Systematic revision of the Olenelloidea (Trilobita, Cambrian)

Phylogenetic analyses for all the available species comprising eight clades of trilobites within the monophyletic superfamily Olenelloidea (Trilobita, Cambrian) are presented….https://elischolar.library.yale.edu/peabody_museum_natural_history_bulletin/1044/thumbnail.jp

Exploration, Registration, and Analysis of High-Throughput 3D Microscopy Data from the Knife-Edge Scanning Microscope

Advances in high-throughput, high-volume microscopy techniques have enabled the acquisition of extremely detailed anatomical structures on human or animal organs. The Knife-Edge Scanning Microscope (KESM) is one of the first instruments to produce sub-micrometer resolution ( ~1 µm^(3)) data from whole small animal brains. We successfully imaged, using the KESM, entire mouse brains stained with Golgi (neuronal morphology), India ink (vascular network), and Nissl (soma distribution). Our data sets fill the gap of most existing data sets which have only partial organ coverage or have orders of magnitude lower resolution. However, even though we have such unprecedented data sets, we still do not have a suitable informatics platform to visualize and quantitatively analyze the data sets. This dissertation is designed to address three key gaps: (1) due to the large volume (several tera voxels) and the multiscale nature, visualization alone is a huge challenge, let alone quantitative connectivity analysis; (2) the size of the uncompressed KESM data exceeds a few terabytes and to compare and combine with other data sets from different imaging modalities, the KESM data must be registered to a standard coordinate space; and (3) quantitative analysis that seeks to count every neuron in our massive, growing, and sparsely labeled data is a serious challenge. The goals of my dissertation are as follows: (1) develop an online neuro-informatics framework for efficient visualization and analysis of the multiscale KESM data sets, (2) develop a robust landmark-based 3D registration method for mapping the KESM Nissl-stained entire mouse data into the Waxholm Space (a canonical coordinate system for the mouse brain), and (3) develop a scalable, incremental learning algorithm for cell detection in high-resolution KESM Nissl data. For the web-based neuroinformatics framework, I prepared multi-scale data sets at different zoom levels from the original data sets. And then I extended Google Maps API to develop atlas features such as scale bars, panel browsing, and transparent overlay for 3D rendering. Next, I adapted the OpenLayers API, which is a free mapping and layering API supporting similar functionality as the Google Maps API. Furthermore, I prepared multi-scale data sets in vector-graphics to improve page loading time by reducing the file size. To better appreciate the full 3D morphology of the objects embedded in the data volumes, I developed a WebGL-based approach that complements the web-based framework for interactive viewing. For the registration work, I adapted and customized a stable 2D rigid deformation method to map our data sets to the Waxholm Space. For the analysis of neuronal distribution, I designed and implemented a scalable, effective quantitative analysis method using supervised learning. I utilized Principal Components Analysis (PCA) in a supervised manner and implemented the algorithm using MapReduce parallelization. I expect my frameworks to enable effective exploration and analysis of our KESM data sets. In addition, I expect my approaches to be broadly applicable to the analysis of other high-throughput medical imaging data

Evolution of Diplodocid Sauropod dinosaurs with emphasis on specimens from Howe Ranch, Wyoming (USA)

