Multispectral imaging for preclinical assessment of rheumatoid arthritis models

Glinton, Sophie L. (2019). Multispectral imaging for preclinical assessment of rheumatoid arthritis models. University of Birmingham. Ph.D.

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Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune condition affecting multiple body systems. Murine models of RA are vital in progressing understanding of the disease. The severity of arthritis symptoms is currently assessed in vivo by observations and subjective scoring which are time-consuming and prone to bias and inaccuracy.

The main aim of this thesis is to determine whether multispectral imaging of murine arthritis models has the potential to assess the severity of arthritis symptoms in vivo in an objective manner. Given that pathology can influence the optical properties of a tissue, changes may be detectable in the spectral response.

Monte Carlo modelling of reflectance and transmittance for varying levels of blood volume fraction, blood oxygen saturation, and water percentage in the mouse paw tissue demonstrated spectral changes consistent with the reported/published physiological markers of arthritis. Subsequent reflectance and transmittance in vivo spectroscopy of the hind paw successfully detected significant spectral differences between normal and arthritic mice. Using a novel non-contact imaging system, multispectral reflectance and transmittance images were simultaneously collected, enabling investigation of arthritis symptoms at different anatomical paw locations. In a blind experiment, Principal Component (PC) analysis of four regions of the paw was successful in identifying all 6 arthritic mice in a total sample of 10. The first PC scores for the TNF dARE arthritis model were found to correlate significantly with bone erosion ratio results from microCT, histology scoring, and the manual scoring method. In a longitudinal study at 5, 7 and 9 weeks the PC scores identified changes in spectral responses at an early stage in arthritis development for the TNF dARE model, before clinical signs were manifest.

Comparison of the multispectral image data with the Monte Carlo simulations suggest that in this study decreased oxygen saturation is likely to be the most significant factor differentiating arthritic mice from their normal littermates.

The results of the experiments are indicative that multispectral imaging performs well as an assessor of arthritis for RA models and may outperform existing techniques. This has implications for better assessment of preclinical arthritis and hence for better experimental outcomes and improvement of animal welfare.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):