Comparison between magnetic resonance imaging,computed tomography,and arthrography to identify artificially induced cartilage defects of the equine carpal joints

While articular cartilage changes are considered to be one of the initial events in the pathological cascade leading to osteoarthritis, these changes remain difficult to detect using conventional diagnostic imaging modalities such as plain radiography. The aim of this prospective, experimental, methods comparison study was to compare the sensitivity of magnetic resonance imaging (MRI), magnetic resonance arthrography, computed tomography (CT), and CT arthrography in the detection of artificially induced articular cartilage defects in the equine carpal joints. Defects were created in the antebrachiocarpal and middle carpal joint using curettage by a board‐certified equine surgeon. Normal articular cartilage thickness varied from a maximum of 1.22 mm at the level of the distal aspect of the radius to a minimum of 0.17 mm in the proximal articular surface of the third carpal bone. Regarding cartilaginous defect measurements the remaining cartilaginous bed range from a maximum of 0.776 mm in the partial thickness defects, and 0 mm (defect reaches the subchondral bone) when total thickness defect were made. Computed tomography and magnetic resonance imaging were performed followed by CT arthrography and magnetic resonance arthrography after antebrachiocarpal and middle carpal intraarticular contrast administration. All images were reviewed by two board‐certified veterinary radiologists, both of whom were blinded to the location, presence of, and thickness of the cartilage defects. A total number of 72 lesions in nine limbs were created. Mean sensitivity for localizing cartilage defects varied between imaging modalities with CT arthrography showing the best sensitivity (69.9%), followed by magnetic resonance arthrography (53.5%), MRI (33.3%), and CT (18.1%) respectively. The addition of contrast arthrography in both magnetic resonance and CT improved the rate of cartilage lesion detection although no statistical significance was found. Computed tomographic arthrography displayed the best sensitivity for detecting articular cartilage defects in the equine antebrachiocarpal and middle‐carpal joints, compared to magnetic resonance arthrography, MRI, and CT.     

CORRELATION OF ARTICULAR CARTILAGE THICKNESS MEASUREMENTS MADE WITH MAGNETIC RESONANCE IMAGING,MAGNETIC RESONANCE ARTHROGRAPHY,AND COMPUTED TOMOGRAPHIC ARTHROGRAPHY WITH GROSS ARTICULAR CARTILAGE THICKNESS IN THE EQUINE METACARPOPHALANGEAL JOINT

Osteoarthritis of the metacarpophalangeal joint is common cause of lameness in equine athletes, and is hallmarked by articular cartilage damage. An accurate, noninvasive method for measuring cartilage thickness would be beneficial to screen for cartilage injury and allow for prompt initiation of interventional therapy. The objective of this methods comparison study was to compare computed tomographic arthrography (CTA), magnetic resonance imaging (MRI), and magnetic resonance arthrography (MRA) measurements of articular cartilage thickness with gross measurements in the metacarpophalangeal joint of Thoroughbred horses. Fourteen cadaveric, equine thoracic limbs were included. Limbs were excluded from the study if pathology of the metacarpophalangeal articular cartilage was observed with any imaging modality. Articular cartilage thickness was measured in nine regions of the third metacarpal bone and proximal phalanx on sagittal plane MRI sequences. After intra‐articular contrast administration, the measurements were repeated on sagittal plane MRA and sagittal CTA reformations. In an effort to increase cartilage conspicuity, the volume of intra‐articular contrast was increased from 14.5 ml, to maximal distention for the second set of seven limbs. Mean and standard deviation values were calculated, and linear regression analysis was used to determine correlations between gross and imaging measurements of cartilage thickness. This study failed to identify one imaging test that consistently yielded measurements correlating with gross cartilage thickness. Even with the use of intra‐articular contrast, cartilage surfaces were difficult to differentiate in regions where the cartilage surfaces of the proximal phalanx and third metacarpal bone were in close contact with each other.     

