Skip to main content
Top
Published in: Arthritis Research & Therapy 1/2020

Open Access 01-12-2020 | Magnetic Resonance Imaging | Research article

Functional MR imaging beyond structure and inflammation—radiographic axial spondyloarthritis is associated with proteoglycan depletion of the lumbar spine

Authors: Daniel B. Abrar, Christoph Schleich, Styliani Tsiami, Anja Müller-Lutz, Karl Ludger Radke, Neela Holthausen, Miriam Frenken, Matthias Boschheidgen, Gerald Antoch, Johanna Mucke, Philipp Sewerin, Juergen Braun, Sven Nebelung, Xenofon Baraliakos

Published in: Arthritis Research & Therapy | Issue 1/2020

Login to get access

Abstract

Background

To compare the glycosaminoglycan (GAG) content of lumbar intervertebral disks (IVDs) of patients with ankylosing spondylitis (AS) and healthy volunteers and to investigate the association of GAG depletion and disease-related clinical and imaging features.

Methods

Lumbar spines of 50 AS patients (mean age 50 ± 10.5 years) and 30 age-matched volunteers were studied with 3-T magnetic resonance imaging (MRI) and conventional radiographs (CR). The MRI protocol included high-resolution morphological sequences and the compositional GAG chemical exchange saturation transfer imaging technique (gagCEST). Morphological images were analyzed by three raters for inflammatory activity, fat deposition, disk degeneration, and structural changes on CR. Clinical and serological measures included the Bath AS Disease Activity (BASDAI) and Bath AS Function (BASFI) Indices and C-reactive protein (CRP) levels. GagCEST values of both groups were compared using a linear mixed model. Kendall-Tau correlation analyses were performed.

Results

GagCEST values were significantly lower in AS patients (2.0 ± 1.7%) vs. healthy volunteers (2.4 ± 1.8%), p = 0.001. Small, yet significant correlations were found between gagCEST values and CRP levels (τ = − 0.14, p = 0.007), BASFI (τ = − 0.18, p < 0.001) and presence of syndesmophytes (τ = − 0.17, p = 0.001). No significant correlations were found with BASDAI, inflammation, and fat deposition MRI scores.