Diplodocidae are among the best known sauropod dinosaurs. Several species were described in the late 1800s or early 1900s. Since then, numerous additional specimens were recovered in the USA, Tanzania, Portugal, as well as possibly Spain, England, and Asia. To date, the clade includes about 12 to 15 different species, some of them with questionable taxonomic status (e.g. ‘Diplodocus’ hayi or Dyslocosaurus polyonychius). However, intrageneric relationships of the multi-species, iconic genera Apatosaurus and Diplodocus are still poorly known. The way to resolve this issue is a specimen-based phylogenetic analysis, which was done for Apatosaurus, but is here performed for the first time for the entire clade of Diplodocidae. New material from different localities and stratigraphic levels on the Howe Ranch (Shell,Wyoming, USA) sheds additional light on the evolution of Diplodocidae. Three new specimens are described herein, considerably increasing our knowledge of the anatomy of the group. The new specimens (SMA 0004, SMA 0011, and SMA 0087) represent two, to possibly three new diplodocid species. They preserve material from all parts of the skeleton, including two nearly complete skulls, as well as fairly complete manus and pedes, material which is generally rare in diplodocids. Thereby, they considerably increase anatomical overlap between the sometimes fragmentary holotype specimens of the earlier described diplodocid species, allowing for significant results in a specimenbased phylogenetic analysis. Furthermore, clavicles and interclavicles are identified, the latter for the first time in dinosaurs. Their presence seems restricted to early sauropods, flagellicaudatans, and early Macronaria, and might thus be a retained plesiomorphy, with the loss of these bones being synapomorphic for Titanosauriformes and possibly Rebbachisauridae. The new material allows to test previous hypotheses of diplodocid phylogeny. In order to do so, any type specimen previously proposed to belong to Diplodocidae was included in the study, as are relatively complete referred specimens, in order to increase the degree of overlapping material. For specimens subsequently suggested to be non-diplodocid sauropods, their hypothesized sister taxa were included as outgroups. The current phylogenetic analysis thus includes 76 operational taxonomic units, 45 of which belong to Diplodocidae. The specimens were scored for 477 morphological characters, representing one of the most extensive phylogenetic analyses done within sauropod dinosaurs. The resulting cladogram recovers the classical arrangement of diplodocid relationships. Basing on a newly developed numerical approach to reduce subjectivity in the decision of specific or generic separation, species that have historically been included into well-known genera like Apatosaurus or Diplodocus, were detected to be actually generically different. Thereby, the famous genus Brontosaurus is resuscitated, and evidence further suggests that also Elosaurus parvus (previously referred to Apatosaurus) or ‘Diplodocus’ hayi represent unique genera. The study increases our knowledge about individual variation, and helps to decide how to score multi-species genera. Such a specimen-based phylogenetic analysis thus proves a valuable tool to validate historic species in sauropods, and in paleontology as a whole.Fundação para a Ciência e a Tecnologia - (SFRH / BD / 66209 / 2009

Porcine Spine Finite Element Model of Progressive Experimental Scoliosis and Assessment of a New Dual-Epiphyseal Growth Modulating Implant

