Pixel-level semantic understanding of ophthalmic images and beyond

Computer-assisted semantic image understanding constitutes the substrate of applications that range from biomarker detection to intraoperative guidance or street scene understanding for self-driving systems. This PhD thesis is on the development of deep learning-based, pixel-level, semantic segmentation methods for medical and natural images. For vessel segmentation in OCT-A, a method comprising iterative refinement of the extracted vessel maps and an auxiliary loss function that penalizes structural inaccuracies, is proposed and tested on data captured from real clinical conditions comprising various pathological cases. Ultimately, the presented method enables the extraction of a detailed vessel map of the retina with potential applications to diagnostics or intraoperative localization. Furthermore, for scene segmentation in cataract surgery, the major challenge of class imbalance is identified among several factors. Subsequently, a method addressing it is proposed, achieving state-of-the-art performance on a challenging public dataset. Accurate semantic segmentation in this domain can be used to monitor interactions between tools and anatomical parts for intraoperative guidance and safety. Finally, this thesis proposes a novel contrastive learning framework for supervised semantic segmentation, that aims to improve the discriminative power of features in deep neural networks. The proposed approach leverages contrastive loss function applied both at multiple model layers and across them. Importantly, the proposed framework is easy to combine with various model architectures and is experimentally shown to significantly improve performance on both natural and medical domain

Σχολικός Εκφοβισμός και Ψυχοκοινωνική Προσαρμογή

Ο σχολικός εκφοβισμός αποτελεί ένα μείζον θέμα που έχει απασχολήσει πλήθος ερευνητών, καθώς έχει διαπιστωθεί πως συνδέεται με πολλαπλές δυσχερείς επιπτώσεις στην ανάπτυξη των συμμετεχόντων στις διεργασίες αυτού. Σκοπός της παρούσας έρευνας ήταν η διερεύνηση της σχέσης μεταξύ διαστάσεων της ψυχοκοινωνικής προσαρμογής και του εκφοβισμού, της θυματοποίησης που αναφέρονται από παιδιά σχολικής ηλικίας. Για τη διεξαγωγή της έρευνας λήφθησαν, επιπλέον, υπόψη παράγοντες φύλου και άλλοι δημογραφικοί παράγοντες. Το δείγμα της έρευνας αποτελείτο από 158 παιδιά (81 αγόρια/ 77 κορίτσια) της Ε’ και ΣΤ’ τάξης του δημοτικού σχολείου. Για τη μέτρηση της μεταβλητής της ψυχοκοινωνικής προσαρμογής χρησιμοποιήθηκε το Τεστ Ψυχοκοινωνικής Προσαρμογής (Χατζηχρήστου, Πολυχρόνη, Μπεζεβέγκης, & Μυλωνάς, 2008) και για τη μέτρηση του εκφοβισμού και της θυματοποίησης χρησιμοποιήθηκαν οι ελληνικές εκδόσεις των Κλιμάκων Εκφοβισμού (Bullying Behavior Scale, Austin & Joseph, 1996) και Θυματοποίησης (Peer-Victimization Scale, Neary & Joseph, 1994). Από τις αναλύσεις των δεδομένων φάνηκε πως τα παιδιά που δηλώνουν ότι ασκούν εκφοβισμό ανέφεραν χαμηλότερη σχολική επάρκεια και αυτοαντίληψη και περισσότερα προβλήματα συμπεριφοράς, σε σχέση με τους μη συμμετέχοντες σε διεργασίες εκφοβισμού/θυματοποίησης, ενώ ανέφεραν παρόμοια επίπεδα γενικής αυτοεκτίμησης με αυτούς. Τα παιδιά που δηλώνουν πως υφίστανται εκφοβισμό, από την άλλη, ανέφεραν χαμηλότερα επίπεδα κοινωνικής, συναισθηματικής επάρκειας και αυτοαντίληψης, ενώ τα παιδιά που δηλώνουν πως και ασκούν και υφίστανται εκφοβισμό ανέφεραν χαμηλότερη κοινωνική επάρκεια και αυτοαντίληψη, σε σχέση με τους μη συμμετέχοντες.Bullying in school constitutes a major issue which has interested a plethora of researchers, as it has been ascertained that it is connected with multiple negative effects on the growth of the participants in its processes. The purpose of the present study was to examine the relationship between aspects of psychosocial adjustment and bullying, victimization reported by school-aged children. For the conduct of the study factors of sex and other demographic factors were taken into consideration. The sample of the study consisted of 158 children (81 boys/ 77 girls) from the fifth and sixth grades of elementary school. For the measurement of the variable of psychosocial adjustment the Test of Psychosocial Adjustment (Hatzichristou, Polychroni, Besevegis, & Mylonas, 2008) was used and for the measurement of bullying and victimization the greek versions of the Bullying Behavior Scale (Austin & Joseph, 1996) and the Peer-Victimization Scale (Neary & Joseph, 1994) were used. From the review of the data it was revealed that children who claim they bully reported lower school competence and self-concept and more behavioral problems, compared to non-paticipants in bullying/victimization processes, whereas they reported similar levels of self-esteem with them. Children who claim being bullied, on the other hand, reported lower levels of social, emotional competence and self-concept, while the children who claim they both bully and are being bullied reported lower social competence and self-concept, compared to the non-participants

