An objective diagnosis of gout and calcium pyrophosphate deposition disease with machine learning of Raman spectra acquired in a point-of-care setting.

OBJECTIVE

Raman spectroscopy is proposed as a next-generation method for the identification of monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals in synovial fluid. As the interpretation of Raman spectra requires specific expertise, the method is not directly applicable for clinicians. We developed an approach to demonstrate that the identification process can be automated with the use of machine learning techniques. The developed system is tested in a point-of-care-setting at our outpatient rheumatology department.

METHODS

We collected synovial fluid samples from 446 patients with various rheumatic diseases from three centres. We analysed all samples with our Raman spectroscope and used 246 samples for training and 200 samples for validation. Trained observers classified every Raman spectrum as MSU, CPP or other. We designed two one-against-all classifiers, one for MSU and one for CPP. These classifiers consisted of a principal component analysis model followed by a support vector machine.

RESULTS

The accuracy for classification of CPP using the 2023 ACR/EULAR CPPD classification criteria was 96.0% (95% CI: 92.3, 98.3), while the accuracy for classification of MSU using the 2015 ACR/EULAR gout classification criteria was 92.5% (95% CI: 87.9, 95.7). Overall, the accuracy for classification of pathological crystals was 88.0% (95% CI: 82.7, 92.2). The model was able to discriminate between pathological crystals, artifacts and other particles such as microplastics.

CONCLUSION

We here demonstrate that potentially complex Raman spectra from clinical patient samples can be successfully classified by a machine learning approach, resulting in an objective diagnosis independent of the opinion of the medical examiner.