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DOI: 10.1148/radiol.2203000461
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(Radiology. 2001;220:696-706.)
© RSNA, 2001

Pediatric Imaging

Knee in Early Juvenile Rheumatoid Arthritis: MR Imaging Findings1

Victoria M. Gylys-Morin, MD, T. Brent Graham, MD, Judy S. Blebea, MD, Bernard J. Dardzinski, PhD, Tal Laor, MD, Neil D. Johnson, MD, Alan E. Oestreich, MD and Murray H. Passo, MD

1 From the Departments of Radiology (V.M.G.M., B.J.D., T.L., N.D.J., A.E.O.) and Rheumatology (T.B.G., M.H.P.), Children’s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229-3039; and the Department of Radiology, Milton Hershey Medical Center, Hershey, Pa (J.S.B.). Received February 8, 2000; revision requested March 27; final revision received February 23, 2001; accepted February 26. Supported by National Institutes of Health grant 1-P60-AR44059-01. Address correspondence to V.M.G.M. (e-mail: gylys.morin@chmcc.org).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
PURPOSE: To determine the magnetic resonance (MR) imaging findings in the knee in early juvenile rheumatoid arthritis.

MATERIALS AND METHODS: MR imaging (1.5 T) was performed in the more symptomatic knee in 30 children with juvenile rheumatoid arthritis with a symptom duration 1 year or less. Conventional, fast spin-echo, three-dimensional gradient-echo, and gadolinium-enhanced T1-weighted images were assessed. Two radiologists independently read the images, and a third resolved disagreements. These images were compared with knee radiographs in 27 children.

RESULTS: Mean maximal synovial thickness was 4.8 mm ± 2.4 (SD). Mean synovial volume was 15.4 mL ± 10.8. Suprapatellar joint effusions were seen in 26 (87%) of 30 knees, meniscal hypoplasia in 11 (37%) of 30 knees, and abnormal epiphyseal marrow in eight (27%) of 30 knees. Three knees had articular cartilage contour irregularity, fissures, and/or thinning. One knee had a bone erosion. Knee radiographs showed suprapatellar fullness in 78% of the knees, joint space narrowing in one knee, and no bone abnormalities.

CONCLUSION: Synovial hypertrophy and joint effusions are the most frequent MR imaging findings of knees in early juvenile rheumatoid arthritis. Early in the disease, radiographically occult cartilage and bone erosions are uncommonly seen at MR imaging. The potential relationship of synovitis to cartilage abnormalities deserves further study.

Index terms: Arthritis, in infants and children, 452.713 • Arthritis, rheumatoid, 452.713 • Knee, arthritis, 452.713 • Knee, MR, 452.121411, 452.121412, 453.121415, 452.12143


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Juvenile rheumatoid arthritis (JRA) is the most common rheumatic disorder of childhood, with 6 to 19.6 incident cases per 100,000 children yearly (1). The knee is the most frequently affected joint (2). With the increasing availability and use of disease-modifying antirheumatic drugs, demonstration of early joint damage has become important (3–5). Physical examination may have low reliability in the assessment of disease activity because of subjectiveness among examiners (6,7). Conventional radiographs, the current standard of reference for initial radiologic evaluation and assessment of disease progression in JRA, are of limited use in early arthritis because they may not show an inflamed synovium, cartilage destruction, and early bone erosions, all of which are depicted with magnetic resonance (MR) imaging (7–12). For this reason, MR imaging findings have been suggested (13–16) as an index of disease activity for arthritis.

To utilize MR imaging to monitor disease progression and response to therapy in children with JRA, imaging findings early in the course of disease must be known for meaningful interpretation of subsequent changes. Prior investigators (8,9,11) have described MR imaging findings in children with JRA of variable disease duration (mean duration, 4–5 years). The purpose of this study was to determine the MR imaging findings in the knee in children with early JRA (symptom duration < 1 year) and clinical synovitis.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Patients
Thirty children and adolescents (21 female, nine male; age range, 5–16 years; mean age, 10.2 years) were enrolled in this prospective study during 31 months (June 20, 1996, to February 16, 1999) after referral to the rheumatology clinic for evaluation of early JRA. They met the American College of Rheumatology criteria for JRA, which are the present standards for diagnosis. These standards require the presence of objective arthritis (defined as either joint swelling or limitation of motion associated with heat, tenderness, or pain) in at least one joint for 6 consecutive weeks and the exclusion of other diagnoses (17). Additional inclusion criteria for our study were the following: clinically evident arthritis in at least one knee (as determined by the attending pediatric rheumatologist [M.H.P.]), disease duration (defined as time since onset of symptoms) of less than 1 year, and no injection of intraarticular steroids into the affected knee.

Patients were recruited as part of a prospective study of MR imaging of JRA in which patients are subsequently undergoing MR imaging and conventional radiography of the knee on a yearly basis. In this 5-year prospective study, clinicians are blinded to MR imaging results, and radiologists are blinded to details of the clinical data in individual patients until the end of the study. As a result, correlation of clinical and imaging data cannot be accomplished at this time. Disease duration of less than 1 year was selected because, unlike the case with rheumatoid arthritis, rapidly progressive erosions are uncommon in JRA within the 1st year of disease (18).

Institutional review board approval and parental informed consent were obtained for MR imaging and radiography. Only children who could undergo imaging without sedation were enrolled. Standard screening safety criteria for MR imaging were observed.

Imaging
MR imaging was performed in the more symptomatic knee with a 1.5-T magnet (Signa; GE Medical Systems, Milwaukee, Wis) by using a dedicated knee coil and the imaging sequences detailed in Table 1. A fat-saturated three-dimensional T1-weighted gradient-echo technique was used to evaluate the morphology of the articular cartilage (19). Fast spin-echo (SE) intermediate- and T2-weighted images were used to depict changes in signal intensity within the articular cartilage (20). Immediately after the intravenous administration of contrast material (gadopentetate dimeglumine [Magnevist]; Berlex Laboratories, Wayne, NJ; 0.1 mmol per kilogram of body weight), T1-weighted fat-saturated images were obtained in the sagittal and coronal planes. Sagittal image acquisition was completed within 3–4 minutes of the administration of contrast material, which is well within the recommended 5 minutes allowed after contrast material administration to capture peak synovial enhancement and prevent volume overestimation due to contrast material diffusion into the joint space (21). Total imaging time was 45–55 minutes.


