Magnetic Resonance Imaging (MRI) is the most prominent non-invasive technique used in clinical diagnosis and biomedical research. Its development as an imaging technique has been aided by contrast agents (CAs) which enhance contrast to noise ratio in the images. This dissertation deals with paramagnetic lanthanide- and superparamagnetic iron-based nanoparticles (NPs) which are potential CAs at clinical field of 3 T and a high field of 9.4 T. Chapter 1 provides a brief overview of colloidal nanoparticles, with an emphasis on their surface chemistry and magnetic properties for bio-applications. Chapter 2 employs europium as an optical probe to illustrate the contribution of inner, second and outer sphere relaxation towards longitudinal and transverse relaxivities of paramagnetic NP-based CAs. Chapter 3 investigates the positive and the negative contrast enhancement abilities and magnetization of paramagnetic NPs comprising a core of sodium dysprosium fluoride with a sodium gadolinium fluoride shell. Their surface chemistry is tuned to target prostate cancer specifically. The application of these NPs is further extended in Chapter 4 to track an intraneuronal protein called tau following mild traumatic brain injury. Chapter 5 deals with facile synthesis and long-term stability of superparamagnetic iron NPs for their potential application as CAs. Chapter 6 illustrates the concept of MRI correlation using ‘T1-only’ and ‘T2-only’ NPs. Chapter 7 investigates on the dynamics involved in the phospholipids coating the surface of NPs. Chapter 8 concludes on the work detailed in the previous chapters and outlines the future outlook. / Graduate / 2020-01-15

In the last decade, traumatic brain injuries (TBIs) and spinal cord injuries (SCIs) has become one of the most scrutinised medical challenges of our time. However, the lower quality of life experienced by the sufferer and the associated socio-economic cost of both TBI and SCI remain a huge burden for society. There is currently no reliable way to evaluate the level of functional damage caused by TBI and SCI related mechanical forces without invasive examination. The types of axonopathy involved in such injuries are the combinations of coupled mechanical-electrophysiological phenomena at multiple length and time scales, extremely challenging to approach by experimental means alone. It is therefore highly desirable to complement experimental studies with computational work to further the understanding of such multiscale problems. This thesis firstly proposes a novel 3D finite element framework coupling mechanics and electrophysiology to model cellular and subcellular phenomena, such as nerve dislocation and membrane damage by micropipette. The former study shows that 1D simulations focussing solely on the stretch component of the axonal damage are unable to capture the same electrophysiological damage that a 3D framework predicts. The latter study shows that local membrane deformation can lead to electrophysiological alterations at the axonal level solely through geometrical effects and without the need to account for ion channel activity alterations. This was demonstrated for micropipette suction in a patch clamp where the consideration of the 3D flow of current was sufficient to alter its electrophysiology, offering an alternative explanation to the damage mechanism hypothesised by published experimental work. At the axonal and tissue scale, previous models have often simplified the modelling of damage by using a single axon model. It is however unclear whether an altered axonal electrophysiology can truly be representative of the compound electrophysiology of multiple axons or fibre. Three different models: axonal, fibre and tissue level models, were evaluated and compared for their ability to model macroscale electrophysiology deficits. The results of the three models suggest that the recovery of compound action potential amplitude post-mechanical stretch can not be straightforwardly scaled from axonal level to fibre level. Furthermore, the electrophysiological recovery may not be solely dependent on mechanical recovery of the tissue. This thesis identified the need for scale specific models in the context of TBI and SCI. In particular, lipid bilayer membrane geometrical distortion following mechanical insult at the subcellular scale and functional tissue alteration at the tissue scale both require a different approach. The models proposed herein successfully identify mechanisms overlooked in previous experimental literature. In order to fully capture experimental behaviour, future models will need to account for other mechanisms such as mechanoporation, reorganisation of paranodal junctions and injury related Calcium ion imbalance.

Wearable assistive robotics have the potential to address an unmet medical need of reducing disability in individuals with chronic hand impairments due to neurological trauma. Despite myriad prior works, few patients have seen the benefits of such devices. Following application experience with tendon-actuated soft robotic gloves and a collaborator's orthosis with novel flat-spring actuators, we identified two common assumptions regarding hand orthosis design. The first was reliance on incomplete studies of grasping forces during activities of daily living as a basis for design criteria, leading to poor optimization. The second was a neglect of increases in muscle tone following neurological trauma, rendering most devices non-applicable to a large subset of the population. To address these gaps, we measured joint torques during activities of daily living with able-bodied subjects using dexterity representative of orthosis-aided motion. Next, we measured assistive torques needed to extend the fingers of individuals with increased flexor tone following TBI. Finally, we applied this knowledge to design a cable actuated orthosis for assisting finger extension, providing a basis for future work focused on an under-represented subgroup of patients.

