Cortical matrix remodeling as a hallmark of relapsing-remitting neuroinflammation in MR elastography and quantitative MRI.
Cerebral cortex
Experimental autoimmune encephalomyelitis
Magnetic resonance elastography
Multiple sclerosis
Perineuronal nets
Tomoelastography
Journal
Acta neuropathologica
ISSN: 1432-0533
Titre abrégé: Acta Neuropathol
Pays: Germany
ID NLM: 0412041
Informations de publication
Date de publication:
04 Jan 2024
04 Jan 2024
Historique:
received:
08
08
2023
accepted:
23
11
2023
revised:
03
11
2023
medline:
4
1
2024
pubmed:
4
1
2024
entrez:
4
1
2024
Statut:
epublish
Résumé
Multiple sclerosis (MS) is a chronic neuroinflammatory disease that involves both white and gray matter. Although gray matter damage is a major contributor to disability in MS patients, conventional clinical magnetic resonance imaging (MRI) fails to accurately detect gray matter pathology and establish a clear correlation with clinical symptoms. Using magnetic resonance elastography (MRE), we previously reported global brain softening in MS and experimental autoimmune encephalomyelitis (EAE). However, it needs to be established if changes of the spatiotemporal patterns of brain tissue mechanics constitute a marker of neuroinflammation. Here, we use advanced multifrequency MRE with tomoelastography postprocessing to investigate longitudinal and regional inflammation-induced tissue changes in EAE and in a small group of MS patients. Surprisingly, we found reversible softening in synchrony with the EAE disease course predominantly in the cortex of the mouse brain. This cortical softening was associated neither with a shift of tissue water compartments as quantified by T2-mapping and diffusion-weighted MRI, nor with leukocyte infiltration as seen by histopathology. Instead, cortical softening correlated with transient structural remodeling of perineuronal nets (PNNs), which involved abnormal chondroitin sulfate expression and microgliosis. These mechanisms also appear to be critical in humans with MS, where tomoelastography for the first time demonstrated marked cortical softening. Taken together, our study shows that neuroinflammation (i) critically affects the integrity of PNNs in cortical brain tissue, in a reversible process that correlates with disease disability in EAE, (ii) reduces the mechanical integrity of brain tissue rather than leading to water accumulation, and (iii) shows similar spatial patterns in humans and mice. These results raise the prospect of leveraging MRE and quantitative MRI for MS staging and monitoring treatment in affected patients.
Identifiants
pubmed: 38175305
doi: 10.1007/s00401-023-02658-x
pii: 10.1007/s00401-023-02658-x
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : 372486779
Organisme : Deutsche Forschungsgemeinschaft
ID : 372486779
Organisme : Deutsche Forschungsgemeinschaft
ID : BO 4484/2-1
Organisme : Deutsche Forschungsgemeinschaft
ID : EXC-2049 - 390688087
Organisme : Bundesministerium für Bildung und Forschung
ID : 01EW1811
Informations de copyright
© 2024. The Author(s).
