Abstract
Objective
To investigate the association between pain and perfusion in bone marrow lesions with and without cysts assessed dynamic contrast-enhanced (DCE)-MRI in patients with knee osteoarthritis.
Subjects and methods
In a cross-sectional setting, perfusion in bone marrow lesions was assessed using 3 Tesla MRI and correlated (Spearman’s rank correlation) to pain using the knee injury and osteoarthritis outcome score (KOOS). Bone marrow lesions were assessed across the whole knee with DCE-MRI using heuristic variable and non-contrast-enhanced-MRI using MRI osteoarthritis knee score.
Results
Data were available from 107 participants. The participants had a mean age of 60.8 years, mean BMI of 34.5 kg/m2, mean KOOS-pain of 63.7 (0–100 scale), and mean bone marrow lesion sum score of 6.5 (0–45 scale). The bivariate association between KOOS-pain and the heuristic perfusion variable time to peak in bone marrow lesions containing subchondral cysts showed a statistically significant correlation (r = 0.40; p = 0.002). The perfusion variables were not correlated with KOOS-pain in bone marrow lesions without cysts.
Conclusion
In this cross-sectional study, the rate of perfusion (TTP) in bone marrow lesions containing subchondral cysts was associated with pain in patients with knee OA. DCE-MRI has a potential to be used for separating subtypes of OA.
This is a preview of subscription content, access via your institution.



Abbreviations
- BMI:
-
Body mass index
- BML:
-
Bone marrow lesion
- DCE-MRI:
-
Dynamic contrast-enhanced MRI
- eGFR:
-
Estimated glomerular filtration rate
- IRE:
-
Initial rate of enhancement
- KLG:
-
Kellgren Lawrence grade
- KOOS:
-
Knee injury and osteoarthritis outcome score
- ME:
-
Maximum enhancement
- MOAKS:
-
MRI osteoarthritis knee score
- MRI:
-
Magnetic resonance imaging
- non-CE MRI:
-
Non-contrast-enhanced MRI
- OA:
-
Osteoarthritis
- TTP:
-
Time to peak
- Vol.Voxel:
-
The volume (ml) of voxels with “plateau” or “washout” patterns, i.e., the most perfused voxels
References
Hunter DJ, Bierma-Zeinstra S. Osteoarthritis Lancet. 2019;393(10182):1745–59.
Hannan MT, Felson DT, Pincus T. Analysis of the discordance between radiographic changes and knee pain in osteoarthritis of the knee. J Rheumatol. 2000;27(6):1513–7.
Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthr Cartil. 2013;21(1):16–21.
Bartlett SJ, Ling SM, Mayo NE, Scott SC, Bingham CO, 3rd. Identifying common trajectories of joint space narrowing over two years in knee osteoarthritis. Arthritis Care Res (Hoboken). 2011; 63(12):1722-1728.
Waarsing JH, Bierma-Zeinstra SMA, Weinans H. Distinct subtypes of knee osteoarthritis: data from the osteoarthritis initiative. Rheumatology. 2015;54(9):1650–8.
Resnick D, Niwayama G, Coutts RD. Subchondral cysts (geodes) in arthritic disorders: pathologic and radiographic appearance of the hip joint. AJR Am J Roentgenol. 1977;128(5):799–806.
Madry H, van Dijk CN, Mueller-Gerbl M. The basic science of the subchondral bone. Knee Surg Sports Traumatol Arthrosc. 2010;18(4):419–33.
Felson DT, Chaisson CE, Hill CL, Totterman SM, Gale ME, Skinner KM, et al. The association of bone marrow lesions with pain in knee osteoarthritis. Ann Intern Med. 2001;134(7):541–9.
Yusuf E, Kortekaas MC, Watt I, Huizinga TW, Kloppenburg M. Do knee abnormalities visualised on MRI explain knee pain in knee osteoarthritis? A systematic review. Ann Rheum Dis. 2011;70(1):60–7.
Axelsen MB, Poggenborg RP, Stoltenberg M, Kubassova O, Boesen M, Horslev-Petersen K, et al. Reliability and responsiveness of dynamic contrast-enhanced magnetic resonance imaging in rheumatoid arthritis. Scand J Rheumatol. 2013;42(2):115–22.
