Digital Mobility Measures: A Window into Real-World Severity and Progression of Parkinson's Disease.

BACKGROUND: Real-world monitoring using wearable sensors has enormous potential for assessing disease severity and symptoms among persons with Parkinson's disease (PD). Many distinct features can be extracted, reflecting multiple mobility domains. However, it is unclear which digital measures are related to PD severity and are sensitive to disease progression. OBJECTIVES: The aim was to identify real-world mobility measures that reflect PD severity and show discriminant ability and sensitivity to disease progression, compared to the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scale. METHODS: Multicenter real-world continuous (24/7) digital mobility data from 587 persons with PD and 68 matched healthy controls were collected using an accelerometer adhered to the lower back. Machine learning feature selection and regression algorithms evaluated associations of the digital measures using the MDS-UPDRS (I-III). Binary logistic regression assessed discriminatory value using controls, and longitudinal observational data from a subgroup (n = 33) evaluated sensitivity to change over time. RESULTS: Digital measures were only moderately correlated with the MDS-UPDRS (part II-r = 0.60 and parts I and III-r = 0.50). Most associated measures reflected activity quantity and distribution patterns. A model with 14 digital measures accurately distinguished recently diagnosed persons with PD from healthy controls (81.1%, area under the curve: 0.87); digital measures showed larger effect sizes (Cohen's d: [0.19-0.66]), for change over time than any of the MDS-UPDRS parts (Cohen's d: [0.04-0.12]). CONCLUSIONS: Real-world mobility measures are moderately associated with clinical assessments, suggesting that they capture different aspects of motor capacity and function. Digital mobility measures are sensitive to early-stage disease and to disease progression, to a larger degree than conventional clinical assessments, demonstrating their utility, primarily for clinical trials but ultimately also for clinical care. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

A Double-Blind, Randomized, Placebo-Controlled Trial of Ursodeoxycholic Acid (UDCA) in Parkinson's Disease.

BACKGROUND: Rescue of mitochondrial function is a promising neuroprotective strategy for Parkinson's disease (PD). Ursodeoxycholic acid (UDCA) has shown considerable promise as a mitochondrial rescue agent across a range of preclinical in vitro and in vivo models of PD. OBJECTIVES: To investigate the safety and tolerability of high-dose UDCA in PD and determine midbrain target engagement. METHODS: The UP (UDCA in PD) study was a phase II, randomized, double-blind, placebo-controlled trial of UDCA (30 mg/kg daily, 2:1 randomization UDCA vs. placebo) in 30 participants with PD for 48 weeks. The primary outcome was safety and tolerability. Secondary outcomes included 31-phosphorus magnetic resonance spectroscopy (31 P-MRS) to explore target engagement of UDCA in PD midbrain and assessment of motor progression, applying both the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) and objective, motion sensor-based quantification of gait impairment. RESULTS: UDCA was safe and well tolerated, and only mild transient gastrointestinal adverse events were more frequent in the UDCA treatment group. Midbrain 31 P-MRS demonstrated an increase in both Gibbs free energy and inorganic phosphate levels in the UDCA treatment group compared to placebo, reflecting improved ATP hydrolysis. Sensor-based gait analysis indicated a possible improvement of cadence (steps per minute) and other gait parameters in the UDCA group compared to placebo. In contrast, subjective assessment applying the MDS-UPDRS-III failed to detect a difference between treatment groups. CONCLUSIONS: High-dose UDCA is safe and well tolerated in early PD. Larger trials are needed to further evaluate the disease-modifying effect of UDCA in PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Assessing real-world gait with digital technology? Validation, insights and recommendations from the Mobilise-D consortium.

