From Fully-Supervised, Single-Task to Scarcely-Supervised, Multi-Task Deep Learning for Medical Image Analysis

Image analysis based on machine learning has gained prominence with the advent of deep learning, particularly in medical imaging. To be effective in addressing challenging image analysis tasks, however, conventional deep neural networks require large corpora of annotated training data, which are unfortunately scarce in the medical domain, thus often rendering fully-supervised learning strategies ineffective.This thesis devises for use in a variety of medical image analysis applications a series of novel deep learning methods, ranging from fully-supervised, single-task learning to scarcely-supervised, multi-task learning that makes efficient use of annotated training data. Specifically, its main contributions include (1) fully-supervised, single-task learning for the segmentation of pulmonary lobes from chest CT scans and the analysis of scoliosis from spine X-ray images; (2) supervised, single-task, domain-generalized pulmonary segmentation in chest X-ray images and retinal vasculature segmentation in fundoscopic images; (3) largely-unsupervised, multiple-task learning via deep generative modeling for the joint synthesis and classification of medical image data; and (4) partly-supervised, multiple-task learning for the combined segmentation and classification of chest and spine X-ray images

Lumbosacral transitional vertebrae morphology: a South African population

Lumbosacral transitional vertebrae (LSTV) are defined as congenital anatomical variations, observed unilaterally or bilaterally, in which the transverse process of the last lumbar vertebra exhibits signs of dysplasia evident as increased craniocaudal height, with varying degrees of articulation or fusion to the ‘first' sacral vertebra. Such variations give rise to vertebral morphology that may display lumbar or sacral characteristics at the terminal lumbar spine, together with subsequent enumeration variation. The purpose of this study was to establish baseline data on the prevalence rates of LSTV and to describe the morphological characteristics (Type, subtype, frequency of side and spinal enumeration) of LSTV in the South African population. This study was subdivided into two main sections, namely Part 1: medical imaging appraisal and Part 2: osteological morphology appraisal. In Part 1, both retrospective and prospective cohort randomised sampling methods of data collection of medical images were used. The appraisal of the medical images included radiographs, magnetic resonance imagers and computerised tomography scans. Prevalence rates, utilising the Castellvi et al. (1984) classification, were established via radiographs only. Additionally, lumbar spine enumeration, namely lumbarisation and sacralisation, was made through the appraisal of lumbar radiographs. Images were obtained from medical radiology practices located at Groote Schuur Hospital in Cape Town, Western Cape Province and Charlotte Maxeke Johannesburg Academic Hospital in Johannesburg, Gauteng Province. The total imaging cohort included 3096 individuals of which 308 individuals (10%) were found to contain LSTV. Prevalence rates were further evaluated by subdivision of the three largest ancestries in South Africa. Ancestries were classified as African (n=1032), Mixed (n=1032) and European (n=1032). The prevalence of LSTV in the three ancestral groups was 10.5%, 9.3% and 9.9% respectively and the sex distribution was greater in females (52.1%) then in males (47.9%). The morphological assessment found the prevalence of LSTV by Type was Type II (67.9%) followed by Types III (27.6%) and IV (4.5%). The most frequent subtype by prevalence was Type IIA (41.9%) followed by Type IIB (26%), Type IIIB (21.8%), and Type IV (5.8%). Additionally, the frequency of side was bilateral (47.7%), left (26.6%), right (21.1%), and other (4.5%). Comparison of ancestry and spinal enumeration analyses established statistical significance for individuals of African-ancestry (67.0%) and Mixed-ancestry (72.9%) both of which demonstrated a greater affinity of prevalence for sacralisation (p=0.008), with a small effect size (V=0.178) over the European-ancestry subgroup (52.4%). Furthermore, a statistical significance with a medium effect size (V=0.256) was found in males (p=0.010) when comparing ancestry and spinal enumeration between sexes. In Part 2, a systematic search of the total cadaveric skeletal collection housed at the University of Witwatersrand (the Dart Collection of skeletons) yielded 1797 human skeletal specimens of between 21 and 65 years of age at time of death. One-hundred and fourteen skeletal remains were identified as containing LSTV. Damage and loss of vertebral elements resulted in a subset of 91 LSTV for study. A sex balanced control group cohort of 30 males and 30 females was selected at random from the Dart Collection for comparative analyses. A number of osteometric measurements were evaluated comparing the LSTV and control group cohorts. Numerous osteometric comparisons were statistically significant highlighting the many changes in lumbar and sacral morphology associated with LSTV. There are several original findings to emerge. Thisis the first study to establish the prevalence of LSTV in a large sample from the South African population, subdivided into the three largest ancestral groups. Novel findings associated with LSTV include iliolumbar articulation, bipartition of the sacral foramen, intra-articular vacuum phenomenon of accessory articulations of LSTV, enlargement of the contralateral TVP associated with Types III and IV LSTV, lumbar ossified bridging syndrome and a novel complex named by the researcher as the transverso-sacro-iliac articulation. Furthermore, the researcher has proposed three modifications to the Castellvi et al. (1984) classification, namely (1) that there should be a sub-classification of the Type IV LSTV into right and left nomenclature, (2) the inclusion of a new subtype of Type II LSTV morphology, a unilateral right or left iliolumbar articulation associated with contralateral Type IIA morphology, and (3) a modified morphological classification of LSTV based on the presence of an extended sacroiliac articulation either directly or via the transverso-sacro-iliac articulation. The latter effectively increases the size of the sacroiliac joint and is thought to increase spinopelvic stability. The transverso-sacroiliac articulation was demonstrated for all clinically significant LSTV Types (II-IV), both unilateral (right or left) and bilateral. Finally, this is the first study to incorporate an in situ and an ex situ study in the same population by examining spinal morphology of LSTV using medical images and skeletal remains for descriptive analyses

