Topographical variation of T2 relaxation time in the young adult knee cartilage at 1.5 T.

OBJECTIVE: To assess the normal topographical variation of T2 relaxation time of articular cartilage in different compartments of the knee joint and at different tissue depths in young healthy adults. METHODS: Twenty asymptomatic young adult volunteers (age range, 21-27 years; mean age, 22.5 years), were studied at 1.5T. Both axial and sagittal multi-slice multi-echo spin echo measurements were performed to determine the T2 relaxation time of cartilage in the femoral, tibial and patellar compartments. The cartilage surfaces were divided into 24 segments and each segment was divided into deep and superficial regions-of-interest (ROIs) of equal thickness. The reproducibility for ROI analysis was assessed for five patients by determining the interclass correlation coefficient (ICC) and the root-mean-square coefficient of variation (CV(RMS)). RESULTS: Cartilage T2 was significantly dependent on joint topography, compartment and tissue depth. For all joint surfaces, superficial T2 values were systematically higher as compared to deep tissue. The data showed a trend toward higher T2 values at the load bearing area of the femoral condyles. The interobserver error varied significantly among different locations and showed mostly good reproducibility with mean ICC of 0.70 and a CV(RMS) of 5.0%. CONCLUSION: The normal variation in cartilage T2 within a joint is significant and should be acknowledged when pathology-related T2 changes are investigated. The knowledge on normal variation can be used for power and sample size calculations in further studies, and the T2 values as control data in future patient studies.

Finer linkage mapping of a primary hip osteoarthritis susceptibility locus on chromosome 6.

Primary osteoarthritis (OA) is a common late-onset disease that exhibits complex genetic transmittance. A previous genome-wide linkage scan of OA affected sibling pair families (ascertained by total joint replacement surgery) identified a region of suggestive linkage on chromosome 6, with a maximum multipoint-LOD score (MLS) of 2.9 in 194 families containing sibling pairs concordant for total hip replacement (THR-families). However, up to 50 cM of the chromosome had a multipoint-LOD score >2.0, indicating that the susceptibility locus was poorly mapped. We have now genotyped chromosome 6 to a higher density in an expanded cohort of 378 THR-families. We obtained an MLS of 2.8 to an 11.4 cM interval defined by markers D6S452 and 509-8B2, which map between 70.5 to 81.9 cM from the 6p-telomere. Stratification by gender revealed that this linkage was completely accounted for by female THR-families (n=146), with an MLS of 4.0 and with the highest two-point LOD score being 4.6 for marker D6S1573 (75.9 cM). The 11.4 cM interval just encompasses the candidate gene COL9A1 (81.9 cM). We identified and then genotyped twenty common single nucleotide polymorphisms (SNPs) from within COL9A1 in the 146 probands from our female THR-families and in 215 age-matched female controls. No SNP allele, genotype or haplotype demonstrated association to disease. Overall, we have narrowed the chromosome 6 OA susceptibility locus to a point at which linkage disequilibrium/association analysis is feasible, we have demonstrated that this locus is female specific, and found no evidence that COL9A1 encodes for the susceptibility.