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  		TABLE 1. MR Imaging Protocol for JRA

 
Twenty-seven patients had frontal and lateral radiographs of the non–weight-bearing knee. These were obtained at the time of MR imaging in all children except one, in whom they were obtained 3 weeks later. Three patients and/or parents declined radiography.

Image Analysis
MR images were interpreted by readers who were blinded to the specific clinical history, including the duration, extent, and severity of symptoms; findings at physical examination; and medications. The primary readers (V.M.G.M., J.S.B.) reviewed the MR images of the 30 enrolled patients. In the event of disagreement between the primary readers, a third reader (T.L.) provided independent interpretation of subjective variables that served as the tiebreaker. Each case was originally assessed for approximately 40 subjective variables (only a portion of which are reported in this article) at the time of MR image interpretation. A third reading was typically required to assess three to six subjective variables per case. Continuous variables were measured once per patient.

The synovium was assessed for signal intensity characteristics, distribution, and maximal thickness. Maximal synovium thickness was measured in the suprapatellar bursa and intercondylar region on sagittal T1-weighted gadolinium-enhanced images. It was measured on digital images magnified by a factor of two and was graded as follows: 1, 0–2 mm; 2, 3–5 mm; 3, 6–9 mm; and 4, 10–14 mm.

Synovial volumes were also calculated on the sagittal T1-weighted fat-saturated images by using semiautomatic segmentation based on gadolinium enhancement and a dedicated software program (INTERACTIVE DATA LANGUAGE; Research Systems, Boulder, Colo). A radiologist (V.M.G.M.) drew regions of interest around the synovium to exclude areas of high signal intensity due to adjacent blood vessels, soft tissues, and physes from the volume calculation. Boundaries were closely drawn around the bright areas within the user-defined regions by using a k-means-clustering algorithm (Fig 1) (22). Volume was calculated from the number of brightest pixels that were automatically segmented by multiplying the in-plane pixel dimensions by the section thickness. Volumes (range, 2–25 mL) of three volume-segmentation phantoms were calculated with varying section thicknesses and different x and y resolutions and were found to be accurate to within 13% of the actual volumes (Dardzinski BJ, unpublished data, 1999); this accuracy is acceptable for this method to be used as a relative measure of joint inflammation (23).



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  		Figure 1. Sagittal gadolinium-enhanced T1-weighted fat-saturated MR image (400/16) demonstrates the boundary of pixels (arrowheads) used for volume calculation in the enhancing synovium. (Fig 3c is an identical image, with boundaries not shown.)

 
The usefulness of maximal synovial thickness versus synovial volume in determining synovitis was assessed by comparing knee MR images in patients with JRA and active synovitis (n = 30) with those of control subjects without clinical synovitis (12 knees in 12 children who underwent MR imaging for other reasons). Active synovitis is defined as swelling or limitation of motion with heat, pain, or tenderness and was required in the patients with JRA for entry into the study (17). Although the investigators did not examine the control subjects, clinical synovitis was thought to be absent on the basis of the history given when the study was requested. Sensitivity and specificity in the diagnosis of synovitis with the use of maximal synovial thickness versus synovial volume were compared by using the clinical diagnosis of synovitis as the standard because this method remains the way JRA is defined (17).

Joint effusion size was subjectively graded within the suprapatellar bursa, intercondylar region, and tibiofibular joint as follows: 1, none or trace; 2, small; 3, moderate; and 4, large or marked. Menisci were graded as normal, hypoplastic (with shortening and/or loss of triangular configuration), torn, or atrophic and/or absent. Articular cartilage was assessed for contour (smooth vs irregular) and focal destruction (intact, superficial loss and/or thinning, or deep erosions to subchondral bone). Joint cartilage thickness of the middle of the medial and lateral femoral condyles and tibial plateaus was measured on digitized three-dimensional fat-saturated spoiled gradient-echo images that were electronically magnified by a factor of five. Bone was assessed for marrow signal intensity abnormalities and focal erosions. The knee joint was evaluated for abnormalities of the infrapatellar fat pad, tenosynovitis, synovial cysts, regional lymphadenopathy, and internal derangements.

Conventional knee radiographs obtained in 27 patients were randomly mixed with 57 age- and sex-matched normal knee radiographs (selected by V.M.G.M.). Radiographs were masked and reviewed by two pediatric musculoskeletal radiologists (N.D.J., A.E.O.) who were blinded to patient history and MR imaging findings. In the event of disagreement, a third reader (T.L.), who served as tiebreaker, read the masked patient and normal radiographs as a batch 6 months after the reading of the MR images. Radiographs were scored by using the Pettersson classification system (24). Independent of this scoring system, radiographs were also assessed for suprapatellar bursa fullness due to effusion and/or pannus (none, small, moderate, or large) and joint space narrowing.

Statistical Analysis
Statistical analysis was completed with SPSS (version 8.0; SPSS, Chicago, Ill) for Windows (Microsoft; Redmond, Wash). A Student t test was used to compare the means of continuous variables. Nonparametric tests were used to compare ordinal variables. When more than one control was used per subject, the mean value was used for comparison purposes and was rounded to the greater number. A Spearman rank correlation was used to assess the correlation between imaging variables when at least one of the variables was ordinal. A Pearson correlation coefficient was calculated when two continuous variables were correlated. Whenever possible, the {kappa} statistic was calculated to assess interobserver reliability (25). A {kappa} value of more than 0.75 denotes excellent reliability; 0.75–0.40, good reliability; and less than 0.40, marginal reliability (26). Because some cells were zero for some variables, {kappa} could not be calculated. In these instances, the percentage of agreement was calculated.

