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As a good and competent surgical simulator, it should provide surgeons with visual, tactile and behavioral illusion of reality. In literature, methods for object deformation range from non-physically based models to physically based models. Early works of non-physically based models focused on pure geometrical models that were originally employed in computer-aided design. These methods could be used to produce vivid deformable effects in computer animation. However, the soft tissue simulation in surgical applications requires more realistic models based on physical properties of human tissues. As a result, the mass-spring model and the finite element model have become the most popular representations for deformable organs in surgical simulation. Our research focuses on the real-time soft tissue deformable model based on the finite element method for surgical application. / Extended from the hybrid condensed finite element model, an interactive hybrid condensed model with hardware acceleration by the graphics processing unit (GPU) is proposed. Two methods are developed in order to map the data onto the GPU in accordance with the application data structure. The performance of the primary calculation task in the solver is enhanced. Furthermore, an improved scheme is presented to conduct the newly applied forces induced by dragging or poking operations in the non-operational region. / In the thesis, new approaches to establish a physically based model for soft tissue deformation and cutting in virtual-reality-based simulators are proposed. A deformable model, called the hybrid condensed finite element model, based on the volumetric finite element method is presented. By this method, three-dimensional organs can be represented as tetrahedral meshes, divided into two regions: the operational region and the non-operational one. Different methods treat the regions with different properties in order to balance the computational time and the level of the simulation realism. The condensation technique is applied to only involve the calculation of the surface nodes in the non-operational region while the fully calculation of the volumetric deformation is processed in the operational part. This model guarantees the smooth simulation of cutting operation with the exact cutting path when users manipulate a virtual scalpel. Moreover, we discuss the relevant aspects on what affect the efficiency of implementing the finite element method, as well as the issues considered for choosing the effective solving method to our problem. Three numerical methods have been examined in our model. / Surgical simulator, which benefits from virtual reality techniques, presents a realistic and feasible approach to train inexperienced surgeons within a safe environment. It plays more and more important role in medical field and also changes the world of surgical training. Especially, the minimally invasive microsurgery, which offers patients various attractive advantages over the traditional surgery, has been widely used in otolaryngology, gastroenterology, gynecology and neurology in the last two decades. / Through the combination of these approaches, a physically based model which allows users to freely perform the soft tissue cutting and detecting, such as poking or dragging operations, with soft tissue deformation is achieved in real-time. / Wu Wen. / "August 2006." / Adviser: Pheng Ann Heng. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1745. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 112-127). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

The main concern of this thesis is with desmoplasia - a process in which excessive connective tissue is deposited in a neoplasm. This is a common phenomenon in neoplasia but one whose mechanisms are poorly understood. To study the process, I used a human malignant melanoma cell line (UCT-Mel 7) that was established in this laboratory and that, when injected into athymic mice, gave rise to tumours that showed a number of interesting features. Firstly, the tumour induced a marked desmoplastic response as evidenced by a high content of hydroxyproline in tumour lysates, intense staining for reticulin in sections of the tumour and infiltration of the tumour by host mesenchymal cells. Secondly, the desmoplasia was associated in UCT-Mel 7-derived tumours with an unusual phasic pattern of growth that was related to the in vitro passage number of the melanoma cells. On occasions, murine tumours developed at the site of inoculation of human tumour cells. I have identified 2 possible mechanisms by which UCT-Mel 7 cells could have induced the desmoplastic response: either the tumour cells could have exerted their effect indirectly, i.e. via macrophages, or they could have stimulated the host's stromal cells directly. UCT-Mel 7 cells were shown to be chemotactic for mouse macrophages and human foreskin fibroblasts were stimulated, in a dose-dependent manner, to synthesize increased amounts of collagen when co-cultured with mouse peritoneal exudate cells. Stimulation could only be effected by direct cell:cell contact; medium conditioned by macrophages was not effective. The amount of stimulation was not dependent on the state of activation of the peritoneal cells nor on the strain of mouse used. Tumour cells were also found to act directly. Co-culture of UCT-Mel 7 cells and fibroblasts resulted in increased collagen synthesis by the fibroblasts. Increased synthesis of the protein was reflected in an increase in the amount of collagen mRNA. UCT-Mel 7 cell stimulated in a dose-dependent manner with an absolute requirement for intimate cell:cell contact with the fibroblasts. DNA synthesis was not required. Dexamethasone, retinoic acid and the tumour promoter, phorbol myristate acetate, had significant primary effects on fibroblast collagen synthesis but did not modify the response to melanoma cells. Indomethacin, however, had a minimal primary effect upon the fibroblasts but significantly augmented the melanoma cell effect. The nature of the stimulatory cell:cell contact is still uncertain. The gap junction inhibitor, α-glycyrrhetinic acid, did not diminish the melanoma cell effect. Preliminary findings suggested that cell-surface proteoglycans may be important. Removal of the proteoglycans with the inhibitor of proteoglycan assembly, 4-methylumbelliferyl-β-D-xyloside, abrogated the melanoma cell:fibroblast interaction. Recombinant basic fibroblast growth factor did. not seem to be involved in the desmoplastic response. It was of incidental interest to note that this compound inhibited fibroblast collagen synthesis in a manner that was augmented by the concomitant addition of heparin. A surprising finding was the production of a potent inhibitor of collagen synthesis by superinduced cells of the mouse macrophage cell line, P388D₁. This inhibitor has not been fully characterised.