Sprains, strains, tears and stress fractures are unfortunately common occurrences in athletes and weekend warriors alike. Detection and quantitation of subtle and, in some cases, subclinical damage to short-T2 tissues using advanced MRI methods, like ultrashort echo time (UTE) and zero echo time (ZTE) imaging, may help to guide the clinical management of injured patients as they recover and return to sport. Audience members will be introduced to common sports injuries involving short-T2 tissues and new and upcoming MRI techniques to diagnose, stage, and monitor tissue injury and recovery by assessing short-T2 tissue properties.
Background:
Sprained ligaments and strained tendons are among the most common of all sports injuries1. Both ligaments and tendons are made of dense viscoelastic networks of highly aligned collagenous fibers that give them tremendous strength under tension and also short-T2 times (<10ms)2. Consequently, healthy ligaments and tendons have little to no signal on standard GRE or FSE sequences. Meniscus injuries are also unfortunately frequent in many sports3 occurring in tissue with an abundance of type I collagen2 that similarly has almost no signal on conventional MRI. Cortical bone stress fractures account for up to 20% of sports medicine clinic injuries4, but due to extremely short-T2 times of mineralized bone and bone water, stress injuries are typically indirectly detected by conventional MRI after evolution of periosteal edema5. Although frank tears and fractures can be inferred from bright signal indicative of fluid infiltration on fluid-sensitive sequences, short-T2 techniques are required for direct imaging of ligaments, tendons and their entheses, intra-substance meniscal integrity, and bone stress injuries6-11.Methods & Results:
UTE: In UTE imaging, read gradients are ramped up as soon as possible after the RF pulse, data sampling begins during the ramp up, and center-out k-space trajectories capture short-T2* signal2,11. The shortest TEs typically achieved with UTE techniques range from microseconds to 1 millisecond. Variable echo time (vTE) GRE imaging, a variant of UTE, uses Cartesian k-space sampling with phase-encoding gradients to vary the effective echo time to achieve sub-millisecond TEs12-14.
Achilles Tendon. [UTE] and [vTE] T2* measurements of Achilles tendon discriminate patients with painful Achilles tendon from controls9,12,15,16. The short-component of bi-exponential T2* analyses provides greater sensitivity to tendinopathy12 with largest differences observed in the region of the calcaneus insertion12,16. Importantly, Achilles [UTE] or [vTE] T2* measures have been correlated to several clinical scoring systems9,12,16. While most short-T2 studies have been conducted at 3T magnetic fields, recent work has shown feasibility for [UTE] T2* imaging of Achilles tendon at low (0.35T) field strength17.
Patellar Tendon. Bi-exponential [UTE] T2* assessment of patellar tendinopathy in high-level athletes detects significant T2* differences compared to controls18, with focal elevations of the short-T2* component and decreased short-T2* fraction observed in proximal patellar tendon of all patient athletes18. In a separate study of basketball players, patellar tendon [UTE] T2* changes over a season of sport correlated to change in pathologic severity19.
Anterior Cruciate Ligament (ACL) and ACL Grafts. ACL graft incorporation following reconstruction surgery has been monitored with [UTE] T2* imaging20,21. T2* indications of earlier maturation in some patients have implications for timing of return to sport21. In animal studies of bio-enhanced ACL repair, models that included volumes of tissue exhibiting short-T2* values (0-12ms)10,22 best predicted mechanical properties. A recent pilot report in women identified variations of T2* in native ACL tissue over the course of the menstrual cycle raising questions about possible periodic variations in ACL mechanical stiffness and whether T2* may be a biomarker for ACL injury risk23.
Menicsi. [UTE] T2* maps of menisci are sensitive to clinically occult intra-substance meniscal degeneration in patients with acute ACL tear7. In patients with knee pain and/or cartilage repair, meniscal [vTE] T2* values, particularly the bi-exponentially derived short-T2* components, differentiate normal menisci from intra-substance degeneration13. Longitudinal [UTE] T2* assessments following meniscal repair and partial menisectomy are sensitive to ultrastructural alterations in meniscus tissue not detected by conventional FSE imaging24.
Bone. Investigations of UTE imaging in cortical bone to assess bone water, macromolecular fraction, porosity and magnetization transfer (MT) effects have attempted to quantitate UTE biomarkers of early stage bone stress injury25-27. In an ex-vivo model of fibular fatigue fracture, UTE-MT imaging detected a decrease of macromolecular fraction and UTE-T2* following cyclic loading likely reflecting rupture to the cortical collagen matrix and increased water in cortical microcracks despite an unchanged bone mineral density25. Efforts are underway to increase scan efficiency to make UTE of bone more clinically applicable28.