Computed tomographic evaluation of canine radioulnar incongruence in vivo

OBJECTIVE: To compare radioulnar incongruence (RUI) of normal canine elbows and elbows with arthroscopically confirmed medial compartment disease in vivo using systematic computed tomography (CT) measurements. STUDY DESIGN: Prospective comparison of RUI measurements in normal and dysplastic canine elbows. SAMPLE POPULATION: Right elbows of 25 medium-large breed, adult dogs with medial compartment disease and 9 medium-large breed, adult dogs with no elbow disease. METHODS: Transverse CT images of proximal radioulnar articulation were reformatted to dorsal and sagittal planes. RUI in 3 locations of the forelimb's medial coronoid was measured. Arthroscopy confirmed diagnosis of medial compartment disease in the diseased group. RUI measurements of the diseased and normal elbows were compared. RESULTS: Cumulative statistical analysis of RUI in all planes revealed no significant difference between the normal and abnormal elbows (P = .61). The abnormal elbows had negative mean RUI at the mid (P = .56) and cranial (P = .24) coronoid regions that were not significantly different from normal elbows and mean positive RUI at the base coronoid that was significantly greater than in normal elbows (P = .00082). CONCLUSION: Canine elbows with established medial compartment disease do not have significant RUI at the medial coronoid region at the time of diagnosis when compared with normal elbows. CLINICAL RELEVANCE: If RUI is a significant factor in the pathophysiology of medial compartment elbow disease in the dog, it does not appear to be present at the time of diagnosis of disease. Ulnar or radial osteotomies do not appear to be indicated for restoration of normal radioulnar articular surface alignment.     

Accuracy of computerized tomographic evaluation of canine radio-ulnar incongruence in vitro

OBJECTIVE: To evaluate the accuracy of linear measurements obtained from computer tomography (CT) images of staged radio-ulnar incongruence in a canine cadaver forelimb model. STUDY DESIGN: CT evaluation of induced progressive radio-ulnar incongruence in canine cadaveric forelimbs. SAMPLE POPULATION: Eight cadaveric canine left forelimbs. PROCEDURE: A type 2 external skeletal fixator (ESF) with linear motors was attached to the radius in 8 cadaveric left canine forelimbs. Contiguous incremental and helical CT images of the proximal radio-ulnar articulation were acquired in the transverse, sagittal and dorsal planes. The radius was shortened by 1, 2, and 4 mm increments and scanning protocols were repeated at each increment. Digital caliper and CT image analysis measured the progressive change in distance between 2 marking spheres and the epiphyseal bone surfaces of the radio-ulnar articulation. Statistical analysis of measurements from incremental and helical CT acquisitions, and direct and reformatted images were compared with inter-sphere distance using Pearson product moment correlation coefficients. RESULTS: The reformatted incremental acquisition series at the mid-coronoid in the oblique plane had the highest correlation coefficient (r-value) at 0.908. The mid-coronoid in the dorsal plane had the second highest r-value (0.856). The coronoid incisure in the sagittal plane had an r-value of 0.826. The reformatted incremental acquisition series at the coronoid incisure in the oblique plane had the lowest r-value, 0.592. CONCLUSION: Measurement of radioulnar incongruence may be best performed using reformatted incremental acquisition CT in the mid-coronoid region in an oblique plane. CLINICAL RELEVANCE: Use of the technique reported in this study may enable determination of the association, if any, between radioulnar incongruence and developmental diseases of the canine elbow.     

Computed tomographic features of incomplete ossification of the canine humeral condyle

Objectives— To describe computed tomographic (CT) features of canine elbows with incomplete ossification of the humeral condyle (IOHC) and investigate co-existing incongruence in the elbow joint.
Study Design— Case control study.
Animals— Dogs with IOHC (n=20; 38 elbows) and 25 normal elbows.
Methods— Elbows with IOHC and normal elbows were assessed by CT. Standardized dorsal and sagittal reconstructions were created at 3 levels using image analysis software to obtain single measurements of the humero-radial and humero-ulnar joint spaces. On dorsal plane reconstructions, joint space measurements were obtained at the center point of the humero-radial and humero-ulnar articulations. Joint incongruity was defined as the difference between the humero-radial and the humero-ulnar joint spaces.
Results— Nineteen dogs (95%), all Spaniel breeds, had either bilateral IOHC demonstrable as a saw-toothed intercondylar complete or incomplete hypoattenuating defect with hyperattenuating margins, or IOHC with contralateral humeral condylar fracture (HCF). Joint incongruity values for IOHC were compared with those of normal elbows. Significant differences were noted at the levels of the medial coronoid apex ( P <.0001) and base ( P <.004) indicative of humero-ulnar incongruence. Evidence of medial coronoid disease in 10 elbows (26%) and degenerative joint disease in 30 elbows (79%) was also found.
Conclusions— Presence of elbow incongruence may be an underlying factor in failure of ossification centers to fuse leading to IOHC.
Clinical Relevance— IOHC is clearly defined by CT, and it should be considered in larger Spaniel breeds, with a chronic forelimb lameness or HCF.     

