In this study we design a succession of three increasingly adept diffuse optical devices towards the simultaneous 3D imaging of blood flow and fluorescence contrasts in relatively deep tissues. These metrics together can provide future insights into the relationship between blood flow distributions and fluorescent or fluorescently tagged agents. A noncontact diffuse correlation tomography (ncDCT) device was firstly developed to recover flow by mechanically scanning a lens-based apparatus across the sample. The novel flow reconstruction technique and measuring boundary curvature were advanced in tandem. The establishment of CCD camera detection with a high sampling density and flow recovery by speckle contrast followed with the next instrument, termed speckle contrast diffuse correlation tomography (scDCT). In scDCT, an optical switch sequenced coherent near-infrared light into contact-based source fibers around the sample surface. A fully noncontact reflectance mode device finalized improvements by combining noncontact scDCT (nc_scDCT) and diffuse fluorescence tomography (DFT) techniques. In the combined device, a galvo-mirror directed polarized light to the sample surface. Filters and a cross polarizer in stackable tubes promoted extracting flow indices, absorption coefficients, and fluorescence concentrations (indocyanine green, ICG). The scDCT instrumentation was validated through detection of a cubical solid tissue-like phantom heterogeneity beneath a liquid phantom (background) surface where recovery of its center and dimensions agreed with the known values. The combined nc_scDCT/DFT identified both a cubical solid phantom and a tube of stepwise varying ICG concentration (absorption and fluorescence contrast). The tube imaged by nc_scDCT/DFT exhibited expected trends in absorption and fluorescence. The tube shape, orientation, and localization were recovered in general agreement with actuality. The flow heterogeneity localization was successfully extracted and its average relative flow values in agreement with previous studies. Increasing ICG concentrations induced notable disturbances in the tube region (≥ 0.25 μM/1 μM for 785 nm/830 nm) suggesting the graduating absorption (320% increase at 785 nm) introduced errors. We observe that 830 nm is lower in the ICG absorption spectrum and the correspondingly measured flow encountered less influence than 785 nm. From these results we anticipate the best practice in future studies to be utilization of a laser source with wavelength in a low region of the ICG absorption spectrum (e.g., 830 nm) or to only monitor flow prior to ICG injection or post-clearance. In addition, ncDCT was initially tested in a mouse tumor model to examine tumor size and averaged flow changes over a four-day interval. The next steps in forwarding the combined device development include the straightforward automation of data acquisition and filter rotation and applying it to in vivo tumor studies. These animal/clinical models may seek information such as simultaneous detection of tumor flow, fluorescence, and absorption contrasts or analyzing the relationship between variably sized fluorescently tagged nanoparticles and their tumor deposition relationship to flow distributions.

Normal movement execution requires proper coupling of motor and sensory activation. An increasing body of literature supports the idea that incorporation of sensory stimulation into motor rehabilitation practices increases its effectiveness. Paired associative stimulation (PAS) studies, in which afferent and efferent pathways are activated in tandem, have brought attention to the importance of well-timed stimulation rather than non-associative (i.e., open-loop) activation. In patients with tetraplegia resulting from spinal cord injury (SCI), varying degrees of upper limb function may remain and could be harnessed for rehabilitation. Incorporating associative sensory stimulation coupled with self-paced motor training would be a means for supplementing sensory deficits and improving functional outcomes. In a motor rehabilitation setting, it seems plausible that sensory feedback stimulation in response to volitional movement execution (to the extent possible), which is not utilized in most PAS protocols, would produce greater benefits. This capability is developed and tested in the present study by implementing a brain-computer interface (BCI) to apply sensory stimulation synchronized with movement execution through the detection of movement intent in real time from electroencephalography (EEG). The results demonstrate that accurate sensory stimulation application in response to movement intent is feasible in SCI patients with chronic motor deficit and often precedes the onset of movement, which is deemed optimal by PAS investigations that do not involve a volitional movement task.