RÉSUMÉ La scoliose est une déformation tridimensionnelle de la colonne vertébrale dont l’étiologie reste encore à élucider. Il est généralement admis que la progression de la déformation scoliotique pédiatrique est liée au principe d’Hueter-Volkmann qui stipule une réduction de la croissance suite à des contraintes en compression excessives au niveau de la concavité de la courbure scoliotique vs. sa convexité. Les stratégies de traitement des courbures sont difficiles, surtout chez les jeunes enfants. Typiquement, une intervention chirurgicale avec une instrumentation rachidienne accompagnée d’une arthrodèse segmentaire est nécessaire pour des courbures progressant au-delà de 40° d’angle de Cobb. De nouveaux dispositifs visent à manipuler la croissance vertébrale en exploitant le principe d’Hueter-Volkmann pour contrôler la progression de et corriger la courbure. Ces implants sans fusion exploitent la croissance vertébrale résiduelle en manipulant des gradients de croissance pour localement inverser la cunéiformisation vertébrale et, au fil du temps, réaligner la colonne vertébrale globalement. Des essais cliniques ont démontré une correction prometteuse pour les courbures généralement inférieures à 45°; cependant, les dispositifs actuels chevauchent l’espace du disque intervertébral et le compriment augmentant les risques de dégénérescence du disque à long terme. Par ailleurs, les implants nouvellement conçus sont généralement testés en utilisant des modèles animaux équivalents pour évaluer leur efficacité à corriger des déformations par l'intermédiaire de l’approche inverse (création d'une déformation) ou l’approche à 2- étapes (création d'une déformation suivie d’une correction). Néanmoins, une plate-forme de conception efficace est nécessaire pour évaluer la manipulation de la croissance à court et long termes par de nouveaux implants et de raccourcir le transfert de connaissances vers des applications cliniques. L’objectif général de cette thèse était de développer et de vérifier un modèle par éléments finis porcin (MEFp) unique en tant qu’une plateforme alternative pour la simulation de scolioses expérimentales progressives et des implants sans fusion, et d’évaluer un nouvel implant double-épiphysaire local ne chevauchant pas l’espace du disque sur des porcs immatures. Ainsi, les objectifs spécifiques suivants ont été complétés : 1) développer et----------ABSTRACT Scoliosis is a complex three-dimensional deformity of the spine whose etiology is yet to be elucidated. The pathomechanism of scoliosis progression is believed to be linked to the Hueter-Volkmann principle, by which growth is reduced due to increased growth plate compression, with the inverse also valid. Treatment strategies are challenging, especially in young children. Curves progressing beyond 40° Cobb angle are typically treated via invasive surgical interventions requiring spinal instrumentation accompanied by segmental spinal arthrodesis, impairing spinal mobility. New devices aim at manipulating vertebral growth by exploiting the Hueter-Volkmann principle to control curvature progression. These fusionless implants harness remaining vertebral growth by manipulating growth gradients to reverse vertebral wedging locally and, over time, globally realign the spine. Clinical trials have demonstrated promising deformity correction for curves generally below 45°; however, current devices bridge the intervertebral disc gap and predominantly compress the disc increasing the risks of longterm disc degeneration. Moreover, in a time-consuming manner, newly designed implants are commonly tested using equivalent animal models to assess their efficacy in correcting spinal deformities via the inverse (creation of a deformity) or the 2-step approaches (creation of a deformity followed by its subsequent correction). Nevertheless, a solid design platform is required to evaluate the short- and long-term growth manipulating efficacy of new implant designs and shorten knowledge transfer to clinical applications. The general objective of this thesis was to develop and verify a unique porcine spine finite element model (pFEM) as an alternative testing platform for the simulation of progressive experimental scoliosis and fusionless implants, and assess a new localized dualepiphyseal implant on immature pigs. Thus, specific objectives were devised as follows: 1) develop and verify a distinctive pFEM of the spine and ribcage, 2) develop and test, in vivo, a dual-epiphyseal implant incorporating a custom expansion mechanism, 3) exploit the developed pFEM to investigate differences between the inverse and 2-step fusionless implant testing approaches, and 4) exploit the pFEM to evaluate the biomechanical contribution of the ribcage in fusionless scoliosis surgery

Reconstruction 3D personnalisée de la colonne vertébrale à partir d'images radiographiques non-calibrées

Les systèmes de reconstruction stéréo-radiographique 3D -- La colonne vertébrale -- La scoliose idiopathique adolescente -- Évolution des systèmes de reconstruction 3D -- Filtres de rehaussement d'images -- Techniques de segmentation -- Les méthodes de calibrage -- Les méthodes de reconstruction 3D -- Problématique, hypothèses, objectifs et méthode générale -- Three-dimensional reconstruction of the scoliotic spine and pelvis from uncalibrated biplanar X-ray images -- A versatile 3D reconstruction system of the spine and pelvis for clinical assessment of spinal deformities -- Simulation experiments -- Clinical validation -- A three-dimensional retrospective analysis of the evolution of spinal instrumentation for the correction of adolescent idiopathic scoliosis -- Auto-calibrage d'un système à rayons-X à partir de primitives de haut niveau -- Segmentation de la colonne vertébrale -- Approche hiérarchique d'auto-calibrage d'un système d'acquisition à rayons-X -- Personalized 3D reconstruction of the scoliotic spine from hybrid statistical and X-ray image-based models -- Validation protocol

Analyse de la relation entre les déformations scoliotiques du tronc et celles des structures osseuses sous-jacentes

