Optical coherence imaging, including tomography (OCT) and microscopy (OCM), has been a growing research field in biomedical optical imaging in the last decade. In this imaging modality, a broadband light source, thus of short temporal coherence length, is used to perform imaging via interferometry. A challenge in optical coherence imaging, as in any imaging system towards biomedical diagnosis, is the quantification of image quality and optimization of the system components, both a primary focus of this research. We concentrated our efforts on the optimization of the imaging system from two main standpoints: axial point spread function (PSF) and practical steps towards compact low-cost solutions. Up to recently, the criteria for the quality of a system was based on speed of imaging, sensitivity, and particularly axial resolution estimated solely from the full-width at half-maximum (FWHM) of the axial PSF with the common practice of assuming a Gaussian source power spectrum. As part of our work to quantify axial resolution we first brought forth two more metrics unlike FWHM, which accounted for side lobes in the axial PSF caused by irregularities in the shape of the source power spectrum, such as spectral dips. Subsequently, we presented a method where the axial PSF was significantly optimized by suppressing the side lobes occurring because of the irregular shape of the source power spectrum. The optimization was performed through optically shaping the source power spectrum via a programmable spectral shaper, which consequentially led to suppression of spurious structures in the images of a layered specimen. The superiority of the demonstrated approach was in performing reshaping before imaging, thus eliminating the need for post-data acquisition digital signal processing. Importantly, towards the optimization and objective image quality assessment in optical coherence imaging, the impact of source spectral shaping was further analyzed in a task-based assessment method based on statistical decision theory. Two classification tasks, a signal-detection task and a resolution task, were investigated. Results showed that reshaping the source power spectrum was a benefit essentially to the resolution task, as opposed to both the detection and resolution tasks, and the importance of the specimen local variations in index of refraction on the resolution task was demonstrated. Finally, towards the optimization of OCT and OCM for use in clinical settings, we analyzed the detection electronics stage, which is a crucial component of the system that is designed to capture extremely weak interferometric signals in biomedical and biological imaging applications. We designed and tested detection electronics to achieve a compact and low-cost solution for portable imaging units and demonstrated that the design provided an equivalent performance to the commercial lock-in amplifier considering the system sensitivity obtained with both detection schemes.

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.

Computational imaging has been playing an important role in understanding and analysing the captured images. Both image segmentation and restoration has been in-tegral parts of computational imaging. The studies performed in this thesis has been focussed toward developing novel algorithms for image segmentation and restoration. Study related to usage of Morozov Discrepancy Principle in Di use Optical Imaging was also presented here to show that hyper parameter selection could be performed with ease. The Laplacian of Gaussian (LoG) and Canny operators use Gaussian smoothing be-fore applying the derivative operator for edge detection in real images. The LoG kernel was based on second derivative and is highly sensitive to noise when compared to the Canny edge detector. A new edge detection kernel, called as Helmholtz of Gaussian (HoG), which provides higher di suavity is developed in this thesis and it was shown that it is more robust to noise. The formulation of the developed HoG kernel is similar to LoG. It was also shown both theoretically and experimentally that LoG is a special case of HoG. This kernel when used as an edge detector exhibited superior performance compared to LoG, Canny and wavelet based edge detector for the standard test cases both in one- and two-dimensions. The linear inverse problem encountered in restoration of blurred noisy images is typically solved via Tikhonov minimization. The outcome (restored image) of such min-imitation is highly dependent on the choice of regularization parameter. In the absence of prior information about the noise levels in the blurred image, ending this regular-inaction/hyper parameter in an automated way becomes extremely challenging. The available methods like Generalized Cross Validation (GCV) may not yield optimal re-salts in all cases. A novel method that relies on minimal residual method for ending the regularization parameter automatically was proposed here and was systematically compared with the GCV method. It was shown that the proposed method performance was superior to the GCV method in providing high quality restored images in cases where the noise levels are high Di use optical tomography uses near infrared (NIR) light as the probing media to recover the distributions of tissue optical properties with an ability to provide functional information of the tissue under investigation. As NIR light propagation in the tissue is dominated by scattering, the image reconstruction problem (inverse problem) is non-linear and ill-posed, requiring usage of advanced computational methods to compensate this. An automated method for selection of regularization/hyper parameter that incorporates Morozov discrepancy principle(MDP) into the Tikhonov method was proposed and shown to be a promising method for the dynamic Di use Optical Tomography.

