Physics-informed UNets for discovering hidden elasticity in heterogeneous materials.

Soft biological tissues often have complex mechanical properties due to variation in structural components. In this paper, we develop a novel UNet-based neural network model for inversion in elasticity (El-UNet) to infer the spatial distributions of mechanical parameters from strain maps as input images, normal stress boundary conditions, and domain physics information. We show superior performance - both in terms of accuracy and computational cost - by El-UNet compared to fully-connected physics-informed neural networks in estimating unknown parameters and stress distributions for isotropic linear elasticity. We characterize different variations of El-UNet and propose a self-adaptive spatial loss weighting approach. To validate our inversion models, we performed various finite-element simulations of isotropic domains with heterogenous distributions of material parameters to generate synthetic data. El-UNet is faster and more accurate than the fully-connected physics-informed implementation in resolving the distribution of unknown fields. Among the tested models, the self-adaptive spatially weighted models had the most accurate reconstructions in equal computation times. The learned spatial weighting distribution visibly corresponded to regions that the unweighted models were resolving inaccurately. Our work demonstrates a computationally efficient inversion algorithm for elasticity imaging using convolutional neural networks and presents a potential fast framework for three-dimensional inverse elasticity problems that have proven unachievable through previously proposed methods.

End to end stroke triage using cerebrovascular morphology and machine learning.

Background: Rapid and accurate triage of acute ischemic stroke (AIS) is essential for early revascularization and improved patient outcomes. Response to acute reperfusion therapies varies significantly based on patient-specific cerebrovascular anatomy that governs cerebral blood flow. We present an end-to-end machine learning approach for automatic stroke triage. Methods: Employing a validated convolutional neural network (CNN) segmentation model for image processing, we extract each patient's cerebrovasculature and its morphological features from baseline non-invasive angiography scans. These features are used to detect occlusion's presence and the site automatically, and for the first time, to estimate collateral circulation without manual intervention. We then use the extracted cerebrovascular features along with commonly used clinical and imaging parameters to predict the 90 days functional outcome for each patient. Results: The CNN model achieved a segmentation accuracy of 94% based on the Dice similarity coefficient (DSC). The automatic stroke detection algorithm had a sensitivity and specificity of 92% and 94%, respectively. The models for occlusion site detection and automatic collateral grading reached 96% and 87.2% accuracy, respectively. Incorporating the automatically extracted cerebrovascular features significantly improved the 90 days outcome prediction accuracy from 0.63 to 0.83. Conclusion: The fast, automatic, and comprehensive model presented here can improve stroke diagnosis, aid collateral assessment, and enhance prognostication for treatment decisions, using cerebrovascular morphology.

Hyper-acute effects of sub-concussive soccer headers on brain function and hemodynamics.

Introduction: Sub-concussive head impacts in soccer are drawing increasing research attention regarding their acute and long-term effects as players may experience thousands of headers in a single season. During these impacts, the head experiences rapid acceleration similar to what occurs during a concussion, but without the clinical implications. The physical mechanism and response to repetitive impacts are not completely understood. The objective of this work was to examine the immediate functional outcomes of sub-concussive level impacts from soccer heading in a natural, non-laboratory environment. Methods: Twenty university level soccer athletes were instrumented with sensor-mounted bite bars to record impacts from 10 consecutive soccer headers. Pre- and post-header measurements were collected to determine hyper-acute changes, i.e., within minutes after exposure. This included measuring blood flow velocity using transcranial Doppler (TCD) ultrasound, oxyhemoglobin concentration using functional near infrared spectroscopy imaging (fNIRS), and upper extremity dual-task (UEF) neurocognitive testing. Results: On average, the athletes experienced 30.7 ± 8.9 g peak linear acceleration and 7.2 ± 3.1 rad/s peak angular velocity, respectively. Results from fNIRS measurements showed an increase in the brain oxygenation for the left prefrontal cortex (PC) (p = 0.002), and the left motor cortex (MC) (p = 0.007) following the soccer headers. Additional analysis of the fNIRS time series demonstrates increased sample entropy of the signal after the headers in the right PC (p = 0.02), right MC (p = 0.004), and left MC (p = 0.04). Discussion: These combined results reveal some variations in brain oxygenation immediately detected after repetitive headers. Significant changes in balance and neurocognitive function were not observed in this study, indicating a mild level of head impacts. This is the first study to observe hemodynamic changes immediately after sub-concussive impacts using non-invasive portable imaging technology. In combination with head kinematic measurements, this information can give new insights and a framework for immediate monitoring of sub-concussive impacts on the head.