BACKGROUND: Although digital mobility outcomes (DMOs) can be readily calculated from real-world data collected with wearable devices and ad-hoc algorithms, technical validation is still required. The aim of this paper is to comparatively assess and validate DMOs estimated using real-world gait data from six different cohorts, focusing on gait sequence detection, foot initial contact detection (ICD), cadence (CAD) and stride length (SL) estimates. METHODS: Twenty healthy older adults, 20 people with Parkinson's disease, 20 with multiple sclerosis, 19 with proximal femoral fracture, 17 with chronic obstructive pulmonary disease and 12 with congestive heart failure were monitored for 2.5 h in the real-world, using a single wearable device worn on the lower back. A reference system combining inertial modules with distance sensors and pressure insoles was used for comparison of DMOs from the single wearable device. We assessed and validated three algorithms for gait sequence detection, four for ICD, three for CAD and four for SL by concurrently comparing their performances (e.g., accuracy, specificity, sensitivity, absolute and relative errors). Additionally, the effects of walking bout (WB) speed and duration on algorithm performance were investigated. RESULTS: We identified two cohort-specific top performing algorithms for gait sequence detection and CAD, and a single best for ICD and SL. Best gait sequence detection algorithms showed good performances (sensitivity > 0.73, positive predictive values > 0.75, specificity > 0.95, accuracy > 0.94). ICD and CAD algorithms presented excellent results, with sensitivity > 0.79, positive predictive values > 0.89 and relative errors < 11% for ICD and < 8.5% for CAD. The best identified SL algorithm showed lower performances than other DMOs (absolute error < 0.21 m). Lower performances across all DMOs were found for the cohort with most severe gait impairments (proximal femoral fracture). Algorithms' performances were lower for short walking bouts; slower gait speeds (< 0.5 m/s) resulted in reduced performance of the CAD and SL algorithms. CONCLUSIONS: Overall, the identified algorithms enabled a robust estimation of key DMOs. Our findings showed that the choice of algorithm for estimation of gait sequence detection and CAD should be cohort-specific (e.g., slow walkers and with gait impairments). Short walking bout length and slow walking speed worsened algorithms' performances. Trial registration ISRCTN - 12246987.

A Single-Sensor Approach to Quantify Gait in Patients with Hereditary Spastic Paraplegia.

Hereditary spastic paraplegia (HSP) is characterised by progressive lower-limb spasticity and weakness resulting in ambulation difficulties. During clinical practice, walking is observed and/or assessed by timed 10-metre walk tests; time, feasibility, and methodological reliability are barriers to detailed characterisation of patients' walking abilities when instrumenting this test. Wearable sensors have the potential to overcome such drawbacks once a validated approach is available for patients with HSP. Therefore, while limiting patients' and assessors' burdens, this study aims to validate the adoption of a single lower-back wearable inertial sensor approach for step detection in HSP patients; this is the first essential algorithmic step in quantifying most gait temporal metrics. After filtering the 3D acceleration signal based on its smoothness and enhancing the step-related peaks, initial contacts (ICs) were identified as positive zero-crossings of the processed signal. The proposed approach was validated on thirteen individuals with HSP while they performed three 10-metre tests and wore pressure insoles used as a gold standard. Overall, the single-sensor approach detected 794 ICs (87% correctly identified) with high accuracy (median absolute errors (mae): 0.05 s) and excellent reliability (ICC = 1.00). Although about 12% of the ICs were missed and the use of walking aids introduced extra ICs, a minor impact was observed on the step time quantifications (mae 0.03 s (5.1%), ICC = 0.89); the use of walking aids caused no significant differences in the average step time quantifications. Therefore, the proposed single-sensor approach provides a reliable methodology for step identification in HSP, augmenting the gait information that can be accurately and objectively extracted from patients with HSP during their clinical assessment.

Design and validation of a multi-task, multi-context protocol for real-world gait simulation.

BACKGROUND: Measuring mobility in daily life entails dealing with confounding factors arising from multiple sources, including pathological characteristics, patient specific walking strategies, environment/context, and purpose of the task. The primary aim of this study is to propose and validate a protocol for simulating real-world gait accounting for all these factors within a single set of observations, while ensuring minimisation of participant burden and safety. METHODS: The protocol included eight motor tasks at varying speed, incline/steps, surface, path shape, cognitive demand, and included postures that may abruptly alter the participants' strategy of walking. It was deployed in a convenience sample of 108 participants recruited from six cohorts that included older healthy adults (HA) and participants with potentially altered mobility due to Parkinson's disease (PD), multiple sclerosis (MS), proximal femoral fracture (PFF), chronic obstructive pulmonary disease (COPD) or congestive heart failure (CHF). A novelty introduced in the protocol was the tiered approach to increase difficulty both within the same task (e.g., by allowing use of aids or armrests) and across tasks. RESULTS: The protocol proved to be safe and feasible (all participants could complete it and no adverse events were recorded) and the addition of the more complex tasks allowed a much greater spread in walking speeds to be achieved compared to standard straight walking trials. Furthermore, it allowed a representation of a variety of daily life relevant mobility aspects and can therefore be used for the validation of monitoring devices used in real life. CONCLUSIONS: The protocol allowed for measuring gait in a variety of pathological conditions suggests that it can also be used to detect changes in gait due to, for example, the onset or progression of a disease, or due to therapy. TRIAL REGISTRATION: ISRCTN-12246987.

