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MR imaging of cartilage lesions of the knee: what is the clinical indication? (radiologist's view).

This commentary focuses on the clinical application of magnetic resonance (MR) imaging in the assessment of articular cartilage of the knee. MR imaging is superior to conventional imaging techniques for evaluation of the articular cartilage. Several pulse sequences are advocated for demonstration of the normal articular cartilage and cartilage lesions. However, a consensus has not yet been reached in regard to the most appropriate sequence for evaluation of the articular cartilage. Early morphological changes in the degenerative cartilage are not reliably diagnosed even with the use of tailored MR imaging techniques. The detection of the biochemical changes of cartilage will serve as an important tool for the early diagnosis of cartilage degeneration in the near future. Further prospective studies are needed to establish the role of MR imaging in clinical use.

Cartilage, Articular↗

[MRI monitoring of autologous hyaline cartilage grafts in the knee joint: a follow-up study over 12 months].

PURPOSE: To evaluate the suitability of different MR sequences for monitoring the stage of maturation of hyaline cartilage grafts in the knee joint and the early detection of complications like hypertrophy. In addition, it was analyzed whether indirect MR arthrography can indicate debonding of the graft. MATERIALS AND METHODS: MRI examinations were performed in 19 patients, aged 17 - 48 years, with autologous transplantation of a hyaline cartilage tissue graft after knee trauma. Examination dates were prior to transplantation to localize the defect, and 6 weeks, 3, 6 and 12 months after transplantation to control morphology and maturation of the autologous graft. Standard T2- and proton-density-weighted turbo spin echo (TSE) sequences and T1-weighted spin echo (SE) sequences were used, as well as gradient echo (GRE) sequences with and without magnetization transfer (MT) prepulses. In some cases, indirect MR arthrography was performed. RESULTS: Cartilage defect and the hyaline cartilage graft could be detected in all 19 patients. Hypertrophy of the graft could be found early in 3 patients and debonding in 1 patient. For depicting the graft a short time after surgery, T2-weighted TSE-sequences showed the best results. Six and 12 months after transplantation, spoiled 3D-GRE-sequences like FLASH3D (fast low angle shot) showed reduced artifacts due to magnetic residues from the surgery. Difference images from GRE-sequences with and without MT pulse provided high contrast between cartilage and surrounding tissue. The quantification of the MT effect showed an assimilation of the graft to the original cartilage within 12 months. Indirect MR arthrography showed subchondral contrast medium even 12 months after transplantation in 3 patients. CONCLUSION: MRI allows a reliable depiction of the hyaline graft and provides very early detection of complications like hypertrophy. The MT effect seems to be correlated with maturation of the graft and allows selective depiction of normal cartilage and engrafted cartilage.

Adolescent↗

[The cartilage guide: a solution for anchoring a columella-prosthesis on footplate].

BACKGROUND: A torp (columella-prosthesis) is the typical ossicular reconstruction in cases of a destroyed stapedial arch. Yet, many unsatisfactory hearing results are due to the lack of a stable, reliable anchoring of the base of the prosthesis on the footplate. Some solutions have been postulated, amongst them the perforation of the footplate with a tiny spike at the lower end of the prosthesis, which, however, many otosurgeons regard as too dangerous for the inner ear. Specially designed silicone sheets cannot guarantee a permanent guide of the columella. METHODS: From our good experience with cartilage in different reconstruction procedures, we therefore developed a cartilage guide for the oval window niche. An oval 2,5 x 3,5 mm cartilage with a central hole is cut out of a thin (0,2 - 0,3 mm) cartilage plate with a help of a cartilage punch, which we had designed in collaboration with Heinz Kurz manufacture. The cartilage is placed into the oval niche and its hole guides the prosthesis onto the centre of the footplate. RESULTS: Temporal bone experiments demonstrated a reliable sound transport through this guide. Revision surgery revealed a stable ingrowth of the cartilage plate into the oval niche, its perforation securely guiding the prosthesis similar to a piston on to the footplate. The first short time hearing results (max. 1 year) in 22 patients confirmed the acoustic quality of this stabilisation of a columella on the footplate as compared to a matched control group. CONCLUSIONS: The stabilization of the columella with a cartilage-guide might solve one of the many problems with unsatisfactory hearing results after the reconstruction of a completely destroyed ossicular chain.