Sensor-Based Assessment of Variability in Daily Physical Activity and Frailty.

INTRODUCTION: Frailty is a common geriatric syndrome associated with decline in physiological reserve. While several digital biomarkers of daily physical activity (DPA) have been used in frailty assessment, the association between DPA variability and frailty is still not clear. The goal of this study was to determine the association between frailty and DPA variability. METHODS: This is an observational cross-sectional study conducted between September 2012 and November 2013. Older adults (≥65 years), without any severe mobility disorder, and the ability to walk 10 m (with or without an assistive device) were eligible for the study. DPA including sitting, standing, walking, lying, and postural transition were recorded for 48 h continuously. DPA variability was analyzed from two perspectives: (i) DPA duration variability in terms of coefficient of variation (CoV) of sitting, standing, walking, and lying down durations; and (ii) DPA performance variability in terms of CoV of sit-to-stand (SiSt) and stand-to-sit (StSi) durations and stride time (i.e., slope of power spectral density - PSD). RESULTS: Data was analyzed from 126 participants (44 non-frail, 60 pre-frail, and 22 frail). For DPA duration variability, CoV of lying and walking duration was significantly larger among non-frail compared to pre-frail and frail groups (p < 0.03, d = 0.89 ± 0.40). For DPA performance variability, StSi CoV and PSD slope were significantly smaller for non-frail compared to pre-frail and frail groups (p < 0.05, d = 0.78 ± 0.19). CONCLUSION: Lower DPA duration variability in pre-frail and frail groups may be attributed to the set daily routines frail older adults tend to follow, compared to variable physical activity routines of non-frail older adults. Higher DPA performance variability in the frail group may be attributed to reduced physiological capabilities toward walking for longer durations and the reduced muscle strength in the lower extremities, leading to incosistency in performing postural transitions.

Ultrasound, photoacoustic, and magnetic resonance imaging to study hyperacute pathophysiology of traumatic and vascular brain injury.

BACKGROUND AND PURPOSE: Cerebrovascular dynamics and pathomechanisms that evolve in the minutes and hours following traumatic vascular injury in the brain remain largely unknown. We investigated the pathophysiology evolution in mice within the first 3 hours after closed-head traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH), two significant traumatic vascular injuries. METHODS: We took a multimodal imaging approach using photoacoustic imaging, color Doppler ultrasound, and MRI to track injury outcomes using a variety of metrics. RESULTS: Brain oxygenation and velocity-weighted volume of blood flow (VVF) values significantly decreased from baseline to 15 minutes after both TBI and SAH. TBI resulted in 19.2% and 41.0% ipsilateral oxygenation and VVF reductions 15 minutes postinjury, while SAH resulted in 43.9% and 85.0% ipsilateral oxygenation and VVF reduction (p < .001). We found partial recovery of oxygenation from 15 minutes to 3 hours after injury for TBI but not SAH. Hemorrhage, edema, reduced perfusion, and altered diffusivity were evident from MRI scans acquired 90-150 minutes after injury in both injury models, although the spatial distribution was mostly focal for TBI and diffuse for SAH. CONCLUSIONS: The results reveal that the cerebral oxygenation deficits immediately following injuries are reversible for TBI and irreversible for SAH. Our findings can inform future studies on mitigating these early responses to improve long-term recovery.

Associating Frailty and Dynamic Dysregulation between Motor and Cardiac Autonomic Systems.

