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Experimental Studies |
1 From the Department of Radiology, Technische Universitaet Muenchen, Ismaninger Str 22, D-81675 Munich, Germany (K.W., J.M., E.J.R.); and the Gerhard Domagk Institute of Pathology, Westfaelische Wilhelms Universitaet Muenster, Germany (H.B.). Received October 24, 2002; revision requested January 7, 2003; final revision received June 3; accepted June 24. Address correspondence to K.W. (e-mail: woertler@roe.med.tu-muenchen.de).
| ABSTRACT |
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MATERIALS AND METHODS: MR imaging was performed in eight human cadaveric patella specimens immediately and 4 hours after placement into a vessel filled with gadopentetate dimeglumine solution (2.5 mmol/L). T1-weighted spin-echo and inversion-recovery turbo spin-echo MR sequences with nulled cartilage signal (inversion time of 300 msec) were used. In a total of 128 articular cartilage areas, MR imaging findings were compared with macroscopic and histopathologic findings. Pathologic evaluation was performed by one musculoskeletal pathologist. With knowledge of pathologic observations, MR images were analyzed by one musculoskeletal radiologist with regard to intrinsic signal intensity characteristics and surface abnormalities of articular cartilage.
RESULTS: Histopathologic findings demonstrated 67 areas of normal articular cartilage and 66 cartilage lesions (grade 1, n = 19; grade 2, n = 15; grade 3, n = 26; grade 4, n = 6). All grade 3 and 4 lesions could be identified on MR images obtained immediately after submersion and after 4 hours. Ninety-four percent of grade 1 and 2 lesions were identified as areas of predominantly decreased contrast enhancement on delayed MR images obtained with both sequences. MR images obtained immediately after submersion demonstrated abnormal signal intensity in only 9% and 12% of grade 1 and 2 lesions, respectively.
CONCLUSION: T1-weighted MR images obtained in vitro after gadopentetate dimeglumine diffusion allow demonstration of articular cartilage surface lesions and early stages of cartilage degradation.
© RSNA, 2004
Index terms: Cartilage, 453.4851 Cartilage, MR, 453.121411, 453.121413, 453.12143 Contrast media, experimental studies Knee, arthrography, 453.4851 Knee, MR, 453.121411, 453.121413, 453.12143 Patella, 453.4851
| INTRODUCTION |
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In addition to arthroscopic exploration, magnetic resonance (MR) imaging has already developed into an important diagnostic test for the diagnosis of articular cartilage damage. However, current MR imaging techniques show substantial limitations in the detection of early stages of cartilage degradation and preclinical osteoarthritis (35).
The diagnosis of structural alterations of hyaline cartilage can be important for several reasons. First, chondromalacia can be symptomatic as a source of chronic pain and disability and can therefore require surgical treatment even if no surface defect is visible (1,6). Second, traumatized areas of articular cartilage may initially appear intact at arthroscopy but can later undergo degeneration with formation of defects, which may progressively enlarge with time (1,2). Third, cartilage degradation is frequently found adjacent to traumatic chondral or osteochondral defects. The definition of the true extent of the damaged area is of great importance for therapeutic decisions and the prognosis of surgical treatment (1). Fourth, with the increasing number of osteochondral transplantions, a reliable test for minimally invasive evaluation of the transplants and the donor sites is required. Further indications might result from future developments in preventative and therapeutic treatment of patients with osteoarthritis.
Results of several experimental studies indicated that T1-weighted MR imaging enhanced with gadopentetate dimeglumine by means of diffusion has the potential to demonstrate structural abnormalities of hyaline cartilage (710). However, this technique has not yet been evaluated sufficiently either in vitro or in vivo, in our opinion, for the visualization of naturally occurring cartilage lesions.
The purpose of this study was to evaluate T1-weighted MR imaging after diffusion of gadopentetate dimeglumine for visualization of articular cartilage lesions.
| MATERIALS AND METHODS |
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After MR imaging, the patella specimens were sectioned with a band saw into 3-mm-thick sections parallel to the imaging plane. Six sections were obtained from each of three patella specimens (18 sections total), and five sections were obtained from each of five specimens (25 sections total). For comparison with pathologic findings, on each of these 43 sections and corresponding MR images, the patellae were subdivided into three regions: the medial facet, the central portion (or the apex of the patella), and the lateral facet. Histologic sections were obtained from all three regions of each patellar section. Since one patellar region had to be excluded because of fixation artifacts of the histologic section, comparison of MR imaging, macroscopic, and histologic findings could be performed in a total of 128 cartilage areas. Cartilage lesions were graded with the use of a modified Shahriaree classification system (11) (Table 1).
