The increasing use of visible and near infrared light in therapeutic and diagnostic techniques has created a need to model its propagation in tissue. One of the fundamental objectives of such a model is the noninvasive evaluation of the optical properties of tissue. The focus of this thesis was the development of the diffusion approximation in the semi-infinite, slab, cylindrical and spherical geometries. This development required the derivation of approximate boundary conditions which included the zero, extrapolated and partial current boundary conditions. Calculations of the fluence and its related quantities arising from the extrapolated boundary condition were found to be in excellent agreement with the results of the more rigorous partial current boundary condition. A preliminary evaluation of the validity of diffusion theory was performed by comparing its predictions to exact analytical calculations of the fluence in an infinite medium as well as Monte Carlo simulations of the reflectance and transmittance in 1-dimensional planar geometries. In all cases the agreement at late times was excellent. A practical test of the diffusion model was accomplished with the analysis of the reflectance data from a phantom of known optical properties in both the semi-infinite and slab geometries. The model performed well at low concentrations of added absorber, but a considerable discrepancy was found at the highest concentration. A systematic examination of the accuracy of the diffusion model as a function of the fundamental parameters is required to resolve this inconsistency. Approximate expressions describing the equivalent information in the frequency domain were also developed for a semi-infinite medium. These expressions were then used to analyze the phase and modulation obtained from phantoms of known optical properties. Once again reasonable results were obtained at low concentrations of added absorber while a significant discrepancy arose at the highest concentration. The resolution of these discrepancies requires further investigation. / Thesis / Master of Engineering (ME)

A holographic recording method using an optical heterodyne 2-D scanning technique for 3-D imaging of fluorescent objects in turbid media is described and experimentally demonstrated. For the first time, 3-D imaging of fluorescentobjects in turbid media by a holographic method is achieved, and the diffused photon rejecting process through a heterodyne technique is analyzed. We also propose and realize a multiplexing and a digital decoding method for removing twin-image noise in optical scanning holography. The holographic method studied can be applied to 3-D biomedical imaging of fluorescent objects in turbid media as well as diffusely reflecting objects. / Master of Science

