There is a huge unmet clinical need for a new, safe and effective minimally invasive treatment for Acute Ascending Aortic Dissection (AAAD) (1). In 2012 AAAD has a mortality rate of 1-2% per hour within the first 24 hours, and even with contemporary surgical techniques, advanced intensive and post operative care, the mortality from AAAD following surgery in most series remains in the unacceptable range of 10-30% at 30 days (2;3). 28% of patients presenting with AAAD are denied life saving surgery often because of age or co-morbidity - medical therapy alone associated with an in hospital mortality rate in excess of 50% (2;4-6). Currently available endovascular stent grafts used in the descending thoracic and abdominal aorta are not adequately designed to be utilised within the ascending aorta. They have a large stowed diameter 22-25 French (F), with a rigid covering of either Dacron or ePTFE, and a stiff inflexible delivery system unlikely to traverse the aortic arch without complication. While the contemporary results of elective surgery for ascending thoracic aortic aneurysm (ATAA) are good, with an elective mortality of <5%, surgical results for AAAD have improved little over the last 20 years, with a 30 day mortality rate between 10-30% (3;7). With the emerging role of endovascular stent grafts in the treatment of thoracic aneurysm and dissection, with shorter hospital stays and improved outcomes I believe now is the time for the development of a percutaneous solution for AAAD. Potential ascending thoracic aortic graft (ATAG) designs must take into account the very close proximity of intimal tear to both the coronary arteries and aortic valve, allowing a 4 good proximal graft seal without compromising coronary flow or aortic valve competence. ATAG should have a low profile, with a thin non porous covering and a flexible delivery sheath with accurate and precise deployment characteristics. Following a literature review and novel anatomical data collection from computerised tomography (CT) and magnetic resonance imaging (MRI) scans of AAAD and ATAA patient cohorts, it seems that 3 embodiments of ATAG should be designed and developed, all sharing advanced core technologies including a laser-cut nitinol stent frame, thin polyurethane (PU) material covering and accurate and precise deployment mechanisms: 1) The “supra-coronary tubular ATAG”, for treating AAAD with an intimal tear in the ascending aorta, no coronary or aortic valve involvement and adequate landing zones above the coronary arteries and before the right brachiocephalic trunk (RBCT). It is likely that this graft will be capable of treating at least a third of all patients with AAAD (8). 2) The “inverted t-shirt ATAG” to proactively protect coronary artery flow and achieve proximal seal within the sinuses in patients with an intimal tear in close association or involving the coronary arteries. 3) The “valved ATAG” to treat patients who have significant aortic regurgitation (AR), to achieve a proximal seal at the annulus when anatomy suggests it would be difficult to achieve with embodiment 1) or 2), and in those patients who have a hugely dilated aortic root, so that the ATAG can seal proximally at a relatively normal annulus size, and seal distally at a normal ascending aorta diameter 5 proximal to the RBCT. This could be the treatment option for the 25-35% of AAAD patients who currently require aortic valve repair or replacement (9). The most complex of the 3 devices above is embodiment 2), the “inverted t-shirt ATAG”, as it must ensure proximal aortic seal within an often dilated sinus, without compromise to aortic valve and proactively protect both coronary arteries with 2 coronary sleeves. Basic proof of concept (PoC) of this embodiment has been demonstrated in vitro within a normal sized aortic glass model, with some important study limitations, nevertheless it does demonstrate that tracking an ATAG branched graft with 2 coronary sleeves is possible over 3 guidewires and deploying accurately within the aortic root under both direct vision and fluoroscopy. Following successful PoC deployment I then specified and had manufactured a 2nd Generation ATAG (2G ATAG), with a laser-cut nitinol frame, longitudinal tie bars, and a novel thin PU graft covering material. The 2G ATAG has been shown to have adequate radial strength when compared to competitor devices, and can be stowed to 28 F for deployment. During ATAG development 2 patents have been filed, and I wrote with Professor Rothman a successful NIHR I4I grant for £743,000 to take ATAG from the current 28 F 2G device, towards the goal of an 18 F device with bench testing, in vitro flow rig and deployment analysis, and in collaboration with the Royal Veterinary College (RVC) into an animal model over the next 3 years (beyond the scope of this thesis). I hope that within this next development cycle ATAG can be iterated into a device that might be ready to embark on a first in man (FIM) trial to offer the AAAD population an effective and less invasive treatment strategy.