ZTE: Zero echo time (ZTE) imaging is an even faster version of the UTE approach wherein the gradient is turned on while the RF signal is applied so that encoding of T2* signal can begin immediately after RF excitation without any delay due to electronic switching from transmit to receive29-31. ZTE imaging provides “CT-like” contrast for bone, and depicts subchondral bony Bankart lesions caused by recurrent anterior shoulder subluxations (a common injury in volleyball and tennis) better than conventional MRI32. Recently, a 3D-T1rho prepared ZTE sequence was proposed for bi-exponential T2* evaluation of semisolid short-T2 tissues including Achilles and patellar tendons, PCL and ACL33. A fundamental limitation of ZTE imaging is an inability to apply slab selection gradients during acquisition necessitating relatively low resolutions for in vivo applications (approximately 1mm isotropic). Further, while ZTE signal from bone likely arises from a combination of bone matrix protons, tightly bound water, and/or other relatively restricted molecules, the exact source of ZTE signal remains to be elucidated.
Discussion - How Low Should You Go?
Although UTE and ZTE sequences are becoming more widely accessible, the decision to employ any of these techniques should take into consideration whether or not acquisition of short or ultrashort echo images are strictly needed for diagnostic detection of the suspected injury. Additional factors to be considered include: the number and spacings of echo images needed for robust mono- or multi-exponential short-T2 signal quantification; innate regional variations of short-T2 signals across different tissues; and the potential for physical activity immediately prior to scanning to transiently alter the short-T2 signals of interest.1. Sports Injuries. 2019. https://medlineplus.gov/sportsinjuries.html. Accessed March 6, 2019.
2. Gatehouse PD, Bydder GM. Magnetic Resonance Imaging of Short T2 Components in Tissue. Clin. Radiol. 2003;58(1):1-19.
3. Mitchell J, Graham W, Best TM, et al. Epidemiology of meniscal injuries in US high school athletes between 2007 and 2013. Knee Surg. Sports Traumatol. Arthrosc. 2016;24(3):715-722.
4. Fredericson M, Jennings F, Beaulieu C, Matheson GO. Stress fractures in athletes. Top. Magn.Reson. Imaging. 2006;17(5):309-325.
5. Kijowski R, Choi J, Shinki K, Del Rio AM, De Smet A. Validation of MRI classification system for tibial stress injuries. AJR Am. J. Roentgenol. 2012;198(4):878-884.
6. Benjamin M, Milz S, Bydder GM. Magnetic resonance imaging of entheses. Part 1. Clin. Radiol. 2008;63(6):691-703.
7. Williams A, Qian Y, Golla S, Chu CR. UTE-T2 * mapping detects sub-clinical meniscus injury after anterior cruciate ligament tear. Osteoarthritis Cartilage. 2012;20(6):486-494.
8. Du J, Bydder GM. Qualitative and quantitative ultrashort-TE MRI of cortical bone. NMR Biomed. 2013;26(5):489-506.
9. Grosse U, Syha R, Hein T, et al. Diagnostic value of T1 and T2 * relaxation times and off-resonance saturation effects in the evaluation of Achilles tendinopathy by MRI at 3T. J. Magn. Reson. Imaging. 2015;41(4):964-973.
10. Beveridge JE, Machan JT, Walsh EG, et al. Magnetic resonance measurements of tissue quantity and quality using T2 * relaxometry predict temporal changes in the biomechanical properties of the healing ACL. J. Orthop. Res. 2018;36(6):1701-1709.
11. Gold GE, Pauly JM, Macovski A, Herfkens RJ. MR spectroscopic imaging of collagen: tendons and knee menisci. Magn. Reson. Med. 1995;34(5):647-654.
12. Juras V, Apprich S, Szomolanyi P, Bieri O, Deligianni X, Trattnig S. Bi-exponential T2 analysis of healthy and diseased Achilles tendons: an in vivo preliminary magnetic resonance study and correlation with clinical score. Eur. Radiol. 2013;23(10):2814-2822.
13. Juras V, Apprich S, Zbyn S, et al. Quantitative MRI analysis of menisci using biexponential T2* fitting with a variable echo time sequence. Magn. Reson. Med. 2014;71(3):1015-1023.
14. Song HK, Wehrli FW. Variable TE gradient and spin echo sequences for in vivo MR microscopy of short T2 species. Magn. Reson. Med. 1998;39(2):251-258.
15. Gardin A, Rasinski P, Berglund J, Shalabi A, Schulte H, Brismar TB. T2 * relaxation time in Achilles tendinosis and controls and its correlation with clinical score. J. Magn. Reson. Imaging. 2016;43(6):1417-1422.