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MR images were evaluated by one experienced musculoskeletal radiologist (K.W.) with knowledge of macroscopic and histologic observations. Image analysis was performed regarding the homogeneity of cartilage signal, presence of areas of increased or decreased contrast enhancement, integrity of the cartilage surface, and presence and depth of surface defects on MR images and subtraction images. Surface defects were graded according to the classification system mentioned previously.
The detectability of cartilage lesions on MR images and corresponding subtraction images was expressed in percentages of the number of pathologically confirmed lesions.
| RESULTS |
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In general, we found almost identical detection rates with both T1-weighted SE and inversion-recovery turbo SE sequences. Both techniques enabled demonstration of homogeneous gadopentetate dimeglumine uptake in areas with intact cartilage, as well as altered contrast material behavior in regions of cartilage degradation. The low signal intensity of articular cartilage on inversion-recovery turbo SE images with an inversion time of 300 msec did not improve lesion detectability compared with that on T1-weighted SE images. Subjectively, grade 1 and 2 lesions were better visualized on T1-weighted SE images.
| DISCUSSION |
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The loss of proteoglycans is one of the first measurable structural changes in cartilage degradation (12,15). Therefore, contrast materialenhanced MR imaging with use of ionic substances is thought to have the potential to demonstrate abnormalities of the cartilage matrix in early osteoarthritis (5,710,13,16). Results of experiments performed by Bacic et al (17) showed that proteoglycan degradation induced by papain in the rabbit knee could be visualized by means of application of cationic (nitroxide) and anionic (gadopentetate dimeglumine) substances. Furthermore, in human cartilage specimens, degenerative changes accompanied by proteoglycan depletion could be demonstrated as areas of T1 shortening with the use of gadopentetate dimeglumineenhanced MR imaging at 3 T (18).
In our study, cartilage areas with normal findings at histologic examination demonstrated a homogeneous increase of signal intensity on delayed MR images in 97% of cases. The two false-positive results observed in this study were possibly caused by alterations of the cartilage matrix, which could not be detected with the use of conventional staining techniques.
The detection of grade 1 and 2 articular cartilage lesions with MR imaging represents an unsolved problem, since SE, fast SE, and gradient-echo MR sequences have not proved sufficiently reliable in identification of structural alterations (35,13,1921). T1-weighted, proton densityweighted, and T2-weighted conventional SE sequences have been reported to have low sensitivities in the detection of chondromalacia, ranging from 0% to 63% for grade 1 lesions and 0% to 68% for grade 2 lesions (19,2224). The use of fast SE and short inversion time inversion-recovery fast SE sequences also could not significantly improve the diagnostic performance of MR imaging in early stages of cartilage degradation (25,26). Although several two- and especially three-dimensional gradient-echo techniques in combination with fat saturation have proved to be reliable in the detection of surface lesions, they showed substantial limitations in the identification of earlier stages of chondromalacia, with sensitivities of less than 50% for the diagnosis of grade 1 lesions (23,27).
Accordingly, the detection rates for histologically proved grade 1 and 2 cartilage lesions in our experimental study were low (7%15%) on T1-weighted SE and inversion-recovery turbo SE MR images obtained immediately after positioning of the specimens in gadopentetate dimeglumine solution. Delayed MR images dramatically increased the visibility of grade 1 and 2 lesions to 89% and 100%, respectively. However, in contradiction to the previously mentioned experimental results of other authors, the contrast affinity of degraded cartilage regions was not increased in most cases. Ninety-one percent of grade 1 and 2 lesions demonstrated decreased contrast enhancement compared with areas of histologically normal cartilage; only three (9%) were visualized as regions of increased gadopentetate dimeglumine uptake. Increased signal intensity in these cases could not be attributed to magic angle effects, since it was observed on T1-weighted SE as well as inversion-recovery turbo SE images. It showed a globular rather than bandlike appearance, and it appeared not to be related to the orientation of articular cartilage relative to the main magnetic field.
