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Magnetic resonance imaging of cartilage and cartilage repair
Clinical Radiology (2004) 59, 674–689
REVIEW
Magnetic resonance imaging of cartilage and cartilage repair K.L. Verstraetea,*, F. Almqvistb, P. Verdonkb,c,d, G. Vanderschuerena, W. Huyssea, R. Verdonkb, G. Verbruggec Departments of aRadiology, bOrthopaedic Surgery, cRheumatology, and dAspirant researcher FWO Vlaanderen, Ghent University Hospital, De Pintelaan 185, Gent, Belgium Received 12 September 2003; received in revised form 11 January 2004; accepted 19 January 2004
KEYWORDS Magnetic resonance (MR); Cartilage, articular; Cartilage, repair procedures; Knee, MR imaging; Knee, surgery; Contrast media
Magnetic resonance (MR) imaging of articular cartilage has assumed increased importance because of the prevalence of cartilage injury and degeneration, as well as the development of new surgical and pharmacological techniques to treat damaged cartilage. This article will review relevant aspects of the structure and biochemistry of cartilage that are important for understanding MR imaging of cartilage, describe optimal MR pulse sequences for its evaluation, and review the role of experimental quantitative MR techniques. These MR aspects are applied to clinical scenarios, including traumatic chondral injury, osteoarthritis, inflammatory arthritis, and cartilage repair procedures. q 2004 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Structure and biochemistry of articular cartilage Hyaline cartilage consists of chondrocytes and a large extracellular matrix, composed primarily of water (75%) with electrolytes (mainly sodium), collagen II fibrils (20%) and highly negatively charged, osmotically active aggregates of proteoglycans (5%) (Fig. 1). A well-organized, multilayered structure provides a high load-bearing capacity, high compressive stiffness and smooth surface to the cartilage, which permits frictionless gliding. An irregularly delineated subchondral bone plate locks the deepest calcified layer of the hyaline cartilage, to avoid dehiscence due to shearing forces. The subchondral bone is a strong shock and load absorber, which is highly vascularized. Some of the arterial terminal branches of the *Guarantor and correspondent: K. L. Verstraete, Department of Radiology, Ghent University Hospital, De Pintelaan 185, B9000 Gent, Belgium. Tel.: þ 32-9-240-2912; fax: þ32-9-2404969. E-mail address: [email protected]
subchondral bone plate penetrate the subchondral bone plate and provide nutrients to the calcified cartilage. The tidemark is the irregular junction between the calcified cartilage and the more superficial, thick radial zone, where collagen II fibrils are oriented vertically. These collagen fibres are anchored in the calcified cartilage. Immediately above the radial zone is the transitional zone, where the collagen fibrils have an arch-like configuration. The superficial zone contains tangentially, parallel-oriented collagen fibres, flat chondrocytes, proteoglycans and abundant water. The water content is maximal in the superficial zone and decreases slightly towards the bone. Proteoglycan concentration increases in the deepest layers. The number of chondrocytes is higher in the radial zone than in the transitional and superficial zone.
MR imaging of articular cartilage Cartilage damage may start from the articular surface (e.g. superficial fissuring) or deep within
0009-9260/$ - see front matter q 2004 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.crad.2004.01.012
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Figure 1 Structure and biochemistry of articular cartilage. Hyaline cartilage consists of a multi-layered structure with chondrocytes and a large extracellular matrix, composed primarily of water with electrolytes, collagen II fibrils and highly negatively charged, aggregates of proteoglycans. At the bottom, an irregularly delineated, highly vascularized subchondral bone plate locks the deepest calcified layer of the hyaline cartilage. The tidemark is the irregular junction between the calcified cartilage and the more superficial, thick radial zone, where collagen II fibrils are orientated vertically. These collagen fibres are anchored in the calcified cartilage. Immediately above the radial zone is the transitional zone, where the collagen fibrils have an arch-like configuration. The superficial zone contains tangentially, parallel-oriented collagen fibres, flat chondrocytes, proteoglycans and abundant water.
the cartilage, with disruption of the collagen framework, allowing the proteoglycans to increase the hydration of cartilage, leading to cartilage thickening and softening. The MR classification system to grade cartilage lesions, described by Yulish et al., is based on the arthroscopic classification of Outerbridge.1,2 Grade 1 corresponds to thickening and softening, without morphologic defect. Grade 2 involves superficial fissuring or fibrillation of the articular surface, or shallow ulceration or erosion composing less than 50% of the total thickness of the cartilage. Grade 3 is a partial-thickness defect of more than 50%, but less than 100%, of the cartilage thickness. A grade 3 lesion does not extend to the underlying bone, whereas a grade 4 lesion is a high-grade lesion with full-thickness cartilage defect extending to the underlying bone (Table 1). An optimal MR pulse sequence for evaluation of cartilage should be able to: 1. show changes in the subchondral bone plate and display the exact thickness of the subchondral bone plate without magnetic susceptibility; 2. detect bone marrow oedema, subchondral cysts and granulation tissue; 3. detect changes in the internal structure (disruption of the collagen framework) and biochemical
composition of articular cartilage (mainly depletion of proteoglycans and increase of water content), with high contrast between normal and abnormal cartilage, both in deep and superficial layers; 4. sharply delineate superficial and deep defects in the articular cartilage; 5. display cartilage with an optimal contrast resolution, high spatial resolution and/or allow segmentation, volume calculation and three-dimensional (3D) display. Currently, three imaging sequences allow good morphologic evaluation of cartilage and chondral abnormalities. The proton-density and T2-weighted fast spin-echo (FSE) sequence, the fat-suppressed, T1-weighted, 3D spoiled gradient-echo (GRE) sequence and the 3D double echo steady state (3D-DESS) sequence have demonstrated excellent sensitivity for detection of grade 2, 3 and 4 chondral lesions. Both proton-density and T2-weighted FSE images with or without fat suppression have been shown to be accurate in the detection of chondral abnormalities, with sensitivity of 73 –87% and specificity of 79 – 94%.3 – 6 In these sequences, articular cartilage shows lower signal intensity than adjacent fluid,
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Table 1 Arthroscopic and MR classification system to grade cartilage lesions Arthroscopic classification
MR classification
Grade 0 Grade 1 Grade 2
Grade 0 Grade 1 Grade 2
Grade 3 Grade 4
Normal Softening, without morphologic defect Superficial blistering or fraying; erosion or ulceration of less than 50% Partial-thickness defect of more than 50% but less than 100% Ulceration and bone exposure
and the subchondral bone is visualized well (Fig. 2). Even in the absence of fluid, the borders of the cartilage are readily visible.6 Moreover, these images can be obtained in a short acquisition time (4 – 5 min) with high resolution, and also allow simultaneous evaluation of other structures in the knee, such as menisci, ligaments and tendons. Therefore, in routine clinical practice, proton density and T2-weighted FSE images are usually sufficient. Without fat suppression, the soft tissues, like menisci, tendons and ligaments are well displayed, in contrast to fat-suppressed FSE images, which are better for detection of bone marrow oedema. As the deepest cartilage layers are not displayed well, overestimation of the depth of a cartilage lesion may occur. Therefore in selected cases the longer, high-resolution 3D techniques are necessary, and will have to be performed immediately after deep cartilage lesions have been detected on the FSE images. In our experience, for detection of grade 2 lesions, fat-suppressed FSE sequences have equal sensitivity to the 3D sequences and are slightly better than FSE sequences without fat suppression. Thin-partitioned, fat-suppressed 3D-spoiled GRE images, either using selective fat suppression (e.g. fat-suppressed 3D-SPGR) or selective water excitation (we; e.g. FLASH-3D we; DESS-3D we) (Fig. 2d and e), provide higher resolution and greater contrast to evaluate cartilage, but require longer acquisition times (7 – 10 min), and are more vulnerable to magnetic susceptibility and metallic artefacts. In fat-suppressed 3D-SPGR and FLASH-3D we, articular cartilage has a very high signal intensity, joint fluid has an intermediate to low signal intensity, and subchondral bone and bone marrow are dark. Sensitivity and specificity for detection of cartilage lesions have been reported to be 75 – 85% and 95 – 97%, respectively.7 – 10 Visualization of deep cartilage layers and focal loss of trabecular bone is much better on 3D-fat-suppressed GRE images than on FSE images. These two fat-suppressed 3D sequences allow high-quality multiplanar reconstructions (MPR),
Grade 3 Grade 4
Normal Normal contour ^ abnormal signal Superficial fraying; erosion or ulceration of less than 50% Partial-thickness defect of more than 50% but less than 100% Full-thickness cartilage loss
