Advanced magnetic resonance imaging of cartilage components in haemophilic joints reveals that cartilage hemosiderin correlates with joint deterioration

Abstract

Evidence suggests that toxic iron is involved in haemophilic joint destruction. To determine whether joint iron deposition is linked to clinical and imaging outcomes in order to optimize management of haemophilic joint disease. Adults with haemophilia A or haemophilia B (n=23, ≥ age 21) of all severities were recruited prospectively to undergo assessment with Hemophilia Joint Health Scores (HJHS), pain scores (visual analogue scale [VAS]) and magnetic resonance imaging (MRI) at 3T using conventional MRI protocols and 4-echo 3D-UTE-Cones sequences for one affected arthropathic joint. MRI was scored blinded by two musculoskeletal radiologists using the International Prophylaxis Study Group (IPSG) MRI scale. Additionally, UTE-T2* values of cartilage were quantified. Correlations between parameters were performed using Spearman rank correlation. Two patients subsequently underwent knee arthroplasty, which permitted linking of histological findings (including Perl's reaction) with MRI results. MRI scores did not correlate with pain scores or HJHS. Sixteen joints had sufficient cartilage for UTE-T2* analysis. T2* values for cartilage correlated inversely with HJHS (rs =-0.81, P<0.001) and MRI scores (rs =-0.52, P=0.037). This was unexpected since UTE-T2* values decrease with better joint status in patients with osteoarthritis, suggesting that iron was present and responsible for the effects. Histological analysis of cartilage confirmed iron deposition within chondrocytes, associated with low UTE-T2* values. Iron accumulation can occur in cartilage (not only in synovium) and shows a clear association with joint health. Cartilage iron is a novel biomarker which, if quantifiable with innovative joint-specific MRI T2* sequences, may guide treatment optimization.