R. Buck

The acutely ACL injured knee assessed by MRI: changes in joint fluid, bone marrow lesions, and cartilage during the first year

OBJECTIVES To investigate changes in the knee during the first year after acute rupture of the anterior cruciate ligament (ACL) of volumes of joint fluid (JF), bone marrow lesions (BMLs), and cartilage volume (VC), and cartilage thickness (ThCcAB) and cartilage surface area (AC). To identify factors associated with these changes. METHODS Fifty-eight subjects (mean age 26 years, 16 women) with an ACL rupture to a previously un-injured knee were followed prospectively using a 1.5T MR imager at baseline (within 5 weeks from injury), 3 months, 6 months, and 1 year. Thirty-four subjects were treated with ACL reconstruction followed by a structured rehabilitation program and 24 subjects were treated with structured rehabilitation only. Morphometric data were acquired from computer-assisted segmentation of MR images. Morphometric cartilage change was reported as mean change divided by the standard deviation of change (standard response mean, SRM). RESULTS JF and BML volumes gradually decreased over the first year, although BML persisted in 62% of the knees after 1 year. One year after the ACL injury, a reduction of VC, AC and ThCcAB (SRM -0.440 or greater) was found in the trochlea femur (TrF), while an increase of VC and ThCcAB was found in the central medial femur (cMF) (SRM greater than 0.477). ACL reconstruction was directly and significantly related to increased JF volume at 3 and 6 months (P<0.001), BML volume at 6 months (P=0.031), VC and ThCcAB in cMF (P<0.002) and decreased cartilage area in TrF (P=0.010) at 12 months. CONCLUSION Following an acute ACL tear, cMF and TrF showed the greatest consistent changes of cartilage morphometry. An ACL reconstruction performed within a mean of 6 weeks from injury was associated with increased ThCcAB and VC in cMF and decreased AC in TrF, compared to knees treated without reconstruction. This may suggest a delayed structural restitution in ACL reconstructed knees.

Precision of 3.0 Tesla quantitative magnetic resonance imaging of cartilage morphology in a multicentre clinical trial

Objective: Quantitative MRI (qMRI) of cartilage morphology is a promising tool for disease-modifying osteoarthritis drug (DMOAD) development. Recent studies at single sites have indicated that measurements at 3.0 Tesla (T) are more reproducible (precise) than those at 1.5 T. Precision errors and stability in multicentre studies with imaging equipment from various vendors have, however, not yet been evaluated. Methods: A total of 158 female participants (97 Kellgren and Lawrence grade (KLG) 0, 31 KLG 2 and 30 KLG 3) were imaged at 7 clinical centres using Siemens Magnetom Trio and GE Signa Excite magnets. Double oblique coronal acquisitions were obtained at baseline and at 3 months, using water excitation spoiled gradient echo sequences (1.0×0.31×0.31 mm3 resolution). Segmentation of femorotibial cartilage morphology was performed using proprietary software (Chondrometrics GmbH, Ainring, Germany). Results: The precision error (root mean square coefficient of variation (RMS CV)%) for cartilage thickness/volume measurements ranged from 2.1%/2.4% (medial tibia) to 2.9%/3.3% (lateral weight-bearing femoral condyle) across all participants. No significant differences in precision errors were observed between KLGs, imaging sites, or scanner manufacturers/types. Mean differences between baseline and 3 months ranged from <0.1% (non-significant) in the medial to 0.94% (p<0.01) in the lateral femorotibial compartment, and were 0.33% (p<0.02) for the total femorotibial subchondral bone area. Conclusions: qMRI performed at 3.0 T provides highly reproducible measurements of cartilage morphology in multicentre clinical trials with equipment from different vendors. The technology thus appears sufficiently robust to be recommended for large-scale multicentre trials.

