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An investigation of the temperature response and corresponding lesion growth resulting from in vivo interstitial laser photocoagulation was performed in order to test the applicability of Arrhenius theory. The irradiations were performed in vivo in rabbit muscle for various exposures at 1.0W using an 805 nm diode laser source coupled to an optical fibre with a pre-charred tip, thereby forcing it to function as a point heat source. Temperature responses were measured using a five-microthermocouple array along a range of radial distances from the point heat source. Each temperature profile was fitted with a curve predicted by the Weinbaum-Jiji bioheat transfer equation. The lesions were resected 48 hours after irradiation and the boundary of thermal damage resulting in necrosis was determined histologically. Numerical integration of the Arrhenius integral using temperature-time data at the lesion boundary produced corresponding activation energy and pre-exponential factor pairs (Eₐ , α) consistent with reported values for various other endpoints and tissue types. As well, theoretical predictions of the lesion growth from Arrhenius theory agreed well with experimental results. However, the thermal parameters, which are generally assumed to be constant when solving the bioheat transfer equation, were found to vary with radial distance from the source, presumably due to dependence on temperature. / Thesis / Master of Science (MS)

L’impact laser obtenu avec les systèmes actuels de photocoagulation laser de la rétine n’est pas maitrisé. L’enjeu est d'obtenir un confinement 3D de l'impact laser, c’est-à-dire de contrôler son positionnement et son extension, pour éviter de porter atteinte aux couches saines de la rétine. Un tel confinement pourrait être réalisé si l’on disposait d’un système laser plus ouvert et d’un dispositif permettant de corriger en temps réel les aberrations de l'œil. L’optique adaptative permet une telle correction ; cette technique est utilisée depuis une vingtaine d’années dans le domaine du diagnostic (imagerie). Cependant, sa mise en œuvre pour des applications thérapeutiques, telles que la photocoagulation laser, nécessite encore d’en améliorer la robustesse : alors qu’en imagerie il suffit de reprendre une image si la précédente est mauvaise, le confinement de l’impact laser doit être assuré en permanence durant toute la procédure chirurgicale. Le but de la thèse est de guider le développement ultérieur d’un système d’optique adaptative médical visant à assister un système de photocoagulation laser de la rétine. Le dimensionnement d’un tel système doit s’appuyer sur une solide connaissance des aberrations oculaires. Ainsi, une étude hautement résolue temporellement et spatialement des aberrations dynamiques de l’œil de grande ampleur a été réalisée et de cette étude, des conclusions sur le dimensionnement d’un système d’optique adaptative pour l’œil ont été tirées. Par ailleurs, un banc de test d’optique adaptative haute cadence a été conçu et intégré pour se confronter aux problèmes pratiques que pose la mise en place d’un système d’optique adaptative pour l’œil. / The laser lesion delivered by current retinal photocoagulation laser systems is not well controlled. The issue is to get a better confinement of the laser lesion that is to control the size of the laser lesion as well as the laser lesion positioning in the retina, in order to prevent any retinal damage. Such a confinement could be reached if the laser system featured a higher numerical aperture and was associated with a real-time correction of the aberrations of the eye. Adaptive optics gives access to such a correction; this technique has been used for the past twenty years for diagnosis (retinal imaging). However, further work is still to be achieved to improve the robustness of current adaptive optics systems before implementing adaptive optics in therapeutic systems, in particular in retinal laser photocoagulation systems. Indeed, unlike imaging where the acquisition can be repeated as many times as necessary, the confinement of the laser lesion must be maintained over time during the whole laser treatment. In this thesis, we provide guidance for the future design of an adaptive optics system for retinal photocoagulation. Such a design has to rely on a thorough knowledge of the ocular aberrations to correct. Thus, a highly temporally as well as spatially resolved aberrometry study on a large population was performed and conclusions on the design of an adaptive optics system for the eye were drawn from this study. Besides, a test bench was designed and set up to face the practical problems coming with the implementation of an adaptive optics system for the eye.

The purpose of this project was to develop a delivery system optimized for laser interstitial thermotherapy of small tumors of the breast. The proposed approach is to combine laser interstitial thermotherapy with stereotactic imaging for fiber guidance and treatment monitoring. The goals of the dissertation were to design a fiber insertion system for cylindrical diffusing tip optical fibers and to derive optimal laser parameters for coagulation of 1 cm tumor plus a surrounding 1 cm thick rim of healthy tissue. A fiber insertion system compatible with a high resolution stereotactic digital X-ray biopsy system was designed to guide the fiber into the tumor site in similar fashion to the insertion of the biopsy needle. An optical-thermal model consisting of a radiation model, a thermal model, and a coagulation model was developed and validated using ex-vivo porcine tissue. A single integrating sphere optical property measurement system and an inverse Monte Carlo algorithm were developed to measure the optical properties of ex-vivo porcine tissue at 830, 940, and 980 nm. An experimental method was developed to determine the parameters of the Arrhenius model (frequency factor (A) and activation energy (Ea)). The optical-thermal model was validated by comparing the predicted temperature and coagulation to results of laser irradiation experiments at 830, 940, and 980 nm. Using published values of the optical properties of the breast, the model predicts that a 3 cm coagulation size can be produced without vaporization in 10 min with 10.4 W at 980 and 940 nm and 13.2 W at 830 nm. The same outcome can be achieved in 20 min with 4.5 W at 980 and 940 nm and 6.1 W at 830 nm.