Frailty is a geriatric syndrome associated with the lack of physiological reserve and consequent adverse outcomes (therapy complications and death) in older adults. Recent research has shown associations between heart rate (HR) dynamics (HR changes during physical activity) with frailty. The goal of the present study was to determine the effect of frailty on the interconnection between motor and cardiac systems during a localized upper-extremity function (UEF) test. Fifty-six older adults aged 65 or older were recruited and performed the UEF task of rapid elbow flexion for 20-seconds with the right arm. Frailty was assessed using the Fried phenotype. Wearable gyroscopes and electrocardiography were used to measure motor function and HR dynamics. Using convergent cross-mapping (CCM) the interconnection between motor (angular displacement) and cardiac (HR) performance was assessed. A significantly weaker interconnection was observed among pre-frail and frail participants compared to non-frail individuals (p<0.01, effect size=0.81±0.08). Using logistic models pre-frailty and frailty were identified with sensitivity and specificity of 82% to 89%, using motor, HR dynamics, and interconnection parameters. Findings suggested a strong association between cardiac-motor interconnection and frailty. Adding CCM parameters in a multimodal model may provide a promising measure of frailty.

Elasticity imaging using physics-informed neural networks: Spatial discovery of elastic modulus and Poisson's ratio.

Elasticity imaging is a technique that discovers the spatial distribution of mechanical properties of tissue using deformation and force measurements under various loading conditions. Given the complexity of this discovery, most existing methods approximate only one material parameter while assuming homogeneous distributions for the others. We employ physics-informed neural networks (PINN) in linear elasticity problems to discover the space-dependent distribution of both elastic modulus (E) and Poisson's ratio (ν) simultaneously, using strain data, normal stress boundary conditions, and the governing physics. We validated our model on three examples. First, we experimentally loaded hydrogel samples with embedded stiff inclusions, representing tumorous tissue, and compared the approximations against ground truth determined through tensile tests. Next, using data from finite element simulation of a rectangular domain containing a stiff circular inclusion, the PINN model accurately localized the inclusion and estimated both E and ν. We observed that in a heterogeneous domain, assuming a homogeneous ν distribution increases estimation error for stiffness as well as the area of the stiff inclusion, which could have clinical importance when determining size and stiffness of tumorous tissue. Finally, our model accurately captured spatial distribution of mechanical properties and the tissue interfaces on data from another computational model, simulating uniaxial loading of a rectangular hydrogel sample containing a human brain slice with distinct gray matter and white matter regions and complex geometrical features. This elasticity imaging implementation has the potential to be used in clinical imaging scenarios to reliably discover the spatial distribution of mechanical parameters and identify material interfaces such as tumors. STATEMENT OF SIGNIFICANCE: Our work is the first implementation of physics-informed neural networks to reconstruct both material parameters - Young's modulus and Poisson's ratio - and stress distributions for isotropic linear elastic materials by having deformation and force measurements. We comprehensively validate our model using experimental measurements and synthetic data generated using finite element modeling. Our method can be implemented in clinical elasticity imaging scenarios to improve diagnosis of tumors and for mechanical characterization of biomaterials and biological tissues in a minimally invasive manner.

Neuroimaging, wearable sensors, and blood-based biomarkers reveal hyperacute changes in the brain after sub-concussive impacts.

Impacts in mixed martial arts (MMA) have been studied mainly in regard to the long-term effects of concussions. However, repetitive sub-concussive head impacts at the hyperacute phase (minutes after impact), are not understood. The head experiences rapid acceleration similar to a concussion, but without clinical symptoms. We utilize portable neuroimaging technology - transcranial Doppler (TCD) ultrasound and functional near infrared spectroscopy (fNIRS) - to estimate the extent of pre- and post-differences following contact and non-contact sparring sessions in nine MMA athletes. In addition, the extent of changes in neurofilament light (NfL) protein biomarker concentrations, and neurocognitive/balance parameters were determined following impacts. Athletes were instrumented with sensor-based mouth guards to record head kinematics. TCD and fNIRS results demonstrated significantly increased blood flow velocity (p = 0.01) as well as prefrontal (p = 0.01) and motor cortex (p = 0.04) oxygenation, only following the contact sparring sessions. This increase after contact was correlated with the cumulative angular acceleration experienced during impacts (p = 0.01). In addition, the NfL biomarker demonstrated positive correlations with angular acceleration (p = 0.03), and maximum principal and fiber strain (p = 0.01). On average athletes experienced 23.9 ± 2.9 g peak linear acceleration, 10.29 ± 1.1 rad/s peak angular velocity, and 1,502.3 ± 532.3 rad/s2 angular acceleration. Balance parameters were significantly increased following contact sparring for medial-lateral (ML) center of mass (COM) sway, and ML ankle angle (p = 0.01), illustrating worsened balance. These combined results reveal significant changes in brain hemodynamics and neurophysiological parameters that occur immediately after sub-concussive impacts and suggest that the physical impact to the head plays an important role in these changes.