Head-to-head comparison of the Lyon Schuss and fixed flexion radiographic techniques. Long-term reproducibility in normal knees and sensitivity to change in osteoarthritic knees

OBJECTIVE The Lyon Schuss (LS) and fixed flexion (FF) views of the knee are superior to a conventional standing anteroposterior view in evaluating joint space narrowing (JSN) in osteoarthritis (OA). Both position the knee identically but only the LS aligns the medial tibial plateau (MTP) with the x-ray beam fluoroscopically. The present study provides the first head-to-head comparison of the LS and FF views. METHODS At baseline and 12 months, 62 OA and 99 control knees were imaged twice on the same day with LS and FF views. Minimum joint space width (mJSW) was measured by computer and MTP alignment was assessed from the distance between anterior and posterior margins of the MTP (intermargin distance, IMD). Reproducibility of measurements of mJSW and sensitivity to change were evaluated. RESULTS In normal knees, JSW did not vary over 12 months with either view. In OA knees, 12-month mJSN was 0.22 (0.43) mm with the LS view and -0.01 (0.46) mm with the FF view (p = 0.0002 and p = 0.92, respectively). Mean IMD was only half as large in LS as in FF views (0.9 (0.5) mm vs 1.9 (1.2) mm, p<0.0001). CONCLUSIONS LS and FF radiographs offer similar reproducibility in JSW measurement. However, presumably due to its superiority in aligning the MTP, the LS view is much more sensitive to JSN in OA knees.

Change in regional cartilage morphology and joint space width in osteoarthritis participants versus healthy controls: a multicentre study using 3.0 Tesla MRI and Lyon–Schuss radiography

Objective: Cartilage morphology displays sensitivity to change in osteoarthritis (OA) with quantitative MRI (qMRI). However, (sub)regional cartilage thickness change at 3.0 Tesla (T) has not been directly compared with radiographic progression of joint space narrowing in OA participants and non-arthritic controls. Methods: A total of 145 women were imaged at 7 clinical centres: 86 were non-obese and asymptomatic without radiographic OA and 55 were obese with symptomatic and radiographic OA (27 Kellgren–Lawrence grade (KLG)2 and 28 KLG3). Lyon–Schuss (LS) and fixed flexion (FF) radiographs were obtained at baseline, 12 and 24 months, and coronal spoiled gradient echo MRI sequences at 3.0 T at baseline, 6, 12 and 24 months. (Sub)regional, femorotibial cartilage thickness and minimum joint space width (mJSW) in the medial femorotibial compartment were measured and the standardised response means (SRMs) determined. Results: At 6 months, qMRI demonstrated a −3.7% “annualised” change in cartilage thickness (SRM −0.33) in the central medial femorotibial compartment (cMFTC) of KLG3 subjects, but no change in KLG2 subjects. The SRM for mJSW in 12-month LS/FF radiographs of KLG3 participants was −0.68/−0.13 and at 24 months was −0.62/−0.20. The SRM for cMFTC changes measured with qMRI was −0.32 (12 months; −2.0%) and −0.48 (24 months; −2.2%), respectively. Conclusions: qMRI and LS radiography detected significant change in KLG3 participants at high risk of progression, but not in KLG2 participants, and only small changes in controls. At 12 and 24 months, LS displayed greater, and FF less, sensitivity to change in KLG3 participants than qMRI.

The acutely ACL injured knee assessed by MRI: are large volume traumatic bone marrow lesions a sign of severe compression injury?

