Features associated with more rapid progression of OA More advanced radiographic disease at the time of initial Evaluation
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1 Parametric Mapping of Cartilage: A Clinical Perspective ISMRM 2012 Hollis G. Potter, MD Chief, Magnetic Resonance Imaging Director of Research, Dept. of Radiology & Imaging Hospital for Special Surgery Professor of Radiology Weill Medical College of Cornell University Imaging of Joint Osteoarthritis Radiographs provide information largely about standing alignment Standardized, reproducible MR sequences should be utilized Objective evaluation of cartilage following repair Quantitative MR evaluation: Should ideally assess both PG and collagen Whereas PG depletion generally precedes collagen disruption, most argue that the collagen network is the most important matrix component Cartilage Structure Deep radial zone (40-60%): collagen oriented perpendicular to subchondral zone strong angular dependence: vertical striations evident and short T2 values Transitional zone (20-30%): more random collagen orientation less angular dependence and longer T2s Superficial zone (<10%): parallel to surface (beyond resolution of clinical MRI) Imaging of Cartilage Structure Free water (accounts for bulk of MRI signal) Bound to PG by electrostatic charge (assess fixed charge density) Sodium MRI Gd-DTPA-2 techniques (dgemric) Correlated to static (compressive) mechanical properties at 9.4T* T1 rho imaging Associated with collagen fibrils Quantitative T2 mapping: Assess alterations in collagen orientation Correlated to dynamic mechanical properties at 1.5T and 9.4T* Diffusion tensor weighted imaging Features associated with more rapid progression of OA More advanced radiographic disease at the time of initial Evaluation High baseline BMI Baseline meniscal tear, extrusion Progressive BME lesion * Maximum BML assoc. with WB pain Eckstein et al; Arthritis Rheum 2009; 61: Roemer et al; Radiology 2009; 252: Biswal et al; Arthritis Rheum 2002;46: Roemer et al; Radiology 2009 Hunter et al; Arthritis Rheum 2006; 54: Roemer et al; Ann Rheum Dis 2009; 68: *Lo et al; Osteoarth Cartilage 2009 (Epub)
2 Whole-Organ MRI (WORMS) Score (Osteoarthritis & Cart 2004; 12: ) Cartilage signal and morphology Marrow edema pattern Subarticular cysts Subarticular bone attrition (subchondral flattening) Osteophytes ACL/PCL (torn, intact) MCL/LCL (torn, intact) Menisci (0-4; include postop changes) Synovitis (0-3 based on % involvement of maximum potential distention; no distinction made between effusion and synovitis) 0-7: none, equivocal, small, small to moderate, moderate, mod-large, large, very large T2 mapping at HSS: Issues of PSD Conventional Spin Echo (SE) (multiple acquisitions) vs. Conventional multi-slice, multi-echo (MSME) sequence Similar range of TEs Stimulated echo component due to imperfect slice-selective refocusing pulses Magnetization transfer contrast (MTC) between slices Substantial inaccuracy in T2 calculation for articular cartilage T2 mapping at 1.5T: Issues of PSD Modified multi-slice, multi-echo (MSME) sequence Slice-selective refocusing pulse gradient amplitude reduced (relative to excitation pulse) Stimulated echo contribution Cross talk Requires interleaved slice acquisition (forced 2 acquisition) Assumes a monoexponential decay T2 calculated by natural logarithm of mean signal of the ROI and performing a weighted least squares fit Maier et al; J MRI 2003; 17(3): Quantitative MR in hip disease Kim et al studied pts with DDH and found the dgemric index was sensitive to OA changes as well as symptoms (WOMAC) (JBJS 2003;85A: ) F/U study of pts with DDH treated with osteotomy showed that pts. who clinically failed osteotomy had more OA on radiographs and lower dgemric indices, but dgemric index was more predictive of failure (Cunningham et al; JBJS 2006; 88A: ) Nishii et al studied pts with DDH with mild or no OA and nl controls with T2 mapping at 3T; prolongation of T2 was noted in the majority of the early OA pts (Osteoarthritis and Cart 2008; 16: ) Articular Cartilage Injury following Acute ACL Tear Spindler et al (AJSM 1993; 21: ) evaluated 54 pts with ACL tear and ACLR 46% (25/54) had articular lesion at arthroscopy (LFC>LTP>MFC>MTP) Johnson et al (AJSM 1998; 26: ) evaluated 10 pts with acute