MRI set up. For imaging the joint plates were placed in the middle of a pot being filled with high viscosity solution. 

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... to 33% of American adults have symptoms of osteoarthritic (OA) cartilage lesions (press release from the Centers for Disease Control and Prevention, 24 October 2002). In particular, in young subjects, cartilage defects often do not affect the entire cartilage plate, but are confined to focal lesions. Focal alterations can also be observed in osteochondrosis dissecans and in acute osteochondral fractures. 1 In both these diseases the aim is to refill the defects with hyaline cartilage tissue, and new therapeutic approaches have recently been described (for example, autologous chondrocyte transplantation, mosaicplasty). 2–6 In this context, it would be highly beneficial to have a diagnostic method available for accurately estimating the defect size non-invasively preoperatively, without the need to subject the patient to an operative, arthroscopic procedure. Follow up studies 2 6 7 have indicated good clinical results for the therapeutic approaches mentioned above, but arthroscopic (and histological) control examinations have shown that at least one third of the transplanted defects display persistent defects. 5 8 9 For these reasons, it would also be advantageous to use an accurate, postoperative technique which would allow measurement of the exact defect size non-invasively. Conventional radiography has been the standard method for diagnosing OA 10 and focal cartilage defects. 11 However, this method cannot delineate cartilage directly, and does not allow determination of the size of focal cartilage defects. 12 Osteochondral and other cartilage lesions can now be described using magnetic resonance imaging (MRI), 13 14 and if the spatial resolution is sufficiently high focal cartilage defects can be detected with high reliability. 15 16 We have recently shown that MRI, in conjunction with three dimensional image analysis techniques (qMRI), allows accurate measurement of cartilage loss in OA. 17 18 In this study we extend these techniques to quantify focal cartilage defects, and we analyse the accuracy of qMRI in measuring focal cartilage defects in different compartments of the knee experimentally. Twenty tibial (medial and lateral) and 16 patellar joint surfaces (cartilage and subchondral bone) were harvested from human knees during knee arthroplasty. These were stored at 2 80 ̊ C and thawed to room temperature before each examination. In the 36 (20 + 16) joint surfaces, 74 cylindrical full thickness defects were artificially created with three different punches (Aesculap, Tuttlingen, Germany), with diameters of 3, 5, and 8 mm, respectively. Up to three defects were created in different areas of each tibial and patellar surface, both in areas with macroscopically intact cartilage and in areas with early OA changes. Note that the cartilage plates were retrieved from patients treated for femorotibial OA, but that substantial portions of normal cartilage and cartilage with early OA changes are generally maintained in these subjects. 18 Although it would have been interesting to also examine cartilage from the femoral condyles, these are removed during arthroplasty in several smaller pieces, precluding experimental analysis of the type presented here. Two types of approach were used for creating the defects (table 1). In 15 specimens (51 defects), the cartilage cylinders inside the punch were removed from the joint plate to create defects as observed, for instance, in osteochondrosis dissecans (approach 1) (fig 1). In nine specimen (23 defects), the cartilage cylinder was left in place and the surrounding cartilage tissue was removed mechanically (approach 2) (fig 2). The actual size of the defects was controlled with a micrometer screw (Hommel Group, Cologne, Germany). For approach 1, the actual diameter of the defects created by the 3 mm punch was 3.08 mm (equivalent to a size of 0.08 cm 2 ). For the 5 mm punch the exact diameter was 5.06 mm (size = 0.2 cm 2 ), and for the 8 mm punch the exact diameter was 8.10 mm (size = 0.52 cm 2 ). For approach 2, the diameter (inside the punch) was 3.96 mm for the 5 mm punch (size = 0.12 cm 2 ), and 6.44 mm for the 8 mm punch (size = 0.33 cm 2 ). Owing to the small inner diameter ( , 1.8 mm) of the 3 mm punch, no reproducible defect size was created and these lesions were thus not included in the analysis. To achieve high contrast between cartilage and bone, specimens were positioned in a container filled with contrast medium (Lumirem, Guerbet, Roissy, France) during imaging. Gelatin was added, to stabilise the specimens mechanically in the liquid contrast medium (fig 3). In this way the cartilage plates were positioned in the middle of the container, avoiding imaging artefacts that might have occurred at its edges. A clinical 1.5 T MRI system (Magnetom Sonata, Siemens, Erlangen, Germany) was used, and a T 1 weighted gradient echo sequence with water excitation, which has been previously validated for quantitative cartilage imaging. 