Diagnosis of Cervical Cancer and Pre-Cancerous Lesions by Artificial Intelligence: A Systematic Review

The likelihood of timely treatment for cervical cancer increases with timely detection of abnormal cervical cells. Automated methods of detecting abnormal cervical cells were established because manual identification requires skilled pathologists and is time consuming and prone to error. The purpose of this systematic review is to evaluate the diagnostic performance of artificial intelligence (AI) technologies for the prediction, screening, and diagnosis of cervical cancer and pre-cancerous lesions

Volumetric Semantic Instance Segmentation of the Plasma Membrane of HeLa Cells

In this work, an unsupervised volumetric semantic instance segmentation of the plasma membrane of HeLa cells as observed with serial block face scanning electron microscopy is described. The resin background of the images was segmented at different slices of a 3D stack of 518 slices with 8192 × 8192 pixels each. The background was used to create a distance map, which helped identify and rank the cells by their size at each slice. The centroids of the cells detected at different slices were linked to identify them as a single cell that spanned a number of slices. A subset of these cells, i.e., the largest ones and those not close to the edges were selected for further processing. The selected cells were then automatically cropped to smaller regions of interest of 2000 × 2000 × 300 voxels that were treated as cell instances. Then, for each of these volumes, the nucleus was segmented, and the cell was separated from any neighbouring cells through a series of traditional image processing steps that followed the plasma membrane. The segmentation process was repeated for all the regions of interest previously selected. For one cell for which the ground truth was available, the algorithm provided excellent results in Accuracy (AC) and the Jaccard similarity Index (JI): nucleus: JI =0.9665, AC =0.9975, cell including nucleus JI =0.8711, AC =0.9655, cell excluding nucleus JI =0.8094, AC =0.9629. A limitation of the algorithm for the plasma membrane segmentation was the presence of background. In samples with tightly packed cells, this may not be available. When tested for these conditions, the segmentation of the nuclear envelope was still possible. All the code and data were released openly through GitHub, Zenodo and EMPIAR

Better prognostic markers for nonmuscle invasive papillary urothelial carcinomas

Bladder cancer is a common type of cancer, especially among men in developed countries. Most cancers in the urinary bladder are papillary urothelial carcinomas. They are characterized by a high recurrence frequency (up to 70 %) after local resection. It is crucial for prognosis to discover these recurrent tumours at an early stage, especially before they become muscle-invasive. Reliable prognostic biomarkers for tumour recurrence and stage progression are lacking. This is why patients diagnosed with a non-muscle invasive bladder cancer follow extensive follow-up regimens with possible serious side effects and with high costs for the healthcare systems. WHO grade and tumour stage are two central biomarkers currently having great impact on both treatment decisions and follow-up regimens. However, there are concerns regarding the reproducibility of WHO grading, and stage classification is challenging in small and fragmented tumour material. In Paper I, we examined the reproducibility and the prognostic value of all the individual microscopic features making up the WHO grading system. Among thirteen extracted features there was considerable variation in both reproducibility and prognostic value. The only feature being both reasonably reproducible and statistically significant prognostic was cell polarity. We concluded that further validation studies are needed on these features, and that future grading systems should be based on well-defined features with true prognostic value. With the implementation of immunotherapy, there is increasing interest in tumour immune response and the tumour microenvironment. In a search for better prognostic biomarkers for tumour recurrence and stage progression, in Paper II, we investigated the prognostic value of tumour infiltrating immune cells (CD4, CD8, CD25 and CD138) and previously investigated cell proliferation markers (Ki-67, PPH3 and MAI). Low Ki 67 and tumour multifocality were associated with increased recurrence risk. Recurrence risk was not affected by the composition of immune cells. For stage progression, the only prognostic immune cell marker was CD25. High values for MAI was also strongly associated with stage progression. However, in a multivariate analysis, the most prognostic feature was a combination of MAI and CD25. BCG-instillations in the bladder are indicated in intermediate and high-risk non-muscle invasive bladder cancer patients. This old-fashion immunotherapy has proved to reduce both recurrence- and progression-risk, although it is frequently followed by unpleasant side-effects. As many as 30-50% of high-risk patients receiving BCG instillations, fail by develop high-grade recurrences. They do not only suffer from unnecessary side-effects, but will also have a delay in further treatment. Together with colleagues at three different Dutch hospitals, in Paper III, we looked at the prognostic and predictive value of T1-substaging. A T1-tumour invades the lamina propria, and we wanted to separate those with micro- from those with extensive invasion. We found that BCG-failure was more common among patients with extensive invasion. Furthermore, T1-substaging was associated with both high-grade recurrence-free and progression-free survival. Finally, in Paper IV, we wanted to investigate the prognostic value of two classical immunohistochemical markers, p53 and CK20, and compare them with previously investigated proliferation markers. p53 is a surrogate marker for mutations in the gene TP53, considered to be a main characteristic for muscle-invasive tumours. CK20 is a surrogate marker for luminal tumours in the molecular classification of bladder cancer, and is frequently used to distinguish reactive urothelial changes from urothelial carcinoma in situ. We found both positivity for p53 and CK20 to be significantly associated with stage progression, although not performing better than WHO grade and stage. The proliferation marker MAI, had the highest prognostic value in our study. Any combination of variables did not perform better in a multivariate analysis than MAI alone