Adolescent↗

Measuring cartilage morphology with quantitative magnetic resonance imaging.

Magnetic resonance imaging (MRI) is a three-dimensional imaging technique with unparalleled ability to delineate articular cartilage morphology in health and disease. In this article we will review work on the assessment of cartilage morphology with quantitative magnetic resonance imaging and its relevance to the study of cartilage anatomy, physiology, deformation, disease status, disease progression, and response to treatment. The review outlines available pulse sequences and techniques for segmentation and morphological analysis of cartilage morphology. It addresses the accuracy (validity) and precision (reproducibility) of these techniques and summarizes studies on cartilage deformation in intact joints. This article will also review work on determinants and functional adaptation of cartilage morphology and describe changes seen in osteoarthritis. We conclude that fat-suppressed or water excitation gradient-echo magnetic resonance sequences and state-of-the-art digital image analysis techniques display high accuracy and adequate precision for quantitative assessment of cartilage morphology. This renders these techniques powerful and promising tools for cartilage and osteoarthritis research.

Cartilage, Articular↗

Articular cartilage, degenerative process, and repair: current progress.

The aim of this paper is to review the current knowledge about degenerative and repair process of articular cartilage, and relationship between osteoarthritis and physical activities. Data Pubmed, ScienceDirect data base are interrogated for the period 1994 - 2003. Key words are: cartilage, osteoarthritis, exercise, rehabilitation. The mechanical biology of the cartilage and the chondrocytes, the effects of physical activity on the cartilage, the main studies on clinical trials on rehabilitation are reviewed. Chondrocyte and cartilage structure and function change with mechanical stresses. Mechanical loads can modulate cartilage matrix turnover. Joint injury increases the risk of osteoarthritis, and sports that subjects joints to repetitive high levels of impact loading increase the risk of injury and degeneration. In human, intensive physical exercises seem associated with osteoarthritis development. None of the current procedures for repairing articular cartilage restores a normal articular zone, however, selected procedures can predictably benefit selected subjects. This article presents the biology and discusses the alteration of cartilage as well as the osteoarthritis process which is not yet well understood. Current medical approaches to the treatment of osteoarthritis also are presented. Rehabilitation programme could be beneficial in the therapeutic management of osteoarthritis.

Cartilage, Articular↗

[Determination of cartilage thickness in the ankle joint. an MRT (1.5)-anatomical comparative study].

PURPOSE: The aim of this study was to evaluate the accuracy of MRI in the measurement of cartilage thickness of the ankle joint in comparison to pathologic and histologic specimens. PATIENTS AND METHODS: The ankle joints of four fresh cadaver feet were imaged on a 1.5T MR-unit in the coronal plane. Standard T1-weighted spin echo (SE) and a T1-weighted 3D-GE (FLASH-3D) sequence with fat saturation were applied. Following MR imaging, the talus was explanted and cut parallel to the MR images for macroscopic evaluation and histologic specimens were prepared. MRI measurements of the cartilage thickness of the talus were carried out in two ways: without and with consideration of a transition zone of intermediate signal intensity between hyperintense cartilage and hypointense cortical bone. The data were compared with the anatomic specimens as the gold standard expressing the difference as a percentage value. On histologic specimens thickness of deep calcified cartilage layer was measured. RESULTS: Measurements without the transition zone showed a mean underestimation of talus cartilage thickness of 46.8% (41.3-52.1) for T1-SE and 47.5% (43.1-52.1) for fat saturated FLASH-3D images. Considering the transition zone the mean values were 25.0% (23.1-26.2) and 14.1% (6.7-21.5). The histologic specimens showed a three-fold increase of thickness of deep calcified cartilage layer. CONCLUSIONS: Measurements of the cartilage layer of the ankle joint on MR images are only accurate if the transition zone (calcified cartilage layer) is considered and the optimal pulse sequence (FLASH-3D-fat-sat) is applied.

Aged↗

[Biological corneal replacement--an alternative to keratoplasty and keratoprosthesis? A pilot study with heterologous hyaline cartilage in the rabbit model].

