A qualitative and quantitative investigation of structural morphology in the neonatal ilium

Cortical and trabecular bone characteristics can be used to make predictions regarding previous loading regimes and developmental milestones which a bone has encountered. This has led to the suggestion that in the adult pelvis, bone patterning is related to the remodeling forces generated during bipedal locomotion. However, during the neonatal period the pelvic complex is non-load bearing, therefore, structural organisation of the ilium cannot reflect direct stance related forces. This study considers the cortical and trabecular bone structure in the ilium of the fetal and newborn infant, a structural configuration which until now has remained largely neglected in the literature. Only recently, with the advent of imaging modalities, has a greater insight and understanding of previously unexplored human bone structural composition and developing bone structure been made possible. In this study, multiple imaging techniques were applied to establish the optimal modality for application to the assessment of bone microstructure. Plain plate macroradiography and micro-computed tomography were identified as the gold standard imaging modalities for bone structural analysis for respective qualitative and quantitative assessment. These techniques were applied to gain a perspective of bone form from a sample of fetal and neonatal ilia selected from the Scheuer collection of juvenile remains. Initially, qualitative analysis highlighted consistent and well-defined patterns of cortical and trabecular bone organisation within the fetal and neonatal ilium, which corresponded with previously recognised regions in the adult that have been attributed directly to forces associated with bipedal locomotion. This was highly unexpected as the early developmental ilium is non-load bearing. Subsequently, quantification of the neonatal cortical and trabecular structure reinforced radiographic observations by identifying regions of significant architectural arrangement. Further investigation of this precocious patterning led to a revised proposal for the mode of growth in the human ilium during the neonatal developmental period. Analysis revealed statistically significant differences in regional trabecular characteristics and cortical thicknesses which have formed the basis of a proposed growth model for the ilium. The presence of ‘progressive growth regions’ and ‘restricted growth regions’ which appear to relate to metaphyseal and non-metaphyseal borders of the ilium have been demonstrated. Analysis of the early iliac bone pattern is important for understanding the relationship between trabecular bone patterning and cortical bone structure during the earliest stages of development in response to the specific functional forces acting during this period. It is suggested that the seemingly organised rudimentary scaffold observed in the early developmental ilium may be attributable to early ossification patterning, non-weight bearing anatomical interactions or even to a predetermined genetic blueprint. It must also be postulated that whilst the observed patterning may be indicative of a predetermined inherent template, early non-load bearing locomotive influences may subsequently be superimposed upon this scaffolding and perhaps reinforced and likely remodelled at a later age. Ultimately, the analysis of this fundamental primary pattern has core implications for understanding the earliest changes in iliac trabecular architecture and provides a baseline insight into future ontogenetic development and bipedal capabilities. Finally, the structural data and statistical analysis presented challenge the current concept of implied centrifugal ossification within the human ilium and present evidence of an alternative pattern of ossification that is largely dictated and controlled by basic anatomical principles.EThOS - Electronic Theses Online ServiceLeng TrustWenner-Gren FoundationBiotechnology and Biological Sciences Research CouncilGBUnited Kingdo

A qualitative and quantitative investigation of structural morphology in the neonatal ilium