Références
Ashburner J, Friston KJ (2000) Voxel-based morphometry—the methods. Neuroimage 11:805–821
doi: 10.1006/nimg.2000.0582
pubmed: 10860804
Batzdorf CS, Morr AS, Bertalan G, Sack I, Silva RV, Infante-Duarte C (2022) Sexual dimorphism in extracellular matrix composition and viscoelasticity of the healthy and inflamed mouse brain. Biology 11:230
doi: 10.3390/biology11020230
pubmed: 35205095
pmcid: 8869215
Bertalan G, Becker J, Tzschätzsch H, Morr A, Herthum H, Shahryari M et al (2023) Mechanical behavior of the hippocampus and corpus callosum: An attempt to reconcile ex vivo with in vivo and micro with macro properties. J Mech Behav Biomed Mater 138:105613. https://doi.org/10.1016/j.jmbbm.2022.105613
doi: 10.1016/j.jmbbm.2022.105613
pubmed: 36549250
Bertalan G, Guo J, Tzschätzsch H, Klein C, Barnhill E, Sack I et al (2019) Fast tomoelastography of the mouse brain by multifrequency single-shot MR elastography. Magn Reson Med 81:2676–2687. https://doi.org/10.1002/mrm.27586
doi: 10.1002/mrm.27586
pubmed: 30393887
Bertalan G, Klein C, Schreyer S, Steiner B, Kreft B, Tzschätzsch H et al (2020) Biomechanical properties of the hypoxic and dying brain quantified by magnetic resonance elastography. Acta Biomater 101:395–402. https://doi.org/10.1016/j.actbio.2019.11.011
doi: 10.1016/j.actbio.2019.11.011
pubmed: 31726251
Bhargava P, Kim S, Reyes AA, Grenningloh R, Boschert U, Absinta M et al (2021) Imaging meningeal inflammation in CNS autoimmunity identifies a therapeutic role for BTK inhibition. Brain 144:1396–1408. https://doi.org/10.1093/brain/awab045
doi: 10.1093/brain/awab045
pubmed: 33724342
pmcid: 8488383
Bigot M, Chauveau F, Beuf O, Lambert SA (2018) Magnetic resonance elastography of rodent brain. Front Neurol 9:1010. https://doi.org/10.3389/fneur.2018.01010
doi: 10.3389/fneur.2018.01010
pubmed: 30538670
pmcid: 6277573
Budday S, Sommer G, Birkl C, Langkammer C, Haybaeck J, Kohnert J et al (2017) Mechanical characterization of human brain tissue. Acta Biomater 48:319–340. https://doi.org/10.1016/j.actbio.2016.10.036
doi: 10.1016/j.actbio.2016.10.036
pubmed: 27989920
Calabrese M, Agosta F, Rinaldi F, Mattisi I, Grossi P, Favaretto A et al (2009) Cortical lesions and atrophy associated with cognitive impairment in relapsing-remitting multiple sclerosis. Arch Neurol 66:1144–1150. https://doi.org/10.1001/archneurol.2009.174
doi: 10.1001/archneurol.2009.174
pubmed: 19752305
Chanaday N, Roth G (2016) Microglia and astrocyte activation in the frontal cortex of rats with experimental autoimmune encephalomyelitis. Neuroscience 314:160–169
doi: 10.1016/j.neuroscience.2015.11.060
pubmed: 26679600
Constantinescu CS, Farooqi N, O’Brien K, Gran B (2011) Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). Br J Pharmacol 164:1079–1106
doi: 10.1111/j.1476-5381.2011.01302.x
pubmed: 21371012
pmcid: 3229753
Dayan M, Hurtado Rúa SM, Monohan E, Fujimoto K, Pandya S, LoCastro EM et al (2017) MRI analysis of white matter myelin water content in multiple sclerosis: a novel approach applied to finding correlates of cortical thinning. Front Neurosci 11:284. https://doi.org/10.3389/fnins.2017.00284
doi: 10.3389/fnins.2017.00284
pubmed: 28603479
pmcid: 5445177
Fawcett JW, Fyhn M, Jendelova P, Kwok JCF, Ruzicka J, Sorg BA (2022) The extracellular matrix and perineuronal nets in memory. Mol Psychiatry. https://doi.org/10.1038/s41380-022-01634-3
doi: 10.1038/s41380-022-01634-3
