Quaternionic Attitude Estimation with Inertial Measuring Unit for Robotic and Human Body Motion Tracking using Sequential Monte Carlo Methods with Hyper-Dimensional Spherical Distributions

This dissertation examined the inertial tracking technology for robotics and human tracking applications. This is a multi-discipline research that builds on the embedded system engineering, Bayesian estimation theory, software engineering, directional statistics, and biomedical engineering. A discussion of the orientation tracking representations and fundamentals of attitude estimation are presented briefly to outline the some of the issues in each approach. In addition, a discussion regarding to inertial tracking sensors gives an insight to the basic science and limitations in each of the sensing components. An initial experiment was conducted with existing inertial tracker to study the feasibility of using this technology in human motion tracking. Several areas of improvement were made based on the results and analyses from the experiment. As the performance of the system relies on multiple factors from different disciplines, the only viable solution is to optimize the performance in each area. Hence, a top-down approach was used in developing this system. The implementations of the new generation of hardware system design and firmware structure are presented in this dissertation. The calibration of the system, which is one of the most important factors to minimize the estimation error to the system, is also discussed in details. A practical approach using sequential Monte Carlo method with hyper-dimensional statistical geometry is taken to develop the algorithm for recursive estimation with quaternions. An analysis conducted from a simulation study provides insights to the capability of the new algorithms. An extensive testing and experiments was conducted with robotic manipulator and free hand human motion to demonstrate the improvements with the new generation of inertial tracker and the accuracy and stability of the algorithm. In addition, the tracking unit is used to demonstrate the potential in multiple biomedical applications including kinematics tracking and diagnosis instrumentation. The inertial tracking technologies presented in this dissertation is aimed to use specifically for human motion tracking. The goal is to integrate this technology into the next generation of medical diagnostic system

Development of Position-Dependent Luminescent Sensors: Spectral Rulers and Chemical Sensing Through Tissue

Assessing the performance of medical devices is critical for understanding device function and monitoring pathologies. With the use of a smart device clinically relevant chemical and mechanical information regarding fracture healing may be deduced. For example, strain on the device may be used as a mechanical indicator of weight-bearing capacity. In addition, changes in chemical environment may indicate the development of implant associated infections. Although optical methods are widely used for ex vivostrain/motion analysis and for chemical analyses in cells and histological tissue sections, there utility is limited through thick tissue because light scattering reduces spatial resolution. This dissertation presents four novel luminescent sensors that overcome this limitation. The sensors are capable of detecting chemical and physical changes by measuring position or orientation-dependent color/wavelength changes through tissue. The first three sensors are spectral rulers comprised of two patterned thin films: an encoder strip and an analyzer mask. The encoder strip is either a thin film patterned with stripes of alternating luminescent materials (quantum dots, particles or dyes) or a film containing alternating stripes of a dye that absorbs luminescence from a particle film placed below. The analyzer mask is patterned with a series of alternating transparent windows and opaque stripes equal in width to the encoder lines. The analyzer is overlaid upon the encoder strip such that displacement of the encoder relative to the analyzer modulates the color/spectrum visible through the windows. Relative displacement of the sensor layers is mechanically confined to a single axis. When the substrates are overlaid in the “home position” one line spectrum is observed, and in the “end position,” another line spectrum is observed. At intermediate positions, spectra are a linear combination of the “home” and “end” spectra. The position-modulated signal is collected by a spectrometer and a spectral intensity ratio from closely spaced emission peaks is calculated. By collecting luminescent spectra, rather than imaging the device surface, the sensors eliminate the need to spatially resolve small features through tissue by measuring displacement as a function of color. We measured micron scale displacements through at least 6 mm of tissue using three types of spectral ruler based upon 1) fluorescence, 2) x-ray excited optical luminescence (XEOL), and 3) near infrared upconversion luminescence. The sensors may be used to investigate strain on orthopedic implants, study interfragmentary motion, or assess tendon/ligament tears. In addition to monitoring mechanical strain it is important to investigate clinically relevant implant pathologies such as infection. To address this application, we have developed a fourth type of sensor. The sensor monitors changes in local pH, an indicator of biofilm formation, and uses magnetic fields to modulate position and orientation-dependent luminescence. This modulation allows the sensor signal to be separated from background tissue autofluorescence for spectrochemical sensing. This final sensor variation contains a cylindrical magnet with a fluorescent pH indicating surface on one side and a mask on the other. When the pH indicating surface is oriented towards the collection optics, the spectrum generated contains both the sensor and autofluorescence signals. Conversely, when the pH sensor is oriented away, the collected signal is composed solely of background signals. All four of the sensors described can be used to build smart devices for monitoring pathologies through tissue. Future work will include the application of the strain and chemical sensors in vivo and ex vivo in animal and cadaveric models