which are useful for evaluating the patellar, trochlear or condylar surfaces with images perpendicular to the curved articular surface (Figs. 2d, e and 4b). Moreover, the thin-section volume acquisitions allow segmentation and accurate 3D reconstructions of articular cartilage (Fig. 3). However, quantitative imaging of cartilage volume by summing the voxels containing cartilage using 3D imaging techniques is very time-consuming. Automated methods for segmentation need to be developed to make this tool clinically valuable. In the 3D-DESS sequence without fat suppression or water excitation, the cartilage has an intermediate signal intensity, but is well delineated because joint fluid exhibits very high signal intensity (Fig. 4). However, if not enough fluid is present delineation of cartilage may become difficult. Due to the intermediate signal intensity of cartilage, segmentation for volume measurements is not possible. The 3D-DESS sequence allows high-quality MPR and provides T1 contrast in the soft tissues (Fig. 5). Therefore it has the advantage of good visualization of menisci, muscles, ligaments and tendons, in contrast to the fat-suppressed 3D-SPGR; FLASH-3D we; DESS-3D we, that can only be used to evaluate the cartilage, because all other tissues are dark and contrast is low. Early cartilage degeneration (grade 1) cannot be reliably imaged using any of these sequences, and therefore novel MR imaging techniques that are sensitive to subtle structural and biochemical changes that occur early in the course of articular cartilage degeneration, before gross morphologic changes become apparent, are being developed.11 Very high-resolution MR images of articular cartilage demonstrate a multilaminar appearance that can be related to the individual histological layers of articular cartilage. In routine clinical MR imaging demonstration of this multilaminar appearance is not possible, because: 1. partial volume artefacts occur when multiple histological layers of cartilage are contained within one imaging voxel;
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Figure 3 Cartilage thickness map of femoral condyle, displaying thickness of cartilage in a 3D reconstruction with a colour-encoded thickness scale. This image was created by semi-automated segmentation and extraction of high signal intensity voxels of cartilage from a thinsection volume acquisition (fat-suppressed 3D-SPGR image) using selective water excitation (we) (FLASH-3D we; 128 slices of 1 mm).
2. the orientation of the cartilage with respect to the main magnetic field affects the signal intensity by prolongation of the T2 relaxation on intermediate TE images. Due to the magic angle effect, the signal intensity of cartilage will be increased in areas where the radial zone is imaged at angles of 558; 3. truncation artefacts may create one or more thin, central bands of low signal intensity in the cartilage, and are commonly seen in fatsuppressed, T1-weighted 3D-SPGR images. Quantitative imaging of the structure and biochemical composition of cartilage might be interesting to detect early stages of chondromalacia and monitor effects of pharmacological therapy. The collagen matrix can be evaluated using T2 relaxation and magnetization transfer coefficient as markers. Proteoglycan depletion can be measured using diffusion imaging, sodium23 imaging, or by imaging Gd-DTPA uptake in cartilage 2 h after intravenous injection (dGEMRIC: delayed gadolinium-DTPA enhanced MR imaging of
Figure 4 High-quality axial reconstructions (MPR) of a 3D-DESS sequence without fat suppression (a) and a fatsuppressed 3D-SPGR sequence, using selective water excitation (we) (FLASH-3D we) through the femoropatellar joint, affected by grade 4 osteoarthritis. On the DESS image (a) the cartilage on the lateral facet has an intermediate signal intensity, and is well delineated because joint fluid exhibits very high signal intensity. Although the extensive cartilage loss at the medial facet is more conspicuous on the fat-suppressed 3D-SPGR image (b), the T1 contrast in the soft tissues provided by the 3DDESS sequence allows better visualization of the soft tissues.
Figure 2 Full-thickness (grade 4) traumatic chondral defect (arrow), with acutely angled margins (arrowheads). Arthroscopic view (a), proton density-weighted image (b), T2-weighted image (c) and fat-suppressed 3D-SPGR images, using selective water excitation (we) (FLASH-3D) in sagittal plane (d) and reconstructed in coronal plane (e). Cartilage is best visualized on the proton density-weighted image (light-grey) and on the GRE images (white). Fluid in the defect is most conspicuous on the T2-weighted image, where the cartilage is dark grey. Other articular structures (meniscus, tendon, capsule, muscle) are best seen on the proton density-weighted image.
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Figure 5 Coronal DESS-3D image shows cartilage thinning, superficial fraying and fissuring (chondromalacia grade 2 and 3) in the central third of the medial femoral condyle. In the inner aspect, the fluid extends down to the subchondral bone plate (chondromalacia grade 4). Normal ligaments and menisci are well visualized.
cartilage). These methods are all in the experimental phase, and still not available for daily clinical practice.11,12 The imaging techniques are listed in Table 2.
MR imaging of abnormal articular cartilage Isolated chondral lesions are found in 25% of arthroscopies.8 These lesions can be difficult to detect clinically, because they may masquerade as meniscal tears. As new surgical cartilage repair procedures have recently been developed, noninvasive detection of these lesions is important. Cartilage specific sequences, such as the protondensity and T2-weighted FSE sequence, the fatsuppressed, T1-weighted 3D-SPGR sequence and the 3D-DESS can be performed to detect isolated or more diffuse abnormal cartilage (traumatic chondral injury, osteoarthritis or inflammatory arthritis). However, detection of arthroscopic softening (grade 1) is not possible with routine MR imaging techniques, nor with the more cartilage-specific sequences. Artefacts, such as the magic angle effect, make it impossible to interpret a signal change as a grade 1 lesion. Therefore, in our opinion, only morphological changes (grades 2, 3 and 4) should be reported (Fig. 5). Apart from grading, the location of cartilage lesions is also important (Table 3). Cartilage lesions in load-bearing areas require different treatment and have worse prognosis than lesions in non-
Figure 6 Sagittal proton density-weighted (a) and fatsuppressed 3D-SPGR image (b) of a traumatic cartilage lesion. The sharply delineated cartilage defect and intracartilaginous fissure (arrows) are best seen on the GRE image, that also better shows the deepest cartilage layer.
weight-bearing areas. Besides grade and location, the size, shape and associated subchondral and ligamentous lesions should be reported.
Traumatic chondral injury Traumatic chondral injuries are solitary lesions with acutely angled margins, that can occur in the deep layers or at the surface of the cartilage (Figs. 2 and 6). Often these lesions are partial thickness or full-thickness tears, with associated subchondral bone marrow oedema. Assessment of the depth of the chondral defect is better on fat-suppressed 3D-GRE images than
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Table 2 MR methods for evaluation of cartilage Pulse sequences for routine clinical MR imaging of cartilage Pulse sequence
Signal of articular cartilage and fluid
Remarks
Proton density- and T2-weighted fast spin-echo ^ fat suppression Fat-suppressed T1-weighted spoiled gradient echo; fatsuppressed 3D-spoiled gradient echo/FLASH-3D we/3D-T1FFE WATSc DESS-3D
Articular cartilage has lower SI than fluid
Other joint structures readily visible
Articular cartilage has very high SI; fluid has low SI
High resolution and contrast; MPR possible; assessment of other joint structures not possible
Cartilage has intermediate SI; joint fluid has very high SI
DESS-3D we
Cartilage has intermediate SI; joint fluid has very high SI
High resolution and contrast; MPR possible; other joint structures readily visible High resolution and contrast; MPR possible; assessment of other joint structures possible
Quantitative MR techniques for evaluation of the structure and/or biochemical composition of cartilage Technique
Principle
Remarks
T1 or T2 relaxation rate Magnetization transfer (MT) Diffusion imaging
Measures T1 or T2 relaxation rate Measures magnetization transfer effect Measures diffusion coefficients
Sodium 23 nuclear MR imaging Gd-(DTPA)22 quantification with T1 relaxation measurements
Measures sodium concentration Measures distribution of Gd-(DTPA)22 in cartilage, 2 h after IV injection (dGEMRIC) Displays cartilage with high SI and greater contrast with fewer artefacts, by use of very short TE , 150ms
T2 affected by changes in collagen network MT affected by changes in collagen network Diffusion affected by changes in collagen network and proteoglycan loss Sodium concentration is marker for proteoglycan loss Represents proteoglycan concentration in cartilage
Projection reconstruction spiral imaging (PRS)
DEFT and 3D-DEFT DRIVESPIR (TSE-PD)
Cartilage has intermediate SI; joint fluid has very high SI
we and WATSc, water excitation; DESS, double echo in steady state; SI, signal intensity; SPGR, spoiled gradient recalled; T1-FFE, T1 fast field echo; PRS, projection reconstruction spiral imaging; SPIR, spectral pre-saturation with inversion recovery; DEFT, driven equilibrium Fourier transform; dGEMRIC, delayed gadolinium-DTPA enhanced MR imaging of cartilage.
