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Imaging of Failed Cartilage Repair
Journal Pre-proof
Imaging of Failed Cartilage Repair Alissa J. Burge MD , Hollis G. Potter MD PII: DOI: Reference:
S1060-1872(19)30084-X https://doi.org/10.1016/j.otsm.2019.150710 YOTSM 150710
To appear in:
Operative Techniques in Sports Medicine
Please cite this article as: Alissa J. Burge MD , Hollis G. Potter MD , Imaging of Failed Cartilage Repair, Operative Techniques in Sports Medicine (2019), doi: https://doi.org/10.1016/j.otsm.2019.150710
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier Inc.
Imaging of Failed Cartilage Repair
Alissa J Burge, MD (Corresponding author) Hospital for Special Surgery 535 E 70th St, New York, NY 10021 Department of Radiology and Imaging (MRI) MRI Laboratory (212)606-1857 [email protected]
Hollis G Potter, MD Hospital for Special Surgery 535 E 70th St, New York NY 10021 Department of Radiology and Imaging MRI Laboratory (212)606-1023 [email protected]
Conflict of Interest Statement Both authors receive funding from NIH/NIAMS Grants RO1AR064840 and 1R01AR066069-01A1. The authors’ institution receives research support from General Electric Healthcare.
1
Abstract
Osteoarthritis is an extremely common cause of morbidity throughout the world. Current standard of care treatment strategies focus on repairing or replacing articular cartilage defects, as methods of regenerating articular cartilage are still largely in experimental stages. Cartilage repair techniques, typically used in the setting of focal defects, allow replacement of focally damaged cartilage utilizing either donor tissue or the patient’s own tissue, with the goal of restoring normal articular surface function, preventing further joint damage, and improving clinical symptoms. While these procedures succeed in many, as with any intervention, outcomes are not universally successful. Imaging can be useful in evaluation of patients following cartilage repair, providing assessment of technical success, evolution of graft tissue over time, and potential complications. Magnetic resonance imaging, in particular, allows comprehensive imaging evaluation of repair tissue, as well as potential alternate causes of clinical symptoms. Familiarity with the expected imaging appearance of cartilage repair, and particularly the expected evolution over time, is crucial for the accurate interpretation of imaging following cartilage repair.
Keywords Cartilage Repair Magnetic Resonance Imaging Osteoarthritis
2
Introduction
Osteoarthritis is one of the most common causes of disability in the world, contributing to extensive human and economic burden (1). Current standard of care treatment strategies focus on replacing worn articular surfaces, as methods of regenerating chondral tissue are still largely at an experimental stage. Approaches to cartilage replacement vary depending on the degree of damage. While extensive damage generally requires replacement of an entire compartment or joint utilizing an arthroplasty, more focal damage can be addressed utilizing cartilage repair techniques, allowing preservation of an individual’s remaining undamaged articular surfaces and bone stock.
Cartilage repair strategies depend on the degree, extent, and location of chondral damage. Relatively mild damage confined to a small area may be addressed with techniques such as microfracture and drilling, while more severe and/or extensive defects typically require some type of graft (2). Imaging is useful in evaluating the degree and extent of existing chondral damage, facilitating appropriate preoperative planning, and is also useful in postoperative assessment of repair tissue and potential complications.
A variety of imaging modalities are available for evaluation of patients who have had or who are potential candidates for cartilage repair. While radiographs and computed tomography do not provide direct visualization of the articular cartilage, they can be helpful in evaluating osseous anatomy and alignment. Ultrasound tends to be less useful in a diagnostic capacity in this area but can be utilized for image-guided interventions such as diagnostic and therapeutic injections. Magnetic resonance imaging (MRI) provides excellent evaluation of the articular cartilage, with optimal sequencing allowing assessment of both chondral signal and morphology. MRI signal depends on the biochemical environment of protons within a given tissue, with differential tissue contrast arising from variability in tissue composition and structure, which results in differences in energy transfer characteristics, and therefore differences in proton relaxation time following the application of a radiofrequency pulse during MR image acquisition (3).
Normal articular cartilage is organized in layers, each of which possesses predictable signal characteristics on MRI due to differential distribution of proteoglycan and orientation of collagen fibers between the layers (4) (Fig 1). Early degeneration of articular cartilage results in depletion of matrix elements and disorganization of collagen fibers, with corresponding prolongation of MR relaxation times and loss of normal chondral stratification on MR images (5). More advanced chondral wear can yield areas of fissuring, flap formation, partial defects, and exposed bone, as well as osteophytes related to osseous remodeling, and synovitis related to joint irritation.
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MR Imaging assessment of cartilage repair
Clinical MR imaging algorithms for evaluation of the articular cartilage should ideally include sequences optimized for evaluation of chondral stratification and morphology. At the authors’ institution, clinical joint imaging protocols generally consist of three planes of high resolution proton density (PD) weighted fast spin echo (FSE) images, plus a single plane of fat suppressed fluid sensitive images, such as inversion recovery (IR). Additional more advanced, quantitative sequences may be added as appropriate. Parametric mapping sequences such as T1rho and T2 mapping allow sensitive quantitative assessment of chondral matrix elements such as proteoglycan and collagen (6). Advanced metal suppression sequences such as MAVRIC (multiacquisition variable resonance image combination) and SEMAC (slice encoding metal artifact correction) may be useful in postoperative patients with metallic fixation devices (7). Zero echo time (ZTE) imaging is an MR sequence capable of yielding CT-like images, allowing assessment of mineralized bone without the use of ionizing radiation (8, 9).