Exposure and Postoperative Stability of Three Medial Surgical Approaches to the Canine Elbow

Articular cartilage exposure and immediate postoperative stability provided by three medial surgical approaches in canine cadaver elbows were compared. The approaches evaluated were a desmotomy of the medial collateral ligament (DMCL) that included a tenotomy of the pronator teres muscle, a longitudinal myotomy of the flexor carpi radialis (MFCR), and an osteotomy of the medial epicondyle (OME). Nondestructive biomechanical testing was performed before the surgical approach and repeated after surgery. The stiffness at 13 valgus deviation of the elbow and energy absorption up to 13 valgus deviation of the elbow were determined from the pre-operative and postoperative torque-rotation curves. The perimeters of the ulnar and humeral articular cartilage that were visualized through the approach were scored with a dental pick. Latex casts were made of articular surfaces of the elbow. The humeral and ulnar articular exposures were determined by computerized planimetric analysis of latex cast photocopies. The humeral cartilage exposure of the OME approach was significantly greater than either the MFCR or DMCL approaches. The DMCL approach provided a significantly greater humeral cartilage exposure than the MFCR approach. All three approaches provided statistically similar percentages of ulnar cartilage exposure. The stiffness and energy absorption of the OME and MFCR approaches were similar and significantly greater than the DMCL approach. The OME approach provided the best combination of exposure and immediate postoperative stability.     

Use of reconstructed computed tomography for the assessment of joint spaces in the canine elbow

OBJECTIVES: To assess the accuracy of reconstructed computed tomography for imaging canine elbow joint spaces. METHODS: Computed tomography scans of eight cadaveric elbows were obtained and reconstructed computed tomography images were formatted in the dorsal and sagittal planes. Humeroradial and humeroulnar joint space measurements were obtained from these images. Intra-observer and inter-observer variations in joint space measurements were assessed, as was the effect of specimen positioning (inter-image variation). After freezing, four elbows were sectioned in the dorsal plane and four in the sagittal plane. In addition to visual comparison of the frozen sections with reconstructed computed tomography images, joint space measurements were obtained from frozen sections and compared with those from reconstructed computed tomography images. Variation was assessed using statistical calculations and graphical techniques. RESULTS: Both inter-image and intra-observer analyses revealed good agreement and low variation between data sets. Inter-observer correlation was only moderate, though variation was low. Visually, the reconstructed computed tomography images accurately reflected the frozen section anatomy. Agreement between frozen section and reconstructed computed tomography joint space measurements was good, with minimal variation. CLINICAL SIGNIFICANCE: These results indicate that reconstructed computed tomography is capable of accurately imaging elbow joint spaces and precise joint space measurements can be obtained. Reconstructed computed tomography may be useful for determining joint space measurements and detecting elbow incongruencies in dogs with elbow dysplasia.     

Accuracy of computed tomographic arthrography for assessment of articular cartilage defects in the ovine stifle

Articular cartilage defects are one of the features of osteoarthritis in animals and humans. Early detection of cartilage defects is a challenge in clinical veterinary practice and also in translational research studies. An accurate, diagnostic imaging method would be desirable for detecting and following up lesions in specific anatomical regions of the articular surface. The current prospective experimental study aimed to describe the accuracy of computed tomographic arthrography (CTA) for detecting cartilage defects in a common animal model used for osteoarthritis research, the ovine stifle (knee, femoropatellar/femorotibial) joint. Joints in cadaver limbs (n = 42) and in living animals under anesthesia (n = 13) were injected with a contrast medium and imaged using a standardized CT protocol. Gross anatomy and histological assessment of specific anatomic regions were used as a gold standard for the evaluation of sensitivity, specificity, negative predictive value, and positive predictive value for CTA identification of articular cartilage defects in those regions. Pooled estimated sensitivity and specificity were 90.32% and 97.30%, respectively, in cadaver limbs, and 81.82% and 95.24%, respectively, in living animals. Pooled estimated positive predictive value and negative predictive values were 98.25% and 85.71%, respectively, in cadaver limbs, and 81.82% and 95.24%, respectively, in living animals. The delineation of cartilage surface was good for anatomical regions most frequently affected by cartilage defects in the ovine stifle: medial femoral condyle, medial tibial condyle, and patella. This study supported the use of CTA as an imaging technique for detecting and monitoring articular cartilage defects in the ovine stifle joint.     

