Accuracy and Reproducibility of Radiographic Knee Joint Space Narrowing Measurements Referenced to the Mid-Coronal Plane
Methods: Radiographs with precisely defined changes in joint space width (JSW) were created from CT imaging of cadaver knees. The mid-coronal plane of the knee was used to measure JSW and calculate JSN. Radiographs and data from the Osteoarthritis Initiative study were used to assess reproducibility and compare mid-coronal plane measurements of JSN to previously reported methods.
Results: The average absolute error in the measured versus known medial JSN was below 0.2 mm. The reproducibility was similar to previously published methods. There was a strong correlation between the mid-coronal plane measurements of JSN and JSN calculated using previously reported methods. There were several discrepancies between the two methods, suggesting that JSN for individual cases may depend on the method used to measure JSN.
Discussion: This study describes an alternative to using the margins of the tibial plateau when calculating JSN. JSN measurements based on the mid-coronal plane of the knee, where cartilage changes are more likely to occur, may have advantages. Keywords: Knee osteoarthritis; Joint space narrowing; Radiographic imaging.
Figure 1. To demonstrate that the anterior and posterior rims of the tibia plateau form the most prominent radiographic features seen in a PA radiograph, a PA radiograph was simulated from a thin-slice CT examination of a cadaver knee (upper right corner). The PA radiograph was simulated with the central X-ray beam tilted +10 deg with respect to the plane of the medial tibial plateau. The typical radiographic features of a tibial plateau can be clearly identified. The rim of the tibia plateau was then isolated (shown in red on the upper left, looking down on the tibial plateau) and digitally set to a density corresponding to cortical bone. A series of simulated radiographs was then simulated representing a central X-ray beam tilted -10, -5 , 0, +5, and +10 deg from the plane of the medial tibial plateau. These rim-enhanced radiographs are shown along the bottom of the figure. Comparing the right-most of the rim-enhanced simulated radiographs along the bottom to the original simulated radiograph in the upper right, it can be seen that the radiographic lines seen in a typical PA radiograph are due to the anterior and posterior rims of the tibial plateau. The magenta arrows on the lower row of images show where the anterior and posterior rims of the tibial plateau meet on the lateral- and medial-most aspects of the tibia plateau. These meeting points are used to identify the mid-coronal plane.
The mid-coronal plane JNS measurement
The mid-coronal plane of the tibia is identified by following the radiographic contour of the anterior and posterior rims, and identifying where they meet at the lateral- and medial-most aspects of the tibial plateau (Figure 3). A line is then drawn between the lateral- and medial-most aspects of the tibial plateau. In practice, these lines are mentally identified and not actually drawn on the images. The length of the line between the lateral- and medial-most points is used to define the width of the tibial plateau. Points are marked on this line that are 20% of the width medial to the lateral-most edge, and 20% lateral to the medial-most edge (Figure 3). These points are where the lateral and medial JSN is measured. Duryea et al. in 2010 reported improved responsiveness of JSN measured at fixed locations . An additional line is drawn that touches the caudal-most points on the medial and lateral femoral condyles. Points are placed on this femoral condyle line, corresponding to the locations where the medial and lateral JSNs are to be measured. These points are placed along lines perpendicular to the points marked on the mid-coronal plane tibial line. Note that these points do not always identify the point where the condyle appears to be in closest apposition to the tibial plateau. The purpose of these points and the measurement methodology are to reliably measure JSN and provide a standardized JSW measurement across subjects and time points, even though the JSW measurement may not correspond to what appears as the minimum JSW in any one radiograph.