OBJECTIVES To map by magnetic resonance imaging (MRI) and quantitative MRI (qMRI) concomitant fractures and meniscal injuries, and location and volume of traumatic bone marrow lesions (BMLs) in the acutely anterior cruciate ligament (ACL) injured knee. To relate BML location and volume to cortical depression fractures, meniscal injuries and patient characteristics. METHODS One hundred and twenty-one subjects (26% women, mean age 26 years) with an ACL rupture to a previously un-injured knee were studied using a 1.5T MR imager within 3 weeks from trauma. Meniscal injuries and fractures were classified by type, size and location. BML location and volume were quantified using a multi-spectral image data set analyzed by computer software, edited by an expert radiologist. RESULTS Fractures were found in 73 (60%) knees. In 67 (92%) of these knees at least one cortical depression fracture was found. Uni-compartmental meniscal tears were found in 44 (36%) subjects and bi-compartmental in 24 (20%). One hundred and nineteen (98%) knees had at least one BML, all but four (97%) located in the lateral compartment. Knees with a cortical depression fracture had larger BML volumes (P<0.001) than knees without a cortical depression fracture, but no associations were found between meniscal tears and BML volume or fractures. Older age at injury was associated with smaller BML volumes (P<0.01). CONCLUSION A majority of the ACL injured knees had a cortical depression fracture, which was associated with larger BML volumes. This indicates strong compressive forces to the articular surface and cartilage at the time of injury, which may constitute an additional risk factor for later knee osteoarthritis development.

Osteoarthritis may not be a one-way-road of cartilage loss--comparison of spatial patterns of cartilage change between osteoarthritic and healthy knees.

OBJECTIVE To explore whether longitudinal change in cartilage thickness in femorotibial subregions of knees with radiographic osteoarthritis (ROA) differs from that in healthy knees. METHODS 3T coronal magnetic resonance (MR) images were acquired in 152 women at seven clinical centers at baseline (BL) and 24 months. Knees from 75 women with signs of ROA in either anterior-posterior or Lyon schuss radiographs were compared with those from 77 asymptomatic healthy controls without ROA to identify knees showing greater change in cartilage thickness than expected based on observations in healthy knees. The femorotibial cartilage thickness was determined in BL and follow-up MR images across five tibial and three femoral subregions in the medial/lateral compartment, respectively. RESULTS A substantial portion of knees with ROA were classified as having longitudinal cartilage thinning (28%) or thickening (20%) in at least one medial femorotibial subregion based on comparisons to longitudinal changes observed in healthy knees; only 5% showed both subregional thinning and thickening across (different) medial subregions at the same time. Whereas the estimated proportion of Kellgren Lawrence grade (KLG) 3 knees (n=28) with significant medial cartilage thinning (46%) was substantially greater than that with cartilage thickening (18%), the estimated percentages of KLG2 knees (n=30) with significant medial thinning (20%) and thickening (23%) were similar. CONCLUSION This exploratory study indicates that OA may not be a one-way-road of cartilage loss. Subregional analysis suggests that, compared with healthy knees, cartilage changes in ROA may occur in both directions. Medial femorotibial cartilage thickening was observed as frequently as cartilage thinning in KLG2 knees.

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.

Does the use of ordered values of subregional change in cartilage thickness improve the detection of disease progression in longitudinal studies of osteoarthritis

OBJECTIVE To propose a novel strategy for more efficiently measuring changes in cartilage thickness in osteoarthritis (OA) using magnetic resonance imaging, and to hypothesize that determining the magnitude of thickness change independent of the anatomic location provides improved discrimination between healthy subjects and OA participants longitudinally. METHODS A total of 148 women were imaged; 90 were Kellgren/Lawrence (K/L) grade 0, 30 were K/L grade 2, and 28 were K/L grade 3. Magnetic resonance images (3T) were acquired at baseline and at 24 months. Changes in femorotibial cartilage thickness were determined in 5 tibial and 3 femoral medial and lateral subregions, respectively (conventional approach). The new strategy provided ordered values of subregional change in each compartment, ranked according to the direction and magnitude of change. RESULTS Using the new ordered values approach, the minimal P value for the differences in 2-year change in medial cartilage thickness of K/L grade 3 and K/L grade 0 participants was 0.001 (Wilcoxon test), with 4 ordered medial subregions differing significantly between both groups. With the conventional approach, only 1 medial subregion differed significantly between K/L grade 3 and K/L grade 0 (P = 0.037). Cartilage thickening was significantly greater in K/L grade 2 versus K/L grade 0 participants in 1 medial subregion using the conventional approach (P = 0.016), and in 2 medial subregions (minimal P = 0.007) using the ordered values approach. CONCLUSION The novel ordered values approach is more sensitive in detecting cartilage thinning in K/L grade 3 and cartilage thickening in K/L grade 2 versus K/L grade 0 participants. The new method may be particularly useful in the context of other comparisons, e.g., a group treated with a disease-modifying OA drug versus one treated with a placebo.