Morphological changes in glial cells arrangement under mechanical loading: A quantitative study.

The mechanical properties and microstructure of brain tissue, as its two main physical parameters, could be affected by mechanical stimuli. In previous studies, microstructural alterations due to mechanical loading have received less attention than the mechanical properties of the tissue. Therefore, the current study aimed to investigate the effect of ex-vivo mechanical forces on the micro-architecture of brain tissue including axons and glial cells. A three-step loading protocol (i.e., loading-recovery-loading) including eight strain levels from 5% to 40% was applied to bovine brain samples with axons aligned in one preferred direction (each sample experienced only one level of strain). After either the first or secondary loading step, the samples were fixed, cut in planes parallel and perpendicular to the loading direction, and stained for histology. The histological images were analyzed to measure the end-to-end length of axons and glial cell-cell distances. The results showed that after both loading steps, as the strain increased, the changes in the cell nuclei arrangement in the direction parallel to axons were more significant compared to the other two perpendicular directions. Based on this evidence, we hypothesized that the spatial pattern of glial cells is highly affected by the orientation of axonal fibers. Moreover, the results revealed that in both loading steps, the maximum cell-cell distance occurred at 15% strain, and this distance decreased for higher strains. Since 15% strain is close to the previously reported brain injury threshold, this evidence could suggest that at higher strains, the axons start to rupture, causing a reduction in the displacement of glial cells. Accordingly, it was concluded that more attention to glial cells' architecture during mechanical loading may lead to introduce a new biomarker for brain injury.

Novel imaging markers for altered cerebrovascular morphology in aging, stroke, and Alzheimer's disease.

BACKGROUND AND PURPOSE: Altered brain vasculature is a key phenomenon in several neurologic disorders. This paper presents a quantitative assessment of the anatomical variations in the Circle of Willis (CoW) and vascular morphology in healthy aging, acute ischemic stroke (AIS) and Alzheimer's Disease (AD). METHODS: We used our novel automatic method to segment and extract geometric features of the cerebral vasculature from MR angiography scans of 175 healthy subjects, which were used to create a probabilistic atlas of cerebrovasculature and to study normal aging and intersubject variations in CoW anatomy. Subsequently, we quantified and analyzed vascular alterations in 45AIS and 50 AD patients, two prominent cerebrovascular and neurodegenerative disorders. RESULTS: In the sampled cohort, we determined that the CoW is fully formed in only 35% of healthy adults and found significantly (p < .05) increased tortuosity and fractality, with increasing age and also with disease in both AIS and AD. We also found significantly lower vessel length, volume, and number of branches in AIS patients, as expected. The AD cerebral vessels exhibited significantly smaller diameter and more complex branching patterns, compared to age-matched healthy adults. These changes were significantly heightened (p < .05) among healthy, early onset mild AD, and moderate/severe dementia groups. CONCLUSION: Although our study does not include longitudinal data due to paucity of such datasets, the specific geometric features and quantitative comparisons demonstrate the potential for using vascular morphology as a noninvasive imaging biomarker for neurologic disorders.

Physics-Informed Neural Networks for Brain Hemodynamic Predictions Using Medical Imaging.

