This is the first study to present longitudinal observations of cartilage change in mediolateral subregions of the weight-bearing femoral condyle, and for minimal cartilage thickness in subregions of tibial and femoral cartilages. Also, this is the first study to examine subregional (specifically central) cartilage thickness changes with 3 Tesla MRI, and the effect of the size of the central subregions on measurements of the rate and sensitivity to change of FT cartilage loss in OA. These observation are important for two reasons: 1) the ability to monitor cartilage change in different subregions of the FT compartments and cartilage plates allows one to more comprehensively describe cartilage loss in OA and therefore better understand the disease and its progression; 2) the ability to determine defined subregions with higher rates of change and in particular sensitivity to change may permit a reduction in the required sample size in clinical studies trying to demonstrate drug effects on disease progression.
Our data show that the central subregions generally display higher rates of change than the total cartilage plates (statistically significant for MT, LT and cMF). The greatest rates of change were observed for “minimal” rather than “mean” cartilage thickness; the sensitivity to change (SRM) of minimal cartilage thickness was, however, inferior to that of the mean thickness, due to a larger inter-subject variability. The sensitivity to change for mean cartilage thickness in the central subregion of the medial tibia was higher than that for the entire cartilage plate, relatively independent of the choice of size of the region (10 to 50% tAB), whereas in cMF and LT the SRM was similar for central subregions and the entire cartilage plate. A limitation of the study is that the biomechanical axis of the leg (neutral, valgus or varus malalignment) was not measured, and future work should therefore address whether the observations made here also apply to subcohorts with different types of knee alignment.
In a previous study, we showed that the algorithm applied here is able to reliably identify regions of interest of a defined proportion of the tAB in FT cartilage plates, and that a test retest precision (RMS CV%) of 1.5% (eMT) to 3.5% (ecMF) can be obtained in the medial FT, and of 1.9% (cLT) to 4.7% (pLT) in the lateral FT compartment 3
. The test retest precision error for minimal thickness (central regions) ranged from 5.0% in cLT to 10.1% in ccLF)3
. Also, we have reported that total plate cartilage loss tended to be higher in those with a BMI > 30 than in those with lower BMI, and higher in those with K–L grade 2 and 3 than in those with other K–L grades in this cohort 5
; however, only trends were observed and non of these or other potential risk factors (age, sex, symptoms) were found to be significantly associated with femorotibial cartilage loss.
In a recent study, Pelletier et al. 2
investigated a subset of 110 patients from a large clinical trial who suffered from symptomatic and radiographic (definite osteophyte) knee OA, a narrower medial than lateral joint space, and a medial joint space width between 2 and 4mm on semiflexed radiographs. The tibial cartilage was divided either into a concentric or a transverse (medial to lateral) central region. The authors 2
also reported that the highest rate of change (over 2 years) occurred in the central areas (-13% in concentric and -15% in transverse cMT, as opposed to - 9.3% in the total MT). The SRM was, however, similar for regional (-1.19 for concentric and - 1.25 for transverse cMT) and for total plate analysis of MT (-1.24). The medial femoral condyle was divided into an anterior, central (cMF) and posterior (pMF) subregion (rate of change = -12.4, -12.0 and -4.4% and SRM = -1.03, -1.04, and -0.56, respectively), but was not divided into medio-lateral subregions, as in the current study. The data were presented as cartilage volume change in these subregions, but not in terms of mean and minimal cartilage thickness.
Despite the use of 3T, the rate of change and SRMs observed in the total and in the high risk subcohort of the present study were lower than those reported by Pelletier et al., 2
even when accounting for the two year observation period in their study. Similar to these authors, however, we find that the central subregions display a higher rate of change than the total cartilage plates, whereas the SRMs are similar for central subregions and the total plate. The only exception to this in our study was the medial tibia, where the SRM for cMT was higher than for the total plate. No significant change was found in the high risk subcohort for the entire MT, whereas a significant loss was observed in cMT.
The minimal central cartilage thickness generally displayed greater rates of change than the mean thickness of the central subregions or total plates, but lower SRMs. In a diseased joint, the minimal cartilage thickness in central areas is likely located at the site of a lesion, where cartilage loss may occur faster than in other parts of the joint. Therefore, it is plausible that the rate of change for minimal cartilage thickness change was higher than that for mean cartilage thickness. However, the intersubject variability in the change in minimal thickness was also higher, likely because of larger changes in subjects without full thickness cartilage loss, or the absence of any loss in minimal thickness in participants with a central denuded area at baseline. In the high risk subcohort, 6 (of 54) participants had already 0mm minimal cartilage thickness in cMT at baseline, and 13 (of 54) in ccMF. Because no loss of minimal cartilage thickness can be measured in these subjects, the standard deviation of the change is larger compared to the standard deviation of change in mean cartilage thickness, with the mean thickness of cMT and ccMF having been greater than zero in all participants. The other potential explanation is the larger precision errors involved in measurement of the minimal cartilage thickness3
, given that measurements are averaged over a much smaller area and therefore much more prone to inconsistencies in local segmentation and are more sensitive to partial volume averaging. Note that the average minimal cartilage thickness was 1.36 mm in cMT and 1.09 mm in cMF, so that the size of one pixel (0.31 mm) amounts to 23% and 28% of that value, respectively.
Similar considerations apply to the choice in size of the subregions. Despite the fact that the higher rate of change was generally observed with a smaller central region of interest, this did not translate into a higher SRM, because of the proportional increase in the standard deviation of the change in the smaller area. Again, a potential explanation may be the larger inter-subject variability of cartilage thickness changes measured in smaller areas compared to larger ones, or greater test-retest precision error in smaller areas. This was previously observed in the medial but not in the lateral FT compartment3
In conclusion, this study shows that the rate of cartilage loss is greater in the central subregions compared to the total cartilage plates. Minimal (central) cartilage thickness displayed a greater rate of change than the mean thickness, but the SRM was less, due to greater variability of the changes. Smaller central subregions generally displayed higher rates of change than larger central subregions, but this did not translate into a higher SRM for the same reason. The sensitivity to change for the central subregions was greater than in the total cartilage plate in the medial tibia and was similar to the entire cartilage plate in the medial femur and lateral tibia.