BACKGROUND: In patients with corneal opacity caused by diseases like okular pemphigoid, Stevens-Johnson-Syndrome or burns, visual rehabilitation can only be achieved with keratoplasty or keratoprosthesis. The first has generally a poor prognosis in these circumstances, and the latter bears several problems in the postoperative course as well. A biological, corneal replacement could possibly combine the advantages offered by keratoplasty (no interaction between host tissue and plastic) and keratoprosthesis (more permanent transparency). Theoretical considerations and practical experience suggest that the best candidate would be hyaline cartilage. MATERIAL AND METHODS: Bovine sterni were used to obtain circular cartilage slices which were approximately 60 microns thick, having a diameter of approximately 6 mm. These slices were implanted in one eye each of 4 rabbits instead of the natural cornea. The eyes were enucleated after 8 to 29 days. RESULTS: The cartilage remained so transparent that the iris and to a certain extent the fundus blood vessels could be visualized. Connective tissue served to bind the host cornea to the cartilage, but did not infiltrate the cartilage. Perforation was observed in 3 animals. The extent of epithelialization of the cartilage slices ranged form ca. 30% to 95%. None of the animals exhibited an intraocular inflammation. The cartilage did not proliferate and remained avascular. Secondary intraocular changes, with the exception of anterior synechiae, could not be detected. CONCLUSIONS: A tissue for biological corneal replacement has to fulfill many requirements which to a certain extent can be achieved with the use of hyaline cartilage. Despite numerous, unsolved problems, a biological corneal replacement as an alternative to keratoplasty and keratoprosthesis in cases of corneal blindness does not seem out of imagination.

Animals↗

[Collagen type VI content in healthy and arthritis knee joint cartilage].

AIM OF THE STUDY: Since collagen type VI seems to play an important role in cartilage metabolism and is increased in osteoarthritis, the aim of this study was to investigate whether different stages of osteoarthritis can be characterised by the content of collagen type VI in human knee cartilage. MATERIAL AND METHODS: Collagen type VI was investigated in 148 histologically normal and 117 osteoarthritic cartilage samples from 18 different localisations of human knee joints. It was quantified in cartilage extracts using an inhibition-ELISA. RESULTS: In normal cartilage the average content of collagen type VI was 0.48 per cent of total collagens. Interestingly, there was a high variability not only in osteoarthritic, but also in normal cartilage. The statistical analysis showed significant differences between normal femoral, tibial or retropatellar cartilage samples. Therefore, normal and osteoarthritic samples from different localizations had to be compared separately. A significant increase of collagen type VI was already found in early osteoarthritic lesions. CONCLUSIONS: Inspite of a statistically significant increase of collagen type VI in osteoarthritic cartilage, the range of concentrations found in normal and osteoarthritic samples overlap. In view of the high interindividual variability, collagen type VI is not very precise in the diagnosis of early osteoarthritic lesions if used as the only marker.

Adult↗

[Synovial membrane and cartilage changes in an arthrosis model. Instability and impact stress model].

UNLABELLED: Surgical instability and repetitive impulsive loading was used to generate degenerative changes in knee joints of rabbits. Light- and electronmicroscopy was carried out at synovial membrane and cartilage samples. The instabilised joints had early synovial inflammation, preceding overall cartilage changes. Synoviocytes were activated and showed more and dilatated cytoplasmatic organells. Invaded round cells--potentially cartilage degenerative--were seen. In the loading model no initial synovial inflammation could be seen. Focal cartilage changes were located at the weight bearing zone. Two different inductive pathways may be involved in cartilage breakdown comparing the two arthrosis models. Mechanical factors seemed to trigger cartilage changes in the loading model, an inflammatory synovial pathway is likely to initiate cartilage breakdown in the instability model. CLINICAL RELEVANCE: The synovial membrane has the key-position for the cartilage degeneration in posttraumatic joint affections. The therapeutic use of antiphlogistic substances is indicated to supreme inflammatory mediators from the synovial membrane. This therapeutic concept seemed not to be useful in primary mechanical induced osteoarthrosis.

Animals↗

[Comparative histomorphometry of subchondral bone density and articular cartilage thickness in the tibial head in early human arthritis].

