High Intensity Focused Ultrasound (HIFU) is a promising technique for the treatment of localized cancers. The ability to focus ultrasound precisely on a predetermined volume allows the possibility of selective tissue destruction at this position without damage to surrounding tissues. However, many difficulties remain in the treatment of deep-seated tumors. In this thesis, new therapeutic and monitoring techniques are proposed to address these problems, by using phased arrays of ultrasound transducers. Two monitoring techniques based on the detection of the displacements of the ultrasonic speckle are developed, and allowed us to image the changes in the temperature and the shear modulus during HIFU therapy. In-vitro ultrasound-guided experiments are performed. Secondly, the problem of organs motion during the treatment is addressed. A method for real-time tracking the 3D motion of tissues is combined with a 2D High Intensity Focused Ultrasound multi-channel system in order to correct the respiratory motion during HIFU therapies. In the last section of this thesis, a high power ultrasonic system is developed for transcranial HIFU brain therapy. The skulls aberrations are corrected using a time reversal mirror thanks to an implanted hydrophone. In-vivo experiments are conducted on 22 sheep with minimally invasive surgery. Finally, a non-invasive protocol based on CT scans of the entire skull is developed and allows the prediction of the skulls aberrations and the skull overheating.

Thesis (Ph. D.)--University of Virginia, 2006. / Includes bibliographical references. Also available online through Digital Dissertations.

Thesis (Ph. D.)--University of Hong Kong, 2006. / Also available online.

Les poissons demoiselles (Pomacentridae) représentent lune des familles les plus importantes des récifs coralliens ; du point de vue du nombre despèces (> 350) et de leur abondance. Malgré cette importance, très peu détudes ont abordé leur diversité trophique et morphologique. Comme la majorité des poissons coralliens, les demoiselles possèdent un cycle de vie complexe divisé en deux phases : (1) une phase larvaire pélagique et océanique potentiellement dispersive et (2) une phase juvénile et adulte sédentaire associée à lhabitat corallien. La fin du stade larvaire coïncide avec la colonisation du récif. Le milieu océanique offre un habitat relativement homogène pour toutes les larves de Pomacentridae et celles-ci se nourrissent exclusivement de copépodes planctoniques. Au contraire, le récif propose une grande variété dhabitats et de ressources alimentaires. Au cours de leur ontogénie, les demoiselles subissent donc un changement de mode de vie qui doit saccompagner de modifications morphologiques, physiologiques et comportementales pour optimiser leur survie dans chaque environnement. La présente thèse a pour premier objectif de tester lhypothèse selon laquelle la plus grande diversité trophique attendue au stade adulte saccompagne dune plus grande disparité (mesure de la diversité morphologique au sein dun taxon) que chez les larves. Répondre à cet objectif a nécessité dorganiser la recherche selon trois axes. Premièrement, Lanalyse des contenus stomacaux et des isotopes stables du carbone et de lazote chez treize espèces a permis de mettre en évidence trois comportements alimentaires : (1) les « pelagic feeders » qui se nourrissent presquexclusivement de copépodes planctoniques, (2) les « benthic feeders » qui sont des espèces principalement herbivores broutant des algues filamenteuses et (3) un groupe intermédiaire incluant des espèces qui se nourrissent en proportions variables dans le compartiment pélagique et benthique (ex : copépodes planctoniques et benthiques, petits invertébrés vagiles et sessiles, algues filamenteuses). La littérature signale en plus deux demoiselles spécialisées dans la consommation exclusive de polypes de coraux. Deuxièmement, une étude écomorphologique a caractérisé la diversité du squelette céphalique chez les adultes. Les variations de forme de quatre unités du squelette céphalique (le neurocrâne, lunité « suspensorium et opercule », la mandibule et le prémaxillaire) ont été explorées au moyen de la morphométrie géométrique chez quatorze espèces adultes montrant des régimes alimentaires différents. Les résultats révèlent un parallélisme entre la diversité du squelette céphalique et la diversité des régimes alimentaires présent au stade adulte. Dune manière générale, les demoiselles planctonophages possèdent des caractères squelettiques optimisant la prise de nourriture par aspiration (ex : hauts suspensoria et opercules, une large crête supraoccipitale, des mandibules courtes formant une petite bouche). Les espèces brouteuses montrent des pièces squelettiques plus robustes (ex : mandibules hautes et massives, hyomandibulaires larges). Parmi les espèces zooplanctonophages, Chromis viridis et C. acares montrent une morphologie céphalique assez divergente de celle des autres. Leurs caractéristiques squelettiques laissent supposer un mode de prise de nourriture où le poisson capture sa proie en nageant vers elle bouche ouverte (type « ram-suction feeder »). La dentition buccale nest pas toujours corrélée au régime alimentaire. Troisièmement, lontogénie post-colonisation et la variation du niveau de disparité squelettique ont été étudiées et comparées chez huit espèces représentant un échantillon complet de la diversité trophique de la famille. Après la colonisation, les demoiselles subissent des allométries de croissance importantes (40 à 87% des variations de forme). La disparité morphologique est plus grande au stade adulte quau stade de la colonisation pour chaque structure squelettique céphalique. Lensemble des paramètres développementaux étudiés ont subi des changements évolutifs. À la colonisation, les formes larvaires sont déjà spécifiques, probablement à cause de différences dans la durée de vie larvaire pélagique des espèces. Laugmentation de la disparité au cours du développement post-colonisation est essentiellement due à la divergence des patrons allométriques. La longueur des trajectoires ontogénétiques et les vitesses de développement apparaissent comme deux facteurs moins variables. Dune manière générale, peu de liens existent entre les données phylogénétiques ou écologiques (régime, durée de vie larvaire,) et les paramètres développementaux. La diversité du genre Dascyllus illustre des cas de gigantisme. Les méthodes de morphométrie géométrique montrent que les petites espèces et les espèces géantes partagent les mêmes trajectoires ontogénétiques pour le neurocrâne et la mandibule. Au sein de ce groupe, lapparition despèces de grande taille au cours de lévolution résulterait de processus hétérochroniques. La morphologie céphalique larvaire suggère une prise de nourriture de type « ram/suction feeding ». Chez toutes les espèces étudiées, les patrons allométriques révèlent une optimisation du système de prise de nourriture par aspiration au cours du développement. Les demoiselles acquièrent au cours de leur croissance des joues et de opercules proportionnellement plus hauts, une crête supraoccipitale plus grande, des mandibules plus courtes et un processus ascendant du prémaxillaire plus long. Chez les espèces herbivores, dautres changements de forme sont liés à lacquisition de capacités de morsure et de découpe. Par exemple, les mandibules et les suspensoria deviennent plus massifs.

