Raman spectroscopic probe provides optical biomarkers of cartilage composition predictive of tissue function
Open accessAbstract
Objective The diagnosis of early osteoarthritis when therapeutic interventions may be most effective at reversing cartilage degeneration presents a clinical challenge. We describe a Raman arthroscopic probe and spectral analysis that measures biomarkers reflective of the content of predominant cartilage extracellular matrix (ECM) constituents-glycosaminoglycans (GAG), collagen, water-essential to cartilage function. We compare the capability of Raman-probe-derived biomarkers to predict functional properties of cartilage to quantitative MRI and histopathology assessments. Design Osteochondral blocks were sectioned from 6 bovine femoral condyles with no macroscopic injury (n=62 blocks) and 6 condyles with a focal chondral lesion (n=32 blocks), but no macroscopic degeneration of surrounding cartilage (n=34 blocks). Blocks from 10 human knees were further analyzed (age 27-75; n=235 blocks). Using a custom arthroscopic Raman spectroscopy probe, spectra of chondral layers were measured and subjected to multivariate linear decomposition to extract ECM biomarker scores, reflecting the contribution of each ECM constituent to the spectra. Blocks were further analyzed for elastic modulus, T2/T2* MRI relaxation times, and OARSI scores. Results For bovine tissues, Raman biomarkers revealed depleted GAG and cartilage softening peripheral to the lesion despite no macroscopic degeneration. Raman biomarkers accounted for 78% of GAG content variation and 71% of modulus variation. For human tissues, Raman biomarkers accounted for 71% of modulus variation. Raman biomarkers accounted for a greater variation of modulus (71%-72%) than OARSI (12-54%), T2* (15%-27%), or T2 (25%-30%). Conclusions These data support the application of Raman-probe-derived biomarkers for molecular assessment of key ECM constituents that define cartilage properties in health and disease.
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Optical imaging excels in preclinical models but faces clinical translation challenges due to limited tissue penetration.
“while optical imaging excels in preclinical models but faces clinical translation challenges due to limited tissue penetration [167].”
From Biomarker-Guided Imaging and AI-Augmented Diagnosis of Degenerative Joint Disease (2025) · cites this paper as [167]
The Discussion (page unavailable) describes potential preclinical uses and acknowledges challenges in moving ex-vivo Raman measurements into surgical settings. The Methods report approximately 270 μm of tissue penetration, but the paper does not say that limited penetration causes clinical translation challenges for optical imaging generally, or that optical imaging excels in preclinical models. (LLM, conf=0.83)
Experimental — accuracy not yet measuredSPECT offers cost-effective bone turnover assessment.
“SPECT offers cost-effective bone turnover assessment”
From Biomarker-Guided Imaging and AI-Augmented Diagnosis of Degenerative Joint Disease (2025) · cites this paper as [167]
The Introduction describes a need for a low-cost platform to assess cartilage composition, and the Methods discuss quantitative MRI; neither addresses SPECT. Searches for SPECT and bone turnover found no passage assessing SPECT’s cost or its use for bone turnover assessment. Page numbers were not available in our copy. (LLM, conf=0.77)
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- Authors
- Kazemi, M., Yu, C., Mehrotra, D. R., Ersland, E. E., Zbyn, S., Korna, F., Staffa, S. J., Engiles, J. B., Li, X., Schaer, T. P., Grinstaff, M. W., Bergholt, M. S., Snyder, B. D., & Albro, M. B.
- Affiliations
- Boston University (US)
- Boston Children's Hospital (US)
- University of Pennsylvania (US)
- Cleveland Clinic (US)
- King's College London (GB)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Albro, Michael B.
- ORCID
- Venue
- Osteoarthritis and Cartilage
- Publisher
- Elsevier BV
- Published
- 2025-04
- Volume
- 33
- Issue
- 4
- Pages
- 461-472
- ISSN
- 1063-4584 (ISSN-L)
- PMC
- PMC11996041
- OpenAlex
- W4406704875
- Cited by
- 10
- References
- 52
- Citations by year
- 2026: 5 · 2025: 5
- FWCI
- 3.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Osteoarthritis and Cartilage (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR081393)
- Arthritis Foundation
- National Institutes of Health
- Boston University
- Missouri Broadcasters Association
- Musculoskeletal Transplant Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Spectroscopy Techniques in Biomedical and Chemical Research
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Physical Sciences › Engineering › Biomedical Engineering › Optical Coherence Tomography Applications
- Keywords
- Raman spectroscopy, cartilage matrix, glycosaminoglycans, collagen, cartilage water content, early osteoarthritis, cartilage defects, OARSI score, cartilage degeneration, quantitative MRI, knee cartilage
- MeSH terms
- Adult, Aged, Animals, Arthroscopy, Cartilage, Articular, Cattle, Collagen, Extracellular Matrix, Female, Glycosaminoglycans, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Spectrum Analysis, Raman, Biomarkers, Osteoarthritis, Knee
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