J. Duryea

Direct comparison of fixed flexion, radiography and MRI in knee osteoarthritis: responsiveness data from the Osteoarthritis Initiative

OBJECTIVE Minimum radiographic joint space width (mJSW) represents the Food and Drug Administration (FDA) standard for demonstrating structural therapeutic benefits for knee osteoarthritis (KOA), but only shows moderate responsiveness (sensitivity to change). We directly compare the responsiveness of magnetic resonance imaging (MRI)-based cartilage thickness and JSW measures from fixed-flexion radiography (FFR) and explore the correlation of region-matched changes between both methods. METHODS Nine hundred and sixty-seven knees of Osteoarthritis Initiative participants with radiographic KOA were studied: 445 over 1 year with coronal FLASH MRI and FFR, and 375/522 over 1/2 years with sagittal DESS MRI and FFR. Standardized response means (SRM) of cartilage thickness and mJSW were compared using the sign-test. RESULTS With FLASH MRI, SRM was -0.28 for medial femorotibial compartment (MFTC) cartilage loss vs -0.15 for mJSW, and -0.32 vs -0.22 for the most sensitive MRI subregion (central MFTC) vs the most sensitive fixed-location JSW(x = 0.25). With DESS MRI, 1-year SRM was -0.34 for MFTC vs -0.22 for mJSW and -0.44 vs -0.28 for central MFTC vs JSW(x = 0.225). Over 2 years, the SRM was significantly greater for MFTC than for mJSW (-0.43 vs -0.31, P = 0.017) and for central MFTC than for JSW(x = 0.225) (-0.51 vs -0.44, P < 0.001). Correlations between changes in spatially matched MRI subregions and fixed-location JSW were not consistently higher (r = 0.10-0.51) than those between non-matched locations (r = 0.15-0.50). CONCLUSIONS MRI displays greater responsiveness in KOA than JSW FFR-based JSW, with the greatest SRM observed in the central medial femorotibial compartment. Fixed-location radiographic measures appear not capable of determining the spatial distribution of femorotibial cartilage loss.

OARSI Clinical Trials Recommendations: Hand imaging in clinical trials in osteoarthritis

Tremendous advances have occurred in our understanding of the pathogenesis of hand osteoarthritis (OA) and these are beginning to be applied to trials targeted at modification of the disease course. The purpose of this expert opinion, consensus driven exercise is to provide detail on how one might use and apply hand imaging assessments in disease modifying clinical trials. It includes information on acquisition methods/techniques (including guidance on positioning for radiography, sequence/protocol recommendations/hardware for MRI); commonly encountered problems (including positioning, hardware and coil failures, sequences artifacts); quality assurance/control procedures; measurement methods; measurement performance (reliability, responsiveness, validity); recommendations for trials; and research recommendations.

Imaging of cartilage and bone: promises and pitfalls in clinical trials of osteoarthritis

Imaging in clinical trials is used to evaluate subject eligibility, and/or efficacy of intervention, supporting decision making in drug development by ascertaining treatment effects on joint structure. This review focusses on imaging of bone and cartilage in clinical trials of (knee) osteoarthritis. We narratively review the full-text literature on imaging of bone and cartilage, adding primary experience in the implementation of imaging methods in clinical trials. Aims and constraints of applying imaging in clinical trials are outlined. The specific uses of semi-quantitative and quantitative imaging biomarkers of bone and cartilage in osteoarthritis trials are summarized, focusing on radiography and magnetic resonance imaging (MRI). Studies having compared both imaging methodologies directly and those having established a relationship between imaging biomarkers and clinical outcomes are highlighted. To make this review of practical use, recommendations are provided as to which imaging protocols are ideal for capturing specific aspects of bone and cartilage tissue, and pitfalls in their usage are highlighted. Further, the longitudinal sensitivity to change, of different imaging methods is reported for various patient strata. From these power calculations can be accomplished, provided the strength of the treatment effect is known. In conclusion, current imaging methodologies provide powerful tools for scoring and measuring morphological and compositional aspects of most articular tissues, capturing longitudinal change with reasonable to excellent sensitivity. When employed properly, imaging has tremendous potential for ascertaining treatment effects on various joint structures, potentially over shorter time scales than required for demonstrating effects on clinical outcomes.

OARSI Clinical Trials Recommendations: Knee imaging in clinical trials inosteoarthritis

Significant advances have occurred in our understanding of the pathogenesis of knee osteoarthritis (OA) and some recent trials have demonstrated the potential for modification of the disease course. The purpose of this expert opinion, consensus driven exercise is to provide detail on how one might use and apply knee imaging in knee OA trials. It includes information on acquisition methods/techniques (including guidance on positioning for radiography, sequence/protocol recommendations/hardware for magnetic resonance imaging (MRI)); commonly encountered problems (including positioning, hardware and coil failures, sequences artifacts); quality assurance (QA)/control procedures; measurement methods; measurement performance (reliability, responsiveness, validity); recommendations for trials; and research recommendations.

