This Dissertation is comprised of two main projects, addressing questions in neuroscience through applications of generative modeling. Project #1 (Chapter 4) explores how neurons encode features of the external world. I combine Helmholtz's "Perception as Unconscious Inference" -- paralleled by modern generative models like variational autoencoders (VAE) -- with the hierarchical structure of the visual cortex. This combination leads to the development of a hierarchical VAE model, which I test for its ability to mimic neurons from the primate visual cortex in response to motion stimuli. Results show that the hierarchical VAE perceives motion similar to the primate brain. Additionally, the model identifies causal factors of retinal motion inputs, such as object- and self-motion, in a completely unsupervised manner. Collectively, these results suggest that hierarchical inference underlines the brain's understanding of the world, and hierarchical VAEs can effectively model this understanding. Project #2 (Chapter 5) investigates the spatiotemporal structure of spontaneous brain activity and its reflection of brain states like rest. Using simultaneous fMRI and wide-field Ca2+ imaging data, this project demonstrates that the mouse cortex can be decomposed into overlapping communities, with around half of the cortical regions belonging to multiple communities. Comparisons reveal similarities and differences between networks inferred from fMRI and Ca2+ signals. The introduction (Chapter 1) is divided similarly to this abstract: sections 1.1 to 1.8 provide background information about Project #1, and sections 1.9 to 1.13 are related to Project #2. Chapter 2 includes historical background, Chapter 3 provides the necessary mathematical background, and finally, Chapter 6 contains concluding remarks and future directions.

Functional magnetic resonance imaging (fMRI) is extensively used in clinical and preclinical settings to study brain function, however, fMRI data is inherently noisy due to physiological processes, hardware, and external noise. Denoising is one of the main preprocessing steps in any fMRI analysis pipeline. This process is challenging in preclinical data in comparison to clinical data due to variations in brain geometry, image resolution, and low signal-to-noise ratios. In this paper, we propose a structure-preserved algorithm based on a 3D Wasserstein generative adversarial network with a 3D dense U-net based discriminator called, 3D U-WGAN. We apply a 4D data configuration to effectively denoise temporal and spatial information in analyzing preclinical fMRI data. GAN-based denoising methods often utilize a discriminator to identify significant differences between denoised and noise-free images, focusing on global or local features. To refine the fMRI denoising model, our method employs a 3D dense U-Net discriminator to learn both global and local distinctions. To tackle potential over-smoothing, we introduce an adversarial loss and enhance perceptual similarity by measuring feature space distances. Experiments illustrate that 3D U-WGAN significantly improves image quality in resting-state and task preclinical fMRI data, enhancing signal-to-noise ratio without introducing excessive structural changes in existing methods. The proposed method outperforms state-of-the-art methods when applied to simulated and real data in a fMRI analysis pipeline.

Vascular anastomosis, the surgical connection of blood vessels, is essential in procedures such as organ transplants and reconstructive surgeries. The precision required limits accessibility due to the extensive training needed, with manual suturing leading to variable outcomes and revision rates up to 7.9%. Existing robotic systems, while promising, are either fully teleoperated or lack the capabilities necessary for autonomous vascular anastomosis. We present the Micro Smart Tissue Autonomous Robot (micro-STAR), an autonomous robotic system designed to perform vascular anastomosis on small-diameter vessels. The micro-STAR system integrates a novel suturing tool equipped with Optical Coherence Tomography (OCT) fiber-optic sensor and a microcamera, enabling real-time tissue detection and classification. Our system autonomously places sutures and manipulates tissue with minimal human intervention. In an ex vivo study, micro-STAR achieved outcomes competitive with experienced surgeons in terms of leak pressure, lumen reduction, and suture placement variation, completing 90% of sutures without human intervention. This represents the first instance of a robotic system autonomously performing vascular anastomosis on real tissue, offering significant potential for improving surgical precision and expanding access to high-quality care.

We consider the inverse acoustic obstacle problem for sound-soft star-shaped obstacles in two dimensions wherein the boundary of the obstacle is determined from measurements of the scattered field at a collection of receivers outside the object. One of the standard approaches for solving this problem is to reformulate it as an optimization problem: finding the boundary of the domain that minimizes the $L^2$ distance between computed values of the scattered field and the given measurement data. The optimization problem is computationally challenging since the local set of convexity shrinks with increasing frequency and results in an increasing number of local minima in the vicinity of the true solution. In many practical experimental settings, low frequency measurements are unavailable due to limitations of the experimental setup or the sensors used for measurement. Thus, obtaining a good initial guess for the optimization problem plays a vital role in this environment. We present a neural network warm-start approach for solving the inverse scattering problem, where an initial guess for the optimization problem is obtained using a trained neural network. We demonstrate the effectiveness of our method with several numerical examples. For high frequency problems, this approach outperforms traditional iterative methods such as Gauss-Newton initialized without any prior (i.e., initialized using a unit circle), or initialized using the solution of a direct method such as the linear sampling method. The algorithm remains robust to noise in the scattered field measurements and also converges to the true solution for limited aperture data. However, the number of training samples required to train the neural network scales exponentially in frequency and the complexity of the obstacles considered. We conclude with a discussion of this phenomenon and potential directions for future research.