Direction Selectivity and Receptive Fields of Zebrafish Tectal and Pretectal Neurons

Optic flow processing by neurons in the diencephalic pretectum is essential for visually guided behaviours in vertebrates, such as the optokinetic and optomotor responses. Animals actively stabilize both their gaze and position relative to their surroundings when exposed to translational and rotational stimuli. Recently, pretectal neurons distinguishing these moving patterns have been identified in the zebrafish brain and they are thought to mediate downstream motor outputs. It is still unclear whether binocular stimulus motion in other planes besides the horizontal plane is also represented in the zebrafish brain. Furthermore, while receptive field sizes and centres of tectal neurons have been reported, those of zebrafish pretectal neurons remain mainly elusive. We elucidate these crucial features with in vivo calcium imaging. First, we find that both pretectal and tectal neurons are each tuned to one out of four (roughly equally spaced) preferred directions. No anatomical segregation of direction-selective tectal neurons was identified. Second, we identified neurons responding to specific translational or rotational whole-field patterns by presenting all possible binocular combinations of the four (monocularly) preferred stimulus directions to both eyes of the fish. These binocular selective neurons could – in principle – directly instruct appropriate compensatory eye and tail movements during optokinetic and optomotor behaviour, respectively. Furthermore, monocular receptive field mapping shows that the vast majority of tectal motion-sensitive neurons are tuned to small-size motion, many with reduced neural activities when the motion-covered region increases. The visual space of the small-size tectal receptive fields is over-represented in the nasal-dorsal visual field. In contrast, many pretectal neurons have large-sized receptive fields (> 60°x30°, in azimuth, and elevation) with centres of receptive fields in the ventral visual field. Finally, besides full-field motion, the larval zebrafish optomotor response was preferably evoked by binocular forward translational motion located in the ventral temporal visual field, which mainly overlaps with the receptive filed centres of the pretectal large-size receptive fields. Our study characterizes fundamental features of tectal and pretectal information processing and provides the basis for further investigations into visuomotor transformations in zebrafish