Football safety has increased over time, in part due to improvements in equipment and body mechanics, but there are still inherent risks involved, including exposure to repetitive head impacts (RHI). Significant head impacts can result in a constellation of symptoms including nausea, vomiting, headache, dizziness, and amnesia, which typically assist in the diagnosis of concussion. However, it has been shown that subconcussive impacts may result in microstructural changes and physiological alterations in the brain. This is particularly concerning because athletes may be undergoing changes in the brain in the absence of outwardly visible symptoms. Poorer neurologic outcomes later in life have been associated with cumulative exposure rather than number of diagnosed concussions. Accelerometers installed in helmets have shown that college football players may receive up to 1,850 head impacts throughout the course of one season. The concussion rate is obviously much lower, indicating there are a high number of head impacts per diagnosed concussion. Axons are especially susceptible to damage from RHI because of their extension throughout the nervous system. The subtle changes thought to result from RHI are not easy to measure, but several modalities have been proposed. These include diffusion tensor imaging (DTI), plasma tau protein, and King-Devick testing. The proposed study will look to quantify cumulative head impact exposure in college football players prior to the start of a season and see if this has any impact on the variables. They will then participate in one season of football wearing helmet accelerometers to measure the number of head impacts sustained. Changes in the variables will be compared to non-contact sport college athletes. Data will be analyzed to determine if number of head impacts correlates with changes in variables and if prior head impact exposure has any effect on these changes. Data obtained from this study will have significant implications in the field of head injury. It may strengthen the use of several markers of brain injury that could be utilized in the future. Additionally, the effects of cumulative head impact exposure and one season of head impacts will be thoroughly examined. This information can be provided to trainers, coaches, and athletes to further improve football safety.

Plusieurs études ont montré que dans les accidents réels, la vitesse d’impact de la tête n’est que rarement normale à la surface et présente une composante tangentielle non négligeable. Aucune norme, à l’heure actuelle ne propose de choc oblique avec enregistrement de l’accélération en translation et en rotation de la fausse tête. Un aspect essentiel de cette recherche a été d’aborder les descriptions d’accidents réels impliquant un motocycliste et un véhicule afin d’évaluer les conditions aux limites de la tête juste avant impact, en termes de vecteur vitesse et de localisation d’impact. Cette étude a permis d’établir le vecteur vitesse possible et de l’angle d’impact de la tête du motocycliste en situation. Une méthode de test pour évaluer le casque a été proposée. Les tests d'impact obliques, sont effectués avec une vitesse d’impact de 8.5 m/s sur une enclume inclinée de 45° permettant la rotation autour de l’axe Y X et Z. Les accélérations 6-D sont implémentés dans le modèle SUFEHM afin d’extraire la déformation axonal maximale et le risque lésionnel. Cette fusion de la méthode expérimentale et numérique donne un avantage par rapport aux normes conventionnelles, tant en termes de conditions d’impact qu’en termes de critère de blessure de la tête. / It is well know that in case of accident the head does not only impact perpendicularly to the impacted structure but presents an oblique impact condition. However none of the today helmet standards do integrate oblique impacts with the recording of the dummy head rotational acceleration. An essential aspect of the present research is to simulate real world accident and to compute the victim’s kinematic in order to extract the head impact conditions. In collaboration with University Florence (Italy) 19 cases were considered and it was shown that the head impact velocity vector presents a significative angle. A novel helmet test method has been proposed. Helmeted headfoml is impacting a 45° inclined anvil at a speed of 8.5 m/s and the 6D acceleration versus time curves are introduced into an existing head FEM in order to compute the axon strains and to derive the brain injury risk.

Neurorehabilitation for people suffering from brain injury has traditionally focused on rehabilitation of the somatic and cognitive functions. Research into the emotional aspects of brain injury has, however, been limited. The theoretical part of this thesis was therefore to map diagnostic tools suitable for the investigation of emotional problems of patients after brain injury and to classify these tools for the needs of neuropsychological practice. In the empirical part the author focused on the adaptation and pilot verification of the EBIQ (European Brain Injury Questionnaire) neuropsychological questionnaire, for a sample of patients having experienced brain injury and their immediate family and friends. The practical outcome of work in addition to the psychometric characteristics is a Czech working version EBIQ-P (version for patients) and EBIQ-R (version for family members), including well-prepared instructions for evaluating the results and examples for use in clinical practice. EBIQ provides an alternative to the previously used questionnaires SCL-90 and MMPI-100, since these, according to our findings and the findings from other studies on the group of patients after brain injury provide invalid results.

