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


OBJECTIVE
To determine whether HA in the F8-/-rat can be visualized using ultrasonography (US) and micro-computed tomography (μCT).


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 μCT, and the observations correlated with histological evaluation.


RESULTS
US and μCT detected pathologies in the knee related to HA. There was a strong correlation between disease severity determined by μCT and histopathology. rhFVIII treatment reduced the pathology identified with both imaging techniques.


CONCLUSIONS
US and μCT are suitable imaging techniques for detection of blood-induced joint disease in F8-/-rats and may be used for longitudinal studies of disease progression.
Translational Haemophilia Pharmacology, Novo Nordisk A/S, Maaloev, Denmark.|Veterinary Disease Biology, University of Copenhagen, Frederiksberg, Denmark.
K R
KR
Christensen
Histology & Bioimaging, Novo Nordisk A/S, Maaloev, Denmark.
K
K
Roepstorff
Histology & Bioimaging, Novo Nordisk A/S, Maaloev, Denmark.
M
M
Petersen
Translational Haemophilia Pharmacology, Novo Nordisk A/S, Maaloev, Denmark.
B
B
Wiinberg
Veterinary Disease Biology, University of Copenhagen, Frederiksberg, Denmark.
A K
AK
Hansen
Translational Haemophilia Pharmacology, Novo Nordisk A/S, Maaloev, Denmark.
M
M
Kjelgaard-Hansen
Translational Haemophilia Pharmacology, Novo Nordisk A/S, Maaloev, Denmark.
L N
LN
Nielsen
D000818:Animals; D004195:Disease Models, Animal; D006467:Hemophilia A / Q000000981:diagnostic imaging*; D006801:Humans; D051381:Rats; D055114:X-Ray Microtomography

rattus
; X-ray microcomputed tomography; animal model; arthropathy; haemarthrosis; ultrasonography