Receiver operating characteristic curves were used to evaluate the ability to distinguish patients from control subjects with both conventional radiographs and MR images. These curves were constructed by using nonparametric methods with software (Analyse-it Software, Leeds, England) for EXCEL (Microsoft; Redmond, Wash). In each instance, analysis of the data clearly revealed points that maximized specificity while not substantially compromising sensitivity. The Hanley and McNeil method was used to compare receiver operating characteristic curves.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Patients
All 30 patients presented with joint swelling, with or without pain and limitation of motion. All had received nonsteroidal antiinflammatory drugs (mean duration of therapy, 2.7 months) prior to MR imaging. All patients were thought to have active knee synovitis when they were examined on the day of MR imaging, but some patients had an improvement in objective arthritis after beginning therapy. Mean symptom duration was 5.1 months (range, 1–12 months); 16 (53%) of 30 patients had pauciarticular, 10 (33%) had polyarticular, and four (13%) had systemic onsets of disease.

MR Imaging Findings
The two most frequent MR imaging findings in our study were synovial proliferation and joint effusions (Fig 2).



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  		Figure 2. Summary of MR imaging findings in the knees of children with early (newly diagnosed) JRA.

 
Synovium.—The synovium was seen in the suprapatellar bursa, lining the infrapatellar fat pad, and adjacent to the posterior femoral condyles in all knees (Figs 3–5). The synovium was also adjacent to or surrounding menisci in 29 (97%) of 30 knees, in the intercondylar region and posterior femoral recess in 28 (93%) knees, in the posterior tibial or popliteus recess in 20 (67%) knees, and in the tibiofibular joint in 18 (60%) knees. Interobserver agreement was 78%–99% in the assessment of synovial distribution.



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  		Figure 3a. (a) Sagittal fast SE T2-weighted MR image (3,000/112) obtained in a 5-year-old girl shows bulky low-signal-intensity pannus (*) in the suprapatellar bursa, which is outlined by high-signal-intensity joint effusion (open arrow). Synovium lining the bursa (arrowheads) is of intermediate to high signal intensity and is difficult to distinguish from adjacent high-signal-intensity effusion. The infrapatellar fat pad (curved arrow) has contour irregularity and signal inhomogeneity. Intermediate to low signal intensity pannus (solid straight arrows) is in the intercondylar region. (b) Pannus has mixed enhancement on this sagittal gadolinium-enhanced T1-weighted fat-saturated MR image (400/16). The peripheral synovium has high signal intensity (arrowheads), while the central bulky pannus (*) does not enhance and is indistinguishable from the surrounding low-signal-intensity joint fluid. (c) More medially, hypervascular synovium is in the posterior femoral recess (white straight solid arrow) and encroaches onto the meniscal surfaces (black arrows) on this sagittal T1-weighted gadolinium-enhanced MR image (400/16). Loss of the triangular configuration in the medial meniscus (black arrows) suggests early meniscal hypoplasia. Prominent radially oriented vessels (open arrows) course through the femoral condyle epiphyseal cartilage. The distal femoral epiphysis has abnormally increased marrow signal intensity (curved arrow).

 


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  		Figure 3b. (a) Sagittal fast SE T2-weighted MR image (3,000/112) obtained in a 5-year-old girl shows bulky low-signal-intensity pannus (*) in the suprapatellar bursa, which is outlined by high-signal-intensity joint effusion (open arrow). Synovium lining the bursa (arrowheads) is of intermediate to high signal intensity and is difficult to distinguish from adjacent high-signal-intensity effusion. The infrapatellar fat pad (curved arrow) has contour irregularity and signal inhomogeneity. Intermediate to low signal intensity pannus (solid straight arrows) is in the intercondylar region. (b) Pannus has mixed enhancement on this sagittal gadolinium-enhanced T1-weighted fat-saturated MR image (400/16). The peripheral synovium has high signal intensity (arrowheads), while the central bulky pannus (*) does not enhance and is indistinguishable from the surrounding low-signal-intensity joint fluid. (c) More medially, hypervascular synovium is in the posterior femoral recess (white straight solid arrow) and encroaches onto the meniscal surfaces (black arrows) on this sagittal T1-weighted gadolinium-enhanced MR image (400/16). Loss of the triangular configuration in the medial meniscus (black arrows) suggests early meniscal hypoplasia. Prominent radially oriented vessels (open arrows) course through the femoral condyle epiphyseal cartilage. The distal femoral epiphysis has abnormally increased marrow signal intensity (curved arrow).

 


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  		Figure 3c. (a) Sagittal fast SE T2-weighted MR image (3,000/112) obtained in a 5-year-old girl shows bulky low-signal-intensity pannus (*) in the suprapatellar bursa, which is outlined by high-signal-intensity joint effusion (open arrow). Synovium lining the bursa (arrowheads) is of intermediate to high signal intensity and is difficult to distinguish from adjacent high-signal-intensity effusion. The infrapatellar fat pad (curved arrow) has contour irregularity and signal inhomogeneity. Intermediate to low signal intensity pannus (solid straight arrows) is in the intercondylar region. (b) Pannus has mixed enhancement on this sagittal gadolinium-enhanced T1-weighted fat-saturated MR image (400/16). The peripheral synovium has high signal intensity (arrowheads), while the central bulky pannus (*) does not enhance and is indistinguishable from the surrounding low-signal-intensity joint fluid. (c) More medially, hypervascular synovium is in the posterior femoral recess (white straight solid arrow) and encroaches onto the meniscal surfaces (black arrows) on this sagittal T1-weighted gadolinium-enhanced MR image (400/16). Loss of the triangular configuration in the medial meniscus (black arrows) suggests early meniscal hypoplasia. Prominent radially oriented vessels (open arrows) course through the femoral condyle epiphyseal cartilage. The distal femoral epiphysis has abnormally increased marrow signal intensity (curved arrow).

