Abstract
A painful, chronic condition, Rheumatoid Arthritis, is marked by bone erosion and soft tissue swelling at the joint. As treatments are investigated in pre-clinical models, characterizing disease progression is integral to assessing treatment efficacy. Here, in vivo and ex vivo micro-computed tomography (µCT) are used in parallel with traditional caliper score measurement to quantify physiological changes in the tarsal region in a murine, collagen-induced arthritis model. In vivo imaging methods, which are validated here through comparison to ex vivo and caliper methods, afford longitudinal analysis of both bone and soft tissue through a single image acquisition. This method removes the subjectivity of swelling quantification which is inherently associated with traditional caliper measurements. Histopathology offers an additional assessment of bone erosion and inflammation by providing a microscopic characterization of disease activity. In comparison to untreated animals, daily prednisolone (glucocorticoid) treatment is shown to restore bone volume, as reflected through in vivo and ex vivo µCT images, as well as histopathology. Prednisolone-associated reduction in inflammation is shown through in vivo µCT soft tissue volume measurements, paw caliper measurements, and histopathology. The findings reported here provide a comprehensive validation of in vivo µCT with a sensitivity that enables characterization of pre-clinical disease assessment in response to treatment in a murine, collagen-induced arthritis model.
Highlights
A painful, chronic condition, Rheumatoid Arthritis, is marked by bone erosion and soft tissue swelling at the joint
Reports in the literature associating ionizing radiation with dose-dependent effects on both blood components and bone necessitate verification that the X-ray dose used in vivo does not impose such effects[16,17]
While the advantages offered by longitudinal scanning of bone architecture with in vivo μCT are e vident[10,18], there is a fine balance between X-ray scan doses required for accurate bone morphology measurements and biological response to radiation[19]
Summary
A painful, chronic condition, Rheumatoid Arthritis, is marked by bone erosion and soft tissue swelling at the joint. In vivo μCT affords the ability to evaluate bone erosion and inflammation through soft tissue volume (STV) changes, while providing for longitudinal studies, reducing the number of animals needed. This versatile tool can be used to monitor anatomical changes in vivo and findings have demonstrated μCT to be a viable, efficient, and sensitive method to characterize disease p rogression[11]. We present quantitative assessment of bone and soft tissue changes throughout disease progression and in response to treatment using high-resolution in vivo μCT and correlate them to traditional caliper measurements and histopathology assessment. We examine the level of agreement of data obtained from in vivo μCT and ex vivo μCT to study bone modeling in an animal model
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