Interpretation of chondral integrity on grayscale clinical MR images involves description of the severity and extent of chondral signal and stratification changes, chondral defects, and exposed bone. Interpretation of postoperative imaging requires knowledge of the procedure performed and of the postoperative timeframe. Imaging findings that may be worrisome in the late postoperative period, such as extensive edema, may be normal in the early postoperative period.
Various grading systems are available for evaluation of cartilage repair. For example, Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) is utilized for the evaluation of chondrocyte based repair techniques such as autologous and allograft chondrocyte implantation, with assessment of nine MR imaging variables, while Osteochondral Allograft MRI Scoring System (OCAMRISS) allows assessment of osteochondral graft repairs based on 13 MR imaging variables (10-12) (Table 1). Both systems incorporate features for evaluation of the chondral repair tissue, such as graft signal, degree of fill, and surface congruity, as well as of the subchondral bone, with the OCAMRISS score also including features pertaining to osseous implant integration. Both systems provide a semi-quantitative numeric score based on the grades of each of their individual components.
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As previously described, parametric mapping of articular cartilage can provide sensitive detection of early chondral matrix depletion. A number of parametric sequences exist. At the authors’ institution, T1rho and T2 mapping are performed; these sequences are sensitive to changes in proteoglycan content and collagen orientation, respectively. Acquisition of images at multiple echo times allows calculation of relaxation times on a pixel by pixel basis. Regions of interest may be placed over chondral repair tissue, in order to calculate the mean relaxation time within graft tissue and compare this with relaxation within normal articular cartilage in a quantitative fashion (6, 13). Additional advanced quantitative techniques for evaluation of articular cartilage include DGEMRIC, which requires the administration of intravenous contrast, sodium MR, which requires specialized hardware, and GAG-CEST, which is best performed at a 7 Tesla field strength (14, 15).
Marrow Stimulation Marrow stimulation techniques, including microfracture, drilling, and abrasion, involve causing mild damage to the subchondral bone beneath a site of cartilage loss, in order to provoke a reparative response with the formation of repair tissue, typically fibrocartilage, over the area. This tissue generally lacks the normal imaging characteristics of hyaline articular cartilage, as the repair tissue does not form normal chondral layers and therefore lacks the typical stratification on imaging. Additionally, as the reparative response provoked by marrow stimulation techniques involves pluripotential stem cells, this response may also result in the formation of bone in addition to chondral tissue, contributing to osseous overgrowth of the subchondral plate (16, 17).
Imaging features of particular relevance in patients post marrow stimulation include the degree of lesion fill, as well as the presence and degree of any osseous proliferative change. Excessive osseous overgrowth at the repair site may result in a stress riser with potential to damage not only the repair site but also to the apposed articular surface. Imaging evidence of a favorable outcome includes complete fill of the defect by repair tissue, which typically lacks the stratified appearance of normal articular cartilage, as well as mild subchondral irregularity without prominent osseous overgrowth (Fig 2). Features suggesting a poor outcome include incomplete lesion fill and persistent or increasing subchondral edema (Fig 3), as well as prominent productive bone formation .
Chondrocyte based techniques Chondrocytes may be used to repair focal chondral defects, and may be harvested from the patient or from a donor. Autologous chondrocyte implantation (ACI) involves harvesting and culturing the patient’s own chondrocytes, with subsequent re-implantation of the cultured tissue into the site of desired chondral repair; originally, the technique involved sealing the repair with a periosteal patch, but ultimately evolved to incorporate scaffolds within which the chondrocytes are cultured and subsequently implanted (18). Allograft
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chondrocytes are also utilized for repair of chondral defects; chondral fragments containing viable chondrocytes from juvenile donors are implanted into a chondral defect and fixed in place with fibrin glue (16, 17, 19-21). Relevant imaging features in patients following chondrocyte based repair techniques include the degree of lesion fill, congruency of the articular surface, signal characteristics of the repair tissue, and integrity of the periosteal seal (if present). The appearance of the repair tissue typically evolves over time, in terms of both the signal intensity of the graft, and the degree of lesion fill. Early in the postoperative course, repair tissue tends to appear hyperintense due to disorganization and water content (Fig 4), and may also fail to completely fill the chondral defect, as graft tissue is expected to hypertrophy to a certain extent over time. As the postoperative time course progresses, signal intensity should decrease as tissue becomes more organized, and lesion fill should increase in the cases where fill was incomplete. Optimally, in addition to normalization of signal intensity, repair tissue may develop a degree of normal stratification as the chondrocytes organize into the distinct layers typical of hyaline articular cartilage (Fig 5). Poor prognostic signs include failure of fill or decreasing fill over time, in addition to persistent or increasing hyperintensity of repair tissue (16, 17, 19) (Fig 6).
