Visualization of haemophilic arthropathy in F8 −/− rats by ultrasonography and micro-computed tomography

A major complication of haemophilia is haemophilic arthropathy (HA), a debilitating disorder with an incompletely defined pathobiology. High-resolution imaging may provide new knowledge about onset and progression of HA, and thereby support identification of new treatment opportunities. Recently, a F8?/? rat model of HA was developed. The size of the rat allows for convenient and high resolution imaging of the joints, which could enable in vivo studies of HA development. Aim: To determine whether HA in the F8?/? rat can be visualized using ultrasonography (US) and micro-computed tomography (lCT). Methods: Sixty F8?/? and 20 wild-type rats were subjected to a single or two induced knee bleeds. F8?/? rats were treated with either recombinant human FVIII (rhFVIII) or vehicle before the induction of knee bleeds. Haemophilic arthropathy was visualized using in vivo US and ex vivo lCT, and the observations correlated with histological evaluation. Results: US and lCT detected pathologies in the knee related to HA. There was a strong correlation between disease severity determined by lCT and histopathology. rhFVIII treatment reduced the pathology identified with both imaging techniques. Conclusion: US and lCT are suitable imaging techniques for detection of blood- induced joint disease in F8?/? rats and may be used for longitudinal studies of disease progression.