Stochastic Segmentation with Conditional Categorical Diffusion Models

Semantic segmentation has made significant progress in recent years thanks to deep neural networks, but the common objective of generating a single segmentation output that accurately matches the image's content may not be suitable for safety-critical domains such as medical diagnostics and autonomous driving. Instead, multiple possible correct segmentation maps may be required to reflect the true distribution of annotation maps. In this context, stochastic semantic segmentation methods must learn to predict conditional distributions of labels given the image, but this is challenging due to the typically multimodal distributions, high-dimensional output spaces, and limited annotation data. To address these challenges, we propose a conditional categorical diffusion model (CCDM) for semantic segmentation based on Denoising Diffusion Probabilistic Models. Our model is conditioned to the input image, enabling it to generate multiple segmentation label maps that account for the aleatoric uncertainty arising from divergent ground truth annotations. Our experimental results show that CCDM achieves state-of-the-art performance on LIDC, a stochastic semantic segmentation dataset, and outperforms established baselines on the classical segmentation dataset Cityscapes.Comment: Code available at https://github.com/LarsDoorenbos/ccdm-stochastic-segmentatio

Surgical biomicroscopy-guided intra-operative optical coherence tomography (iOCT) image super-resolution

Purpose: Intra-retinal delivery of novel sight-restoring therapies will require the precision of robotic systems accompanied by excellent visualisation of retinal layers. Intra-operative Optical Coherence Tomography (iOCT) provides cross-sectional retinal images in real time but at the cost of image quality that is insufficient for intra-retinal therapy delivery.This paper proposes a super-resolution methodology that improves iOCT image quality leveraging spatiotemporal consistency of incoming iOCT video streams. Methods: To overcome the absence of ground truth high-resolution (HR) images, we first generate HR iOCT images by fusing spatially aligned iOCT video frames. Then, we automatically assess the quality of the HR images on key retinal layers using a deep semantic segmentation model. Finally, we use image-to-image translation models (Pix2Pix and CycleGAN) to enhance the quality of LR images via quality transfer from the estimated HR domain. Results: Our proposed methodology generates iOCT images of improved quality according to both full-reference and no-reference metrics. A qualitative study with expert clinicians also confirms the improvement in the delineation of pertinent layers and in the reduction of artefacts. Furthermore, our approach outperforms conventional denoising filters and the learning-based state-of-the-art. Conclusions: The results indicate that the learning-based methods using the estimated, through our pipeline, HR domain can be used to enhance the iOCT image quality. Therefore, the proposed method can computationally augment the capabilities of iOCT imaging helping this modality support the vitreoretinal surgical interventions of the future

Cytochrome c as a potentially clinical useful marker of mitochondrial and cellular damage

Mitochondria are evolutionary endosymbionts derived from bacteria. Thus they bear molecules, such as mitochondrial DNA that contains CpG DNA repeats and N-formyl peptides, found in bacteria. Upon cell necrosis or apoptosis these molecules are released into the interstitial space and the circulation and recognized by the immune cells through the same receptors that recognize pathogen associated molecular patterns, leading to inflammation. Other mitochondrial molecules are not of bacterial origin, but they may serve as danger associated molecular patterns (DAMPs) when due to cell injury are translocated into inappropriate compartments. There they are recognized by pattern recognition receptors of the immune cells. Cytochrome c is such a molecule. In this review experimental and clinical data are presented that confirms cytochrome c release into the extracellular space in pathological conditions characterized by cell death. This indicates that serum cytochrome c, which can be easily measured, may be a clinically useful marker for diagnosing and assessing the severity of such pathological entities. Reasonably, detection of high cytochrome c level into the circulation means release of various other molecules that serves as DAMPs when found extracellularly, the mitochondrial DNA and N-formyl peptides included. Finally, because the release of this universally found compound into the extracellular space makes cytochrome c an ideal molecule to play the role of a DAMP per se, the available experimental and clinical data that support such a role are provided

