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.