Although the major functions of the lymphatic system are fairly well defined, its vasculature has yet to be well characterized in comparison to its blood vasculature counterpart. Recent advances in optical imaging techniques have allowed for more detailed and quantitative evaluations of lymph flow dynamics and mechanism. A rat tail is often used for investigations of lymph flow because of the simple geometry, superficial nature, and disease progression models of its collecting lymphatic vessels. In this study, a pressure cuff system was fabricated and coupled with an existing functional near infrared (NIR) imaging system to measure the overall pumping pressure of the lymphatic vessels of a rat tail. In addition to adapting the system for use on rodents, previous systems used for measuring lymphatic pumping pressure in humans were improved upon in several ways. The system defined here utilizes closed-loop feedback control of pressure application at smaller, more precise intervals. Using this device, a significant difference in lymphatic vessel pumping pressure was detected between a control case and a treatment case in which a vasoactive substance with a nitric oxide donor (GTNO ointment) was applied to the tail. Although it is known that nitric oxide plays a crucial physiologic role in propagation of flow through lymphatic vessels, this study has quantified its significant pharmacological reduction of pumping pressure for the first time.

This thesis describes the development of a combined label-free imaging and analytical strategy for intraoperative characterization of cancer lesions using the coherent anti-Stokes Raman scattering imaging (CARS) technique. A cell morphology-based analytical platform is developed to characterize CARS images and, hence, provide diagnostic information using disease-related pathology features. This strategy is validated for three different applications, including margin detection for radical prostatectomy, differential diagnosis of lung cancer, as well as detection and differentiation of breast cancer subtypes for in situ analysis of margin status during lumpectomy. As the major contribution of this thesis, the developed analytical strategy shows high accuracy and specificity for all three diseases and thus has introduced the CARS imaging technique into the field of human cancer diagnosis, which holds substantial potential for clinical translations. In addition, I have contributed a project aimed at miniaturizing the CARS imaging device into a microendoscope setup through a fiber-delivery strategy. A four-wave-mixing (FWM) background signal, which is caused by simultaneous delivery of the two CARS-generating excitation laser beams, is initially identified. A polarization-based strategy is then introduced and tested for suppression of this FWM noise. The approach shows effective suppression of the FWM signal, both on microscopic and prototype endoscopic setups, indicating the potential of developing a novel microendoscope with a compatible size for clinical use. These positive results show promise for the development of an all-fiber-based, label-free imaging and analytical platform for minimally invasive detection and diagnosis of cancers during surgery or surgical-biopsy, thus improving surgical outcomes and reducing patients' suffering.

Cancer is a world menace. After years of endeavor seeking the end of it, people started to realize that no matter how powerful the therapy could be, detection at early stage is always a cheaper, easier and more successful solution compared with curative methods for cancer developed onto its advanced stage. However, relatively few early-detection approaches have proven sufficiently effective and practical for mass use as a point-of-care tool. An early-cancer screening tool integrating the desired features of sensitive, informative, portable, and cost-effective is in need for the doctors. The progress in optical imaging and Micro-electro-mechanical system (MEMS) technology offers a promise for an innovative cancer screening alternative that is non-invasive, radiation-free, portable and potentially cost-effective. This dissertation investigates handheld instrumentation as multi-modalities of miniature imaging probes with various designs of MEMS devices, to obtain real-time images of epithelial tissue optical and physiological properties, combining the quantitative advantages of spectral analysis with the qualitative benefits of imaging to distinguish early cancer. This dissertation in sequence presents the handheld instruments in the fashions of Laser-scanning confocal microscopy (LSCM), optical diffuse reflectance imaging, nonlinear optical imaging modalities with their subsequent image-guided managements in oral cancer, skin cancer detection, circulating tumor cell (CTC) imaging, and imaging guided surgeries. One of the main challenges facing miniaturization lies in the mechanism of beam deflection across the sample. This dissertation introduces two generations of MEMS devices desgined, fabricated