹O₂ -mediated oxidative damage due to the optical absorption improvement by gold nanoparticles.This work has been partially supported by the project MAT2012-38664-C02-01 of the Spanish Ministery of Economy and Competitiveness

Polarized light Monte Carlo analysis of birefringence-induced depolarization in biological tissues

In this work we analyze the impact of linear birefringence on biological tissues depolarization, which is essential for correctly interpreting experimental results. Our approach is based on the polarized light Monte Carlo method in transmission. We present a comparative analysis of light depolarization in biological tissues with different values of linear birefringence and particle sizes, in order to evaluate its impact on the calculated parameters

Analysis of optical neural stimulation effects on neural networks affected by neurodegenerative diseases

The number of people in risk of developing a neurodegenerative disease increases as the life expectancy grows due to medical advances. Multiple techniques have been developed to improve patient’s condition, from pharmacological to invasive electrodes approaches, but no definite cure has yet been discovered. In this work Optical Neural Stimulation (ONS) has been studied. ONS stimulates noninvasively the outer regions of the brain, mainly the neocortex. The relationship between the stimulation parameters and the therapeutic response is not totally clear. In order to find optimal ONS parameters to treat a particular neurodegenerative disease, mathematical modeling is necessary. Neural networks models have been employed to study the neural spiking activity change induced by ONS. Healthy and pathological neocortical networks have been considered to study the required stimulation to restore the normal activity. The network consisted of a group of interconnected neurons, which were assigned 2D spatial coordinates. The optical stimulation spatial profile was assumed to be Gaussian. The stimulation effects were modeled as synaptic current increases in the affected neurons, proportional to the stimulation fluence. Pathological networks were defined as the healthy ones with some neurons being inactivated, which presented no synaptic conductance. Neurons’ electrical activity was also studied in the frequency domain, focusing specially on the changes of the spectral bands corresponding to brain waves. The complete model could be used to determine the optimal ONS parameters in order to achieve the specific neural spiking patterns or the required local neural activity increase to treat particular neurodegenerative pathologies.This work has been partially supported by the project MAT2012-38664-C02-01 of the Spanish Ministery of Economy and Competitiveness and by San Cándido Foundation