Since aggressive cancers are frequently hypermetabolic with angiogenic vessels, quantification of blood flow (BF) can be vital for cancer diagnosis. Our laboratory has developed a noncontact diffuse correlation tomography (ncDCT) system for 3-D imaging of BF distribution in deep tissues (up to centimeters). The ncDCT system employs two sets of optical lenses to project source and detector fibers respectively onto the tissue surface, and applies finite element framework to model light transportation in complex tissue geometries. This thesis reports our first step to adapt the ncDCT system for 3-D imaging of BF contrasts in human breast tumors. A commercial 3-D camera was used to obtain breast surface geometry which was then converted to a solid volume mesh. An ncDCT probe scanned over a region of interest on the breast mesh surface and the measured boundary data were used for 3-D image reconstruction of BF distribution. This technique was tested with computer simulations and in 28 patients with breast tumors. Results from computer simulations suggest that relatively high accuracy can be achieved when the entire tumor was within the sensitive region of diffuse light. Image reconstruction with a priori knowledge of the tumor volume and location can significantly improve the accuracy in recovery of tumor BF contrasts. In vivo ncDCT imaging results from the majority of breast tumors showed higher BF contrasts in the tumor regions compared to the surrounding tissues. Reconstructed tumor depths and dimensions matched ultrasound imaging results when the tumors were within the sensitive region of light propagation. The results demonstrate that ncDCT system has the potential to image BF distributions in soft and vulnerable tissues without distorting tissue hemodynamics. In addition to this primary study, detector fibers with different modes (i.e., single-mode, few-mode, multimode) for photon collection were experimentally explored to improve the signal-to-noise ratio of diffuse correlation spectroscopy flow-oximeter measurements.

Systemic inflammation involves a complex array of cytokines that can result in organ dysfunction. Mortality remains high despite the vast amount of research conducted to find an effective biomarker. The cause of systemic inflammation can be broad and non-specific; therefore, this research investigates using transendothelial electrical resistance (TEER) measurements to better define systemic inflammatory response syndrome (SIRS)/sepsis within a patient. Results show a difference in TEER measurements between healthy individuals and SIRS-rated patients. This research also displays correlations between TEER measurements and biomarkers currently studied with systemic inflammation (tumor necrosis factor-α, C- reactive protein, procalcitonin). Furthermore, this research also presents the groundwork for developing a microfluidic cell-based biosensor using low temperature co-fired ceramic materials. An LTCC TEER-based microfluidic device has the potential to aid in a more effective treatment strategy for patients and potentially save lives.

The knee joint plays an essential role in the human musculoskeletal system. It has evolved to withstand extreme loading conditions, while providing almost frictionless joint movement. However, its performance may be disrupted by disease, anatomical deformities, soft tissue imbalance or injury. Knee disorders are often puzzling, and accurate diagnosis may be challenging. Current evaluation approach is usually limited to a detailed interview with the patient, careful physical examination and radiographic imaging. The X-ray screening may reveal bone degeneration, but does not carry sufficient information of the soft tissue conditions. More advanced imaging tools such as MRI or CT are available, but expensive, time consuming and can be used only under static conditions. Moreover, due to limited resolution the radiographic techniques cannot reveal early stage arthritis. The arthroscopy is often the only reliable option, however due to its semi-invasive nature, it cannot be considered as a practical diagnostic tool. Therefore, the motivation for this work was to combine three scientific methods to provide a comprehensive, non-invasive evaluation tool bringing insight into the in vivo, dynamic conditions of the knee joint and articular cartilage degeneration. Electromyography and inverse dynamics were employed to independently determine the forces present in several muscles spanning the knee joint. Though both methods have certain limitations, the current work demonstrates how the use of these two methods concurrently enhances the biomechanical analysis of the knee joint conditions, especially the performance of the extensor mechanism. The kinetic analysis was performed for 12 TKA, 4 healthy individuals in advanced age and 4 young subjects. Several differences in the knee biomechanics were found between the three groups, identifying age-related and post-operative decrease in the extensor mechanism efficiency, explaining the increased effort of performing everyday activities experienced by the elderly and TKA subjects. The concept of using accelerometers to assess the cartilage degeneration has been proven based on a group of 23 subjects with non-symptomatic knees and 52 patients suffering from knee arthritis. Very high success (96.2%) of pattern classification obtained in this work clearly demonstrates that vibroarthrography is a promising, non-invasive and low-cost technique offering screening capabilities.