pubmed: 35760878
pmcid: 9708575
Fawcett JW, Oohashi T, Pizzorusso T (2019) The roles of perineuronal nets and the perinodal extracellular matrix in neuronal function. Nat Rev Neurosci 20:451–465
doi: 10.1038/s41583-019-0196-3
pubmed: 31263252
Fehlner A, Behrens JR, Streitberger KJ, Papazoglou S, Braun J, Bellmann-Strobl J et al (2016) Higher-resolution MR elastography reveals early mechanical signatures of neuroinflammation in patients with clinically isolated syndrome. J Magn Reson Imaging 44:51–58
doi: 10.1002/jmri.25129
pubmed: 26714969
Fehlner A, Hirsch S, Weygandt M, Christophel T, Barnhill E, Kadobianskyi M et al (2017) Increasing the spatial resolution and sensitivity of magnetic resonance elastography by correcting for subject motion and susceptibility-induced image distortions. J Magn Reson Imaging 46:134–141. https://doi.org/10.1002/jmri.25516
doi: 10.1002/jmri.25516
pubmed: 27764537
Filippi M, Rocca MA, Barkhof F, Brück W, Chen JT, Comi G et al (2012) Association between pathological and MRI findings in multiple sclerosis. Lancet Neurol 11:349–360. https://doi.org/10.1016/s1474-4422(12)70003-0
doi: 10.1016/s1474-4422(12)70003-0
pubmed: 22441196
Ghorbani S, Yong VW (2021) The extracellular matrix as modifier of neuroinflammation and remyelination in multiple sclerosis. Brain 144(7):1958–1973
doi: 10.1093/brain/awab059
pubmed: 33889940
pmcid: 8370400
Gray E, Thomas TL, Betmouni S, Scolding N, Love S (2008) Elevated matrix metalloproteinase-9 and degradation of perineuronal nets in cerebrocortical multiple sclerosis plaques. J Neuropathol Exp Neurol 67:888–899. https://doi.org/10.1097/NEN.0b013e318183d003
doi: 10.1097/NEN.0b013e318183d003
pubmed: 18716555
Green MA, Bilston LE, Sinkus R (2008) In vivo brain viscoelastic properties measured by magnetic resonance elastography. NMR Biomed 21:755–764. https://doi.org/10.1002/nbm.1254
doi: 10.1002/nbm.1254
pubmed: 18457350
Griswold MA, Jakob PM, Heidemann RM, Nittka M, Jellus V, Wang J et al (2002) Generalized autocalibrating partially parallel acquisitions (GRAPPA). Magn Reson Med 47:1202–1210. https://doi.org/10.1002/mrm.10171
doi: 10.1002/mrm.10171
pubmed: 12111967
Guo J, Bertalan G, Meierhofer D, Klein C, Schreyer S, Steiner B et al (2019) Brain maturation is associated with increasing tissue stiffness and decreasing tissue fluidity. Acta Biomater 99:433–442
doi: 10.1016/j.actbio.2019.08.036
pubmed: 31449927
Hametner S, Dal Bianco A, Trattnig S, Lassmann H (2018) Iron related changes in MS lesions and their validity to characterize MS lesion types and dynamics with ultra-high field magnetic resonance imaging. Brain Pathol 28:743–749. https://doi.org/10.1111/bpa.12643
doi: 10.1111/bpa.12643
pubmed: 30020556
pmcid: 8028547
Herthum H, Dempsey SCH, Samani A, Schrank F, Shahryari M, Warmuth C et al (2021) Superviscous properties of the in vivo brain at large scales. Acta Biomater 121:393–404. https://doi.org/10.1016/j.actbio.2020.12.027
doi: 10.1016/j.actbio.2020.12.027
pubmed: 33326885
Herthum H, Hetzer S, Kreft B, Tzschätzsch H, Shahryari M, Meyer T et al (2022) Cerebral tomoelastography based on multifrequency MR elastography in two and three dimensions. Front Bioeng Biotechnol 10:1056131. https://doi.org/10.3389/fbioe.2022.1056131
doi: 10.3389/fbioe.2022.1056131
pubmed: 36532573
pmcid: 9755504