Avhandlingen behandlar de teoretiska och praktiska aspekterna av att använda spektrala vinkelupplösta reflektansmätningar för optisk karakterisering av fiberbaserade material såsom papper och kartong. En spektral goniofotometer används för att mäta det reflekterade ljusets vinkelfördelning. En stor del av arbetet utgörs av att utvärdera instrumentets noggrannhet, samt utreda hur de vinkelupplösta mätningarna skall utföras på bästa sätt för att erhålla en så fullständig karakterisering som möjligt. Det reflekterade ljuset består av tre komponenter; ytreflektans, bulkreflektans samt fluorescens. En fullständig karakterisering förutsätter att dessa tre komponenter kan analyseras separat, vilket i detta arbete görs genom nyutvecklade metoder. En metod har utvecklats för separation av ytreflektans och bulkreflektans. Metoden bygger på att analysera hur den totala reflektansen förändras vid ökande absorption i det reflekterande materialet. Absorptionen kontrolleras genom inkjet-tryckning där tryckfärg appliceras på substratet i sådan mängd att bulkreflektansen helt släcks ut. Genom att kombinera mätningar på tryckt och otryckt substrat kan de båda komponenterna separeras. Trots att ytreflektansen från ett matt papper är liten i förhållande till bulkreflektansen, så visar resultaten att den ökar markant med ökande betraktningsvinkel och kan därmed ha stor inverkan på den totala reflektansen. Bidraget från fluorescens kan kvantitativt analyseras genom att kombinera mätningar utförda med respektive utan UV-filter. Vinkelupplösta mätningar och Monte Carlo-simuleringar av fluorescensens vinkelfördelning visar att dess anisotropi är relaterad till det medeldjup vid vilket fluorescensen emitteras. Resultaten förklarar observerade skillnader och motstridigheter i tidigare rapporterade studier kring huruvida fluorescens kan anses vara Lamberskt fördelad. Samtliga goniofotometriska mätningar är utförda med ett kompakt, kommersiellt tillgängligt, dubbelstråleinstrument. För att undersöka instrumentets lämplighet för absoluta reflektansmätningar utförs en analys av dess mätnoggrannhet. Resultaten visar att instrumentets kompakta storlek i kombination med den anisotropa reflektansen från papper introducerar systematiska fel av samma storleksordning som den totala mätnoggrannheten. Dessa fel uppstår på grund av den relativt stora detektorapertur som måste användas vid mätningar av diffus reflektans, vilket är karakteristiskt för papper och kartong. Resultaten visar även att felen är störst vid flacka mätvinklar och för prover med hög grad av anisotropisk reflektans, och en geometrisk korrektionsmetod för denna typ av systematiska fel föreslås. Spektrala och vinkelupplösta mätningar medför per automatik stora mängder mätdata. Genom att använda strålningstransportteori som en matematisk modell för hur ljus sprids i papper kan mätdatat reduceras till en uppsättning beskrivande materialparameterar. Att uppskatta dessa optiska parametrar utifrån vinkelupplösta reflektansmätningar är i sig ett komplicerat problem, vilket dessutom är känsligt för mätfel och val av mätvinklar. Detta inversa problem analyseras i detalj, och speciellt hur valet av mätvinklar kan reduceras utan att försämra förutsättningarna för estimeringen. Simuleringar visar att mätningarna kan begränsas till infallsplanet, eller till och med enbart framåtriktningen, så länge tillräckligt flacka mätvinklar är inkluderade i mätsekvensen. / This thesis is about measuring and modelling light reflected from paper by using goniophotometric measurements. Measuring bidirectional reflectance requires highly accurate instruments, and a large part of the work in this thesis is about establishing the requirements that must be fulfilled to ensure valid data. A spectral goniophotometer is used for measuring the light reflected from paper and methods are developed for analyzing the different components, i.e. the fluorescence, surface reflectance and bulk reflectance, separately. A separation of the surface and bulk reflectance is obtained by inkjet printing and analyzing the total reflectance in the absorption band of the ink. The main principle of the method is to add dye to the paper until the bulk scattered light is completely absorbed. The remaining reflectance is solely surface reflectance, which is subtracted from the total reflectance of the undyed sample to give the bulk reflectance. The results show that although the surface reflectance of a matte paper is small in comparison with the bulk reflectance, it grows rapidly with increasing viewing angle, and can have a large influence on the overall reflectance. A method for quantitative fluorescence measurements is developed, and used for analyzing the angular distribution of the fluoresced light. The long-standing issue whether fluorescence from turbid (or amorphous) media is Lambertian or not, is resolved by using both angle-resolved luminescence measurements and radiative transfer based Monte Carlo simulations. It is concluded that the degree of anisotropy of the fluoresced light is related to the average depth of emission, which in turn depends on factors such as concentration of fluorophores, angle of incident light and the absorption coefficient at the excitation wavelength. All measurements are conducted with a commercially available benchtop sized double-beam spectral goniophotometer designed for laboratory use. To obtain reliable results, its absolute measurement capability is evaluated in terms of measurement accuracy. The results show that the compact size of the instrument, combined with the anisotropic nature of reflectance from paper, can introduce significant systematic errors of the same order as the overall measurement uncertainty. The errors are related to the relatively large detection solid angle that is required when measuring diffusely reflecting materials. Situations where the errors are most severe, oblique viewing angles and samples with high degree of anisotropic scattering, are identified, and a geometrical correction is developed. Estimating optical properties of a material from bidirectional measurements has proved to be a challenging problem and the outcome is highly dependent on both the quality and quantity of the measurements. This problem is analyzed in detail for optically thick turbid media, and the study targets the case when a restricted set of detection angles are available. This is the case when e.g. an unobstructed view of the sample is not possible. Simulations show that the measurements can be restricted to the plane of incidence (in-plane), and even the forward direction only, without any significant reduction in the precision or stability of the estimation, as long as sufficiently oblique angles are included.