Class III malocclusion in orthodontic patients typically results from midfacial retrognathia. However, the etiology of the midfacial retrognathia remains unclear. The cranial base is considered to play an important role in the emergence of midfacial morphology due to its location within the craniofacial region as well as its dramatic growth activity during the later prenatal and early postnatal periods. Previously, the nasal septum was considered a key cranial base component which functioned to pull the maxilla anteriorly during growth. Although this nasal septal theory of midfacial advancement is generally accepted, certain midfacial abnormalities occur in the presence of normal nasal septal morphology and growth indicating that additional craniofacial regions must contribute to the control of midfacial prognathism. The purpose of this study was to describe a mouse mutant which displays midfacial retrognathia and to delineate regions of cranial base malgrowth. Further, cellular growth mechanisms responsible for causing the abnormal cranial base growth trajectories were identified. Adult 3H1 Brachyrrhine (Br) male mice, displaying midfacial retrognathia with a characteristic Class III malocclusion, were bred to normal C3H females. Litters were examined to determine whether Br offspring could be distinguished from one another between Theiler stages 23 (E15) and 27 (E19) using qualitative and quantitative methods. Results showed that two distinct groups of offspring were derived: one with midfacial retrognathia and the other without. The cranial base of Br mutants displayed a malformed sphenoidal region while the nasal septum appeared much less affected as revealed by finite element morphometric analysis. In vivo autoradiographic analysis demonstrated the existence of temporal growth sites (TGS). TGS in the sphenoidal regions were deficient in the prenatal Br mouse. Using immunohistochemistry, insulin growth factor (IGF-I) and epidermal growth factor (EGF) as well as their receptors (IGF-IR and EGF-R) were found to be expressed in cranial base chondrocytes. In order to determine whether chondrocytic responses to these growth factors were deficient in the mutant, cell cultures were established, treated with IGF-I or EGF, and cellular proliferation and differentiation were measured using (³H) -thymidine and (³⁵S) -sulfate incorporation. Results from this analysis showed that chondrocytes from the Br posterior cranial base were less responsive to EGF compared to cells from normal posterior cranial bases. Data from this study suggest that the Br mouse displays midfacial retrognathia in a heritable fashion. Deficient growth of the Br sphenoid, particularly in the presphenoidal and sphenoethmoid region, is crucial for the establishment of midfacial retrognathia. In the Br mouse, the sphenoidal deficiency is associated with depressed proliferation in TGS. IGF-I and EGF, as well as their receptors, are expressed within the murine cranial base and the depressed level of cellular proliferation in the Br sphenoidal region results, at least in part, from a diminished response to EGF. Based on this study, I propose a "sphenoidal mechanism of midfacial advancement" whereby the sphenoid actively propels the midface forward in order to achieve proper maxillary prognathism during later prenatal and early postnatal period.