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May be combined with spectroscopic analysis of water content; might be used to differentiate repair (fibro) cartilage from hyaline cartilage High resolution and contrast images of cartilage and other joint structures
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Table 3 Location of cartilage lesions Location of cartilage lesions Medial femoral condylea Lateral femoral condylea Medial tibial plateau Lateral tibial plateau Trochlea Patella a
Anterior 1/3 Anterior 1/3 Anterior 1/3 Anterior 1/3 Medial Medial facet
Central 1/3 Central 1/3 Central 1/3 Central 1/3 Median ridge
Posterior 1/3 Posterior 1/3 Posterior 1/3 Posterior 1/3 Lateral Lateral facet
With respect to weight-bearing areas of the femoral condyles.
on FSE images, because of better visualization of deep cartilage layers (Fig. 7). Chondral or osteochondral parts may be avulsed and cause locking, as in displaced meniscal tears.
In traumatic osteochondral lesions and osteochondritis dissecans, MR imaging (eventually MR arthrography) can evaluate the state of the over lying cartilage and differentiate between stable and
Figure 7 Sagittal proton density-weighted (a), T2-weighted (b) and fat-suppressed 3D-SPGR image (c), and coronal DESS 3D image (d) of a sharply delineated traumatic cartilage defect. Correct grading of the severity of the lesion as focal thinning, less than 50% of the total cartilage thickness is only possible on the fat suppressed GRE image (c), which better shows the deepest cartilage layer. Overestimation of the depth is largest on the T2-weighted image, followed by the proton density weighted image and limited on the DESS-3D image.
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K.L. Verstraete et al. unstable injury.13,14 Unstable osteochondral lesions are completely loose fragments, or lesions that are covered by cartilage that is torn and shows no continuity with normal neighbouring cartilage. Conversely stable lesions are covered by cartilage that is continuous with the normal surrounding articular cartilage (Fig. 8). Direct MR arthrography with injection of diluted gadolinium may improve joint assessment by helping to delineate intra-articular structures, separating otherwise closely-apposed structures, and filling potential spaces that lie within or communicate with the joint. This technique is most useful for evaluation of post-operative menisci and for assessing the stability of osteochondral lesions or detection of de-lamination after chondrocyte implantation, by demonstration of high signal of the contrast agent at the interface with the underlying bone. It is not routinely used for delineating traumatic articular cartilage defects, as routine sequences usually provide enough information and because after knee trauma there is often an accompanying effusion, which provides a natural arthrographic effect.
Osteoarthritis and inflammatory arthritis In osteoarthritis articular cartilage becomes thinner and degenerates with superficial fraying, deeper fissuring, ulceration and full-thickness loss of the joint surface (Figs. 4 and 5). Associated findings are formation of osteophytes, subchondral sclerosis, bone marrow changes and cyst formation.15 The early stages of superficial fraying and deeper fissuring are occasionally detected on MR images, whereas in the more advanced osteoarthritis, MR imaging reveals multiple areas of chondral thinning of varying size and depth, often at opposing articular surfaces, or near meniscal lesions.15 The margins of osteoarthritic areas have obtuse angles, in contrast to traumatic chondral lesions that show sharply angled margins. In inflammatory arthritis, cartilage thinning is uniform and diffuse, usually without focal defects, except where pannus erodes the cartilage and bone. Inflammatory changes occur in the subchondral bone, synovium and para-articular soft tissues (Fig. 9). Figure 8 Sagittal proton density-weighted (a) and fatsuppressed 3D-SPGR image (b) of a stable osteochondritis dissecans, covered by cartilage that is continuous with the normal surrounding articular cartilage. Focal subchondral bone resorption is only seen on the GRE image.
MR imaging of cartilage after surgery As surgical treatment of cartilage defects becomes more widely performed, there is an increased need
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Figure 9 Sagittal proton density-weighted (a) and fatsuppressed 3D-SPGR image (b) in a 16-year-old female with juvenile chronic arthritis (morbus Still). There is focal chondral thinning in the central third of the lateral femoral condyle (arrow). There is complete absence of cartilage where pannus erodes the bone (P).
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Figure 10 Coronal DESS-3D (a), fat-suppressed T1weighted image after intravenous contrast administration (b) and fat-suppressed 3D-SPGR image (c) 2 months after allograft chondrocyte implantation. There is enhancing subchondral bone marrow oedema (b) and a swollen periosteal membrane (arrowheads in a and c), that has a low signal intensity due to micrometallic artefacts after harvesting. Enhancing tissue (arrows in b) surrounds the central repair tissue that has a signal intensity resembling normal cartilage (asterisk).
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Figure 11 Sagittal proton density-weighted (a), T2-weighted (b) and fat-suppressed 3D-SPGR image (c) 3 months after allograft chondrocyte implantation and allograft lateral meniscal transplantation. The cultured allograft chondrocytes have filled the large cartilage defect (between arrowheads), except for the posterior part (white arrow), where there is still under-filling and incomplete edge integration. In c, the hypointense foci in the posterior part are due to micrometallic artefacts. There is an area of focal chondral thinning (black arrow) anterior to the transplantation area.
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Figure 12 Sagittal proton density-weighted (a) and fat-suppressed 3D-SPGR image (b) and coronal post-contrast fatsuppressed T1-weighted image (c) 2 months after allograft chondrocyte implantation. There is severe under-filling (arrow) of the defect (between arrowheads). There is a small enhancing area of subchondral bone marrow oedema (c).
for post-operative MR imaging. Imaging sequences used for post-operative evaluation are the same as for routine cartilage imaging mentioned above. However, it should be noted that intra-articular metallic hardware and micrometallic debris lead to magnetic susceptibility artefacts, which are more prominent in GRE sequences than in FSE sequences. Surgical techniques for cartilage repair have been developed because the two types of repair that exist to restore damaged cartilage in a joint are insufficient:16 (1) “intrinsic repair” with formation clumps or clones of chondrocytes that produce a cartilage matrix with disorganized collagen fibres and lower concentration of
proteoglycans of lower quality. (2) “Extrinsic repair” with ingrowth of fibrovascular tissue from the subchondral region into a cartilaginous defect, producing lesser quality repair cartilage with disorganized type I cartilage. Two of the more common cartilage repair procedures are autologous chondrocyte implantation (ACI), and autologous osteochondral transplantation (AOT). ACI was introduced in Sweden in 1994 for the treatment of full-thickness chondral defects of the knee.17 After arthroscopic harvesting 200 –300 mg healthy articular cartilage from a nonweight-bearing surface, the chondrocytes are cultured for about 4 weeks. In a second, open surgical
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Figure 13 Sagittal proton density-weighted (a) and coronal DESS-3D image (b) after autologous osteochondral transplantation. There is a good alignment in the coronal plane and focal depression in the sagittal plane (arrow). Along the margins of the osteochondral plugs there are micrometallic artefacts, that do not interfere significantly with the assessment of cartilage.