A Quality Control Check to Ensure Comparability of Stereophotogrammetric Data between Sessions and Systems.

Optoelectronic stereophotogrammetric (SP) systems are widely used in human movement research for clinical diagnostics, interventional applications, and as a reference system for validating alternative technologies. Regardless of the application, SP systems exhibit different random and systematic errors depending on camera specifications, system setup and laboratory environment, which hinders comparing SP data between sessions and across different systems. While many methods have been proposed to quantify and report the errors of SP systems, they are rarely utilized due to their complexity and need for additional equipment. In response, an easy-to-use quality control (QC) check has been designed that can be completed immediately prior to a data collection. This QC check requires minimal training for the operator and no additional equipment. In addition, a custom graphical user interface ensures automatic processing of the errors in an easy-to-read format for immediate interpretation. On initial deployment in a multicentric study, the check (i) proved to be feasible to perform in a short timeframe with minimal burden to the operator, and (ii) quantified the level of random and systematic errors between sessions and systems, ensuring comparability of data in a variety of protocol setups, including repeated measures, longitudinal studies and multicentric studies.

An Objective Methodology for the Selection of a Device for Continuous Mobility Assessment.

Continuous monitoring by wearable technology is ideal for quantifying mobility outcomes in "real-world" conditions. Concurrent factors such as validity, usability, and acceptability of such technology need to be accounted for when choosing a monitoring device. This study proposes a bespoke methodology focused on defining a decision matrix to allow for effective decision making. A weighting system based on responses (n = 69) from a purpose-built questionnaire circulated within the IMI Mobilise-D consortium and its external collaborators was established, accounting for respondents' background and level of expertise in using wearables in clinical practice. Four domains (concurrent validity, CV; human factors, HF; wearability and usability, WU; and data capture process, CP), associated evaluation criteria, and scores were established through literature research and group discussions. While the CV was perceived as the most relevant domain (37%), the others were also considered highly relevant (WU: 30%, HF: 17%, CP: 16%). Respondents (~90%) preferred a hidden fixation and identified the lower back as an ideal sensor location for mobility outcomes. Overall, this study provides a novel, holistic, objective, as well as a standardized approach accounting for complementary aspects that should be considered by professionals and researchers when selecting a solution for continuous mobility monitoring.

Toward a Regulatory Qualification of Real-World Mobility Performance Biomarkers in Parkinson's Patients Using Digital Mobility Outcomes.

Wearable inertial sensors can be used to monitor mobility in real-world settings over extended periods. Although these technologies are widely used in human movement research, they have not yet been qualified by drug regulatory agencies for their use in regulatory drug trials. This is because the first generation of these sensors was unreliable when used on slow-walking subjects. However, intense research in this area is now offering a new generation of algorithms to quantify Digital Mobility Outcomes so accurate they may be considered as biomarkers in regulatory drug trials. This perspective paper summarises the work in the Mobilise-D consortium around the regulatory qualification of the use of wearable sensors to quantify real-world mobility performance in patients affected by Parkinson's Disease. The paper describes the qualification strategy and both the technical and clinical validation plans, which have recently received highly supportive qualification advice from the European Medicines Agency. The scope is to provide detailed guidance for the preparation of similar qualification submissions to broaden the use of real-world mobility assessment in regulatory drug trials.

Is a Wearable Sensor-Based Characterisation of Gait Robust Enough to Overcome Differences Between Measurement Protocols? A Multi-Centric Pragmatic Study in Patients with Multiple Sclerosis.

