A framework for tumor segmentation and interactive immersive visualization of medical image data for surgical planning

This dissertation presents the framework for analyzing and visualizing digital medical images. Two new segmentation methods have been developed: a probability based segmentation algorithm, and a segmentation algorithm that uses a fuzzy rule based system to generate similarity values for segmentation. A visualization software application has also been developed to effectively view and manipulate digital medical images on a desktop computer as well as in an immersive environment.;For the probabilistic segmentation algorithm, image data are first enhanced by manually setting the appropriate window center and width, and if needed a sharpening or noise removal filter is applied. To initialize the segmentation process, a user places a seed point within the object of interest and defines a search region for segmentation. Based on the pixels\u27 spatial and intensity properties, a probabilistic selection criterion is used to extract pixels with a high probability of belonging to the object. To facilitate the segmentation of multiple slices, an automatic seed selection algorithm was developed to keep the seeds in the object as its shape and/or location changes between consecutive slices.;The second segmentation method, a new segmentation method using a fuzzy rule based system to segment tumors in a three-dimensional CT data was also developed. To initialize the segmentation process, the user selects a region of interest (ROI) within the tumor in the first image of the CT study set. Using the ROI\u27s spatial and intensity properties, fuzzy inputs are generated for use in the fuzzy rules inference system. Using a set of predefined fuzzy rules, the system generates a defuzzified output for every pixel in terms of similarity to the object. Pixels with the highest similarity values are selected as tumor. This process is automatically repeated for every subsequent slice in the CT set without further user input, as the segmented region from the previous slice is used as the ROI for the current slice. This creates a propagation of information from the previous slices, used to segment the current slice. The membership functions used during the fuzzification and defuzzification processes are adaptive to the changes in the size and pixel intensities of the current ROI. The proposed method is highly customizable to suit different needs of a user, requiring information from only a single two-dimensional image.;Segmentation results from both algorithms showed success in segmenting the tumor from seven of the ten CT datasets with less than 10% false positive errors and five test cases with less than 10% false negative errors. The consistency of the segmentation results statistics also showed a high repeatability factor, with low values of inter- and intra-user variability for both methods.;The visualization software developed is designed to load and display any DICOM/PACS compatible three-dimensional image data for visualization and interaction in an immersive virtual environment. The software uses the open-source libraries DCMTK: DICOM Toolkit for parsing of digital medical images, Coin3D and SimVoleon for scenegraph management and volume rendering, and VRJuggler for virtual reality display and interaction. A user can apply pseudo-coloring in real time with multiple interactive clipping planes to slice into the volume for an interior view. A windowing feature controls the tissue density ranges to display. A wireless gamepad controller as well as a simple and intuitive menu interface control user interactions. The software is highly scalable as it can be used on a single desktop computer to a cluster of computers for an immersive multi-projection virtual environment. By wearing a pair of stereo goggles, the surgeon is immersed within the model itself, thus providing a sense of realism as if the surgeon is inside the patient.;The tools developed in this framework are designed to improve patient care by fostering the widespread use of advanced visualization and computational intelligence in preoperative planning, surgical training, and diagnostic assistance. Future work includes further improvements to both segmentation methods with plans to incorporate the use of deformable models and level set techniques to include tumor shape features as part of the segmentation criteria. For the surgical planning components, additional controls and interactions with the simulated endoscopic camera and the ability to segment the colon or a selected region of the airway for a fixed-path navigation as a full virtual endoscopy tool will also be implemented. (Abstract shortened by UMI.

A parallel implementation of particle swarm optimization using digital pheromones

A parallel implementation of Particle Swarm Optimization (PSO) using digital pheromones to coordinate the movements of the swarm within an n-dimensional design space is presented in this paper. Digital pheromones are models simulating real pheromones emitted by insects for communication to indicate a source of food or a nesting location. This principle of communication and organization between each insect in a swarm offers substantial improvement when integrated into a Particle Swarm Optimization algorithm. Digital swarms are used to search a design space with digital pheromones aiding communication within the swarm to improve search efficiency. With statistical analysis, the pheromone strength in a region of the design space is determined. The swarm then reacts accordingly based on the probability that this region may contain an optimum. When implemented in a parallel computing architecture, significant performance increases were observed. This paper presents the method development and results from several test cases

