Fully Unsupervised Image Denoising, Diversity Denoising and Image Segmentation with Limited Annotations

Understanding the processes of cellular development and the interplay of cell shape changes, division and migration requires investigation of developmental processes at the spatial resolution of single cell. Biomedical imaging experiments enable the study of dynamic processes as they occur in living organisms. While biomedical imaging is essential, a key component of exposing unknown biological phenomena is quantitative image analysis. Biomedical images, especially microscopy images, are usually noisy owing to practical limitations such as available photon budget, sample sensitivity, etc. Additionally, microscopy images often contain artefacts due to the optical aberrations in microscopes or due to imperfections in camera sensor and internal electronics. The noisy nature of images as well as the artefacts prohibit accurate downstream analysis such as cell segmentation. Although countless approaches have been proposed for image denoising, artefact removal and segmentation, supervised Deep Learning (DL) based content-aware algorithms are currently the best performing for all these tasks. Supervised DL based methods are plagued by many practical limitations. Supervised denoising and artefact removal algorithms require paired corrupted and high quality images for training. Obtaining such image pairs can be very hard and virtually impossible in most biomedical imaging applications owing to photosensitivity and the dynamic nature of the samples being imaged. Similarly, supervised DL based segmentation methods need copious amounts of annotated data for training, which is often very expensive to obtain. Owing to these restrictions, it is imperative to look beyond supervised methods. The objective of this thesis is to develop novel unsupervised alternatives for image denoising, and artefact removal as well as semisupervised approaches for image segmentation. The first part of this thesis deals with unsupervised image denoising and artefact removal. For unsupervised image denoising task, this thesis first introduces a probabilistic approach for training DL based methods using parametric models of imaging noise. Next, a novel unsupervised diversity denoising framework is presented which addresses the fundamentally non-unique inverse nature of image denoising by generating multiple plausible denoised solutions for any given noisy image. Finally, interesting properties of the diversity denoising methods are presented which make them suitable for unsupervised spatial artefact removal in microscopy and medical imaging applications. In the second part of this thesis, the problem of cell/nucleus segmentation is addressed. The focus is especially on practical scenarios where ground truth annotations for training DL based segmentation methods are scarcely available. Unsupervised denoising is used as an aid to improve segmentation performance in the presence of limited annotations. Several training strategies are presented in this work to leverage the representations learned by unsupervised denoising networks to enable better cell/nucleus segmentation in microscopy data. Apart from DL based segmentation methods, a proof-of-concept is introduced which views cell/nucleus segmentation from the perspective of solving a label fusion problem. This method, through limited human interaction, learns to choose the best possible segmentation for each cell/nucleus using only a pool of diverse (and possibly faulty) segmentation hypotheses as input. In summary, this thesis seeks to introduce new unsupervised denoising and artefact removal methods as well as semi-supervised segmentation methods which can be easily deployed to directly and immediately benefit biomedical practitioners with their research

Distributed Apportioning in a Power Network for providing Demand Response Services

Greater penetration of Distributed Energy Resources (DERs) in power networks requires coordination strategies that allow for self-adjustment of contributions in a network of DERs, owing to variability in generation and demand. In this article, a distributed scheme is proposed that enables a DER in a network to arrive at viable power reference commands that satisfies the DERs local constraints on its generation and loads it has to service, while, the aggregated behavior of multiple DERs in the network and their respective loads meet the ancillary services demanded by the grid. The Net-load Management system for a single unit is referred to as the Local Inverter System (LIS) in this article . A distinguishing feature of the proposed consensus based solution is the distributed finite time termination of the algorithm that allows each LIS unit in the network to determine power reference commands in the presence of communication delays in a distributed manner. The proposed scheme allows prioritization of Renewable Energy Sources (RES) in the network and also enables auto-adjustment of contributions from LIS units with lower priority resources (non-RES). The methods are validated using hardware-in-the-loop simulations with Raspberry PI devices as distributed control units, implementing the proposed distributed algorithm and responsible for determining and dispatching realtime power reference commands to simulated power electronics interface emulating LIS units for demand response.Comment: 7 pages, 11 Figures, IEEE International Conference on Smart Grid Communication

Fully Unsupervised Probabilistic Noise2Void

Image denoising is the first step in many biomedical image analysis pipelines and Deep Learning (DL) based methods are currently best performing. A new category of DL methods such as Noise2Void or Noise2Self can be used fully unsupervised, requiring nothing but the noisy data. However, this comes at the price of reduced reconstruction quality. The recently proposed Probabilistic Noise2Void (PN2V) improves results, but requires an additional noise model for which calibration data needs to be acquired. Here, we present improvements to PN2V that (i) replace histogram based noise models by parametric noise models, and (ii) show how suitable noise models can be created even in the absence of calibration data. This is a major step since it actually renders PN2V fully unsupervised. We demonstrate that all proposed improvements are not only academic but indeed relevant.Comment: Accepted at ISBI 202

