This pilot study for the Osteoarthritis Initiative (OAI) extends previous work on cross-validating DESS image contrast for quantitative analysis of cartilage morphology 14
. The DESS sequence was compared with SPGR/FLASH, because the latter represents the currently accepted and validated standard for quantitative MRI of cartilage morphology 5,6,19
A limitation of this study clearly is the small sample size. However, this is the first study to apply a paired analysis design at two time points (quadruple images) to the analysis of precision errors of cartilage morphometry, the first to compare DESS and FLASH in a longitudinal study, and the first to compare change in aggregate values of cartilage morphology in the medial (MFTC) and lateral (LFCT) femorotibial compartment to single femorotibial cartilage plates longitudinally. Although this pilot study only involved few OA patients, the OAI is acquiring longitudinal data on more than 4500 subjects over 5 years, and these data should become available for analysis in the near future.
Previous findings 14
indicate that corFLASH, sagDESS, and corMPR-DESS display similar precision in the analysis of cartilage morphology, when being read in an unpaired, completely blinded manner. These precision errors examine the differences in image contrast 14
, but are not directly applicable for use in longitudinal studies where baseline and follow-up images are usually processed as pairs. Other studies investigating test-retest-precision have been confined to one time point only 14
, but this approach may introduce bias towards conformance of segmentation in repeat data sets. The advantage of the current design, in which quadruples were processed (with blinding to BL and Y1 time points) is that the readers were aware that change may have occurred between acquisitions, so that this bias was minimized. In contrast with our previous unpaired analysis 14
results, the paired analysis precision errors of the sagDESS, and in particular that of the corMPR-DESS were generally higher, than those with the corFLASH. Precision errors of the corFLASH were at lower end of those reported in the literature 5
The changes seen at Y1 and Y2 were small, given that annual rates of cartilage volume loss of up to 7% have been reported in the literature 5,7–10
. This may be due to the patients having relatively mild OA. Interestingly, the sagDESS tended to display higher sensitivity to change (ratio of % loss to its SD) than corFLASH, and corFLASH higher sensitivity than corMPR-DESS. Given that the image contrast of corMPR-DESS and sagDESS is similar and that previous studies have revealed lower precision errors of coronal FLASH in the weight-bearing femorotibial joint compared with sagittal FLASH 5,20,21
, we assume that the potentially higher sensitivity of sagDESS compared to cor FLASH and corMPR-DESS is most likely due to the higher spatial resolution (lower slice thickness) rather than to the different image orientation and contrast. While exciting, these initial results are based on a small data set and must be confirmed in a larger cohort. Also, the potential advantages of increased spatial resolution are often offset by increases in both image acquisition time and, in particular, the segmentation time, which doubles if the number of slices doubles.
At this stage, the technique applied here is not intended for use in diagnosing osteoarthritis in a single patient, in particular because the predictive value of imaging outcomes for clinical endpoints (e.g. indicating for total knee arthroplasty) has so far only been reported in one relatively small study 22
. Establishing the relationship between imaging endpoints (such as changes in cartilage morphology) and clinical endpoints, however, is one of the goals of the OA Initiative. The technique presented here has particularly high potential for the evaluation of DMOADs in clinical trials. At this point, however, it is still unclear how much of a change in cartilage morphology (and how much of a modulation of this change by a DMOAD) is clinically significant.
While the focus of this work was on the comparison of FLASH and DESS for the analysis of cartilage morphology, other MRI-based methods for rating changes in OA have also been described: Semi-quantitative scoring of conventional proton density-, T1-, and T2-weighted MR images has been used to rate alterations of cartilage and other articular tissues 23
, but their responsiveness to changes has been reported to be relatively low 24
. While conventional proton density-, T1-, and T2-weighted MR images are acquired in the OAI, these cannot be used to quantify changes of cartilage morphology, because of the lower spatial resolution and the presence of susceptibility artifact at the bone cartilage interface 4,5
. For the purpose of analysis of cartilage composition (specifically collage content, collagen structure and hydration), T2 mapping has been included as part of the OAI acquisition protocol 25
, but no longitudinal changes in OA have so far been reported. Compositional techniques for analysis of cartilage proteoglycan content, such as dGEMRIC and T1rho
have also been developed 6,26
, but have not been included in the OAI acquisition protocol.
One of the most difficult tasks in the segmentation process of cartilage morphology is to accurately identify the contact zone between femorotibial cartilage, since the contrast is often very low where the femorotibial cartilage plates are in direct contact. The variation introduced by this difficulty can be reduced by additionally analyzing aggregate measures of cartilage volume (VC) and thickness (ThC) in the medial (MFTC) and lateral femorotibial compartment (LFTC) 9
. Our results indicate that morphometric measurements in MFTC and LFTC not only tend to be more reproducible, but also more sensitive to change than individual femorotibial plates (MT, cMF, LT, cLF). Although the comparison between protocols is limited by the relatively small longitudinal change in cartilage morphology in this pilot study and the small number of participants, the data suggest that significant change can be detected with MRI in a small sample of OA subjects over 2 years. The results on longitudinal change should be confirmed in a larger sample, and the OAI will provide the opportunity to do so in the future.