ACL tear underwent biopsy of LFC during ACLR Chondrocyte degeneration, loss of PG, osteocyte necrosis and empty lacunae degeneration Tiderius et al (Arthritis and Rheumatism 2005; 52: ) evaluated cartilage glycosaminoglycan loss in the acute ACL injury with delayed post-gadolinium MRI 15 out of 24 patients (63%) had loss of GAG in both medial and lateral femorotibial surfaces Suggests generalized alteration in matrix within the knee cartilage following ACL injury Isolated ACL tear as a traumatic model of OA Adjusting for age, sex and type of surgery: 100% of isolated ACL tears sustain chondral damage at the time of pivot shift Risk of cartilage loss doubled from baseline to year one for LFC, LTP and MFC (tripled for patella)
3 By year 7-11, risk for LFC was 50 times baseline (30x for patella, 19x for MFC) Progressive prolongation of T2 compared to year 1 for LFC and patella Each increase in MFC OB score resulted in 13 pt decrease in IKDC (p=0.0002) Each level increase in MTP resulted in 2.4 point decrease in ARS (p=0.0015) Cartilage Repair: Methods of Repair Articular cartilage has little to no capacity to undergo spontaneous repair avascular; unable to regenerate across a physical gap Debridement Marrow stimulation (microfracture) Osteochondral transfer autologous (mosaicplasty; OATS) allograft (fresh cadaveric tissue) Tissue Engineered Cartilage (three requirements) matrix scaffold carbohydrate based polymers (polylactic acid) protein based polymers (collagen, fibrin) cells chondrocytes chondroprogenitor cell pools (cambial layer of periosteum and perichondrium) mesenchymal stem cells from the bone marrow or synovial membrane signaling molecules (growth factors or genes) Synthetic acellular techniques (scaffold) polylactide-co-glycolide copolymer and calcium sulfate (porous) MRI as Primary Outcome Measure: Cartilage Repair Signal intensity of tissue (ROI) Integrity/hypertrophy of periosteal flap Morphology; presence/absence of displacement (ACI/ OCA) Interface with native cartilage Volume of repair fill Appearance/morphology of subchondral bone Assess adjacent/opposite articular cartilage Presence/absence of inflammatory synovitis MR observation of cartilage repair tissue (MOCART) Marlovits et al; Eur J Radiol 2006; 57:16-23 Correlated to KOOS and VAS; significant correlation for fill, structure, subchondral bone, SI ICC (3 readers); κ range: Imaging of Microfracture Prospective study of 48 patients treated with microfracture evaluated by validated clinical outcome instruments and cartilage sensitive MRI bony overgrowth was noted in 25% of patients, but did not have a negative effect on clinical outcome scores adverse functional scores after 24 months did correlate with poor percentage fill J Bone Joint Surg 2005; 87(9): year-old professional football player with unstable lesion MFC Welsch et al (Radiology 2008; 247: ) studied 20 pts following MFX or MACT with mean F/U 28.6 vs 27.4 mo MFX tissue showed reduced mean T2 whereas MACT showed mean T2 similar to control tissue (56.4msec); MFX showed no stratification while MACT did from deep to superficial areas Imaging of Osteochondral Allografts Prospective, longitudinal study of cartilage defects treated with hypothermically stored fresh osteochondral allografts
4 Allografts remain intact without displacement fissures noted at the graft/host interspace in 78% poor incorporation was noted in 22% grafts: persistent bone marrow edema pattern and/or subchondral marrow fibrosis collapse of the subchondral bone in the graft was correlated to lack of bony integration based on signal characteristics Sirlin et al. correlated MRI of shell osteochondral allografts to the results of antihuman leukocyte antigen antibody screening (Radiology 2001;219:35-43) Pts. who expressed positive humoral immune responses were associated with decreased incorporation, greater marrow edema pattern and a higher proportion of surface collapse of their graft T2* of meniscal repair Morphologic grading correlated well to T2*; however, T2* was more predictive of healing based on histology as standard T2* values are predictive of meniscal healing and show potential as a biomarker for meniscal integrity Regional differences indicating collagen disruption are detectable Imaging & Cartilage OA/Repair Trials: cartilage morphology