Advanced imaging techniques show progressive arthropathy following experimentally induced knee bleeding in a factor VIII-/- rat model

Background: Joint pathology is most commonly assessed by radiogra-phy, but ultrasonography (US) is increasingly recognized for its acces-sibility, safety and ability to show soft tissue changes, the earliestindicators of haemophilic arthropathy (HA). US, however, lacks theability to visualize the extent of bone deformation. Here advancedradiography such as computed tomography (CT) may play an impor-tant part. Little is known about the early phases in the development ofHA. We recently developed a Factor VIII/(FVIII) rat model andcombining micro-CT (lCT) with US in this model allows for studiesof early joint changes and progression of disease in vivo.Aims: (i) Characterize joint changes in HA using US and lCT in a newhaemophilic FVIII/rat and compare to human HA. ii) Establish thepotential of these techniques as tools for assessing progression of HAin vivo.Methods: 20 wild type and 40 FVIII/rats received a single jointinjury to one knee on day 0 and were euthanized on day 14, or twojoint bleeds, on day 0 and 14, and euthanized on day 28. The injuredknee of each rat was examined by US for changes in the patella liga-ment and fat pad, oedema or bone and cartilage degeneration, andin vivo lCT on day 0, 14 and 28. Post mortem, both legs were scannedex vivo by lCT and examined by histopathology.Results: FVIII/rats developed pathophysiological changes compa-rable to human HA. US changes were found in all parameters, and insome cases with pathological progression from day 14 to 28. Likewise,lCT scans revealed dramatic intra- and periarticular changes in thebones.Conclusion: Joint bleeding in FVIII/rats led to joint deteriorationthat was histopathologically comparable to human HA and evident onboth US and lCT. These new imaging techniques can be used to assesssoft tissue and bone deformation in the progression of HA in vivo andare promising tools for studying cause and mechanisms driving thepathological changes following haemarthrosis