DenoiSeg: Joint Denoising and Segmentation

Microscopy image analysis often requires the segmentation of objects, but training data for this task is typically scarce and hard to obtain. Here we propose DenoiSeg, a new method that can be trained end-to-end on only a few annotated ground truth segmentations. We achieve this by extending Noise2Void, a self-supervised denoising scheme that can be trained on noisy images alone, to also predict dense 3-class segmentations. The reason for the success of our method is that segmentation can profit from denoising, especially when performed jointly within the same network. The network becomes a denoising expert by seeing all available raw data, while co-learning to segment, even if only a few segmentation labels are available. This hypothesis is additionally fueled by our observation that the best segmentation results on high quality (very low noise) raw data are obtained when moderate amounts of synthetic noise are added. This renders the denoising-task non-trivial and unleashes the desired co-learning effect. We believe that DenoiSeg offers a viable way to circumvent the tremendous hunger for high quality training data and effectively enables few-shot learning of dense segmentations.Comment: 10 pages, 4 figures, 2 pages supplement (4 figures

Leveraging Self-supervised Denoising for Image Segmentation

Deep learning (DL) has arguably emerged as the method of choice for the detection and segmentation of biological structures in microscopy images. However, DL typically needs copious amounts of annotated training data that is for biomedical projects typically not available and excessively expensive to generate. Additionally, tasks become harder in the presence of noise, requiring even more high-quality training data. Hence, we propose to use denoising networks to improve the performance of other DL-based image segmentation methods. More specifically, we present ideas on how state-of-the-art self-supervised CARE networks can improve cell/nuclei segmentation in microscopy data. Using two state-of-the-art baseline methods, U-Net and StarDist, we show that our ideas consistently improve the quality of resulting segmentations, especially when only limited training data for noisy micrographs are available.Comment: accepted at ISBI 202

A Primal-Dual Solver for Large-Scale Tracking-by-Assignment

We propose a fast approximate solver for the combinatorial problem known as tracking-by-assignment, which we apply to cell tracking. The latter plays a key role in discovery in many life sciences, especially in cell and developmental biology. So far, in the most general setting this problem was addressed by off-the-shelf solvers like Gurobi, whose run time and memory requirements rapidly grow with the size of the input. In contrast, for our method this growth is nearly linear. Our contribution consists of a new (1) decomposable compact representation of the problem; (2) dual block-coordinate ascent method for optimizing the decomposition-based dual; and (3) primal heuristics that reconstructs a feasible integer solution based on the dual information. Compared to solving the problem with Gurobi, we observe an up to~60~times speed-up, while reducing the memory footprint significantly. We demonstrate the efficacy of our method on real-world tracking problems.Comment: 23rd International Conference on Artificial Intelligence and Statistics (AISTATS), 202

Probabilistic Noise2Void: Unsupervised Content-Aware Denoising

Today, Convolutional Neural Networks (CNNs) are the leading method for image denoising. They are traditionally trained on pairs of images, which are often hard to obtain for practical applications. This motivates self-supervised training methods, such as Noise2Void (N2V) that operate on single noisy images. Self-supervised methods are, unfortunately, not competitive with models trained on image pairs. Here, we present Probabilistic Noise2Void (PN2V), a method to train CNNs to predict per-pixel intensity distributions. Combining these with a suitable description of the noise, we obtain a complete probabilistic model for the noisy observations and true signal in every pixel. We evaluate PN2V on publicly available microscopy datasets, under a broad range of noise regimes, and achieve competitive results with respect to supervised state-of-the-art methods

Identification and authentication of Agnimantha plant species used in Ayurveda on the basis of anatomical and molecular phylogenetic analysis

Agnimantha plant species have been used in the Ayurvedic system of medicine for many years and is widely used as an ingredient in many ayurvedic formulations. However, the source for Agnimantha remained controversial as it is difficult to authenticate from various reports. Hence, the present study aims to identify and authenticate its original and substitute sources. As per the literature sources Clerodendrum phlomidis L.f., C. inerme (L.) Gaertn. and Premna serratifolia L. are considered Agnimantha species. The anatomy of the above mentioned species confirmed the presence of patches of up to 20 cells in the sclerenchyma of the root cortex, while in the absence of sclerenchyma of the stem cortex, abundant chambered crystals were also present in the bark of the stem and root in C. phlomidis as compared to C. inerme and P. serratifolia. Phylogenetic analysis using chloroplast (matK, trnH-psbA) and nuclear markers (ITS, rbcl) also indicates the close relation between C. inerme and P. serratifolia and hence places them both in the same clade, though C. phlomidis is closely related to the other species but placed in the adjacent clade. Hence, the study concludes that anatomical as well as molecular phylogenetic analysis reflect close relation between C. inerme and P. serratifolia. while a distant relation with C. phlomidis