Kubassova O, Boesen M, Boyle RD, Cimmino MA, Jensen KE, Bliddal H, et al. Fast and robust analysis of dynamic contrast enhanced MRI datasets. Med Image Comput Comput Assist Interv. 2007;10(Pt 2):261–9.
Tofts PS. Modeling tracer kinetics in dynamic Gd-DTPA MR imaging. J Magn Reson Imaging. 1997;7(1):91–101.
Paldino MJ, Barboriak DP. Fundamentals of quantitative dynamic contrast-enhanced MR imaging. Magn Reson Imaging Clin N Am. 2009;17(2):277–89.
d’Arcy JA, Collins DJ, Rowland IJ, Padhani AR, Leach MO. Applications of sliding window reconstruction with cartesian sampling for dynamic contrast enhanced MRI. NMR Biomed. 2002;15(2):174–83.
Kuhl CK, Mielcareck P, Klaschik S, Leutner C, Wardelmann E, Gieseke J, et al. Dynamic breast MR imaging: are signal intensity time course data useful for differential diagnosis of enhancing lesions? Radiology. 1999;211(1):101–10.
Budzik JF, Ding J, Norberciak L, Pascart T, Toumi H, Verclytte S, et al. Perfusion of subchondral bone marrow in knee osteoarthritis: a dynamic contrast-enhanced magnetic resonance imaging preliminary study. Eur J Radiol. 2017;88:129–34.
Seah S, Wheaton D, Li L, Dyke JP, Talmo C, Harvey WF, et al. The relationship of tibial bone perfusion to pain in knee osteoarthritis. Osteoarthr Cartil. 2012;20(12):1527–33.
Gait AD, Hodgson R, Parkes MJ, Hutchinson CE, O’Neill TW, Maricar N, et al. Synovial volume vs synovial measurements from dynamic contrast enhanced MRI as measures of response in osteoarthritis. Osteoarthr Cartil. 2016;24(8):1392–8.
Riis RG, Gudbergsen H, Henriksen M, Ballegaard C, Bandak E, Rottger D, et al. Synovitis assessed on static and dynamic contrast-enhanced magnetic resonance imaging and its association with pain in knee osteoarthritis: a cross-sectional study. Eur J Radiol. 2016;85(6):1099–108.
Roos EM, Lohmander LS. The knee injury and osteoarthritis outcome score (KOOS): from joint injury to osteoarthritis. Health Qual Life Outcomes. 2003;1:64.
KOOS scoring. http://www.koos.nu/KOOSscoring2012.pdf. 2012.
Gudbergsen H, Bartels EM, Krusager P, Waehrens EE, Christensen R, Danneskiold-Samsoe B, et al. Test-retest of computerized health status questionnaires frequently used in the monitoring of knee osteoarthritis: a randomized crossover trial. BMC Musculoskelet Disord. 2011;12:190.
Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis. 1957;16(4):494–502.
Kubassova O, Boesen M, Cimmino MA, Bliddal H. A computer-aided detection system for rheumatoid arthritis MRI data interpretation and quantification of synovial activity. Eur J Radiol. 2010;74(3):e67–72.
Boesen M, Kubassova O, Parodi M, Bliddal H, Innocenti S, Garlaschi G, et al. Comparison of the manual and computer-aided techniques for evaluation of wrist synovitis using dynamic contrast-enhanced MRI on a dedicated scanner. Eur J Radiol. 2011;77(2):202–6.
Axelsen MB, Stoltenberg M, Poggenborg RP, Kubassova O, Boesen M, Bliddal H, et al. Dynamic gadolinium-enhanced magnetic resonance imaging allows accurate assessment of the synovial inflammatory activity in rheumatoid arthritis knee joints: a comparison with synovial histology. Scand J Rheumatol. 2012;41(2):89–94.
Ballegaard C, Riis RG, Bliddal H, Christensen R, Henriksen M, Bartels EM, et al. Knee pain and inflammation in the infrapatellar fat pad estimated by conventional and dynamic contrast-enhanced magnetic resonance imaging in obese patients with osteoarthritis: a cross-sectional study. Osteoarthr Cartil. 2014;22(7):933–40.