Detection and analysis of nanoparticles in patients: A critical review of the status quo of clinical nanotoxicology

International audienceOn the cusp of massive commercialization of nanotechnology-enhanced products and services, the physical and chemical analysis of nanoparticles in human specimens merits immediate attention from the research community as a prerequisite for a confident clinical interpretationof their occurrence in the human organism. In this review, we describe the caveats in current practices of extracting and isolating nanoparticles from clinical samples and show that they do not help truly define the clinical significance of any detected exogenous nano-sized objects. Finally, we suggest a systematic way of tackling these demanding scientific tasks. More specifically, a precise and true qualitative evaluation of nanoparticles in human biological samples still remains difficult to achieve because of various technical reasons. Such a procedure is more refined when the nature of the pollutants is known, like in the case of nano-sized wear debris originating from biomedical prostheses. Nevertheless, nearly all available analytical methods provide unknown quantitative accuracy and qualitative precision due to the challenging physical and chemical nature of nanoparticles. Without trustworthy information to detect and describe the nanoparticulate load of clinical samples, it is impossible to accurately assess its pathological impact on isolated cases or allow for relevant epidemiological surveys on large populations. Therefore, we suggest that the many and various specimens stored in hospitals be used for the refinement of methods of exhaustive quantitative and qualitative characterization of prominent nanoparticles in complex human milieu

Spatial Sensors for Quantitative Assessment of Retrieved Arthroplasty Bearings

Evaluation of retrieved joint arthroplasty bearings provides unique evidence related to the physiological environment in which bearing materials are expected to perform. This dissertation describes the development of novel spatial sensors and measurement strategies for standardized, quantitative assessments of arthroplasty bearings, including total knee replacements, unicompartmental knee replacements, and total hip replacements. The approach is to assess bearings that endured a finite duration of function in patients, with particular emphasis on expanding our understanding of the biomechanical conditions specific to bearing function and wear in the physiological environment. Several quantifiable parameters are identified that prove comparable to pre-clinical in vitro tibological evaluations, including knee wear simulation and analytical modeling. These comparisons provide clinical relevance to the existing methodologies, helping to verify that the biomechanical simulations accurately represent the in vivo conditions they are meant to simulate. The broad objective of this dissertation is to improve the longevity and function of arthroplasty bearing materials and designs. Assessments from the retrieved prostheses are discussed within the context of developing comprehensive approaches for the prospective evaluation of new materials and designs in joint replacements

Book of Abstracts 15th International Symposium on Computer Methods in Biomechanics and Biomedical Engineering and 3rd Conference on Imaging and Visualization

In this edition, the two events will run together as a single conference, highlighting the strong connection with the Taylor & Francis journals: Computer Methods in Biomechanics and Biomedical Engineering (John Middleton and Christopher Jacobs, Eds.) and Computer Methods in Biomechanics and Biomedical Engineering: Imaging and Visualization (JoãoManuel R.S. Tavares, Ed.). The conference has become a major international meeting on computational biomechanics, imaging andvisualization. In this edition, the main program includes 212 presentations. In addition, sixteen renowned researchers will give plenary keynotes, addressing current challenges in computational biomechanics and biomedical imaging. In Lisbon, for the first time, a session dedicated to award the winner of the Best Paper in CMBBE Journal will take place. We believe that CMBBE2018 will have a strong impact on the development of computational biomechanics and biomedical imaging and visualization, identifying emerging areas of research and promoting the collaboration and networking between participants. This impact is evidenced through the well-known research groups, commercial companies and scientific organizations, who continue to support and sponsor the CMBBE meeting series. In fact, the conference is enriched with five workshops on specific scientific topics and commercial software.info:eu-repo/semantics/draf