Lateral light scattering in fibrous media is investigated by computing the modulation transfer function (MTF) of 22 paper samples using a Monte Carlo model. The simulation tool uses phase functions from infinitely long homogenous cylinders and the directional inhomogeneity of paper is achieved by aligning the cylinders in the plane. The inverse frequency at half maximum of the MTF is compared to both measurements and previous simulations with isotropic and strongly forward single scattering phase functions. It is found that the conical scattering by cylinders enhances the lateral scattering and therefore predicts a larger extent of lateral light scattering than models using rotationally invariant single scattering phase functions. However, it does not fully reach the levels of lateral scattering observed in measurements. It is argued that the hollow lumen of a wood fiber or dependent scattering effects must be considered for a complete description of lateral light scattering in paper. / PaperOpt

Modeling of light propagation through turbid (highly-scattering) media such as living tissue is important for a number of medical applications including diagnostics and therapeutics. This thesis studies methods of performing such simulations quickly and accurately. It begins with a formal definition of the problem, a review of solution methods, and an overview of the current state of the art in fast simulation methods encompassing both traditional software and more specialized hardware acceleration approaches (GPU, custom logic). It introduces FullMonte, the fastest mesh-based Monte Carlo software model available and highlights its novel optimiza- tions. Additionally, it demonstrates the first fully three-dimensional hardware simulator using Field-Programmable Gate Array (FPGA) custom logic, offering large (40x) power-efficiency and performance (3x) gains. Next, a plan for significant future feature enhancements and performance scale-out is sketched out. Lastly, it proposes applying the simulators developed to a number of problems relevant to current clinical and research practice.

Modeling of light propagation through turbid (highly-scattering) media such as living tissue is important for a number of medical applications including diagnostics and therapeutics. This thesis studies methods of performing such simulations quickly and accurately. It begins with a formal definition of the problem, a review of solution methods, and an overview of the current state of the art in fast simulation methods encompassing both traditional software and more specialized hardware acceleration approaches (GPU, custom logic). It introduces FullMonte, the fastest mesh-based Monte Carlo software model available and highlights its novel optimiza- tions. Additionally, it demonstrates the first fully three-dimensional hardware simulator using Field-Programmable Gate Array (FPGA) custom logic, offering large (40x) power-efficiency and performance (3x) gains. Next, a plan for significant future feature enhancements and performance scale-out is sketched out. Lastly, it proposes applying the simulators developed to a number of problems relevant to current clinical and research practice.

<p>Diffuse reflectance spectroscopy (DRS) is a simple, yet powerful technique that has the potential to offer practical, non-invasive, and cost effective information for op- tical diagnostics and therapeutics guidance. Any progress towards moving DRS systems from their current laboratory settings to clinical settings, field settings and ambitiously to home settings, is a significant contribution to society in terms of reducing ever growing healthcare expenditures of an aging society. Additionally, im- proving on the existing mathematical models used to analyze DRS signals; in terms of speed, robustness, accuracy, and capability in accounting for larger feature space dimensionality (i.e. extraction of more tissue-relevant information) is equally im- portant for real-time diagnosis in the desired settings and to enable use of DRS in as many biomedical applications (e.g. skin cancer diagnosis, diabetics care, tissue oxygenation monitoring) as possible. Improving the reflectance signal complexity and density through novel DRS instrumentation, would facilitate development of the desired models or put the existing ones built on simulations in practical use; which otherwise could not go beyond being a theoretical demonstration.</p><p>DRS studies tissue morphology and composition through quantification of one or more (ideally all of them) of the tissue- and wavelength-specific optical properties: absorption coefficient (μa), reduced scattering coefficient (μ1s), scattering anisotropy (g), tissue thickness, and scattering phase function details (e.g. higher order moments of the scattering phase function). DRS involves sampling of diffusely reflected photons which experience multiple scattering and absorption as they travel within the tissue, at the tissue surface. Spatially resolved diffuse reflectance spectroscopy (SRDRS) is a subset of general DRS technique, which involves sampling of diffuse reflectance signals at multiple distances to an illumination source. SRDRS provides additional spatial information about the photon path; yielding depth-resolved tissue information critical to layered tissue analysis and early cancer diagnostics. Exist- ing SRDRS systems use fiber optic probes, which are limited in accommodation of large number and high-density collection fibers (i.e. yielding more and dense spa- tially resolved diffuse reflectance (SRDR) measurement data) due to difficulty of fiber multiplexing. The circular shape of the fibers restricts the implementable probe ge- ometries and reduces the fill factor for a given source to detector (i.e. collection fiber) separation (SDS); resulting in reduced light collection efficiency. The finite fiber nu- merical aperture (NA) reduces the light collection efficiency well as; and prevents selective interrogation of superficial tissues where most cancers emerge. Addition- ally, SRDR systems using fiber optic probes for photon collection, require one or more photodetectors (i.e. a cooled CCD); which are often expensive components of the systems.</p><p>This thesis deals with development of an innovative silicon SRDRS probe, which partially addresses the challenge of realizing high measurement density, miniaturized, and inexpensive SRDRS systems. The probe is fabricated by conventional, flexible and inexpensive silicon fabrication technology, which demonstrates the feasibility of developing SRDRS probes in any desired geometry and complexity. Although this approach is simple and straightforward, it has been overlooked by the DRS community due to availability of the conventional fiber optic probe technology. This new probe accommodates large number and high density of detectors; and it is in the form of a concentric semi-annular photodiode (PD) array (CMPA) with a central illumination aperture. This is the first multiple source-detector spacing Si SRDRS probe reported to date, and the most densely packed SRDRS probe reported to date for all types of SRDRS systems. The closely spaced and densely packed detectors enable higher density SRDR measurements compared to fiber-based SRDR probes, and the higher PD NA compared to that of fibers results in a higher SNR increasing light collection efficiency. The higher NA of the PDs and the presence of PDs positioned at very short distances from the illumination aperture center enable superficial tissue analysis as well as depth analysis.</p> / Dissertation