16. Qiao Y, Tao HY, Ma K, Wu ZY, Qu JX, Chen S. UTE-T2() Analysis of Diseased and Healthy Achilles Tendons and Correlation with Clinical Score: An In Vivo Preliminary Study. BioMed research international. 2017;2017:2729807.
17. Chen X, Qiu B. A pilot study of short T2* measurements with ultrashort echo time imaging at 0.35 T. Biomedical engineering online. 2018;17(1):70.
18. Kijowski R, Wilson JJ, Liu F. Bicomponent ultrashort echo time T2* analysis for assessment of patients with patellar tendinopathy. J. Magn. Reson. Imaging. 2017;46(5):1441-1447.
19. Argentieri EC, Koff MF, Lin B, Shah PH, Potter HG, Nwawka OK. Longitudinal Changes in Quantitative MRI and Ultrasound Metrics of Patellar Tendon are Associated with Tendon Degenerationand Leg Dominance within of Collegiate Basketball Players over One Season of Play. 2018 Annual Meeting of the International Society for Magnetic Research in Medicine, Paper #1044, Paris, FR.
20. Tashman S, Zandiyeh P, Warth R, et al. ACL Graft Remodeling Revealed by Serial UTE T2* MRI. 2019 Annual Meeting of the Orthopaedic Research Society; Poster #974, Austin, TX.
21. Williams A, Chu CR. MRI UTE-T2* Shows Evidence for Continued Human ACL Graft Maturation Between 1 and 2 Years After Reconstructive Surgery: A Pilot Clinical Study. 2019 Annual Meeting of the Orthopaedic Reserach Society; Paper#251, Austin, TX.
22. Biercevicz AM, Murray MM, Walsh EG, Miranda DL, Machan JT, Fleming BC. T2 * MR relaxometry and ligament volume are associated with the structural properties of the healing ACL. J. Orthop. Res. 2014;32(4):492-499.
23. Argentieri EC, Braun TW, Breighner RE, Nguyen JT, Koff MT, Potter HG. Pre-Ovulatory to Post-Ovulatory Changes in ACL T2*: New Biomarker for ACL Injury Risk? 2019 Annual Meeting of the Orthopaedic Research Society, Paper #358, Austin, TX.
24. Sneag DB, Shah P, Koff MF, Lim WY, Rodeo SA, Potter HG. Quantitative Ultrashort Echo Time Magnetic Resonance Imaging Evaluation of Postoperative Menisci: a Pilot Study. HSS J. 2015;11(2):123-129.
25. Jerban S, Ma Y, Nazaran A, et al. Detecting stress injury (fatigue fracture) in fibular cortical bone using quantitative ultrashort echo time-magnetization transfer (UTE-MT): An ex vivo study. NMR Biomed. 2018;31(11):e3994.
26. Jerban S, Ma Y, Wan L, et al. Collagen proton fraction from ultrashort echo time magnetization transfer (UTE-MT) MRI modelling correlates significantly with cortical bone porosity measured with micro-computed tomography (muCT). NMR Biomed. 2019;32(2):e4045.
27. Bae WC, Chen PC, Chung CB, Masuda K, D'Lima D, Du J. Quantitative ultrashort echo time (UTE) MRI of human cortical bone: correlation with porosity and biomechanical properties. J. Bone Miner. Res. 2012;27(4):848-857.
28. Wan L, Zhao W, Ma Y, et al. Fast quantitative 3D ultrashort echo time MRI of cortical bone using extended cones sampling. Magn. Reson. Med. 2019.
29. Hafner S. Fast imaging in liquids and solids with the Back-projection Low Angle ShoT (BLAST) technique. Magn. Reson. Imaging. 1994;12(7):1047-1051.
30. Madio DP, Lowe IJ. Ultra-fast imaging using low flip angles and FIDs. Magn. Reson. Med. 1995;34(4):525-529.
31. Weiger M. MRI with zero echo time. eMagRes. 2012;1(2):311-321.
32. Breighner RE, Endo Y, Konin GP, Gulotta LV, Koff MF, Potter HG. Technical Developments: Zero Echo Time Imaging of the Shoulder: Enhanced Osseous Detail by Using MR Imaging. Radiology. 2018;286(3):960-966.
33. Sharafi A, Baboli R, Chang G, Regatte RR. 3D-T1rho prepared zero echo time-based PETRA sequence for in vivo biexponential relaxation mapping of semisolid short-T2 tissues at 3 T. J. Magn Reson. Imaging. 2019.