 


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  		Figure 4a. (a) Sagittal fast SE T2-weighted fat-saturated MR image (4,000/126) obtained in a 7-year-old boy shows a large knee joint effusion (*) that distends the suprapatellar bursa, posterior femoral recess, and posterior tibial recess. The effusion is lined by nearly imperceptible synovium (arrowheads). (b) The synovium (curved arrows) is readily seen on this gadolinium-enhanced sagittal T1-weighted fat-saturated MR image (400/17). Curvilinear high signal intensity at the cartilage-epiphysis junction (straight solid arrows) and enhancing vessels (open arrows) in the growth cartilage are normal findings.

 


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  		Figure 4b. (a) Sagittal fast SE T2-weighted fat-saturated MR image (4,000/126) obtained in a 7-year-old boy shows a large knee joint effusion (*) that distends the suprapatellar bursa, posterior femoral recess, and posterior tibial recess. The effusion is lined by nearly imperceptible synovium (arrowheads). (b) The synovium (curved arrows) is readily seen on this gadolinium-enhanced sagittal T1-weighted fat-saturated MR image (400/17). Curvilinear high signal intensity at the cartilage-epiphysis junction (straight solid arrows) and enhancing vessels (open arrows) in the growth cartilage are normal findings.

 


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  		Figure 5a. (a) Coronal T1-weighted gadolinium-enhanced MR image (450/16) obtained in a 15-year-old female adolescent shows abnormal subchondral enhancement (arrowheads). (b) Sagittal T1-weighted gadolinium-enhanced fat-saturated MR image (400/16) shows the abnormal subchondral enhancement of the tibial plateau (arrowheads) and posterior femoral condyle (white arrows). At arthroscopy, diffuse articular cartilage thinning, pitting, and fissures of the tibial plateau were seen. Enhancing synovium lifts the inferior aspect of the medial meniscus (black arrow), with loss of the normal meniscal triangular configuration. At arthroscopy, the meniscus was compressed by the bulky pannus but was otherwise normal. (c) Corresponding sagittal fast SE T2-weighted MR image (3,500/120) shows normal subchondral signal intensity (arrowhead) and intermediate-signal-intensity synovium surrounding the meniscal tips (white arrows). Large joint effusion in the suprapatellar bursa contains material (black arrows) with intermediate to low signal intensity that does not enhance with gadolinium-based contrast material; these findings are compatible with the mixed enhancement pattern. At arthroscopy, this material was free-floating curdlike clumps of fibrin.

 


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  		Figure 5b. (a) Coronal T1-weighted gadolinium-enhanced MR image (450/16) obtained in a 15-year-old female adolescent shows abnormal subchondral enhancement (arrowheads). (b) Sagittal T1-weighted gadolinium-enhanced fat-saturated MR image (400/16) shows the abnormal subchondral enhancement of the tibial plateau (arrowheads) and posterior femoral condyle (white arrows). At arthroscopy, diffuse articular cartilage thinning, pitting, and fissures of the tibial plateau were seen. Enhancing synovium lifts the inferior aspect of the medial meniscus (black arrow), with loss of the normal meniscal triangular configuration. At arthroscopy, the meniscus was compressed by the bulky pannus but was otherwise normal. (c) Corresponding sagittal fast SE T2-weighted MR image (3,500/120) shows normal subchondral signal intensity (arrowhead) and intermediate-signal-intensity synovium surrounding the meniscal tips (white arrows). Large joint effusion in the suprapatellar bursa contains material (black arrows) with intermediate to low signal intensity that does not enhance with gadolinium-based contrast material; these findings are compatible with the mixed enhancement pattern. At arthroscopy, this material was free-floating curdlike clumps of fibrin.

 


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  		Figure 5c. (a) Coronal T1-weighted gadolinium-enhanced MR image (450/16) obtained in a 15-year-old female adolescent shows abnormal subchondral enhancement (arrowheads). (b) Sagittal T1-weighted gadolinium-enhanced fat-saturated MR image (400/16) shows the abnormal subchondral enhancement of the tibial plateau (arrowheads) and posterior femoral condyle (white arrows). At arthroscopy, diffuse articular cartilage thinning, pitting, and fissures of the tibial plateau were seen. Enhancing synovium lifts the inferior aspect of the medial meniscus (black arrow), with loss of the normal meniscal triangular configuration. At arthroscopy, the meniscus was compressed by the bulky pannus but was otherwise normal. (c) Corresponding sagittal fast SE T2-weighted MR image (3,500/120) shows normal subchondral signal intensity (arrowhead) and intermediate-signal-intensity synovium surrounding the meniscal tips (white arrows). Large joint effusion in the suprapatellar bursa contains material (black arrows) with intermediate to low signal intensity that does not enhance with gadolinium-based contrast material; these findings are compatible with the mixed enhancement pattern. At arthroscopy, this material was free-floating curdlike clumps of fibrin.

 
Synovial signal intensity characteristics varied with the pulse sequences (Figs 3–5), with 80%–85% interobserver agreement. On nonenhanced T1-weighted images, the synovial signal intensity was intermediate (similar to that of muscle) in 23 (77%) of 30 knees, low to intermediate in two (7%), and not visible in five (17%). Compared with that of muscle, the signal intensity on fast SE intermediate-weighted images was low to intermediate in 18 (60%) knees, intermediate or isointense in eight (27%), and not distinguishable in four (13%). Compared with the high signal intensity of joint effusions on fast SE T2-weighted images, the signal intensity was mixed low to intermediate in 13 (43%) knees, intermediate in eight (27%), mixed intermediate to high in five (17%), and not distinguishable in four (13%).

Following the intravenous administration of gadolinium-based contrast material, enhancing synovium was seen in all knees on T1-weighted fat-saturated images in one of two enhancement patterns: (a) a hypervascular pattern (Fig 4) of homogeneously high signal intensity in 16 (53%) of 30 knees or (b) a mixed pattern (Figs 3, 5) of heterogeneous signal intensity in 14 (47%) knees. The Cohen {kappa} value for interobserver reliability for the enhancement pattern was 0.543, which indicated good agreement. Knees with the mixed enhancement pattern had a greater mean maximal synovial thickness (6.3 mm ± 1.8 [SD] vs 3.4 mm ± 2.2; P < .001) and had a trend toward higher mean synovial volumes (20.9 mL ± 6.7 vs 7.4 mL ± 6.1; P = .08) compared with those with the hypervascular pattern.