Contagion and downside risk in the REIT market during the subprime mortgage crisis

This study empirically tests the contagion effects in stock and real estate investment trust (REIT) markets during the subprime mortgage crisis by using daily stock- and REIT-markets data from the following countries and international bodies: the United States, the European Union, Japan, Hong Kong, Singapore, Australia, and the global REIT market. We found a significant and positive dynamic conditional correlation (DCC) coefficient between stock returns and REIT returns. The results revealed that the REIT markets responded early to market shocks and that the variances were higher in the post-crisis period than in the pre-crisis period. Evidence supporting the contagion effects includes increases in the means of the DCC coefficients during the post-crisis period. The Japanese and Australian REIT markets possess the lowest time-varying downside systematic risks. We also demonstrated that the “DCC E-beta” captures more significant downside linkages between market portfolios and expected REIT returns than does the standard CAPM beta

Epinephrine administration via a laryngeal mask airway: what is the optimal dose?

Background. The aim of this animal study was to clarify the effects of laryngeal mask airway (LMA)-administrated epinephrine and to assess the optimal dose. Methods. Thirty pigs were anesthetized and intubated with a cuffed tracheal tube (TT) and an LMA. Then they were assigned to one of five groups. The control group received distilled water 10 mL via the TT; the TT group received epinephrine 50 μg/kg via the TT; and the other three groups received two, four or six times the TT dose of epinephrine via the LMA. Heart rate (HR) and arterial pressure were monitored before and after drug administration for 15 minutes. Results. After epinephrine administration, the LMA-6 and TT groups had elevated systolic, diastolic and mean arterial pressures at 1 min and there was no significant difference between the two groups. In the TT group, these parameters peaked at 2 min then declined rapidly. In the LMA-6 group, they increased more slowly, and then maintained a plateau. The control, LMA-2 and LMA-4 groups failed to display significant persistent (>2 min) hemodynamic changes. Conclusions. We could not identify an optimal LMA-administrated epinephrine dose. The TT route is suitable when a high peak drug effect is required and the LMA route may be preferable if a persistent plateau effect is desired. Effective LMA administration of drugs may require larger doses than those given via TT

An exclusively dopamine secreting paraganglioma in the retroperitoneum: a first clinical case in Korea

Exclusively dopamine producing retroperitoneal paragangliomas are extremely rare. We have experienced the first Korean case managed successfully based on the proper evaluation. A 26-year-old female patient came to our attention after the accidental detection of an adrenal mass. She had no symptoms and denied any family history. Laboratory evaluations were normal but serum dopamine (425 ng/L) and 24-hour urine dopamine levels (1,565.3 µg/day) were elevated. She underwent laparoscopic right adrenalectomy. Histopathological diagnosis was a paraganglioma. After operation, dopamine levels in serum and 24-hour urine dropped to 0.09 ng/L and 388.4 µg/day. Dopamine producing paraganglioma elicit no clinical symptoms. Only the dopamine level is elevated in serum and 24-hour urine samples. Surgical resection without using preoperative alpha blockage is the treatment of choice. The prognosis for patients with this tumor tends to be poor because the diagnosis is usually delayed due to lack of symptoms

Severe fever with thrombocytopenia syndrome phlebovirus non-structural protein activates TPL2 signalling pathway for viral immunopathogenesis

