MRI Assessments of Cartilage

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SNR IMPACTS THE ACCURACY AND PRECISION OF KNEE ARTICULAR CARTILAGE T2 RELAXATION TIME MEASUREMENTS B.J. Dardzinski 1, E. Schneider 2 1 Merck Sharp & Dohme Corp., West Point, PA USA 2 Imaging Institute, Cleveland Clinic, Cleveland, OH USA and SciTrials LLC, Rocky River, OH The authors have no conflicts with the work reported in this study. MRI Assessments of Cartilage Morphological MRI Insensitive to early stage cartilage lesions Outerbridge I softening / swelling Unexposed (no risk) and Incidence (at risk, no symptoms or ROA) have equal incidence of early defects (WORMS <5) T2 collagen integrity, [GAG], orientation dependent T1 (dgemric) [GAG] charge-based, orientation independent T1rho collagen integrity, [GAG], orientation dependent (less than T2)

T2 Assessments Are not absolute Values are: Spatially dependent Knee positioning (magic angle) Cartilage plate Cartilage zone MR System Dependent Magnetic Field Strength Refocusing flip angle Acquisition sequence Analysis method Image noise, particularly last echo Introduction OAI opted for 3T Increased SNR allowed higher spatial resolution In 2003: Not many 3T MR systems Only one knee coil (USAI) However other options in development Pilot study to evaluate impact two different knee coils Similar transmit design (similar excitation / refocusing pulses) Different detection design (different SNR)

Structure of Articular Cartilage Proteoglycans Type II Collagen Matrix Water Fiber reinforced composite matrix Effect of Collagen Orientation on MR Signal Intensity B 0 B 0 Images courtesy of Doug Goodwin, MD Dartmouth Medical School

SNR 1.5T vs. 3T SNR (BW = 125) ROI Bone 1.5T 53 SNR (BW = 250) 3T Ratio 1.5T 109 2.1 61 3T 95 Ratio 1.6 Cartilage 22 46 2.1 29 45 1.6 Fat 74 132 1.8 84 112 1.3 Muscle 26 42 1.6 31 44 1.4 SNR = S σn T2 Map Comparison 1.5 vs. 3 Tesla 1.5T 3T T2 (msec) 25 255 80 0

T2 Comparison Objective Determine the accuracy and precision of cartilage T2 measurements using two different RF Coils Similar transmit (quadrature) Dissimilar receive (quadrature vs 8 channel phased array)

QTR vs. QT8PAR Min inner height 130 mm Inner height Inner width Inner Circumference Equivalent diameter 180 mm 190 mm 580 mm 184 mm Min inner width Inner Circumference Equivalent diameter Thigh/Calf inner height Thigh/Calf inner width 140 mm 420 mm 134 mm 180 mm 185 mm Methods 10 subjects (3 men) 52.2 yrs, 28.2 BMI 12 knees (6 progression, 6 incident) 10 femoro-tibial joints were eligible

ROIs for SNR Calculation SNR @ 10 msec Echo Time Tibial Cartilage SI = 256 σ noise = 18.9 SNR = 13.5 SI = 39.5 σ noise = 1.88 SNR = 21 QTR QT8PAR

SNR @ 70 msec echo time Tibial Marrow Mean ± SD * * 5.0% 5.3% 3.5% 2.5% * = P < 0.001 RMS CV % SNR @ 70 msec echo time Tibial Cartilage Mean ± SD * * 8.1% 3.4% 7.7% 4.3% * = P < 0.001 RMS CV %

Signal Intensity Time (msec) Weight Bearing Region ROIs for T2 Comparison

Femwtbear_USAI T2 (msec) 90 80 70 60 50 40 30 20 10 0.0 0.2 0.4 0.6 0.8 1.0 80 Normalized Distance 70 T2 (msec) 90 60 50 40 30 20 10 Deep 360A 360B 361A 361B 362A 362B 363A 363B 364A 364B 365A 365B 366A 367A 367B 368A 368B 369A 369B 370A 370B 371A 371B 372A 372B Femwtbear_InVivo Central Superficial 0.0 0.2 0.4 0.6 0.8 1.0 Normalized Distance 460A 460B 461A 461B 462A 462B 463A 463B 464A 464B 466A 466B 467A 468B 469A 469B 470A 470B 471A 471B T2 Map 255 80 0 QTR QT8PAR

* = P < 0.001 T2 Relaxation Mean ± SD * * * * = P < 0.001 Deep Zone * * *

* = P < 0.001 Central Zone * * * * = P < 0.01 Superficial Zone * *

RMS CV (%) 12 10 QT8PAR RMS CV% 8 6 4 CcMF ScMF ScLT DMT DcMF CLT ScLF GcMF DLT GcLF GLT Fat Muscle CMT CcLF ScMT DcLF 2 GMT Marrow GMT 0 0 2 4 6 8 10 12 QTR RMS CV%

Some Caveats on T2 T2 Example - Infrapatellar Fat Pad 94.7 ± 6.5 msec

T2 Error Maps 6 pt fit 7 pt fit QTR 100ms QT8PAR 0ms Whole Knee T2 Error

Tibial Cartilage QT8PAR 6pt Fit 100 Correlation Map T2 err T2 Map T2 err Map 0 T2

T2 Differences 75 0-10 QT8PAR 7-6 QT8PAR 2-6 Findings SNR higher in QT8PAR Global T2 longer with QT8PAR cmf (45.9ms/50.7ms) MT (41.6ms/48.2ms) muscle (37.9ms/40.7ms) T2 precision better with QT8PAR clf, cmf, and infrapatellar fat

Findings Due to anatomy, T2 values differ spatially clf has the longest value (52ms) LT has the shortest (40.6ms) SNR can vary spatially depending upon coil With higher SNR, significantly longer T2 values Deep cartilage T2 values were most affected T2 changes with SNR can be larger than the impact of changing magnetic field strength What does this mean for analyzing the OAI data? Same USAI QTR coils Used from 2004 early 2012 Failing quality assurance No replacements have been available for past 2yrs Replaced with InVivo QT8PAR Spring 2012

T2 Summary Monitors rotational freedom of water motion Sensitive to both collagen integrity, [GAG] in cartilage hydration Orientation dependent Equipment, acquisition and analysis dependent Analysis precision varies with plate and zone (0.5-2% RMS CV%) Measurement precision varies with plate and zone (3.3-10.9% RMS CV%) Include quality control ROIs Accommodate for noise in analysis T2 values are higher in disease, possibly sensitive to early OA Reversible (exercise) Small changes, 1-3ms Higher T2 in Knee Pain Cartilage or meniscal defects Weaker quadriceps muscles Increases with age, but no diff in rate of change with early OA

T2 in Clinical Research Pair the acquisition and analysis Ensure accuracy and sensitivity to change with phantoms Perform within subject comparisons for longitudinal change Use an intrinsic reference tissue (if possible) Cartilage in a different compartment No gold standard Tailor the acquisition to the clinical question cartilage repair vs. OA vs. deep cartilage change due to trauma Difficult to perform meta-analyses Acknowledgments The OAI and this pilot study are conducted and supported by NIAMS in collaboration with the OAI Investigators and Consultants The research reported in this abstract was supported in part by contracts N01-AR-2-2261, N01-AR-2-2262 and N01-AR-2-2258 We are grateful to the Ohio State University and Memorial Hospital of Rhode Island OAI study teams for recruitment of the study subjects and acquisition of the MR exams