In this study we have compared the longitudinal performance of MR sequences of the OAI imaging protocol2
in identical knees, specifically a near-isotropic 0.7mm sagDESS 8,12-14
with a previously validated 1.5mm corFLASH 3-9
. Also, this is the first study to explore the impact of analyzing every 2nd
slice of the 0.7mm sagDESS compared with the analysis of every slice, and the sensitivity to change for a 60% and a 75% region of interest in the weight-bearing medial femoral condyle. A high agreement was found for (cross sectional) baseline cartilage thickness measurements between corFLASH, sagDESS and the corMPR DESS. Longitudinally, the rate of and the sensitivity to change were similar for the three protocols for the (central) medial femorotibial compartment and for the weight-bearing femur. In the tibia, the rate of and the sensitivity to change in cartilage thickness were less for the corFLASH than for the sagDESS or corMPR DESS, except for the external subregion, where the greatest changes were observed throughout MT. Correlations of the baseline values were high and those of the longitudinal changes were moderate between the protocols. The rate of and the sensitivity to change were not affected by the dimension of the femoral ROI (60% or 75%), or by using only every 2nd
slice of the 0.7mm sagittal DESS.
The intra-reader test retest precision errors for the three protocols used here have been thoroughly examined in the OAI pilot studies 8,14,15
and were reported to range from 1.3% to 1.9% of the baseline cartilage thickness in MFTC for paired analysis. A recent study by Bae et al. (using a semi-automated approach) reported inter-reader precision errors in the same range as intra-reader errors for cartilage volume with the sagittal DESS26
Limitations of the study include that no formal assessment of the inter-reader precision errors was performed, as these may differ between the three protocols. Although the data set pairs (baseline and follow-up) for each of the three protocols were not processed at the same point in time and not necessarily by the same person, the baseline and follow-up images of each protocol were always analyzed by the same reader, and quality control readings were performed for all segmented slices of all data sets by a single expert, to ensure consistency between the readers. Further limitations of the study include the limited number of analyzed knees, and the small number of participants showing change in cartilage thickness over one year (i.e. larger than the SDD). This is the first study, however, to provide a thorough validation of the DESS for the longitudinal measurement of cartilage loss in comparison with the previously validated coronal FLASH protocol 3-9
. Because few subjects displayed cartilage loss (i.e. larger than the SDD) over one year, the Pearson correlation coefficients of longitudinal changes between the protocols were greater than the Spearman coefficients, the reason being that the Spearman coefficients are determined to a lesser degree than the Pearson coefficient by those cases with the greatest reductions in cartilage thickness. Also, another limitation is that the current analysis was confined to the medial femorotibial compartment, because the participants had medial disease and therefore this compartment was of primary interest 18
. The results cannot therefore be extrapolated to the lateral compartment.
The high agreement seen for the baseline values confirms earlier cross sectional findings8
and suggests that quantitative data from FLASH and DESS from different subcohorts of the OAI can be analyzed together (pooled) for the purpose of cross-sectional analyses. The longitudinal performance of the protocols is in agreement with the observation of nine participants over two years in the OAI pilot study 15
, in which the rate of change in cartilage thickness was also somewhat higher for the sagDESS than for the corFLASH or for the corMPR DESS. The results are also in principle agreement with two recent studies in the first release of the OAI 16,17
that showed similar spatial distribution patterns of thickness changes between femorotibial cartilage plates for corFLASH 16
and sagDESS 17
The current study shows a similar performance (sensitivity to change) of FLASH and DESS in joint regions where high rates of change occur (cMF and subregions, cMFTC, external MT, and lowest ranks (=ordered values with greatest changes), whereas a higher sensitivity to change for the sagittal DESS was observed in regions where the changes were small. However, these findings should be confirmed in other (and possibly larger) cohorts, before they are generalized. The comparison of ordered values (ranks) is particularly useful in revealing these relationships, because the subregions with the greatest (or lowest) longitudinal changes are averaged across individuals independent of their anatomical locations. This is done in order to account for the fact that cartilage loss is spatially heterogeneous, depending on individual risk factors and patho-physiology, and that therefore the subregions with the greatest cartilage loss vary substantially between participants.
The correlations of the longitudinal changes between the protocols were only moderate, but were generally higher in cartilage plates, subregions or ranks showing relatively high changes. This is because the relationship between the magnitude of the actual changes and the precision errors is likely more favorable for regions or ranks with relatively large changes, whereas in subregions and ranks with only small change the correlations are more strongly affected by the precision errors. Additionally, the lower correlations in some of the peripheral subregions may result from partial volume effects that are higher in the anterior and posterior tibia with coronal, and higher in the internal tibia with sagittal protocols. Still, the current data indicate that for total and central regions of the medial femorotibial compartment and for ordered values with the relatively greatest reduction in cartilage thickness, longitudinal analyses from different OAI subcohorts (analyzed with different OAI protocols) may be combined (pooled), in order to gain increased statistical power for the identification of risk factors of OA progression.
Other isotropic or near isotropic options for cartilage imaging where fluid is delineated as hyperintense have been proposed, i.e. balanced steady state free precession (bSSFP)28
, vastly undersampled isotropic projection steady-state free precession (VIPR)29
, and 3D isotropic resolution fast spin-echo MR imaging (3D-FSE)30
. Given the encouraging results with DESS, these may provide possible future choices for quantitative cartilage analysis, once they are validated for this purpose.
Baseline and one year follow-up JSN readings (OARSI atlas) for 59 of the 80 knees studied here have recently been made publicly available. Two knees (3.4%) showed an increase by two medial JSN grades, and both were identified as “progressors” (change in MFTC larger than SDD) by all three MRI protocols used. Seven knees (11.9%) displayed an increase by one medial JSN grade: three of those were identified as progressors by all three protocols, one by corFLASH only, and three by none of the protocols. Fifty (84.7%) knees maintained the same medial JSN grade: Of those six were identified as “progressors” by corFLASH, five by corMPR DESS, and 16 by sagDESS. These findings suggest a somewhat higher agreement between corFLASH “progression” with increases in radiographic JSN than for sagDESS.
Although the larger femoral ROI (75%) of the sagDESS covered a greater (47%) part of the femoral condyle, the rate and sensitivity to change was similar to the 60% ROI, corresponding with the region measured in coronal views 8
. The current study also showed that analysis of every 2nd
slice in the sagDESS was sufficient to adequately characterize longitudinal changes, and the rates and sensitivity to change were not lower than for analyses covering every slice. This permits to cut segmentation time and cost substantially, as long as fully automated segmentation algorithms are not available and validated.
In conclusion, the results of this study suggest that cartilage morphometry with FLASH and DESS display similar longitudinal sensitivity to change in cartilage thickness in anatomical subregions of the femorotibial joint that display the greatest change over time, or in ordered values (ranks) which average the greatest magnitude of subregional change across subjects, independent of the anatomical location. The high correlations for the baseline measurements show that data from the different OAI subcohort analyzed with different protocols can be combined (pooled) for cross-sectional analyses. The correlations for longitudinal thickness changes were moderate to high, indicating that pooling data from different subcohorts analyzed with different OAI protocols may also be feasible for longitudinal studies. Segmentation of every 2nd slice of the 0.7mm sagittal DESS is adequately to characterize cartilage loss longitudinally, allowing for considerable savings in segmentation time and cost.