title: Functional perfusion MRI predicts later occurrence of steroid-associated osteonecrosis: an experimental study in rabbits.
abstract: Ischemia is the defined pathway leading to steroid-associated osteonecrosis (ON). Early detection of ischemic condition may help predict later ON occurrence. Bone marrow perfusion function evaluation by perfusion magnetic resonance imaging (MRI) may be a unique modality for this application. Twenty-five adult male New Zealand white rabbits were used in this study. Lipopolysaccharide (LPS) and methylprednisolone (MPS) were administrated for ON induction based on a published protocol. T1-weighted and fat suppression T2-weighted MR imaging (conventional MRI) were performed for ON lesion detection based on the abnormal signal in the proximal femora at week 0 as the baseline (before LPS injection), and week 1 and week 2 after MPS injection. At the same time, the blood perfusion function in the proximal femora was measured by perfusion MRI. Maximum enhancement (ME)--an index of MRI perfusion function was analyzed. After MRI scanning, the proximal femora were prepared histopathologically for ON lesion analysis. The rabbit with bilateral histopathological ON lesions was defined as an ON+ rabbit and included in the ON+ group evaluated at week 1 and week 2, respectively, and the rabbit without ON lesions in bilateral femora was classified into the ON- group. For the underlying mechanism of perfusion change, the extravascular marrow fat cells were measured and the intravascular endothelium inflammation injury indicator of tissue factor (TF) expression and thrombus formation were detected. In ON+ group, ME in perfusion MRI showed a significant decrease at week 1 and week 2 as compared with the baseline (p < 0.01). There was a more than 50% decrease in ME at week 1 in ON+ group; whereas there were no detectable ON lesions by conventional MRI at week 1, though 93% (14/15) rabbits could be detected at week 2 in ON+ group. In ON- group, ME showed a slight decrease at week 1 (less than 30%), and nearly recovered to normal at week 2 as compared with the baseline. Histological results showed a much larger average marrow fat area and more severe marrow blood sinusoids compression from surrounding crowded fat cells, and stronger positive TF expression in marrow endothelium and more thrombus formation in ON+ rabbits than ON- rabbits. This study demonstrated that functional perfusion MRI could predict development of steroid-associated ON. Our experimental data suggested that perfusion MRI might be a sensitive noninvasive modality for monitoring steroid-associated ON in patients.
authors.affiliation: Musculoskeletal Research Laboratory of the Department of Orthopaedics and Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Sheng
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.forename: Yi-Xiang
authors.initials: YX
authors.lastname: Wang
authors.forename: David Ka-Wai
authors.initials: DK
authors.lastname: Yeung
authors.forename: James Francis
authors.initials: JF
authors.lastname: Griffith
authors.forename: Kwok-Sui
authors.initials: KS
authors.lastname: Leung
authors.forename: Ling
authors.initials: L
authors.lastname: Qin
mesh_terms: D000273:Adipose Tissue / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001853:Bone Marrow / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism; D005938:Glucocorticoids / Q000633:toxicity*; D007511:Ischemia / Q000139:chemically induced / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D008297:Male; D008775:Methylprednisolone / Q000633:toxicity*; D010020:Osteonecrosis / Q000139:chemically induced* / Q000473:pathology*; D011237:Predictive Value of Tests; D011817:Rabbits; D012680:Sensitivity and Specificity; D013925:Thromboplastin / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D008070:Lipopolysaccharides; D013925:Thromboplastin; D008775:Methylprednisolone