Osteochondral grafts Osteochondral repairs may be performed utilizing autograft, allograft, or synthetic tissue (2, 22). Autografts, being harvested from the patient, are generally utilized for smaller repairs, while allografts may be used for larger repairs (5, 23). Synthetic plugs are most commonly used to fill autograft donor sites in order to restore the congruity of the articular surface following graft harvest (24). Because these osteochondral grafts consist of both osseous and chondral phases, imaging assessment of graft health necessitates attention to imaging characteristics of both phases. Again, postoperative timeframe is a crucial consideration in determining whether a particular imaging finding is expected or worrisome. Early in the postoperative time course, the osseous portion of the graft and surrounding native bone typically display signal hyperintensity, and a discernable margin is present between the graft and adjacent native bone. Over time, signal hyperintensity should decrease, and crossing trabeculae should bridge the area along the graft interfaces as osseous incorporation occurs (Fig 7). Due to the difficulty of matching the exact chondral thickness and contour of the repair site and graft, areas of mild subchondral step-off are not unexpected; however, the chondral articular surface should be congruent, with restoration of the articular contour. Additionally, discernable margins are typically present at the interfaces between repair and native chondral tissue; however, the tissue should be closely apposed, without a frank fluid cleft or gap. In autografts and allografts, because the repair tissue is true hyaline articular cartilage, the signal characteristics and organization of the repair tissue should closely approximate the patient’s normal articular cartilage (Figs 8,9). In patients who have undergone repair utilizing an autograft, the status of the donor site is also of concern (25). Often, particularly in the setting of large defects, the donor site is backfilled utilizing allograft or synthetic tissue in order to restore the articular surface contour and prevent damage to adjacent cartilage (Fig 10).
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Conclusion
MR imaging is useful in cartilage repair patients, both in terms of preoperative planning and postoperative follow up. Following cartilage repair, imaging can provide assessment of the status of the repair, as well as potential alternate causes of symptoms in patients with persistent or new onset of pain. Routine clinical imaging sequences are capable of providing detailed evaluation regarding lesion fill, surface congruity, and incorporation of repair tissue, while more advanced parametric sequences provide more sensitive, quantitative assessment of the quality of repair tissue. Familiarity with relevant imaging features, and in particular the expected evolution of postsurgical appearance over time, is critical in facilitating accurate interpretation of imaging in patients following cartilage repair.
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Figure Legends
Figure 1: Normal hyaline articular cartilage demonstrates a stratified gray scale appearance on certain MRI sequences, such as this axial proton density (PD) weighted fast spin echo (FSE) image of the patella, due to differences in collagen orientation and proteoglycan content between the layers. The deepest layer, the tidemark (TM) is comprised of calcified cartilage and is therefore hypointense and indistinguishable from the subchondral plate. The next deepest layer, the radial zone (RA) is comprised of highly ordered parallel collagen fibers, which facilitate energy transfer and therefore result in short relaxation times with relative hypointensity on images. The next layer is the transitional zone (TR), in which the collagen fibers are oriented in arcades, which results in slightly longer relaxation times and higher signal intensity on images. The most superficial layer, the lamina splendens (LS), is comprised of horizontally oriented parallel collagen fibers, resulting in relative hypointensity on images.
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Figure 2: Coronal PD FSE image (A) in a 33 year-old man demonstrates focal area of full thickness chondral loss (black arrow) over the inner aspect of the medial tibial plateau. Subsequent coronal PS FSE image (B) obtained 1 year following microfracture demonstrates inhomogeneous repair tissue (black arrow) which lacks normal chondral stratification, and subjacent subchondral irregularity with mild productive bone formation; however, there is overall good fill of the lesion with restoration of the articular surface contour.
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Figure 3: Sagittal IR (A) and PD FSE (B) images in a 35 year-old woman demonstrate full thickness chondral loss (white arrowheads) over the posterior aspect of the lateral femoral condyle. Sagittal IR (C) and PD FSE (D) images obtained 1 year following microfracture demonstrate incomplete fill with persistent exposed bone (white arrowhead), with interval increase in subchondral edema, and subchondral irregularity with mild productive bone formation related to the procedure.
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Figure 4: Axial PD FSE (A) image in a 28 year-old woman demonstrates full thickness chondral loss (black arrowhead) over the patellar apex and inner aspect of the lateral facet. Subsequent axial PD FSE image (B) obtained 5 months following MACI demonstrates excellent fill of the defect with uniformly hyperintense repair tissue (black arrowhead), a normal appearance for the postoperative timeframe.
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Figure 5: Axial T2 Fat saturated image (A) in a 25 year-old woman following lateral patellar dislocation demonstrates focal full thickness chondral defect over the patellar apex (white arrowhead). Axial PD FSE (B) obtained 3 months following cartilage repair utilizing particulated juvenile allograft cartilage demonstrates excellent fill by hyperintense repair tissue, a normal appearance for the postoperative timeframe. Subsequent axial PD FSE (C) and T2 map (D) performed 6 months following cartilage repair demonstrate persistent graft hyperintensity with corresponding prolongation of relaxation times on mapping images (white arrowheads); however, graft signal appears decreased compared to the prior study. Axial PD FSE (E) and T2 map at one year following repair demonstrate further interval decrease in graft intensity, with reduced prolongation of relaxation times and the suggestion of developing chondral stratification (white arrowheads) on mapping images.
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Figure 6: Axial PD FSE (A) in a 25 year-old woman 3 months following chondral repair utilizing particulated juvenile allograft cartilage demonstrates hyperintense material within the full thickness defect over the patellar apex and lateral facet (black arrowhead). While this may be a normal appearance for the postoperative timeframe, there is the suggestion of a subtle, relatively hyperintense linear cleft along the base of the repair site (white arrowhead) parallel to the subchondral plate. Subsequent axial PD FSE image (B) obtained 3 months later demonstrates increased signal of material within the defect with apparent decrease in fill, suggesting partial delamination of the graft.