The tibia and fibula were digitally removed from thin-slice (0.625 mm), high resolution (0.31 mm/pixel) CT imaging of semi-flexed knees from three adult male cadavers (CT imaging obtained by contract with Advanced Technology in Orthopedics, Houston, TX). All overlying soft tissues (skin, fat, muscles, etc) were intact when the CT images were obtained. The CT images were first interpolated to 0.275 mm isotropic resolution to provide higher resolution simulated radiographs. The tibia and fibula were then digitally added back to the CT data after applying precise cranial or caudal displacements. This provided known amounts of JSN. JSN (as well as mild joint space widening) of between 0 and 3.5 mm was simulated in 0.5 mm increments. Small (1-3 deg) rotations in the transverse plane were also applied to some of the images to simulate variability in patient positioning and central X-ray beam orientation. The modified CT images were then used to create PA radiographic images of the knee, using digitally reconstructed radiograph (DRR) software that is extensively used for radiation treatment planning (Plastimatch DRR, url: www.plastimatch.org/drr.html). The radiograph-like images created using DRR simulated X-ray scatter and X-ray parallax, which are primary sources of error in radiographs. The central X-ray beam path was varied from perfectly co-planar with the medial tibial plateau and up to 15 deg oblique to the medial tibial plateau (Figure 4). Obliquity of the X-ray beam with respect to the tibial plateau is referred to as out-of-plane (OOP) in this paper.
To assess intraobserver variability of the mid-coronal plane JSN measurements, three trained analysts independently stabilized the tibia and femur from 18 paired baseline and 4-year radiographs from the OAI study. JSN was calculated by the QMA® software. Variability was assessed using descriptive statistics and Bland-Altman limits-of-agreement analysis (Stata version 13; College Station, TX). RESULTS
The simulated radiographs were of lower quality than typically obtained in clinical practice or in the OAI study (Figure 5). This did not prevent stabilization of the mid-coronal plane using QMA®, although stabilization is easier using actual radiographs. The absolute error in the measured JSN measured was dependent on compartment (medial or lateral, p=0.0004) and on the amount of OOP applied relative to the medial tibial plateau on the simulated radiographs (p<0.0001, Figure 6). When the central X-ray beam was oriented to be co-planar with the tibial plateau, absolute errors relative to the known narrowing averaged 0.1±0.08 mm (medial and lateral compartments combined). In the medial compartment, including all levels of OOP, the average error was 0.17±0.16 mm. The largest errors (0.78±0.58 mm) were with JSN measured in the lateral compartment when the X-ray beam was >10 deg from the plane of the medial tibial plateau. Note that OOP was applied to the radiographs relative to the medial compartment of the tibial plateau. The OOP was greater in the lateral compartment than in the medial compartment in some radiograph pairs.
The accuracy of using the mid-coronal plane to measure JSN was determined using simulated radiographs with precisely applied changes to JSW. When the central X-ray beam is co-planar or nearly co-planar with the tibial plateau, the accuracy of the mid-coronal plane approach to measuring JSN is similar to the accuracy reported for methods that use the radiographic shadows of the tibial plateau margins . In the Dupuis et al. study that previously reported the accuracy of radiographic measurements of JSN, the displacement of the tibia relative to the femur was applied by a testing machine . Owing to concern about the reliability of the applied displacements, a roentgen stereophotogrammetric analysis (RSA) was used to measure relative displacements. The overlying skin and soft tissues had been removed (although the immediate periarticular structures were maintained), so the radiographic quality would likely have been excellent with radiographs obtained with the central X-ray beam co-planar with the tibial plateau. It is not known how the presence of soft tissues or variability in orientation of the central X-ray beam with respect to the tibial plateau would have affected the accuracy reported by Dupuis el al. .