Conclusions

Lumbar spines of r-AS patients undergo significant GAG depletion, independently associated with syndesmophyte formation, functional disability, and increased serological inflammation markers. Beyond establishing a pathophysiological role of the cartilage in AS, these findings suggest that gagCEST imaging may have an adjunct confirmatory role in the assessment of disease-related pathological MRI findings in axial spondyloarthritis.
Literature
2.
go back to reference Braun J. Axial spondyloarthritis including ankylosing spondylitis. Rheumatology (Oxford). 2018;57(suppl_6):vi1–3.CrossRef Braun J. Axial spondyloarthritis including ankylosing spondylitis. Rheumatology (Oxford). 2018;57(suppl_6):vi1–3.CrossRef
3.
go back to reference Baraliakos X, Hermann K-GA, Xu S, et al. Spinal mobility in the cervical and lumbar spine correlates with magnetic resonance imaging findings for inflammatory and structural changes in patients with active ankylosing spondylitis. Clin Exp Rheumatol. 2020;38(3):467–71. Baraliakos X, Hermann K-GA, Xu S, et al. Spinal mobility in the cervical and lumbar spine correlates with magnetic resonance imaging findings for inflammatory and structural changes in patients with active ankylosing spondylitis. Clin Exp Rheumatol. 2020;38(3):467–71.
4.
go back to reference Baraliakos X, Davis J, Tsuji W, et al. Magnetic resonance imaging examinations of the spine in patients with ankylosing spondylitis before and after therapy with the tumor necrosis factor alpha receptor fusion protein etanercept. Arthritis Rheum. 2005;52(4):1216–23.CrossRef Baraliakos X, Davis J, Tsuji W, et al. Magnetic resonance imaging examinations of the spine in patients with ankylosing spondylitis before and after therapy with the tumor necrosis factor alpha receptor fusion protein etanercept. Arthritis Rheum. 2005;52(4):1216–23.CrossRef
5.
go back to reference Sieper J, Rudwaleit M, Baraliakos X, et al. The Assessment of SpondyloArthritis international Society (ASAS) handbook: a guide to assess spondyloarthritis. Ann Rheum Dis. 2009;68(Suppl 2):ii1–44.CrossRef Sieper J, Rudwaleit M, Baraliakos X, et al. The Assessment of SpondyloArthritis international Society (ASAS) handbook: a guide to assess spondyloarthritis. Ann Rheum Dis. 2009;68(Suppl 2):ii1–44.CrossRef
6.
go back to reference Hermann K-GA, Baraliakos X, van der Heijde DMFM, et al. Descriptions of spinal MRI lesions and definition of a positive MRI of the spine in axial spondyloarthritis: a consensual approach by the ASAS/OMERACT MRI study group. Ann Rheum Dis. 2012;71(8):1278–88.CrossRef Hermann K-GA, Baraliakos X, van der Heijde DMFM, et al. Descriptions of spinal MRI lesions and definition of a positive MRI of the spine in axial spondyloarthritis: a consensual approach by the ASAS/OMERACT MRI study group. Ann Rheum Dis. 2012;71(8):1278–88.CrossRef
7.
go back to reference Landewé R, Dougados M, Mielants H, et al. Physical function in ankylosing spondylitis is independently determined by both disease activity and radiographic damage of the spine. Ann Rheum Dis. 2009;68(6):863–7.CrossRef Landewé R, Dougados M, Mielants H, et al. Physical function in ankylosing spondylitis is independently determined by both disease activity and radiographic damage of the spine. Ann Rheum Dis. 2009;68(6):863–7.CrossRef
8.
go back to reference de Koning A, Schoones JW, van der Heijde D, et al. Pathophysiology of axial spondyloarthritis: consensus and controversies. Eur J Clin Investig. 2018;48(5):e12913.CrossRef de Koning A, Schoones JW, van der Heijde D, et al. Pathophysiology of axial spondyloarthritis: consensus and controversies. Eur J Clin Investig. 2018;48(5):e12913.CrossRef
9.
go back to reference Machado P, Landewé R, Braun J, et al. Both structural damage and inflammation of the spine contribute to impairment of spinal mobility in patients with ankylosing spondylitis. Ann Rheum Dis. 2010;69(8):1465–70.CrossRef Machado P, Landewé R, Braun J, et al. Both structural damage and inflammation of the spine contribute to impairment of spinal mobility in patients with ankylosing spondylitis. Ann Rheum Dis. 2010;69(8):1465–70.CrossRef
10.
go back to reference Bleil J, Maier R, Hempfing A, et al. Histomorphologic and histomorphometric characteristics of zygapophyseal joint remodeling in ankylosing spondylitis. Arthritis Rheumatol (Hoboken, N.J.). 2014;66(7):1745–54.CrossRef Bleil J, Maier R, Hempfing A, et al. Histomorphologic and histomorphometric characteristics of zygapophyseal joint remodeling in ankylosing spondylitis. Arthritis Rheumatol (Hoboken, N.J.). 2014;66(7):1745–54.CrossRef
11.
go back to reference Appel H, Kuhne M, Spiekermann S, et al. Immunohistochemical analysis of hip arthritis in ankylosing spondylitis: evaluation of the bone-cartilage interface and subchondral bone marrow. Arthritis Rheum. 2006;54(6):1805–13.CrossRef Appel H, Kuhne M, Spiekermann S, et al. Immunohistochemical analysis of hip arthritis in ankylosing spondylitis: evaluation of the bone-cartilage interface and subchondral bone marrow. Arthritis Rheum. 2006;54(6):1805–13.CrossRef
12.