Cortical and trabecular bone characteristics can be used to make predictions regarding previous loading regimes and developmental milestones which a bone has encountered. This has led to the suggestion that in the adult pelvis, bone patterning is related to the remodeling forces generated during bipedal locomotion. However, during the neonatal period the pelvic complex is non-load bearing, therefore, structural organisation of the ilium cannot reflect direct stance related forces. This study considers the cortical and trabecular bone structure in the ilium of the fetal and newborn infant, a structural configuration which until now has remained largely neglected in the literature. Only recently, with the advent of imaging modalities, has a greater insight and understanding of previously unexplored human bone structural composition and developing bone structure been made possible. In this study, multiple imaging techniques were applied to establish the optimal modality for application to the assessment of bone microstructure. Plain plate macroradiography and micro-computed tomography were identified as the gold standard imaging modalities for bone structural analysis for respective qualitative and quantitative assessment. These techniques were applied to gain a perspective of bone form from a sample of fetal and neonatal ilia selected from the Scheuer collection of juvenile remains. Initially, qualitative analysis highlighted consistent and well-defined patterns of cortical and trabecular bone organisation within the fetal and neonatal ilium, which corresponded with previously recognised regions in the adult that have been attributed directly to forces associated with bipedal locomotion. This was highly unexpected as the early developmental ilium is non-load bearing. Subsequently, quantification of the neonatal cortical and trabecular structure reinforced radiographic observations by identifying regions of significant architectural arrangement. Further investigation of this precocious patterning led to a revised proposal for the mode of growth in the human ilium during the neonatal developmental period. Analysis revealed statistically significant differences in regional trabecular characteristics and cortical thicknesses which have formed the basis of a proposed growth model for the ilium. The presence of ‘progressive growth regions’ and ‘restricted growth regions’ which appear to relate to metaphyseal and non-metaphyseal borders of the ilium have been demonstrated. Analysis of the early iliac bone pattern is important for understanding the relationship between trabecular bone patterning and cortical bone structure during the earliest stages of development in response to the specific functional forces acting during this period. It is suggested that the seemingly organised rudimentary scaffold observed in the early developmental ilium may be attributable to early ossification patterning, non-weight bearing anatomical interactions or even to a predetermined genetic blueprint. It must also be postulated that whilst the observed patterning may be indicative of a predetermined inherent template, early non-load bearing locomotive influences may subsequently be superimposed upon this scaffolding and perhaps reinforced and likely remodelled at a later age. Ultimately, the analysis of this fundamental primary pattern has core implications for understanding the earliest changes in iliac trabecular architecture and provides a baseline insight into future ontogenetic development and bipedal capabilities. Finally, the structural data and statistical analysis presented challenge the current concept of implied centrifugal ossification within the human ilium and present evidence of an alternative pattern of ossification that is largely dictated and controlled by basic anatomical principles.EThOS - Electronic Theses Online ServiceLeng TrustWenner-Gren FoundationBiotechnology and Biological Sciences Research CouncilGBUnited Kingdo

Hamstrings muscle anatomy and function, and implications for strain injury

The main aim of this thesis was to examine hamstrings anatomy and its influence on knee flexor muscle function in healthy young men. A secondary aim was to better understand the implications of hamstrings anatomy and function, and their variability, in relation to the risk of strain injury. The functional and conventional H:Q ratios (examined up to high angular velocities) as well as the knee joint angle-specific isometric H:Q ratio exhibited good test-retest reliability at joint positions that closely replicated the conditions of high injury risk. Football players did not exhibit any differences in angle-specific or peak torque H:Q ratios compared to recreationally active controls. Knee extensor and flexor strength, relative to body mass, of footballers and controls was similar for all velocities, except concentric knee flexor strength at 400° s-1 (footballers +40%; P < 0.01). Muscle volume explained 30-71% and 38-58% of the differences between individuals in knee extensors and flexors torque respectively across a range of velocities. A moderate correlation was also found between the volume of these antagonistic muscle groups (R2= 0.41). The relative volume of the knee extensors and flexors explained ~20% of the variance in the isometric H:Q ratio and ~31% in the high velocity functional H:Q ratio. Biceps femoris long head exhibited a balanced myosin heavy chain isoform distribution (47.1% type I and 52.9 % total type II) in young healthy men, while BFlh muscle composition was not related to any measure of knee flexor maximal or explosive strength. Biceps femoris long head proximal aponeurosis area varied considerably between participants (>4-fold) and was not related to biceps femoris long head maximal anatomical cross-sectional area (r= 0.04, P= 0.83). Consequently, the aponeurosis:muscle area ratio exhibited 6-fold variability (range, 0.53 to 3.09; CV= 32.5%). Aponeurosis size was not related to isometric or eccentric knee flexion strength. The findings of this thesis suggest that the main anatomical factor that contributes to knee flexors function in vivo is hamstrings muscle size, while muscle composition and aponeurosis size do not seem to have a significant influence. The high inter-individual variability of the biceps femoris long head proximal aponeurosis size suggests that a disproportionately small aponeurosis may be a risk factor for strain injury. In contrast, biceps femoris long head muscle composition does not seem to explain the high incidence of strain injuries in this muscle. Quadriceps and hamstrings muscle size imbalances contribute to functional imbalances that may predispose to strain injury and correction of any size imbalance may be a useful injury prevention tool. Finally, regular exposure to football training and match-play does not seem to influence the balance of muscle strength around the knee joint

Towards Individualized Transcranial Electric Stimulation Therapy through Computer Simulation

