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

A fully-automatic caudate nucleus segmentation of brain MRI: Application in volumetric analysis of pediatric attention-deficit/hyperactivity disorder

Background Accurate automatic segmentation of the caudate nucleus in magnetic resonance images (MRI) of the brain is of great interest in the analysis of developmental disorders. Segmentation methods based on a single atlas or on multiple atlases have been shown to suitably localize caudate structure. However, the atlas prior information may not represent the structure of interest correctly. It may therefore be useful to introduce a more flexible technique for accurate segmentations. Method We present Cau-dateCut: a new fully-automatic method of segmenting the caudate nucleus in MRI. CaudateCut combines an atlas-based segmentation strategy with the Graph Cut energy-minimization framework. We adapt the Graph Cut model to make it suitable for segmenting small, low-contrast structures, such as the caudate nucleus, by defining new energy function data and boundary potentials. In particular, we exploit information concerning the intensity and geometry, and we add supervised energies based on contextual brain structures. Furthermore, we reinforce boundary detection using a new multi-scale edgeness measure. Results We apply the novel CaudateCut method to the segmentation of the caudate nucleus to a new set of 39 pediatric attention-deficit/hyperactivity disorder (ADHD) patients and 40 control children, as well as to a public database of 18 subjects. We evaluate the quality of the segmentation using several volumetric and voxel by voxel measures. Our results show improved performance in terms of segmentation compared to state-of-the-art approaches, obtaining a mean overlap of 80.75%. Moreover, we present a quantitative volumetric analysis of caudate abnormalities in pediatric ADHD, the results of which show strong correlation with expert manual analysis. Conclusion CaudateCut generates segmentation results that are comparable to gold-standard segmentations and which are reliable in the analysis of differentiating neuroanatomical abnormalities between healthy controls and pediatric ADHD

Deep active learning for suggestive segmentation of biomedical image stacks via optimisation of Dice scores and traced boundary length

Manual segmentation of stacks of 2D biomedical images (e.g., histology) is a time-consuming task which can be sped up with semi-automated techniques. In this article, we present a suggestive deep active learning framework that seeks to minimise the annotation effort required to achieve a certain level of accuracy when labelling such a stack. The framework suggests, at every iteration, a specific region of interest (ROI) in one of the images for manual delineation. Using a deep segmentation neural network and a mixed cross-entropy loss function, we propose a principled strategy to estimate class probabilities for the whole stack, conditioned on heterogeneous partial segmentations of the 2D images, as well as on weak supervision in the form of image indices that bound each ROI. Using the estimated probabilities, we propose a novel active learning criterion based on predictions for the estimated segmentation performance and delineation effort, measured with average Dice scores and total delineated boundary length, respectively, rather than common surrogates such as entropy. The query strategy suggests the ROI that is expected to maximise the ratio between performance and effort, while considering the adjacency of structures that may have already been labelled – which decrease the length of the boundary to trace. We provide quantitative results on synthetically deformed MRI scans and real histological data, showing that our framework can reduce labelling effort by up to 60–70% without compromising accuracy

Unsupervised Pathology Detection: A Deep Dive Into the State of the Art

Deep unsupervised approaches are gathering increased attention for applications such as pathology detection and segmentation in medical images since they promise to alleviate the need for large labeled datasets and are more generalizable than their supervised counterparts in detecting any kind of rare pathology. As the Unsupervised Anomaly Detection (UAD) literature continuously grows and new paradigms emerge, it is vital to continuously evaluate and benchmark new methods in a common framework, in order to reassess the state-of-the-art (SOTA) and identify promising research directions. To this end, we evaluate a diverse selection of cutting-edge UAD methods on multiple medical datasets, comparing them against the established SOTA in UAD for brain MRI. Our experiments demonstrate that newly developed feature-modeling methods from the industrial and medical literature achieve increased performance compared to previous work and set the new SOTA in a variety of modalities and datasets. Additionally, we show that such methods are capable of benefiting from recently developed self-supervised pre-training algorithms, further increasing their performance. Finally, we perform a series of experiments in order to gain further insights into some unique characteristics of selected models and datasets. Our code can be found under https://github.com/iolag/UPD_study/.Comment: 12 pages, 4 figures, accepted for publication in IEEE Transactions on Medical Imaging (added copyright, DOI information

Medical Image Segmentation with Deep Convolutional Neural Networks

Medical imaging is the technique and process of creating visual representations of the body of a patient for clinical analysis and medical intervention. Healthcare professionals rely heavily on medical images and image documentation for proper diagnosis and treatment. However, manual interpretation and analysis of medical images are time-consuming, and inaccurate when the interpreter is not well-trained. Fully automatic segmentation of the region of interest from medical images has been researched for years to enhance the efficiency and accuracy of understanding such images. With the advance of deep learning, various neural network models have gained great success in semantic segmentation and sparked research interests in medical image segmentation using deep learning. We propose three convolutional frameworks to segment tissues from different types of medical images. Comprehensive experiments and analyses are conducted on various segmentation neural networks to demonstrate the effectiveness of our methods. Furthermore, datasets built for training our networks and full implementations are published