The application of artificial intelligence and image analysis to novel prognostic classification systems of colorectal cancer

Summary: pp. IV-V

Towards Developing Computer Vision Algorithms and Architectures for Real-world Applications

abstract: Computer vision technology automatically extracts high level, meaningful information from visual data such as images or videos, and the object recognition and detection algorithms are essential in most computer vision applications. In this dissertation, we focus on developing algorithms used for real life computer vision applications, presenting innovative algorithms for object segmentation and feature extraction for objects and actions recognition in video data, and sparse feature selection algorithms for medical image analysis, as well as automated feature extraction using convolutional neural network for blood cancer grading. To detect and classify objects in video, the objects have to be separated from the background, and then the discriminant features are extracted from the region of interest before feeding to a classifier. Effective object segmentation and feature extraction are often application specific, and posing major challenges for object detection and classification tasks. In this dissertation, we address effective object flow based ROI generation algorithm for segmenting moving objects in video data, which can be applied in surveillance and self driving vehicle areas. Optical flow can also be used as features in human action recognition algorithm, and we present using optical flow feature in pre-trained convolutional neural network to improve performance of human action recognition algorithms. Both algorithms outperform the state-of-the-arts at their time. Medical images and videos pose unique challenges for image understanding mainly due to the fact that the tissues and cells are often irregularly shaped, colored, and textured, and hand selecting most discriminant features is often difficult, thus an automated feature selection method is desired. Sparse learning is a technique to extract the most discriminant and representative features from raw visual data. However, sparse learning with \textit{L1} regularization only takes the sparsity in feature dimension into consideration; we improve the algorithm so it selects the type of features as well; less important or noisy feature types are entirely removed from the feature set. We demonstrate this algorithm to analyze the endoscopy images to detect unhealthy abnormalities in esophagus and stomach, such as ulcer and cancer. Besides sparsity constraint, other application specific constraints and prior knowledge may also need to be incorporated in the loss function in sparse learning to obtain the desired results. We demonstrate how to incorporate similar-inhibition constraint, gaze and attention prior in sparse dictionary selection for gastroscopic video summarization that enable intelligent key frame extraction from gastroscopic video data. With recent advancement in multi-layer neural networks, the automatic end-to-end feature learning becomes feasible. Convolutional neural network mimics the mammal visual cortex and can extract most discriminant features automatically from training samples. We present using convolutinal neural network with hierarchical classifier to grade the severity of Follicular Lymphoma, a type of blood cancer, and it reaches 91\% accuracy, on par with analysis by expert pathologists. Developing real world computer vision applications is more than just developing core vision algorithms to extract and understand information from visual data; it is also subject to many practical requirements and constraints, such as hardware and computing infrastructure, cost, robustness to lighting changes and deformation, ease of use and deployment, etc.The general processing pipeline and system architecture for the computer vision based applications share many similar design principles and architecture. We developed common processing components and a generic framework for computer vision application, and a versatile scale adaptive template matching algorithm for object detection. We demonstrate the design principle and best practices by developing and deploying a complete computer vision application in real life, building a multi-channel water level monitoring system, where the techniques and design methodology can be generalized to other real life applications. The general software engineering principles, such as modularity, abstraction, robust to requirement change, generality, etc., are all demonstrated in this research.Dissertation/ThesisDoctoral Dissertation Computer Science 201