The past decade has seen the release of numerous software packages aimed at enhancing anatomical education. However, there has been little research undertaken by the manufacturers of these products into the benefit or otherwise of these packages for student learning. In addition, while many of the existing software packages include interactive three-dimensional models, none of them truly offer virtual dissection i.e. the cutting through anatomical layers with a haptic (tactile) interface. This study investigated the haptic ‘dissection’ of a three dimensional digital model of the hand and wrist in anatomy education at both undergraduate (UG) and postgraduate (PG) levels. The model was used as a teaching and revision aid both prior to and after dissection of a real cadaver. A haptic enabled version of the model, allowing for real-time cutting was compared with a non-haptic version, using instead a keyboard and mouse ‘point and click’ style interface. Both versions were tested on students of gross anatomy in relation to test results and student experience. The model was based upon Computerised Tomography (CT) and photographic slice data from the Visible Human Project female data set. It was segmented and reconstructed using Amira® 5.2.2. From here each structure was exported as a separate STL file and imported into Geomagic Freeform® Modelling TM. Once imported into Freeform® Modelling TM, the individual structures each required varying degrees of re-modelling where detail had been lost during the segmentation process. Some smaller structures such as the nerves, veins and arteries were modelled freehand. The final model could be dissected using FreeForm® ModellingTM, the same software in which it was created. Using FreeForm® ModellingTM as a prototype VR dissector, each anatomical structure could be selected and virtually ‘dissected’ with the PHANTOM® Desktop™ haptic tool. Three methods of interacting with the model were identified: 1) using a cutting tool to cut through the selected layer; 2) using a selection paintball to first select and then delete the layer; and 3) using planes to cut the selected structure in standard anatomical views. The study ran over five successive years and was split into three discreet phases. Phase one compared the results of PG students across control, non-haptic and haptic groups. Phase two compared the results of UG students between control and haptic groups. Phase three compared the results of UG students across control, non-haptic and haptic groups. Due to small group sizes and a largely non-normal distributions the results were analysed using Mann-Whitney U tests. Results for all phases indicate that use of the model, both through haptic and non-haptic interfaces produced some significantly improved test results. The non-haptic version of the model performing equal or better than those with access to the haptic version. This is likely due to cognitive load being adversely affected by the addition of the haptic device. Some students reported that the haptic device was not intuitive to use and took some time to get used to, if at all. No student used either version of the model for more than five hours, with over 40% using it for less than one hour. It is possible that with increased exposure to the haptic device students may find it easier and thus beneficial. The findings of this study indicate that when used for a short period of time only ( < 5 hours) the haptic device may impede rather than enhance learning.

Diss.--Stuttgart, 2000. / Notes bibliogr. Index.

Thèse d'exercice : Médecine. Imagerie médicale et radiodiagnostic : Nantes : 2007. / Bibliogr.

No description available.

Thesis (MSc.(Anatomy)--Faculty of Health Sciences)-University of Pretoria, 2007. / Includes bibliographical references.

Interactive dissection simulation is an important research topic in the virtual reality (VR) community. There are many efforts on this topic; however, most of them focus on building a realistic simulation system regardless of the cost, and they often require expensive workstations and specialized haptic devices which prevent broader adoption. We show how to build a realistic dissection simulation at an affordable cost, which opens up applications in elementary education for virtual dissections which are currently not feasible. In this thesis, we present a fast and robust haptic system for interactive dissection simulations of finite elements based deformable objects which supports two type of haptic interactions: point contacts and cuts. We design a semi-progressive virtual dissection scheme of deformable objects in a real-time application. The quality and performance of visual/haptic feedback is demonstrated on a low-end commercial desktop PC with a haptic device.

𝘚𝘵𝘳𝘦𝘱𝘵𝘰𝘮𝘺𝘤𝘦𝘴 initiate a complex developmental program during their 5-day life cycle, consisting of aerial mycelium formation and antibiotic production. Several developmental genes are involved in regulating these events, one of which is 𝘣𝘭𝘥𝘉. I have complemented a 𝘣𝘭𝘥𝘉 null mutant, which demonstrated the loss of aerial mycelium formation and antibiotic production, restoring both characteristics. This demonstrated that 𝘣𝘭𝘥𝘉 is essential for 𝘚. 𝘤𝘰𝘦𝘭𝘪𝘤𝘰𝘭𝘰𝘳 morphogenesis but not viability. Using a bacterial two hybrid system devised, I screened the 𝘚. 𝘤𝘰𝘦𝘭𝘪𝘤𝘰𝘭𝘰𝘳 genome using BldB as "bait" for binding partners of BldB. The two most compelling candidates were bbpl, a homologue of UspA in 𝘌. 𝘤𝘰𝘭𝘪, and bbp2, a homologue of SrmR in 𝘚. 𝘢𝘮𝘣𝘰𝘧𝘢𝘤𝘪𝘦𝘯𝘴. Furthermore, I have investigated these interactions biochemically by affinity chromatography to further elucidate the details involved in these interactions. Preliminary results showed three protein bands obtained at approximately 68kDa, 55kDa and 35kDa, respectively. / Thesis / Master of Science (MS)

