Advertisement

Differentiation of human cartilage degeneration by functional MRI mapping—an ex vivo study

  • Daniel TruhnEmail author
  • Björn Sondern
  • Simon Oehrl
  • Markus Tingart
  • Matthias Knobe
  • Dorit Merhof
  • Christiane Kuhl
  • Johannes Thüring
  • Sven Nebelung
Magnetic Resonance
  • 20 Downloads

Abstract

Objective

To evaluate whether the response to loading of cartilage samples as assessed ex vivo by quantitative MRI (qMRI) mapping techniques can differentiate intact and early degenerative cartilage.

Methods

Upon IRB approval and written informed consent, 59 macroscopically intact osteochondral samples were obtained from the central lateral femoral condyles of patients undergoing total knee replacement. Spatially resolved T1, T2, T2*, and T1ρ maps were generated prior to and during displacement-controlled quasi-static indentation loading to 405 μm (Δ1/2) and 810 μm (Δ1). Upon manual segmentation, absolute qMRI parameters and loading-induced relative changes (δ1/2, δ1) were determined for the entire cartilage sample and distinct zones and regions. Based on their histologically determined degeneration as quantified according to Mankin (Mankin sum scores [MSS], range 0–14), samples were dichotomised into intact (int; MSS 0–4, n = 35) and early degenerative (ed, MSS 5–8, n = 24).

Results

For T1ρ, consistent loading-induced increases were found for δ1/2 and δ1. Throughout the entire sample, increases in T1ρ were significantly higher in early degenerative than in intact samples (Δ1/2(ed) = 23.8 [q25 = 18.1, q75 = 29.0] %; Δ1/2(int) = 12.7 [q25 = 5.9, q75 = 19.5] %; p < 0.0005), according to Wilcoxon’s signed-rank test). Zonal and regional analysis revealed these changes to be most pronounced in the sub-pistonal area. No significant degeneration-dependent loading-induced changes were found for T1, T2, or T2*.

Conclusion

Aberrant load-bearing of early degenerative cartilage may be detected using T1ρ mapping as a function of loading. Hence, the diagnostic differentiation of intact versus early degenerative cartilage may allow the reliable identification of early and potentially reversible cartilage degeneration, thereby opening new opportunities for diagnosis and treatment of cartilage pathologies.

Key Points

• T1ρ mapping of the cartilage response to loading allows the reliable identification of early degenerative changes ex vivo.

• Distinct response-to-loading patterns of cartilage tissue as assessed by functional MRI techniques are associated with biomechanical and histological tissue properties.

• Non-invasive functional MR imaging techniques may facilitate the more sensitive monitoring of therapeutic outcomes and treatment strategies.

Keywords

Magnetic resonance imaging Cartilage Knee joint 

Abbreviations

δx

Indentation position x

∆δx

Relative change of MRI parameter at indentation position x

ρ

Spearman’s correlation coefficient

DZ

Deep zone

ECS

Entire cartilage sample

ed

Early degenerative

FT

Full thickness

int

Intact

IYM

Instantaneous Young’s modulus

KL

Kellgren-Lawrence grade

MSS

Mankin sum score

OA

Osteoarthritis

PPA

Peri-pistonal area

SPA

Sub-pistonal area

SZ

Superficial zone

TZ

Transitional zone

Notes

Funding

This study has received funding by the START programme of the Faculty of Medicine, RWTH Aachen, Germany, through means of a grant given to SN (691702) and through the START rotation programme granted to DT.

Compliance with ethical standards

Guarantor

The scientific guarantor of this publication is Daniel Truhn.

Conflict of interest

The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

Statistics and biometry

One of the authors has significant statistical expertise.

Informed consent

Written informed consent was obtained from all subjects (patients) in this study.

Ethical approval

Institutional Review Board approval was obtained.

