Modern Statistical/Machine Learning Techniques for Bio/Neuro-imaging Applications

Developments in modern bio-imaging techniques have allowed the routine collection of a vast amount of data from various techniques. The challenges lie in how to build accurate and efficient models to draw conclusions from the data and facilitate scientific discoveries. Fortunately, recent advances in statistics, machine learning, and deep learning provide valuable tools. This thesis describes some of our efforts to build scalable Bayesian models for four bio-imaging applications: (1) Stochastic Optical Reconstruction Microscopy (STORM) Imaging, (2) particle tracking, (3) voltage smoothing, (4) detect color-labeled neurons in c elegans and assign identity to the detections

Maximum-a-posteriori estimation with Bayesian confidence regions

Solutions to inverse problems that are ill-conditioned or ill-posed may have significant intrinsic uncertainty. Unfortunately, analysing and quantifying this uncertainty is very challenging, particularly in high-dimensional problems. As a result, while most modern mathematical imaging methods produce impressive point estimation results, they are generally unable to quantify the uncertainty in the solutions delivered. This paper presents a new general methodology for approximating Bayesian high-posterior-density credibility regions in inverse problems that are convex and potentially very high-dimensional. The approximations are derived by using recent concentration of measure results related to information theory for log-concave random vectors. A remarkable property of the approximations is that they can be computed very efficiently, even in large-scale problems, by using standard convex optimisation techniques. In particular, they are available as a by-product in problems solved by maximum-a-posteriori estimation. The approximations also have favourable theoretical properties, namely they outer-bound the true high-posterior-density credibility regions, and they are stable with respect to model dimension. The proposed methodology is illustrated on two high-dimensional imaging inverse problems related to tomographic reconstruction and sparse deconvolution, where the approximations are used to perform Bayesian hypothesis tests and explore the uncertainty about the solutions, and where proximal Markov chain Monte Carlo algorithms are used as benchmark to compute exact credible regions and measure the approximation error

Teaching deep neural networks to localize sources in super-resolution microscopy by combining simulation-based learning and unsupervised learning

Single-molecule localization microscopy constructs super-resolution images by the sequential imaging and computational localization of sparsely activated fluorophores. Accurate and efficient fluorophore localization algorithms are key to the success of this computational microscopy method. We present a novel localization algorithm based on deep learning which significantly improves upon the state of the art. Our contributions are a novel network architecture for simultaneous detection and localization, and a new training algorithm which enables this deep network to solve the Bayesian inverse problem of detecting and localizing single molecules. Our network architecture uses temporal context from multiple sequentially imaged frames to detect and localize molecules. Our training algorithm combines simulation-based supervised learning with autoencoder-based unsupervised learning to make it more robust against mismatch in the generative model. We demonstrate the performance of our method on datasets imaged using a variety of point spread functions and fluorophore densities. While existing localization algorithms can achieve optimal localization accuracy in data with low fluorophore density, they are confounded by high densities. Our method significantly outperforms the state of the art at high densities and thus, enables faster imaging than previous approaches. Our work also more generally shows how to train deep networks to solve challenging Bayesian inverse problems in biology and physics

Illumination coding meets uncertainty learning: toward reliable AI-augmented phase imaging

We propose a physics-assisted deep learning (DL) framework for large space-bandwidth product (SBP) phase imaging. We design an asymmetric coded illumination scheme to encode high-resolution phase information across a wide field-of-view. We then develop a matching DL algorithm to provide large-SBP phase estimation. We show that this illumination coding scheme is highly scalable in achieving flexible resolution, and robust to experimental variations. We demonstrate this technique on both static and dynamic biological samples, and show that it can reliably achieve 5X resolution enhancement across 4X FOVs using only five multiplexed measurements -- more than 10X data reduction over the state-of-the-art. Typical DL algorithms tend to provide over-confident predictions, whose errors are only discovered in hindsight. We develop an uncertainty learning framework to overcome this limitation and provide predictive assessment to the reliability of the DL prediction. We show that the predicted uncertainty maps can be used as a surrogate to the true error. We validate the robustness of our technique by analyzing the model uncertainty. We quantify the effect of noise, model errors, incomplete training data, and "out-of-distribution" testing data by assessing the data uncertainty. We further demonstrate that the predicted credibility maps allow identifying spatially and temporally rare biological events. Our technique enables scalable AI-augmented large-SBP phase imaging with dependable predictions.Published versio

Task adapted reconstruction for inverse problems

The paper considers the problem of performing a task defined on a model parameter that is only observed indirectly through noisy data in an ill-posed inverse problem. A key aspect is to formalize the steps of reconstruction and task as appropriate estimators (non-randomized decision rules) in statistical estimation problems. The implementation makes use of (deep) neural networks to provide a differentiable parametrization of the family of estimators for both steps. These networks are combined and jointly trained against suitable supervised training data in order to minimize a joint differentiable loss function, resulting in an end-to-end task adapted reconstruction method. The suggested framework is generic, yet adaptable, with a plug-and-play structure for adjusting both the inverse problem and the task at hand. More precisely, the data model (forward operator and statistical model of the noise) associated with the inverse problem is exchangeable, e.g., by using neural network architecture given by a learned iterative method. Furthermore, any task that is encodable as a trainable neural network can be used. The approach is demonstrated on joint tomographic image reconstruction, classification and joint tomographic image reconstruction segmentation

Review : Deep learning in electron microscopy

Deep learning is transforming most areas of science and technology, including electron microscopy. This review paper offers a practical perspective aimed at developers with limited familiarity. For context, we review popular applications of deep learning in electron microscopy. Following, we discuss hardware and software needed to get started with deep learning and interface with electron microscopes. We then review neural network components, popular architectures, and their optimization. Finally, we discuss future directions of deep learning in electron microscopy