Severe fever with thrombocytopenia syndrome phlebovirus (SFTSV), listed in the World Health Organization Prioritized Pathogens, is an emerging phlebovirus with a high fatality . Owing to the lack of therapies and vaccines , there is a pressing need to understand SFTSV pathogenesis. SFSTV non-structural protein (NSs) has been shown to block type I interferon induction and facilitate disease progression . Here, we report that SFTSV-NSs targets the tumour progression locus 2 (TPL2)-A20-binding inhibitor of NF-κB activation 2 (ABIN2)-p105 complex to induce the expression of interleukin-10 (IL-10) for viral pathogenesis. Using a combination of reverse genetics, a TPL2 kinase inhibitor and Tpl2 mice showed that NSs interacted with ABIN2 and promoted TPL2 complex formation and signalling activity, resulting in the marked upregulation of Il10 expression. Whereas SFTSV infection of wild-type mice led to rapid weight loss and death, Tpl2 mice or Il10 mice survived an infection. Furthermore, SFTSV-NSs P A and SFTSV-NSs K R that lost the ability to induce TPL2 signalling and IL-10 production showed drastically reduced pathogenesis. Remarkably, the exogenous administration of recombinant IL-10 effectively rescued the attenuated pathogenic activity of SFTSV-NSs P A, resulting in a lethal infection. Our study demonstrates that SFTSV-NSs targets the TPL2 signalling pathway to induce immune-suppressive IL-10 cytokine production as a means to dampen the host defence and promote viral pathogenesis

Destabilization of β Cell FIT2 by saturated fatty acids alter lipid droplet numbers and contribute to ER stress and diabetes

Western-type diets are linked to obesity and diabetes partly because of their high–saturated fatty acid (SFA) content. We found that SFAs, but not unsaturated fatty acids (USFAs), reduced lipid droplets (LDs) within pancreatic β cells. Mechanistically, SFAs, but not USFAs, reduced LD formation by inducing S-acylation and proteasomal, mediated degradation of fat storage–inducing transmembrane protein 2 (FIT2), an endoplasmic reticulum (ER) resident protein important for LD formation. Targeted ablation of FIT2 reduced β cell LD numbers, lowered β cell ATP levels, reduced Ca(2+) signaling, dampened vesicle exocytosis, down-regulated β cell transcription factors, up-regulated unfolded protein response genes, and finally, exacerbated diet-induced diabetes in mice. Subsequent mass spectrometry studies revealed increased C16:0 ceramide accumulation in islets of diet-induced diabetes mice lacking β cell FIT2. Inhibition of ceramide synthases ameliorated the enhanced ER stress and improved insulin secretion. FIT2 was reduced in mouse diabetic islets, and separately, overexpression of FIT2 increased the number of intracellular LDs and rescued SFA-induced ER stress and apoptosis, thereby highlighting the protective role of FIT2 and LDs against β cell lipotoxicity

Single-Cell Analysis of Blood-Brain Barrier Response to Pericyte Loss

Rationale: Pericytes are capillary mural cells playing a role in stabilizing newly formed blood vessels during development and tissue repair. Loss of pericytes has been described in several brain disorders, and genetically induced pericyte deficiency in the brain leads to increased macromolecular leakage across the blood-brain barrier (BBB). However, the molecular details of the endothelial response to pericyte deficiency remain elusive. Objective: To map the transcriptional changes in brain endothelial cells resulting from lack of pericyte contact at single-cell level, and to correlate them with regional heterogeneities in BBB function and vascular phenotype. Methods and Results: We reveal transcriptional, morphological and functional consequences of pericyte absence for brain endothelial cells using a combination of methodologies, including single-cell RNA sequencing, tracer analyses and immunofluorescent detection of protein expression in pericyte-deficient adult Pdgfbret/ret mice. We find that endothelial cells without pericyte contact retain a general BBB-specific gene expression profile, however, they acquire a venous-shifted molecular pattern and become transformed regarding the expression of numerous growth factors and regulatory proteins. Adult Pdgfbret/ret brains display ongoing angiogenic sprouting without concomitant cell proliferation providing unique insights into the endothelial tip cell transcriptome. We also reveal heterogeneous modes of pericyte-deficient BBB impairment, where hotspot leakage sites display arteriolar-shifted identity and pinpoint putative BBB regulators. By testing the causal involvement of some of these using reverse genetics, we uncover a reinforcing role for angiopoietin 2 at the BBB. Conclusions: By elucidating the complexity of endothelial response to pericyte deficiency at cellular resolution, our study provides insight into the importance of brain pericytes for endothelial arterio-venous zonation, angiogenic quiescence and a limited set of BBB functions. The BBB-reinforcing role of ANGPT2 is paradoxical given its wider role as TIE2 receptor antagonist and may suggest a unique and context-dependent function of ANGPT2 in the brain