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Figure 7: Sagittal Zero Echo Time (ZTE) image (A) in a 51 year-old woman 6 months following lateral femoral condyle osteochondral allograft demonstrates areas of trabeculae bridging the interface between the graft and underlying native bone (black arrowheads). Subsequent ZTE image (B) obtained 1 year following repair demonstrates progressive osseous incorporation (black arrowheads).
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Figure 8: Sagittal IR (A) and PD FSE (B) images in a 25 year-old man, 2 years status post osteochondral allograft repair of the lateral femoral condyle, demonstrate overall good fill with restoration of the articular surface contour. However, there is pronounced edema with areas of cystic change along the osseous portion of the graft, and a focal linear hyperintense cleft subjacent to the subchondral plate along the posterior aspect of the graft (white arrowheads), suggesting impending delamination. Subsequent sagittal IR (C) and PD FSE (D) images obtained one year later demonstrate interval complete delamination with in situ osteochondral fragment (white arrowheads). Sagittal IR (E) and PD FSE (F) images obtained 6 months following revision allograft repair demonstrate excellent fill by repair tissue with restoration of the articular surface contour (white arrowheads). Subsequent sagittal IR (G) and PD FSE (H) images obtained 2 years following graft revision demonstrate persistent excellent fill (white arrowheads) with progressive osseous incorporation along the graft margins.
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Figure 9: Sagittal IR (A) and PD FSE (B) images in a 16 year-old boy 2 years status post osteochondral allograft repair of the lateral femoral condyle demonstrate large defect at the repair site (white arrowhead), with graft displaced into the infrapatellar region (black arrowhead). Sagittal IR (A) and PD FSE (B) images obtained 2 years following subsequent revision allograft repair demonstrate edema and cystic change along the osseous interfaces of the graft with areas of subchondral irregularity and depression, as well as overlying chondral thinning and focal area of delaminating repair tissue along the posterior aspect of the graft (white arrowheads), leading to the decision to perform a chondroplasty 1 month later. Sagittal PD (E) obtained 1 year following chondroplasty demonstrates persistent subchondral irregularity; however, there is improved fill by chondral repair tissue (white arrowhead). Sagittal T2 map (F) demonstrates corresponding prolongation of chondral relaxation times over the repair site.
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Figure 10: Sagittal (A) and axial (B) PD FSE images in a 34 year-old man, 7 months following cartilage repair, demonstrates good fill over the repair site along the lateral femoral condyle by two osteochondral autografts (black arrowheads). The trochlear donor sites (white arrowheads) have been backfilled utilizing two synthetic biphasic plugs (white arrowheads), which are slightly depressed relative to the articular surface. Subsequent sagittal (C) and axial (D) PD FSE images obtained approximately one year following repair demonstrate persistent good fill over the repair site (black arrowheads); however, there has been loss of osseous fill over the trochlear donor sites (white arrowheads), as well as the development of new adjacent full thickness chondral loss (gray arrowhead) in the interval since the prior study.
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13. Eagle S, Potter HG, Koff MF. Morphologic and quantitative magnetic resonance imaging of knee articular cartilage for the assessment of post-traumatic osteoarthritis. J Orthop Res. 2017;35(3):412-23. Epub 2016/06/22. doi: 10.1002/jor.23345. PubMed PMID: 27325163. 14. Jazrawi LM, Alaia MJ, et al. Advances in magnetic resonance imaging of articular cartilage. J Am Acad Orthop Surg.19(7):420-9. Epub 2011/07/05. doi: 19/7/420 [pii]. PubMed PMID: 21724921. 15. Singh A, Haris M, et al. Chemical exchange saturation transfer magnetic resonance imaging of human knee cartilage at 3 T and 7 T. Magn Reson Med. 2012;68(2):588-94. Epub 2012/01/04. doi: 10.1002/mrm.23250. PubMed PMID: 22213239; PubMed Central PMCID: PMCPMC4067761. 16. Brown WE, Potter HG, et al. Magnetic resonance imaging appearance of cartilage repair in the knee. Clin Orthop Relat Res. 2004(422):214-23. Epub 2004/06/10. doi: 10.1097/01.blo.0000129162.36302.4f. PubMed PMID: 15187860. 17. Guermazi A, Roemer FW, et al. State of the Art: MR Imaging after Knee Cartilage Repair Surgery. Radiology. 2015;277(1):23-43. Epub 2015/09/25. doi: 10.1148/radiol.2015141146. PubMed PMID: 26402492. 18. Mestriner AB, Ackermann J, Gomoll AH. Patellofemoral Cartilage Repair. Curr Rev Musculoskelet Med. 2018;11(2):188-200. Epub 2018/05/20. doi: 10.1007/s12178-018-9474-3. PubMed PMID: 29777422; PubMed Central PMCID: PMCPMC5970109. 19. Hayashi D, Li X, et al. Understanding Magnetic Resonance Imaging of Knee Cartilage Repair: A Focus on Clinical Relevance. Cartilage. 2018;9(3):223-36. Epub 2017/06/06. doi: 10.1177/1947603517710309. PubMed PMID: 28580842; PubMed Central PMCID: PMCPMC6042034. 20. Grawe B, Burge A, et al. Cartilage Regeneration in Full-Thickness Patellar Chondral Defects Treated with Particulated Juvenile Articular Allograft Cartilage: An MRI Analysis. Cartilage. 2017;8(4):374-83. Epub 2017/06/13. doi: 10.1177/1947603517710308. PubMed PMID: 28604062; PubMed Central PMCID: PMCPMC5613900. 21. Wang T, Belkin NS, et al. Patellofemoral Cartilage Lesions Treated With Particulated Juvenile Allograft Cartilage: A Prospective Study With Minimum 2-Year Clinical and Magnetic Resonance Imaging Outcomes. Arthroscopy. 2018;34(5):1498-505. Epub 2018/02/06. doi: 10.1016/j.arthro.2017.11.021. PubMed PMID: 29395552.