Isolation, Characterisation and Software Development for Polymeric Wear Particles from In Vitro Joint Simulators

Wear of the Ultra-high molecular weight polyethylene (UHMWPE) articulating against metal in joint replacements is one of the primary reasons for long-term failure of prosthesis due to implant loosening. Amount, size and morphology of wear debris are important factors that affect the clinical performance of a joint implant. Major developments in UHMWPE as an orthopaedic bearing material are radiation crosslinking and recent introduction of vitamin E as an antioxidant. This thesis aims to investigate the size and shape characteristics of UHMWPE wear debris produced by current state-of-the-art noncrosslinked and vitamin E containing highly crosslinked UHMWPE implants in artificial hip, knee and ankle joint articulations. Current polyethylene wear debris isolation methods were assessed for isolating wear particles from serum based simulator lubricants. The limitations of current isolation methods were incomplete digestion, presence of impurities, bacterial contamination and low reproducibility. Consequently, a novel UHMWPE wear debris isolation method was developed to overcome these limitations. This method successfully isolated UHMWPE wear debris by digesting simulator lubricants using 5M potassium hydroxide and by purifying particles using a two-stage density gradient ultracentrifugation. High-resolution scanning electron microscopy was used to capture digital images of wear debris particles deposited on 15 nm pore size membrane filters. Two current commercial size analysers Nanosight and Mastersizer were compared to SEM image analysis for characterising UHMWPE wear debris. Large size range and complex shape of wear debris made both Nanosight and Mastersizer unsuitable for complete characterisation of UHMWPE particles. Moreover, no shape analysis was available in both commercial particle analysers. Therefore, SEM image analysis was chosen for particle characterisation. Custom software was developed to automatically analyse SEM images and characterise particles using a range of size and shape descriptors. The isolation and characterisation methods developed in this study were used to investigate the influence of crosslinking, addition of vitamin E and change in molecular architecture on size and morphology of wear debris. All wear particles analysed in this study were found to be predominantly submicron in size. Crosslinking reduced the size of UHMWPE wear debris for particles generated in knee and multidirectional pin-on-plate. Noncrosslinked direct compression moulded (DCM) ArCom UHMWPE generated more elongated and fibrillar wear particles. Higher chain mobility and higher elongation to break was believed to be the reason for this particle morphology. Alternatively, highly crosslinked UHMWPE generated less elongated and more compact shaped particles. Addition of vitamin E by blending, followed by crosslinking and annealing in ECiMA UHMWPE generated more elongated and fibrillar particles in comparison to vitamin E diffused highly crosslinked (E1) UHMWPE in hip. Multidirectional pin-on-plate wear testing of DCM UHMWPE moulded at 175°C and at 145°C generated similar particle size distribution and shapes. Influence of type of joint articulation on size and morphology of wear particles was investigated by isolating and characterising E1 UHMWPE wear debris produced by ankle, knee, hip and multistation pin-on-plate articulation. E1 wear particles generated by ankle and knee had similar particle size and morphology. Moreover, both ankle and knee generated submicron as well as large micron sized particles. Submicron sized particles were more round, while large particles were elongated and fibrillar. Alternatively, hip generated mostly submicron-sized particles with rounder morphology. Wear particles generated in multidirectional pin-on-plate tester were also mainly submicron in size. However, morphology of these particles was more fibrillar and elongated. In conclusion: Crosslinking, method of addition of vitamin E, change in processing conditions and type of joint articulation could influence the size and shape characteristics of UHMWPE wear debris

Dynamic \u3ci\u3eIn Vivo\u3c/i\u3e Skeletal Feature Tracking Via Fluoroscopy Using a Human Gait Model