Determining brain hemodynamics plays a critical role in the diagnosis and treatment of various cerebrovascular diseases. In this work, we put forth a physics-informed deep learning framework that augments sparse clinical measurements with one-dimensional (1D) reduced-order model (ROM) simulations to generate physically consistent brain hemodynamic parameters with high spatiotemporal resolution. Transcranial Doppler (TCD) ultrasound is one of the most common techniques in the current clinical workflow that enables noninvasive and instantaneous evaluation of blood flow velocity within the cerebral arteries. However, it is spatially limited to only a handful of locations across the cerebrovasculature due to the constrained accessibility through the skull's acoustic windows. Our deep learning framework uses in vivo real-time TCD velocity measurements at several locations in the brain combined with baseline vessel cross-sectional areas acquired from 3D angiography images and provides high-resolution maps of velocity, area, and pressure in the entire brain vasculature. We validate the predictions of our model against in vivo velocity measurements obtained via four-dimensional (4D) flow magnetic resonance imaging (MRI) scans. We then showcase the clinical significance of this technique in diagnosing cerebral vasospasm (CVS) by successfully predicting the changes in vasospastic local vessel diameters based on corresponding sparse velocity measurements. We show this capability by generating synthetic blood flow data after cerebral vasospasm at various levels of stenosis. Here, we demonstrate that the physics-based deep learning approach can estimate and quantify the subject-specific cerebral hemodynamic variables with high accuracy despite lacking knowledge of inlet and outlet boundary conditions, which is a significant limitation for the accuracy of the conventional purely physics-based computational models.

4D Reconstruction and Identification of Carotid Artery Stenosis Utilizing a Novel Pulsatile Ultrasound Phantom.

As a major application focus of vascular ultrasonography, the carotid artery has long been the subject of phantom design and procedure focus. It is therefore important to devise procedures that are minimally invasive and informative, initially using a physiologically accurate anthropomorphic phantom to validate the methodology. In this article, a novel phantom design protocol is presented that enables the efficient production of a pulsatile ultrasound phantom consisting of soft and vascular tissue mimics, as well as a blood surrogate fluid. These components when combined give the phantom high acoustic compatibility and lifelike mechanical properties. The phantom was developed using "at-home" purchasable components and 3D printing technology. The phantom was subsequently used to develop a 4D reconstruction algorithm of the pulsing vessel in MATLAB. In pattern with recent developments in medical imaging, the 4D reconstruction enables clinicians to view vessel wall motion in a 3D space without the need for manual intervention. The reconstruction algorithm also produces measured inner luminal areas and vessel wall thickness, providing further information relating to structural properties and stenosis, as well as elastic properties such as arterial stiffness, which could provide helpful markers for disease diagnosis. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Constructing a pulsatile ultrasound phantom model Support Protocol: Creating a vascular mimic mold Basic Protocol 2: Creating a 4D reconstruction from ultrasound frames.

Dual-task performance is associated with brain MRI Morphometry in individuals with mild cognitive impairment.

BACKGROUND AND PURPOSE: Cognitive impairment is a critical health problem in the elderly population. Research has shown that patients with mild cognitive impairment (MCI) may develop dementia in later years. Therefore, early identification of MCI could allow for interventions to help delay the progression of this devastating disease. Our objective in this study was to detect the early presence of MCI in elderly patients via neuroimaging and dual-task performance. METHODS: Brain MRI scans from 21 older adult volunteers, including cognitively healthy adults (HA, n = 9, age = 68-79 years) and mild cognitively impaired (MCI, n = 12, age = 66-92 years) were analyzed using automatic segmentation techniques. Regional volume, surface area, and thickness measures were correlated with simultaneous performance of motor and cognitive tasks (dual-task) within a novel upper-extremity function (UEF) test, using multivariate analysis of variance models. RESULTS: We found significant associations of dual-task performance with volume of five cortical brain regions (P ≤ .048) and thickness of 13 regions (P ≤ .043) within the frontal, temporal, and parietal lobes. There was a significant interaction effect of cognitive group on dual-task score for the inferior temporal gyrus volume (P ≤ .034), and the inferior parietal lobule, inferior temporal gyrus, and middle temporal gyrus average thickness (P ≤ .037). CONCLUSIONS: This study highlighted the potential of dual-tasking and MRI morphometric changes as a simple and accurate tool for early detection of cognitive impairment among community-dwelling older adults. The strong interaction effects of cognitive group on UEF dual-task score suggest higher association between atrophy of these brain structures and compromised dual-task performance among the MCI group.