Interventional techniques in the management of persistent atrial fibrillation

Atrial fibrillation (AF) is a common cardiac rhythm problem experienced by patients and comprises an increasing demand on healthcare systems. AF is characterised by advanced neurohormonal remodelling in the atria resulting in dilation and variable degree of atrial fibrosis that can be measured by imaging techniques with difficulty in developing methods of identifying and quantifying left atrial (LA) fibrosis. LA fibrosis can be estimated by measuring LA scar using non-invasive imaging methods such as strain imaging in advanced echocardiography and in cardiac magnetic resonance (CMR) imaging. Achieving rhythm control strategy utilising catheter ablation (CA) has shown to be advantageous in improving quality of life (QOL) in patients with paroxysmal AF. The most effective method in management of AF has remained elusive in non-paroxysmal AF. Thoracoscopic surgical ablation (TSA) has been developed over the last decade by experienced surgeons with some promising early results but has not been investigated in long-standing persistent AF (LSPAF). I have attempted to answer some of the relevant questions that have remained in management of LSPAF by conducting a multicentre randomised control trial comparing efficacy between CA and TSA (CASA-AF RCT) and improvements in quality of life indices. In a sub-study, I measured LA volumes using echocardiography and CMR to determine reverse remodelling and LA function using tissue Doppler imaging and strain imaging to predict AF recurrence. In a CMR sub-study, a novel automatic LA segmentation algorithm was used to quantify LA fibrosis before and after ablation. I was able to quantify the response of the autonomic nervous system to targeted ganglionic plexi (GP) ablation as part of TSA compared to CA by measuring heart rate variability. I am hopeful that the knowledge gained from this thesis will help with an appropriate selection that will improve the management of patients with LSPAF.Open Acces

Machine Learning Approaches for Semantic Segmentation on Partly-Annotated Medical Images

Semantic segmentation of medical images plays a crucial role in assisting medical practitioners in providing accurate and swift diagnoses; nevertheless, deep neural networks require extensive labelled data to learn and generalise appropriately. This is a major issue in medical imagery because most of the datasets are not fully annotated. Training models with partly-annotated datasets generate plenty of predictions that belong to correct unannotated areas that are categorised as false positives; as a result, standard segmentation metrics and objective functions do not work correctly, affecting the overall performance of the models. In this thesis, the semantic segmentation of partly-annotated medical datasets is extensively and thoroughly studied. The general objective is to improve the segmentation results of medical images via innovative supervised and semi-supervised approaches. The main contributions of this work are the following. Firstly, a new metric, specifically designed for this kind of dataset, can provide a reliable score to partly-annotated datasets with positive expert feedback in their generated predictions by exploiting all the confusion matrix values except the false positives. Secondly, an innovative approach to generating better pseudo-labels when applying co-training with the disagreement selection strategy. This method expands the pixels in disagreement utilising the combined predictions as a guide. Thirdly, original attention mechanisms based on disagreement are designed for two cases: intra-model and inter-model. These attention modules leverage the disagreement between layers (from the same or different model instances) to enhance the overall learning process and generalisation of the models. Lastly, innovative deep supervision methods improve the segmentation results by training neural networks one subnetwork at a time following the order of the supervision branches. The methods are thoroughly evaluated on several histopathological datasets showing significant improvements