RÉSUMÉ La scoliose idiopathique adolescente est une déformation tridimensionnelle complexe de la colonne vertébrale et de la cage thoracique qui entraine des déformations visibles à la surface du tronc. On remarque généralement une asymétrie des épaules, des omoplates, de la taille et du bassin ainsi qu’une bosse dans le dos. Ces déformations esthétiques constituent, d’une part, les premiers signes d’une scoliose, et d’autre part, la principale préoccupation des jeunes patients qui voient leur corps se développer différemment des jeunes de leur âge. Les outils cliniques utilisés pour quantifier les déformations du tronc, comme le scoliomètre ou le fil à plomb, sont peu fiables. C’est pourquoi, aujourd’hui, l’évaluation de la scoliose repose principalement sur des radiographies de face et de profil du tronc complet. Celles-ci permettent d’apprécier le type de courbure rachidienne et de quantifier son degré de sévérité, en fonction de quoi une stratégie de traitement sera décidée. Cependant, une exposition répétée des patients aux rayons X peut entrainer des effets indésirables sur leur santé. De plus, ces paramètres radiographiques ne permettent pas de documenter les déformations esthétiques. Cette différence notable entre ce que le patient perçoit, et ce que le clinicien est capable d’évaluer, peut mener à l’insatisfaction des patients suite au traitement. Comparativement aux radiographies, la surface du tronc reconstruite par les systèmes de numériseurs optiques 3D représente mieux les déformations que les patients observent et dont ils se soucient principalement, comme la gibbosité. De plus, l’absence de rayonnement ionisant est un avantage majeur de ces systèmes optiques, qui favorise une évaluation aussi fréquente que souhaité. Toutefois, l’absence de consensus sur un ensemble de mesures des déformations de la surface du tronc fait en sorte qu’elles restent encore considérées comme secondaires dans l’évaluation clinique; pourtant elles sont au coeur des préoccupations des patients. De cette double problématique, découle la question de recherche globale de cette thèse : comment compléter, voire remplacer, les évaluations clinique et radiographique actuelles de la scoliose par de l’information quantitative obtenue de manière non irradiante et qui permet de prendre davantage en considération les préoccupations des patients par rapport à leurs déformations esthétiques du tronc ? Parmi les premiers signes de scoliose, la gibbosité est une déformation esthétique qui ne peut être évaluée sur des radiographies, ni sur une reconstruction 3D de la colonne vertébrale.----------ABSTRACT Adolescent idiopathic scoliosis is a complex three-dimensional deformation of the spine and rib cage which leads to visible deformations at the trunk surface. The first signs of scoliosis include a hump on the back, a lateral shift of the trunk and asymmetries of the shoulders, the scapula, the waist and the hips. These esthetic deformities constitute major concern of patients and the reason for which they seek treatment. Currently, the tools available in clinical practice to quantify trunk deformations have limited reliability. For this reason, current scoliosis assessment is mainly based on frontal and lateral radiographs of the entire spine. These images allow clinicians to determine the type of the spinal curvature and its severity, according to which the treatment strategy is decided. However, the repeated exposure of patients to X-ray radiation can be harmful. Moreover, these radiographic measures do not give an indication as to the esthetic deformities of the trunk. This significant difference between what patients perceive and what clinicians are able to evaluate can lead to patient dissatisfaction following treatment. Compared to X-rays, the trunk surface acquired and reconstructed in 3D using optical digitizers better represents the deformations that patients observe and are primarily concerned with, such as the rib hump. In addition, the major advantage of these optical systems is their lack of ionizing radiation, thus allowing for a more frequent scoliosis assessment when compared to X-rays. However, there is currently no consensus on a set of indices that optimally quantifies trunk surface deformations. For this reason, trunk surface indices are still considered as secondary in the clinical evaluation, even though they are at the heart of the patients’ preoccupations. These problems lead to the main research question of this thesis: How can we complete, or even replace, the current clinical and radiographic evaluations of scoliosis with quantitative information obtained without ionizing radiation that takes more into account the patients’ concerns about their cosmetic trunk deformities? Among the first signs of scoliosis, the rib hump is a cosmetic deformity that cannot be assessed on radiographs, nor on a 3D reconstruction of the spine. It is mainly associated with rib cage deformity. It is therefore intuitive to suppose that the axial rotations of the ribs and of the back surface are highly correlated. Nevertheless, previous works have failed to demonstrate a strong relationship between these measurements. This might be explained by the limited accuracy of the technique used for the 3D reconstruction of the ribs. Consequently, in this work, a novel metho