Inertial measurement units (IMUs) allow accurate quantification of gait impairment of people with multiple sclerosis (pwMS). Nonetheless, it is not clear how IMU-based metrics might be influenced by pragmatic aspects associated with clinical translation of this approach, such as data collection settings and gait protocols. In this study, we hypothesised that these aspects do not significantly alter those characteristics of gait that are more related to quality and energetic efficiency and are quantifiable via acceleration related metrics, such as intensity, smoothness, stability, symmetry, and regularity. To test this hypothesis, we compared 33 IMU-based metrics extracted from data, retrospectively collected by two independent centres on two matched cohorts of pwMS. As a worst-case scenario, a walking test was performed in the two centres at a different speed along corridors of different lengths, using different IMU systems, which were also positioned differently. The results showed that the majority of the temporal metrics (9 out of 12) exhibited significant between-centre differences. Conversely, the between-centre differences in the gait quality metrics were small and comparable to those associated with a test-retest analysis under equivalent conditions. Therefore, the gait quality metrics are promising candidates for reliable multi-centric studies aiming at assessing rehabilitation interventions within a routine clinical context.

Developing a toolkit for the assessment and monitoring of musculoskeletal ageing.

The complexities and heterogeneity of the ageing process have slowed the development of consensus on appropriate biomarkers of healthy ageing. The Medical Research Council-Arthritis Research UK Centre for Integrated research into Musculoskeletal Ageing (CIMA) is a collaboration between researchers and clinicians at the Universities of Liverpool, Sheffield and Newcastle. One of CIMA's objectives is to 'Identify and share optimal techniques and approaches to monitor age-related changes in all musculoskeletal tissues, and to provide an integrated assessment of musculoskeletal function'-in other words to develop a toolkit for assessing musculoskeletal ageing. This toolkit is envisaged as an instrument that can be used to characterise and quantify musculoskeletal function during 'normal' ageing, lend itself to use in large-scale, internationally important cohorts, and provide a set of biomarker outcome measures for epidemiological and intervention studies designed to enhance healthy musculoskeletal ageing. Such potential biomarkers include: biochemical measurements in biofluids or tissue samples, in vivo measurements of body composition, imaging of structural and physical properties, and functional tests. This review assesses candidate biomarkers of musculoskeletal ageing under these four headings, details their biological bases, strengths and limitations, and makes practical recommendations for their use. In addition, we identify gaps in the evidence base and priorities for further research on biomarkers of musculoskeletal ageing.

A comfort assessment of existing cervical orthoses.

PURPOSE: Identify location and intensity of discomfort experienced by healthy participants wearing cervical orthoses. METHOD: Convenience sample of 34 healthy participants wore Stro II, Philadelphia, Headmaster, and AspenVista® cervical orthoses for four-hour periods. Participants reported discomfort level (scale 0-6) and location. RESULTS: Participants reported mean discomfort for all orthoses over the four-hour test between 'a little discomfort' and 'very uncomfortable' (mean discomfort score = 1.64, SD = 1.50). Seven participants prematurely stopped tests due to pain and six reported maximum discomfort scores. Significant linear increase in discomfort with duration of wear was found for all orthoses. Significantly less discomfort was reported with Stro II than Headmaster and Philadelphia. Age correlated with greater perceived discomfort. Orthoses differed in the location discomfort was experienced. CONCLUSION: Existing cervical orthoses cause discomfort influenced by design and duration of wear with orthoses' design the more significant factor. This work informed the design of a new orthosis and future orthoses developments. Practitioner Summary: The purpose of this study was to gain greater knowledge about the discomfort caused by wearing of existing neck orthoses in order to inform the design and development of a new neck orthosis. This study gathers empirical data from a surrogate population and concludes that orthosis design is more influential than the duration of wear.

Reliability of inertial sensors in the assessment of patients with vestibular disorders: a feasibility study.