The Tracking Fluoroscope System II, a mobile robotic fluoroscopy platform, developed and built at the University of Tennessee, Knoxville, presently employs a pattern matching algorithm in order to identify and track a marker placed upon a subject’s knee joint of interest. The purpose of this research is to generate a new tracking algorithm based around the human gait cycle for prediction and improving the overall accuracy of joint tracking. This research centers around processing the acquired x-ray images of the desired knee joint obtained during standard clinical operation in order to identify and track directly through the acquired image. Due to the inability for tracking through x-ray imaging during knee crossovers (when both knees enter and align within the x-ray image), a form of prediction is developed around the kinematics of human gait motion. This gait model is designed to consider the natural swinging motion of the knee during walking in order to predict path for the x-ray system to follow when active tracking is not possible. During the later stages of research, modifications were made in the setup and testing in order to accommodate changes put in place upon the research environment. Individually, the processing of the x-ray images and the prediction ability of the gait model have shown decent success. The overall controlling algorithm which manages the tracking system has demonstrated some downfalls, however, which have been attributed to the modified setup of the testing. Therefore, while the final results of this research demonstrated some shortcomings, it has confirmed its usability in a real-time environment with the capability of tracking the complete joint implant, and the human gait model developed provides a means of accounting for the natural swing motion of the knee joints during leg motion. The end results provide evidence for a feasible system should it be possible to test and employ it in the scenario to which it was first intended, i.e. in conjunction with x-ray images

Role of the Synovial Membrane in Osteoarthritis Pathogenesis and Cartilage Repair

Osteoarthritis (OA) affects an estimated 250 million people worldwide, representing an enormous economic and social burden across demographic groups. While classically attributed to ‘wear and tear’ of the articular cartilage, there is a growing appreciation that OA is a whole-joint disease with a complex etiology involving the synovium and surrounding tissues. The synovium is a specialized connective tissue membrane that envelops the diarthrodial joint and maintains the synovial fluid environment through molecular secretion as well as bi-directional filtration of these constituents, nutrients, and cellular waste products. Moreover, synovium-derived cells have been directly implicated in both the native repair response as well as degradation of articular cartilage. Much of the existing research of synovium has been conducted in the context of rheumatoid arthritis (RA). And while synovitis is a key feature of both RA and OA, clinical reports have described OA synovium as distinct in its cellular and structural composition, molecular secretion, and chronic onset. However, literature studies have not adequately addressed the mechanisms by which alterations in synovium structure-function affect joint and cartilage health, particularly the contribution of different cell types within the synovium to solute transport and lubrication. The work described in this dissertation addresses these knowledge gaps in the context of existing and emerging OA therapies, namely glucocorticoids and electrical stimulation. We anticipate that a more comprehensive characterization of changes to the synovium composition, secretion of key metabolic mediators, lubrication properties, as well as its ability to regulate solute transport in and out of the joint space will not only contribute to our basic science understanding of the synovium but also the development and modification of therapeutic strategies aimed at restoring and maintaining joint health. This characterization will be facilitated by our laboratory’s expertise in tissue engineering and explant culture, IL-1 and DEX stimulation, and electrical stimulation of joint tissues. The approach of using an engineered synovium model is attractive in that quantitative high throughput in vitro mechanistic studies can be performed on tissues that are fabricated from cells derived from normal and OA synovium of patients and corresponding immune cells at defined density and cell type ratios. It also facilitates isolating effects of certain cell types or starting composition that are found in explant specimens. Intra-articular glucocorticoid injections are commonly administered to patients in an effort to control inflammation and pain. And while these high dose injections are known to have significant detrimental local and systemic effects, comparatively low doses of dexamethasone (DEX), a synthetic glucocorticoid, are known to have pro-anabolic and anti-catabolic effects on cartilage cultures. Our laboratory has published extensively on the benefits of DEX stimulation in growth and maintenance of engineered and explanted cartilage as well as chondroprotection from pro-inflammatory cytokines (e.g interleukin-1; IL-1), both in juvenile bovine basic science and adult canine preclinical systems. However, the concomitant effects of DEX on synovium structure-function have not been elucidated. In Part I, we describe a functional tissue engineered synovium model that was validated against explant behavior. We were able to recapitulate many of the unique structural and functional characteristics of synovium, including protein expression, intimal lining formation, solute transport, and friction coefficient. Additionally, changes in engineered synovium structure-function mirrored that of explants when treated with IL-1 or DEX. The engineered synovium model was then expanded to include resident macrophage-like synoviocytes (MLS), demonstrating the key role that these cells play in structural reorganization of synovium. The model was also translated to human cells, showing the potential of the system for personalized medicine. Finally, motivated by insights into solute transport in the synovium as well as its strong anti-inflammatory response to DEX, we developed a sustained low-dose DEX delivery platform for mitigating synovial inflammation while simultaneously stimulating cartilage growth. Utilizing a preclinical adult canine model, we showed that extended intra-articular delivery of DEX improved functional outcomes and cartilage tissue quality. In Part II, we evaluated synovium behavior and cartilage repair in response to modes of electrical stimulation. Electrical stimulation of cells and tissues has been a topic of interest for decades, owed in part to the knowledge that endogenous electric field (EF) gradients guide cell behavior during embryogenesis and wound healing. Pulsed electromagnetic fields (PEMFs) have been used in a clinical setting to stimulate bone repair and alleviate pain, however their use for OA and cartilage repair is controversial. Culture studied of PEMFs have shown anti-catabolic and pro-anabolic effects on isolated FLS and cartilage, respectively. And previous work in our laboratory demonstrated directed 2D migration of synoviocytes and chondrocytes in response to direct current (DC) EF stimulation. These modes of electrical stimulation have not been explored in synovium explants, so it is unclear to what extent the observed phenomena translate to the 3D tissue environment. For the first time, we characterized the biological response of both healthy bovine and OA human synovium explants, showing distinct anti-inflammatory behavior in bovine tissues and a highly variable response in arthritic human tissues, likely due to different inflammatory cell content. Motivated by the potent anti-inflammatory effect seen in normal tissue and previous work showing a pro-anabolic effect on cartilage, the PEMF system was then adapted for use with a preclinical adult canine model of engineered cartilage repair. In this model, PEMFs significantly enhanced functional outcomes and cartilage tissue quality. Finally, we investigated the potential for direct synovial cell-mediated cartilage repair via induced migration with DC EFs. By developing and validating a novel tissue-scale bioreactor capable of applying DC EFs in sterile culture conditions to three-dimensional constructs, we showed increased recruitment of synovial repair cells to the site of a cartilage wound. Taken together, the sum of the work builds on existing therapeutic strategies by developing models to understand the contribution of the synovium to joint maintenance and repair. By modeling dexamethasone- and electrical- induced changes to composition and function of synovium and cartilage, via complementary explant and engineered approaches, valuable mechanistic insights into osteoarthritis pathogenesis and cartilage repair were gathered. These findings lay the groundwork for more complex and personalized in vitro models of OA and motivate future work to capitalize on knowledge of the functional plasticity of the synovium to develop synovium-targeted strategies for OA treatment and prevention

