ORIGINAL ARTICLE Musculoskeletal USPIO-related T1 and T2 mapping MRI of cartilage in a rabbit model of blood-induced arthritis: a pilot study A. AMIRABADI,* L. VIDARSSON,* E. MILLER, † M. S. SUSSMAN, ‡ K. PATIL,* H. GAHUNIA,* S. A. F. PEEL,§ A. ZHONG,* R. WEISS,* G. DETZLER,* H. L. M. CHENG,* R. MOINEDDIN ¶ and A. S. DORIA* *Department of Diagnostic Imaging, The Hospital for Sick Children, University of Toronto, Toronto; †Department of Diagnostic Imaging, Children’s Hospital for Eastern Ontario, Ottawa; ‡Department of Medical Imaging, Toronto General Hospital, the University Health Network; §Department of Oral and Maxillofacial Surgery, Faculty of Dentistry University of Toronto; and ¶Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada Summary. Ultrasmall paramagnetic iron oxide (USPIO)-enhanced MRI is promising for evaluating inflammation. The aims of this study were to investigate the effect of USPIO on cartilage T1 and T2 mapping, and to evaluate a proposed rapid vs. conventional T2 map method for imaging cartilage in a blood-induced arthritis model. Knees of nine arthritic (induction by intra-articular autologous blood injection) and six control rabbits were imaged over time (baseline, weeks 1, 5, 10) by 1.5T MRI. All rabbits had USPIO (35–75 lmol Fe/kg)-enhanced MRI at each time point. T1 and T2 (conventional and rapid) maps and signal-to-noise ratios (SNR) were obtained pre- and post-USPIO administration. Cartilage biochemistry and histology were compared with MRI. Excellent correlations were noted between T1 map values and histologic scores at week 10 pre- USPIO (medial, r= 0.93, P= 0.0007; lateral, r= 0.87,P= 0.005) in the arthritic group, but not between T2 map and histology. Marginally and significant differences were observed between pre- and post-USPIO T2 values at weeks 5 (P= 0.06) and 10 (P = 0.02), but only with the administration of high USPIO doses in the arthritic group using the conventional method. No significant differences were noted between pre- and post-USPIO T1 values at any imaging time points. Cartilage T2 maps with short-TR and conventional protocols provided similar T2 values [(decreased trend)] (P > 0.05). Concomitant use of USPIO to T1 and T2 mapping of cartilage would not impair the identification of interval changes of T1 and T2 maps. Rapid T2 map provides similar results compared to conventional method, but its validation warrants further investigation. Keywords: arthritis, haemophilia, rabbits, T1 map, T2 map, ultrasmall paramagnetic iron oxide Introduction Haemophilia is an inherited bleeding disorder caused by deficiencies of clotting factors VIII and IX [1,2]. Car- tilage degeneration contributes to most of the disease morbidity and is one of the primary outcome measures for assessment of failure to treatment in haemophilic arthropathy [3]. Non-invasive identification of early cartilage changes can direct early treatment of haemo- philia and reduce long-term joint morbidity [4]. Proteoglycan (GAG) depletion is one of the earliest manifestations of arthropathy [5,6] and has been shown to correspond to lower T1 values [7]. T2 mapping is a non-invasive imaging technique sensitive to alterations in collagen structure [8–10]. Therefore, both T1 and T2 mapping techniques hold potential for being diagnostic and prognostic tools for the assessment of early cartilaginous changes in haemo- philic arthropathy. The use of ultrasmall paramag- netic iron oxide (USPIO) nanoparticles enables imaging of pathologic conditions associated with high macrophage concentration such as synovium in arthritis [10–15]. USPIO particles can be taken up by macrophages and other phagocytic cells involved in the arthritic inflammatory process causing shortening of T1, T2 and T2*, thus changing the MR signal [16,17]. Correspondence: Andrea S. Doria, Department of Diagnostic Imaging, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. Tel.: 416 813 6079; fax: 416 813 8067; e-mail: andrea. doria@sickkids.ca Accepted after revision 4 November 2014 © 2014 John Wiley & Sons Ltd e59 Haemophilia (2015), 21, e59–e69 DOI: 10.1111/hae.12601