Transkranielle Elektrostimulation (tES) beschreibt eine Gruppe von Hirnstimulationstechniken, die einen schwachen elektrischen Strom über zwei nicht-invasiv am Kopf angebrachten Elektroden applizieren. Handelt es sich dabei um einen Gleichstrom, spricht man von transkranieller Gleichstromstimulation, auch tDCS abgekürzt. Die allgemeine Zielstellung aller Hirnstimulationstechniken ist Hirnfunktion durch ein Verstärken oder Dämpfen von Hirnaktivität zu beeinflussen. Unter den Stimulationstechniken wird die transkranielle Gleichstromstimulation als ein adjuvantes Werkzeug zur Unterstützung der mikroskopischen Reorganisation des Gehirnes in Folge von Lernprozessen und besonders der Rehabilitationstherapie nach einem Schlaganfall untersucht. Aktuelle Herausforderungen dieser Forschung sind eine hohe Variabilität im erreichten Stimulationseffekt zwischen den Probanden sowie ein unvollständiges Verständnis des Zusammenspiels der der Stimulation zugrundeliegenden Mechanismen. Als Schlüsselkomponente für das Verständnis der Stimulationsmechanismen wird das zwischen den Elektroden im Kopf des Probanden aufgebaute elektrische Feld erachtet. Einem grundlegenden Konzept folgend wird angenommen, dass Hirnareale, die einer größeren elektrischen Feldstärke ausgesetzt sind, ebenso einen höheren Stimulationseffekt erfahren. Damit kommt der Positionierung der Elektroden eine entscheidende Rolle für die Stimulation zu. Allerdings verteilt sich das elektrische Feld wegen des heterogenen elektrischen Leitfähigkeitsprofil des menschlichen Kopfes nicht uniform im Gehirn der Probanden. Außerdem ist das Verteilungsmuster auf Grund anatomischer Unterschiede zwischen den Probanden verschieden. Die triviale Abschätzung der Ausbreitung des elektrischen Feldes anhand der bloßen Position der Stimulationselektroden ist daher nicht ausreichend genau für eine zielgerichtete Stimulation. Computerbasierte, biophysikalische Simulationen der transkraniellen Elektrostimulation ermöglichen die individuelle Approximation des Verteilungsmusters des elektrischen Feldes in Probanden basierend auf deren medizinischen Bildgebungsdaten. Sie werden daher zunehmend verwendet, um tDCS-Anwendungen zu planen und verifizieren, und stellen ein wesentliches Hilfswerkzeug auf dem Weg zu individualisierter Schlaganfall-Rehabilitationstherapie dar. Softwaresysteme, die den dahinterstehenden individualisierten Verarbeitungsprozess erleichtern und für ein breites Feld an Forschern zugänglich machen, wurden in den vergangenen Jahren für den Anwendungsfall in gesunden Erwachsenen entwickelt. Jedoch bleibt die Simulation von Patienten mit krankhaftem Hirngewebe und strukturzerstörenden Läsionen eine nicht-triviale Aufgabe. Daher befasst sich das hier vorgestellte Projekt mit dem Aufbau und der praktischen Anwendung eines Arbeitsablaufes zur Simulation transkranieller Elektrostimulation. Dabei stand die Anforderung im Vordergrund medizinische Bildgebungsdaten insbesondere neurologischer Patienten mit krankhaft verändertem Hirngewebe verarbeiten zu können. Der grundlegende Arbeitsablauf zur Simulation wurde zunächst für gesunde Erwachsene entworfen und validiert. Dies umfasste die Zusammenstellung medizinischer Bildverarbeitungsalgorithmen zu einer umfangreichen Verarbeitungskette, um elektrisch relevante Strukturen in den Magnetresonanztomographiebildern des Kopfes und des Oberkörpers der Probanden zu identifizieren und zu extrahieren. Die identifizierten Strukturen mussten in Computermodelle überführt werden und das zugrundeliegende, physikalische Problem der elektrischen Volumenleitung in biologischen Geweben mit Hilfe numerischer Simulation gelöst werden. Im Verlauf des normalen Alterns ist das Gehirn strukturellen Veränderungen unterworfen, unter denen ein Verlust des Hirnvolumens sowie die Ausbildung mikroskopischer Veränderungen seiner Nervenfaserstruktur die Bedeutendsten sind. In einem zweiten Schritt wurde der Arbeitsablauf daher erweitert, um diese Phänomene des normalen Alterns zu berücksichtigen. Die vordergründige Herausforderung in diesem Teilprojekt war die biophysikalische Modellierung der veränderten Hirnmikrostruktur, da die resultierenden Veränderungen im Leitfähigkeitsprofil des Gehirns bisher noch nicht in der Literatur quantifiziert wurden. Die Erweiterung des Simulationsablauf zeichnete sich vorrangig dadurch aus, dass mit unsicheren elektrischen Leitfähigkeitswerten gearbeitet werden konnte. Damit war es möglich den Einfluss der ungenau bestimmbaren elektrischen Leitfähigkeit der verschiedenen biologischen Strukturen des menschlichen Kopfes auf das elektrische Feld zu ermitteln. In einer Simulationsstudie, in der Bilddaten von 88 Probanden einflossen, wurde die Auswirkung der veränderten Hirnfaserstruktur auf das elektrische Feld dann systematisch untersucht. Es wurde festgestellt, dass sich diese Gewebsveränderungen hochgradig lokal und im Allgemeinen gering auswirken. Schließlich wurden in einem dritten Schritt Simulationen für Schlaganfallpatienten durchgeführt. Ihre