Mathematics, physics, biology, and computer science are combined to create computational modeling, which studies the behaviors and reactions of complex biomedical problems. Modern biomedical research relies significantly on realistic computational human models or “virtual humans�. Relevant study areas utilizing computational human models include electromagnetics, solid mechanics, fluid dynamics, optics, ultrasound propagation, thermal propagation, and automotive safety research. These and other applications provide ample justification for the realization of the Visible Human Project® (VHP)-Female v. 4.0, a new platform-independent full body electromagnetic computational model. Along with the VHP-Female v. 4.0, a realistic and anatomically justified Dynamic Breathing Sequence is developed. The creation of such model is essential to the development of biomedical devices and procedures that are affected by the dynamics of human breathing, such as Magnetic Resonance Imaging and the calculation of Specific Absorption Rate. The model can be used in numerous application, including Breath-Detection Radar for human search and rescue.

Simulation of the electromagnetic response of the human body relies heavily upon efficient computational CAD models or phantoms. The Visible Human Project (VHP)-Female v. 3.1 - a new platform-independent full-body electromagnetic computational model is revealed. This is a part of a significant international initiative to develop powerful computational models representing the human body. This model’s unique feature is full compatibility both with MATLAB and specialized FEM computational software packages such as ANSYS HFSS/Maxwell 3D and CST MWS. Various mesh processing algorithms such as automatic intersection resolver, Boolean operation on meshes, etc. used for the development of the Visible Human Project (VHP)-Female are presented. The VHP - Female CAD Model is applied to two specific low frequency applications: Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS). TMS and tDCS are increasingly used as diagnostic and therapeutic tools for numerous neuropsychiatric disorders. The development of a CAD model based on an existing voxel model of a Japanese pregnant woman is also presented. TMS for treatment of depression is an appealing alternative to drugs which are teratogenic for pregnant women. This CAD model was used to study fetal wellbeing during induced peak currents by TMS in two possible scenarios: (i) pregnant woman as a patient; and (ii) pregnant woman as an operator. An insight into future work and potential areas of research such as a deformable phantom, implants, and RF applications will be presented.

Le cancer du col utérin est un des cancers les plus prévalents dans le monde et représente une cause majeure de mortalité par cancer chez la femme. Le dépistage de ce cancer est actuellement basé sur l’examen clinique, la colposcopie, la cytologie du col utérin et l’histopathologie dont la reproductibilité inter observateur est médiocre surtout en ce qui concerne les lésions de bas grade (CIN 1). Bien qu’amélioré par de nouveaux marqueurs (p16INK4A), la recherche de nouveaux marqueurs spécifiques des lésions du col utérin nécessite l’élucidation des mécanismes de la cancérogenèse parmi lesquels les altérations épigénétiques, but de notre recherche. Nous avons évalué au cours des différentes étapes de la cancérogenèse du col utérin la méthylation globale de l'ADN par immunohistochimie et HPLC. L’hyperméthylation des îlots de CpG de trois gènes candidats impliqués dans la signalisation cellulaire (CDH13, DAPK1, TWIST1) a été étudié par une technique de PCR – méthylation spécifique (MSP) après modification de l’ADN au bisulfite de sodium. L’étude immunohistochimique à l'aide d’anticorps dirigés contre la 5-MeCyd objective une hypométhylation globale de l’ADN tardive n’apparaissant que dans les cancers invasifs. Ces résultats ont été confirmés par HPLC. Par contre, l’hyperméthylation des îlots de CpG des gènes candidats étudiés est présente dés le stade lésions précancéreuses. Ces résultats suggèrent qu’au cours de la cancérogenèse du col utérin, l’hypométhylation globale et l’hyperméthylation des îlots de CpG sont deux mécanismes indépendants. L’étude du profil de méthylation des régions promotrices des gènes CDH13, DAPK1, TWIST1 pourrait constituer un marqueur potentiel des lésions précancéreuses et cancéreuses du col de l’utérus / Background: The uterine cervix cancer is one of the main cancer among women worldwide and represents an important cause of death in women especially in developing countries. The screening of this cancer is based on clinic tests, colposcopy, cytology and histopathology which have a low inter observer reproducibility, specially concerning CIN1 lesions. Although improved by new markers (p16INK4A), the discovery of new specific markers requires the elucidation of mechanisms of carcinogenesis such as epigenetic alterations, aim of our study. Material and methods: We evaluated during uterine cervix carcinogenesis global DNA methylation by immunohistochemistry and HPLC. CpGs islands hypermethylation of three genes implied in cellular signalizing (CDH13, DAPK1, TWIST1) were evaluated using specific methylation PCR (MSP) after bisulfite DNA modification. Results: Immunohistochemistry study using anti 5-MeCyd antibodies objectives a late global DNA hypomethylation appearing only in invasive uterine cervix carcinoma. These results were confirmed by HPLC. However, CpGs islands hypermethylation of the promoter of CDH13, DAPK1 and TWIST1 genes studied were detected in precancerous lesions. Conclusions: Our results suggest that during uterine cervix carcinogenesis, global DNA hypomethylation and gene hypermethylation were two independent mechanisms. The methylation profile of the promoter regions of CDH13, DAPK1 and TWIST1 genes would represent a potential marker for the diagnosis of the precancerous and cancerous uterine cervix lesions

Computational modeling offers better insight into a wide range of bioelectrical and biomechanical problems with improved tools for the design of medical devices and the diagnosis of pathologies. Electromagnetic modeling at low and high frequencies is particularly necessary. Modeling electromagnetic, structural, thermal, and acoustic response of the human body to different internal and external stimuli is limited by the availability of numerically efficient computational human models. This study describes the development to date of a computational full-body human model - Visible Human Project (VHP) - Female Model. Its unique feature is full compatibility both with MATLAB and specialized FEM computational software packages such as ANSYS HFSS/Maxwell 3D. This study also describes progress made to date in using the newly developed tools for segmentation. A visualization tool is implemented within MATLAB and is based on customized version of the constrained 2D Delaunay triangulation method for intersecting objects. This thesis applies a VHP - Female Model to a specific application, transcranial Direct Current Stimulation (tDCS). Transcranial Direct Current Stimulation has been beneficial in the stimulation of cortical activity and treatment of neurological disorders in humans. The placement of electrodes, which is cephalic versus extracephalic montages, is studied for optimal targeting of currents for a given functional area. Given the difficulty of obtaining in vivo measurements of current density, modeling of conventional and alternative electrode montages via the FEM has been utilized to provide insight into the tDCS montage performance. An insight into future work and potential areas of research, such as study of bone quality have been presented too.