In Vivo Evaluation Of Early Disease Progression By X-ray Phase Contrast Imaging In The Adjuvant Arthritic Rat

Background and ObjectiveRheumatoid arthritis (RA) is a chronic autoimmune symmetric polyarthritis characterized by synovitis and bone erosion. The chronic nature of this disease results in a progressive joint destruction, which leads to severe locomotive disability and deterioration quality of life quality. RA is not characterized by a single pathognomonic measure such as blood pressure in hypertension or cholesterol in hyperlipidemia, which can be used in the diagnosis, prognosis, and monitoring of patient status. Measures such as swollen joints and an elevated erythrocyte sedimentation rate are certainly valuable, but many individuals with abnormal values have conditions other than RA, and many people with RA may have favorable values for one or more of these measures. Therefore, the rheumatology community has developed indices of several measures, such as classification criteria, the disease activity score (DAS), and the ACVR Core Data Set with 20%, 50% and 70% improvement (ACVR 20, ACVR 50, ACVR 70) to classify and monitor patients with RA. While these indices have greatly advanced clinical research, databases for long-term observations, differ in 20-50% of included data, and the software platforms for these databases differ sufficiently to render it difficult to merge the data to compare one data set to another. It has been proposed that a uniform database for early arthritis clinical research could help advance clinical research in early arthritis. One example of such a database, termed a "standard protocol to evaluate rheumatoid arthritis" (SPERA), has been in use for almost two decades inone clinical site, and has proven valuable in a number of ways, including the demonstration of early radiographic damage, development of a 28-joint count, and documentation that patient questionnaire data are correlated significantly with laboratory, joint count and radiographic data, although questionnaire data are the strongest predictors of severe outcomes including work disability and premature mortality. The use of a uniform database in no way precludes the collection of additional data at particular centers including immunogenetic, serologic, or structural magnetic resonance imaging (MRI) data. However, the availability of an infrastructure of standard data in all RA databases would enhance clinical research in early RA.Adjuvant induced arthritis (AIA) in rat has much character similar to human RA in pathological mechanism, immunity, clinical representation and so on, so the model is very ideal in investigating RA and selecting drugs of anti-inflammation. But the disease progression in early phase of AIA is so tiny that conventional radiography (CVR) is hardly able to demonstrate it. MRI may be more sensitive than CVR, because it can depict early inflammatory changes in the joint, especially synovitis and tenosynovitis. Furthermore, MRI detects bone erosions earlier than CVR. But MRI manifestation for bone changes does not reflect signal change in bone matrix itself, it depends on signal change of the neighboring soft tissue. The signal produce of MRI is also very comprehensive. So, the "pathophysiological correlation" of these MR imaging changes remains poorly defined. Careful validation of MRI findings and the evaluation of MRI as a tool to follow the effect of therapy remain to be performed before MRI may be used as a clinical tool to follow therapy or as a surrogate for evaluating osseous changes over time.Recently a novel imaging method, called X-ray phase contrast imaging (XPCI), has been developed with synchrotron X-ray sources and micro-focus tubes that providea high degree of spatial coherence of the X-ray at the observation point. The image contrast of this method can be explained by shift of the phase of X-ray wave when different objects are placed before it, i.e. the incident X-ray refraction at the boundary of objects that have different X-ray refractive indices. The fringe image of the object on an X-ray film is enhanced by light and dark lines, the so-called edge effect. Contrast and resolut...