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Figure 14 Sagittal proton density-weighted (a) and fatsuppressed 3D-SPGR image (b) after autologous osteochondral transplantation. Although the osseous part of the osteochondral plug protrudes compared with the neighbouring subchondral bone (arrowheads), there is a good alignment of the cartilage of the graft with the neighbouring cartilage, because the plug was harvested in a donor area with thinner cartilage.
procedure, the cartilage defect is debrided to the subchondral bone, filled with the cultured suspension, and covered by a periosteal flap. After 3 months a hyaline-like cartilage repair tissue with
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type II collagen network and proteoglycans, as firm as native cartilage has formed. Recently, at our institution a one-stage variant of this procedure using cultured allograft chondrocytes instead of autologous chondrocytes has been developed. MR imaging has been shown to be accurate in the evaluation of the repair tissue, the subchondral bone and the interface between the repair tissue and the neighbouring native cartilage.18 – 20 Although micrometallic remnants may cause susceptibility artefacts in GRE sequences, these techniques can be used for follow-up in addition to the routine FSE sequences, because the artefacts are usually very small. After ACI the repair tissue heals in different stages. In the proliferative phase (0 – 8 weeks) soft, primitive repair tissue with a signal intensity like water fills the defect. Sometimes, associated subchondral bone marrow oedema and enhancement in the margin of the defect can be seen (Fig. 10). The subchondral bone plate is usually slightly irregular, especially when small perforations were made in the subchondral bone plate upon preparation of the implantation site. The depth of the defect is variable depending on what sort of defect has been filled, e.g. deep defect after treatment of osteochondritis dissecans and shallow defect after treatment of a traumatic cartilage lesion without bone involvement. In the transitional phase (3 – 6 months) more matrix is formed and the tissue is better defined on MR imaging, with a lower and sometimes inhomogeneous signal intensity (Fig. 11). There is progressive edge integration of the transplanted cartilage with the native cartilage. T2-weighted images are useful to differentiate persistent cartilage defects (filled with hyperintense joint fluid) from maturing cartilage (lower signal intensity). The bone marrow oedema progressively disappears in this period, but can last for 1 year. In the final, remodelling phase (6 – 18 months), there is further matrix remodelling and maturation to repair cartilage (mixture of hyaline-like and fibrous cartilage), with near-normal stiffness and hardness. The signal progressively changes to that of normal cartilage. Complete edge integration of the transplanted cartilage with the native cartilage may take up to 2 years. Edge integration is complete when no fluid signal is visualized any more between the native and transplanted cartilage and when both have the same signal intensity. MR imaging can demonstrate complications such as de-lamination of the repair tissue, hypertrophy of the repair tissue, and rarely loose fragments or under-filling of the defect and formation of
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intra-articular adhesions attached to the ACI grafts18 – 20 (Fig. 12). AOT is an articular resurfacing technique in which cylinders of autologous bone with overlying cartilage are harvested from a relatively nonweight-bearing area (donor site) into a similarly sized cored hole created within the articular defect to be treated (recipient site).18 – 20 MR imaging permits the evaluation of the graft incorporation, the vascularity of the grafts, the status of the subchondral bone, the thickness of the cartilage cover, the congruity of the articular surface, as well as the status of the donor site18,19,21 (Figs. 13 and 14). Bone marrow oedema is a normal, early postoperative finding. There is a larger extent of the bone marrow oedema when more grafts are transferred and impacted into the acceptor area (Fig. 15). As micrometallic artefacts usually occur in the bone along the margins of the osteochondral plugs, they do not interfere with interpretation of the cartilaginous component of the graft. Complications are formation of subchondral cystic cavities, subsidence of the graft, poor integration of the graft and incongruity of the articular surface (Fig. 13). Too deeply placed grafts may be overgrown by surrounding cartilage (Fig. 16). Other cartilage repair techniques are microfracture, fresh osteochondral allografting, and fixation of chondral flap tears and osteochondral lesions with biodegradable pins.19 In the microfracture technique small perforations are created in the subchondral bone plate after debridement of the cartilage defect.
Figure 15 Sagittal post-contrast fat-suppressed T1weighted image shows extensive early post-operative bone marrow oedema, because more grafts (arrows) were impacted into the acceptor area. There is also early postoperative synovitis with hydrops (asterisk).
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are used for fixation of chondral flap tears, osteochondral fractures and osteochondritis dissecans. These pins are visible on MR imaging as linear tracts of low signal intensity on T1-weighted images in the first 6 months after surgery. By 1 year, the tracts will become more conspicuous on T2weighted images due to resorption, and after 2 years they will become completely invisible. Focal chondral defects at the insertion sites of the pins and bone marrow oedema along the pin channels are normal post-operative findings.19
Conclusion MR imaging has become the primary technique for non-invasively evaluating cartilage and cartilage repair. Adequate selection of pulse sequences and thorough knowledge of the imaging findings and pitfalls are required to answer the questions of the referring physician and ultimately help the patient.
Acknowledgements Supported in part by FWO Vlaanderen Grant G.0186.03.
References Figure 16 Sagittal proton density-weighted (a) and fatsuppressed 3D-SPGR image (b) after autologous osteochondral transplantation. Native cartilage (arrowheads) overgrows a too deeply inserted osteochondral plug.
Fibrocartilaginous repair tissue will fill the defect. Early MR imaging shows subchondral bone marrow oedema. Later the defect is filled with repair cartilage. When failure occurs, the bone marrow oedema persists and the defect is incompletely filled with thinned and irregular repair tissue.19 In osteochondral allografting a shell of bone and cartilage harvested from a cadaver is transplanted to fill a full-thickness chondral or osteochondral lesion.19,22 For assessment of successful incorporation of the osteochondral allograft, the signal intensity of the graft marrow, the graft – host interface and the graft congruity have to be studied. Extensive and persistent oedema, thick interface with surrounding bone marrow of the host, and surface collapse indicate incomplete incorporation or rejection. Biodegradable pins composed of polydioxanone
1. Yulish BS, Montanez J, Goodfellow DB, et al. Chondromalacia patellae: assessment with MR imaging. Radiology 1987;164: 763—6. 2. Outerbridge RE. The etiology of chondromalacia patellae. J Bone Joint Surg Br 1961;43:752—67. 3. Potter HG, Linlater JM, Allen AA, Hannafin JA, Haa SB. MR imaging of articular cartilage of the knee: a prospective evaluation using fast spin-echo imaging. J Bone Joint Surg Am 1998;80:1276—84. 4. Broderick LS, Turner DA, Renfrew DL, Schnitzer TJ, Huff JP, Harris C. Severity of articular cartilage abnormality in patients with osteoarthritis: evaluation with fast spin-echo MR versus arthroscopy. AJR Am J Roentgenol 1994;162: 99—103. 5. Bredella MA, Tirman PFJ, Peterfy CG, et al. Accuracy of T2-weighted fast spin-echo MR imaging with fat saturation in detecting cartilage defects in the knee: comparison with arthroscopy in 130 patients. AJR Am J Roentgenol 1999;172: 1073—80. 6. Sonin AH, Pensy RA, Mulligan ME, Hatem S. Grading articular cartilage of the knee using fast spin-echo proton densityweighted MR imaging without fat suppression. AJR Am J Roentgenol 2002;179:1159—66. 7. Recht MP, Piraino DW, Paletta GA, et al. Accuracy of fatsuppressed three-dimensional spoiled gradient-echo FLASH MR imaging in the detection of patellofemoral articular cartilage abnormalities. Radiology 1996;198:209—12. 8. Disler DG, McCauley TR, Kelman CG, et al. Fat-suppressed three-dimensional spoiled gradient-echo MR imaging hyaline
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cartilage defects in the knee: comparison with standard MR imaging and arthroscopy. AJR Am J Roentgenol 1996;167: 127—32. Trattnig S, Mlyna ´rik V, Huber M, Ba-Ssalamah A, Puig S, Imhof H. Magnetic resonance imaging of articular cartilage and evaluation of cartilage disease. Invest Radiol 2000;35: 595—601. Ruehm S, Zanetti M, Romero J, Hodler J. MRI of patellar articular cartilage: evaluation of an optimized gradient-echo sequence (3D-DESS). J Magn Reson Imaging 1998;8:1246—51. Peterfy CG. Scratching the surface. Articular cartilage disorders in the knee. MRI Clin North Am 2000;8:409—30. Burnstein D, Bashir A, Gray M. MRI techniques in early stages of cartilage disease. Invest Radiol 2000;35:622—38. Kramer J, Stiglbauer R, Engel A, Prayer L, Imhof H. MR contrast arthrography (MRA) in osteochondritis dissecans. J Comput Assist Tomogr 1992;16:254—60. De Smet AA, Fisher DR, Graf BK, Lange RH. Osteochondritis dissecans of the knee: value of MR imaging in determining lesion stability and the presence of articular cartilage defects. AJR Am J Roentgenol 1990;155:549—53. Guermazi A, Zaim S, Taouli B, Miaux Y, Peterfy CG, Genant HG. MR findings in knee osteoarthritis. Eur Radiol 2003;13: 1370—86.