Biomedical optical imaging is capable of providing functional information of the soft bi-ological tissues, whose applications include imaging large tissues, such breastand brain in-vivo. Biomedical optical imaging uses near infrared light (600nm-900nm) as the probing media, givin ganaddedadvantageofbeingnon-ionizingimagingmodality. The tomographic technologies for imaging large tissues encompasses diffuse optical tomogra-phyandphotoacoustictomography. Traditional image reconstruction methods indiffuse optical tomographyemploysa �2-norm based regularization, which is known to remove high frequency no is either econstructed images and make the mappearsmooth. Hence as parsity based image reconstruction has been deployed for diffuse optical tomography, these sparserecov-ery methods utilize the �p-norm based regularization in the estimation problem with 0≤ p<1. These sparse recovery methods, along with an approximation to utilizethe �0-norm, have been used forther econstruction of diffus eopticaltomographic images.The comparison of these methods was performed by increasing the sparsityinthesolu-tion. Further a model resolution matrix based framework was proposed and shown to in-duceblurinthe�2-norm based regularization framework for diffuse optical tomography. This model-resolution matrix framework was utilized in the optical imaged econvolution framework. A basis pursuitdeconvolution based on Split AugmentedLagrangianShrink-ageAlgorithm(SALSA)algorithm was used along with the Tikhonovregularization step making the image reconstruction into a two-step procedure. This new two-step approach was found to be robust with no iseandwasabletobetterdelineatethestructureswhichwasevaluatedusingnumericalandgelatinphantom experiments. Modern diffuse optical imaging systems are multi-modalin nature, where diffuse optical imaging is combined with traditional imaging modalitiessuc has Magnetic Res-onanceImaging(MRI),or Computed Tomography(CT). Image-guided diffuse optical tomography has the advantage of reducingthetota lnumber of optical parameters beingreconstructedtothenumber of distinct tissue types identified by the traditional imaging modality, converting the optical image-reconstruction problem fromunder-determined innaturetoover-determined. In such cases, the minimum required measurements might be farless compared to those of the traditional diffuse optical imaging. An approach to choose these measurements optimally based on a data-resolution matrix is proposed, and it is shown that it drastically reduces the minimum required measurements (typicalcaseof240to6) without compromising the image reconstruction performance. In the last part of the work , a model-based image reconstruction approaches in pho-toacoustic tomography (which combines light and ultra sound) arestudied as it is know that these methods have a distinct advantage compared to traditionalanalytical methods in limited datacase. These model-based methods deployTikhonovbasedregularizationschemetoreconstruct the initial pressure from the boundary acoustic data. Again a model-resolution for these cases tend to represent the blurinduced by the regularization scheme. A method that utilizes this blurringmodelandper forms the basis pursuit econ-volution to improve the quantitative accuracy of the reconstructed photoacoustic image is proposed and shown to be superior compared to other traditional methods. Moreover, this deconvolution including the building of model-resolution matrixis achievedvia the Lanczosbidiagonalization (least-squares QR) making this approach computationally ef-ficient and deployable inreal-time. Keywords Medical imaging, biomedical optical imaging, diffuse optical tomography, photoacous-tictomography, multi-modalimaging, inverse problems,sparse recovery,computational methods inbiomedical optical imaging.

Diffuse optical tomography uses near infrared (NIR) light as the probing media to recover the distributions of tissue optical properties. It has a potential to become an adjunct imaging modality for breast and brain imaging, that is capable of providing functional information of the tissue under investigation. As NIR light propagation in the tissue is dominated by scattering, the image reconstruction problem (inverse problem) tends to be non-linear and ill-posed, requiring usage of advanced computational methods to compensate this. Traditional image reconstruction methods in diffuse optical tomography employ l2 –norm based regularization, which is known to remove high frequency noises in the re-constructed images and make them appear smooth. The recovered contrast in the reconstructed image in these type of methods are typically dependent on the iterative nature of the method employed, in which the non-linear iterative technique is known to perform better in comparison to linear techniques. The usage of non-linear iterative techniques in the real-time, especially in dynamical imaging, becomes prohibitive due to the computational complexity associated with them. In the rapid dynamic diffuse optical imaging, assumption of a linear dependency in the solutions between successive frames results in a linear inverse problem. This new frame work along with the l1–norm based regularization can provide better robustness to noise and results in a better contrast recovery compared to conventional l2 –based techniques. Moreover, it is shown that the proposed l1-based technique is computationally efficient compared to its counterpart(l2 –based one). The proposed framework requires a reasonably close estimate of the actual solution for the initial frame and any suboptimal estimate leads to erroneous reconstruction results for the subsequent frames. Modern diffuse optical imaging systems are multi-modal in nature, where diffuse optical imaging is combined with traditional imaging modalities such as MRI, CT, and Ultrasound. A novel approach that can more effectively use the structural information provided by the traditional imaging modalities in these scenarios is introduced, which is based on prior image constrained- l1 minimization scheme. This method has been motivated by the recent progress in the sparse image reconstruction techniques. It is shown that the- l1 based frame work is more effective in terms of localizing the tumor region and recovering the optical property values both in numerical and gelatin phantom cases compared to the traditional methods that use structural information.

