MRI-based extended ordered values more efficiently differentiate cartilage loss in knees with and without joint space narrowing than region-specific approaches using MRI or radiography--data from the OA initiative

Abstract

Objective: The sensitivity to change of quantitative analysis of cartilage in knee osteoarthritis using magnetic resonance imaging (MRI) is compromised by the spatial heterogeneity of cartilage loss. We explore whether extended (medial-lateral) "ordered values" (OVs) are superior to conventional approaches of analyzing subregional cartilage thickness loss and to radiography, in differentiating rates of progression in knees with and without joint space narrowing (JSN).

Methods: 607 Osteoarthritis Initiative (OAI) participants (308 without and 299 with baseline JSN at baseline) were studied over 12 months. Subregional femorotibial cartilage loss was determined in all knees, and changes in minimum joint space width (mJSW) in a subset of 290 knees. Subregional thickness changes in medial and lateral tibial and femoral cartilages were sorted in ascending order (OV1-16). A Wilcoxon rank-sum test was used to compare rates of change in knees with and without JSN.

Results: JSN-knees displayed greater cartilage loss than those without JSN, with minimal P-values of 0.008 for femorotibial subregions, 3.3×10(-4) for medial OV1, and 5.4×10(-7) for extended (medial and lateral) OV1. mJSW measurements (n=290) did not discriminate between longitudinal rates of change in JSN vs no-JSN knees (P=0.386), whereas medial OV1 (P=5.1×10(-4)) and extended OV1 did (P=2.1×10(-5)).

Conclusion: Extended OVs showed higher sensitivity to detecting differences in longitudinal rates of cartilage loss in knees with and without baseline JSN than anatomical (sub)regions and radiography. The OV technique also circumvents challenges of selecting particular regions "a priori" in clinical trials and may thus provide a powerful tool in studying risk factors or treatment efficacy in osteoarthritis.

Figure 1

Double oblique coronal fast low angle shot (FLASH) MR image with water excitation showing the regions of interest analyzed: MFTC = medial femorotibial compartment (=MT+cMF), LFTC = lateral femorotbial compartment (=LT+cLF); MT = medial tibia, cMF = central, weight-bearing part of the medial femoral condyle, LT = lateral tibia, cLF = central, weight-bearing part of the lateral femoral condyle. The top part of the figures shows a reconstruction of the weight-bearing parts of the femoral condyles (cMF and cLF) and the lower part a reconstruction of the tibiae (MT and LT). (c|e|i|a|p = central|external|internal|anterior|posterior subregion of MT or LT. c|e|i = central|external|internal subregion of the central part of cMF or cLF.

Figure 2

Graph showing the ordered values approach: A) The top spreadsheet shows the results (change in cartilage thickness [ThCtAB] in µm) in the femorotibial subregions (see Figure 1) of four example OAI subjects. B) The rates of change are ranked according to their magnitude in the middle spread sheet. C) The magnitudes of the changes (in µm) are then attributed to the orders in the bottom spread sheet. The subregion with the most negative change (decrease in ThCtAB) in each subject is assigned to order 1, the subregion showing the second most negative change assigned to order 2, and the subregion showing the smallest negative or the greatest positive change (increase in ThCtAB) assigned to order 16. Note that differently located subregions contribute to order 1 in the four subjects shown.

Figure 3

Graphs showing the distribution of p-values obtained from A) the bootstrapping method and from B) the randomization of changes in JSN knees. The distribution is shown for the entire medial (MFTC) and lateral (LFTC) femorotibial compartment, the anterior subregion of the medial tibia (aMT), the medial ordered value 1 (mOV1), and the extended ordered values 1 and 16 (eOV1, eOV 16).