Unsatisfying accuracy of learning methods is mostly caused by omitting the influence of important parameters such as membership assignments, type of data objects, and distance or similarity functions. The proposed method, called Bounded Fuzzy Possibilistic Method (BFPM) addresses different issues that previous clustering or classification methods have not sufficiently considered in their membership assignments. In fuzzy methods, the object's memberships should sum to 1. Hence, any data object may obtain full membership in at most one cluster or class. Possibilistic methods relax this condition, but the method can be satisfied with the results even if just an arbitrary object obtains the membership from just one cluster, which prevents the objects' movement analysis. Whereas, BFPM differs from previous fuzzy and possibilistic approaches by removing these restrictions. Furthermore, BFPM provides the flexible search space for objects' movement analysis. Data objects are also considered as fundamental keys in learning methods, and knowing the exact type of objects results in providing a suitable environment for learning algorithms. The Thesis introduces a new type of object, called critical, as well as categorizing data objects into two different categories: structural-based and behavioural-based. Critical objects are considered as causes of miss-classification and miss-assignment in learning procedures. The Thesis also proposes new methodologies to study the behaviour of critical objects with the aim of evaluating objects' movements (mutation) from one cluster or class to another. The Thesis also introduces a new type of feature, called dominant, that is considered as one of the causes of miss-classification and miss-assignments. Then the Thesis proposes new sets of similarity functions, called Weighted Feature Distance (WFD) and Prioritized Weighted Feature Distance (PWFD).

Quantitative susceptibility mapping (QSM) estimates the underlying tissue magnetic susceptibility from MRI gradient-echo phase signal and typically requires several processing steps. These steps involve phase unwrapping, brain volume extraction, background phase removal and solving an ill-posed inverse problem. The resulting susceptibility map is known to suffer from inaccuracy near the edges of the brain tissues, in part due to imperfect brain extraction, edge erosion of the brain tissue and the lack of phase measurement outside the brain. This inaccuracy has thus hindered the application of QSM for measuring the susceptibility of tissues near the brain edges, e.g., quantifying cortical layers and generating superficial venography. To address these challenges, we propose a learning-based QSM reconstruction method that directly estimates the magnetic susceptibility from total phase images without the need for brain extraction and background phase removal, referred to as autoQSM. The neural network has a modified U-net structure and is trained using QSM maps computed by a two-step QSM method. 209 healthy subjects with ages ranging from 11 to 82 years were employed for patch-wise network training. The network was validated on data dissimilar to the training data, e.g. in vivo mouse brain data and brains with lesions, which suggests that the network has generalized and learned the underlying mathematical relationship between magnetic field perturbation and magnetic susceptibility. AutoQSM was able to recover magnetic susceptibility of anatomical structures near the edges of the brain including the veins covering the cortical surface, spinal cord and nerve tracts near the mouse brain boundaries. The advantages of high-quality maps, no need for brain volume extraction and high reconstruction speed demonstrate its potential for future applications.

BILLERICA, Mass., Feb. 15, 2018 (GLOBE NEWSWIRE) -- OrboGraph, a premier developer and supplier of intelligent electronic/paper automation leveraging recognition technologies, image validation and check fraud detection for the U.S. check processing and healthcare revenue cycle markets, was recently highlighted in the February edition of The TECHNOLOGY HEADLINES: "Top 10 Artificial Intelligence (AI) Solution Providers to Watch in 2018". Artificial Intelligence investment will reach around $150 billion by 2030 across major industries such as automotive, banking and healthcare. OrboGraph's focus is to automate payments via Intelligent Payment Automation technology. The company looks at AI to improve efficiencies into the entire payment mix and facilitate electronification of payments, which ultimately reduces payment costs. Walk down the isle of any banking or healthcare trade show and it seems like almost every vendor has an AI story.

Objective: In this work, we perform margin assessment of human breast tissue from optical coherence tomography (OCT) images using deep neural networks (DNNs). This work simulates an intraoperative setting for breast cancer lumpectomy. Methods: To train the DNNs, we use both the state-of-the-art methods (Weight Decay and DropOut) and a newly introduced regularization method based on function norms. Commonly used methods can fail when only a small database is available. The use of a function norm introduces a direct control over the complexity of the function with the aim of diminishing the risk of overfitting. Results: As neither the code nor the data of previous results are publicly available, the obtained results are compared with reported results in the literature for a conservative comparison. Moreover, our method is applied to locally collected data on several data configurations. The reported results are the average over the different trials. Conclusion: The experimental results show that the use of DNNs yields significantly better results than other techniques when evaluated in terms of sensitivity, specificity, F1 score, G-mean and Matthews correlation coefficient. Function norm regularization yielded higher and more robust results than competing methods. Significance: We have demonstrated a system that shows high promise for (partially) automated margin assessment of human breast tissue, Equal error rate (EER) is reduced from approximately 12\% (the lowest reported in the literature) to 5\%\,--\,a 58\% reduction. The method is computationally feasible for intraoperative application (less than 2 seconds per image).

An Amazon warehouse is a flurry of activity. Towering hydraulic arms lift heavy boxes toward the rafters. And an army of stubby orange robots slide along the floor like giant, sentient hockey pucks, piled high with towers of consumer gratification ranging from bestsellers to kitchenware. Those are Kiva robots, once the marvel of warehouses everywhere. Amazon whipped out its wallet and threw down US 775 million to purchase these robot legions in 2012.

An Amazon warehouse is a flurry of activity. Towering hydraulic arms lift heavy boxes toward the rafters. And an army of stubby orange robots slide along the floor like giant, sentient hockey pucks, piled high with towers of consumer gratification ranging from bestsellers to kitchenware. Those are Kiva robots, once the marvel of warehouses everywhere. Amazon whipped out its wallet and threw down 775 million to purchase these robot legions in 2012.