Diffuse optical tomography (DOT) is one of the promising imaging modalities that pro- vides functional information of the soft biological tissues in-vivo, such as breast and brain tissues. The near infrared (NIR) light (600-1000 nm) is the interrogating radiation, which is typically delivered and collected using fiber bundles placed on the boundary of the tissue. The internal optical property distribution is estimated via model-based image reconstruction algorithm using these limited boundary measurements. Image reconstruction problem in DOT is known to be non-linear, ill-posed, and some times under-determined due to the multiple scattering of NIR light in the tissue. Solving this inverse problem requires regularization to obtain meaningful results, with Tikhonov-type regularization being the most popular one. The choice of the regularization parameter dictates the reconstructed optical image quality and is typically chosen empirically or based on prior experience. An automated method for optimal selection of regularization parameter that is based on regularized minimal residual method (MRM) is proposed and is compared with the traditional generalized cross-validation method. The results obtained using numerical and gelatin phantom data indicate that the MRM-based method is capable of providing the optimal regularization parameter. A new approach that can easily incorporate any generic penalty function into the diffuse optical tomographic image reconstruction is introduced to show the utility of non-quadratic penalty functions. The penalty functions that were used include, quadratic (`2), absolute (`1), Cauchy, and Geman-McClure. The regularization parameter in each of these cases were obtained automatically using the generalized cross-validation (GCV) method. The reconstruction results were systematically compared with each other via utilization of quantitative metrics, such as relative error and Pearson correlation. The reconstruction results indicate that while quadratic penalty may be able to provide better separation between two closely spaced targets, it's contrast recovery capability is limited and the sparseness promoting penalties, such as `1, Cauchy, Geman-McClure have better utility in reconstructing high-contrast and complex-shaped targets with Geman-McClure penalty being the most optimal one. Effective usage of image guidance by incorporating the refractive index (RI) variation in computational modeling of light propagation in tissue is investigated to assess its impact on optical-property estimation. With the aid of realistic patient breast three-dimensional models, the variation in RI for different regions of tissue under investigation is shown to influence the estimation of optical properties in image-guided diffuse optical tomography (IG-DOT) using numerical simulations. It is also shown that by assuming identical RI for all regions of tissue would lead to erroneous estimation of optical properties. The a priori knowledge of the RI for the segmented regions of tissue in IG-DOT, which is difficult to obtain for the in vivo cases, leads to more accurate estimates of optical properties. Even inclusion of approximated RI values, obtained from the literature, for the regions of tissue resulted in better estimates of optical properties, with values comparable to that of having the correct knowledge of RI for different regions of tissue. Image reconstruction in IG-DOT procedure involves reduction of the number of optical parameters to be reconstructed equal to the number of distinct regions identified in the structural information provided by the traditional imaging modality. This makes the image reconstruction problem to be well-determined compared to traditional under- determined case. Still, the methods that are deployed in this case are same as the one used for traditional diffuse optical image reconstruction, which involves regularization term as well as computation of the Jacobian. A gradient-free Nelder-Mead simplex method was proposed here to perform the image reconstruction procedure and shown to be providing solutions that are closely matching with ones obtained using established methods. The proposed method also has the distinctive advantage of being more efficient due to being regularization free, involving only repeated forward calculations.