The mean maximal thickness of the synovium was 4.8 mm ± 2.4 (range, 1–10 mm). In the suprapatellar bursa, maximal synovium thickness was 1–2 mm in seven (23%) of 30 knees, 3–5 mm in 15 (50%), 6–9 mm in seven (23%), and 10–14 mm in one (3%). In the intercondylar region, maximal synovial thickness was 1–2 mm in nine (30%) knees, 3–5 mm in 12 (40%), and 6–9 mm in nine (30%). The grade of maximal synovial thickness within the suprapatellar bursa was well correlated with that of the intercondylar region (Spearman {rho} = 0.73; P < .01). The mean maximal synovial thickness in knees with cartilage or bone erosions was greater than that of knees without destructive changes (7.3 mm ± 0.6 vs 4.5 mm ± 2.4; P < .05).

The mean synovial volume was 15.4 mL ± 10.8 (range, 2–44 mL). Synovial volume was well correlated with synovial thickness grade in the suprapatellar bursa and intercondylar region (Spearman {rho} = 0.70 and 0.74, respectively; P < .01). Good correlation between synovial volume and maximal synovial thickness in the suprapatellar bursa was seen (Pearson correlation coefficient, 0.73; P < .01). Trend analysis was performed (Fig 6); a cubic regression line fit the data well (R2 = 0.588).



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  		Figure 6. Graph shows the relationship between maximal synovial thickness and synovial volume; the cubic regression line indicates a strong positive correlation.

 
To determine the usefulness of maximal synovial thickness versus synovial volume in assessing synovitis at MR imaging, receiver operating characteristic curves were generated; these were used to find the optimum values for maximal synovial thickness and synovial volume for use in comparing patients with and those without the clinical diagnosis of synovitis. A maximal synovial thickness of 3 mm or more yielded 100% specificity and 77% sensitivity for the diagnosis of synovitis (Table 2) (area under the curve = 0.90; 95% CI: 0.81, 0.99). With a synovial volume of 3 mL or more as the MR imaging definition of synovitis, specificity was 100% and sensitivity was 97% (Table 2) (area under the curve = 1.00; 95% CI: 0.98, 1.00). Use of volume was superior to use of maximal synovial thickness in distinguishing clinical synovitis (P < .05).


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  		TABLE 2. Number of Knees with Clinical Synovitis

 
Joint effusions.—Joint effusions had high signal intensity on T2- or intermediate-weighted images and low signal intensity on gadolinium-enhanced T1-weighted images (Figs 3–5, 7). They were most common in the suprapatellar bursa, and moderate or large effusions were seen in 17 (57%) of 30 knees (Table 3). {kappa} values for interobserver reliability in the detection of moderate or large effusions were 0.86 for the suprapatellar bursa, 0.75 for the intercondylar region, and 0.65 for the tibiofibular joint. Joint effusion size in the suprapatellar bursa was correlated with that in the intercondylar region (Spearman {rho} = 0.63; P < .01) but not with that in the tibiofibular joint (Spearman {rho} = -0.24). Size of the suprapatellar joint effusion was correlated with maximal synovial thickness (Spearman {rho} = 0.55; P < .01) and synovial volume (Spearman {rho} = 0.66; P < .01).



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  		Figure 7a. (a) Cartilage destruction in knees of patients with early JRA. Adjacent transverse fast SE intermediate-weighted fat-saturated MR images (4,000/30) show areas with heterogeneous high signal intensity (white arrows) and contour irregularity (black arrow) in the patellar articular cartilage in a 15-year-old female adolescent. High-signal-intensity effusion (*) is seen in the adjacent joint space. (b) Transverse intermediate-weighted fat-saturated fast SE MR image (4,000/28) obtained in a 14-year-old female adolescent demonstrates two fissures (arrows) that extend to the subchondral bone. These are accentuated by high-signal-intensity joint effusion (*).

 


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  		Figure 7b. (a) Cartilage destruction in knees of patients with early JRA. Adjacent transverse fast SE intermediate-weighted fat-saturated MR images (4,000/30) show areas with heterogeneous high signal intensity (white arrows) and contour irregularity (black arrow) in the patellar articular cartilage in a 15-year-old female adolescent. High-signal-intensity effusion (*) is seen in the adjacent joint space. (b) Transverse intermediate-weighted fat-saturated fast SE MR image (4,000/28) obtained in a 14-year-old female adolescent demonstrates two fissures (arrows) that extend to the subchondral bone. These are accentuated by high-signal-intensity joint effusion (*).

 

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  		TABLE 3. Frequency and Size of Joint Effusions at MR Imaging in Patients with Clinical Synovitis

 
Menisci.—Medial meniscal hypoplasia was seen in 11 (37%) knees (Figs 3, 5). Three (10%) of all imaged knees also had lateral meniscal hypoplasia. Interobserver agreement was good (Cohen {kappa} values were 0.68 for medial meniscal hypoplasia and 0.78 for lateral meniscal hypoplasia). No meniscal tears or complete atrophy was seen. Meniscal hypoplasia was positively correlated with larger suprapatellar joint effusions, maximal synovial thickness, synovial volume, and the mixed synovial enhancement pattern (Spearman {rho} = 0.54, 0.56, 0.59, 0.59, respectively; P < .01). Although none of the knees with meniscal hypoplasia had focal cartilage or bone erosions, one had abnormal subchondral enhancement and diffuse cartilage thinning.

Cartilage.—Total articular and epiphyseal (growth) cartilage thickness decreased with age in our series of children with JRA. Mean cartilage thickness in skeletally immature knees (with open physes) was significantly greater than cartilage thickness in mature knees (with closed physes) (Table 4).


