Digital wearable insole-based identification of knee arthropathies and gait signatures using machine learning
- Regeneron, United States
Abstract
Gait is impaired in musculoskeletal conditions, such as knee arthropathy. Gait analysis is used in clinical practice to inform diagnosis and to monitor disease progression or intervention response. However, clinical gait analysis relies on subjective visual observation of walking, as objective gait analysis has not been possible within clinical settings due to the expensive equipment, large-scale facilities, and highly trained staff required. Relatively low-cost wearable digital insoles may offer a solution to these challenges. In this work, we demonstrate how a digital insole measuring osteoarthritis-specific gait signatures yields similar results to the clinical gait-lab standard. To achieve this, we constructed a machine learning model, trained on force plate data collected in participants with knee arthropathy and controls. This model was highly predictive of force plate data from a validation set (area under the receiver operating characteristics curve [auROC] = 0.86; area under the precision-recall curve [auPR] = 0.90) and of a separate, independent digital insole dataset containing control and knee osteoarthritis subjects (auROC = 0.83; auPR = 0.86). After showing that digital insole derived gait characteristics are comparable to traditional gait measurements, we next showed that a single stride of raw sensor time series data could be accurately assigned to each subject, highlighting that individuals using digital insoles can be identified by their gait characteristics. This work provides a framework for a promising alternative to traditional clinical gait analysis methods, adds to the growing body of knowledge regarding wearable technology analytical pipelines, and supports clinical development of at-home gait assessments, with the potential to improve the ease, frequency, and depth of patient monitoring.
Data availability
Anonymized data and computer code to reproduce all figures will be made available as supplementary files to this manuscript. All relevant demographic and clinical information, all vGRF, derived gait characteristics, and raw sensor time series data, will be provided, in addition to R and Python scripts used to perform the analysis. Additionally, this information will be uploaded to a Regeneron GitHub account here: https://github.com/regeneron-mpds. This data will be made fully available prior to final publication of this manuscript. The GaitRec dataset is available online here: https://www.nature.com/articles/s41597-020-0481-z
Article and author information
Author details
Matthew F Wipperman
Funding
Regeneron Pharmaceuticals (N/A)
- Matthew F Wipperman
- Allen Z Lin
- Kaitlyn M Gayvert
- Benjamin Lahner
- Selin Somersan-Karakaya
- Xuefang Wu
- Joseph Im
- Minji Lee
- Bharatkumar Koyani
- Ian Setliff
- Malika Thakur
- Daoyu Duan
- Aurora Breazna
- Fang Wang
- Wei Keat Lim
- Gabor Halasz
- Jacek Urbanek
- Yamini Patel
- Gurinder S Atwal
- Jennifer D Hamilton
- Oren Levy
- Andreja Avbersek
- Rinol Alaj
- Sara C Hamon
- Olivier Harari
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: For the pilot study, participants were recruited internally within the Regeneron facility located in Tarrytown, NY, USA, and were provided written informed consent prior to participation. The study was considered exempt research under the Common Rule (45 CFR Sec 46.104). The R5069-OA-1849 study protocol received Institutional Review Board and ethics committee approvals from Moldova Medicines and Medical Device Agency and National Ethics Committee for Moldova, and the Western Institutional Review Board.
Copyright
© 2024, Wipperman et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 831
- views
-
- 128
- downloads
-
- 0
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Digital wearable insole-based identification of knee arthropathies and gait signatures using machine learning
eLife 13:e86132.
https://doi.org/10.7554/eLife.86132
Further reading
-
- Medicine
- Neuroscience
Background:
Alcohol use disorder (AUD) is a global health problem with limited therapeutic options. The biochemical mechanisms that lead to this disorder are not yet fully understood, and in this respect, metabolomics represents a promising approach to decipher metabolic events related to AUD. The plasma metabolome contains a plethora of bioactive molecules that reflects the functional changes in host metabolism but also the impact of the gut microbiome and nutritional habits.
Methods:
In this study, we investigated the impact of severe AUD (sAUD), and of a 3-week period of alcohol abstinence, on the blood metabolome (non-targeted LC-MS metabolomics analysis) in 96 sAUD patients hospitalized for alcohol withdrawal.
Results:
We found that the plasma levels of different lipids ((lyso)phosphatidylcholines, long-chain fatty acids), short-chain fatty acids (i.e. 3-hydroxyvaleric acid) and bile acids were altered in sAUD patients. In addition, several microbial metabolites, including indole-3-propionic acid, p-cresol sulfate, hippuric acid, pyrocatechol sulfate, and metabolites belonging to xanthine class (paraxanthine, theobromine and theophylline) were sensitive to alcohol exposure and alcohol withdrawal. 3-Hydroxyvaleric acid, caffeine metabolites (theobromine, paraxanthine, and theophylline) and microbial metabolites (hippuric acid and pyrocatechol sulfate) were correlated with anxiety, depression and alcohol craving. Metabolomics analysis in postmortem samples of frontal cortex and cerebrospinal fluid of those consuming a high level of alcohol revealed that those metabolites can be found also in brain tissue.
Conclusions:
Our data allow the identification of neuroactive metabolites, from interactions between food components and microbiota, which may represent new targets arising in the management of neuropsychiatric diseases such as sAUD.
Funding:
Gut2Behave project was initiated from ERA-NET NEURON network (Joint Transnational Call 2019) and was financed by Academy of Finland, French National Research Agency (ANR-19-NEUR-0003-03) and the Fonds de la Recherche Scientifique (FRS-FNRS; PINT-MULTI R.8013.19, Belgium). Metabolomics analysis of the TSDS samples was supported by grant from the Finnish Foundation for Alcohol Studies.
-
- Medicine
- Neuroscience
The advent of midazolam holds profound implications for modern clinical practice. The hypnotic and sedative effects of midazolam afford it broad clinical applicability. However, the specific mechanisms underlying the modulation of altered consciousness by midazolam remain elusive. Herein, using pharmacology, optogenetics, chemogenetics, fiber photometry, and gene knockdown, this in vivo research revealed the role of locus coeruleus (LC)-ventrolateral preoptic nucleus noradrenergic neural circuit in regulating midazolam-induced altered consciousness. This effect was mediated by α1 adrenergic receptors. Moreover, gamma-aminobutyric acid receptor type A (GABAA-R) represents a mechanistically crucial binding site in the LC for midazolam. These findings will provide novel insights into the neural circuit mechanisms underlying the recovery of consciousness after midazolam administration and will help guide the timing of clinical dosing and propose effective intervention targets for timely recovery from midazolam-induced loss of consciousness.
