Christensen K R, Roepstorff K, Petersen M, Wiinberg B, Hansen A K, Kjelgaard-Hansen M, Nielsen L N
Translational Haemophilia Pharmacology, Novo Nordisk A/S, Maaloev, Denmark.
Veterinary Disease Biology, University of Copenhagen, Frederiksberg, Denmark.
Haemophilia. 2017 Jan;23(1):152-162. doi: 10.1111/hae.13080. Epub 2016 Sep 9.
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.
To determine whether HA in the F8 rat can be visualized using ultrasonography (US) and micro-computed tomography (μCT).
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.
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.
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.
血友病的一个主要并发症是血友病性关节病（HA），这是一种病理生物学尚未完全明确的使人衰弱的疾病。高分辨率成像可能会提供有关HA发病和进展的新知识，从而有助于确定新的治疗机会。最近，建立了一种HA的F8大鼠模型。大鼠的体型便于对关节进行便捷的高分辨率成像，这能够开展HA发展的体内研究。
确定是否可以使用超声检查（US）和微型计算机断层扫描（μCT）来观察F8大鼠的HA。
60只F8大鼠和20只野生型大鼠接受了一次或两次诱导性膝关节出血。在诱导膝关节出血前，F8大鼠接受重组人FVIII（rhFVIII）或赋形剂治疗。使用体内US和离体μCT观察血友病性关节病，并将观察结果与组织学评估相关联。
US和μCT检测到了与HA相关的膝关节病变。μCT确定的疾病严重程度与组织病理学之间存在很强的相关性。rhFVIII治疗减轻了两种成像技术所识别的病变。
US和μCT是检测F8大鼠血液诱导性关节疾病的合适成像技术，可用于疾病进展的纵向研究。