Methodology

• prospective

• experimental

• performed at one institution

Supplementary material

330_2019_6283_MOESM1_ESM.docx (27 kb)
ESM 1 (DOCX 27 kb)

References

  1. 1.
    Bay-Jensen AC, Hoegh-Madsen S, Dam E et al (2010) Which elements are involved in reversible and irreversible cartilage degradation in osteoarthritis? Rheumatol Int 30:435–442CrossRefGoogle Scholar
  2. 2.
    Palmer AJ, Brown CP, McNally EG et al (2013) Non-invasive imaging of cartilage in early osteoarthritis. Bone Joint J 95-B:738–746CrossRefGoogle Scholar
  3. 3.
    Guermazi A, Alizai H, Crema MD, Trattnig S, Regatte RR, Roemer FW (2015) Compositional MRI techniques for evaluation of cartilage degeneration in osteoarthritis. Osteoarthritis Cartilage 23:1639–1653CrossRefGoogle Scholar
  4. 4.
    Saarakkala S, Julkunen P, Kiviranta P, Mäkitalo J, Jurvelin JS, Korhonen RK (2010) Depth-wise progression of osteoarthritis in human articular cartilage: investigation of composition, structure and biomechanics. Osteoarthritis Cartilage 18:73–81CrossRefGoogle Scholar
  5. 5.
    Neu CP (2014) Functional imaging in OA: role of imaging in the evaluation of tissue biomechanics. Osteoarthritis Cartilage 22:1349–1359CrossRefGoogle Scholar
  6. 6.
    Xia Y, Wang N, Lee J, Badar F (2011) Strain-dependent T1 relaxation profiles in articular cartilage by MRI at microscopic resolutions. Magn Reson Med 65:1733–1737CrossRefGoogle Scholar
  7. 7.
    Nebelung S, Brill N, Tingart M et al (2016) Quantitative OCT and MRI biomarkers for the differentiation of cartilage degeneration. Skeletal Radiol 45:505–516CrossRefGoogle Scholar
  8. 8.
    Shiomi T, Nishii T, Tanaka H et al (2010) Loading and knee alignment have significant influence on cartilage MRI T2 in porcine knee joints. Osteoarthritis Cartilage 18:902–908CrossRefGoogle Scholar
  9. 9.
    Hamada H, Nishii T, Tamura S, Tanaka H, Wakayama T, Sugano N (2015) Comparison of load responsiveness of cartilage T1rho and T2 in porcine knee joints: an experimental loading MRI study. Osteoarthritis Cartilage 23:1776–1779CrossRefGoogle Scholar
  10. 10.
    Souza RB, Kumar D, Calixto N et al (2014) Response of knee cartilage T1rho and T2 relaxation times to in vivo mechanical loading in individuals with and without knee osteoarthritis. Osteoarthritis Cartilage 22:1367–1376CrossRefGoogle Scholar
  11. 11.
    Subburaj K, Souza RB, Stehling C et al (2012) Association of MR relaxation and cartilage deformation in knee osteoarthritis. J Orthop Res 30:919–926CrossRefGoogle Scholar
  12. 12.
    Lange T, Knowles BR, Herbst M, Izadpanah K, Zaitsev M (2017) Comparative T2 and T1rho mapping of patellofemoral cartilage under in situ mechanical loading with prospective motion correction. J Magn Reson Imaging 46:452–460CrossRefGoogle Scholar
  13. 13.
    Souza RB, Stehling C, Wyman BT et al (2010) The effects of acute loading on T1rho and T2 relaxation times of tibiofemoral articular cartilage. Osteoarthritis Cartilage 18:1557–1563CrossRefGoogle Scholar
  14. 14.
    Nebelung S, Sondern B, Oehrl S et al (2017) Functional MR imaging mapping of human articular cartilage response to loading. Radiology 282:464–474CrossRefGoogle Scholar
  15. 15.
    Nebelung S, Post M, Raith S et al (2017) Functional in situ assessment of human articular cartilage using MRI: a whole-knee joint loading device. Biomech Model Mechanobiol 16:1971–1986.  https://doi.org/10.1007/s10237-017-0932-4 CrossRefGoogle Scholar
  16. 16.
    Cameron ML, Briggs KK, Steadman JR (2003) Reproducibility and reliability of the outerbridge classification for grading chondral lesions of the knee arthroscopically. Am J Sports Med 31:83–86CrossRefGoogle Scholar
  17. 17.
    Nebelung S, Brill N, Müller F et al (2016) Towards optical coherence tomography-based elastographic evaluation of human cartilage. J Mech Behav Biomed Mater 56:106–119CrossRefGoogle Scholar
  18. 18.
    Nebelung S, Sondern B, Jahr H et al (2018) Non-invasive T1rho mapping of the human cartilage response to loading and unloading. Osteoarthritis Cartilage 26:236–244CrossRefGoogle Scholar