Herthum H, Hetzer S, Scheel M, Shahryari M, Braun J, Paul F et al (2022) In vivo stiffness of multiple sclerosis lesions is similar to that of normal-appearing white matter. Acta Biomater 138:410–421. https://doi.org/10.1016/j.actbio.2021.10.038
doi: 10.1016/j.actbio.2021.10.038
pubmed: 34757062
Herthum H, Shahryari M, Tzschätzsch H, Schrank F, Warmuth C, Görner S et al (2021) Real-time multifrequency MR elastography of the human brain reveals rapid changes in viscoelasticity in response to the valsalva maneuver. Front Bioeng Biotechnol 9:666456. https://doi.org/10.3389/fbioe.2021.666456
doi: 10.3389/fbioe.2021.666456
pubmed: 34026743
pmcid: 8131519
Hirsch S, Braun J, Sack I (2017) Magnetic resonance elastography: physical background and medical applications. Wiley, New York
Howell OW, Reeves CA, Nicholas R, Carassiti D, Radotra B, Gentleman SM et al (2011) Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis. Brain 134:2755–2771. https://doi.org/10.1093/brain/awr182
doi: 10.1093/brain/awr182
pubmed: 21840891
Hulst HE, Geurts JJ (2011) Gray matter imaging in multiple sclerosis: what have we learned? BMC Neurol 11:1–11
doi: 10.1186/1471-2377-11-153
Junker A, Wozniak J, Voigt D, Scheidt U, Antel J, Wegner C et al (2020) Extensive subpial cortical demyelination is specific to multiple sclerosis. Brain Pathol 30:641–652. https://doi.org/10.1111/bpa.12813
doi: 10.1111/bpa.12813
pubmed: 31916298
pmcid: 8018087
Kerbrat A, Gros C, Badji A, Bannier E, Galassi F, Combès B et al (2020) Multiple sclerosis lesions in motor tracts from brain to cervical cord: spatial distribution and correlation with disability. Brain 143:2089–2105. https://doi.org/10.1093/brain/awaa162
doi: 10.1093/brain/awaa162
pubmed: 32572488
pmcid: 7364770
Klein S, Staring M, Murphy K, Viergever MA, Pluim JP (2009) Elastix: a toolbox for intensity-based medical image registration. IEEE Trans Med Imaging 29:196–205
doi: 10.1109/TMI.2009.2035616
pubmed: 19923044
Koch S, Mueller S, Foddis M, Bienert T, von Elverfeldt D, Knab F et al (2019) Atlas registration for edema-corrected MRI lesion volume in mouse stroke models. J Cereb Blood Flow Metab 39:313–323
doi: 10.1177/0271678X17726635
pubmed: 28829217
Kruse SA, Rose GH, Glaser KJ, Manduca A, Felmlee JP, Jack CR Jr et al (2008) Magnetic resonance elastography of the brain. Neuroimage 39:231–237. https://doi.org/10.1016/j.neuroimage.2007.08.030
doi: 10.1016/j.neuroimage.2007.08.030
pubmed: 17913514
Kunzetsova A, Brockhoff P, Christensen R (2017) lmerTest package: tests in linear mixed effect models. J Stat Softw 82:1–26
Leach JB, Powell EM (2015) Extracellular matrix. Springer, New York
doi: 10.1007/978-1-4939-2083-9
Lipp A, Trbojevic R, Paul F, Fehlner A, Hirsch S, Scheel M et al (2013) Cerebral magnetic resonance elastography in supranuclear palsy and idiopathic Parkinson’s disease. Neuroimage Clin 3:381–387. https://doi.org/10.1016/j.nicl.2013.09.006
doi: 10.1016/j.nicl.2013.09.006
pubmed: 24273721
pmcid: 3814959
Lu Y-B, Franze K, Seifert G, Steinhäuser C, Kirchhoff F, Wolburg H et al (2006) Viscoelastic properties of individual glial cells and neurons in the CNS. Proc Natl Acad Sci 103:17759–17764
doi: 10.1073/pnas.0606150103
pubmed: 17093050
pmcid: 1693820
Lucchinetti CF, Popescu BF, Bunyan RF, Moll NM, Roemer SF, Lassmann H et al (2011) Inflammatory cortical demyelination in early multiple sclerosis. N Engl J Med 365:2188–2197
doi: 10.1056/NEJMoa1100648
pubmed: 22150037
pmcid: 3282172