FAT‐SUPPRESSED SPOILED GRADIENT‐RECALLED IMAGING OF EQUINE METACARPOPHALANGEAL ARTICULAR CARTILAGE

The purpose was to evaluate the capacity of 1.5 T magnetic resonance (MR) imaging to assess articular cartilage in racehorses with naturally occurring metacarpophalangeal joint osteoarthritis. A sagittal, three‐dimensional spoiled gradient‐recalled echo (SPGR) with fat saturation (FS) sequence was acquired ex vivo on 20 joints. Following joint dissection, specific areas on the third metacarpal condyle were designated for subsequent sampling for histologic cartilage thickness measurement and modified Mankin scoring. Cartilage thickness was measured and cartilage signal intensity was also graded (0–3) on MR images at these selected metacarpal sites. Cartilage structure was graded (0–3) macroscopically and on MR images by two examiners in defined subregions of the proximal phalanx, third metacarpal, and proximal sesamoid bones. There was good precision (mean error 0.11 mm) and moderate correlation (r=0.44; P<0.0001) of cartilage thickness measurements between MR images (0.90±0.17 mm) and histology (0.79±0.16 mm). There was moderate correlation between modified Mankin histologic score and signal intensity of cartilage (r=0.36; P<0.01) or MR cartilage structure assessment (r=0.49, P>0.001) on SPGR‐FS. The sensitivity to detect full‐thickness cartilage erosion on MR was only moderate (0.56), and these lesions were often underestimated, particularly when linear in nature. However, the specificity to detect such lesions on MR was high (0.92). While few limitations were identified, the use of a clinically applicable SPGR‐FS sequence allows a reasonably accurate method to assess structural changes affecting the articular cartilage of the equine metacarpophalangeal joint.     

COMPUTED TOMOGRAPHIC ARTHROGRAPHY OF THE NORMAL CANINE STIFLE

Computed tomographic (CT) imaging of eight normal cadaveric canine stifles was performed before and after intra-articular administration of iodinated contrast medium. Transverse CT images were reconstructed in dorsal, parasagittal, and oblique planes. The following ligamentous structures were identified on transverse CT images in all stifles: cranial cruciate ligament, caudal cruciate ligament, medial meniscus, lateral meniscus, and the medial and lateral collateral ligaments. The following ligamentous structures were identified on transverse computed tomographic arthrography (CTA) images in all stifles: cranial cruciate ligament, caudal cruciate ligament, medial meniscus, lateral meniscus, meniscofemoral ligament, cranial meniscotibial ligaments, caudal meniscotibial ligaments, intermeniscal (transverse) ligament, and the medial and lateral collateral ligaments. The patellar tendon was identified on transverse and reconstructed dorsal and sagittal CT and CTA images in all stifles. Multiplanar reconstructions enabled further evaluation of the continuity of the cranial and caudal cruciate ligaments and menisci. The medial and lateral collateral ligaments were not clearly identified on CT or CTA multiplanar reconstructed images.     

Relationships among measurements obtained by use of computed tomography and radiography and scores of cartilage microdamage in hip joints with moderate to severe joint laxity of adult dogs