No / The purpose of this research was to correlate in vivo spatial and spectral morphologic changes of short- to long-pulse 532 nm Nd:YAG retinal laser lesions using Fourier-domain optical coherence tomography (FD OCT), autofluorescence (AF), fluorescein angiography (FA), and multispectral imaging. Ten eyes with treatment-naive preproliferative or proliferative diabetic retinopathy were studied. A titration grid of laser burns at 20, 100, and 200 milliseconds was applied to the nasal retina and laser fluence titrated to produce four grades of laser lesion visibility: subvisible (SV), barely visible (BV, light-gray), threshold (TH, gray-white), and suprathreshold (ST, white). The AF, FA, FD-OCT, and multispectral imaging were performed 1 week before laser, and 1 hour, 4 weeks, and 3 and 6 months post-laser. Multispectral imaging measured relative tissue oxygen concentration. Laser burn visibility and lesion size increased in a linear relationship according to fixed fluence levels. At fixed pulse durations, there was a semilogarithmic increase in lesion size over 6 months. At 20 milliseconds, all grades of laser lesion were reduced significantly in size after 6 months: SV, 51%; BV, 54%; TH, 49%; and ST, 50% (P < 0.001), with retinal pigment epithelial proliferation and photoreceptor infilling. At 20 milliseconds, there was healing of photoreceptor inner segment/outer segment junction layers compared with 100- and 200-millisecond lesions. Significant increases in mean tissue oxygenation (range, four to six units) within the laser titration area and in oxygen concentration across the laser lesions (P < 0.01) were detected at 6 months. For patients undergoing therapeutic laser, there may be improved tissue oxygenation, higher predictability of burn morphology, and more spatial localization of healing responses of burns at 20 milliseconds compared with longer pulse durations over time / Optimedica Corp., the Manchester Academic Health Sciences Centre, and the NIHR Manchester Biomedical Research Centre. JD was funded by a College of Optometrists PhD Studentship, United Kingdom.

O presente trabalho trata-se do desenvolvimento de uma cavidade Laser de estado sólido e geração de segundo harmônico, para fins oftalmológicos. A cavidade faz parte de um projeto maior que se refere a um fotocoagulador portátil, utilizado em diversos protocolos clínicos relacionados às doenças da retina e câmara anterior, como retinopatia diabética, retinopatia da prematuridade, glaucoma, edema macular e descolamento de retina. A cavidade proposta é composta por três espelhos dispostos em uma arquitetura em V. Um laser de diodo bombeia um cristal de Nd:YAG para a geração de laser em 1064nm que passa por um cristal de KTP para a geração de segundo harmônico em 532nm (laser verde). O sistema de acoplamento indexado à cavidade acopla até 90% da potência de saída em uma fibra óptica com núcleo de 100\'mü\'m. A cavidade projetada e implementada, produz um feixe com comprimento de onda de 532nm (laser verde), largura de banda de 0,5nm, potência máxima em torno de 2,5W na saída da fibra óptica e pulsos com duração máxima de 3s, que são requisitos para os tratamentos oftalmológicos associados a este tipo de equipamento. É importante destacar que a cavidade foi projetada e desenvolvida inteiramente com tecnologia nacional, sendo o primeiro trabalho desenvolvido no Brasil, que se tornou efetivamente um equipamento final para uso clínico. Além do projeto da cavidade laser, são descritos neste trabalho os sistemas mecânico e eletrônico, que possibilitaram seu funcionamento na integração do fotocoagulador. O fotocoagulador foi testado em pacientes voluntários da Escola Paulista de Medicina da UNIFESP, apresentando resultados comparáveis aos sistemas importados. / This work presents the research and the development of a solid state laser cavity with second harmonic generation for ophthalmological purpose. The laser cavity is part of a major project intended to produce a handle photocoagulator. This medical equipment is applied in several clinical protocols related to retinal and anterior chamber pathologies, such as diabetic retinopathy, retinopathy of prematurity, glaucoma, macular edema and retinal detachment. The present cavity is composed by three mirrors disposed in a V shape architecture. One laser diode pumps the Nd:YAG crystal to generate the 1064nm laser that is converted by second harmonic generation in 532nm through the KTP crystal (green laser). The coupling system attached in the cavity is able to collimate until 90% of the laser beam inside a optical fiber with 100 \'mü\'m core. The developed cavity produces a beam with wavelength of 532nm, spectral width of 0.5nm, maximum power around 2.5W in the end of the optical fiber and maximum pulse duration of 3s. Those parameters are requirements for ophthalmological treatments related to this kind of equipment. It is important to declare that the cavity was projected and developed in Brazil. This is the first work in this country that becomes effectively a device to clinical application. Besides the cavity design project, in this work also describes the mechanical and electronic sub systems that was responsible to the laser control and photocoagulator assembler. This product was tested in patients eyes from UNIFESP (Escola Paulista de Medicina), and showed similar results compared to the systems on the market.