and incorporated in the imaging probes. A two-axis vertical comb driven silicon micromirror was used in the development of a handheld LSCM for oral cancer detection. Though obtaining numerous advantages, this first generation silicon MEMS micromirror suffers from small aperture size and high voltage requirement for actuation, which result in low collection efficiency in fluorescence imaging and medial safety concerns, respectively. Therefore a stainless steel scanner compatible with electrical discharge machining (EDM) process was fabricated with simplified process, low-voltage magnetic actuation and large fluorescence collection efficiency, with its capability demonstrated in the incorporation and embodiment of a handheld hyperspectral nonlinear imaging probe. Besides, software and controlling innovations for handheld imaging modalities are presented. A feedback controlling system for MEMS scanning status monitoring was developed for stabilized imaging rendering. For the sake of further improved imaging stability in handheld imaging and to enable on-site mosaic for large field viewing, a handheld mosaic system was developed and presented. / text

L’étude du cerveau humain est un domaine en plein essor et les techniques non-invasives de l’étudier sont très prometteuses. Afin de l’étudier de manière non-invasive, notre laboratoire utilise principalement l’imagerie par résonance magnétique fonctionnelle (IRMf) et l’imagerie optique diffuse (IOD) continue pour mesurer et localiser l’activité cérébrale induite par une tâche visuelle, cognitive ou motrice. Le signal de ces deux techniques repose, entre autres, sur les concentrations d’hémoglobine cérébrale à cause du couplage qui existe entre l’activité neuronale et le flux sanguin local dans le cerveau. Pour être en mesure de comparer les deux signaux (et éventuellement calibrer le signal d’IRMf par l’IOD), où chaque signal est relatif à son propre niveau de base physiologique inconnu, une nouvelle technique ayant la capacité de mesurer le niveau de base physiologique est nécessaire. Cette nouvelle technique est l’IOD résolue temporellement qui permet d’estimer les concentrations d’hémoglobine cérébrale. Ce nouveau système permet donc de quantifier le niveau de base physiologique en termes de concentrations d’hémoglobine cérébrale absolue. L’objectif général de ma maîtrise était de développer un tel système afin de l’utiliser dans une large étude portant sur la condition cardiovasculaire, le vieillissement, la neuroimagerie ainsi que les performances cognitives. Il a fallu tout d’abord construire le système, le caractériser puis valider les résultats avant de pouvoir l’utiliser sur les sujets de recherche. La validation s’est premièrement réalisée sur des fantômes homogènes ainsi qu’hétérogènes (deux couches) qui ont été développés. La validation des concentrations d’hémoglobine cérébrale a été réalisée via une tâche cognitive et appuyée par les tests sanguins des sujets de recherche. Finalement, on présente les résultats obtenus dans une large étude employant le système d’IOD résolue temporellement en se concentrant sur les différences reliées au vieillissement. / Our understanding of the functional organization of the human brain has been greatly influenced by the development of new medical imaging techniques. Pr. Hoge’s research has focused on the use of functional magnetic resonance imaging (fMRI) and continuous diffuse optical imaging (DOI) for non-invasive localization and quantification of brain activity associated with behavioral stimuli or tasks (e.g. cognitive, motor or visual). The respective signals of both techniques are based on cerebral haemoglobin concentrations because of the coupling that exists between neuronal activity and cerebral blood flow. Relating BOLD fMRI signals with those acquired using DOI has been complicated by the fact that fMRI yields fractional change values, while the majority of DOI methods have provided absolute changes from an unknown baseline. To address this, we adopted a newer technique known as time-resolved DOI, which allows absolute quantification of cerebral haemoglobin concentrations. Time-resolved DOI thus has the capacity to quantify the subject’s resting hemoglobin concentrations in absolute micromolar units. The main objective of my masters’ project was to implement and optimize a time-resolved DOI system for use in a large study exploring the links between cardiovascular fitness, aging, neuroimaging markers, and cognitive performance. In this thesis we describe the fabrication of the system, followed by its characterisation and validation using solid optical phantoms (homogeneous and heterogeneous) developed for this purpose. Haemoglobin concentrations obtained non-invasively with the system are validated against blood draws, while the sensitivity to variations in concentration are assessed during a cognitive task. Finally, we present the results of a large study in which the time-resolved DOI system was used to characterize age-related vascular changes in the brain.