The articular cartilage thickness and subchondral bone density of 50 human tibial heads were histomorphometrically measured by an image analysing system and topographically examined in relation to age, sex and grade of osteoarthrosis (OA). Altogether we evaluated 12,000 items. Independent of OA the lateral tibial plateau shows a significant thicker cartilage layer than the medial. In central joint areas we find a thicker cartilage cover than in marginal. Corresponding to the literature cartilage fibrillation according to OA grade 1 and 2 (Otte 1969, Fassbender 1975) accumulates in the lateral and dorsal tibial head including the meniscus covered area. The cartilage thickness decreases with age independent of OA. Without major alterations of the topographical pattern the cartilage thickness however shows a significant increase in early OA (grade 1). For that reason measurements of the cartilage thickness and joint space narrowing are not appropriate for defining early OA. The subchondral bone density shows high values ventromedially and dorsolaterally independent of sex, age or OA. Beneath central joint areas higher values are found than marginally. Corresponding to the topical literature our results point at the model of the real loaded knee joint, which says that the mean loading forces do not act on the middle of the joint but on the medial plateau. The dorsolateral density centre could be an expression of the functional adaptation of the bended knee joint. In joint areas with cartilage fibrillation (OA grade 1) we find a significant higher subchondral bone density without major alterations of the topographical pattern. It is not possible to define cause and effect, we interpret both as result of higher joint loading.

Adolescent↗

The organization of aggrecan in human articular cartilage. Evidence for age-related changes in the rate of aggregation of newly synthesized molecules.

The effect of age on the incorporation of newly synthesized aggrecan into the extracellular matrix of human articular cartilage was investigated. This property was measured in a pulse-chase explant culture system by determining the distribution of radiolabeled molecules ([(35)S]sulfate-labeled) between a nondissociating extract (phosphate-buffered saline), which extracts mainly nonaggregated macromolecules, and a dissociating extract (4 M GnHCl) containing mainly aggrecan that was complexed in situ with hyaluronan. The rate of incorporation of aggrecan into aggregates was much slower in mature cartilage than in tissue obtained from younger individuals. Furthermore, autoradiography showed that in mature cartilage, newly synthesized aggrecan is not transported from the pericellular environment within the first 18 h of chase culture, whereas in immature cartilage, it moves into the intercellular space during the same period, i.e. aggrecan is processed in the extracellular space very differently in young and adult articular cartilage. Experiments were also performed to show that the interaction of link protein with newly synthesized aggrecan depends on the maturity of the G(1) domain of aggrecan. This investigation has shown that the extracellular aggregation of aggrecan in adult human articular cartilage involves a number of intermediate structures. These have not been identified in the very young cartilage obtained from laboratory animals or in porcine and bovine articular cartilage obtained from the abattoir.

Age Factors↗

Anatomical localization of cartilage degradation markers in a surgically induced rat osteoarthritis model.

Osteoarthritis (OA) is a degenerative disease characterized by an irreversible loss of articular cartilage. Although surgically induced animal OA models are commonly used in drug efficacy assessment, degradation of type II collagen, an important component of articular cartilage is not routinely evaluated. Here, the medial meniscectomy surgical model (MMT) in Lewis rats was evaluated for proteoglycan loss with toluidine blue staining and collagen degradation with immunohistochemical staining for a collagen cleavage C-neoepitope, using a novel anti-type II collagen neoepitope antigen (TIINE) antibody. Femorotibial joints were collected for histology at 0 (no surgery), 3, 7, 14, 21, 28, 35, and 42 days postsurgery. Following MMT surgery, the medial tibial articular cartilage had proteoglycan matrix loss by day 3 that reached subchondral bone by days 28-42. Femoral cartilage damage occurred by day 14. TIINE staining was present at basal levels in growth plates and articular cartilage of all joints while all MMT-treated animals had increased intensity and area of staining in erosions that colocalized with proteoglycan loss. The MMT model produces a progressive pattern of cartilage damage resembling human OA lesions, making it useful, when evaluated with cartilage biomarkers, for assessing changes in cartilage degradation.

Animals↗

Microscopic change in macroscopically normal equine cartilage from osteoarthritic joints.