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22. Jeuken RM, Roth AK, et al. Polymers in Cartilage Defect Repair of the Knee: Current Status and Future Prospects. Polymers (Basel). 2016;8(6). Epub 2016/06/04. doi: 10.3390/polym8060219. PubMed PMID: 30979313; PubMed Central PMCID: PMCPMC6432241. 23. Wang T, Wang DX, et al. Clinical and MRI Outcomes of Fresh Osteochondral Allograft Transplantation After Failed Cartilage Repair Surgery in the Knee. J Bone Joint Surg Am. 2018;100(22):1949-59. Epub 2018/11/28. doi: 10.2106/JBJS.17.01418. PubMed PMID: 30480599. 24. Williams RJ, Gamradt SC. Articular cartilage repair using a resorbable matrix scaffold. Instr Course Lect. 2008;57:563-71. Epub 2008/04/11. PubMed PMID: 18399610. 25. Andrade R, Vasta S, et al. Knee donor-site morbidity after mosaicplasty - a systematic review. J Exp Orthop. 2016;3(1):31. Epub 2016/11/05. doi: 10.1186/s40634-016-0066-0. PubMed PMID: 27813019; PubMed Central PMCID: PMCPMC5095115.
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Imaging of Failed Cartilage Repair Alissa J. Burge MD , Hollis G. Potter MD PII: DOI: Reference:
S1060-1872(19)30084-X https://doi.org/10.1016/j.otsm.2019.150710 YOTSM 150710
To appear in:
Operative Techniques in Sports Medicine
Please cite this article as: Alissa J. Burge MD , Hollis G. Potter MD , Imaging of Failed Cartilage Repair, Operative Techniques in Sports Medicine (2019), doi: https://doi.org/10.1016/j.otsm.2019.150710
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier Inc.
Imaging of Failed Cartilage Repair
Alissa J Burge, MD (Corresponding author) Hospital for Special Surgery 535 E 70th St, New York, NY 10021 Department of Radiology and Imaging (MRI) MRI Laboratory (212)606-1857 [email protected]
Hollis G Potter, MD Hospital for Special Surgery 535 E 70th St, New York NY 10021 Department of Radiology and Imaging MRI Laboratory (212)606-1023 [email protected]
Conflict of Interest Statement Both authors receive funding from NIH/NIAMS Grants RO1AR064840 and 1R01AR066069-01A1. The authors’ institution receives research support from General Electric Healthcare.
1
Abstract
Osteoarthritis is an extremely common cause of morbidity throughout the world. Current standard of care treatment strategies focus on repairing or replacing articular cartilage defects, as methods of regenerating articular cartilage are still largely in experimental stages. Cartilage repair techniques, typically used in the setting of focal defects, allow replacement of focally damaged cartilage utilizing either donor tissue or the patient’s own tissue, with the goal of restoring normal articular surface function, preventing further joint damage, and improving clinical symptoms. While these procedures succeed in many, as with any intervention, outcomes are not universally successful. Imaging can be useful in evaluation of patients following cartilage repair, providing assessment of technical success, evolution of graft tissue over time, and potential complications. Magnetic resonance imaging, in particular, allows comprehensive imaging evaluation of repair tissue, as well as potential alternate causes of clinical symptoms. Familiarity with the expected imaging appearance of cartilage repair, and particularly the expected evolution over time, is crucial for the accurate interpretation of imaging following cartilage repair.
Keywords Cartilage Repair Magnetic Resonance Imaging Osteoarthritis
2
Introduction
Osteoarthritis is one of the most common causes of disability in the world, contributing to extensive human and economic burden (1). Current standard of care treatment strategies focus on replacing worn articular surfaces, as methods of regenerating chondral tissue are still largely at an experimental stage. Approaches to cartilage replacement vary depending on the degree of damage. While extensive damage generally requires replacement of an entire compartment or joint utilizing an arthroplasty, more focal damage can be addressed utilizing cartilage repair techniques, allowing preservation of an individual’s remaining undamaged articular surfaces and bone stock.
Cartilage repair strategies depend on the degree, extent, and location of chondral damage. Relatively mild damage confined to a small area may be addressed with techniques such as microfracture and drilling, while more severe and/or extensive defects typically require some type of graft (2). Imaging is useful in evaluating the degree and extent of existing chondral damage, facilitating appropriate preoperative planning, and is also useful in postoperative assessment of repair tissue and potential complications.