No description available.

Electrical stimulation of the retina affected by photoreceptor loss (e.g., cases of retinitis pigmentosa) elicits the perception of luminous spots (so-called phosphenes) in the visual field. This phenomenon, attributed to the relatively high survival rates of neurons comprising the retina's inner layer, serves as the cornerstone of efforts to provide a microelectronic retinal prosthesis -- a device analogous to the cochlear implant. This thesis concerns phosphenes -- their elicitation and modulation, and, in turn, image analysis for use in a prosthesis. This thesis begins with a comparative review of visual modelling of electrical epiretinal stimulation and analogous acoustic modelling of electrical cochlear stimulation. The latter models involve coloured noise played to normal listeners so as to investigate speech processing and electrode design for use in cochlear implants. Subsequently, four experiments (three psychophysical and one numerical), and two statistical analyses, are presented. Intrinsic signal optical imaging in cerebral cortex is canvassed appendically. The first experiment describes a visual tracking task administered to 20 normal observers afforded simulated prosthetic vision. Fixation, saccade, and smooth pursuit, and the effect of practice, were assessed. Further, an image analysis scheme is demonstrated that, compared to existing approaches, assisted fixation and pursuit (but not saccade) accuracy (35.8% and 6.8%, respectively), and required less phosphene array scanning. Subsequently, (numerical) information-theoretic reasoning is provided for the scheme's superiority. This reasoning was then employed to further optimise the scheme (resulting in a filter comprising overlapping Gaussian kernels), and may be readily extended to arbitrary arrangements of many phosphenes. A face recognition study, wherein stimuli comprised either size- or intensity-modulated phosphenes, is then presented. The study involved unpracticed observers (n=85), and showed no 'size' --versus--'intensity' effect. Overall, a 400-phosphene (100-phosphene) image afforded subjects 89.0% (64.0%) correct recognition (two-interval forced-choice paradigm) when five seconds' scanning was allowed. Performance fell (64.5%) when the 400-phosphene image was stabilised on the retina and presented briefly. Scanning was similar in 400- and 100-phosphene tasks. The final chapter presents the statistical effects of sampling and rendering jitter on the phosphene image. These results may generalise to low-resolution imaging systems involving loosely packed pixels.

Made available in DSpace on 2016-06-02T20:15:28Z (GMT). No. of bitstreams: 1 5177.pdf: 16843754 bytes, checksum: 0b2e8c0ee3f79df315d62b9151b7e100 (MD5) Previous issue date: 2013-04-12 / Universidade Federal de Minas Gerais / Avalanches are sudden dramatic phenomena that occur in nature. The technique of magneto-optical imaging (MOI) has allowed us to observe abrupt flux entrances in superconductors, the so-called ux avalanches, due to thermomagnetic instabilities in the vortex matter. Their morphology is fascinating, especially in superconducting thin films, where they develop in dendritic patterns. From a practical point of view, the flux avalanches undermine applications of superconducting thin films. In the last years, however, several steps have been reached to fully understand the fundamental physics of the phenomenon and also on how to suppress their occurrence. The present thesis deals with the study of flux avalanches in structured superconducting thin films. We have studied crystalline Nb and amorphous Mo79Ge21 thin films decorated with arrays of antidots (ADs or holes) produced by electron beam lithography. The magnetic response of these specimens has been investigated by means of MOI, dc magnetization and ac susceptibility. Firstly, we have established a link among those three techniques in the regime dominated by flux avalanches. We have observed that the reentrant behavior in the ac susceptibility at low temperatures occurs as a consequence of flux avalanches. Essentially, there is reuse of the channels created by the first ac cycle in a regime where the signal is weakly dependent on the temperature. Our results show that measurements of ac susceptibility versus ac field amplitude can be used to detect flux avalanches, since the signature of the flux avalanches appears as noisy curves of both ac susceptibility components. As a consequence, the critical current density as a function of temperature [Jc.T ] obtained by using the Bean model whose validity is assured by Cole-Cole plots is smooth for higher temperatures and, below a certain temperature onset, a non-smooth and noisy behavior takes place due to the avalanches. The temperature dependence of Jc.T,H was determined for different values of the applied magnetic field. The stability/instability frontier was then identified as the limiting temperature below which the curve Jc.T,H becomes noisy, indicating the occurrence of avalanches. Associated with this limiting temperature, the threshold critical current density to trigger avalanches is essentially independent of the magnetic field. This frontier corresponds to the upper threshold limit for the occurrence of avalanches. The effect in a thin film of a graded distribution of ADs which follows nearly the flux profile described by the Bean model has been studied. Compared to the uniform distribution, there is an increase of the critical current density at low fields. Moreover, viii the flux avalanches, highly induced by the presence of an array of ADs, have their activity reduced in temperature and magnetic field. For the first time, flux avalanches have been visualized in amorphous Mo79Ge21 thin film, both in plain and decorated thin films. Finally, we have investigated the influence of the lattice symmetry and AD geometry on the flux avalanche morphology. We have observed avalanches with the habit of forming trees where the trunk is parallel to the main axis of the square lattice and the branches form angles of 45 degrees. In addition to that, we have found an anisotropic penetration in a Nb thin film decorated with a square lattice of triangular ADs. Besides that, a sample having one half of the ADs in the form of squares, and the other half being circles, has been observed to present avalanches of different morphologies on each of its halves. We have also studied an a-MoGe thin film with a centered rectangular 2D Bravais lattice with square ADs which shows penetrations with different angles depending on the edge. The overall features of the avalanches, and in particular the 45-degree direction of the branches, have been confirmed by numerical simulations using the thermomagnetic model. Superconductivity, structured thin films, flux avalanches, magneto-optical imaging. / Avalanches são eventos repentinos e dramáticos que ocorrem na natureza. A técnica de imageamento por magneto-ótica (MOI) tem permitido visualizar a penetração abrupta de fluxo em supercondutores, as chamadas avalanches de fluxo, que ocorrem devido a instabilidades termomagnéticas na matéria de vórtices. A morfologia dessas avalanches de fluxo em filmes finos supercondutores prístinos é singular e se desenvolve de maneira dendrítica, isto é, com ramificações. Do ponto de vista prático, as avalanches de fluxo são prejudiciais para aplicações dos filmes finos supercondutores. Nos últimos anos, no entanto, tem-se alcançado um bom entendimento da física básica do fenômeno, bem como maneiras para suprimir essas avalanches. Esta tese trata do estudo de avalanches de fluxo em filmes finos com uma estrutura de defeitos. Para tal, usamos filmes finos cristalinos de Nb e amorfos da liga Mo79Ge21 decorados com arranjos de antidots (ADs), ou buracos, produzidos por litografia por feixe de elétrons. A resposta magnética desses filmes foi investigada através de MOI, magnetização dc e suscetibilidade ac. Na primeira parte dos resultados, uma conexão entre essas técnicas foi estabelecida no regime de avalanches de fluxo. Foi observado que o comportamento reentrante da suscetibilidade ac em baixas temperaturas ocorre devido `as avalanches de fluxo. Essencialmente, há o reuso dos caminhos ou canais criados pelo primeiro ciclo ac em um regime em que o sinal é fracamente dependente da temperatura. Esses resultados também mostraram que a suscetibilidade ac pode ser usada para detectar avalanches de fluxo, seja pela construção da curva de corrente critica dependente da temperatura Jc.T ou monitorando o ruído nas curvas do tipo Cole-Cole. Assim, a fronteira de instabilidades termomagnéticas/estabilidade foi construída variando-se o campo dc aplicado, tendo sido obtido, um limiar constante de Jc.T para o disparo das avalanches. Essa observação está de acordo com o modelo termomagnético e refere-se ao limite superior da ocorrência das avalanches de fluxo. Também foi estudado o efeito da inserção de um arranjo de antidots distribuídos de maneira gradiente, que segue aproximadamente a distribuição de fluxo descrita pelo Modelo de