Dentre as diversas aplicações da luz em nosso dia-a-dia, as ligadas à área biomédica merecem destaque e são frequentemente objetos de pesquisa tanto para o desenvolvimento quanto para o aprimoramento de técnicas para o diagnóstico e terapias. Os tecidos biológicos são, em sua maioria, estruturas complexas, não-homogêneas e opticamente muito espalhadoras. Apesar das centenas de estudos existentes acerca da propagação da luz em tecidos biológicos, sua complexidade exige que novos estudos sejam conduzidos a fim de aprimorar o conhecimento já existente, que ainda apresenta muitas lacunas. A presença de heterogeneidades nos tecidos (vasos sanguíneos, hematomas, cistos, tumores e outras alterações macroscópicas) mudam a propagação da luz e dificultam a previsibilidade do seu comportamento por modelos matemáticos. O presente trabalho teve por objetivo estabelecer um método empírico que utiliza imagens de refletância difusa obtidas através de uma instrumentação simples, baseada em uma fonte de luz contínua no visível (laser de diodo em 660 nm) e uma câmera CMOS monocromática, para verificar a possibilidade de localização de inclusões absorvedoras embebidas em phantoms altamente espalhadores. Foi avaliada a capacidade de detectar inclusões de dois diferentes tipos de materiais em diversas geometrias e tamanhos, posicionadas em diferentes profundidades. O ângulo de incidência do feixe laser também foi variado, bem como a distância entre a fonte e o objeto, a fim de avaliar quais as melhores condições experimentais. Os resultados obtidos mostraram que os objetos puderam ser detectados, e suas formas puderam ser satisfatoriamente recuperadas através de um algoritmo desenvolvido para o processamento das imagens. Em algumas situações, mesmo para a maior profundidade utilizada, que foi de 20 mm, a inclusão pôde ser detectada nas imagens de refletância difusa processadas. Apesar da capacidade de detecção das formas geométricas representar um avanço com relação às possibilidades de identificação de estruturas em meios túrbidos, a determinação da profundidade ainda é um desafio a ser superado. / Among the various applications of light in our daily life, those connected with biomedicine should be highlighted and are frequently subject of researches aiming for the development and for the enhancement of techniques for diagnosis and therapy. Biological tissues are mostly complex, non-homogeneous and optically highly scattering structures. Despite the hundreds of existent studies on the propagation of light in biological tissues, its complexity requires new studies to be conducted in order to improve the existing knowledge, which still has many gaps. The presence of heterogeneities in tissue (blood vessels, bruises, cysts, tumors and other macroscopic alteration) changes the light propagation and impedes the predictability of its behavior by mathematical models. This work aimed to establish an empirical method using diffuse reflectance images acquired with simple instrumentation, based on a source of continuous light in the visible (diode laser at 660 nm) and a monochromatic CMOS camera, to check the possibility of the location of absorbing inclusions embedded in highly scattering phantoms. The ability to detect inclusions of two different kinds of materials in different sizes and geometries, positioned at different depths were evaluated. The laser beam angle of incidence was also varied, as well as the distance between the source and the object, in order to evaluate the best experimental conditions. The results showed that the objects could be detected, and their shapes might be satisfactorily recovered by an algorithm developed for image processing. In some situations, even at the greatest depth used, which was 20 mm, the inclusion could be detected in diffuse reflectance processed images. Although the detection capability of geometric shapes represents an improvement over the structures of identification possibilities in turbid media, the determination of depth is still a challenge to be overcome.