Possible explanations for this phenomenon include that, at histologic examination, the cartilage lesions in our study (unlike those in other studies) could already be visualized by means of standard staining techniques and did not represent potential early precursor lesions of manifest cartilage degradation. Alterations consistent with the pathologic diagnosis of grade 1 and 2 lesions, in addition to loss of proteoglycans, also include alterations of the collagen network and chondrocytes (12,15). Furthermore, structural alterations occurring in the degradation process lead to an impaired diffusion capacity and an increased water content of articular cartilage (15), which might also alter contrast enhancement kinetics.
Subtle disruptions of the integrity of the cartilage surface can be invisible at macroscopic and even histologic examination with standard techniques and therefore might also be present in lesions classified as grade 1 rather than grade 2. In an experimental study with human cartilage specimens, Mlynarik and co-workers (18) observed that the expected shortening of T1 relaxation times caused by increased gadopentetate dimeglumine uptake in degraded cartilage could be reversed if fissuring of articular cartilage was already present. Therefore, as in our in vitro study, they could also identify at least two mechanisms of contrast enhancement. This, in our opinion, suggests that gadopentetate dimeglumine enhancement in articular cartilage degradation might be influenced by factors other than proteoglycan content alone.
In our study, grade 3 and 4 lesions could already be detected and graded correctly to correspond to macro- and microcopic findings on MR images obtained immediately after submersion in all cases. On delayed MR images, the visualization of surface lesions was neither improved nor impaired. Our observations correspond to the results of other authors, who investigated direct MR arthrography by using T1-weighted pulse sequences and contrast media containing gadolinium in vitro and in vivo and who reported high sensitivities (85%100%) in the detection of grade 3 and 4 articular cartilage lesions (23,25,28).
The present study has several limitations. First, data obtained in an experimental setting with the use of cadaveric specimens cannot generally be referred to living subjects. On the other hand, the experimental character of our investigations allowed a direct correlation of imaging and histopathologic findings. Second, the fact that only patellar lesions were studied might have positively influenced the detection rates, since cartilage lesions of the patella are generally more easily identified than cartilage defects located at other anatomic sites (eg, the tibial plateau). Third, the fact that several sections were obtained from each patella specimen might also have an influence on the results, because contiguous sections might have included the same cartilage lesion. Fourth, the penetration of articular cartilage by gadopentetate dimeglumine by means of diffusion following intraarticular or intravenous administration in vivo might be less effective than it would be under experimental conditions, where a constant concentration of the contrast media can be provided. Fifth, the detection rates calculated in this study represent the percentage of articular cartilage lesions, which could be identified on MR images when they were evaluated together with macroscopic and histologic sections. Therefore, the detection rates do not equal the sensitivity of this technique as evaluated in, for instance, a multireader analysis with blinded readings.
In summary, on the basis of results of our in vitro experiments, T1-weighted MR imaging enhanced with gadopentetate dimeglumine by means of diffusion appears to have the potential to provide demonstration of articular cartilage surface defects and earlier stages of chondromalacia. Further investigations will have to be conducted to evaluate the diagnostic performance of delayed MR imaging following direct or indirect MR arthrography in vivo.
Practical applications: The results of this experimental study suggest that delayed MR imaging after application of gadopentetate dimeglumine might be used to improve the diagnostic performance of MR imaging in detection of stage 1 and 2 chondromalacia in vivo. Since our experimental model simulated a direct MR arthrography approach, however, the data can only be referred to imaging following intraarticular administration of gadopentetate dimeglumine at a concentration of 2.5 mmol/L, which appears to be acceptable for direct MR arthrography. Possible indications include imaging prior to surgical treatment of chondral defects, evaluation of donor sites for osteochondral transplants, postoperative imaging following chondral or osteochondral transplantation, and monitoring of therapeutic effects of pharmacologic treatment. Furthermore, our data suggest that delayed contrast-enhanced MR imaging of articular cartilage can be performed with the use of standard T1-weighted SE sequences instead of inversion-recovery turbo SE sequences without loss of information.
| FOOTNOTES |
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Author contributions: Guarantor of integrity of entire study, K.W.; study concepts and design, K.W.; literature research, K.W.; experimental studies, K.W., H.B., J.M.; data acquisition, K.W., H.B., J.M.; data analysis/interpretation, K.W., H.B.; statistical analysis, K.W.; manuscript preparation, K.W.; manuscript definition of intellectual content, K.W., E.J.R.; manuscript editing, K.W.; manuscript revision/review and final version approval, K.W., E.J.R.
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