The objective of this study was to assess whether macroscopically normal articular cartilage taken from joints containing focal osteoarthritic lesions is histologically similar to articular cartilage taken from macroscopically normal joints. Metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints were obtained from 10 horses following euthanasia. Gross articular cartilage damage was scored and the cartilage assigned to one of two groups: (1) macroscopically normal cartilage from normal joints (control) and (2) macroscopically normal cartilage from diseased joints in which there were focal osteoarthritic lesions. Chondrocytes expressing specific cytokines and cytokine receptors were identified by immunohistochemistry. The total number of chondrocytes, and percentage of chondrocytes positive for these cytokines and receptors, was recorded in the superficial, middle, and deep cartilage zones. There was a significant increase in the expression of interleukin-1beta in the superficial and middle zones and interleukin-18 receptor in the superficial zone in Group 2 compared with Group 1 control samples. A significant positive correlation also was found between the grade of osteoarthritis and the percentage of chondrocytes positive for interleukin-1beta in the superficial and middle zones, and for interleukin-18 and interleukin-18R in the superficial zone. There was a significant increase in histology score for glycosaminoglycan loss in Group 2 compared with that in Group 1. In joints with focal osteoarthritis lesions, all the articular cartilage, even if macroscopically apparently normal, may have microscopic changes associated with osteoarthritis.

Animals↗

Syndecan-1 expression is upregulated in degenerating articular cartilage in a transgenic mouse model for osteoarthritis.

OBJECTIVE: Mice heterozygous for the Del1 transgene locus with a short deletion mutation in the type II collagen gene develop early-onset degenerative changes in the knee joints that progress to end-stage osteoarthritis by the age of 12-15 months. This study focuses on the expression and distribution of syndecan-1, a cell-surface heparan sulfate proteoglycan, during the development of osteoarthritic cartilage degeneration, to better understand its role in this disease. METHODS: Northern analyses of total RNA extracted from knee joints of transgenic Del1 mice and their nontransgenic controls were used to monitor changes in syndecan-1 mRNA levels during development, growth, ageing, and cartilage degeneration. Immunohistochemistry was used to study the distribution of syndecan-1 in the knee joints at different stages of cartilage degeneration. RESULTS: Syndecan-1 mRNA was present in knee joints throughout life, with the highest mRNA levels in ageing knee joints. In Del1 mice, a transient upregulation of syndecan-1 mRNA synthesis was observed at the age of 6 months coinciding with early stages of cartilage degeneration and a period of attempted repair. Immunostaining for syndecan-1 was most intense in chondrocytes of superficial and intermediate zones of articular cartilage adjacent to defect areas. Chondrocyte clusters also stained strongly for syndecan-1. CONCLUSION: The present temporospatial expression data on upregulation of syndecan-1 in articular cartilage during early stages of cartilage degeneration suggest that this molecule is involved in the attempted repair of cartilage fibrillations. Combined with the known role of syndecan-1 during skeletal development and wound healing, this interesting finding warrants further validation.

Animals↗

Alterations in mechanical behaviour of articular cartilage due to changes in depth varying material properties--a nonhomogeneous poroelastic model study.

The depth dependence of the material properties is present in normal adult cartilage and is believed to have significant implications in its normal mechanical function. Cartilage pathology may alter the depth dependence, e.g. a reduced depth dependence of the fibril stiffness has been observed in osteoarthritic cartilage. The objective of the present study is to investigate the alterations in the mechanical response of articular cartilage when the depth dependence of the material properties is varied to simulate healthy and pathological situations. This study is made possible by a recently developed nonhomogeneous poroelastic model. Depth variations of the strains and stresses for individual material phases (collagen, proteoglycan and fluid) are obtained for cartilage disks in unconfined compression using the finite element method. The mean nominal axial strain considered is up to 15%, while the axial strain at the articular surface can reach 33%. This paper demonstrates how the mechanical behaviours of cartilage are affected by individual depth dependent cartilage properties, while such observations are not fully available in experimental investigations. This study suggests the possibility of diagnosing cartilage health by analysing its mechanical behaviours.

Animals↗

Domains of type X collagen: alteration of cartilage matrix by fibril association and proteoglycan accumulation.