großen, strukturzerstörenden Läsionen wurden dabei mit einem höheren Detailgrad als in bisherigen Arbeiten modelliert und physikalisch abermals mit unsicheren Leitfähigkeiten gearbeitet, was zu unsicheren elektrischen Feldabschätzungen führte. Es wurden individuell berechnete elektrische Felddaten mit der Hirnaktivierung von 18 Patienten in Verbindung gesetzt, unter Berücksichtigung der inhärenten Unsicherheit in der Bestimmung der elektrischen Felder. Das Ziel war zu ergründen, ob die Hirnstimulation einen positiven Einfluss auf die Hirnaktivität der Patienten im Kontext von Rehabilitationstherapie ausüben und so die Neuorganisierung des Gehirns nach einem Schlaganfall unterstützen kann. Während ein schwacher Zusammenhang hergestellt werden konnte, sind weitere Untersuchungen nötig, um diese Frage abschließend zu klären.:Kurzfassung Abstract Contents 1 Overview 2 Anatomical structures in magnetic resonance images 2 Anatomical structures in magnetic resonance images 2.1 Neuroanatomy 2.2 Magnetic resonance imaging 2.3 Segmentation of MR images 2.4 Image morphology 2.5 Summary 3 Magnetic resonance image processing pipeline 3.1 Introduction to human body modeling 3.2 Description of the processing pipeline 3.3 Intermediate and final outcomes in two subjects 3.4 Discussion, limitations & future work 3.5 Conclusion 4 Numerical simulation of transcranial electric stimulation 4.1 Electrostatic foundations 4.2 Discretization of electrostatic quantities 4.3 The numeric solution process 4.4 Spatial discretization by volume meshing 4.5 Summary 5 Simulation workflow 5.1 Overview of tES simulation pipelines 5.2 My implementation of a tES simulation workflow 5.3 Verification & application examples 5.4 Discussion & Conclusion 6 Transcranial direct current stimulation in the aging brain 6.1 Handling age-related brain changes in tES simulations 6.2 Procedure of the simulation study 6.3 Results of the uncertainty analysis 6.4 Findings, limitations and discussion 7 Transcranial direct current stimulation in stroke patients 7.1 Bridging the gap between simulated electric fields and brain activation in stroke patients 7.2 Methodology for relating simulated electric fields to functional MRI data 7.3 Evaluation of the simulation study and correlation analysis 7.4 Discussion & Conclusion 8 Outlooks for simulations of transcranial electric stimulation List of Figures List of Tables Glossary of Neuroscience Terms Glossary of Technical Terms BibliographyTranscranial electric current stimulation (tES) denotes a group of brain stimulation techniques that apply a weak electric current over two or more non-invasively, head-mounted electrodes. When employing a direct-current, this method is denoted transcranial direct current stimulation (tDCS). The general aim of all tES techniques is the modulation of brain function by an up- or downregulation of brain activity. Among these, transcranial direct current stimulation is investigated as an adjuvant tool to promote processes of the microscopic reorganization of the brain as a consequence of learning and, more specifically, rehabilitation therapy after a stroke. Current challenges of this research are a high variability in the achieved stimulation effects across subjects and an incomplete understanding of the interplay between its underlying mechanisms. A key component to understanding the stimulation mechanism is considered the electric field, which is exerted by the electrodes and distributes in the subjects' heads. A principle concept assumes that brain areas exposed to a higher electric field strength likewise experience a higher stimulation. This attributes the positioning of the electrodes a decisive role for the stimulation. However, the electric field distributes non-uniformly across subjects' brains due to the heterogeneous electrical conductivity profile of the human head. Moreover, the distribution pattern is variable between subjects due to their individual anatomy. A trivial estimation of the distribution of the electric field solely based on the position of the stimulating electrodes is, therefore, not precise enough for a well-targeted stimulation. Computer-based biophysical simulations of transcranial electric stimulation enable the individual approximation of the distribution pattern of the electric field in subjects based on their medical imaging data. They are, thus, increasingly employed for the planning and verification of tDCS applications and constitute an essential tool on the way to individualized stroke rehabilitation therapy. Software pipelines facilitating the underlying individualized processing for a wide range of researchers have been developed for use in healthy adults over the past years, but, to date, the simulation of patients with abnormal brain tissue and structure disrupting lesions remains a non-trivial task. Therefore, the presented project was dedicated to establishing and practically applying a tES simulation workflow. The processing of medical imaging data of neurological patients with abnormal