BACKGROUND: Vestibular disorders affect an individual's stability, balance, and gait and predispose them to falls. Traditional laboratory-based semi-objective vestibular assessments are intrusive and cumbersome provide little information about their functional ability. Commercially available wearable inertial sensors allow us to make this real life assessments objective, with a detailed view of their functional abilities. Timed Up and Go (TUG) and Postural Sway tests are commonly used tests for gait and balance assessments. Our aim was to assess the feasibility, test-retest reliability and ability to classify fall status in individuals with vestibular disorders using parameters derived from the commercially available wearable system (inertial sensors and the Mobility Lab Software, APDM, Inc.). METHODS: We recruited 27 individuals diagnosed either with unilateral or bilateral vestibular loss on vestibular function testing. Instrumented Timed Up and Go (iTUG) and Postural Sway (iSway) were administered three times during the first session and then repeated at a similar time the following week. To evaluate within and between sessions reliability of the parameters the Intra-Class Correlation coefficient (ICC) was used. Subsequently, the ability of reliable parameters (ICC ≥ 0.8) to classify fallers from non-fallers was estimated. RESULTS: The iTUG test parameters showed good within and between sessions' reliability with mean ICC (between-sessions) values of 0.81 ± 0.17 and 0.69 ± 0.15, respectively. For the iSway test, the relative figures were; 0.76 ± 0.13 and 0.71 ± 0.14, respectively. A retrospective falls classification analysis with past 12 months falls history data yielded an accuracy of 66.70% with an area under the curve of 0.79. Mean Distance from centre of COP (mm) of accelerometer's trajectory (m/s2) from the iSway test was the only significant parameter to classify fallers from non-fallers. CONCLUSIONS: Using a commercially available wearable system a subset of reliable iTUG and iSway parameters were identified and their ability to classify fallers were estimated. These parameters have potential to augment assessments of vestibular patients to enable clinicians and therapists to provide objective, tailored, personalised interventions for their gait and postural control and also to objectively evaluate and monitor the efficiency of their interventions.

A New Proxy Measurement Algorithm with Application to the Estimation of Vertical Ground Reaction Forces Using Wearable Sensors.

Measurement of the ground reaction forces (GRF) during walking is typically limited to laboratory settings, and only short observations using wearable pressure insoles have been reported so far. In this study, a new proxy measurement method is proposed to estimate the vertical component of the GRF (vGRF) from wearable accelerometer signals. The accelerations are used as the proxy variable. An orthogonal forward regression algorithm (OFR) is employed to identify the dynamic relationships between the proxy variables and the measured vGRF using pressure-sensing insoles. The obtained model, which represents the connection between the proxy variable and the vGRF, is then used to predict the latter. The results have been validated using pressure insoles data collected from nine healthy individuals under two outdoor walking tasks in non-laboratory settings. The results show that the vGRFs can be reconstructed with high accuracy (with an average prediction error of less than 5.0%) using only one wearable sensor mounted at the waist (L5, fifth lumbar vertebra). Proxy measures with different sensor positions are also discussed. Results show that the waist acceleration-based proxy measurement is more stable with less inter-task and inter-subject variability than the proxy measures based on forehead level accelerations. The proposed proxy measure provides a promising low-cost method for monitoring ground reaction forces in real-life settings and introduces a novel generic approach for replacing the direct determination of difficult to measure variables in many applications.

Free-living monitoring of Parkinson's disease: Lessons from the field.

Wearable technology comprises miniaturized sensors (eg, accelerometers) worn on the body and/or paired with mobile devices (eg, smart phones) allowing continuous patient monitoring in unsupervised, habitual environments (termed free-living). Wearable technologies are revolutionizing approaches to health care as a result of their utility, accessibility, and affordability. They are positioned to transform Parkinson's disease (PD) management through the provision of individualized, comprehensive, and representative data. This is particularly relevant in PD where symptoms are often triggered by task and free-living environmental challenges that cannot be replicated with sufficient veracity elsewhere. This review concerns use of wearable technology in free-living environments for people with PD. It outlines the potential advantages of wearable technologies and evidence for these to accurately detect and measure clinically relevant features including motor symptoms, falls risk, freezing of gait, gait, functional mobility, and physical activity. Technological limitations and challenges are highlighted, and advances concerning broader aspects are discussed. Recommendations to overcome key challenges are made. To date there is no fully validated system to monitor clinical features or activities in free-living environments. Robust accuracy and validity metrics for some features have been reported, and wearable technology may be used in these cases with a degree of confidence. Utility and acceptability appears reasonable, although testing has largely been informal. Key recommendations include adopting a multidisciplinary approach for standardizing definitions, protocols, and outcomes. Robust validation of developed algorithms and sensor-based metrics is required along with testing of utility. These advances are required before widespread clinical adoption of wearable technology can be realized. © 2016 International Parkinson and Movement Disorder Society.