A variety of imaging modalities are available for evaluation of patients who have had or who are potential candidates for cartilage repair. While radiographs and computed tomography do not provide direct visualization of the articular cartilage, they can be helpful in evaluating osseous anatomy and alignment. Ultrasound tends to be less useful in a diagnostic capacity in this area but can be utilized for image-guided interventions such as diagnostic and therapeutic injections. Magnetic resonance imaging (MRI) provides excellent evaluation of the articular cartilage, with optimal sequencing allowing assessment of both chondral signal and morphology. MRI signal depends on the biochemical environment of protons within a given tissue, with differential tissue contrast arising from variability in tissue composition and structure, which results in differences in energy transfer characteristics, and therefore differences in proton relaxation time following the application of a radiofrequency pulse during MR image acquisition (3).
Normal articular cartilage is organized in layers, each of which possesses predictable signal characteristics on MRI due to differential distribution of proteoglycan and orientation of collagen fibers between the layers (4) (Fig 1). Early degeneration of articular cartilage results in depletion of matrix elements and disorganization of collagen fibers, with corresponding prolongation of MR relaxation times and loss of normal chondral stratification on MR images (5). More advanced chondral wear can yield areas of fissuring, flap formation, partial defects, and exposed bone, as well as osteophytes related to osseous remodeling, and synovitis related to joint irritation.
3
MR Imaging assessment of cartilage repair
Clinical MR imaging algorithms for evaluation of the articular cartilage should ideally include sequences optimized for evaluation of chondral stratification and morphology. At the authors’ institution, clinical joint imaging protocols generally consist of three planes of high resolution proton density (PD) weighted fast spin echo (FSE) images, plus a single plane of fat suppressed fluid sensitive images, such as inversion recovery (IR). Additional more advanced, quantitative sequences may be added as appropriate. Parametric mapping sequences such as T1rho and T2 mapping allow sensitive quantitative assessment of chondral matrix elements such as proteoglycan and collagen (6). Advanced metal suppression sequences such as MAVRIC (multiacquisition variable resonance image combination) and SEMAC (slice encoding metal artifact correction) may be useful in postoperative patients with metallic fixation devices (7). Zero echo time (ZTE) imaging is an MR sequence capable of yielding CT-like images, allowing assessment of mineralized bone without the use of ionizing radiation (8, 9).
Interpretation of chondral integrity on grayscale clinical MR images involves description of the severity and extent of chondral signal and stratification changes, chondral defects, and exposed bone. Interpretation of postoperative imaging requires knowledge of the procedure performed and of the postoperative timeframe. Imaging findings that may be worrisome in the late postoperative period, such as extensive edema, may be normal in the early postoperative period.
Various grading systems are available for evaluation of cartilage repair. For example, Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) is utilized for the evaluation of chondrocyte based repair techniques such as autologous and allograft chondrocyte implantation, with assessment of nine MR imaging variables, while Osteochondral Allograft MRI Scoring System (OCAMRISS) allows assessment of osteochondral graft repairs based on 13 MR imaging variables (10-12) (Table 1). Both systems incorporate features for evaluation of the chondral repair tissue, such as graft signal, degree of fill, and surface congruity, as well as of the subchondral bone, with the OCAMRISS score also including features pertaining to osseous implant integration. Both systems provide a semi-quantitative numeric score based on the grades of each of their individual components.
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As previously described, parametric mapping of articular cartilage can provide sensitive detection of early chondral matrix depletion. A number of parametric sequences exist. At the authors’ institution, T1rho and T2 mapping are performed; these sequences are sensitive to changes in proteoglycan content and collagen orientation, respectively. Acquisition of images at multiple echo times allows calculation of relaxation times on a pixel by pixel basis. Regions of interest may be placed over chondral repair tissue, in order to calculate the mean relaxation time within graft tissue and compare this with relaxation within normal articular cartilage in a quantitative fashion (6, 13). Additional advanced quantitative techniques for evaluation of articular cartilage include DGEMRIC, which requires the administration of intravenous contrast, sodium MR, which requires specialized hardware, and GAG-CEST, which is best performed at a 7 Tesla field strength (14, 15).
Marrow Stimulation Marrow stimulation techniques, including microfracture, drilling, and abrasion, involve causing mild damage to the subchondral bone beneath a site of cartilage loss, in order to provoke a reparative response with the formation of repair tissue, typically fibrocartilage, over the area. This tissue generally lacks the normal imaging characteristics of hyaline articular cartilage, as the repair tissue does not form normal chondral layers and therefore lacks the typical stratification on imaging. Additionally, as the reparative response provoked by marrow stimulation techniques involves pluripotential stem cells, this response may also result in the formation of bone in addition to chondral tissue, contributing to osseous overgrowth of the subchondral plate (16, 17).
Imaging features of particular relevance in patients post marrow stimulation include the degree of lesion fill, as well as the presence and degree of any osseous proliferative change. Excessive osseous overgrowth at the repair site may result in a stress riser with potential to damage not only the repair site but also to the apposed articular surface. Imaging evidence of a favorable outcome includes complete fill of the defect by repair tissue, which typically lacks the stratified appearance of normal articular cartilage, as well as mild subchondral irregularity without prominent osseous overgrowth (Fig 2). Features suggesting a poor outcome include incomplete lesion fill and persistent or increasing subchondral edema (Fig 3), as well as prominent productive bone formation .