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  		TABLE 4. Cartilage Thickness at MR Imaging in Skeletally Immature or Mature Knees in Patients with Clinical Synovitis

 
Prominent radial enhancement of epiphyseal growth cartilage was seen in three (10%) of 30 knees, with a mean patient age of 6.3 years (Fig 3c). Cartilage destruction, seen best on fast SE intermediate-weighted and three-dimensional spoiled gradient-echo fat-saturated images, was identified in three (10%) of 30 knees (93% interobserver agreement), all of which had fused or nearly fused physes. One exhibited contour irregularity and signal intensity heterogeneity in the patellar cartilage (Fig 7a). Another had two articular cartilage fissures extending to the subchondral bone of the patella (Fig 7b). The third knee had femoral and tibial cartilage thinning (Fig 5a, 5b), which was verified at arthroscopy. These three knees also exhibited abnormal subchondral linear enhancement on T1-weighted fat-saturated gadolinium-enhanced images (Fig 5a, 5b). Additional abnormalities included moderate or large joint effusions, grade III synovial hypertrophy, 19–34-mL synovial volumes, and a radiographically occult bone erosion (Fig 8).



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  		Figure 8a. (a) Bone erosion in a 15-year-old female adolescent. Coronal fast SE intermediate-weighted fat-saturated MR image (4,000/14) depicts 13 x 6 x 11-mm focus (arrows) of high signal intensity with well-defined margins at the tibial insertion site of the posterior cruciate ligament. (b) Compared with the nonenhancing joint effusion (*), this focus (arrow) is enhancing on this sagittal T1-weighted fat-saturated gadolinium-enhanced MR image (400/16) and likely represents intraosseous pannus.

 


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  		Figure 8b. (a) Bone erosion in a 15-year-old female adolescent. Coronal fast SE intermediate-weighted fat-saturated MR image (4,000/14) depicts 13 x 6 x 11-mm focus (arrows) of high signal intensity with well-defined margins at the tibial insertion site of the posterior cruciate ligament. (b) Compared with the nonenhancing joint effusion (*), this focus (arrow) is enhancing on this sagittal T1-weighted fat-saturated gadolinium-enhanced MR image (400/16) and likely represents intraosseous pannus.

 
Bone changes.—Focal bone erosion was seen in one knee (Fig 8), with 100% interobserver agreement. This knee also had patellar cartilage irregularity (Fig 7a), abnormal subchondral enhancement, 8-mm maximal synovial thickness, 22-mL synovial volume, and an abnormal infrapatellar fat pad.

Marrow signal intensity was abnormally increased in eight (27%) of 30 knees on T2-weighted and gadolinium-enhanced T1-weighted fat-saturated images. Marrow signal intensity was focally increased in one knee and diffusely increased in the femoral, tibial, and/or patellar epiphyses of seven knees (Fig 9). Marrow signal hyperintensity was not correlated with cartilage or bone erosions or the size of joint effusions. It was seen both in knees with abundant synovial proliferation (Fig 3) and in knees with minimal or no synovial proliferation (Fig 9).



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  		Figure 9a. (a) Coronal fast SE T2-weighted fat-saturated MR image (4,000/102) shows abnormal marrow in a 9-year-old girl. Diffuse areas of high signal intensity in the proximal tibial (arrows) and fibular (*) epiphyses have ill-defined borders compared with the well-defined borders of bone erosions. (b) After the intravenous administration of gadolinium-based contrast material, sagittal T1-weighted fat-saturated MR image (400/12) shows diffuse enhancement in these areas, as well as in the patella (*) and distal femoral epiphysis (arrow). Although this patient had mild synovitis at clinical examination, no substantial joint effusion or synovial proliferation was seen at MR imaging.

 


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  		Figure 9b. (a) Coronal fast SE T2-weighted fat-saturated MR image (4,000/102) shows abnormal marrow in a 9-year-old girl. Diffuse areas of high signal intensity in the proximal tibial (arrows) and fibular (*) epiphyses have ill-defined borders compared with the well-defined borders of bone erosions. (b) After the intravenous administration of gadolinium-based contrast material, sagittal T1-weighted fat-saturated MR image (400/12) shows diffuse enhancement in these areas, as well as in the patella (*) and distal femoral epiphysis (arrow). Although this patient had mild synovitis at clinical examination, no substantial joint effusion or synovial proliferation was seen at MR imaging.

 
No avascular necrosis, medullary infarcts, marginal osseous defects and/or erosions, intraarticular fragments, or epiphyseal overgrowths were seen.

Soft-tissue changes.—The infratentorial fat pad showed thickening, contour irregularity, and/or signal intensity heterogeneity on T2-weighted images in 21 (70%) of 30 knees ({kappa} = 0.71). These knees had a greater maximal synovial thickness (5.7 mm ± 2.1 vs 2.6 mm ± 1.6; P < .01) and synovial volume (19.0 mL ± 10.6 vs 7.2 mL ± 5.6; P < .01), compared with knees with a normal infrapatellar fat pad.

Popliteal synovial cysts were seen in six (20%) of 30 knees and measured 1.0–4.2 cm3. One patient had two intact synovial cysts and a ruptured synovial cyst that extended inferiorly into the calf. The presence of popliteal cysts was not correlated with the size of joint effusion (Spearman {rho} = 0.19), synovial proliferation, or number and size of lymph nodes.

Popliteal lymph nodes were seen in 28 (93%) of 30 knees. They numbered one or two in five (18%) of 28 knees, three to five in 21 (75%) knees, and more than six in two (7%) knees. The mean maximal lymph node length was 10.6 mm ± 4.2 (range, 6–20 mm). There was no correla-tion between the number of lymph nodes and maximal lymph node size, joint effusion, and synovial volume (Spearman {rho} = 0.29, 0.1, and 0.32, respectively).