<p>Child head injury is a very costly problem, both in terms of morbidity/mortality and direct medical costs. In fact, it is the leading cause of death and disability for those in the United States under age 18-years-old. Currently, head injury in children ages newborn to 19-years-old is responsible for 7500 deaths per year--30% of all childhood deaths in the United States. Given its importance and effect on the population, the study of pediatric head injury is greatly hindered by the lack of available pediatric post mortem human specimen (PMHS) data. As a substitute for PMHS testing, anthropometric test devices (ATDs) and finite element models (FEMs) have been developed to model the head. However, there is a dearth of data for the design and validation of these models. </p><p>The goal of this study was to use pediatric PMHSs to both advance the study of pediatric head injury and to provide validation data for ATD and finite element head models. 14 pediatric heads, 8 adult heads, and 6 ATD heads were studied to obtain geometrical, inertial, structural stiffness, and impact properties. The computational tomography (CT) method was used on pediatric heads to get inertial properties, and clinical CT scans were used to develop average head and skull contours for 12 different age groups. To obtain impact properties, the heads were dropped onto a rigid plate from 15cm and 30cm, and the acceleration-time pulses were analyzed to obtain acceleration HIC and other impact properties. The heads were then placed between two aluminum plates and compressed at four different rates to obtain structural stiffness values. Using the PMHS results, the ATD heads were compared against age-matched human heads, and the scaling rules used for ATD production were tested for accuracy. </p><p>The study found that between the ages of 5-months-old and 22-months-old, the human head was susceptible to fracture from drops as low as 15cm. The structural stiffness of the human head was shown to increase by three orders of magnitude from neonate to adult. For the impact properties, the human head's peak acceleration and head injury criteria increased with age, while the human head's pulse duration and coefficient of restitution decreased with age. The 50th percentile Hybrid III head was found to adequately model the response of the adult head for multiple head impact locations, while the 3-year-old Q3 child ATD was found to be too stiff during impact. Overall, this study provides novel data that can be directly applied to pediatric head injury curves, and pediatric ATD and finite element head models.</p> / Dissertation

Not available / text

No description available.

The Mexican tetra, Astyanax mexicanus, exists as two morphs of a single species, a sighted surface morph and a blind cavefish. In addition to eye regression, cavefish have an increased number of taste buds, maxillary teeth and have an altered craniofacial skeleton. I investigated the effect the lens has on the development of the surrounding skull by ablating the lens over early ontogeny. This unique long-term study sheds light on how early embryonic manipulations on the eye can affect the shape of the adult skull. The effects of lens ablation were analyzed using landmark based morphometric analyzes. Morphometric analyzes indicate that there is a significant difference in the shape of the supraorbital bone and suborbital bones four through six. These bones expand into the eye orbit exhibiting variability in their shape. Interestingly, the number of caudal teeth on the lower jaw is also affected by lens ablation. I compared these findings between morphs and across two teleost species. I conducted lens removal in the surface fish to determine if it would produce a cavefish phenotype. Lens removal in the surface fish only partially results in a cavefish phenotype, indicating that lens loss is not solely responsible for the phenotypic differences between the two morphs. The effects of lens removal were then compared in the Mexican tetra and zebrafish. Surprisingly, the results indicate that the same bones are variable in shape in both species, indicating that the variability of these bones is conserved across species. Finally, I compared laser lens damage and full lens removal, to investigate the capacity for both lens regeneration and healing in the Mexican tetra. Together, the lens healing and regeneration studies indicate that lens absence in early development does not influence the shape of the skull. Lens absence during later development influences the mechanical forces in the skull resulting in the bones of the orbital region changing in size and shape. This study highlights the dynamic nature of the skull and sheds light on the influence the eyes (a soft tissue) have on the surrounding skull (a hard tissue) a topic which has been overlooked in the literature.

No description available.