Only a small proportion of patients lose significant joint space in some studies of knee joint osteoarthritis or of treatments for knee OA [10-12]. The average rate of JSN is small in most studies [11,13]. It is therefore important to accurately identify all subjects with a significant change in joint space. Conversely, a study in which treatment goal is to improve knee health would benefit from identifying all cases with a true improvement in JSW. A study comparing treatment options for knee OA will require a smaller sample size if the measurements of JSN are both accurate and repeatable. In large population-based studies, the natural history of JSN or treatment effect on JSN can be documented using appropriate large sample statistics, even if the measurement reliability is limited. However, in a study where JSN might be used to identify a positive treatment effect in each subject, or to identify treatment failures, an accurate measurement is desirable for each subject. Multiple publications describe the reproducibility of JSN methodology [14-16]. Reproducibility is undeniably important. However, reproducibly getting the wrong measurement is not helpful, so accuracy should also be documented. Assessment of measurement accuracy is difficult owing to the challenge of finding a “gold standard” that can be used as a reference. It is difficult to experimentally measure motion between the tibia and femur in living subjects, so physical measurements of motion are generally limited to ex vivo cadaver studies, eg Thompson et al. . Some of the available options for experimentally measuring relative motion between bones may have similar measurement error to radiographic measurements and thus are a suboptimal “gold standard.” It is for this reason that a virtual simulation of JSN was used in our study as the “gold standard.” If all radiographs could be attained such that the radiographic contours of the posterior and anterior margins of the tibial plateau are superimposed and cannot be individually identified, the method described in this paper would not be needed. Unfortunately, uniformly perfect radiographs would require that a fluoroscopy system be available to determine the optimum central beam orientation with respect to the knee in each subject . This is not practical in many studies. The intermargin distance is the distance between the anterior and posterior rims of the tibial plateau on the PA or AP radiograph. The intermargin distance was shown to influence JSN measurements using methodology that relies on the rims of the tibial plateau . Some studies prospectively define a rule that the intermargin distance must be under a threshold level such as 1.0 or 1.5 mm [19,20]. Without careful control of how the radiographs are obtained, this restriction may eliminate a substantial number of radiographs within a typical clinical study. The data reported in this paper suggest that use of the mid-coronal plane when measuring JSN may reduce the dependency of the JSN measurements on OOP, although severe OOP will increase error in the JSN measurements.
There was a strong correlation between JSN measurements reported in the OAI study, and JSN measured using the mid-coronal plane method. This correlation would support that in a study with a large sample size, with a study hypothesis that is addressed by comparing the mean and standard deviation in JSN between groups, either method for measuring JSN would likely provide a similar answer to the research question. If the study design requires classifying each subject as a success or failure in part based on JSN, the method used to measure JSN may prove significant.
Limitations of the study include calculating measurement accuracy using simulated radiographs that were of lower quality than typically used in clinical practice. However, it might be expected that the accuracy would improve with better-quality radiographs. CONCLUSIONS
The radiographic projection of the anterior or posterior border of the tibial plateau is commonly used to measure JSN. Anatomically, in the sagittal plane, these borders are distant from the point where JSN would be measured if using 3D CT or MRI data. JSN accurately and reproducibly measured near the mid-coronal plane of the knee may be more effective in clinical research. This study supports that measurements of JSN about the mid-coronal plane of the knee can be accurately and reproducibly obtained and may potentially avoid errors in measurements made using the anterior or posterior borders of the plateau as reference. REFERENCES
 Simon LS. OARSI Clinical Trials Recommendations: an abbreviated regulatory guide to the clinical requirements for development of therapeutics in osteoarthritis. Osteoarthritis Cartilage. 2015;23:674-6.
 Conaghan PG, Hunter DJ, Maillefert JF, Reichmann WM, Losina E. Summary and recommendations of the OARSI FDA osteoarthritis Assessment of Structural Working Group. Osteoarthritis Cartilage. 2011;19:606-10.
 McAlindon TE, Driban JB, Henrotin Y, Hunter DJ, Jiang GL, Skou ST, et al. OARSI Clinical Trials Recommendations: design, conduct, and reporting of clinical trials for knee osteoarthritis. Osteoarthritis Cartilage. 2015;23:747-60.
 Hellio LE, Graverand MP, Mazzuca S, Duryea J, Brett A. Radiographic-based grading methods and radiographic measurement of joint space width in osteoarthritis. Radiol Clin North Am. 2009;47:567-79.
 Conrozier T, Mathieu P, Piperno M, Favret H, Colson F, Vignon M, et al. Selection of knee radiographs for trials of structure-modifying drugs in patients with knee osteoarthritis: a prospective, longitudinal study of Lyon Schuss knee radiographs with the definition of adequate alignment of the medial tibial plateau. Arthritis Rheum. 2005;52:1411-7.
