Alzheimer’s Disease (AD) represents a major and rapidly growing burden to the healthcare ecosystem. A growing body of evidence indicates that cognitive, behavioral, sensory, and motor changes may precede clinical manifestations of AD by several years. Existing tests designed to diagnose neurodegenerative diseases, while well-validated, are often less effective in detecting deviations from normal cognitive decline trajectory in the earliest stages of the disease. In the quest for gold standards for AD assessment, there is a growing interest in the identification of readily accessible digital biomarkers, which harness advances in consumer grade mobile and wearable technologies. Topics examined include a review of existing early clinical manifestations of AD and a path to the respective sensor and mobile/wearable device usage to acquire domain-centric data towards objective, high frequency and passive digital phenotyping.

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The use of guided waves has recently drawn significant interest in the ultrasonic characterization of bone aiming at supplementing the information provided by traditional velocity measurements. This work presents a three-dimensional finite element study of guided wave propagation in intact and healing bones. A model of the fracture callus was constructed and the healing course was simulated as a three-stage process. The dispersion of guided modes generated by a broadband 1-MHz excitation was represented in the time-frequency domain. Wave propagation in the intact bone model was first investigated and comparisons were then made with a simplified geometry using analytical dispersion curves of the tube modes. Then, the effect of callus consolidation on the propagation characteristics was examined. It was shown that the dispersion of guided waves was significantly influenced by the irregularity and anisotropy of the bone. Also, guided waves were sensitive to material and geometrical changes that take place during healing. Conversely, when the first-arriving signal at the receiver corresponded to a nondispersive lateral wave, its propagation velocity was almost unaffected by the elastic symmetry and geometry of the bone and also could not characterize the callus tissue throughout its thickness. In conclusion, guided waves can enhance the capabilities of ultrasonic evaluation.

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Purpose: To test the feasibility and accuracy of measuring joint motion with real-time MRI in a 1.5T scanner and in a 0.5T open-bore scanner and to assess the dependence of measurement accuracy on movement speed. Materials and Methods:We developed an MRI-compatible motion phantom to evaluate the accuracy of tracking bone positions with real-time MRI for varying movement speeds. The measurement error was determined by comparing phantom positions estimated from real-time MRI to those measured using optical motion capture techniques. To assess the feasibility of measuring in vivo joint motion, we calculated 2D knee joint kinematics during knee extension in six subjects and compared them to previously reported measurements.Results: Measurement accuracy decreased as the phantom's movement speed increased. The measurement accuracy was within 2 mm for velocities up to 217 mm/s in the 1.5T scanner and 38 mm/s in the 0.5T scanner. We measured knee joint kinematics with small intraobserver variation (variance of 0.8°for rotation and 3.6% of patellar width for translation). Conclusion:Our results suggest that real-time MRI can be used to measure joint kinematics when 2 mm accuracy is sufficient. They can also be used to prescribe the speed of joint motion necessary to achieve certain measurement accuracy.

Hydrogel polymers comprise a novel category of synthetic materials being investigated for use in cartilage replacement. One candidate compound, a poly(ethylene glycol)/poly(acrylic acid) (PEG/PAA) interpenetrating polymer network (IPN), was developed for use in corneal prostheses and was recently engineered for potential orthopedic use. The current study examined the effects of particles of this compound on two cell lines (MG-63 osteoblast-like cells and RAW 264.7 macrophages) over a 48-h time course. To mimic the effects of wear debris, particles of the compound were generated and introduced to the cells. In the MG-63 cell line, the particles had no significant effect on cell viability measured by PicoGreen assay and trypan blue exclusion. In contrast, a significant decrease in cell viability was detected in the Raw 264.7 macrophage cells at the final timepoint with the highest concentration of hydrogel (3.0% v:v). A concentration- and time-dependent increase in TNF-alpha release characteristic of other known biocompatible materials was also detected in RAW 264.7 cells, but nitric oxide and interleukin (IL)-1beta showed no response. In addition, the MG-63 cell line demonstrated no IL-6 response. Particles of the PEG/PAA IPN thus seem to stimulate biological responses similar to those in other biocompatible materials.

Cartilage material properties are important for understanding joint function and diseases, but can be challenging to obtain. Three biphasic material properties (aggregate modulus, Poisson's ratio and permeability) can be determined using an analytical or finite element model combined with optimisation to find the material properties values that best reproduce an experimental creep curve. The purpose of this study was to develop an easy-to-use resource to determine biphasic cartilage material properties. A Cartilage Interpolant Response Surface was generated from interpolation of finite element simulations of creep indentation tests. Creep indentation tests were performed on five sites across a tibial plateau. A least-squares residual search of the Cartilage Interpolant Response Surface resulted in a best-fit curve for each experimental condition with corresponding material properties. These sites provided a representative range of aggregate moduli (0.48-1.58 MPa), Poisson's ratio (0.00-0.05) and permeability (1.7 × 10 −15 −5.4 × 10 −15 m 4 /N s) values found in human cartilage.

Three-point bending tests are often used to determine the apparent or effective elastic modulus of long bones. The use of beam theory equations to interpret such tests can result in a substantial underestimation of the true effective modulus. In this study three-dimensional, nonlinear finite element analysis is used to quantify the errors inherent in beam theory and to create plots that can be used to correct the elastic modulus calculated from beam theory. Correction plots are generated for long bones representative of a variety of species commonly used in research studies. For a long bone with dimensions comparable to the mouse femur, the majority of the error in the effective elastic modulus results from deformations to the bone cross section that are not accounted for in the equations from beam theory. In some cases, the effective modulus calculated from beam theory can be less than one-third of the true effective modulus. Errors are larger: (1) for bones having short spans relative to bone length; (2) for bones with thin vs. thick cortices relative to periosteal diameter; and (3) when using a small radius or "knife-edge" geometry for the center loading ram and the outer supports in the three-point testing system. The use of these correction plots will enable researchers to compare results for long bones from different animal strains and to compare results obtained using testing systems that differ with regard to length between the outer supports and the radius used for the loading ram and outer supports.