Este trabalho tem por objetivo o desenvolvimento e otimização de uma cavidade laser self-Raman de aplicações oftalmológicas. A cavidade laser é do tipo estado sólido bombeada longitudinalmente por um diodo laser infravermelho. A cavidade é dita self-Raman pois um cristal Raman intracavidade faz o papel de meio ativo e deslocador Raman. Esse tipo de configuração é extremamente vantajoso uma vez que promove uma redução dimensional, de custos e de perdas intracavidade. Outro elemento não linear intracavidade é responsável pela geração do segundo harmônico da primeira linha Stokes gerada pelo cristal Raman. Dessa maneira obtém-se radiação em 586.5 nm da cavidade laser, o que corresponde a porção amarela do espectro eletromagnético. Essa região amarelo-alaranjada do espectro é de muita importância e aplicabilidade na indústria, ciências e na medicina. Na oftalmologia, em particular, é de enorme interesse que se construa um laser amarelo para fotocoagulação da retina uma vez que há muito tempo sabe-se que essa porção do espectro possui uma absorção desprezível pela Xantofila, cromóforo abundantemente presente na mácula. A mácula é a porção da retina responsável pela visão central e não deve absorver radiação laser pois isso seria desastroso para o paciente. / The objective of this work is the development and optimization of a self-Raman laser cavity with ophthalmological applications. The laser cavity is a longitudinally diode pumped solid state laser. The laser cavity is so-called self-Raman because an intracavity Raman crystal plays a role as an active media and Raman shifter. This type of configuration is extremely advantageous because it promotes a reduction in costs, dimensions and intracavity losses. Another non linear intracavity element is responsible for the second harmonic generation of the first Stokes line generated by the Raman crystal. Thereby one obtains 586.5 nm radiation coming out of the laser cavity, a wavelength in the yellow portion of the electromagnetic spectra. This yellow-orange range of the spectra is of great importance because and has many and increasingly applications in science, industry and medicine. Particularly in ophthalmology, a yellow laser for retina photocoagulation is of great interest once it is well known that this portion of the spectra is negligibly absorbed by the Xanthophylls, pigment strongly present at the macula. The macula is the portion of the retina responsible for the central vision and because of this laser absorption would be disastrous for the patients eye.

Este trabalho tem por objetivo o desenvolvimento e otimização de uma cavidade laser self-Raman de aplicações oftalmológicas. A cavidade laser é do tipo estado sólido bombeada longitudinalmente por um diodo laser infravermelho. A cavidade é dita self-Raman pois um cristal Raman intracavidade faz o papel de meio ativo e deslocador Raman. Esse tipo de configuração é extremamente vantajoso uma vez que promove uma redução dimensional, de custos e de perdas intracavidade. Outro elemento não linear intracavidade é responsável pela geração do segundo harmônico da primeira linha Stokes gerada pelo cristal Raman. Dessa maneira obtém-se radiação em 586.5 nm da cavidade laser, o que corresponde a porção amarela do espectro eletromagnético. Essa região amarelo-alaranjada do espectro é de muita importância e aplicabilidade na indústria, ciências e na medicina. Na oftalmologia, em particular, é de enorme interesse que se construa um laser amarelo para fotocoagulação da retina uma vez que há muito tempo sabe-se que essa porção do espectro possui uma absorção desprezível pela Xantofila, cromóforo abundantemente presente na mácula. A mácula é a porção da retina responsável pela visão central e não deve absorver radiação laser pois isso seria desastroso para o paciente. / The objective of this work is the development and optimization of a self-Raman laser cavity with ophthalmological applications. The laser cavity is a longitudinally diode pumped solid state laser. The laser cavity is so-called self-Raman because an intracavity Raman crystal plays a role as an active media and Raman shifter. This type of configuration is extremely advantageous because it promotes a reduction in costs, dimensions and intracavity losses. Another non linear intracavity element is responsible for the second harmonic generation of the first Stokes line generated by the Raman crystal. Thereby one obtains 586.5 nm radiation coming out of the laser cavity, a wavelength in the yellow portion of the electromagnetic spectra. This yellow-orange range of the spectra is of great importance because and has many and increasingly applications in science, industry and medicine. Particularly in ophthalmology, a yellow laser for retina photocoagulation is of great interest once it is well known that this portion of the spectra is negligibly absorbed by the Xanthophylls, pigment strongly present at the macula. The macula is the portion of the retina responsible for the central vision and because of this laser absorption would be disastrous for the patients eye.