Diffuse optical tomography uses near infrared (NIR) light as the probing media to re-cover the distributions of tissue optical properties with an ability to provide functional information of the tissue under investigation. As NIR light propagation in the tissue is dominated by scattering, the image reconstruction problem (inverse problem) is non-linear and ill-posed, requiring usage of advanced computational methods to compensate this. Diffuse optical image reconstruction problem is always rank-deficient, where finding the independent measurements among the available measurements becomes challenging problem. Knowing these independent measurements will help in designing better data acquisition set-ups and lowering the costs associated with it. An optimal measurement selection strategy based on incoherence among rows (corresponding to measurements) of the sensitivity (or weight) matrix for the near infrared diffuse optical tomography is proposed. As incoherence among the measurements can be seen as providing maximum independent information into the estimation of optical properties, this provides high level of optimization required for knowing the independency of a particular measurement on its counterparts. The utility of the proposed scheme is demonstrated using simulated and experimental gelatin phantom data set comparing it with the state-of-the-art methods. The traditional image reconstruction methods employ ℓ2-norm in the regularization functional, resulting in smooth solutions, where the sharp image features are absent. The sparse recovery methods utilize the ℓp-norm with p being between 0 and 1 (0 ≤ p1), along with an approximation to utilize the ℓ0-norm, have been deployed for the reconstruction of diffuse optical images. These methods are shown to have better utility in terms of being more quantitative in reconstructing realistic diffuse optical images compared to traditional methods. Utilization of ℓp-norm based regularization makes the objective (cost) function non-convex and the algorithms that implement ℓp-norm minimization utilizes approximations to the original ℓp-norm function. Three methods for implementing the ℓp-norm were con-sidered, namely Iteratively Reweigthed ℓ1-minimization (IRL1), Iteratively Reweigthed Least-Squares (IRLS), and Iteratively Thresholding Method (ITM). These results in-dicated that IRL1 implementation of ℓp-minimization provides optimal performance in terms of shape recovery and quantitative accuracy of the reconstructed diffuse optical tomographic images. Photoacoustic tomography (PAT) is an emerging hybrid imaging modality combining optics with ultrasound imaging. PAT provides structural and functional imaging in diverse application areas, such as breast cancer and brain imaging. A model-based iterative reconstruction schemes are the most-popular for recovering the initial pressure in limited data case, wherein a large linear system of equations needs to be solved. Often, these iterative methods requires regularization parameter estimation, which tends to be a computationally expensive procedure, making the image reconstruction process to be performed off-line. To overcome this limitation, a computationally efficient approach that computes the optimal regularization parameter is developed for PAT. This approach is based on the least squares-QR (LSQR) decomposition, a well-known dimensionality reduction technique for a large system of equations. It is shown that the proposed framework is effective in terms of quantitative and qualitative reconstructions of initial pressure distribution.

Diffuse optical tomography is a promising imaging modality that provides functional information of the soft biological tissues, with prime imaging applications including breast and brain tissue in-vivo. This modality uses near infrared light( 600nm-900nm) as the probing media, giving an advantage of being non-ionizing imaging modality. The image reconstruction problem in diffuse optical tomography is typically posed as a least-squares problem that minimizes the difference between experimental and modeled data with respect to optical properties. This problem is non-linear and ill-posed, due to multiple scattering of the near infrared light in the biological tissues, leading to infinitely many possible solutions. The traditional methods employ a regularization term to constrain the solution space as well as stabilize the solution, with Tikhonov type regularization being the most popular one. The choice of this regularization parameter, also known as hyper parameter, dictates the reconstructed optical image quality and is typically chosen empirically or based on prior experience. In this thesis, a simple back projection type image reconstruction algorithm is taken up, as they are known to provide computationally efficient solution compared to regularized solutions. In these algorithms, the hyper parameter becomes equivalent to filter factor and choice of which is typically dependent on the sampling interval used for acquiring data in each projection and the angle of projection. Determining these parameters for diffuse optical tomography is not so straightforward and requires usage of advanced computational models. In this thesis, a computationally efficient simplex Method based optimization scheme for automatically finding this filter factor is proposed and its performances is evaluated through numerical and experimental phantom data. As back projection type algorithms are approximations to traditional methods, the absolute quantitative accuracy of the reconstructed optical properties is poor .In scenarios, like dynamic imaging, where the emphasis is on recovering relative difference in the optical properties, these algorithms are effective in comparison to traditional methods, with an added advantage being highly computationally efficient. In the second part of this thesis, this hyper parameter choice for traditional Tikhonov type regularization is attempted with the help of Least-Squares QR-decompisition (LSQR) method. The established techniques that enable the automated choice of hyper parameters include Generalized Cross-Validation(GCV) and regularized Minimal Residual Method(MRM), where both of them come with higher over head of computation time, making it prohibitive to be used in the real-time. The proposed LSQR algorithm uses bidiagonalization of the system matrix to result in less computational cost. The proposed LSQR-based algorithm for automated choice of hyper parameter is compared with MRM methods and is proven to be computationally optimal technique through numerical and experimental phantom cases.