go back to reference Schleich C, Müller-Lutz A, Matuschke F, et al. Glycosaminoglycan chemical exchange saturation transfer of lumbar intervertebral discs in patients with spondyloarthritis. J Magn Reson Imaging. 2015;42(4):1057–63.CrossRef Schleich C, Müller-Lutz A, Matuschke F, et al. Glycosaminoglycan chemical exchange saturation transfer of lumbar intervertebral discs in patients with spondyloarthritis. J Magn Reson Imaging. 2015;42(4):1057–63.CrossRef
13.
go back to reference Kogan F, Hariharan H, Reddy R. Chemical exchange saturation transfer (CEST) imaging: description of technique and potential clinical applications. Curr Radiol Rep. 2013;1(2):102–14.CrossRef Kogan F, Hariharan H, Reddy R. Chemical exchange saturation transfer (CEST) imaging: description of technique and potential clinical applications. Curr Radiol Rep. 2013;1(2):102–14.CrossRef
14.
go back to reference Vinogradov E, Sherry AD, Lenkinski RE. CEST: from basic principles to applications, challenges and opportunities. J Magn Reson. 2012;229:155–72.CrossRef Vinogradov E, Sherry AD, Lenkinski RE. CEST: from basic principles to applications, challenges and opportunities. J Magn Reson. 2012;229:155–72.CrossRef
15.
go back to reference Schleich C, Müller-Lutz A, Zimmermann L, et al. Biochemical imaging of cervical intervertebral discs with glycosaminoglycan chemical exchange saturation transfer magnetic resonance imaging: feasibility and initial results. Skelet Radiol. 2016;45(1):79–85.CrossRef Schleich C, Müller-Lutz A, Zimmermann L, et al. Biochemical imaging of cervical intervertebral discs with glycosaminoglycan chemical exchange saturation transfer magnetic resonance imaging: feasibility and initial results. Skelet Radiol. 2016;45(1):79–85.CrossRef
16.
go back to reference Wang D, Yin H, Liu W, et al. Comparative analysis of the diagnostic values of T2 mapping and diffusion-weighted imaging for sacroiliitis in ankylosing spondylitis. Skelet Radiol. 2020. Wang D, Yin H, Liu W, et al. Comparative analysis of the diagnostic values of T2 mapping and diffusion-weighted imaging for sacroiliitis in ankylosing spondylitis. Skelet Radiol. 2020.
17.
go back to reference Zhang M, Le Zhou HN, et al. Assessment of active and inactive sacroiliitis in patients with ankylosing spondylitis using quantitative dynamic contrast-enhanced MRI. J Magn Reson Imaging. 2017;46(1):71–8.CrossRef Zhang M, Le Zhou HN, et al. Assessment of active and inactive sacroiliitis in patients with ankylosing spondylitis using quantitative dynamic contrast-enhanced MRI. J Magn Reson Imaging. 2017;46(1):71–8.CrossRef
18.
go back to reference Slobodin G, Eshed I. Non-radiographic axial spondyloarthritis. Isr Med Assoc J. 2015;17(12):770–6.PubMed Slobodin G, Eshed I. Non-radiographic axial spondyloarthritis. Isr Med Assoc J. 2015;17(12):770–6.PubMed
19.
go back to reference van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum. 1984;27(4):361–8.CrossRef van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum. 1984;27(4):361–8.CrossRef
20.
go back to reference Pfirrmann CW, Metzdorf A, Zanetti M, et al. Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine. 2001;26(17):1873–8.CrossRef Pfirrmann CW, Metzdorf A, Zanetti M, et al. Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine. 2001;26(17):1873–8.CrossRef
21.
go back to reference Maksymowych WP, Inman RD, Salonen D, et al. Spondyloarthritis Research Consortium of Canada magnetic resonance imaging index for assessment of spinal inflammation in ankylosing spondylitis. Arthritis Rheum. 2005;53(4):502–9.CrossRef Maksymowych WP, Inman RD, Salonen D, et al. Spondyloarthritis Research Consortium of Canada magnetic resonance imaging index for assessment of spinal inflammation in ankylosing spondylitis. Arthritis Rheum. 2005;53(4):502–9.CrossRef
22.
go back to reference Schleich C, Müller-Lutz A, Eichner M, et al. Glycosaminoglycan chemical exchange saturation transfer of lumbar intervertebral discs in healthy volunteers. Spine. 2016;41(2):146–52.CrossRef Schleich C, Müller-Lutz A, Eichner M, et al. Glycosaminoglycan chemical exchange saturation transfer of lumbar intervertebral discs in healthy volunteers. Spine. 2016;41(2):146–52.CrossRef
23.
go back to reference Schleich C, Müller-Lutz A, Blum K, et al. Facet tropism and facet joint orientation: risk factors for the development of early biochemical alterations of lumbar intervertebral discs. Osteoarthr Cartil. 2016;24(10):1761–8.CrossRef Schleich C, Müller-Lutz A, Blum K, et al. Facet tropism and facet joint orientation: risk factors for the development of early biochemical alterations of lumbar intervertebral discs. Osteoarthr Cartil. 2016;24(10):1761–8.CrossRef
24.
go back to reference Müller-Lutz A, Schleich C, Schmitt B, et al. Improvement of gagCEST imaging in the human lumbar intervertebral disc by motion correction. Skelet Radiol. 2015;44(4):505–11.CrossRef Müller-Lutz A, Schleich C, Schmitt B, et al. Improvement of gagCEST imaging in the human lumbar intervertebral disc by motion correction. Skelet Radiol. 2015;44(4):505–11.CrossRef
25.