Are gait variability and stability measures influenced by directional changes?

BACKGROUND: Many gait variability and stability measures have been proposed in the literature, with the aim to quantify gait impairment, degree of neuro-motor control and balance disorders in healthy and pathological subjects. These measures are often obtained from lower trunk acceleration data, typically acquired during rectilinear gait, but relevant experimental protocols and data processing techniques lack in standardization. Since directional changes represent an essential aspect of gait, the assessment of their influence on such measures is essential for standardization. In addition, their investigation is needed to evaluate the applicability of these measures in laboratory trials and in daily life activity analysis. A further methodological aspect to be standardized concerns the assessment of the sampling frequency, which could affect stability measures. The aim of the present study was hence to assess if gait variability and stability measures are affected by directional changes, and to evaluate the influence of sampling frequency of trunk acceleration data on the results. METHODS: Fifty-one healthy young adults performed a 6-minute walk test along a 30 m straight pathway, turning by 180 deg at each end of the pathway. Nine variability and stability measures (Standard deviation, Coefficient of variation, Poincaré plots, maximum Floquet multipliers, short-term Lyapunov exponents, Recurrence quantification analysis, Multiscale entropy, Harmonic ratio and Index of harmonicity) were calculated on stride duration and trunk acceleration data (acquired at 100 Hz and 200 Hz) coming from straight walking windows and from windows including both straight walking and the directional change. RESULTS: Harmonic ratio was the only measure that resulted to be affected by directional changes and sampling frequency, decreasing with the presence of a directional change task. HR was affected in the AP and V directions for the 200 Hz, but only in AP direction for the 100 Hz group. CONCLUSION: Multiscale entropy, short term Lyapunov exponents and Recurrence quantification analysis were generally not affected by directional changes nor by sampling frequency, and could contribute to the definition of a fall risk index in free-walking conditions.

Large-scale finite element analysis of human cancellous bone tissue micro computer tomography data: a convergence study.

The complex geometry of cancellous bone tissue makes it difficult to generate finite element (FE) models. Only a few studies investigated the convergence behavior at the tissue scale using Cartesian meshes. However, these studies were not conducted according to an ideal patch test and the postelastic convergence behavior was not reported. In this study, the third principal strain and stress, and the displacement obtained from human micro finite element (microFE) models of lower resolutions were compared against the model of 19.5 µm as a reference, representing the original spatial resolution of microCT data. Uni-axial compression simulations using both linear-elastic and nonlinear constitutive equations were performed. The results showed a decrease in percentage difference in all three values as the element size decreased, with the displacement converging the fastest among the three. Simulations carried out using a nonlinear constitutive equation however, failed to show convergence for the third principal strains and stresses. It was concluded that at the tissue level, Cartesian meshes of human cancellous bone tissue were able to reach a converged solution in all three parameters investigated for linear simulation and only in displacement for nonlinear simulation. These parameters can be used as references in the future for studies in local biomechanical behavior of human cancellous bone tissues with linear simulation. The convergence behavior for human cancellous bone tissue using nonlinear constitutive equations needs further investigation.

Automatic segmentation of lower limb muscles from MR images of post-menopausal women based on deep learning and data augmentation.

Individual muscle segmentation is the process of partitioning medical images into regions representing each muscle. It can be used to isolate spatially structured quantitative muscle characteristics, such as volume, geometry, and the level of fat infiltration. These features are pivotal to measuring the state of muscle functional health and in tracking the response of the body to musculoskeletal and neuromusculoskeletal disorders. The gold standard approach to perform muscle segmentation requires manual processing of large numbers of images and is associated with significant operator repeatability issues and high time requirements. Deep learning-based techniques have been recently suggested to be capable of automating the process, which would catalyse research into the effects of musculoskeletal disorders on the muscular system. In this study, three convolutional neural networks were explored in their capacity to automatically segment twenty-three lower limb muscles from the hips, thigh, and calves from magnetic resonance images. The three neural networks (UNet, Attention UNet, and a novel Spatial Channel UNet) were trained independently with augmented images to segment 6 subjects and were able to segment the muscles with an average Relative Volume Error (RVE) between -8.6% and 2.9%, average Dice Similarity Coefficient (DSC) between 0.70 and 0.84, and average Hausdorff Distance (HD) between 12.2 and 46.5 mm, with performance dependent on both the subject and the network used. The trained convolutional neural networks designed, and data used in this study are openly available for use, either through re-training for other medical images, or application to automatically segment new T1-weighted lower limb magnetic resonance images captured with similar acquisition parameters.

