“Spectromics”: Holistic Optical Assessment of Human Cartilage via Complementary Vibrational Spectroscopy for Osteoarthritis Diagnosis

Osteoarthritis (OA) is the most common degenerative joint disease, presented as wearing down of articular cartilage and resulting in pain and limited mobility for 1 in 10 adults in the UK. [1][1] There is an unmet need for patient friendly paradigms for clinical assessment that do not require ionising radiation (CT), exogenous contrast enhancing dyes (MRI), biopsy, and/or instrumentation approaches (arthroscopy or endoscopy). Hence, techniques that use non-destructive, near- and shortwave infrared light (NIR, SWIR) may be ideal providing for non-invasive, label-free and deep tissue interrogation. This study demonstrates multimodal “spectromics”, low-level abstraction data fusion of non-destructive NIR Raman scattering spectroscopy and NIR-SWIR absorption spectroscopy, providing an enhanced, interpretable “fingerprint” for diagnosis of OA in human cartilage. Samples were excised from femoral heads post hip arthroplasty from OA patients (n=13) and age-matched control (osteoporosis) patients (n=14). Under multivariate statistical analysis and supervised machine learning, tissue was classified to high precision: 100% segregation of tissue classes, and a classification accuracy of 95% (control) and 80% (OA), using the combined vibrational data. There was a marked performance improvement (5 to 6-fold for multivariate analysis) using the spectromics fingerprint compared to results obtained from solely Raman or NIR-SWIR data. Furthermore, discriminatory spectral features in the enhanced fingerprint elucidated clinically relevant tissue components (OA biomarkers). In summary, spectromics provides comprehensive information for early OA detection and disease stratification, imperative for effective intervention in treating the degenerative onset disease for an aging demographic. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by the EPSRC Doctoral Training grant (EP/N509747/1) to the School of Chemistry, University of Southampton and the EPSRC InLightenUS programme (EP/T020997/1) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics Committee of University of Southampton gave ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors [1]: #ref-1