Asymptomatic hyperuricemia and chronic kidney disease: Narrative review of a treatment controversial

Today there is plausible evidence both on experimental and epidemiological basis, that hyperuricemia represents a risk factor for the development and progression of chronic kidney disease (CKD). Nevertheless, the role of serum uric acid lowering treatment in CKD is still a matter of serious controversy. Review of randomised controlled trials, suggests that there may be an improvement of renal function with allopurinol treatment in CKD stage 3–5. However, these studies have included a relatively limited number of participants and provide insufficient information on adverse events and on the incidence of the end stage renal disease. Therefore, before adequately powered randomised, placebo-controlled trials are completed we cannot recommend treating asymptomatic hyperuricemia in patients with CKD

Crystalline silica activates the T-cell and the B-cell antigen receptor complexes and induces T-cell and B-cell proliferation

Silicosis is an occupational fibrotic lung disease, which is associated with an increased incidence of autoimmune diseases. The effect of crystalline silica on the immune system is thought to be mediated by the antigen presenting cells. However, the direct effect of silica on T-cells and B-cells has not been evaluated adequately. For this purpose, CD4(+)T-cells and B-cells from 10 healthy individuals were isolated and cultured with or without Min-U-Sil 5. Cell proliferation was assessed with BrdU assay. In cell proliferation experiments, tacrolimus, an inhibitor of the signal transduction derived from the activation of the T-cell or the B-cell antigen receptor (BCR) complex, was also used. The levels of phosphorylated zeta and phosphorylated Igα, indicative of the T-cell and BCR complex activation respectively, and of the transcription factor c-Myc, required for cell proliferation, were assessed by Western blotting. Crystalline silica triggered CD4(+)T-cell and B-cell proliferation, while tacrolimus significantly decreased the silica-induced proliferation in both cell types. Crystalline silica enhanced the level of phosphorylated zeta and phosphorylated Igα in CD4(+)T-cells and B-cells, respectively. In both cell types, treatment with silica increased c-Myc expression. Thus, crystalline silica may induce T-cell and B-cell proliferation by activating T-cell and BCR complexes. It is likely that the direct activation of CD4(+)T-cells and B-cells by silica crystals detected in this study circumvents many self-tolerance check-points and offers a mechanistic explanation for the crystalline silica-induced autoimmune diseases

Cell Death Patterns Due to Warm Ischemia or Reperfusion in Renal Tubular Epithelial Cells Originating from Human, Mouse, or the Native Hibernator Hamster

Ischemia⁻reperfusion injury contributes to the pathogenesis of many diseases, with acute kidney injury included. Hibernating mammals survive prolonged bouts of deep torpor with a dramatic drop in blood pressure, heart, and breathing rates, interspersed with short periods of arousal and, consequently, ischemia⁻reperfusion injury. Clarifying the differences under warm anoxia or reoxygenation between human cells and cells from a native hibernator may reveal interventions for rendering human cells resistant to ischemia⁻reperfusion injury. Human and hamster renal proximal tubular epithelial cells (RPTECs) were cultured under warm anoxia or reoxygenation. Mouse RPTECs were used as a phylogenetic control for hamster cells. Cell death was assessed by both cell imaging and lactate dehydrogenase (LDH) release assay, apoptosis by cleaved caspase-3, autophagy by microtubule-associated protein 1-light chain 3 B II (LC3B-II) to LC3B-I ratio, necroptosis by phosphorylated mixed-lineage kinase domain-like pseudokinase, reactive oxygen species (ROS) fluorometrically, and lipid peroxidation, the end-point of ferroptosis, by malondialdehyde. Human cells died after short periods of warm anoxia or reoxygenation, whereas hamster cells were extremely resistant. In human cells, apoptosis contributed to cell death under both anoxia and reoxygenation. Although under reoxygenation, ROS increased in both human and hamster RPTECs, lipid peroxidation-induced cell death was detected only in human cells. Autophagy was observed only in human cells under both conditions. Necroptosis was not detected in any of the evaluated cells. Clarifying the ways that are responsible for hamster RPTECs escaping from apoptosis and lipid peroxidation-induced cell death may reveal interventions for preventing ischemia⁻reperfusion-induced acute kidney injury in humans