Made available in DSpace on 2014-12-17T14:55:41Z (GMT). No. of bitstreams: 1 ViniciusSVS.pdf: 2441901 bytes, checksum: 1246fceb24d0749c8833cd005b384269 (MD5) Previous issue date: 2010-05-07 / The incorporate of industrial automation in the medical are requires mechanisms to safety and efficient establishment of communication between biomedical devices. One solution to this problem is the MP-HA (Multicycles Protocol to Hospital Automation) that down a segmented network by beds coordinated by an element called Service Provider. The goal of this work is to model this Service Provider and to do performance analysis of the activities executed by in establishment and maintenance of hospital networks / Com a incorpora??o de conceitos da automa??o industrial na ?rea m?dica, surge a necessidade de estabelecer mecanismos que permitam a comunica??o entre os dispositivos biom?dicos de maneira segura e eficiente. Dentre as solu??es para esse problema tem-se o PM-AH (Protocolo Multiciclos para Automa??o Hospitalar) que estabelece uma rede segmentada por leitos e coordenada por um elemento chamado Provedor de Servi?os. O objetivo desse trabalho ? modelar esse Provedor de Servi?os e efetuar an?lises de desempenho sobre as tarefas realizadas pelo mesmo no estabelecimento e manuten??o da rede hospitalar

The purpose of this study was to evaluate the incidence of corrosion and fretting in 48 retrieved titanium-6aluminum-4vanadium and/or cobalt-chromium-molybdenum modular total hip prosthesis with respect to alloy material microstructure and design parameters. The results revealed vastly different performance results for the wide array of microstructures examined. Severe corrosion/fretting was seen in 100% of as-cast, 24% of low carbon wrought, 9% of high carbon wrought and 5% of solution heat treated cobalt-chrome. Severe corrosion/fretting was observed in 60% of Ti-6Al-4V components. Design features which allow for fluid entry and stagnation, amplification of contact pressure and/or increased micromotion were also shown to play a role. 75% of prosthesis with high femoral head-trunnion offset exhibited poor performance compared to 15% with a low offset. Large femoral heads (>32mm) did not exhibit poor corrosion or fretting. Implantation time was not sufficient to cause poor performance; 54% of prosthesis with greater than 10 years in-vivo demonstrated none or mild corrosion/fretting.

L’enregistrement et la stimulation in vivo de l’activité neuronale peuvent aussi bien servir pour la recherche médicale que pour les interfaces cerveau-machine. Les dispositifs à base d’électronique organique sont de prometteurs candidats pour ce faire, grâce à leur flexibilité et leur biocompatibilité. Le contrôle local de l’activité neuronale est la clé de nombreuses stratégies thérapeutiques visant à traiter les troubles neurologiques. Une solution idéale serait donc de fabriquer un dispositif capable de détecter l’activité neuronale et, en réponse, d’injecter des molécules endogènes. L’un des objectifs de cette thèse est de s’attaquer à cette problématique à l’aide d’un dispositif permettant à la fois de stimuler les cellules, et de mesurer l’activité neuronale, au même endroit, à l’échelle cellulaire. Nous présentons un dispositif organique capable de délivrer précisément des neurotransmetteurs in vitro et in vivo. En convertissant un signal électrique en la délivrance de neurotransmetteurs, le dispositif mime le fonctionnement d’une synapse. Le neurotransmetteur inhibiteur, l’acide γ- aminobutyrique (GABA), est relargué au niveau des électrodes d’enregistrement par l’activation d’une pompe ionique électronique. L’injection du GABA engendre l’arrêt de l’activité épileptique qui a été enregistré au niveau des électrodes. Des dispositifs multifonctionnels ouvrent de nombreuses possibilités, incluant des dispositifs thérapeutiques avec des boucles de retour, avec lesquels l’enregistrement local de signaux régule la délivrance d’agents thérapeutiques. De plus, nous avons également réalisé pendant cette thèse l’intégration de transistors organiques sur un film organique ultra fin, pour mesurer les signaux électrophysiologiques in vivo à la surface d’un cerveau de rat. Le dispositif, implanté de façon épidurale, montre des résultats surpassant certains dispositifs subduraux de taille similaire, permettant ainsi une approche moins invasive et efficace pour mesurer l’activité neuronale. / Recordings and stimulation of in vivo neural activity are necessary for diagnostic purposes and for brain-machine interfaces. Organic electronic devices constitute a promising candidate due to their mechanical flexibility and biocompatibility. Local control of neuronal activity is central to many therapeutic strategies aiming to treat neurological disorders. Arguably, the best solution would make use of endogenous highly localized and specialized regulatory mechanisms of neuronal activity, and an ideal therapeutic technology should sense activity and deliver endogenous molecules simultaneously to achieve the most efficient feedback regulation. Thus, there is a need for novel devices to specifically interface nerve cells. Here, we demonstrate an organic electronic device capable of precisely delivering neurotransmit- ters in vitro and in vivo. In converting electronic addressing into delivery of neurotransmit- ters, the device mimics the nerve synapse. The inhibitory neurotransmitter, -aminobutyric acid (GABA), was actively delivered and stopped epileptiform activity, recorded simultaneously and colocally. These multifunctional devices create a range of opportunities, including implantable therapeutic devices with automated feedback, where locally recorded signals regulate local release of specific therapeutic agents. In addition, we demonstrate the engineering of an organic electrochemical transistor embedded in an ultrathin organic film designed to record electrophysiological signals on the surface of the brain. The device was applied in vivo and epidurally implanted could reach capabilities beyond similar sized electrodes allowing minimally invasive monitoring of brain activity.