Subregional femorotibial cartilage morphology in women – comparison between healthy controls and participants with different grades of radiographic knee osteoarthritis

OBJECTIVE To identify subregional differences in femorotibial cartilage morphology between healthy controls and women with different grades of radiographic knee osteoarthritis (OA). DESIGN 158 women aged > or =40 years were studied. Weight-bearing extended anterior-posterior (AP) and Lyon schuss radiographs were obtained and the Kellgren Lawrence grade (KLG) determined. 97 women had a body mass index (BMI)< or =28, no symptoms, and were AP KLG0. 61 women had a BMI> or =30, symptoms in the target knee, and mild (KLG2=31) to moderate (KLG3=30) medial femorotibial radiographic OA in the AP views. Coronal spoiled gradient echo water excitation sequences were acquired at 3.0 Tesla. Total plate and regional measures of cartilage morphology of the weight-bearing femorotibial joint were quantified. RESULTS KLG2 participants displayed, on average, thicker cartilage than healthy controls in the medial femorotibial compartment (particularly anterior subregion of the medial tibia (MT) and peripheral [external, internal] subregions of the medial femur), and in the lateral femur. KLG3 participants displayed significantly thinner cartilage than KLG0 participants in the medial weight-bearing femur (central subregion), in the external subregion of the MT, and in the internal subregion of the lateral tibia. These differences were generally unaffected when possible effects of demographic covariates were considered. CONCLUSIONS The results indicate that in femorotibial OA regional cartilage thickening and thinning may occur, dependent on the (radiographic) disease status of the joint. These changes appear to display a heterogeneous spatial pattern, where certain subregions are more strongly affected than others.

Clinical, radiographic, molecular and MRI-based predictors of cartilage loss in knee osteoarthritis

Objective To examine the relationship of baseline clinical, radiographic, molecular and MRI measures with structural progression (subregional MRI-based femorotibial cartilage loss) in knee osteoarthritis (OA). Methods Single knees of 75 female participants with radiographic knee OA (and 77 healthy control participants) were examined over 24 months using MRI. Subregional femorotibial cartilage thickness was determined at baseline and follow-up. Baseline clinical, radiographic, molecular (n=16) and quantitative MRI-based measures of the meniscus and cartilage, including delayed gadolinium-enhanced MRI (dGEMRIC) and T2, were obtained. Differences in these baseline measures between radiographic osteoarthritic knees with longitudinal cartilage thinning (or thickening) and those with no significant change were evaluated by receiver operator characteristic analyses and Wilcoxon rank sum tests. Results The relatively strongest predictors of longitudinal cartilage thinning were reduced baseline cartilage thickness in the medial femur (area under the curve (AUC)=0.81), varus malalignment (AUC=0.77), reduced minimum joint space width and a greater radiographic joint space narrowing (JSN) score (both AUC=0.74). These remained significant after adjusting for multiple comparisons using false discovery rates. Reduced bone resorption (C-terminal telopeptide of type I collagen; AUC=0.65) and a low dGEMRIC index (reflecting low proteoglycan content) in the medial tibia (AUC=0.68) were associated with longitudinal cartilage thinning, but failed to reach statistical significance after correction for multiple testing in this (small) sample. Conclusions This exploratory study indicates that baseline molecular or MRI cartilage compositional markers may not provide better discrimination between knees with cartilage thinning and those without longitudinal change than simple radiographic measures, such as greater JSN score.