Chondrocyte based techniques Chondrocytes may be used to repair focal chondral defects, and may be harvested from the patient or from a donor. Autologous chondrocyte implantation (ACI) involves harvesting and culturing the patient’s own chondrocytes, with subsequent re-implantation of the cultured tissue into the site of desired chondral repair; originally, the technique involved sealing the repair with a periosteal patch, but ultimately evolved to incorporate scaffolds within which the chondrocytes are cultured and subsequently implanted (18). Allograft
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chondrocytes are also utilized for repair of chondral defects; chondral fragments containing viable chondrocytes from juvenile donors are implanted into a chondral defect and fixed in place with fibrin glue (16, 17, 19-21). Relevant imaging features in patients following chondrocyte based repair techniques include the degree of lesion fill, congruency of the articular surface, signal characteristics of the repair tissue, and integrity of the periosteal seal (if present). The appearance of the repair tissue typically evolves over time, in terms of both the signal intensity of the graft, and the degree of lesion fill. Early in the postoperative course, repair tissue tends to appear hyperintense due to disorganization and water content (Fig 4), and may also fail to completely fill the chondral defect, as graft tissue is expected to hypertrophy to a certain extent over time. As the postoperative time course progresses, signal intensity should decrease as tissue becomes more organized, and lesion fill should increase in the cases where fill was incomplete. Optimally, in addition to normalization of signal intensity, repair tissue may develop a degree of normal stratification as the chondrocytes organize into the distinct layers typical of hyaline articular cartilage (Fig 5). Poor prognostic signs include failure of fill or decreasing fill over time, in addition to persistent or increasing hyperintensity of repair tissue (16, 17, 19) (Fig 6).
Osteochondral grafts Osteochondral repairs may be performed utilizing autograft, allograft, or synthetic tissue (2, 22). Autografts, being harvested from the patient, are generally utilized for smaller repairs, while allografts may be used for larger repairs (5, 23). Synthetic plugs are most commonly used to fill autograft donor sites in order to restore the congruity of the articular surface following graft harvest (24). Because these osteochondral grafts consist of both osseous and chondral phases, imaging assessment of graft health necessitates attention to imaging characteristics of both phases. Again, postoperative timeframe is a crucial consideration in determining whether a particular imaging finding is expected or worrisome. Early in the postoperative time course, the osseous portion of the graft and surrounding native bone typically display signal hyperintensity, and a discernable margin is present between the graft and adjacent native bone. Over time, signal hyperintensity should decrease, and crossing trabeculae should bridge the area along the graft interfaces as osseous incorporation occurs (Fig 7). Due to the difficulty of matching the exact chondral thickness and contour of the repair site and graft, areas of mild subchondral step-off are not unexpected; however, the chondral articular surface should be congruent, with restoration of the articular contour. Additionally, discernable margins are typically present at the interfaces between repair and native chondral tissue; however, the tissue should be closely apposed, without a frank fluid cleft or gap. In autografts and allografts, because the repair tissue is true hyaline articular cartilage, the signal characteristics and organization of the repair tissue should closely approximate the patient’s normal articular cartilage (Figs 8,9). In patients who have undergone repair utilizing an autograft, the status of the donor site is also of concern (25). Often, particularly in the setting of large defects, the donor site is backfilled utilizing allograft or synthetic tissue in order to restore the articular surface contour and prevent damage to adjacent cartilage (Fig 10).
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Conclusion
MR imaging is useful in cartilage repair patients, both in terms of preoperative planning and postoperative follow up. Following cartilage repair, imaging can provide assessment of the status of the repair, as well as potential alternate causes of symptoms in patients with persistent or new onset of pain. Routine clinical imaging sequences are capable of providing detailed evaluation regarding lesion fill, surface congruity, and incorporation of repair tissue, while more advanced parametric sequences provide more sensitive, quantitative assessment of the quality of repair tissue. Familiarity with relevant imaging features, and in particular the expected evolution of postsurgical appearance over time, is critical in facilitating accurate interpretation of imaging in patients following cartilage repair.
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Figure Legends
Figure 1: Normal hyaline articular cartilage demonstrates a stratified gray scale appearance on certain MRI sequences, such as this axial proton density (PD) weighted fast spin echo (FSE) image of the patella, due to differences in collagen orientation and proteoglycan content between the layers. The deepest layer, the tidemark (TM) is comprised of calcified cartilage and is therefore hypointense and indistinguishable from the subchondral plate. The next deepest layer, the radial zone (RA) is comprised of highly ordered parallel collagen fibers, which facilitate energy transfer and therefore result in short relaxation times with relative hypointensity on images. The next layer is the transitional zone (TR), in which the collagen fibers are oriented in arcades, which results in slightly longer relaxation times and higher signal intensity on images. The most superficial layer, the lamina splendens (LS), is comprised of horizontally oriented parallel collagen fibers, resulting in relative hypointensity on images.
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Figure 2: Coronal PD FSE image (A) in a 33 year-old man demonstrates focal area of full thickness chondral loss (black arrow) over the inner aspect of the medial tibial plateau. Subsequent coronal PS FSE image (B) obtained 1 year following microfracture demonstrates inhomogeneous repair tissue (black arrow) which lacks normal chondral stratification, and subjacent subchondral irregularity with mild productive bone formation; however, there is overall good fill of the lesion with restoration of the articular surface contour.