Virtual aperture culling of the eigenmodes of a resonator (VACER) is a technique to focus light within turbid media at arbitrary locations. A seed pulse of light is directed through a phase-conjugate mirror (PCM) into a turbid medium. Though much of the light may be lost, any light which reaches the second PCM is phase conjugated and thus returned to the first PCM where the light will be phase conjugated again. Amplification by the PCMs can prevent decay of the light cycling between the PCMs. Introducing a mechanism which filters light based on position enables attenuation of the modes not traveling through the center of the virtual aperture resulting in a focusing of light at the center of the virtual aperture. The seed pulse and the positioning of the PCMs on opposite sides of the virtual aperture ensure that modes cannot bypass the virtual aperture. Magnetic fields and ultrasound waves are potential means for implementation of a virtual aperture. Generally, only weak filtration mechanisms like magnetic fields and ultrasound waves are innocuous to turbid media. Fortunately, weak effects can strongly cull modes in VACER because the filtration mechanism affects the modes during each pass between PCMs and the modes compete. A combination of theory and computational modeling prove that sound physical principles underlie VACER. Moreover, computational modeling reveals how mode overlap, the seed pulse, and other variables impact VACER performance. Good experimental performance is predicted. / text

Nous présentons un nouveau type d'imageur plénoptique appelé LOFI (Laser Optical Feedback Imaging). Le grand avantage de cette technique est qu'elle est auto-alignée, car le laser sert à la fois de source et de détecteur de photons. De plus, grâce à un effet d'amplification intra-cavité produit par la dynamique du laser, et grâce à un marquage acoustique des photons réinjectés, ce dispositif possède une sensibilité ultime au photon unique. Cette sensibilité est nécessaire si l'on veut réaliser des images à travers des milieux diffusants. L'autre intérêt présenté par le caractère plénoptique de notre imageur, est qu'il permet d'obtenir simultanément une double information: la position et la direction de propagation des rayons lumineux. Cette propriété offre des possibilités inhabituelles, comme celle de conserver la résolution d'un objectif de microscope bien au-delà de sa distance de travail, ou encore de pouvoir corriger par un post-traitement numérique les aberrations causées par la traversée d'un milieu hétérogène. Le dispositif LOFI plénoptique semble donc idéal pour une imagerie en profondeur à travers des milieux complexes, tels que les milieux biologiques. Les performances très intéressantes de cette imageur sont cependant obtenues au prix d'un filtrage spatial très coûteux en photons et au prix d'une acquisition des images réalisées point par point, donc relativement lente. / We present LOFI (Laser Optical Feedback Imaging). The main advantage of this technique is that it is auto-aligned, as the laser plays both the role of an emitter and a receiver of photons. Furthermore, thanks to an intra-cavity amplification effect caused by the laser dynamics and an acoustic tagging of re-injected photons, this setup reaches a shot noise sensitivity (single photon sensitive). This sensitivity is necessary if our aim is to make images through scattering media. The other interest, which comes from the plenoptic property of our setup, is that one have access to a complete information about light rays (position and direction of propagation). This property implies unusual possibilities like keeping a constant resolution beyond microscope objectives working distance or being able to numerically compensate, after acquisition, aberrations caused by the propagation through heterogeneous media. Our setup is thus ideal for deep imaging through complex media (turbid and heterogeneous) like biological ones. These interesting properties are achieved at the price of a spatial filtering degrading photon collection efficiency and of a point by point image acquisition which is slow.