Bean. Comparada com uma distribuição uniforme, um aumento da densidade de corrente crítica foi observada para a região de baixos campos. Além disso, as avalanches de fluxo, que são altamente induzidas pela presença de ADs, apresentaram uma redução em sua ocorrência, tanto em magnitude do campo magnético aplicado quanto em temperatura. Pela primeira vez, foram observadas avalanches de fluxo em filmes finos amorfos de Mo79Ge21 com e sem uma rede de ADs. x Por fim, a influência da simetria da rede e da geometria do antidot na morfologia das avalanches de fluxo foi investigada. Para filmes finos decorados com uma rede quadrada de ADs quadrados, as avalanches têm o tronco paralelo ao eixo principal da rede de ADs, com ramificações em ângulos de 45 graus como em uma árvore de Natal. Além disso, penetrações abruptas anisotrópicas foram vistas em um filme fino de Nb decorado com uma rede quadrada de ADs triangulares. Uma mudança na morfologia das avalanches também foi observada em um filme com metade dos ADs quadrados e a outra metade circular. Também foram observadas penetrações com diferentes ângulos em uma rede retangular centrada de ADs quadrados dependendo da borda. Por fim, as características gerais das avalanches, em particular a de ramificações em 45 graus, foram confirmadas por simulações numéricas usando o modelo termomagnético.

Les nanoparticules (NPs) à luminescence persistante de gallate de zinc dopée chrome (ZnGa1.995Cr0.005 O4) sont des matériaux innovants avec des propriétés optiques particulières qui permettent leur utilisation pour l'imagerie optique in vivo. Leur caractérisation a été effectuée par une méthode émergente dans ce domaine, l'électrophorèse capillaire. Les résultats ont démontré le potentiel de cette méthode pour garantir le contrôle et la qualité des NPs. Un ensemble général des tests de toxicité a été réalisé in vitro et in vivo après administration aiguë, à court et à long terme des ZnGa1.995Cr0.005O4, afin d'évaluer leur biocompatibilité. Lors de l'administration de NPs hydroxylés, différentes conséquences négatives ont été notées, ainsi comme l'effet protecteur du polyéthylène glycol fonctionnalisé en surface des NPs. En raison de l'importance des interactions des NPs avec les protéines plasmatiques lors de leur administration, nous avons évalué et appliqué pour la première fois la méthode électrocinétique de Hummel-Dreyer pour la détermination des interactions non spécifiques entre les NPs PEGylés et des protéines. Finalement, l'évaluation des interactions entre les ZnGa1.995Cr0.005O4 et un système binaire de protéines (albumine et Apolipoprotéine-E) a été effectuée par des méthodes électrocinétiques. Ces analyses ont montré une affinité plus forte entre la surface des NPs PEGylés et l'apolipoprotéine-E par rapport à l'albumine, ce qui pourrait représenter une stratégie novatrice pour la vectorisation des NPs vers la région du cerveau. Toutes les méthodes mentionnées ci-dessus peuvent être extrapolées pour l'analyse des autres NPs avec plusieurs des applications. / The chromium doped zinc gallate (ZnGa1.995Cr0.005O4) nanoparticles (NPs) are innovative materials with specific optical properties, notably the persistent luminescence, which allow their use for in vivo optical imaging. Their characterization was carried out by an emergent method in this area, the capillary electrophoresis. The obtained results demonstrated the potential of this method to ensure the control and quality of NPs. A general set of toxicity tests were performed in vitro and in vivo after acute, short- and long-term administration of the NPs to assess their biocompatibility. Various negative effects were noted upon administration of hydroxylated NPs, as well as the protective effect of NP PEGylation. Because of the importance of NP interactions with plasma proteins after their in vivo administration, we evaluated and applied for the first time the Hummel-Dreyer electrokinetic method for the determination of non-specific interactions between PEGylated NPs and proteins. Finally, the evaluation of the interactions between the ZnGa1.995Cr0.005O4 and a binary system of proteins (albumin and apolipoprotein-E) was carried out by electrokinetic methods. The results revealed greater affinity between the surface of the PEGylated NPs and the apolipoprotein-E compared to albumin, which could represent a novel strategy for the vectorization of NPs towards the brain region. All the above mentioned methods can be extrapolated for the analysis of other NPs with several potential applications.