Automatic segmentation, feature extraction and comparison of healthy and stroke cerebral vasculature.

Accurate segmentation of cerebral vasculature and a quantitative assessment of its morphology is critical to various diagnostic and therapeutic purposes and is pertinent to studying brain health and disease. However, this is still a challenging task due to the complexity of the vascular imaging data. We propose an automated method for cerebral vascular segmentation without the need of any manual intervention as well as a method to skeletonize the binary segmented map to extract vascular geometric features and characterize vessel structure. We combine a Hessian-based probabilistic vessel-enhancing filtering with an active-contour-based technique to segment magnetic resonance and computed tomography angiograms (MRA and CTA) and subsequently extract the vessel centerlines and diameters to calculate the geometrical properties of the vasculature. Our method was validated using a 3D phantom of the Circle-of-Willis region, demonstrating 84% mean Dice similarity coefficient (DSC) and 85% mean Pearson's correlation coefficient (PCC) with minimal modified Hausdorff distance (MHD) error (3 surface pixels at most), and showed superior performance compared to existing segmentation algorithms upon quantitative comparison using DSC, PCC and MHD. We subsequently applied our algorithm to a dataset of 40 subjects, including 1) MRA scans of healthy subjects (n = 10, age = 30 ± 9), 2) MRA scans of stroke patients (n = 10, age = 51 ± 15), 3) CTA scans of healthy subjects (n = 10, age = 62 ± 12), and 4) CTA scans of stroke patients (n = 10, age = 68 ± 11), and obtained a quantitative comparison between the stroke and normal vasculature for both imaging modalities. The vascular network in stroke patients compared to age-adjusted healthy subjects was found to have a significantly (p < 0.05) higher tortuosity (3.24 ± 0.88 rad/cm vs. 7.17 ± 1.61 rad/cm for MRA, and 4.36 ± 1.32 rad/cm vs. 7.80 ± 0.92 rad/cm for CTA), higher fractal dimension (1.36 ± 0.28 vs. 1.71 ± 0.14 for MRA, and 1.56 ± 0.05 vs. 1.69 ± 0.20 for CTA), lower total length (3.46 ± 0.99 m vs. 2.20 ± 0.67 m for CTA), lower total volume (61.80 ± 18.79 ml vs. 34.43 ± 22.9 ml for CTA), lower average diameter (2.4 ± 0.21 mm vs. 2.18 ± 0.07 mm for CTA), and lower average branch length (4.81 ± 1.97 mm vs. 8.68 ± 2.03 mm for MRA), respectively. We additionally studied the change in vascular features with respect to aging and imaging modality. While we observed differences between features as a result of aging, statistical analysis did not show any significant differences, whereas we found that the number of branches were significantly different (p < 0.05) between the two imaging modalities (201 ± 73 for MRA vs. 189 ± 69 for CTA). Our segmentation and feature extraction algorithm can be applied on any imaging modality and can be used in the future to automatically obtain the 3D segmented vasculature for diagnosis and treatment planning as well as to study morphological changes due to stroke and other cerebrovascular diseases (CVD) in the clinic.

Viscoelasticity of children and adolescent brains through MR elastography.