Preclinical outcome measures should parallel Phase I and Phase II clinical measures for repaired tissue Clinical trial challenges: morphology Sufficient spatial resolution to detect partial thickness lesion, abnormal synovium, subchondral sclerosis Standardize protocol, field strength, coils Used cartilage sequence previously validated for accuracy and reproducibility for cartilage morphology Issues of availability of QMRI sequences and standardization of postprocessing Quantitative MRI in OA assessment: Issues of Data Acquisition Ideally assess both PG and collagen Clinical trial challenges for reproducibility: QMRI Add to scan time!! Software availability Magnetic field strength (Na 23, T1rho) Contrast agents (dgemric) Magic angle prolongation (T2, T1rho) Coil choice (Na 23 ) Parameters of acquisition (SNR, resolution, # echoes) Post-processing algorithm (2 vs. 3 parameter fit) Registration software Quantitative MRI in OA assessment: Issues of Data Interpretation Issues of sampling: Thin cartilage: hip, ankle, wrist, shoulder Avoid sampling the tidemark and the synovial fluid Standardize # pixels for sampling and site of sampling Need laminar data with deep and superficial sampling For OA, may do 1-2 slices per compartment For cartilage repair, sample within repair, native hyaline cartilage and at interface with host tissue Clinical applications of QMRI of cartilage Provides objective assessment of matrix alteration in cartilage that often precedes morphologic alterations QMRI is best applied in conjunction with standardized, reproducible MR sequences and standardized OA scoring systems Objective evaluation of cartilage following repair that may obviate the need for surgical biopsy of repair tissue
5 Quantitative MR evaluation: should ideally assess both PG and collagen Registration methodology helpful for longitudinal analysis Need more longitudinal REGISTRY data performed on populations at increased risk for OA to provide information suitable for powering pharmaceutical intervention DDH, FAI, PF dysmorphism, ACL tears References 1. Potter HG, Linklater JA, Allen AA, et al. Magnetic resonance imaging of articular cartilage in the knee: An evaluation with use of fast spin-echo imaging. J Bone Joint Surg Am 1998; 80(A): Bredella MA, Tirman PF, 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 1999; 172: Gold GE, Busse RE, Beehler C, et al. Isotopic MRI of the knee with 3D fast spin-echo extended echo-train acquisition (XETA): Initial Experience. AJR 2007; 188: Eckstein F, Glaser C. Measuring cartilage morphology with quantitative magnetic resonance imaging. Sem Musculoskelet Radiol 2004; 8(4): Cicuttini FM, Wluka AE, Forbes A, et al. Comparison of tibial cartilage volume and radiologic grade of the tibiofemoral joint. Arthritis Rheum 2003; 48: Raynauld JP, Martel-Pelletier J, Berthiaume MJ, et al. Quantitative magnetic resonance imaging evaluation of knee osteoarthritis progression over two years and correlation with clinical symptoms and radiologic changes. Arthritis Rheum 2004; 50(2): Bashir A, Gray ML, Boutin RD, et al. Glycosaminoglycan in articular cartilage: in vivo assessment with delayed Gd (DTPA) 2- -enhanced MR imaging. Radiology 1997; 205: Williams A, Gillis A, McKenzie C, et al. Glycosaminoglycan distribution in cartilage as determined by delayed gadolinium-enhanced MRI of cartilage (dgemric): Potential clinical applications. AJR 2004; 182: Wheaton AJ, Casey FL, Gougoutas AJ, et al. Correlation of T 1ρ with fixed charge density in cartilage. J Magn Reson Imaging 2004; 20: Wheaton A.J., Dodge G.R., Borthakur A., et al. Detection of changes in articular cartilage proteoglycan by T1ρ magnetic resonance imaging. J Orthop Res 2005; 23: Benjamin M, Bydder GJM. Magnetic resonance imaging of entheses using ultrashort TE (UTE) pulse sequences. J Magn Reson Imaging 2007; 25: Xia Y, Moody JB, Burton-Wurster N, et al. Quantitative in situ correlation between microscopic MRI and polarized light microscopy studies of articular cartilage. Osteoarthritis Cartilage 2001; 9: Goodwin DW, Wadghiri YZ, Zhu H, et al. Macroscopic structure of articular cartilage of the tibial plateau: influence of a characteristic matrix architecture on MRI appearance. AJR 2004; 182: Maier CF, Tan SG, Hariharan H, Potter HG. T 2 quantitation of articular cartilage at 1.5T. J