In Vivo Longitudinal Monitoring of Disease Progression in Inflammatory Arthritis Animal Models Using Raman Spectroscopy.
Anders Runge WaltherElzbieta StepulaNicholas DitzelMoustapha KassemMads S BergholtMartin A B HedegaardPublished in: Analytical chemistry (2023)
Current techniques for monitoring disease progression and testing drug efficacy in animal models of inflammatory arthritis are either destructive, time-consuming, subjective, or require ionizing radiation. To accommodate this, we have developed a non-invasive and label-free optical system based on Raman spectroscopy for monitoring tissue alterations in rodent models of arthritis at the biomolecular level. To test different sampling geometries, the system was designed to collect both transmission and reflection mode spectra. Mice with collagen antibody-induced arthritis and controls were subject to in vivo Raman spectroscopy at the tibiotarsal joint every 3 days for 14 days. Raman-derived measures of bone content correlated well with micro-computed tomography bone mineral densities. This allowed for time-resolved quantitation of bone densities, which indicated gradual bone erosion in mice with arthritis. Inflammatory pannus formation, bone erosion, and bone marrow inflammation were confirmed by histological analysis. In addition, using library-based spectral decomposition, we quantified the progression of bone and soft tissue components. In general, the tissue components followed significantly different tendencies in mice developing arthritis compared to the control group in line with the histological analysis. In total, this demonstrates Raman spectroscopy as a versatile technique for monitoring alterations to both mineralized and soft tissues simultaneously in rodent models of musculoskeletal disorders. Furthermore, the technique presented herein allows for objective repeated within-animal measurements potentially refining and reducing the use of animals in research while improving the development of novel antiarthritic therapeutics.
Keyphrases
- raman spectroscopy
- soft tissue
- rheumatoid arthritis
- bone mineral density
- bone regeneration
- computed tomography
- bone loss
- bone marrow
- oxidative stress
- magnetic resonance imaging
- gene expression
- positron emission tomography
- mesenchymal stem cells
- high fat diet induced
- ms ms
- mass spectrometry
- body composition
- emergency department
- metabolic syndrome
- magnetic resonance
- physical activity
- skeletal muscle
- optical coherence tomography
- contrast enhanced
- endothelial cells
- tandem mass spectrometry
- drug induced
- insulin resistance
- adipose tissue
- high glucose
- dual energy
- simultaneous determination
- liquid chromatography