Magnetic Resonance Elastography (MRE) is an elasticity imaging technique that allows a safe, fast, and non-invasive evaluation of the mechanical properties of biological tissues in vivo. Since mechanical properties reflect a tissue's composition and arrangement, MRE is a powerful tool for the investigation of the microstructural changes that take place in the brain during childhood and adolescence. The goal of this study was to evaluate the viscoelastic properties of the brain in a population of healthy children and adolescents in order to identify potential age and sex dependencies. We hypothesize that because of myelination, age dependent changes in the mechanical properties of the brain will occur during childhood and adolescence. Our sample consisted of 26 healthy individuals (13 M, 13 F) with age that ranged from 7-17 years (mean: 11.9 years). We performed multifrequency MRE at 40, 60, and 80 Hz actuation frequencies to acquire the complex-valued shear modulus G = G' + iG″ with the fundamental MRE parameters being the storage modulus (G'), the loss modulus (G″), and the magnitude of complex-valued shear modulus (|G|). We fitted a springpot model to these frequency-dependent MRE parameters in order to obtain the parameter α, which is related to tissue's microstructure, and the elasticity parameter k, which was converted to a shear modulus parameter (µ) through viscosity (η). We observed no statistically significant variation in the parameter µ, but a significant increase of the microstructural parameter α of the white matter with increasing age (p < 0.05). Therefore, our MRE results suggest that subtle microstructural changes such as neural tissue's enhanced alignment and geometrical reorganization during childhood and adolescence could result in significant biomechanical changes. In line with previously reported MRE data for adults, we also report significantly higher shear modulus (µ) for female brains when compared to males (p < 0.05). The data presented here can serve as a clinical baseline in the analysis of the pediatric and adolescent brain's viscoelasticity over this age span, as well as extending our understanding of the biomechanics of brain development.

Between-day repeatability of sensor-based in-home gait assessment among older adults: assessing the effect of frailty.

BACKGROUND: While sensor-based daily physical activity (DPA) gait assessment has been demonstrated to be an effective measure of physical frailty and fall-risk, the repeatability of DPA gait parameters between different days of measurement is not clear. AIMS: To evaluate test-retest reliability (repeatability) of DPA gait performance parameters, representing the quality of walking, and quantitative gait measures (e.g. number of steps) between two separate days of assessment among older adults. METHODS: DPA was acquired for 48-h from older adults (age ≥ 65 years) using a tri-axial accelerometer. Continuous walking bouts (≥ 60 s) were identified from acceleration data and used to extract gait performance parameters, including time- and frequency-domain gait parameters, representing walking speed, variability, and irregularity. To assess repeatability, intraclass correlation coefficient (ICC) was calculated using two-way mixed effects F-test models for day-1 vs. day-2 as the independent random effect. Repeatability tests were performed for all participants and also within frailty groups (non-frail and pre-frail/frail identified using Fried phenotype). RESULTS: Data was analyzed from 63 older adults (29 non-frail and 34 pre-frail/frail). Most of the time- and frequency-domain gait performance parameters showed good to excellent repeatability (ICC ≥ 0.70), while quantitative parameters, including number of steps and walking duration showed poor repeatability (ICC < 0.30). Among majority of the gait performance parameters, we observed higher repeatability among the pre-frail/frail group (ICC > 0.78) compared to non-frail individuals (0.39 < ICC < 0.55). CONCLUSION: Gait performance parameters, showed higher repeatability compared to quantitative measures. Higher repeatability among pre-frail/frail individuals may be attributed to a reduced functional capacity for performing more intense and variable physical tasks. TRIAL REGISTRATION: The clinical trial was retrospectively registered on June 18th, 2013 with ClinicalTrials.gov, identifier NCT01880229.

Tension Strain-Softening and Compression Strain-Stiffening Behavior of Brain White Matter.

Brain, the most important component of the central nervous system (CNS), is a soft tissue with a complex structure. Understanding the role of brain tissue microstructure in mechanical properties is essential to have a more profound knowledge of how brain development, disease, and injury occur. While many studies have investigated the mechanical behavior of brain tissue under various loading conditions, there has not been a clear explanation for variation reported for material properties of brain tissue. The current study compares the ex-vivo mechanical properties of brain tissue under two loading modes, namely compression and tension, and aims to explain the differences observed by closely examining the microstructure under loading. We tested bovine brain samples under uniaxial tension and compression loading conditions, and fitted hyperelastic material parameters. At 20% strain, we observed that the shear modulus of brain tissue in compression is about 6 times higher than in tension. In addition, we observed that brain tissue exhibited strain-stiffening in compression and strain-softening in tension. In order to investigate the effect of loading modes on the tissue microstructure, we fixed the samples using a novel method that enabled keeping the samples at the loaded stage during the fixation process. Based on the results of histology, we hypothesize that during compressive loading, the strain-stiffening behavior of the tissue could be attributed to glial cell bodies being pushed against surroundings, contacting each other and resisting compression, while during tension, cell connections are detached and the tissue displays softening behavior.