Magn Reson Imaging 2003; 17: Kelly BT, Potter HG, Deng X, et al. Meniscal allograft transplantation in the sheep knee: evaluation of chondroprotective effects. Am J Sports Med 2006; 34: Lammentausta E, Kiviranta P, Nissi MJ, et al. T2 relaxation time and delayed gadolinium-enhanced MRI of cartilage (dgemric) of human patellar cartilage at 1.5T and 9.4T: Relationships with tissue mechanical properties. J Orthop Res 2006; 24: Welsch GH, Mamisch TC, Domayer SE, et al. Cartilage T2 assessment at 3-T MR imaging: In vivo differentiation of normal hyaline cartilage from reparative tissue after two cartilage repair procedures initial experience. Radiology 2008; 247: Gillis A, Bashir A, McKeon B et al. Magnetic resonance imaging of relative glycosaminoglycan distribution in patients with autologous chondrocyte transplants. Invest Radiol 2001; 36: Williams R III, Ranawat A, Carter, T, et al. Fresh stored allografts for the treatment of osteochondral defects of the knee. J Bone Joint Surg 2007; 89: Sirlin CB, Brossmann J, Boutin RD, et al. Shell osteochondral allografts of the knee: Comparison of MR imaging findings and immunologic responses. Radiology 2001; 219: Brown WE, Potter HG, Marx RG et al. Magnetic resonance imaging appearance of cartilage repair in the knee. Clin Orthop Rel Res 2004; 422:
6 22. Marlovits S, Singer P, Zeller P, et al. Magnetic resonance observation of cartilage repair tissue (MOCART) for the evaluation of autologous chondrocyte transplantation: Determination of interobserver variability and correlation to clinical outcome after 2 years. Eur J Rad 2006; 57: Nho SJ, Foo LF, Green DM, et al. MRI and Clinical Evaluation of patella resurfacing with press-fit osteochondral autograft plugs. Am J Sports Med 2008; 36(6): Spindler KP, Schils P, Bergfeld JA, et al. Prospective study of osseous, articular, and meniscal lesions in recent anterior cruciate ligament tears by magnetic resonance imaging and arthroscopy Am J Sports Med July : Johnson DL, Urban WP, Jr, Caborn DNM, et al. Articular Cartilage Changes Seen With Magnetic Resonance Imaging-Detected Bone Bruises Associated With Acute Anterior Cruciate Ligament Rupture. Am J Sports Med May : Tiderius CJ, Olsson LE, Nyquist F, et al. Cartilage glycosaminoglycan loss in the acute phase after an anterior cruciate ligament injury: delayed gadolinium-enhanced magnetic resonance imaging of cartilage and synovial fluid analysis. Arthritis Rheum 2005;52: Peterfy CG, Guermazi A, Zaim S, et al. Whole-Organ Magnetic Resonance Imaging Score (WORMS) of the knee in osteoarthritis. Osteoarthritis Cartilage. 2004;12(3): Eckstein F, Benichou O, Wirth W, et al. Osteoarthritis Initiative Investigators. Magnetic resonance imaging-based cartilage loss in painful contralateral knees with and without radiographic joint space narrowing: Data from the Osteoarthritis Initiative.Arthritis Rheum Sep 15;61(9): Roemer FW, Zhang Y, Niu J, et al. Multicenter Osteoarthritis Study Investigators. Tibiofemoral joint osteoarthritis: risk factors for MR-depicted fast cartilage loss over a 30-month period in the multicenter osteoarthritis study. Radiology Sep;252(3): Biswal S, Hastie T, Andriacchi TP, Bergman et al. Risk factors for progressive cartilage loss in the knee: a longitudinal magnetic resonance imaging study in forty-three patients. Arthritis Rheum. 2002;46(11): Hunter DJ, Zhang Y, Niu J, et al. Increase in bone marrow lesions associated with cartilageloss: a longitudinal magnetic resonance imaging study of knee osteoarthritis.arthritis Rheum May;54(5): Roemer FW, Guermazi A, Javaid MK, Lynch et al. MOST Study investigators. Change in MRI-detected subchondral bone marrow lesions is associated with cartilage loss: the MOST Study. A longitudinal multicentre study of knee osteoarthritis. Ann Rheum Dis.2009 Sep;68(9): Lo GH, Hunter DJ, Nevitt M, et al. OAI Investigators Group Strong association of MRI meniscal derangement and bone marrow lesions in knee osteoarthritis: data from the osteoarthritis initiative. Osteoarthritis Cartilage Jun;17(6): Cunningham T, Jessel R, Zurakowski D, et al. Delayed gadolinium-enhanced magnetic resonance imaging of cartilage to predict early failure of Bernese periacetabular osteotomy for hip dysplasia. J Bone Joint Surg Am Jul;88(7):
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