Bandak E, Boesen M, Bliddal H, Riis RG, Gudbergsen H, Henriksen M. Associations between muscle perfusion and symptoms in knee osteoarthritis: a cross sectional study. Osteoarthr Cartil. 2015;23(10):1721–7.
Hunter DJ, Guermazi A, Lo GH, Grainger AJ, Conaghan PG, Boudreau RM, et al. Evolution of semi-quantitative whole joint assessment of knee OA: MOAKS (MRI Osteoarthritis Knee Score). Osteoarthr Cartil. 2011;19(8):990–1002.
Jafarzadeh SR, Clancy M, Li JS, Apovian CM, Guermazi A, Eckstein F, et al. Changes in the structural features of osteoarthritis in a year of weight loss. Osteoarthr Cartil. 2018;26(6):775–82.
Torres L, Dunlop DD, Peterfy C, Guermazi A, Prasad P, Hayes KW, et al. The relationship between specific tissue lesions and pain severity in persons with knee osteoarthritis. Osteoarthr Cartil. 2006;14(10):1033–40.
Kornaat PR, Bloem JL, Ceulemans RY, Riyazi N, Rosendaal FR, Nelissen RG, et al. Osteoarthritis of the knee: association between clinical features and MR imaging findings. Radiology. 2006;239(3):811–7.
Ferguson AB Jr. The pathological changes in degenerative arthritis of the hip and treatment by rotational osteotomy. J Bone Joint Surg Am. 1964;46:1337–52.
Rhaney K, Lamb DW. The cysts of osteoarthritis of the hip; a radiological and pathological study. J Bone Joint Surg Br. 1955; 37-b(4):663-675.
Landells JW. The bone cysts of osteoarthritis. J Bone Joint Surg Br. 1953; 35-b(4):643-649.
Freund E. The pathological significance of intra-articular pressure. Edinb Med J. 1940;47(3):192–203.
Pouders C, De Maeseneer M, Van Roy P, Gielen J, Goossens A, Shahabpour M. Prevalence and MRI-anatomic correlation of bone cysts in osteoarthritic knees. AJR Am J Roentgenol. 2008;190(1):17–21.
Yusup A, Kaneko H, Liu L, Ning L, Sadatsuki R, Hada S, et al. Bone marrow lesions, subchondral bone cysts and subchondral bone attrition are associated with histological synovitis in patients with end-stage knee osteoarthritis: a cross-sectional study. Osteoarthr Cartil. 2015;23(11):1858–64.
Crema MD, Roemer FW, Marra MD, Niu J, Lynch JA, Felson DT, et al. Contrast-enhanced MRI of subchondral cysts in patients with or at risk for knee osteoarthritis: the MOST study. Eur J Radiol. 2010;75(1):e92–6.
Lane LB, Villacin A, Bullough PG. The vascularity and remodelling of subchondrial bone and calcified cartilage in adult human femoral and humeral heads. An age- and stress-related phenomenon. J Bone Joint Surg (Br). 1977;59(3):272–8.
Acknowledgments
The authors would like to thank the participants involved in the trial and the staff at the Department of Radiology, Copenhagen University Hospital Bispebjerg-Frederiksberg, Denmark for assisting with image acquisitions, as well as the Image Analysis Group (IAG), London, UK, for providing unrestricted access to use the Dynamika® platform to analyze the DCE-MRI data.
Funding
The trial was initiated by the Parker Institute and supported by Cambridge Weight Plan UK and Novo A/S. The Parker Institute is supported by a core grant from The Oak Foundation (OCAY-18-774-OFIL). None of the funders influenced the study design, collection, analysis and interpretation of data, writing, or the decision to submit the manuscript for publication.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
All procedures performed were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Written and oral informed consent was obtained from each patient. The trial was initiated in November 2016 and terminated in February 2019.
Competing interests
MB is a shareholder and consultant for Image Analysis Group LTD, London, UK. The other authors declare that they have no competing interests.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Daugaard, C.L., Riis, R.G., Bandak, E. et al. Perfusion in bone marrow lesions assessed on DCE-MRI and its association with pain in knee osteoarthritis: a cross-sectional study. Skeletal Radiol 49, 757–764 (2020). https://doi.org/10.1007/s00256-019-03336-4
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00256-019-03336-4