Structural Anisotropy vs. Mechanical Anisotropy: The Contribution of Axonal Fibers to the Material Properties of Brain White Matter.

Brain's micro-structure plays a critical role in its macro-structure material properties. Since the structural anisotropy in the brain white matter has been introduced due to axonal fibers, considering the direction of axons in the continuum models has been mediated to improve the results of computational simulations. The aim of the current study was to investigate the role of fiber direction in the material properties of brain white matter and compare the mechanical behavior of the anisotropic white matter and the isotropic gray matter. Diffusion tensor imaging (DTI) was employed to detect the direction of axons in white matter samples, and tensile stress-relaxation loads up to 20% strains were applied on bovine gray and white matter samples. In order to calculate the nonlinear and time-dependent properties of white matter and gray matter, a visco-hyperelastic model was used. The results indicated that the mechanical behavior of white matter in two orthogonal directions, parallel and perpendicular to axonal fibers, are significantly different. This difference indicates that brain white matter could be assumed as an anisotropic material and axons have contribution in the mechanical properties. Also, up to 15% strain, white matter samples with axons parallel to the force direction are significantly stiffer than both the gray matter samples and white matter samples with axons perpendicular to the force direction. Moreover, the elastic moduli of white matter samples with axons both parallel and perpendicular to the loading direction and gray matter samples at 15-20% strain are not significantly different. According to these observations, it is suggested that axons have negligible roles in the material properties of white matter when it is loaded in the direction perpendicular to the axon direction. Finally, this observation showed that the anisotropy of brain tissue not only has effects on the elastic behavior, but also has effects on the viscoelastic behavior.

The importance of axonal directions in the brainstem injury during neurosurgical interventions.

Brainstem, which connects the distal part of the brain and the spinal cord, contains main motor and sensory nerves and facilitates communication between the cerebrum, cerebellum, and spinal cord. Due to the complicated anatomy and neurostructure of brainstem, surgical interventions to resect brainstem tumors are particularly challenging, and new approaches to reduce the risk of surgical brain injury are of utmost importance. Although previous studies have investigated the structural anisotropy of brain white matter, the effect of axonal fibers on the mechanical properties of white matter has not yet been fully understood. The current study aims to compare the effect of axonal orientation on changes in material properties of brainstem under large deformations and failure through a novel approach. Using diffusion tensor imaging (DTI) on ex-vivo bovine brains, we determined the orientation of axons in brainstem. We extracted brainstem samples in two orthogonal directions, parallel and perpendicular to the axons, and subjected to uniaxial tension to reach the failure at loading rates of 50 mm/min and 150 mm/min. The results showed that the tearing energy and failure strain of samples with axons parallel to the force direction were approximately 1.5 times higher than the samples with axons perpendicular to the force direction. The results also revealed that as the sample's initial length increases, its failure strain decreases. These results emphasize the importance of the axon orientation in the mechanical properties of brainstem, and suggest that considering the directional-dependent behavior for this tissue could help to propose new surgical interventions for reducing the risk of injury during tumor resection.

Mind the gap: A mechanobiological hypothesis for the role of gap junctions in the mechanical properties of injured brain tissue.

Despite more than half a century of work on the brain biomechanics, there are still significant unknowns about this tissue. Since the brain is highly susceptible to injury, damage biomechanics has been one of the main areas of interest to the researchers in the field of brain biomechanics. In many previous studies, mechanical properties of brain tissue under sub-injury and injury level loading conditions have been addressed; however, to the best of our knowledge, the role of cell-cell interactions in the mechanical behavior of brain tissue has not been well examined yet. This note introduces the hypothesis that gap junctions as the major type of cell-cell junctions in the brain tissue play a pivotal role in the mechanical properties of the tissue and their failure during injury leads to changes in brain's material properties. According to this hypothesis, during an injury, the gap junctions are damaged, leading to a decrease in tissue stiffness, whereas following the injury, new junction proteins are expressed, leading to an increase in tissue stiffness. We suggest that considering the mechanobiological effect of gap junctions in the material properties of brain tissue may help better understand the brain injury mechanism.