Conventional Radiographs
The mean Pettersson score was 0.63 ± 1.18 (range, 0–4; median, 0; mode, 0), with 63% agreement. This score was significantly different from the mean Pettersson score of 0.05 ± 0.29 (median, 0; mode, 0) for normal knee radiographs (P < .05, signed rank test). In patients with JRA, Pettersson scores were 0 in 20 (74%) of 27 knees, 1 in one (4%) knee, 2 in three (11%) knees, 3 in two (7%) knees, and 4 in one (4%) knee. The ability to distinguish patients with JRA from control subjects by using abnormal (>0) Pettersson scores was not significant (area under the receiver operating characteristic curve, 0.60; 95% CI: 0.47, 0.73; P = .07). Although bone erosions were interpreted in four knee radiographs in patients with JRA, corresponding MR images showed none. The one focal bone erosion seen on MR images was not identified on radiographs; the Pettersson score was 0.

In patients with JRA, suprapatellar joint fullness was mild on 10 (37%) of 27 knee radiographs, moderate on seven (26%), and large on four (15%), with 52% overall agreement. In these patients, moderate or large suprapatellar fullness on radiographs was highly correlated with moderate or large suprapatellar effusions in MR images (Spearman {rho} = 0.80; P < .01).

Joint space narrowing was seen on one (4%) of 27 JRA knee radiographs, with complete agreement. Corresponding knee MR images showed meniscal hypoplasia and diffuse cartilage thinning.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
 
In early JRA, these MR imaging findings reflect the underlying pathologic process in which synovial hypertrophy results in the increased secretion of joint fluid.

At MR imaging, synovial abnormality is best seen by using both T2-weighted and gadolinium-enhanced T1-weighted fat-saturated images (Figs 3–5). On nonenhanced images alone, the synovium may be difficult to distinguish from joint fluid or adjacent soft tissues due to insufficient signal intensity contrast (Fig 4). On the other hand, the pannus (seen on T2-weighted images as low-signal-intensity material outlined by high-signal-intensity joint effusion), which is minimally enhancing or nonenhancing, is not visible on gadolinium-enhanced T1-weighted images (Figs 3, 5). In our series, this type of pannus had mixed signal intensity characteristics, which were similar to those described in patients with adult rheumatoid arthritis (27,28). This synovium with mixed enhancement was bulkier (greater maximal thickness and synovial volume) than synovium with the hypervascular enhancement pattern. Mixed synovial enhancement might indicate more long-standing or more severe inflammation wherein high-signal-intensity vascular proliferation and villous hypertrophy combine with the lower-signal-intensity fibrin and hemosiderin (29).

To assess disease activity with MR imaging, investigators use intravenously administered gadolinium-based contrast material to measure synovial inflammation with time-activity curves of enhancement (27,30,31), maximal synovial thickness (23), or synovial volumes (15, 16,32,33). We found a maximal synovial thickness of 3 mm or more and synovial volume of 3 mL or more to be useful measures of synovitis. Although synovial volume had higher sensitivity than maximal synovial thickness in the diagnosis of synovitis, synovial thickness may be more practical to use because it is easily measured, requires no special postprocessing, and is well correlated with synovial volume. Care should be taken to avoid overestimating synovitis with the use of maximal synovial thickness when the synovium is irregular or nodular. Conversely, synovitis might be underestimated by measuring thickness only when the synovium is thin in the presence of a very large joint effusion. Synovial volume measurements are practical to use in the clinical setting, requiring approximately 5 minutes of postprocessing per case. Regions of interest were drawn by a radiologist (V.M.G.M.) who was cognizant of joint anatomy; then, measurements were completed by another author (B.J.D.), with the two working together at the workstation.

Destructive changes in cartilage and bone were seen only in skeletally mature knees in our series. This finding, combined with the observation that joint cartilage thickness decreases with age, supports the speculation that thicker cartilage, along with intact growth cartilage blood supply and better repair processes in skeletally immature children, may account for the fewer erosive changes seen in JRA compared with those seen in adult rheumatoid arthritis (18,34). As children mature into adults, their joints might also be at greater risk for joint destruction if synovitis persists.

The infrequent occurrence of destructive changes in cartilage and bone in early JRA is not entirely surprising. Data obtained in the 1980s (18) demonstrated that even in polyarticular and systemic disease, the median time to the development of destructive changes that are detectable at conventional radiography was longer than 2 years. More frequent and aggressive use of methotrexate in the ensuing years is expected to decrease the rate of development of erosions even further (3). Nevertheless, MR imaging is more sensitive in the detection of cartilaginous destructive changes in JRA (8–10,14). The prevalence of such changes in cross-sectional studies (8–10,14) involving patients with JRA has been estimated to be 50%–88%. The data presented here are new because sensitive MR imaging techniques were applied to the assessment of early disease. Data about the development of erosions will continue to evolve as imaging techniques and pharmacologic treatments improve.

Cartilage destruction in rheumatoid arthritis occurs either on the joint surface by degradative enzymes released by the synovium or from subchondral resorption resulting in diffuse cartilage thinning (35,36). The abnormal subchondral linear enhancement pattern seen on gadolinium-enhanced T1-weighted images in three skeletally mature knees in our series may represent the increased vascularization of the basilar layers that leads to cartilage resorption. This appearance is distinct from the normal hyperintense rim seen around immature epiphyseal ossification centers, which represents metabolic activity at the edge of growing epiphyses (37). A patient with this abnormal subchondral linear enhancement did indeed have tibial articular cartilage thinning (verified at arthroscopy), which was seemingly due to a combination of surface scalloping by the pannus and subchondral resorption. We postulate that this abnormal enhancement pattern is an early MR imaging indicator of subsequent cartilage loss. It is not seen in asymptomatic knees at skeletal maturity (Gylys-Morin VM, unpublished data, 1999) or in adults (38).

