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Imaging of joint response to exercise with MRI and PET

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Abstract

Imaging of the joint in response to loading stress may provide additional measures of joint structure and function beyond conventional, static imaging studies. Exercise such as running, stair climbing, and squatting allows evaluation of the joint response to larger loading forces than during weight bearing. Quantitative MRI (qMRI) may assess properties of cartilage and meniscus hydration and organization in vivo that have been investigated to assess the functional response of these tissues to physiological stress. [18F]sodium fluoride ([18F]NaF) interrogates areas of newly mineralizing bone and provides an opportunity to study bone physiology, including perfusion and mineralization rate, as a measure of joint loading stress. In this review article, methods utilizing quantitative MRI, PET, and hybrid PET-MRI systems for assessment of the joint response to loading from exercise in vivo are examined. Both methodology and results of various studies performed are outlined and discussed. Lastly, the technical considerations, challenges, and future opportunities for these approaches are addressed.

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References

  1. Skou ST, Bricca A, Roos EM. The impact of physical activity level on the short- and long-term pain relief from supervised exercise therapy and education: a study of 12,796 Danish patients with knee osteoarthritis. Osteoarthr Cartil. 2018;26(11):1474–8.

    Article  CAS  PubMed  Google Scholar 

  2. Burr DB. Changes in bone matrix properties with aging. Bone. 2019;120:85–93.

    Article  CAS  PubMed  Google Scholar 

  3. Chang SH, Mori D, Kobayashi H, Mori Y, Nakamoto H, Okada K, et al. Excessive mechanical loading promotes osteoarthritis through the gremlin-1-NF-kappaB pathway. Nat Commun. 2019;10(1):1442.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Roemer FW, Demehri S, Omoumi P, Link TM, Kijowski R, Saarakkala S, et al. State of the art: imaging of osteoarthritis-revisited 2020. Radiology. 2020;296(1):5–21.

    Article  PubMed  Google Scholar 

  5. Oei EH, van Tiel J, Robinson WH, Gold GE. Quantitative radiological imaging techniques for articular cartilage composition: towards early diagnosis and development of disease-modifying therapeutics for osteoarthritis. Arthritis Care Res. 2014;66(8):1129–41.

    Article  Google Scholar 

  6. Bae WC, Du J, Bydder GM, Chung CB. Conventional and ultrashort time-to-echo magnetic resonance imaging of articular cartilage, meniscus, and intervertebral disk. Top Magn Reson Imaging. 2010;21(5):275–89.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Czernin J, Satyamurthy N, Schiepers C. Molecular mechanisms of bone 18F-NaF deposition. J Nucl Med. 2010;51(12):1826–9.

    Article  CAS  PubMed  Google Scholar 

  8. Turmezei TD, Low SB, Rupret S, Treece GM, Gee AH, MacKay JW, et al. Multiparametric 3-D analysis of bone and joint space width at the knee from weight bearing computed tomography. Osteoarthr Imaging. 2022;2(2):100069.

  9. Barg A, Bailey T, Richter M, de Cesar NC, Lintz F, Burssens A, et al. Weightbearing computed tomography of the foot and ankle: emerging technology topical review. Foot Ankle Int. 2018;39(3):376–86.

    Article  PubMed  Google Scholar 

  10. Zevenbergen L, Gsell W, Cai L, Chan DD, Famaey N, Vander Sloten J, et al. Cartilage-on-cartilage contact: effect of compressive loading on tissue deformations and structural integrity of bovine articular cartilage. Osteoarthr Cartil. 2018;26(12):1699–709.

    Article  CAS  PubMed  Google Scholar 

  11. Jerban S, Chang EY, Du J. Magnetic resonance imaging (MRI) studies of knee joint under mechanical loading: Review. Magn Reson Imaging. 2020;65:27–36.

    Article  PubMed  Google Scholar 

  12. Bruno F, Barile A, Arrigoni F, Laporta A, Russo A, Carotti M, et al. Weight-bearing MRI of the knee: a review of advantages and limits. Acta Biomed. 2018;89(1-S):78–88.

    PubMed  PubMed Central  Google Scholar 

  13. Ye D, Sun X, Zhang C, Zhang S, Zhang X, Wang S, et al. In vivo foot and ankle kinematics during activities measured by using a dual fluoroscopic imaging system: a narrative review. Front Bioeng Biotechnol. 2021;9:693806.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Li X, Majumdar S. Quantitative MRI of articular cartilage and its clinical applications. J Magn Reson Imaging. 2013;38(5):991–1008.