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16. Buckwalter JA, Mankin HJ. Articular cartilage. II. Degeneration and osteoarthrosis, repair, regeneration, and transplantation. J Bone Joint Surg [Am] 1997;79:612—32. 17. Brittberg M, Lindahl A, Nilsson A, et al. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 1994;331:889—95. 18. Winalski CS, Minas T. Evaluation of chondral injuries by magnetic resonance imaging: repair assessments. Oper Tech Sports Med 2000;8:108—19. 19. Alparslan L, Winalski C, Boutin R, Minas T. Postoperative magnetic resonance imaging of articular cartilage repair. Semin Musculoskelet Radiol 2001;5:345—63. 20. Alparslan L, Minas T, Winalski C. Magnetic resonance imaging of autologous chondrocyte implantation. Semin Ultrasound CT MRI 2001;22:341—51. 21. Sanders TG, Mentzer KD, Miller MD, et al. Autogenous osteochondral “plug” transfer for the treatment of focal chondral defects: postoperative MR appearance with clinical correlation. Skeletal Radiol 2001;30:570—8. 22. Sirlin CB, Brossman J, Boutin RD, et al. Shell osteochondral allografts of the knee: comparison of MR imaging findings and immunologic responses. Radiology 2001;219:35—43.
REVIEW
Magnetic resonance imaging of cartilage and cartilage repair K.L. Verstraetea,*, F. Almqvistb, P. Verdonkb,c,d, G. Vanderschuerena, W. Huyssea, R. Verdonkb, G. Verbruggec Departments of aRadiology, bOrthopaedic Surgery, cRheumatology, and dAspirant researcher FWO Vlaanderen, Ghent University Hospital, De Pintelaan 185, Gent, Belgium Received 12 September 2003; received in revised form 11 January 2004; accepted 19 January 2004
KEYWORDS Magnetic resonance (MR); Cartilage, articular; Cartilage, repair procedures; Knee, MR imaging; Knee, surgery; Contrast media
Magnetic resonance (MR) imaging of articular cartilage has assumed increased importance because of the prevalence of cartilage injury and degeneration, as well as the development of new surgical and pharmacological techniques to treat damaged cartilage. This article will review relevant aspects of the structure and biochemistry of cartilage that are important for understanding MR imaging of cartilage, describe optimal MR pulse sequences for its evaluation, and review the role of experimental quantitative MR techniques. These MR aspects are applied to clinical scenarios, including traumatic chondral injury, osteoarthritis, inflammatory arthritis, and cartilage repair procedures. q 2004 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Structure and biochemistry of articular cartilage Hyaline cartilage consists of chondrocytes and a large extracellular matrix, composed primarily of water (75%) with electrolytes (mainly sodium), collagen II fibrils (20%) and highly negatively charged, osmotically active aggregates of proteoglycans (5%) (Fig. 1). A well-organized, multilayered structure provides a high load-bearing capacity, high compressive stiffness and smooth surface to the cartilage, which permits frictionless gliding. An irregularly delineated subchondral bone plate locks the deepest calcified layer of the hyaline cartilage, to avoid dehiscence due to shearing forces. The subchondral bone is a strong shock and load absorber, which is highly vascularized. Some of the arterial terminal branches of the *Guarantor and correspondent: K. L. Verstraete, Department of Radiology, Ghent University Hospital, De Pintelaan 185, B9000 Gent, Belgium. Tel.: þ 32-9-240-2912; fax: þ32-9-2404969. E-mail address: [email protected]
subchondral bone plate penetrate the subchondral bone plate and provide nutrients to the calcified cartilage. The tidemark is the irregular junction between the calcified cartilage and the more superficial, thick radial zone, where collagen II fibrils are oriented vertically. These collagen fibres are anchored in the calcified cartilage. Immediately above the radial zone is the transitional zone, where the collagen fibrils have an arch-like configuration. The superficial zone contains tangentially, parallel-oriented collagen fibres, flat chondrocytes, proteoglycans and abundant water. The water content is maximal in the superficial zone and decreases slightly towards the bone. Proteoglycan concentration increases in the deepest layers. The number of chondrocytes is higher in the radial zone than in the transitional and superficial zone.
MR imaging of articular cartilage Cartilage damage may start from the articular surface (e.g. superficial fissuring) or deep within
0009-9260/$ - see front matter q 2004 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.crad.2004.01.012
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Figure 1 Structure and biochemistry of articular cartilage. Hyaline cartilage consists of a multi-layered structure with chondrocytes and a large extracellular matrix, composed primarily of water with electrolytes, collagen II fibrils and highly negatively charged, aggregates of proteoglycans. At the bottom, an irregularly delineated, highly vascularized subchondral bone plate locks the deepest calcified layer of the hyaline cartilage. The tidemark is the irregular junction between the calcified cartilage and the more superficial, thick radial zone, where collagen II fibrils are orientated vertically. These collagen fibres are anchored in the calcified cartilage. Immediately above the radial zone is the transitional zone, where the collagen fibrils have an arch-like configuration. The superficial zone contains tangentially, parallel-oriented collagen fibres, flat chondrocytes, proteoglycans and abundant water.