Smartphone-Based Assessment of Mobility and Manual Dexterity in Adult People with Spinal Muscular Atrophy.

Background: More responsive, reliable, and clinically valid endpoints of disability are essential to reduce size, duration, and burden of clinical trials in adult persons with spinal muscular atrophy (aPwSMA). Objective: The aim is to investigate the feasibility of smartphone-based assessments in aPwSMA and provide evidence on the reliability and construct validity of sensor-derived measures (SDMs) of mobility and manual dexterity collected remotely in aPwSMA. Methods: Data were collected from 59 aPwSMA (23 walkers, 20 sitters and 16 non-sitters) and 30 age-matched healthy controls (HC). SDMs were extracted from five smartphone-based tests capturing mobility and manual dexterity, which were administered in-clinic and remotely in daily life for four weeks. Reliability (Intraclass Correlation Coefficients, ICC) and construct validity (ability to discriminate between HC and aPwSMA and correlations with Revised Upper Limb Module, RULM and Hammersmith Functional Scale - Expanded HFMSE) were quantified for all SDMs. Results: The smartphone-based assessments proved feasible, with 92.1% average adherence in aPwSMA. The SDMs allowed to reliably assess both mobility and dexterity (ICC > 0.75 for 14/22 SDMs). Twenty-one out of 22 SDMs significantly discriminated between HC and aPwSMA. The highest correlations with the RULM were observed for SDMs from the manual dexterity tests in both non-sitters (Typing, ρ= 0.78) and sitters (Pinching, ρ= 0.75). In walkers, the highest correlation was between mobility tests and HFMSE (5 U-Turns, ρ= 0.79). Conclusions: This exploratory study provides preliminary evidence for the usability of smartphone-based assessments of mobility and manual dexterity in aPwSMA when deployed remotely in participants' daily life. Reliability and construct validity of SDMs remotely collected in real-life was demonstrated, which is a pre-requisite for their use in longitudinal trials. Additionally, three novel smartphone-based performance outcome assessments were successfully established for aPwSMA. Upon further validation of responsiveness to interventions, this technology holds potential to increase the efficiency of clinical trials in aPwSMA.

Mobilise-D insights to estimate real-world walking speed in multiple conditions with a wearable device.

This study aimed to validate a wearable device's walking speed estimation pipeline, considering complexity, speed, and walking bout duration. The goal was to provide recommendations on the use of wearable devices for real-world mobility analysis. Participants with Parkinson's Disease, Multiple Sclerosis, Proximal Femoral Fracture, Chronic Obstructive Pulmonary Disease, Congestive Heart Failure, and healthy older adults (n = 97) were monitored in the laboratory and the real-world (2.5 h), using a lower back wearable device. Two walking speed estimation pipelines were validated across 4408/1298 (2.5 h/laboratory) detected walking bouts, compared to 4620/1365 bouts detected by a multi-sensor reference system. In the laboratory, the mean absolute error (MAE) and mean relative error (MRE) for walking speed estimation ranged from 0.06 to 0.12 m/s and - 2.1 to 14.4%, with ICCs (Intraclass correlation coefficients) between good (0.79) and excellent (0.91). Real-world MAE ranged from 0.09 to 0.13, MARE from 1.3 to 22.7%, with ICCs indicating moderate (0.57) to good (0.88) agreement. Lower errors were observed for cohorts without major gait impairments, less complex tasks, and longer walking bouts. The analytical pipelines demonstrated moderate to good accuracy in estimating walking speed. Accuracy depended on confounding factors, emphasizing the need for robust technical validation before clinical application.Trial registration: ISRCTN - 12246987.