A graph-based approach for the retrieval of multi-modality medical images

Medical imaging has revolutionised modern medicine and is now an integral aspect of diagnosis and patient monitoring. The development of new imaging devices for a wide variety of clinical cases has spurred an increase in the data volume acquired in hospitals. These large data collections offer opportunities for search-based applications in evidence-based diagnosis, education, and biomedical research. However, conventional search methods that operate upon manual annotations are not feasible for this data volume. Content-based image retrieval (CBIR) is an image search technique that uses automatically derived visual features as search criteria and has demonstrable clinical benefits. However, very few studies have investigated the CBIR of multi-modality medical images, which are making a monumental impact in healthcare, e.g., combined positron emission tomography and computed tomography (PET-CT) for cancer diagnosis. In this thesis, we propose a new graph-based method for the CBIR of multi-modality medical images. We derive a graph representation that emphasises the spatial relationships between modalities by structurally constraining the graph based on image features, e.g., spatial proximity of tumours and organs. We also introduce a graph similarity calculation algorithm that prioritises the relationships between tumours and related organs. To enable effective human interpretation of retrieved multi-modality images, we also present a user interface that displays graph abstractions alongside complex multi-modality images. Our results demonstrated that our method achieved a high precision when retrieving images on the basis of tumour location within organs. The evaluation of our proposed UI design by user surveys revealed that it improved the ability of users to interpret and understand the similarity between retrieved PET-CT images. The work in this thesis advances the state-of-the-art by enabling a novel approach for the retrieval of multi-modality medical images

Musculoskeletal Diseases 2021-2024

This open access book focuses on imaging of the musculoskeletal diseases. Over the last few years, there have been considerable advances in this area, driven by clinical as well as technological developments. The authors are all internationally renowned experts in their field. They are also excellent teachers, and provide didactically outstanding chapters. The book is disease-oriented and covers all relevant imaging modalities, with particular emphasis on magnetic resonance imaging. Important aspects of pediatric imaging are also included. IDKD books are completely re-written every four years. As a result, they offer a comprehensive review of the state of the art in imaging. The book is clearly structured with learning objectives, abstracts, subheadings, tables and take-home points, supported by design elements to help readers easily navigate through the text. As an IDKD book, it is particularly valuable for general radiologists, radiology residents, and interventional radiologists who want to update their diagnostic knowledge, and for clinicians interested in imaging as it relates to their specialty

Contributions for a new body representation paradigm in pattern design. Generation of basic patterns after the mobile body

Tese apresentada à Faculdade de Arquitectura de Lisboa da Universidade Técnica de Lisboa, para obtenção do grau de Doutor em Design

A systems genetics approach to the characterization of differential low dose radiation responses in BXD recombinant inbred mice

High doses of radiation (HDR) are clearly detrimental to human health, but relatively little is known about the health consequences following exposure to low doses of radiation (LDR, \u3c10cGy). Understanding the risks associated with LDR is of great importance to the general public due to the recent dramatic increase in diagnostic radiological imaging. While HDR clearly suppress immune function, there is evidence that LDR can be immunostimulatory. Within the organism, defining the consequences of LDR is further complicated by the impact of genetic background, particularly in systems such as the immune system for which both radiosensitivity and genetic effects are profound. We addressed the issue of genetic susceptibility to LDR using the immune system as a target system and treated the LDR response as a complex trait analyzed using a systems genetics framework. Using the BXD recombinant inbred strain mouse panel as a genetic reference population allowed us to address the radiation response within the context of natural genetic variation. Our overarching hypothesis is that, within a population, the immunological effects of LDR exposure depend in part on the individual’s baseline immunoprofile and gene expression which are ultimately dependent upon genetic background. We began by establishing the immunophenotypic variation (i.e., T:B cell ratio, CD4:CD8 ratio) within the BXD panel and used baseline spleen transcriptome profiling to identify putative candidate genes controlling these traits, specifically Acp1 and Ptprk for CD4:CD8 ratio. The same set of BXD strains was exposed to LDR (10cGy gamma radiation) to determine effects on immune function and oxidative stress. LDR significantly enhanced neutrophil phagocytosis in a manner that was independent of genetic background. In contrast, genetic background significantly impacted LDR-induced changes in spleen superoxide dismutase activity. By integrating these results with our previous analyses of BXD RI strains, we have demonstrated that baseline expression of Sod2 correlates with LDR-induced SOD activity, and baseline CD4:CD8 ratio is inversely correlated with LDR-induced neutrophil phagocytosis. In addition, spleen transcriptomic data from the BXD parental strains further highlighted the impact of genetic background on LDR responses. These data provide the groundwork for predicting LDR responses using baseline expression, immunophenotypes, and/or genotype