17–21 The spatial resolution was 0.31 mm 6 0.31 mm (in plane) and the slice thickness 1.5 mm. The acquisition time was 9 minutes 50 seconds for each tibial compartment, and 10 minutes 30 seconds for the patella. After transfer of the image data to a multiprocessing computer (Octane Duo, Silicon Graphics Inc, Mountain View, CA), the cartilage was segmented semiautomatically using a B-spline snake algorithm. 22 The person who performed the image analysis (DA) was unaware of the number of defects for each surface, their position, or their size (diameter). In the next step, the defects themselves (approach 1) were segmented using the same image analysis techniques mentioned above (fig 4). The depth of the defect was defined by the thickness of the cartilage surrounding this tissue. 23 The diameter of the defect was then calculated from the volume of the defect and its depth (thickness of surrounding tissue) using the following formula: r 2 = V/ p h r = ! r 2 d = 2r where h = mean cartilage thickness, V = defect volume. In approach 2, the remaining cartilage cylinders were segmented directly (fig 5). The same software 23 and procedure was then used to compute the volume and thickness of the cartilage defect and its diameter. This second approach was performed to find out whether the interpolated cartilage/joint and cartilage/bone surface of approach 1 has an influence on the results. The systematic (mean deviation) and random pairwise differences (mean over- or underestimation when eliminat- ing the + and 2 signs) between the actual defect size (as determined with the micrometre screw) and the digital analysis results from the MR images were assessed and evaluated for statistical significance using a paired Student’s t test. Finally, the data were displayed using a box and whiskers plot (fig 6). The number and location of all cartilage defects were accurately detected by MRI analysis. This applied to all cartilage plates, all lesion diameters, and both approach 1 and 2. For approach 1, the accuracy of the MR based measurement technique clearly improved with the size of the defect: Random differences with physical measurements were 1.3 (0.58) mm ( ¡ 42%) for the 3 mm defects, 1.0 (0.57) mm ( ¡ 20.7%) and 0.1 (0.39) mm ( ¡ 3.9%) for the 5 mm and 8 mm defects, respectively. While there was a significant overestimation of defect size with MR imaging in the 3 mm ( ¡ 42%; p , 0.05) and 5 mm lesions ( ¡ 21%; p , 0.05), no systematic error ( ¡ 3.9 %; p = NS) was seen for the 8 mm defects (table 2). With approach 2, the degree of accuracy was somewhat higher than with approach 1 for 5 mm defects, with random differences amounting to 0.51 (0.53) mm ( ¡ 13.4%). However, for 8 mm defects the level of accuracy was similar, with random difference amounting to 0.12 (0.45) mm ( ¡ 5.0%). Although there was a significant overestimation of the defect size in 5 mm defects ( ¡ 13.4 %; p , 0.05), there was no significant over- or underestimation with this approach in the 8 mm defects ( ¡ 5%, p = 0.44) (table 3). No difference was seen between the joint plates (patella, medial tibia, lateral tibia). In all localisations approach 1 showed smaller differences (0.07–0.34 mm; 8.9–10.7%) than approach 2 (0.62–0.71 mm; 13.3–16.1%), but this difference was not significant. In this study we examined the ability of qMRI to determine accurately focal cartilage lesions of various diameters. Only one previous study has examined these relationships, 24 but those authors examined only patellar defects with diameters of 1–5 mm in elderly donors. Here we show that qMRI yields a high degree of accuracy, at least for larger cartilage defects in patellar, medial tibial, and lateral tibial cartilage, both in normal, healthy cartilage and in early OA cartilage. Although MRI significantly overestimated the small 3 mm defects, the difference was much smaller in the 8 mm defects. A limitation of this study is that experimental cartilage defects were evaluated and these experimental defects may be structurally different from cartilage defects occurring under real pathophysiological conditions. The results presented here thus need to be confirmed under clinical conditions, but the current data suggest that the approach is promising and displays potential to obtain accurate results in clinical studies. Strengths of the current study are that defects of different sizes were compared systematically, and that the results were obtained in various cartilage plates of the human knee, both in normal and early OA cartilage. Preoperative quantification of cartilage defects would be very helpful ...