Background: It is often considered that, following paediatric acquired brain injury (pABI) and epilepsy, higher-level cognitive deficits, such as prospective memory (PM), are impaired and may only become apparent over time when these abilities are expected to develop and mature in a typically developing child. Interventions supporting PM have the potential to increase independence and enhance social participation. Despite research indicating PM difficulties in children and adolescents with pABI and epilepsy, and also in children with PM difficulties with unknown aetiology, currently, there is a limited evidence-base for interventions, although previous research has attempted to address this following pABI (Rous, 2011). Objective: The objective of this empirical paper was to build upon the work of Rous (2011) and optimise the effectiveness of brief metacognitive 'Remembering Goals' Training (RGT) and external content-free cueing (in the form of 'STOP' text messages) on PM task performance and the achievement of real-life goals. Method: The research employed a single-case series design with a randomised, alternating treatment (Barlow & Hayes, 1979). Eight participants (aged 10-15 years) completed the study. Three participants had an ABI, two participants had epilepsy, and three participants experienced PM difficulties with unknown aetiology. The PM task required participants to send three text messages at set times and to complete three real-life goals each working day for a four-week period. After a baseline period, participants completed brief RGT via Skype twice during the study (once following baseline, and again half way through the study). The brief RGT facilitated metacognitive skills and participants learnt to associate texts reading 'STOP' with mentally reviewing their goals and tasks for that day. Six 'STOP' text messages (cues) were sent at random times on half of the days of the intervention. The number and accuracy of texts messages, and the achievement of real-life goals, were compared across cued and un-cued days to evaluate the efficacy of the intervention for each participant. Results: Five participants demonstrated improved PM text message performance and seven participants demonstrated improved performance in real-life goals. Most of the participants reported positive gains in self-reported PM abilities, and most parents of children with acquired neurological conditions reported reduced levels of family stress and burden following the intervention. Conclusions: This research offers some evidence in support of the efficacy of content-free cueing and RGT for facilitating PM abilities. The majority of participants engaged in more frequent and accurate PM tasks and, most importantly, achieved more of their real-life goals as a result of the intervention.

The objective of this work presented here is to extend the capabilities of siloxane waveguide technology in the field of biochemical sensing. Recent advances in the integration of polymeric optical waveguides with electronics onto standard printed circuit boards (PCBs) allow the formation of cost-effective lab-on-achip modules suitable for mass production. This technology has been primarily designed for on-board data communication. The focus of this research is to investigate the possibility of realising a Siloxane polymer based lab-on-chip sensor. Different siloxane-polymer-based optical waveguide sensor structures have been designed and analysed from the aspect of biochemical sensing. An evanescent-wave absorption sensor based on mode-selective asymmetric waveguide junctions is proposed for the first time. The device mitigates the common optical effect of spurious response in absorption sensors due to the analyte transport fluid. Head injury is the leading cause of death in the population of people under 40 years. Currently, 3 out of 5 deaths in emergency rooms are due to severe brain injuries in the developed world. Researchers at the Neurosciences Critical Care Unit (NCCU) at Addenbrooke's Hospital have managed to correlate biochemical changes with the severeness of the injury and the likelihood of patient recovery. Considerable progress has been made to develop a lab-on-chip sensor capable of continuously monitoring glucose, lactate and pyruvate concentrations in the brain fluid, hence the contribution to the current trend in the advancement of portable lab-on-chip technologies for the deployment of point-of-care diagnostic tools. A novel recognition layer has been developed based on porphyrin in combination with glucose, lactate and pyruvate oxidase for measuring all the analytes, enabling fast and reversible chemical reactions to be monitored by optical interrogation. The operational wavelength of the developed recognition layer is 425 nm, which required the formation of polymer features that were beyond the fabrication capabilities at the time. Through considerable process development and the adoption of nanoimprinting lithography, siloxane polymer based optical waveguides were fabricated allowing the realisation of highly sensitive optical sensors. Based on the results that are presented here, it can be concluded the functionalization of siloxane polymer waveguide have a potential for realising biochemical sensors in the future. The new fabrication technique will allow the formation of more robust and complex lab-on-chip sensors based on this material.