go back to reference Müller-Lutz A, Schleich C, Pentang G, et al. Age-dependency of glycosaminoglycan content in lumbar discs: a 3t gagcEST study. J Magn Reson Imaging. 2015;42(6):1517–23.CrossRef Müller-Lutz A, Schleich C, Pentang G, et al. Age-dependency of glycosaminoglycan content in lumbar discs: a 3t gagcEST study. J Magn Reson Imaging. 2015;42(6):1517–23.CrossRef
26.
go back to reference Müller-Lutz A, Schleich C, Schmitt B, et al. Gender, BMI and T2 dependencies of glycosaminoglycan chemical exchange saturation transfer in intervertebral discs. Magn Reson Imaging. 2016;34(3):271–5.CrossRef Müller-Lutz A, Schleich C, Schmitt B, et al. Gender, BMI and T2 dependencies of glycosaminoglycan chemical exchange saturation transfer in intervertebral discs. Magn Reson Imaging. 2016;34(3):271–5.CrossRef
27.
29.
go back to reference Garrett S, Jenkinson T, Kennedy LG, et al. A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol. 1994;21(12):2286–91. Garrett S, Jenkinson T, Kennedy LG, et al. A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol. 1994;21(12):2286–91.
30.
go back to reference Beaumont C. Comparison of Henderson’s Method I and restricted maximum likelihood estimation of genetic parameters of reproductive traits. Poult Sci. 1991;70(7):1462–8.CrossRef Beaumont C. Comparison of Henderson’s Method I and restricted maximum likelihood estimation of genetic parameters of reproductive traits. Poult Sci. 1991;70(7):1462–8.CrossRef
32.
go back to reference Braun HJ, Gold GE. Advanced MRI of articular cartilage. Imaging Med. 2011;3(5):541–55.CrossRef Braun HJ, Gold GE. Advanced MRI of articular cartilage. Imaging Med. 2011;3(5):541–55.CrossRef
33.
go back to reference Oei EHG, Wick MC, Müller-Lutz A, et al. Cartilage imaging: techniques and developments. Semin Musculoskelet Radiol. 2018;22(2):245–60.CrossRef Oei EHG, Wick MC, Müller-Lutz A, et al. Cartilage imaging: techniques and developments. Semin Musculoskelet Radiol. 2018;22(2):245–60.CrossRef
34.
go back to reference Cruickshank B. Histopathology of diarthrodial joints in ankylosing spondylitis. Ann Rheum Dis. 1951;10(4):393–404.CrossRef Cruickshank B. Histopathology of diarthrodial joints in ankylosing spondylitis. Ann Rheum Dis. 1951;10(4):393–404.CrossRef
35.
go back to reference Cruickshank B. Lesions of cartilaginous joints in ankylosing spondylitis. J Pathol Bacteriol. 1956;71(1):73–84.CrossRef Cruickshank B. Lesions of cartilaginous joints in ankylosing spondylitis. J Pathol Bacteriol. 1956;71(1):73–84.CrossRef
36.
go back to reference Bleil J, Maier R, Hempfing A, et al. Granulation tissue eroding the subchondral bone also promotes new bone formation in ankylosing spondylitis. Arthritis Rheumatol (Hoboken, N.J.). 2016;68(10):2456–65.CrossRef Bleil J, Maier R, Hempfing A, et al. Granulation tissue eroding the subchondral bone also promotes new bone formation in ankylosing spondylitis. Arthritis Rheumatol (Hoboken, N.J.). 2016;68(10):2456–65.CrossRef
37.
go back to reference Bleil J, Sieper J, Maier R, et al. Cartilage in facet joints of patients with ankylosing spondylitis (AS) shows signs of cartilage degeneration rather than chondrocyte hypertrophy: implications for joint remodeling in AS. Arthritis Res Ther. 2015;17:170.CrossRef Bleil J, Sieper J, Maier R, et al. Cartilage in facet joints of patients with ankylosing spondylitis (AS) shows signs of cartilage degeneration rather than chondrocyte hypertrophy: implications for joint remodeling in AS. Arthritis Res Ther. 2015;17:170.CrossRef
38.
go back to reference Baraliakos X, Østergaard M, Gensler LS, et al. Comparison of the effects of secukinumab and adalimumab biosimilar on radiographic progression in patients with ankylosing spondylitis: design of a randomized, phase IIIb study (SURPASS). Clin Drug Investig. 2020;40(3):269–78.CrossRef Baraliakos X, Østergaard M, Gensler LS, et al. Comparison of the effects of secukinumab and adalimumab biosimilar on radiographic progression in patients with ankylosing spondylitis: design of a randomized, phase IIIb study (SURPASS). Clin Drug Investig. 2020;40(3):269–78.CrossRef
39.
go back to reference Roos EM, Dahlberg L. Positive effects of moderate exercise on glycosaminoglycan content in knee cartilage: a four-month, randomized, controlled trial in patients at risk of osteoarthritis. Arthritis Rheum. 2005;52(11):3507–14.CrossRef Roos EM, Dahlberg L. Positive effects of moderate exercise on glycosaminoglycan content in knee cartilage: a four-month, randomized, controlled trial in patients at risk of osteoarthritis. Arthritis Rheum. 2005;52(11):3507–14.CrossRef
Metadata
Title
Functional MR imaging beyond structure and inflammation—radiographic axial spondyloarthritis is associated with proteoglycan depletion of the lumbar spine
Authors
Daniel B. Abrar
Christoph Schleich
Styliani Tsiami
Anja Müller-Lutz
Karl Ludger Radke
Neela Holthausen
Miriam Frenken
Matthias Boschheidgen
Gerald Antoch
Johanna Mucke
Philipp Sewerin
Juergen Braun
Sven Nebelung
Xenofon Baraliakos
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2020
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-020-02312-x

Other articles of this Issue 1/2020

Arthritis Research & Therapy 1/2020 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.