OBJECTIVE: To evaluate correlations among measurements on radiographic and computed tomography (CT) images with articular cartilage microdamage in lax hip joints of dogs. ANIMALS: 12 adult mixed-breed hounds. PROCEDURES: Pelvic CT and radiography were performed. Hip joints were harvested following euthanasia. Orthopedic Foundation for Animals (OFA) and PennHIP radiograph reports were obtained. Norberg angle (NA) and radiographic percentage femoral head coverage (RPC) were determined. Center-edge angle (CEA), horizontal toit externe angle (HTEA), ventral acetabular sector angle (VASA), dorsal acetabular sector angle (DASA), horizontal acetabular sector angle (HASA), acetabular index (AI), and CT percentage femoral head coverage (CPC) were measured on 2-dimensional CT images. Femoral head-acetabular shelf percentage was measured on sagittal 3-dimensional CT (SCT) and transverse 3-dimensional CT (TCT) images. Light microscopy was used to score joint cartilage. Relationships of OFA confirmation and PennHIP osteoarthritis scores with radiography, CT, and cartilage variables and relationships of cartilage scores with radiography and CT measurements were evaluated with Spearman rank correlations. Pearson correlation was used for relationships of distraction index (DI) with radiography, CT, and cartilage variables. RESULTS: Significant relationships included PennHIP osteoarthritis score with cartilage score, CEA, HTEA, DASA, AI, CPC, and TCT; OFA confirmation score with cartilage score, NA, RPC, CEA, HTEA, DASA, AI, CPC, and TCT; cartilage score with NA, RPC, CEA, HTEA, DASA, HASA, AI, and TCT; and DI with cartilage score, CEA, HTEA, DASA, HASA, AI, and CPC. CONCLUSIONS AND CLINICAL RELEVANCE: CT appeared to be a valuable imaging modality for predicting cartilage microdamage in canine hip joints.     

Post natal development of the canine elbow joint: a light and electron microscopical study.

The elbows of 13 puppy cadavers were dissected, samples were taken for light and electron microscopy, and the thickness of the articular cartilage of the distal humerus and proximal ulna was measured. Throughout post natal development differences were found in the arrangement of the growth plate and articular chondrocytes. At birth, the articular surface had remnants of a fibrous limiting membrane that was continuous with the perichondrium, a finding not previously recorded in dogs. Orientation of the collagen fibrils within the matrix of the articular cartilage was initially lacking but became established by three weeks. In the humerus cartilage canals were present up to 12 weeks old. The articular cartilage of the humeral condyle varied in thickness across the joint surface, being thicker on the medial than on the lateral side; it was also thicker at the apex of the medial coronoid process. These regions of thick cartilage correspond with the sites where cartilage defects arise in elbow osteochondrosis. No histological evidence was found that the medial cornoid process of the ulna is a separate centre of ossification.     

Computed tomographic osteoabsorptiometry of the elbow joint in clinically normal dogs

OBJECTIVE: To evaluate subchondral bone density patterns in elbow joints of clinically normal dogs by use of computed tomographic (CT) osteoabsorptiometry. SAMPLE POPULATION: 20 cadaver forelimbs from 10 clinically normal dogs. PROCEDURE: Each elbow joint was imaged in parasagittal and transverse planes of 1.5-mm thickness. Slice data were converted to dipotassium phosphate equivalent density (PPED) values. Sagittal, parasagittal, and transverse medial coronoid process topographic maps were constructed. Defined zones were created for each of the 3 CT planes, and confluence and peak PPED values were determined. RESULTS: The lowest PPED value was 340 mg/ml (articular and subchondral confluence), and the highest was 1780 mg/ml (peak subchondral density). Detectable effects of joint laterality were not found in the confluence or peak PPED measurements or in the peak-to-confluence PPED ratio for all 3 CT planes. Significant differences were found among zones in all 3 planes for confluence and peak PPED measurements and between sagittal and transverse planes for peak-to-confluence PPED ratios. Subjectively, the pattern of density distribution among dogs was fairly consistent for the sagittal and parasagittal slices. Three specific patterns of density distribution were apparent on the transverse topographic maps of the medial coronoid process that corresponded to conformational differences. CONCLUSIONS AND CLINICAL RELEVANCE: The use of CT osteoabsorptiometry provides a repeatable technique that can be used to noninvasively examine bone density and the effects of stress acting on joints in vivo. Variability in density values for any of the CT planes was not identified among clinically normal dogs.     