Monitoring of cerebral oxygenation, cerebrovascular reactivity and circulatory function in preterm infants Brain injury in the preterm infant is associated with death and lifelong disability. Cerebral hypoxia and fluctuations in cerebral blood flow in the first two days of life have been implicated in the pathophysiology of haemorrhagic and ischaemic brain injury. Monitoring of haemodynamic changes during the early transitional circulation from in-utero to ex-utero life are currently based on standard measurements of systemic oxygenation and mean arterial blood pressure, with no reliable assessment of end-organ perfusion. In this thesis, measurements using near-infrared spectroscopy (NIRS) and functional echocardiography were made to assess cerebral perfusion and systemic blood flow in a cohort of preterm infants undergoing intensive care. This thesis is divided into four sections: i) The feasibility of continuous monitoring of cerebral oxygenation and cerebrovascular reactivity is demonstrated in a series of case reviews, and the association between cerebral oxygenation and cerebrovascular reactivity with outcome of brain injury and mortality is described. ii) Combining measurements of systemic blood flow with end organ perfusion was applied to define MABPOPT in preterm infants based on an index of cerebrovascular reactivity. Deviations below MABPOPT were associated with intraventricular haemorrhage and mortality. iii) The complexity of brain and systemic signals was studied by using multi-scale entropy analysis. Most studies using cerebral NIRS or systemic measurements of blood flow use linear analysis; however, a complex biological system, such as the human brain, includes many regulatory mechanisms that interact in a complex manner, resulting in effects that cannot be understood wholly through the analysis of its individual constituents. Lower complexity of brain signals was observed in infants who developed intraventricular hemorrhage or died. iv) Changes in systemic and cerebral oxygenation in a cohort of preterm infants in the first 48 hours of life was assessed using functional echocardiography. The patterns of changes in cardiac output and cerebral oxygenation in infants who did and did not have intraventricular haemorrhage are discussed. Furthermore, the relationship between the presence of a haemodynamically significant ductus arteriosus and brain injury is assessed.

Submitted by Silvana Teresinha Dornelles Studzinski (sstudzinski) on 2016-11-18T12:09:41Z No. of bitstreams: 1 Roberto Oliveira Rodrigues_.pdf: 1330100 bytes, checksum: 8ee5aecb5382bb35a0d509f9898574a8 (MD5) / Made available in DSpace on 2016-11-18T12:09:41Z (GMT). No. of bitstreams: 1 Roberto Oliveira Rodrigues_.pdf: 1330100 bytes, checksum: 8ee5aecb5382bb35a0d509f9898574a8 (MD5) Previous issue date: 2016-09-30 / UEMA – Universidade Estadual do Maranhão / TCE se caracteriza como uma lesão resultante do impacto físico interno ou externo com grande impacto socioeconômico desta forma, a assistência qualificada é de fundamental importância para reduzir os índices de morbimortalidade. Objetivo: elaborar um guia assistencial para atendimento de pacientes adultos com traumatismo cranioencefpalico no serviço de emergência do Hospital Municipal Gentil filho de Caxias/MA. Método: revisão de literatura, os Descritores de Ciências da Saúde (DeCS) e Medical Subject Headings (MeSH) definidos para a busca nas bases de dados foram: craniocerebral trauma, protocols e nursing. A coleta de dados foi realizada nos meses de agosto a setembro de 2015. Os estudos utilizados na confecção deste guia foram selecionados com base nos critérios: a) inclusão: artigos completos e gratuitos, publicados em periódicos indexados que abordaram a temática do estudo; publicados no período de 2000 a 2016, considerando as duas últimas atualização do Colégio Americano de Cirurgiões; estudos anteriores ao período estipulado (2000) que são considerados relevantes e não apresentam evidências melhores; teses e dissertações; manuais nacionais e internacionais relacionados à temática deste estudo; b) critérios exclusão: monografias; resumos simples e expandidos publicados em anais de congressos. Resultados: foram encontradas 2872 publicações disponíveis nas bases de dados selecionadas, sendo 852 da MEDLINE; 743 da BDENF; 589 no SciELO; 390 no LILACS; e 297 no COCHRANE. Após aplicação dos critérios de inclusão e exclusão, destes restaram 32 estudos. Conclusão: Observou-se a importância da utilização de um guia assistencial para atendimentos a vitimas de Traumatismo Cranioencefálico, pois os cuidados iniciais como: ABCDE do trauma, elevação de cabeceira, monitoração hidroeletrolítica e controle da hipotensão diminuem significativamente os índices de morbidade e mortalidade. / TCE is characterized as an injury resulting from internal or external physical impact with great socio-economic impact in this way, quality care is crucial to reduce morbidity and mortality rates. Objective: To prepare a nursing care guide for the treatment of adult patients suffering from traumatic brain injury in the emergency response of the General Hospital of Caixas – MA. Methods: The Medical Subject Headings (MeSH) used for database search were: craniocerebral trauma, protocols and nursing. The data collection was performed during 2015 between August and September and the studies used as references on this protocol were selected through the following criteria: published papers on periodic in the last 10 years talking about the theme, thesis and dissertations, international and national manuals related to our subject; papers published on events were not used in our study. Results: found 2872 publications available in selected databases, with 852 of MEDLINE; 743 of BDENF; 589 in SciELO; 390 in LILACS; and 297 COCHRANE. After application of the inclusion and exclusion criteria, these remaining 32 studies. Conclusion: there was the importance of using a clinical protocol for nurses to care to victims of Traumatic brain injury, because the initial care as ABCDE trauma, head elevation, electrolyte monitoring and control of hypotension significantly decrease the morbidity and mortality.