Le domaine du proche infrarouge a une importance majeure pour l'imagerie optique en raison de la faible autofluorescence des systèmes biologiques et de la diffusion limitée de la lumière permettant l’amélioration du rapport signal-sur-bruit et une pénétration plus profonde dans les tissus. Les sondes fluorescentes proche-infrarouges les plus couramment utilisées à ce jour sont les fluorophores organiques ou les nanocristaux semi-conducteurs qui sont affectés par un certain nombre d’inconvénients. Plusieurs cations lanthanide possèdent des propriétés optiques uniques comme des bandes d'émissions étroites dont les longueurs d'ondes sont très peu sensibles à l’environnement, de grandes différences d’énergie entre longueurs d’onde d’excitation et d'émission et une forte résistance au photoblanchiment. Afin de bénéficier de la luminescence des lanthanides, les faibles absorbances des cations lanthanides libres doivent être compensées par l'utilisation de groupes chromophores appropriés fonctionnant comme sensibilisateurs. On parle d’effet d’"antenne". Nous présentons dans ce travail plusieurs familles de sondes à base de lanthanides (i) de petites molécules, plus spécifiquement des complexes monométalliques constitués par la coordination de Ln³⁺ par un ligand de type TTHA-anthraquinone et des métallacrowns polymétalliques Ln³⁺/Zn²⁺ auto-assemblés; (ii) de nouveaux nanomatériaux basés sur des billes de polystyrène possédant deux types de chargements différents, à savoir (i) un complexe bimétallique d-f Cr³⁺-Ln³⁺ ainsi que (ii) des antennes dérivées d’hydroxyanthraquinone et des cations lanthanide libres; (iii) des macromolécules de type dendrimère polyamidoamine de génération 3 fonctionnalisés avec sensibilisateurs aza-BODIPY en leurs périphéries et qui encapsulent des lanthanide luminescents. Les propriétés photophysiques, la cytotoxicité et l'incorporation cellulaire ont été décrites et discutées pour chacun des types de sondes. En outre, ces sondes ont été testées en imagerie in vitro visible et/ou proche-infrarouge par des expériences de microscopie confocale et d’épifluorescence. L’ensemble des sondes décrites dans ce travail, en raison de leurs propriétés avantageuses et nouvelles, constituent des avancées majeures pour le développement de nouvelles générations d'agents d'imagerie optique. / The near-infrared (NIR) region has a significant importance for optical imaging due to the minimal autofluorescence and reduced light scattering thus allowing for improved signal-to-noise ratio and deeper penetration through tissues. Nowadays, the most commonly used NIR-emitting fluorescent probes rely mainly on organic fluorophores or quantum dots and exhibit drawbacks. Several lanthanide(III) ions (Ln³⁺) possess unique optical properties e.g. sharp emission bands the wavelengths of which have minimal sensitivity to the microenvironment, large differences between excitation and emission wavelengths and strong resistance toward photobleaching. In order to obtain the luminescence of lanthanides, the low absorbances of the free Ln³⁺ have to be overcome by the use of appropriate chromophoric groups functioning as a sensitizing “antenna”. We present here several families of Ln³⁺-based probes: (i) small molecules, in particular monometallic complexes constituted by the TTHA-anthraquinone moiety and Ln³⁺, and polymetallic self-assembled Ln³⁺/Zn²⁺ metallacrowns; (ii) novel nanomaterials based on polystyrene beads with two different loadings, i.e. d-f bimetallic Cr³⁺- Ln³⁺+ complex and hydroxyanthraquinone antennae and Ln³⁺ ; (iii) macromolecular generation-3 polyamidoamine dendrimers functionalized with aza-BODIPY sensitizers at their periphery and encapsulating the luminescent Ln³⁺. The photophysical properties, cytotoxicity and cellular uptake were reported and discussed for each of the presented types of Ln³⁺-based probes. Moreover, these probes were successfully tested for visible and/or NIR in vitro imaging by confocal or epifluorescence microscopy experiments. Finally, the reported Ln³⁺-based probes, due to the number of advantageous properties, represent significant breakthroughs toward the developments of new generations of optical imaging agents.