Imaging of Osteoarthritis

Osteoarthritis (OA) is the most prevalent joint disorder in the elderly, and there is no effective treatment. Imaging is essential for evaluating the synovial joint structures (including cartilage, meniscus, subchondral bone marrow and synovium) for diagnosis, prognosis, and follow-up. This article describes the roles and limitations of both conventional radiography and magnetic resonance (MR) imaging, and considers the use of other modalities (eg, ultrasonography, nuclear medicine, computed tomography [CT], and CT/MR arthrography) in clinical practice and OA research. The emphasis throughout is on OA of the knee. This article emphasizes research developments and literature evidence published since 2008.

Cartilage thickening in early radiographic knee osteoarthritis: A within‐person, between‐knee comparison

To determine whether the presence of definite osteophytes (in the absence of joint space narrowing [JSN]) on radiographs is associated with (subregional) increases in cartilage thickness in a within‐person, between‐knee cross‐sectional comparison of participants in the Osteoarthritis Initiative. Based on previous results, the external weight‐bearing medial femoral condyle (ecMF) and external weight‐bearing lateral femoral condyle (ecLF) subregions were selected as primary end points.

Equivalence and precision of knee cartilage morphometry between different segmentation teams, cartilage regions, and MR acquisitions

OBJECTIVE To compare precision and evaluate equivalence of femorotibial cartilage volume (VC) and mean cartilage thickness over total area of bone (ThCtAB.Me) from independent segmentation teams using identical Magnetic Resonance (MR) images from three series: sagittal 3D Dual Echo in the Steady State (DESS), coronal multi-planar reformat (DESS-MPR) of DESS and coronal 3D Fast Low Angle SHot (FLASH). DESIGN Nineteen subjects underwent test-retest MR imaging at 3 T. Four teams segmented the cartilage using prospectively defined plate regions and rules. Mixed models analysis of the pooled data were used to evaluate the effect of acquisition, team and plate on precision and Pearson correlations and mixed models were used to evaluate equivalence. RESULTS Segmentation team differences dominated measurement variability in most cartilage regions for all image series. Precision of VC and ThCtAB.Me differed significantly by team and cartilage plate, but not between FLASH and DESS. Mean values of VC and ThCtAB.Me differed by team (P < 0.05) for DESS, FLASH and DESS-MPR. FLASH VC was 4-6% larger than DESS in the medial tibia and lateral central femur, and FLASH ThCtAB.Me was 5-6% larger in the medial tibia, but 4-8% smaller in the medial central femur. Correlations between DESS and FLASH for VC and ThCtAB.Me were high (r = 0.90-0.97), except for DESS vs FLASH medial central femur ThCtAB.Me (r = 0.81-0.83). CONCLUSIONS Cartilage morphology metrics from different image contrasts had similar precision, were generally equivalent, and may be combined for cross-sectional analyses if potential systematic offsets are accounted for. Data from different teams should not be pooled unless equivalence is demonstrated for cartilage metrics of interest.

One-Year Change in Radiographic Joint Space Width in Patients With Unilateral Joint Space Narrowing: Data From The Osteoarthritis Initiative

To examine the rate of joint space width (JSW) loss in both knees of patients with unilateral medial joint space narrowing (JSN) at baseline.

Contribution of regional 3D meniscus and cartilage morphometry by MRI to joint space width in fixed flexion knee radiography--a between-knee comparison in subjects with unilateral joint space narrowing.

BACKGROUND Radiographic joint space width (JSW) is considered the reference standard for demonstrating structural therapeutic benefits in knee osteoarthritis. Our objective was to determine the proportion by which 3D (regional) meniscus and cartilage measures explain between-knee differences of JSW in the fixed flexion radiographs. METHODS Segmentation of the medial meniscus and tibial and femoral cartilage was performed in double echo steady state (DESS) images. Quantitative measures of meniscus size and position, femorotibial cartilage thickness, and radiographic JSW (minimum, and fixed locations) were compared between both knees of 60 participants of the Osteoarthritis Initiative, with strictly unilateral medial joint space narrowing (JSN). Statistical analyses (between-knee, within-person comparison) were performed using regression analysis. RESULTS A strong relationship with side-differences in minimum and a central fixed location JSW was observed for percent tibial plateau coverage by the meniscus (r = .59 and .47; p<.01) and central femoral cartilage thickness (r = .69 and .75; p<.01); other meniscus and cartilage measures displayed lower coefficients. The correlation of central femoral cartilage thickness with JSW (but not that of meniscus measures) was greater (r = .78 and .85; p<.01) when excluding knees with non-optimal alignment between the tibia and X-ray beam. CONCLUSION 3D measures of meniscus and cartilage provide significant, independent information in explaining side-differences in radiographic JSW in fixed flexion radiographs. Tibial coverage by the meniscus and central femoral cartilage explained two thirds of the variability in minimum and fixed location JSW. JSW provides a better representation of (central) femorotibial cartilage thickness, when optimal positioning of the fixed flexion radiographs is achieved.

Radiographic grading and measurement of joint space width in osteoarthritis.

The progression of osteoarthritis is traditionally measured using radiographic joint space width (JSW). Numerous knee radiograph protocols have been developed with various levels of complexity and performance as it relates to detecting JSW loss (ie, joint space narrowing). Sensitivity to joint space narrowing is improved when radioanatomic alignment of the medial tibial plateau is achieved. Semiautomated software has been developed to improve the accuracy of JSW measurement over manual methods. JSW measurements include minimum JSW, mean JSW or joint space area, and JSW at fixed locations.