  19. 19.
    Mankin HJ, Dorfman H, Lippiello L, Zarins A (1971) Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data. J Bone Joint Surg Am 53:523–537CrossRefGoogle Scholar
  20. 20.
    Gahunia HK, Lemaire C, Babyn PS, Cross AR, Kessler MJ, Pritzker KP (1995) Osteoarthritis in rhesus macaque knee joint: quantitative magnetic resonance imaging tissue characterization of articular cartilage. J Rheumatol 22:1747–1756Google Scholar
  21. 21.
    Thuring J, Linka K, Itskov M et al (2018) Multiparametric MRI and computational modelling in the assessment of human articular cartilage properties: a comprehensive approach. Biomed Res Int 2018:9460456CrossRefGoogle Scholar
  22. 22.
    van Tiel J, Kotek G, Reijman M et al (2016) Is T1rho mapping an alternative to delayed gadolinium-enhanced MR imaging of cartilage in the assessment of sulphated glycosaminoglycan content in human osteoarthritic knees? An in vivo validation study. Radiology 279:523–531CrossRefGoogle Scholar
  23. 23.
    Li X, Cheng J, Lin K et al (2011) Quantitative MRI using T1rho and T2 in human osteoarthritic cartilage specimens: correlation with biochemical measurements and histology. Magn Reson Imaging 29:324–334CrossRefGoogle Scholar
  24. 24.
    Gründer W, Kanowski M, Wagner M, Werner A (2000) Visualization of pressure distribution within loaded joint cartilage by application of angle-sensitive NMR microscopy. Magn Reson Med 43:884–891CrossRefGoogle Scholar
  25. 25.
    Gründer W (2006) MRI assessment of cartilage ultrastructure. NMR Biomed 19:855–876CrossRefGoogle Scholar
  26. 26.
    Hesper T, Miese FR, Hosalkar HS et al (2015) Quantitative T2(*) assessment of knee joint cartilage after running a marathon. Eur J Radiol 84:284–289CrossRefGoogle Scholar
  27. 27.
    Chavhan GB, Babyn PS, Thomas B, Shroff MM, Haacke EM (2009) Principles, techniques, and applications of T2*-based MR imaging and its special applications. Radiographics 29:1433–1449CrossRefGoogle Scholar
  28. 28.
    Kim T, Min BH, Yoon SH et al (2014) An in vitro comparative study of T2 and T2* mappings of human articular cartilage at 3-Tesla MRI using histology as the standard of reference. Skeletal Radiol 43:947–954CrossRefGoogle Scholar
  29. 29.
    Bittersohl B, Hosalkar HS, Miese FR et al (2015) Zonal T2* and T1Gd assessment of knee joint cartilage in various histological grades of cartilage degeneration: an observational in vitro study. BMJ Open 5:e006895CrossRefGoogle Scholar
  30. 30.
    Xia Y, Wang N, Lee J, Badar F (2011) Strain-dependent T1 relaxation profiles in articular cartilage by MRI at microscopic resolutions. Magn Reson Med 65(6):1733–1737.  https://doi.org/10.1002/mrm.22933
  31. 31.
    Kleemann RU, Krocker D, Cedraro A, Tuischer J, Duda GN (2005) Altered cartilage mechanics and histology in knee osteoarthritis: relation to clinical assessment (ICRS grade). Osteoarthritis Cartilage 13:958–963CrossRefGoogle Scholar
  32. 32.
    Franz T, Hasler EM, Hagg R, Weiler C, Jakob RP, Mainil-Varlet P (2001) In situ compressive stiffness, biochemical composition, and structural integrity of articular cartilage of the human knee joint. Osteoarthritis Cartilage 9:582–592CrossRefGoogle Scholar
  33. 33.
    Chan DD, Cai L, Butz KD, Trippel SB, Nauman EA, Neu CP (2016) In vivo articular cartilage deformation: noninvasive quantification of intratissue strain during joint contact in the human knee. Sci Rep 6:19220CrossRefGoogle Scholar
  34. 34.
    Du YP, Parker DL, Davis WL, Cao G (1994) Reduction of partial-volume artifacts with zero-filled interpolation in three-dimensional MR angiography. J Magn Reson Imaging 4:733–741CrossRefGoogle Scholar

Copyright information

© European Society of Radiology 2019

Authors and Affiliations

  1. 1.Department of Diagnostic and Interventional RadiologyAachen University HospitalAachenGermany
  2. 2.Department of OrthopaedicsAachen University HospitalAachenGermany
  3. 3.Department of Trauma SurgeryAachen University HospitalAachenGermany
  4. 4.Institute of Imaging and Computer VisionRWTH AachenAachenGermany

Personalised recommendations