the cartilage, with disruption of the collagen framework, allowing the proteoglycans to increase the hydration of cartilage, leading to cartilage thickening and softening. The MR classification system to grade cartilage lesions, described by Yulish et al., is based on the arthroscopic classification of Outerbridge.1,2 Grade 1 corresponds to thickening and softening, without morphologic defect. Grade 2 involves superficial fissuring or fibrillation of the articular surface, or shallow ulceration or erosion composing less than 50% of the total thickness of the cartilage. Grade 3 is a partial-thickness defect of more than 50%, but less than 100%, of the cartilage thickness. A grade 3 lesion does not extend to the underlying bone, whereas a grade 4 lesion is a high-grade lesion with full-thickness cartilage defect extending to the underlying bone (Table 1). An optimal MR pulse sequence for evaluation of cartilage should be able to: 1. show changes in the subchondral bone plate and display the exact thickness of the subchondral bone plate without magnetic susceptibility; 2. detect bone marrow oedema, subchondral cysts and granulation tissue; 3. detect changes in the internal structure (disruption of the collagen framework) and biochemical
composition of articular cartilage (mainly depletion of proteoglycans and increase of water content), with high contrast between normal and abnormal cartilage, both in deep and superficial layers; 4. sharply delineate superficial and deep defects in the articular cartilage; 5. display cartilage with an optimal contrast resolution, high spatial resolution and/or allow segmentation, volume calculation and three-dimensional (3D) display. Currently, three imaging sequences allow good morphologic evaluation of cartilage and chondral abnormalities. The proton-density and T2-weighted fast spin-echo (FSE) sequence, the fat-suppressed, T1-weighted, 3D spoiled gradient-echo (GRE) sequence and the 3D double echo steady state (3D-DESS) sequence have demonstrated excellent sensitivity for detection of grade 2, 3 and 4 chondral lesions. Both proton-density and T2-weighted FSE images with or without fat suppression have been shown to be accurate in the detection of chondral abnormalities, with sensitivity of 73 –87% and specificity of 79 – 94%.3 – 6 In these sequences, articular cartilage shows lower signal intensity than adjacent fluid,
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Table 1 Arthroscopic and MR classification system to grade cartilage lesions Arthroscopic classification
MR classification
Grade 0 Grade 1 Grade 2
Grade 0 Grade 1 Grade 2
Grade 3 Grade 4
Normal Softening, without morphologic defect Superficial blistering or fraying; erosion or ulceration of less than 50% Partial-thickness defect of more than 50% but less than 100% Ulceration and bone exposure
and the subchondral bone is visualized well (Fig. 2). Even in the absence of fluid, the borders of the cartilage are readily visible.6 Moreover, these images can be obtained in a short acquisition time (4 – 5 min) with high resolution, and also allow simultaneous evaluation of other structures in the knee, such as menisci, ligaments and tendons. Therefore, in routine clinical practice, proton density and T2-weighted FSE images are usually sufficient. Without fat suppression, the soft tissues, like menisci, tendons and ligaments are well displayed, in contrast to fat-suppressed FSE images, which are better for detection of bone marrow oedema. As the deepest cartilage layers are not displayed well, overestimation of the depth of a cartilage lesion may occur. Therefore in selected cases the longer, high-resolution 3D techniques are necessary, and will have to be performed immediately after deep cartilage lesions have been detected on the FSE images. In our experience, for detection of grade 2 lesions, fat-suppressed FSE sequences have equal sensitivity to the 3D sequences and are slightly better than FSE sequences without fat suppression. Thin-partitioned, fat-suppressed 3D-spoiled GRE images, either using selective fat suppression (e.g. fat-suppressed 3D-SPGR) or selective water excitation (we; e.g. FLASH-3D we; DESS-3D we) (Fig. 2d and e), provide higher resolution and greater contrast to evaluate cartilage, but require longer acquisition times (7 – 10 min), and are more vulnerable to magnetic susceptibility and metallic artefacts. In fat-suppressed 3D-SPGR and FLASH-3D we, articular cartilage has a very high signal intensity, joint fluid has an intermediate to low signal intensity, and subchondral bone and bone marrow are dark. Sensitivity and specificity for detection of cartilage lesions have been reported to be 75 – 85% and 95 – 97%, respectively.7 – 10 Visualization of deep cartilage layers and focal loss of trabecular bone is much better on 3D-fat-suppressed GRE images than on FSE images. These two fat-suppressed 3D sequences allow high-quality multiplanar reconstructions (MPR),
Grade 3 Grade 4
Normal Normal contour ^ abnormal signal Superficial fraying; erosion or ulceration of less than 50% Partial-thickness defect of more than 50% but less than 100% Full-thickness cartilage loss
which are useful for evaluating the patellar, trochlear or condylar surfaces with images perpendicular to the curved articular surface (Figs. 2d, e and 4b). Moreover, the thin-section volume acquisitions allow segmentation and accurate 3D reconstructions of articular cartilage (Fig. 3). However, quantitative imaging of cartilage volume by summing the voxels containing cartilage using 3D imaging techniques is very time-consuming. Automated methods for segmentation need to be developed to make this tool clinically valuable. In the 3D-DESS sequence without fat suppression or water excitation, the cartilage has an intermediate signal intensity, but is well delineated because joint fluid exhibits very high signal intensity (Fig. 4). However, if not enough fluid is present delineation of cartilage may become difficult. Due to the intermediate signal intensity of cartilage, segmentation for volume measurements is not possible. The 3D-DESS sequence allows high-quality MPR and provides T1 contrast in the soft tissues (Fig. 5). Therefore it has the advantage of good visualization of menisci, muscles, ligaments and tendons, in contrast to the fat-suppressed 3D-SPGR; FLASH-3D we; DESS-3D we, that can only be used to evaluate the cartilage, because all other tissues are dark and contrast is low. Early cartilage degeneration (grade 1) cannot be reliably imaged using any of these sequences, and therefore novel MR imaging techniques that are sensitive to subtle structural and biochemical changes that occur early in the course of articular cartilage degeneration, before gross morphologic changes become apparent, are being developed.11 Very high-resolution MR images of articular cartilage demonstrate a multilaminar appearance that can be related to the individual histological layers of articular cartilage. In routine clinical MR imaging demonstration of this multilaminar appearance is not possible, because: 1. partial volume artefacts occur when multiple histological layers of cartilage are contained within one imaging voxel;
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Figure 3 Cartilage thickness map of femoral condyle, displaying thickness of cartilage in a 3D reconstruction with a colour-encoded thickness scale. This image was created by semi-automated segmentation and extraction of high signal intensity voxels of cartilage from a thinsection volume acquisition (fat-suppressed 3D-SPGR image) using selective water excitation (we) (FLASH-3D we; 128 slices of 1 mm).
2. the orientation of the cartilage with respect to the main magnetic field affects the signal intensity by prolongation of the T2 relaxation on intermediate TE images. Due to the magic angle effect, the signal intensity of cartilage will be increased in areas where the radial zone is imaged at angles of 558; 3. truncation artefacts may create one or more thin, central bands of low signal intensity in the cartilage, and are commonly seen in fatsuppressed, T1-weighted 3D-SPGR images. Quantitative imaging of the structure and biochemical composition of cartilage might be interesting to detect early stages of chondromalacia and monitor effects of pharmacological therapy. The collagen matrix can be evaluated using T2 relaxation and magnetization transfer coefficient as markers. Proteoglycan depletion can be measured using diffusion imaging, sodium23 imaging, or by imaging Gd-DTPA uptake in cartilage 2 h after intravenous injection (dGEMRIC: delayed gadolinium-DTPA enhanced MR imaging of
Figure 4 High-quality axial reconstructions (MPR) of a 3D-DESS sequence without fat suppression (a) and a fatsuppressed 3D-SPGR sequence, using selective water excitation (we) (FLASH-3D we) through the femoropatellar joint, affected by grade 4 osteoarthritis. On the DESS image (a) the cartilage on the lateral facet has an intermediate signal intensity, and is well delineated because joint fluid exhibits very high signal intensity. Although the extensive cartilage loss at the medial facet is more conspicuous on the fat-suppressed 3D-SPGR image (b), the T1 contrast in the soft tissues provided by the 3DDESS sequence allows better visualization of the soft tissues.
Figure 2 Full-thickness (grade 4) traumatic chondral defect (arrow), with acutely angled margins (arrowheads). Arthroscopic view (a), proton density-weighted image (b), T2-weighted image (c) and fat-suppressed 3D-SPGR images, using selective water excitation (we) (FLASH-3D) in sagittal plane (d) and reconstructed in coronal plane (e). Cartilage is best visualized on the proton density-weighted image (light-grey) and on the GRE images (white). Fluid in the defect is most conspicuous on the T2-weighted image, where the cartilage is dark grey. Other articular structures (meniscus, tendon, capsule, muscle) are best seen on the proton density-weighted image.
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Figure 5 Coronal DESS-3D image shows cartilage thinning, superficial fraying and fissuring (chondromalacia grade 2 and 3) in the central third of the medial femoral condyle. In the inner aspect, the fluid extends down to the subchondral bone plate (chondromalacia grade 4). Normal ligaments and menisci are well visualized.
cartilage). These methods are all in the experimental phase, and still not available for daily clinical practice.11,12 The imaging techniques are listed in Table 2.
MR imaging of abnormal articular cartilage Isolated chondral lesions are found in 25% of arthroscopies.8 These lesions can be difficult to detect clinically, because they may masquerade as meniscal tears. As new surgical cartilage repair procedures have recently been developed, noninvasive detection of these lesions is important. Cartilage specific sequences, such as the protondensity and T2-weighted FSE sequence, the fatsuppressed, T1-weighted 3D-SPGR sequence and the 3D-DESS can be performed to detect isolated or more diffuse abnormal cartilage (traumatic chondral injury, osteoarthritis or inflammatory arthritis). However, detection of arthroscopic softening (grade 1) is not possible with routine MR imaging techniques, nor with the more cartilage-specific sequences. Artefacts, such as the magic angle effect, make it impossible to interpret a signal change as a grade 1 lesion. Therefore, in our opinion, only morphological changes (grades 2, 3 and 4) should be reported (Fig. 5). Apart from grading, the location of cartilage lesions is also important (Table 3). Cartilage lesions in load-bearing areas require different treatment and have worse prognosis than lesions in non-
Figure 6 Sagittal proton density-weighted (a) and fatsuppressed 3D-SPGR image (b) of a traumatic cartilage lesion. The sharply delineated cartilage defect and intracartilaginous fissure (arrows) are best seen on the GRE image, that also better shows the deepest cartilage layer.
weight-bearing areas. Besides grade and location, the size, shape and associated subchondral and ligamentous lesions should be reported.