Accentuated spoke-wheel enhancement of growth cartilage on gadolinium-enhanced images may be a secondary MR imaging sign of inflammation in JRA. A similar finding in two knees in patients with juvenile chronic arthritis was shown to be vessels at Doppler ultrasonography (13). This prominent enhancement is distinct from the fine radial pattern of enhancement seen in normal developing cartilaginous epiphyses, which represents vascular canals that supply nutrients to cartilage and induce ossification (37). With active inflammation, these vessels may enlarge and eventually contribute to growth disturbances, such as epiphyseal enlargement, increased maturation, and premature physeal closure.

The most common bone abnormality seen at MR imaging in the knees of children with early JRA was marrow signal intensity abnormality. This finding may represent bone marrow edema or hyperemia that eventually contributes to epiphyseal overgrowth.

Although bone erosions are infrequent in early JRA, MR imaging is inherently well suited to depict them due to its high signal intensity contrast and multiplanar tomographic nature. The finding of one radiologically occult bone erosion in our series suggests that erosions may occur earlier than previously described (8–10,14). Conventional radiographs do not depict bone erosions or subchondral cysts smaller than 8 mm in diameter due to bone density summation; centrally located cysts are even more difficult to identify (39). Thus, MR imaging might be especially useful in the detection of small bone lesions in therapeutic trials involving large joints.

We found meniscal hypoplasia early in JRA. Previous investigations (8,9) involving patients with JRA with a mean disease duration of 4–5 years reported a prevalence of meniscal hypoplasia of 65%–96%. The early occurrence of these changes was not appreciated, given the longer disease duration. Since meniscal hypoplasia in our series was well correlated with increased synovial volume, some meniscal changes in our study may have been caused by simple mechanical compression due to bulky pannus. Other described (35,40) mechanisms for meniscal hypoplasia may play a more important role in continued inflammation.

Infrapatellar fat pad abnormalities were the only MR imaging soft-tissue findings that we found to be useful as a secondary sign of inflammation in early JRA. This finding was well correlated with increased synovial proliferation and joint effusions. Popliteal cysts and lymphadenopathy were not correlated with synovial proliferation or joint effusions well enough to serve as useful secondary signs of synovitis.

In our series, conventional radiography of the knee was insensitive and nonspecific to early pathologic changes in JRA, as seen at MR imaging. To our knowledge, the only radiographic scoring system currently available to grade disease severity of the knee in JRA is the Pettersson classification system (24). This system, however, allows assessment of only bone abnormalities, which are late and irreversible manifestations of the disease process. Thus, it is impractical for the grading of early disease.

Our study has several limitations. The current results are limited in clinical applicability by the lack of correlation with clinical and follow-up imaging data. These issues are being addressed in an ongoing trial (therapeutic control groups are not being used). Measurement of synovial volume at MR imaging is relevant to the outcome in adult rheumatoid arthritis and is expected to be similarly useful in JRA (16,30,33). Another limitation is the lack of a surgical or pathologic standard for the verification of MR imaging findings in all patients except one, who underwent arthroscopy and synovectomy. Although biopsy proof of synovitis is desirable, it is not practical in the clinical setting with children. The clinical definition of synovitis, despite its limitations, remains the standard because it is the way in which JRA is defined (17). Especially in small joints, MR imaging may be more sensitive than clinical examination (41). Nevertheless, to date, MR imaging has not been accepted as a diagnostic criterion standard. The accuracy in calculating phantom volumes was acceptable (23). Even in patients who undergo synovectomy, synovial volume cannot be accurately measured in an excised specimen. The high sensitivity and specificity of synovial volumes in the detection of clinically evident synovitis in the knee joint validate both clinical assessment and MR imaging for the knee joint.

A further limitation is that, with the exception of synovitis, imaging findings in JRA were not compared with findings in other diseases, because this comparison was beyond the scope of this project. Furthermore, images in one joint may be misleading representations of polyarticular disease. Finally, it is difficult to draw meaningful relationships between cartilage destruction, the presence of osseous lesions, and severity of synovial inflammation because few patients exhibited cartilage or bone destruction. Sample size is a limitation. The primary area in which lack of power is a concern is in the factors associated with cartilage abnormalities, given the low number of such abnormalities. We expect that, with continued enrollment and serial follow-up, the necessary power to make inferences in this regard can be achieved. These limitations, however, do not negate the MR imaging findings presented because each knee can provide its own baseline findings for future comparison in the assessment of disease progression or response to therapy.

In summary, MR imaging of the knee depicts the synovium and its effects on joint structures in children with early JRA. A maximal synovial thickness of 3 mm more or a synovial volume of 3 mL or more is a sensitive and specific MR imaging criterion for active synovitis in the knee. Although synovial hypertrophy and joint effusions are the most frequent MR imaging findings in knees in early JRA, radiographically occult cartilage and bone erosions may also be identified. Thus, MR imaging may potentially aid therapeutic decisions, particularly early in the disease process, by helping in the quantification of synovitis and by depicting cartilage and bone destruction not evident on conventional radiographs.


   ACKNOWLEDGMENTS
 
We thank Scott K. Holland, PhD, for assistance with volume segmentation; Vincent J. Schmithorst, PhD, for writing the dedicated INTERACTIVE DATA LANGUAGE software to perform automatic volume segmentation; David Glass, MD, and Bill Ball, MD, for helpful suggestions; and Ed Giannini, PhD, for statistical advice.


   FOOTNOTES
 
Abbreviations: JRA = juvenile rheumatoid arthritis, SE = spin echo

Author contributions: Guarantor of integrity of entire study, V.M.G.M.; study concepts and design, V.M.G.M., J.S.B.; literature research, V.M.G.M., T.B.G.; clinical studies, V.M.G.M., T.B.G., M.H.P., B.J.D.; experimental studies, V.M.G.M., B.J.D.; data acquisition, V.M.G.M., B.J.D., J.S.B., T.L., A.E.O., N.D.J., M.H.P.; data analysis/interpretation, V.M.G.M., T.B.G.; statistical analysis, V.M.G.M., T.B.G.; manuscript preparation, definition of intellectual content, and editing, V.M.G.M., T.B.G.; manuscript revision/review and final version approval, all authors.


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