Investigation of cellular microenvironments and heterogeneity with biodynamic imaging

Imaging of biological tissue in a relevant environment is critical to accurately assessing the effectiveness of chemotherapeutic agents in combatting cancer. Though many three-dimensional (3D) culture models exist, conventional in vitro assays continue to use two-dimensional (2D) cultures because of the difficulty in imaging through deep tissue. 3D tomographic imaging techniques exist and are being used in the development of 3D efficacy assays. However, most of these assays look at therapy endpoint (dead or living cancer cell count) and do not capture the dynamics of tissue response. Biodynamic imaging (BDI) is a 3D tomographic imaging and assay technique that uses the dynamics of scattered coherent light, or speckle, to measure dynamic response of tissue to perturbations. Dynamic measurements allow BDI to not only assess overall efficacy, but to also measure phenotypic changes in cancer tissue as it responds to therapy. Because BDI captures the phenotypic response of tissue, it naturally accounts for genetic and microenvironmental factors, and shows promise as an accurate predictor of in vivo chemotherapeutic response. This thesis presents the development of BDI into a predictive assay for assisting in chemotherapy selection. It shows how microenvironmental factors alter BDI response measurements. It reports how different BDI biomarkers can accurately assess sensitivity to platinum treatment in xenograpft models of ovarian cancer. Changes in sensitivity during metastasis are observed, and a method for addressing sample variability and heterogeneity is presented. A predictive model for chemotherapeutic selection is developed and applied retrospectively to primary esophageal cancer. Finally, a new imaging modality called tissue dynamic spectroscopic imaging (TDSI) is presented, which is capable of directly assessing spatial functional patterns in patient samples