Traumatic chondral injury Traumatic chondral injuries are solitary lesions with acutely angled margins, that can occur in the deep layers or at the surface of the cartilage (Figs. 2 and 6). Often these lesions are partial thickness or full-thickness tears, with associated subchondral bone marrow oedema. Assessment of the depth of the chondral defect is better on fat-suppressed 3D-GRE images than
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Table 2 MR methods for evaluation of cartilage Pulse sequences for routine clinical MR imaging of cartilage Pulse sequence
Signal of articular cartilage and fluid
Remarks
Proton density- and T2-weighted fast spin-echo ^ fat suppression Fat-suppressed T1-weighted spoiled gradient echo; fatsuppressed 3D-spoiled gradient echo/FLASH-3D we/3D-T1FFE WATSc DESS-3D
Articular cartilage has lower SI than fluid
Other joint structures readily visible
Articular cartilage has very high SI; fluid has low SI
High resolution and contrast; MPR possible; assessment of other joint structures not possible
Cartilage has intermediate SI; joint fluid has very high SI
DESS-3D we
Cartilage has intermediate SI; joint fluid has very high SI
High resolution and contrast; MPR possible; other joint structures readily visible High resolution and contrast; MPR possible; assessment of other joint structures possible
Quantitative MR techniques for evaluation of the structure and/or biochemical composition of cartilage Technique
Principle
Remarks
T1 or T2 relaxation rate Magnetization transfer (MT) Diffusion imaging
Measures T1 or T2 relaxation rate Measures magnetization transfer effect Measures diffusion coefficients
Sodium 23 nuclear MR imaging Gd-(DTPA)22 quantification with T1 relaxation measurements
Measures sodium concentration Measures distribution of Gd-(DTPA)22 in cartilage, 2 h after IV injection (dGEMRIC) Displays cartilage with high SI and greater contrast with fewer artefacts, by use of very short TE , 150ms
T2 affected by changes in collagen network MT affected by changes in collagen network Diffusion affected by changes in collagen network and proteoglycan loss Sodium concentration is marker for proteoglycan loss Represents proteoglycan concentration in cartilage
Projection reconstruction spiral imaging (PRS)
DEFT and 3D-DEFT DRIVESPIR (TSE-PD)
Cartilage has intermediate SI; joint fluid has very high SI
we and WATSc, water excitation; DESS, double echo in steady state; SI, signal intensity; SPGR, spoiled gradient recalled; T1-FFE, T1 fast field echo; PRS, projection reconstruction spiral imaging; SPIR, spectral pre-saturation with inversion recovery; DEFT, driven equilibrium Fourier transform; dGEMRIC, delayed gadolinium-DTPA enhanced MR imaging of cartilage.
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May be combined with spectroscopic analysis of water content; might be used to differentiate repair (fibro) cartilage from hyaline cartilage High resolution and contrast images of cartilage and other joint structures
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Table 3 Location of cartilage lesions Location of cartilage lesions Medial femoral condylea Lateral femoral condylea Medial tibial plateau Lateral tibial plateau Trochlea Patella a
Anterior 1/3 Anterior 1/3 Anterior 1/3 Anterior 1/3 Medial Medial facet
Central 1/3 Central 1/3 Central 1/3 Central 1/3 Median ridge
Posterior 1/3 Posterior 1/3 Posterior 1/3 Posterior 1/3 Lateral Lateral facet
With respect to weight-bearing areas of the femoral condyles.
on FSE images, because of better visualization of deep cartilage layers (Fig. 7). Chondral or osteochondral parts may be avulsed and cause locking, as in displaced meniscal tears.
In traumatic osteochondral lesions and osteochondritis dissecans, MR imaging (eventually MR arthrography) can evaluate the state of the over lying cartilage and differentiate between stable and
Figure 7 Sagittal proton density-weighted (a), T2-weighted (b) and fat-suppressed 3D-SPGR image (c), and coronal DESS 3D image (d) of a sharply delineated traumatic cartilage defect. Correct grading of the severity of the lesion as focal thinning, less than 50% of the total cartilage thickness is only possible on the fat suppressed GRE image (c), which better shows the deepest cartilage layer. Overestimation of the depth is largest on the T2-weighted image, followed by the proton density weighted image and limited on the DESS-3D image.
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K.L. Verstraete et al. unstable injury.13,14 Unstable osteochondral lesions are completely loose fragments, or lesions that are covered by cartilage that is torn and shows no continuity with normal neighbouring cartilage. Conversely stable lesions are covered by cartilage that is continuous with the normal surrounding articular cartilage (Fig. 8). Direct MR arthrography with injection of diluted gadolinium may improve joint assessment by helping to delineate intra-articular structures, separating otherwise closely-apposed structures, and filling potential spaces that lie within or communicate with the joint. This technique is most useful for evaluation of post-operative menisci and for assessing the stability of osteochondral lesions or detection of de-lamination after chondrocyte implantation, by demonstration of high signal of the contrast agent at the interface with the underlying bone. It is not routinely used for delineating traumatic articular cartilage defects, as routine sequences usually provide enough information and because after knee trauma there is often an accompanying effusion, which provides a natural arthrographic effect.
Osteoarthritis and inflammatory arthritis In osteoarthritis articular cartilage becomes thinner and degenerates with superficial fraying, deeper fissuring, ulceration and full-thickness loss of the joint surface (Figs. 4 and 5). Associated findings are formation of osteophytes, subchondral sclerosis, bone marrow changes and cyst formation.15 The early stages of superficial fraying and deeper fissuring are occasionally detected on MR images, whereas in the more advanced osteoarthritis, MR imaging reveals multiple areas of chondral thinning of varying size and depth, often at opposing articular surfaces, or near meniscal lesions.15 The margins of osteoarthritic areas have obtuse angles, in contrast to traumatic chondral lesions that show sharply angled margins. In inflammatory arthritis, cartilage thinning is uniform and diffuse, usually without focal defects, except where pannus erodes the cartilage and bone. Inflammatory changes occur in the subchondral bone, synovium and para-articular soft tissues (Fig. 9). Figure 8 Sagittal proton density-weighted (a) and fatsuppressed 3D-SPGR image (b) of a stable osteochondritis dissecans, covered by cartilage that is continuous with the normal surrounding articular cartilage. Focal subchondral bone resorption is only seen on the GRE image.
MR imaging of cartilage after surgery As surgical treatment of cartilage defects becomes more widely performed, there is an increased need
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Figure 9 Sagittal proton density-weighted (a) and fatsuppressed 3D-SPGR image (b) in a 16-year-old female with juvenile chronic arthritis (morbus Still). There is focal chondral thinning in the central third of the lateral femoral condyle (arrow). There is complete absence of cartilage where pannus erodes the bone (P).
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Figure 10 Coronal DESS-3D (a), fat-suppressed T1weighted image after intravenous contrast administration (b) and fat-suppressed 3D-SPGR image (c) 2 months after allograft chondrocyte implantation. There is enhancing subchondral bone marrow oedema (b) and a swollen periosteal membrane (arrowheads in a and c), that has a low signal intensity due to micrometallic artefacts after harvesting. Enhancing tissue (arrows in b) surrounds the central repair tissue that has a signal intensity resembling normal cartilage (asterisk).