    Article  PubMed  Google Scholar 

  15. Chu CR, Williams AA. Quantitative MRI UTE-T2* and T2* show progressive and continued graft maturation over 2 years in human patients after anterior cruciate ligament reconstruction. Orthop J Sports Med. 2019;7(8):2325967119863056.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Mazzoli V, Uhlrich S, Rubin EB, Kogan F, Hargreaves B, Delp S, et al. editors. Gait retraining as a conservative treatment for medial knee OA: preliminary findings. In: Proceedings of 27th Annual Meeting of ISMRM; May 11–16, 2019. Montreal, Quebec, Canada: Abstract 0864.

  17. Chaudhari AS, Sveinsson B, Moran CJ, McWalter EJ, Johnson EM, Zhang T, et al. Imaging and T2 relaxometry of short-T2 connective tissues in the knee using ultrashort echo-time double-echo steady-state (UTEDESS). Magn Reson Med. 2017;78(6):2136–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Borthakur A, Mellon E, Niyogi S, Witschey W, Kneeland JB, Reddy R. Sodium and T1rho MRI for molecular and diagnostic imaging of articular cartilage. NMR Biomed. 2006;19(7):781–821.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Khan MCM, O’Donovan J, Charlton JM, Roy JS, Hunt MA, Esculier JF. The influence of running on lower limb cartilage: a systematic review and meta-analysis. Sports Med. 2022;52(1):55–74.

    Article  PubMed  Google Scholar 

  20. Esculier JF, Jarrett M, Krowchuk NM, Rauscher A, Wiggermann V, Taunton JE, et al. Cartilage recovery in runners with and without knee osteoarthritis: a pilot study. Knee. 2019;26(5):1049–57.

    Article  PubMed  Google Scholar 

  21. Gatti AA, Noseworthy MD, Stratford PW, Brenneman EC, Totterman S, Tamez-Pena J, et al. Acute changes in knee cartilage transverse relaxation time after running and bicycling. J Biomech. 2017;53:171–7.

    Article  PubMed  Google Scholar 

  22. Chen M, Qiu L, Shen S, Wang F, Zhang J, Zhang C, et al. The influences of walking, running and stair activity on knee articular cartilage: quantitative MRI using T1 rho and T2 map**. PLoS One. 2017;12(11):e0187008.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Subburaj K, Kumar D, Souza RB, Alizai H, Li X, Link TM, et al. The acute effect of running on knee articular cartilage and meniscus magnetic resonance relaxation times in young healthy adults. Am J Sports Med. 2012;40(9):2134–41.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Behzadi C, Welsch GH, Laqmani A, Henes FO, Kaul MG, Schoen G, et al. The immediate effect of long-distance running on T2 and T2* relaxation times of articular cartilage of the knee in young healthy adults at 3.0 T MR imaging. Br J Radiol. 2016;89(1064):20151075.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Mosher TJ, Smith HE, Collins C, Liu Y, Hancy J, Dardzinski BJ, et al. Change in knee cartilage T2 at MR imaging after running: a feasibility study. Radiology. 2005;234(1):245–9.

    Article  PubMed  Google Scholar 

  26. Crowder HA, Mazzoli V, Black MS, Watkins LE, Kogan F, Hargreaves BA, et al. Characterizing the transient response of knee cartilage to running: decreases in cartilage T2 of female recreational runners. J Orthop Res. 2021;39(11):2340–52.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Kyung Kim H, Fernandez J, Logan C, Tarr GP, Doyle A, Mirjalili SA. T2 relaxation time measurements in tibiotalar cartilage after barefoot running and its relationship to ankle biomechanics. J Biomech. 2019;90:103–12.

    Article  PubMed  Google Scholar 

  28. Mosher TJ, Liu Y, Torok CM. Functional cartilage MRI T2 map**: evaluating the effect of age and training on knee cartilage response to running. Osteoarthr Cartil. 2010;18(3):358–64.

    Article  CAS  Google Scholar 

  29. Wang Z, Ai S, Tian F, Liow MHL, Wang S, Zhao J, et al. Higher body mass index is associated with biochemical changes in knee articular cartilage after marathon running: a quantitative T2-relaxation MRI study. Orthop J Sports Med. 2020;8(8):2325967120943874.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Brenneman Wilson EC, Gatti AA, Keir PJ, Maly MR. Daily cumulative load and body mass index alter knee cartilage response to running in women. Gait Posture. 2021;88:192–7.