brain tissue was a central requirement in this process. The basic simulation workflow was first designed and validated for the simulation of healthy adults. This comprised compiling medical image processing algorithms into a comprehensive workflow to identify and extract electrically relevant physiological structures of the human head and upper torso from magnetic resonance images. The identified structures had to be converted to computational models. The underlying physical problem of electric volume conduction in biological tissue was solved by means of numeric simulation. Over the course of normal aging, the brain is subjected to structural alterations, among which a loss of brain volume and the development of microscopic alterations of its fiber structure are the most relevant. In a second step, the workflow was, thus, extended to incorporate these phenomena of normal aging. The main challenge in this subproject was the biophysical modeling of the altered brain microstructure as the resulting alterations to the conductivity profile of the brain were so far not quantified in the literature. Therefore, the augmentation of the workflow most notably included the modeling of uncertain electrical properties. With this, the influence of the uncertain electrical conductivity of the biological structures of the human head on the electric field could be assessed. In a simulation study, including imaging data of 88 subjects, the influence of the altered brain fiber structure on the electric field was then systematically investigated. These tissue alterations were found to exhibit a highly localized and generally low impact. Finally, in a third step, tDCS simulations of stroke patients were conducted. Their large, structure-disrupting lesions were modeled in a more detailed manner than in previous stroke simulation studies, and they were physically, again, modeled by uncertain electrical conductivity resulting in uncertain electric field estimates. Individually simulated electric fields were related to the brain activation of 18 patients, considering the inherently uncertain electric field estimations. The goal was to clarify whether the stimulation exerts a positive influence on brain function in the context of rehabilitation therapy supporting brain reorganization following a stroke. While a weak correlation could be established, further investigation will be necessary to answer that research question.:Kurzfassung Abstract Contents 1 Overview 2 Anatomical structures in magnetic resonance images 2 Anatomical structures in magnetic resonance images 2.1 Neuroanatomy 2.2 Magnetic resonance imaging 2.3 Segmentation of MR images 2.4 Image morphology 2.5 Summary 3 Magnetic resonance image processing pipeline 3.1 Introduction to human body modeling 3.2 Description of the processing pipeline 3.3 Intermediate and final outcomes in two subjects 3.4 Discussion, limitations & future work 3.5 Conclusion 4 Numerical simulation of transcranial electric stimulation 4.1 Electrostatic foundations 4.2 Discretization of electrostatic quantities 4.3 The numeric solution process 4.4 Spatial discretization by volume meshing 4.5 Summary 5 Simulation workflow 5.1 Overview of tES simulation pipelines 5.2 My implementation of a tES simulation workflow 5.3 Verification & application examples 5.4 Discussion & Conclusion 6 Transcranial direct current stimulation in the aging brain 6.1 Handling age-related brain changes in tES simulations 6.2 Procedure of the simulation study 6.3 Results of the uncertainty analysis 6.4 Findings, limitations and discussion 7 Transcranial direct current stimulation in stroke patients 7.1 Bridging the gap between simulated electric fields and brain activation in stroke patients 7.2 Methodology for relating simulated electric fields to functional MRI data 7.3 Evaluation of the simulation study and correlation analysis 7.4 Discussion & Conclusion 8 Outlooks for simulations of transcranial electric stimulation List of Figures List of Tables Glossary of Neuroscience Terms Glossary of Technical Terms Bibliograph

Haptics Rendering and Applications

There has been significant progress in haptic technologies but the incorporation of haptics into virtual environments is still in its infancy. A wide range of the new society's human activities including communication, education, art, entertainment, commerce and science would forever change if we learned how to capture, manipulate and reproduce haptic sensory stimuli that are nearly indistinguishable from reality. For the field to move forward, many commercial and technological barriers need to be overcome. By rendering how objects feel through haptic technology, we communicate information that might reflect a desire to speak a physically- based language that has never been explored before. Due to constant improvement in haptics technology and increasing levels of research into and development of haptics-related algorithms, protocols and devices, there is a belief that haptics technology has a promising future