La connaissance de la morphologie des faisceaux de fibres blanches, qui connectent des régions cérébrales distantes, est indispensable à la compréhension du fonctionnement cérébral. La tractographie par IRM de diffusion reconstruit indirectement cette anatomie à partir d'algorithmes mathématiques complexes. Après une revue des méthodes proposées pour la validation de la tractographie, nous proposons une méthode originale basée sur la reconstruction 3D de faisceaux disséqués. Notre méthode, FIBRASCAN, utilise des acquisitions itératives de surface en cours de dissection. Les faisceaux étaient segmentés sur chaque surface puis reconstruits par empilement. Un support rigide permettait le recalage entre surfaces puis vers l'IRM. Nous avons démontré la précision de chaque étape de reconstruction, et sa faisabilité sur plusieurs faisceaux. Dans la dernière partie de ce travail, la structure des fibres blanches et les modifications induites par la préparation et la dissection sont explorées en microscopie électronique. Nous avons montré que la dissection préservait la structure des axones et peut ainsi être considérée comme un outil de validation de la tractographie. / The knowledge of the morphology of white matter fiber tracts, which connect distant cerebral areas, is essential to better understand brain functions. Diffusion MR tractography indirectly reconstructs this anatomy using complex mathematical algorithms. After a review of the existing methods for tractography validation, we propose an original method based on 3D reconstruction of dissected tracts. Our method, FIBRASCAN, used iterative surface acquisitions during dissection. The tracts were segmented on each surface and then reconstructed by stacking these surfaces. A rigid support allowed registration between surfaces and then registration to MRI. We demonstrated the accuracy of each reconstructing step, and the feasibility of our method on several tracts. In the last part of this work, the structure of white matter fibers and the changes induced by preparation and dissection were investigated using electron microscopy. We showed that dissection preserves the structure of axons and can thus be considered as a validation tool for tractography.

BACKGROUND: It is well established that thoracic aortic aneurysms (TAA) and abdominal aortic aneurysms (AAA) have different risk factors, clinical features, and genetic influences. Differences between and amongst subtypes of TAAs have received less attention. Despite observations of divergent clinical outcomes between ascending thoracic aortic aneurysms (ATAAs) and descending thoracic aortic aneurysms (DTAAs), etiologic factors determining the anatomic distribution of these aneurysms are not well understood. METHODS: From 3,247 patients registered in an institutional Thoracic Aortic Center Database from July 1992 through August 2013, we identified 921 patients with full aortic dimensional imaging by CT or MRI scan with TAA > 3.5 cm and without evidence of aortic dissection (AoD). Patients were analyzed in three groups: isolated ATAA (n=677), isolated DTAA (n=97), and combined ATAA and DTAA (n=146). RESULTS: Patients with a DTAA, alone or with coexistent ATAA, had significantly more hypertension (80.6% vs. 61.8%, p<.001) and a higher burden of atherosclerotic disease ( 86.7% vs. 7.5%, p<.001) ) and were more likely to be female (59.3% vs. 29.5%, P<.001). Conversely, patients with isolated ATAA were significantly younger (average age 59.5 vs. 71, p<.001), and contained almost every case of overt genetically-triggered TAA. Patients with isolated DTAA were demographically indistinguishable from patients with combined ATAA and DTAA. In follow up, patients with isolated DTAA, or with ATAA and DTAA, experienced significantly more aortic events (aortic dissection/rupture) and had higher mortality than patients with isolated ATAA. CONCLUSIONS: Based on patient characteristics and outcomes, subtypes of TAA emerge. DTAA with or without associated ATAA or AAA appears to be a disease more highly associated with atherosclerosis, hypertension, and advanced age. In contrast, isolated ATAA appears to be a clinically distinct entity with a higher burden of genetically triggered disease. These data have important implications for familial screening recommendations for TAA.