    Article  PubMed  Google Scholar 

  31. Collins AT, Kulvaranon ML, Cutcliffe HC, Utturkar GM, Smith WAR, Spritzer CE, et al. Obesity alters the in vivo mechanical response and biochemical properties of cartilage as measured by MRI. Arthritis Res Ther. 2018;20(1):232.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Zhang X, Li J, Ren C, Zhang P, Zeng Y, Zhang R, et al. Periodical assessment of four horns of knee meniscus using MR T2 map** imaging in volunteers before and after amateur marathons. Sci Rep. 2022;12(1):12093.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Liess C, Lusse S, Karger N, Heller M, Gluer CC. Detection of changes in cartilage water content using MRI T2-map** in vivo. Osteoarthr Cartil. 2002;10(12):907–13.

    Article  CAS  Google Scholar 

  34. Watkins LE, Haddock B, MacKay JW, Baker J, Uhlrich SD, Mazzoli V, et al. [(18)F]Sodium fluoride PET-MRI detects increased metabolic bone response to whole-joint loading stress in osteoarthritic knees. Osteoarthr Cartil. 2022;30(11):1515–25.

    Article  CAS  Google Scholar 

  35. Goyal A, Gold G, Kogan F, Watkins L, editors. Changes in meniscus T2 relaxation times due to acute exercise in individuals with knee osteoarthritis. Proceedings of 29th Annual Meeting of ISMRM; May 15–21, 2021; Online; Abstract 4236.

  36. Lu XL, Mow VC. Biomechanics of articular cartilage and determination of material properties. Med Sci Sports Exerc. 2008;40(2):193–9.

    Article  PubMed  Google Scholar 

  37. Gatti AA, Keir PJ, Noseworthy MD, Maly MR. Investigating acute changes in osteoarthritic cartilage by integrating biomechanics and statistical shape models of bone: data from the osteoarthritis initiative. MAGMA. 2022;35(5):861–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Farrokhi S, Colletti PM, Powers CM. Differences in patellar cartilage thickness, transverse relaxation time, and deformational behavior: a comparison of young women with and without patellofemoral pain. Am J Sports Med. 2011;39(2):384–91.

    Article  PubMed  Google Scholar 

  39. Cha JG, Lee JC, Kim HJ, Han JK, Lee EH, Kim YD, et al. Comparison of MRI T2 relaxation changes of knee articular cartilage before and after running between young and old amateur athletes. Korean J Radiol. 2012;13(5):594–601.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Karanfil Y, Babayeva N, Donmez G, Diren HB, Eryilmaz M, Doral MN, et al. Thirty minutes of running exercise decreases T2 signal intensity but not thickness of the knee joint cartilage: a 3.0-T magnetic resonance imaging study. Cartilage. 2019;10(4):444–50.

    Article  PubMed  Google Scholar 

  41. Qiu L, Perez J, Emerson C, Barrera CM, Zhong J, Nham F, et al. Biochemical changes in knee articular cartilage of novice half-marathon runners. J Int Med Res. 2019;47(11):5671–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Zheng W, Wu X, Zhang Y, Zhao G, Wei H, Wan L, et al. Biochemical cartilage alteration in T2 map** in knee joints of amateur marathon runners before and after competition. Res Square. 2022. https://doi.org/10.21203/rs.3.rs-1470249/v1.

  43. Luke AC, Stehling C, Stahl R, Li X, Kay T, Takamoto S, et al. High-field magnetic resonance imaging assessment of articular cartilage before and after marathon running: does long-distance running lead to cartilage damage? Am J Sports Med. 2010;38(11):2273–80.

    Article  PubMed  Google Scholar 

  44. Stehling C, Luke A, Stahl R, Baum T, Joseph G, Pan J, et al. Meniscal T1rho and T2 measured with 3.0T MRI increases directly after running a marathon. Skelet Radiol. 2011;40(6):725–35.

  45. Nathani A, Gold GE, Monu U, Hargreaves B, Finlay AK, Rubin EB, et al. Does injection of hyaluronic acid protect against early cartilage injury seen after marathon running? A randomized controlled trial utilizing high-field magnetic resonance imaging. Am J Sports Med. 2019;47(14):3414–22.

    Article  PubMed  Google Scholar 

  46. Kessler DA, MacKay JW, McDonald S, McDonnell S, Grainger AJ, Roberts AR, et al. Effectively measuring exercise-related variations in T1rho and T2 relaxation times of healthy articular cartilage. J Magn Reson Imaging. 2020;52(6):1753–64.