Near infrared spectroscopy (NIRS) is an emerging non-invasive optical neuro imaging technique that monitors the hemodynamic response to brain activation with ms-scale temporal resolution and sub-cm spatial resolution. The overall goal of my dissertation was to develop and apply NIRS towards investigation of neurological response to language, joint attention and planning and execution of motor skills in healthy adults. Language studies were performed to investigate the hemodynamic response, synchrony and dominance feature of the frontal and fronto-temporal cortex of healthy adults in response to language reception and expression. The mathematical model developed based on granger causality explicated the directional flow of information during the processing of language stimuli by the fronto-temporal cortex. Joint attention and planning/ execution of motor skill studies were performed to investigate the hemodynamic response, synchrony and dominance feature of the frontal cortex of healthy adults and in children (5-8 years old) with autism (for joint attention studies) and individuals with cerebral palsy (for planning/execution of motor skills studies). The joint attention studies on healthy adults showed differences in activation as well as intensity and phase dependent connectivity in the frontal cortex during joint attention in comparison to rest. The joint attention studies on typically developing children showed differences in frontal cortical activation in comparison to that in children with autism. The planning and execution of motor skills studies on healthy adults and individuals with cerebral palsy (CP) showed difference in the frontal cortical dominance, that is, bilateral and ipsilateral dominance, respectively. The planning and execution of motor skills studies also demonstrated the plastic and learning behavior of brain wherein correlation was found between the relative change in total hemoglobin in the frontal cortex and the kinematics of the activity performed by the participants. Thus, during my dissertation the NIRS neuroimaging technique was successfully implemented to investigate the neurological response of language, joint attention and planning and execution of motor skills in healthy adults as well as preliminarily on children with autism and individuals with cerebral palsy. These NIRS studies have long-term potential for the design of early stage interventions in children with autism and customized rehabilitation in individuals with cerebral palsy.

Intraoperative neurophysiologic monitoring is an integral part of spinal surgeries and involves the recording of somatosensory evoked potentials (SSEP). However, clinical application of IONM still requires anywhere between 200 to 2000 trials to obtain an SSEP signal, which is excessive and introduces a significant delay during surgery to detect a possible neurological damage. The aim of this study is to develop a means to obtain the SSEP using a much less, twelve number of recordings. The preliminary step involved was to distinguish the SSEP with the ongoing brain activity. We first establish that the brain activity is indeed quasi-stationary whereas an SSEP is expected to be identical every time a trial is recorded. An algorithm was developed using Chebychev time windowing for preconditioning of SSEP trials to retain the morphological characteristics of somatosensory evoked potentials (SSEP). This preconditioning was followed by the application of a principal component analysis (PCA)-based algorithm utilizing quasi-stationarity of EEG on 12 preconditioned trials. A unique Walsh transform operation was then used to identify the position of the SSEP event. An alarm is raised when there is a 10% time in latency deviation and/or 50% peak-to-peak amplitude deviation, as per the clinical requirements. The algorithm shows consistency in the results in monitoring SSEP in up to 6-hour surgical procedures even under this significantly reduced number of trials. In this study, the analysis was performed on the data recorded in 29 patients undergoing surgery during which the posterior tibial nerve was stimulated and SSEP response was recorded from scalp. This method is shown empirically to be more clinically viable than present day approaches. In all 29 cases, the algorithm takes 4sec to extract an SSEP signal, as compared to conventional methods, which take several minutes. The monitoring process using the algorithm was successful and proved conclusive under the clinical constraints throughout the different surgical procedures with an accuracy of 91.5%. Higher accuracy and faster execution time, observed in the present study, in determining the SSEP signals provide a much improved and effective neurophysiological monitoring process.