DISTAL INTERPHALANGEAL ARTICULAR CARTILAGE ASSESSMENT USING LOW‐FIELD MAGNETIC RESONANCE IMAGING

The suitability of low‐field magnetic resonance (MR) imaging for assessment of articular cartilage has been questioned, based on insufficient image quality. The purposes of this study were to describe the MR anatomy of the normal distal interphalangeal (DIP) cartilage, and to evaluate the sensitivity and accuracy of low‐field MR imaging for identification of cartilage erosions that were created ex vivo. Imaging sequences included sagittal and dorsal multiple‐oblique T1‐weighted gradient‐recalled echo (GRE) and sagittal dual echo sequences. In the thickest regions, normal cartilage appeared as a trilaminar structure on high‐resolution T1‐weighted GRE sequences. All 8 mm large full‐thickness erosions were correctly identified (100% sensitivity and accuracy) using T1‐weighted GRE sequences. Sensitivity and accuracy ranged from 80% to 100% and 10% to 80%, respectively, for detecting focal full‐thickness erosions and from 35% to 80% and 35% to 60%, respectively, for detecting partial thickness erosions, using T1‐weighted GRE sequences. Superficial irregularities were not diagnosed using any sequence. Overall, fewer cartilage alterations were detected with sagittal dual echo sequences than with sagittal T1‐weighted GRE sequences. The dorsal multiple‐oblique plane was useful to detect linear dorsopalmar erosions. A combination of T1‐weighted GRE sequences in two planes has potential for identification of severe DIP cartilage erosion in anesthetized horses using low‐field MR imaging.     

Validation of magnetic resonance imaging for measurement of equine articular cartilage and subchondral bone thickness

OBJECTIVE: To validate use of magnetic resonance images (MRIs) for measurement of equine articular cartilage and subchondral bone thickness by comparison with measurements in histologic specimens. SAMPLE POPULATION: 32 cadaveric carpal joints from 16 horses. PROCEDURE: Magnetic resonance imaging was performed by use of 3-dimensional fast spoiled gradient echo (SPGR) and T2* 3-dimensional fast gradient echo (GRE) pulse sequences with and without fat saturation. Standard sites on the medial and lateral facets of the intermediate, radial, and third carpal bones were used for subchondral bone and articular cartilage thickness measurements. Digital image analysis software was used for MRI measurements 10 mm from the dorsal extent and perpendicular to the articular surface. Histomorphometric measurements of hyaline, calcified cartilage, and subchondral bone thickness were obtained at selected sites. Comparisons between histomorphometric and MRI measurements and between magnetic resonance pulse sequences were evaluated. RESULTS: There were significant correlations between GRE and SPGR and SPGR and histologic measurements of articular cartilage, with no significant difference between measurements and good agreement. When calcified cartilage was excluded from the histologic measurement, MRI measurements were significantly greater than histologic measurements. For subchondral bone thickness, there was significant correlation between GRE and SPGR but GRE was significantly greater than SPGR measurements. Histomorphometric and MRI measurements were strongly correlated and not significantly different. CONCLUSIONS AND CLINICAL RELEVANCE: Magnetic resonance imaging provides a good representation of cartilage and subchondral bone thickness, supporting its use in the study and clinical diagnosis of osteochondral structure and alteration.     

Evaluation of a Collagenase Generated Osteoarthritis Biomarker in the Synovial Fluid from Elbow Joints of Dogs with Medial Coronoid Disease and Unaffected Dogs

Objective— To evaluate whether synovial fluid concentrations of an osteoarthritis biomarker in dysplastic canine elbows with medial coronoid disease (MCD) are elevated compared with unaffected elbows and to determine if these concentrations correlate to the degree of articular cartilage damage.
Study Design— Cross sectional clinical study.
Animals— Dogs (n=19; 35 elbows) with MCD and dogs (8; 16 elbows) with unaffected elbows.
Methods— Concentrations of a collagenase-generated cleavage neoepitope of type II collagen (Col2-3/4C_{long mono}, or C2C) in joint fluid from elbows were analyzed and compared between dogs with MCD and unaffected dogs. Correlation of C2C concentration with subjective grading of articular cartilage surface damage was also evaluated.
Results— Mean (±SD) C2C concentration from MCD dogs was significantly higher (112.3±24.8 ng/mL) than in unaffected dogs (76.1±16.9 ng/mL; P <.05). There was a moderate correlation between cartilage damage grade and increasing C2C concentrations ( P <.05, r=0.62)
Conclusion— C2C concentrations are elevated in the synovial fluid of dogs with MCD compared with unaffected elbows, and a moderate, significant correlation was identified between these concentrations and subjective grading of articular cartilage damage.
Clinical Relevance— This preliminary data suggest that C2C concentrations in synovial fluid may have potential as a biomarker for diagnosis of articular cartilage damage associated with MCD and as a means of objectively determining the degree of articular cartilage damage.