    Article  PubMed  Google Scholar 

  47. Heckelman LN, Smith WAR, Riofrio AD, Vinson EN, Collins AT, Gwynn OR, et al. Quantifying the biochemical state of knee cartilage in response to running using T1rho magnetic resonance imaging. Sci Rep. 2020;10(1):1870.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Schutz UH, Ellermann J, Schoss D, Wiedelbach H, Beer M, Billich C. Biochemical cartilage alteration and unexpected signal recovery in T2* map** observed in ankle joints with mobile MRI during a transcontinental multistage footrace over 4486 km. Osteoarthr Cartil. 2014;22(11):1840–50.

    Article  CAS  PubMed  Google Scholar 

  49. Hesper T, Miese FR, Hosalkar HS, Behringer M, Zilkens C, Antoch G, et al. Quantitative T2(*) assessment of knee joint cartilage after running a marathon. Eur J Radiol. 2015;84(2):284–9.

    Article  PubMed  Google Scholar 

  50. Schutz U, Ehrhardt M, God S, Billich C, Beer M, Trattnig S. A mobile MRI field study of the biochemical cartilage reaction of the knee joint during a 4,486 km transcontinental multistage ultra-marathon using T2* map**. Sci Rep. 2020;10(1):8157.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Zhang P, Yu B, Zhang R, Chen X, Shao S, Zeng Y, et al. Longitudinal study of the morphological and T2* changes of knee cartilages of marathon runners using prototype software for automatic cartilage segmentation. Br J Radiol. 2021;94(1119):20200833.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Schutz U, Martensen T, Kleiner S, Dreyhaupt J, Wegener M, Wilke HJ, et al. T2*-map** of knee cartilage in response to mechanical loading in alpine skiing: a feasibility study. Diagnostics (Basel). 2022;12(6).

  53. Kersting UG, Stubendorff JJ, Schmidt MC, Bruggemann GP. Changes in knee cartilage volume and serum COMP concentration after running exercise. Osteoarthr Cartil. 2005;13(10):925–34.

    Article  Google Scholar 

  54. Eckstein F, Lemberger B, Gratzke C, Hudelmaier M, Glaser C, Englmeier KH, et al. In vivo cartilage deformation after different types of activity and its dependence on physical training status. Ann Rheum Dis. 2005;64(2):291–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Kessler MA, Glaser C, Tittel S, Reiser M, Imhoff AB. Volume changes in the menisci and articular cartilage of runners: an in vivo investigation based on 3-D magnetic resonance imaging. Am J Sports Med. 2006;34(5):832–6.

    Article  PubMed  Google Scholar 

  56. Kessler MA, Glaser C, Tittel S, Reiser M, Imhoff AB. Recovery of the menisci and articular cartilage of runners after cessation of exercise: additional aspects of in vivo investigation based on 3-dimensional magnetic resonance imaging. Am J Sports Med. 2008;36(5):966–70.

    Article  PubMed  Google Scholar 

  57. Boocock M, McNair P, Cicuttini F, Stuart A, Sinclair T. The short-term effects of running on the deformation of knee articular cartilage and its relationship to biomechanical loads at the knee. Osteoarthr Cartil. 2009;17(7):883–90.

    Article  CAS  Google Scholar 

  58. Niehoff A, Muller M, Bruggemann L, Savage T, Zaucke F, Eckstein F, et al. Deformational behaviour of knee cartilage and changes in serum cartilage oligomeric matrix protein (COMP) after running and drop landing. Osteoarthr Cartil. 2011;19(8):1003–10.

    Article  CAS  Google Scholar 

  59. Bratke G, Bruggemann GP, Willwacher S, Mahlich D, Trudeau MB, Rohr E, et al. Does footwear affect articular cartilage volume change after a prolonged run? Scand J Med Sci Sports. 2020;30(2):332–8.

    Article  PubMed  Google Scholar 

  60. Chalian M, Li X, Guermazi A, Obuchowski NA, Carrino JA, Oei EH, et al. The QIBA profile for MRI-based compositional imaging of knee cartilage. Radiology. 2021;301(2):423–32.

    Article  PubMed  Google Scholar 

  61. Du J, Bydder M, Takahashi AM, Carl M, Chung CB, Bydder GM. Short T2 contrast with three-dimensional ultrashort echo time imaging. Magn Reson Imaging. 2011;29(4):470–82.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Silva MJ, Uthgenannt BA, Rutlin JR, Wohl GR, Lewis JS, Welch MJ. In vivo skeletal imaging of 18F-fluoride with positron emission tomography reveals damage- and time-dependent responses to fatigue loading in the rat ulna. Bone. 2006;39(2):229–36.