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Figure 3: Sagittal IR (A) and PD FSE (B) images in a 35 year-old woman demonstrate full thickness chondral loss (white arrowheads) over the posterior aspect of the lateral femoral condyle. Sagittal IR (C) and PD FSE (D) images obtained 1 year following microfracture demonstrate incomplete fill with persistent exposed bone (white arrowhead), with interval increase in subchondral edema, and subchondral irregularity with mild productive bone formation related to the procedure.
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Figure 4: Axial PD FSE (A) image in a 28 year-old woman demonstrates full thickness chondral loss (black arrowhead) over the patellar apex and inner aspect of the lateral facet. Subsequent axial PD FSE image (B) obtained 5 months following MACI demonstrates excellent fill of the defect with uniformly hyperintense repair tissue (black arrowhead), a normal appearance for the postoperative timeframe.
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Figure 5: Axial T2 Fat saturated image (A) in a 25 year-old woman following lateral patellar dislocation demonstrates focal full thickness chondral defect over the patellar apex (white arrowhead). Axial PD FSE (B) obtained 3 months following cartilage repair utilizing particulated juvenile allograft cartilage demonstrates excellent fill by hyperintense repair tissue, a normal appearance for the postoperative timeframe. Subsequent axial PD FSE (C) and T2 map (D) performed 6 months following cartilage repair demonstrate persistent graft hyperintensity with corresponding prolongation of relaxation times on mapping images (white arrowheads); however, graft signal appears decreased compared to the prior study. Axial PD FSE (E) and T2 map at one year following repair demonstrate further interval decrease in graft intensity, with reduced prolongation of relaxation times and the suggestion of developing chondral stratification (white arrowheads) on mapping images.
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Figure 6: Axial PD FSE (A) in a 25 year-old woman 3 months following chondral repair utilizing particulated juvenile allograft cartilage demonstrates hyperintense material within the full thickness defect over the patellar apex and lateral facet (black arrowhead). While this may be a normal appearance for the postoperative timeframe, there is the suggestion of a subtle, relatively hyperintense linear cleft along the base of the repair site (white arrowhead) parallel to the subchondral plate. Subsequent axial PD FSE image (B) obtained 3 months later demonstrates increased signal of material within the defect with apparent decrease in fill, suggesting partial delamination of the graft.
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Figure 7: Sagittal Zero Echo Time (ZTE) image (A) in a 51 year-old woman 6 months following lateral femoral condyle osteochondral allograft demonstrates areas of trabeculae bridging the interface between the graft and underlying native bone (black arrowheads). Subsequent ZTE image (B) obtained 1 year following repair demonstrates progressive osseous incorporation (black arrowheads).
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Figure 8: Sagittal IR (A) and PD FSE (B) images in a 25 year-old man, 2 years status post osteochondral allograft repair of the lateral femoral condyle, demonstrate overall good fill with restoration of the articular surface contour. However, there is pronounced edema with areas of cystic change along the osseous portion of the graft, and a focal linear hyperintense cleft subjacent to the subchondral plate along the posterior aspect of the graft (white arrowheads), suggesting impending delamination. Subsequent sagittal IR (C) and PD FSE (D) images obtained one year later demonstrate interval complete delamination with in situ osteochondral fragment (white arrowheads). Sagittal IR (E) and PD FSE (F) images obtained 6 months following revision allograft repair demonstrate excellent fill by repair tissue with restoration of the articular surface contour (white arrowheads). Subsequent sagittal IR (G) and PD FSE (H) images obtained 2 years following graft revision demonstrate persistent excellent fill (white arrowheads) with progressive osseous incorporation along the graft margins.
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Figure 9: Sagittal IR (A) and PD FSE (B) images in a 16 year-old boy 2 years status post osteochondral allograft repair of the lateral femoral condyle demonstrate large defect at the repair site (white arrowhead), with graft displaced into the infrapatellar region (black arrowhead). Sagittal IR (A) and PD FSE (B) images obtained 2 years following subsequent revision allograft repair demonstrate edema and cystic change along the osseous interfaces of the graft with areas of subchondral irregularity and depression, as well as overlying chondral thinning and focal area of delaminating repair tissue along the posterior aspect of the graft (white arrowheads), leading to the decision to perform a chondroplasty 1 month later. Sagittal PD (E) obtained 1 year following chondroplasty demonstrates persistent subchondral irregularity; however, there is improved fill by chondral repair tissue (white arrowhead). Sagittal T2 map (F) demonstrates corresponding prolongation of chondral relaxation times over the repair site.
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Figure 10: Sagittal (A) and axial (B) PD FSE images in a 34 year-old man, 7 months following cartilage repair, demonstrates good fill over the repair site along the lateral femoral condyle by two osteochondral autografts (black arrowheads). The trochlear donor sites (white arrowheads) have been backfilled utilizing two synthetic biphasic plugs (white arrowheads), which are slightly depressed relative to the articular surface. Subsequent sagittal (C) and axial (D) PD FSE images obtained approximately one year following repair demonstrate persistent good fill over the repair site (black arrowheads); however, there has been loss of osseous fill over the trochlear donor sites (white arrowheads), as well as the development of new adjacent full thickness chondral loss (gray arrowhead) in the interval since the prior study.
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