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Figure 11 Sagittal proton density-weighted (a), T2-weighted (b) and fat-suppressed 3D-SPGR image (c) 3 months after allograft chondrocyte implantation and allograft lateral meniscal transplantation. The cultured allograft chondrocytes have filled the large cartilage defect (between arrowheads), except for the posterior part (white arrow), where there is still under-filling and incomplete edge integration. In c, the hypointense foci in the posterior part are due to micrometallic artefacts. There is an area of focal chondral thinning (black arrow) anterior to the transplantation area.
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Figure 12 Sagittal proton density-weighted (a) and fat-suppressed 3D-SPGR image (b) and coronal post-contrast fatsuppressed T1-weighted image (c) 2 months after allograft chondrocyte implantation. There is severe under-filling (arrow) of the defect (between arrowheads). There is a small enhancing area of subchondral bone marrow oedema (c).
for post-operative MR imaging. Imaging sequences used for post-operative evaluation are the same as for routine cartilage imaging mentioned above. However, it should be noted that intra-articular metallic hardware and micrometallic debris lead to magnetic susceptibility artefacts, which are more prominent in GRE sequences than in FSE sequences. Surgical techniques for cartilage repair have been developed because the two types of repair that exist to restore damaged cartilage in a joint are insufficient:16 (1) “intrinsic repair” with formation clumps or clones of chondrocytes that produce a cartilage matrix with disorganized collagen fibres and lower concentration of
proteoglycans of lower quality. (2) “Extrinsic repair” with ingrowth of fibrovascular tissue from the subchondral region into a cartilaginous defect, producing lesser quality repair cartilage with disorganized type I cartilage. Two of the more common cartilage repair procedures are autologous chondrocyte implantation (ACI), and autologous osteochondral transplantation (AOT). ACI was introduced in Sweden in 1994 for the treatment of full-thickness chondral defects of the knee.17 After arthroscopic harvesting 200 –300 mg healthy articular cartilage from a nonweight-bearing surface, the chondrocytes are cultured for about 4 weeks. In a second, open surgical
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Figure 13 Sagittal proton density-weighted (a) and coronal DESS-3D image (b) after autologous osteochondral transplantation. There is a good alignment in the coronal plane and focal depression in the sagittal plane (arrow). Along the margins of the osteochondral plugs there are micrometallic artefacts, that do not interfere significantly with the assessment of cartilage.
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Figure 14 Sagittal proton density-weighted (a) and fatsuppressed 3D-SPGR image (b) after autologous osteochondral transplantation. Although the osseous part of the osteochondral plug protrudes compared with the neighbouring subchondral bone (arrowheads), there is a good alignment of the cartilage of the graft with the neighbouring cartilage, because the plug was harvested in a donor area with thinner cartilage.
procedure, the cartilage defect is debrided to the subchondral bone, filled with the cultured suspension, and covered by a periosteal flap. After 3 months a hyaline-like cartilage repair tissue with
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type II collagen network and proteoglycans, as firm as native cartilage has formed. Recently, at our institution a one-stage variant of this procedure using cultured allograft chondrocytes instead of autologous chondrocytes has been developed. MR imaging has been shown to be accurate in the evaluation of the repair tissue, the subchondral bone and the interface between the repair tissue and the neighbouring native cartilage.18 – 20 Although micrometallic remnants may cause susceptibility artefacts in GRE sequences, these techniques can be used for follow-up in addition to the routine FSE sequences, because the artefacts are usually very small. After ACI the repair tissue heals in different stages. In the proliferative phase (0 – 8 weeks) soft, primitive repair tissue with a signal intensity like water fills the defect. Sometimes, associated subchondral bone marrow oedema and enhancement in the margin of the defect can be seen (Fig. 10). The subchondral bone plate is usually slightly irregular, especially when small perforations were made in the subchondral bone plate upon preparation of the implantation site. The depth of the defect is variable depending on what sort of defect has been filled, e.g. deep defect after treatment of osteochondritis dissecans and shallow defect after treatment of a traumatic cartilage lesion without bone involvement. In the transitional phase (3 – 6 months) more matrix is formed and the tissue is better defined on MR imaging, with a lower and sometimes inhomogeneous signal intensity (Fig. 11). There is progressive edge integration of the transplanted cartilage with the native cartilage. T2-weighted images are useful to differentiate persistent cartilage defects (filled with hyperintense joint fluid) from maturing cartilage (lower signal intensity). The bone marrow oedema progressively disappears in this period, but can last for 1 year. In the final, remodelling phase (6 – 18 months), there is further matrix remodelling and maturation to repair cartilage (mixture of hyaline-like and fibrous cartilage), with near-normal stiffness and hardness. The signal progressively changes to that of normal cartilage. Complete edge integration of the transplanted cartilage with the native cartilage may take up to 2 years. Edge integration is complete when no fluid signal is visualized any more between the native and transplanted cartilage and when both have the same signal intensity. MR imaging can demonstrate complications such as de-lamination of the repair tissue, hypertrophy of the repair tissue, and rarely loose fragments or under-filling of the defect and formation of
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intra-articular adhesions attached to the ACI grafts18 – 20 (Fig. 12). AOT is an articular resurfacing technique in which cylinders of autologous bone with overlying cartilage are harvested from a relatively nonweight-bearing area (donor site) into a similarly sized cored hole created within the articular defect to be treated (recipient site).18 – 20 MR imaging permits the evaluation of the graft incorporation, the vascularity of the grafts, the status of the subchondral bone, the thickness of the cartilage cover, the congruity of the articular surface, as well as the status of the donor site18,19,21 (Figs. 13 and 14). Bone marrow oedema is a normal, early postoperative finding. There is a larger extent of the bone marrow oedema when more grafts are transferred and impacted into the acceptor area (Fig. 15). As micrometallic artefacts usually occur in the bone along the margins of the osteochondral plugs, they do not interfere with interpretation of the cartilaginous component of the graft. Complications are formation of subchondral cystic cavities, subsidence of the graft, poor integration of the graft and incongruity of the articular surface (Fig. 13). Too deeply placed grafts may be overgrown by surrounding cartilage (Fig. 16). Other cartilage repair techniques are microfracture, fresh osteochondral allografting, and fixation of chondral flap tears and osteochondral lesions with biodegradable pins.19 In the microfracture technique small perforations are created in the subchondral bone plate after debridement of the cartilage defect.
Figure 15 Sagittal post-contrast fat-suppressed T1weighted image shows extensive early post-operative bone marrow oedema, because more grafts (arrows) were impacted into the acceptor area. There is also early postoperative synovitis with hydrops (asterisk).
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are used for fixation of chondral flap tears, osteochondral fractures and osteochondritis dissecans. These pins are visible on MR imaging as linear tracts of low signal intensity on T1-weighted images in the first 6 months after surgery. By 1 year, the tracts will become more conspicuous on T2weighted images due to resorption, and after 2 years they will become completely invisible. Focal chondral defects at the insertion sites of the pins and bone marrow oedema along the pin channels are normal post-operative findings.19
Conclusion MR imaging has become the primary technique for non-invasively evaluating cartilage and cartilage repair. Adequate selection of pulse sequences and thorough knowledge of the imaging findings and pitfalls are required to answer the questions of the referring physician and ultimately help the patient.
Acknowledgements Supported in part by FWO Vlaanderen Grant G.0186.03.
References Figure 16 Sagittal proton density-weighted (a) and fatsuppressed 3D-SPGR image (b) after autologous osteochondral transplantation. Native cartilage (arrowheads) overgrows a too deeply inserted osteochondral plug.
Fibrocartilaginous repair tissue will fill the defect. Early MR imaging shows subchondral bone marrow oedema. Later the defect is filled with repair cartilage. When failure occurs, the bone marrow oedema persists and the defect is incompletely filled with thinned and irregular repair tissue.19 In osteochondral allografting a shell of bone and cartilage harvested from a cadaver is transplanted to fill a full-thickness chondral or osteochondral lesion.19,22 For assessment of successful incorporation of the osteochondral allograft, the signal intensity of the graft marrow, the graft – host interface and the graft congruity have to be studied. Extensive and persistent oedema, thick interface with surrounding bone marrow of the host, and surface collapse indicate incomplete incorporation or rejection. Biodegradable pins composed of polydioxanone
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