    Article  CAS  PubMed  Google Scholar 

  63. Tomlinson RE, Silva MJ, Shoghi KI. Quantification of skeletal blood flow and fluoride metabolism in rats using PET in a pre-clinical stress fracture model. Mol Imaging Biol. 2012;14(3):348–54.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Haddock B, Fan AP, Uhlrich SD, Jorgensen NR, Suetta C, Gold GE, et al. Assessment of acute bone loading in humans using [(18)F]NaF PET/MRI. Eur J Nucl Med Mol Imaging. 2019;46(12):2452–63.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Hawkins RA, Choi Y, Huang SC, Hoh CK, Dahlbom M, Schiepers C, et al. Evaluation of the skeletal kinetics of fluorine-18-fluoride ion with PET. J Nucl Med. 1992;33(5):633–42.

    CAS  PubMed  Google Scholar 

  66. Puri T, Frost ML, Cook GJ, Blake GM. [(18)F] Sodium fluoride PET kinetic parameters in bone imaging. Tomography. 2021;7(4):843–54.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Besier TF, Gold GE, Delp SL, Fredericson M, Beaupre GS. The influence of femoral internal and external rotation on cartilage stresses within the patellofemoral joint. J Orthop Res. 2008;26(12):1627–35.

    Article  PubMed  Google Scholar 

  68. Gatti A, Haddock B, Alcantara R, St. Pierre S, Peirlinck M, Uhlrich S, et al. editors. Validation of [18F]NaF PET as a measure of bone remodeling using finite element analysis. North American Congress on Biomechanics; 2022.

  69. Klein-Nulend J, van Oers RF, Bakker AD, Bacabac RG. Bone cell mechanosensitivity, estrogen deficiency, and osteoporosis. J Biomech. 2015;48(5):855–65.

    Article  PubMed  Google Scholar 

  70. Hemmatian H, Bakker AD, Klein-Nulend J, van Lenthe GH. Aging, osteocytes, and mechanotransduction. Curr Osteoporos Rep. 2017;15(5):401–11.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Watkins L, MacKay J, Haddock B, Mazzoli V, Uhlrich S, Gold G, et al. Assessment of quantitative [(18)F]Sodium fluoride PET measures of knee subchondral bone perfusion and mineralization in osteoarthritic and healthy subjects. Osteoarthr Cartil. 2021.

  72. Savic D, Pedoia V, Seo Y, Yang J, Bucknor M, Franc BL, et al. Imaging bone-cartilage interactions in osteoarthritis using [18F]-NaF PET-MRI. Mol Imaging. 2016;15:1–12.

    Article  CAS  PubMed  Google Scholar 

  73. Tibrewala R, Bahroos E, Mehrabian H, Foreman SC, Link TM, Pedoia V, et al. [(18) F]-Sodium fluoride PET/MR imaging for bone-cartilage interactions in hip osteoarthritis: a feasibility study. J Orthop Res. 2019;37(12):2671–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Tibrewala R, Pedoia V, Bucknor M, Majumdar S. Principal component analysis of simultaneous PET-MRI reveals patterns of bone-cartilage interactions in osteoarthritis. J Magn Reson Imaging. 2020;52(5):1462–74.

    Article  PubMed  Google Scholar 

  75. Kogan F, Fan AP, Monu UD, Iagaru A, Hargreaves BA, Gold GE. Quantitative imaging of bone-cartilage interactions in ACL-injured patients with PET-MRI. Osteoarthr Cartil. 2018;26(6):790–6.

    Article  CAS  Google Scholar 

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  1. Steadman Philippon Research Institute, Vail, CO, USA

    Lauren E. Watkins

  2. Department of Radiology, Stanford University, 1201 Welch Rd, Stanford, CA, 94305, USA

    Ananya Goyal, Anthony A. Gatti & Feliks Kogan

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FK receives research support from GE Healthcare. AAG is the founder of NeuralSeg Ltd. a medical image analysis company. All authors have no other conflicts of interest to declare.

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Watkins, L.E., Goyal, A., Gatti, A.A. et al. Imaging of joint response to exercise with MRI and PET. Skeletal Radiol 52, 2159–2183 (2023). https://doi.org/10.1007/s00256-022-04271-7

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