Correlates and consequences of varus knee thrust in osteoarthritis

Varus knee thrust is an abnormal frontal-plane movement (i.e., an out-bowing) of the knee that occurs during the weight-acceptance phase of gait. Varus thrust is of clinical interest, as it is a potentially-modifiable biomechanical risk factor for knee osteoarthritis (OA) progression and has been associated with knee pain. The overall aim of this dissertation is to identify the structural and symptomatic consequences of varus thrust at the knee and along the lower limb, and the possible anatomical and sensorimotor causes of varus thrust in older adults with or at risk for OA. Varus thrust was assessed in Multicenter Osteoarthritis (MOST) Study participants using high-speed videos of self-paced walking. Varus thrust was observed in 31.3% of 3730 knees. We investigated the longitudinal relation of varus thrust to MRI lesions and found that thrust was associated with increased odds of incident and worsening bone marrow lesions and worsening cartilage loss. We then investigated the longitudinal association of varus thrust with WOMAC knee pain and found that thrust was associated with increased odds of incident and worsening total WOMAC knee pain and worsening pain during weight-bearing and non-weight bearing activities. In an ancillary quantitative gait analysis of a single subject with unilateral varus thrust, we found altered joint moments at the hip, knee, and ankle in the thrust limb compared to the non-thrust limb. We bolstered this pilot data with an investigation of low back and lower extremity pain in the presence of thrust in MOST participants: limbs with thrust had increased odds of incident frequent pain proximal (hip or low back) and distal (ankle and foot) to the knee compared to limbs without thrust. Finally, we investigated the cross-sectional relation of anatomical and sensorimotor impairments at the knee and lower extremity to the prevalence of varus thrust. Thrust was most prevalent in limbs with static varus malalignment and supinated feet during gait, while increasing static knee laxity had a protective effect against thrust. These results fill substantial gaps in the narrative regarding the role of varus thrust in OA development

3-D visualization and prediction of spine fractures under axial loading

Thesis (Ph.D.)--Boston UniversityVertebral fractures are the hallmark of osteoporosis, yet the failure mechanisms involved in these fractures are not well understood. Current approaches to predicting fracture risk rely on average measures of bone mineral density in the vertebra, which are imperfect predictors of vertebral strength and poor predictors of fracture risk. Prior research has established that substantial regional variations in density exist throughout the vertebra and has suggested several biomechanical consequences of these variations. The overall goal of this dissertation was to characterize failure mechanisms in human vertebrae, with specific emphasis on the role of intra-vertebral heterogeneity in density and microstructure and on identifying clinically feasible techniques for predicting fracture risk. Using images obtained from micro-computed tomography (μCT) and quantitative computed tomography (QCT), the intra-vertebral heterogeneity in bone density was quantified in cadaveric specimens. Quantitative measures of this heterogeneity improved predictions of vertebral strength as compared to predictions based only on mean density. Subsequently, the intra-vertebral heterogeneity in density was measured via QCT in a cohort of post-menopausal women and was found to be lower in those who had sustained a vertebral fracture vs. in age-matched individuals without fracture. The next set of studies focused on assessing the accuracy of finite element (FE) models for predicting vertebral failure. Digital volume correlation (DVC) was used to measure the deformations sustained throughout the vertebra during compression tests. These results were compared against deformation patterns predicted using FE models created from QCT images of the vertebrae. Good agreement was found between predicted and measured deformations when the boundary conditions were accurately defined, despite simplifications made in representing material properties. The outcomes from this dissertation demonstrate that the intra-vertebral heterogeneity in density contributes to bone strength and has promise as a clinically feasible indicator of fracture risk. OCT-based FE models, which by definition account for this heterogeneity, are another promising technique, yet will likely require non-invasive techniques for estimating vertebral loading to provide the requisite accuracy in failure predictions. These two engineering approaches that account for the spatial heterogeneity in density within the vertebra may lead to more sensitive and specific indicators of fracture risk