 Duryea J, Neumann G, Niu J, Totterman S, Tamez J, Dabrowski C, et al. Comparison of radiographic joint space width with magnetic resonance imaging cartilage morphometry: analysis of longitudinal data from the Osteoarthritis Initiative. Arthritis Care Res. 2010;62:932-7.
 Thompson MT, Conditt MA, Ismaily SK, Agarwal A, Noble PC. Brief report: validation of a system for automated measurement of knee laxity. Clin Biomech. 2004;19:308-12.
 Zhao K, Yang C, Zhao C, An KN. Assessment of noninvasive intervertebral motion measurements in the lumbar spine. J Biomech. 2005;38:1943-6.
 Dupuis DE, Beynnon BD, Richard MJ, Novotny JE, Skelly JM, Cooper SM. Precision and accuracy of joint space width measurements of the medial compartment of the knee using standardized MTP semi-flexed radiographs. Osteoarthritis Cartilage. 2003;11:716-24.
 Eckstein F, Nevitt M, Gimona A, Picha K, Lee JH, Davies RY, et al. Rates of change and sensitivity to change in cartilage morphology in healthy knees and in knees with mild, moderate, and end‐stage radiographic osteoarthritis: Results from 831 participants from the Osteoarthritis Initiative. Arthritis Care Res. 2011;63:311-9.
 Hunter DJ, Niu J, Zhang Y, Totterman S, Tamez J, Dabrowski C, et al. Change in cartilage morphometry: a sample of the progression cohort of the Osteoarthritis Initiative. Ann Rheum Dis. 2009;68:349-56.
 Bingham CO, Buckland‐Wright JC, Garnero P, Cohen SB, Dougados M, Adami S, et al. Risedronate decreases biochemical markers of cartilage degradation but does not decrease symptoms or slow radiographic progression in patients with medial compartment osteoarthritis of the knee: Results of the two‐year multinational knee osteoarthritis structural arthritis study. Arthritis Rheum. 2006;54:3494-507.
 Ward RJ, Buckland-Wright JC. Rates of medial tibiofemoral joint space narrowing in osteoarthritis studies consistent despite methodological differences. Osteoarthritis Cartilage. 2008;16:330-6.
 Mazzuca SA, Brandt KD, Lane KA, Katz BP. Knee pain reduces joint space width in conventional standing anteroposterior radiographs of osteoarthritic knees. Arthritis Rheum. 2002;46:1223-7.
 Duryea J, Zaim S, Genant HK. New radiographic-based surrogate outcome measures for osteoarthritis of the knee. Osteoarthritis Cartilage. 2003;11:102-10.
 Gensburger D, Roux JP, Arlot M, Sor-day-Rendu E, Ravaud P, Chapurlat R. Influence of blinding sequence of radiographs on the reproducibility and sensitivity to change of joint space width measurement in knee osteoarthritis. Arthritis Care Res. 2010;62:1699-705.
 Buckland-Wright C. Review of the anatomical and radiological differences between fluoroscopic and non-fluoroscopic positioning of osteoarthritic knees. Osteoarthritis Cartilage. 2006;14 Suppl A:A19-31.
 Mercier C, Piperno M, Vignon E, Brandt K, Hochberg M, Le Graverand M-P. In normal knees, joint space width (JSW) is correlated with the intermargin distance (IMD), a measure of medial tibial plateau alignment. Variations in IMD explain variability in JSW in serial radiographs. Joint Bone Spine. 2013;80:183-7.
 Vignon E, Brandt KD, Mercier C, Hochberg M, Hunter D, Mazzuca S, et al. Alignment of the medial tibial plateau affects the rate of joint space narrowing in the osteoarthritic knee. Osteoarthritis Cartilage. 2010;18:1436-40.
 Buckland-Wright JC, Ward RJ, Peterfy C, Mojcik CF, Leff RL. Reproducibility of the semiflexed (metatarsophalangeal) radiographic knee position and automated measurements of medial tibiofemoral joint space width in a multicenter clinical trial of knee osteoarthritis. J Rheumatol. 2004;31:1588-97.