During endochondral bone formation, hypertrophic cartilage is replaced by bone or by a marrow cavity. The matrix of hypertrophic cartilage contains at least one tissue-specific component, type X collagen. Structurally type X collagen contains both a collagenous domain and a COOH-terminal non-collagenous one. However, the function(s) of this molecule have remained largely speculative. To examine the behavior and functions of type X collagen within hypertrophic cartilage, we (Chen, Q., E. Gibney, J. M. Fitch, C. Linsenmayer, T. M. Schmid, and T. F. Linsenmayer. 1990. Proc. Natl. Acad. Sci. USA. 87:8046-8050) recently devised an in vitro system in which exogenous type X collagen rapidly (15 min to several hours) moves into non-hypertrophic cartilage. There the molecule becomes associated with preexisting cartilage collagen fibrils. In the present investigation, we find that the isolated collagenous domain of type X collagen is sufficient for its association with fibrils. Furthermore, when non-hypertrophic cartilage is incubated for a longer time (overnight) with "intact" type X collagen, the molecule is found both in the matrix and inside of the chondrocytes. The properties of the matrix of such type X collagen-infiltrated cartilage become altered. Such changes include: (a) antigenic masking of type X collagen by proteoglycans; (b) loss of the permissiveness for further infiltration by type X collagen; and (c) enhanced accumulation of proteoglycans. Some of these changes are dependent on the presence of the COOH-terminal non-collagenous domain of the molecule. In fact, the isolated collagenous domain of type X collagen appears to exert an opposite effect on proteoglycan accumulation, producing a net decrease in their accumulation, particularly of the light form(s) of proteoglycans. Certain of these matrix alterations are similar to ones that have been observed to occur in vivo. This suggests that within hypertrophic cartilage type X collagen has regulatory as well as structural functions, and that these functions are achieved specifically by its two different domains.

Animals↗

Transglutaminase-catalyzed matrix cross-linking in differentiating cartilage: identification of osteonectin as a major glutaminyl substrate.

The expression of tissue transglutaminase in skeletal tissues is strictly regulated and correlates with chondrocyte differentiation and cartilage calcification in endochondral bone formation and in maturation of tracheal cartilage (Aeschlimann, D., A. Wetterwald, H. Fleisch, and M. Paulsson. 1993. J. Cell Biol. 120:1461-1470). We now demonstrate the transglutaminase reaction product, the gamma-glutamyl-epsilon-lysine cross-link, in the matrix of hypertrophic cartilage using a novel cross-link specific antibody. Incorporation of the synthetic transglutaminase substrate monodansylcadaverine (amine donor) in cultured tracheal explants reveals enzyme activity in the pericellular matrix of hypertrophic chondrocytes in the central, calcifying areas of the horseshoe-shaped cartilages. One predominant glutaminyl substrate (amine acceptor) in the chondrocyte matrix is osteonectin as revealed by incorporation of the dansyl label in culture. Indeed, nonreducible osteonectin-containing complexes of approximately 65, 90, and 175 kD can be extracted from mature tracheal cartilage. In vitro cross-linking of osteonectin by tissue transglutaminase gives similar products of approximately 90 and 175 kD, indicating that the complexes in cartilage represent osteonectin oligomers. The demonstration of extracellular transglutaminase activity in differentiating cartilage, i.e., cross-linking of osteonectin in situ, shows that tissue transglutaminase-catalyzed cross-linking is a physiological mechanism for cartilage matrix stabilization.

Antibody Specificity↗

Studies on ultrastructural identification and distribution of protein-polysaccharide in cartilage matrix.

Previous reports on the ultrastructure of cartilage matrix have described fibers, amorphous ground substance and, in some instances, dense matrix granules. The fibers are presumably collagen, but the nature of the granules is unknown. The primary purpose of this study has been to investigate the ultrastructure of cartilage matrix ih chick embryos with particular emphasis on the distribution and composition of these granules. In matrix of the zone of articular cartilage, mature collagen fibers can be seen but granules are not present. In matrix of all other zones of cartilage, fibers are smaller and granules are present. When the matrix of epiphyseal cartilage is compared to that of the zone of hypertrophic cells, fibers are similar but the granules in the latter zone are larger and more numerous. The granules in both zones were digested by hyaluronidase and positive to colloidal iron staining. Chemical analyses of cartilage from these zones indicate the hexosamine and radiosulfate content of the zone of hypertrophic cells to be higher than that of the zone of epiphyseal cartilage. The increased hexosamine was shown by column chromatography to be principally sulfated mucopolysaccharide, thereby indicating a direct correlation between size and number of granules and sulfated mucopolysaccharide content in the two zones. These data and the results of the electron microscopic histochemical studies are consistent with the concept that the granules in cartilage matrix contain acidic mucopolysaccharide.

Animals↗