Near Infrared (NIR) and Photoacoustic (PA) Imaging are promising imaging modalities that provides functional information of the soft biological tissues in-vivo, with applica-tions in breast and brain tissue imaging. These techniques use near infrared light in the wavelength range of (600 nm - 900 nm), giving an advantage of being non-ionizing imaging modality. This makes the prolong bed-side monitoring of tissue feasible, making them highly desirable medical imaging modalities in the clinic. The computation models that are deployed in these imaging scenarios are computationally demanding and often require a high performance computing systems to deploy them in real-time. This the-sis presents three computationally e cient models for near-infrared and photoacoustic imaging, without compromising the quality of measured functional properties, to make them more appealing in clinical scenarios. The attenuation of near-infrared (NIR) light intensity as it propagates in a turbid medium like biological tissue is described by modi ed the BeerLambert law (MBLL). The MBLL is generally used to quantify the changes in tissue chromophore concen-trations for NIR spectroscopic data analysis. Even though MBLL is e ective in terms of providing qualitative comparison, it su ers from its applicability across tissue types and tissue dimensions. A Lambert-W function-based modeling for light propagation in biological tissues is proposed and introduced, which is a generalized version of the Beer-Lambert model. The proposed modeling provides parametrization of tissue properties, which includes two attenuation coe cients o and . The model is validated against the Monte Carlo simulation, which is the gold standard for modeling NIR light propagation in biological tissue. Numerous human and animal tissues are included to validate the proposed empirical model, including an inhomogeneous adult human head model. The proposed model, which has a closed form (analytical), is rst of its kind in providing accurate modeling of NIR light propagation in biological tissues. Model based image reconstruction techniques yield better quantitative accuracy in photoacoustic (PA) image reconstruction, especially in limited data cases. An exponen-tial ltering of singular values is proposed for carrying out the image reconstruction in photoacoustic tomography. The results were compared with widely popular Tikhonov regularization, time reversal, and the state of the art least-squares QR based reconstruc-tion algorithms for three digital phantom cases with varying signal-to-noise ratios of data. The exponential ltering provided superior photoacoustic images of better quanti-tative accuracy. Moreover, the proposed ltering approach was observed to be less biased towards regularization parameter and did not come with any additional computational burden as it was implemented within the Tikhonov ltering framework. It was also shown that the standard Tikhonov ltering becomes an approximation to the proposed exponential ltering. The model based image reconstruction techniques for photoacoustic tomography re-quire an explicit regularization. An error estimate minimization based approach was proposed and developed for the determination of regularization parameter for PA imag-ing. The regularization was used within Lanczos bidiagonalization framework, which provides the advantage of dimensionality reduction for a large system of equations. The proposed method was computationally faster than the state of the art techniques and provided similar performance in terms of quantitative accuracy in reconstructed im-ages.The estimate can also be utilized in determining suitable regularization parameter for other popular techniques such as Tikhonov,exponential ltering and `1 norm based regularization methods.