Lüsebrink F, Wollrab A, Speck O (2013) Cortical thickness determination of the human brain using high resolution 3T and 7T MRI data. Neuroimage 70:122–131. https://doi.org/10.1016/j.neuroimage.2012.12.016
doi: 10.1016/j.neuroimage.2012.12.016
pubmed: 23261638
Madsen MAJ, Wiggermann V, Bramow S, Christensen JR, Sellebjerg F, Siebner HR (2021) Imaging cortical multiple sclerosis lesions with ultra-high field MRI. Neuroimage Clin 32:102847. https://doi.org/10.1016/j.nicl.2021.102847
doi: 10.1016/j.nicl.2021.102847
pubmed: 34653837
pmcid: 8517925
Meyer T, Marticorena Garcia S, Tzschätzsch H, Herthum H, Shahryari M, Stencel L et al (2022) Comparison of inversion methods in MR elastography: an open-access pipeline for processing multifrequency shear-wave data and demonstration in a phantom, human kidneys, and brain. Magn Reson Med 88:1840–1850. https://doi.org/10.1002/mrm.29320
doi: 10.1002/mrm.29320
pubmed: 35691940
Millward JM, Guo J, Berndt D, Braun J, Sack I, Infante-Duarte C (2015) Tissue structure and inflammatory processes shape viscoelastic properties of the mouse brain. NMR Biomed 28:831–839. https://doi.org/10.1002/nbm.3319
doi: 10.1002/nbm.3319
pubmed: 25963743
Millward JM, Schnorr J, Taupitz M, Wagner S, Wuerfel JT, Infante-Duarte C (2013) Iron oxide magnetic nanoparticles highlight early involvement of the choroid plexus in central nervous system inflammation. ASN Neuro 5:e00110. https://doi.org/10.1042/an20120081
doi: 10.1042/an20120081
pubmed: 23452162
pmcid: 3610189
Morr AS, Nowicki M, Bertalan G, Vieira Silva R, Infante Duarte C, Koch SP et al (2022) Mechanical properties of murine hippocampal subregions investigated by atomic force microscopy and in vivo magnetic resonance elastography. Sci Rep 12:16723. https://doi.org/10.1038/s41598-022-21105-7
doi: 10.1038/s41598-022-21105-7
pubmed: 36202964
pmcid: 9537158
Murphy MC, Huston J 3rd, Ehman RL (2019) MR elastography of the brain and its application in neurological diseases. Neuroimage 187:176–183. https://doi.org/10.1016/j.neuroimage.2017.10.008
doi: 10.1016/j.neuroimage.2017.10.008
pubmed: 28993232
Nagy N, de la Zerda A, Kaber G, Johnson PY, Hu KH, Kratochvil MJ et al (2018) Hyaluronan content governs tissue stiffness in pancreatic islet inflammation. J Biol Chem 293:567–578. https://doi.org/10.1074/jbc.RA117.000148
doi: 10.1074/jbc.RA117.000148
pubmed: 29183997
Paul F (2016) Pathology and MRI: exploring cognitive impairment in MS. Acta Neurol Scand 134(Suppl 200):24–33. https://doi.org/10.1111/ane.12649
doi: 10.1111/ane.12649
pubmed: 27580903
Paylor JW, Wendlandt E, Freeman TS, Greba Q, Marks WN, Howland JG et al (2018) Impaired cognitive function after perineuronal net degradation in the medial prefrontal cortex. eNeuro. https://doi.org/10.1523/eneuro.0253-18.2018
doi: 10.1523/eneuro.0253-18.2018
pubmed: 30627657
pmcid: 6325561
Pengo M, Miante S, Franciotta S, Ponzano M, Torresin T, Bovis F et al (2022) Retinal hyperreflecting foci associate with cortical pathology in multiple sclerosis. Neurol Neuroimmunol Neuroinflamm. https://doi.org/10.1212/nxi.0000000000001180
doi: 10.1212/nxi.0000000000001180
pubmed: 35606113
pmcid: 9128002
Penny WFK, Ashburner J, Kiebel S, Nichols T (2011) Statistical parametric mapping: the analysis of functional brain images. Elsevier, London
Potter LE, Paylor JW, Suh JS, Tenorio G, Caliaperumal J, Colbourne F et al (2016) Altered excitatory-inhibitory balance within somatosensory cortex is associated with enhanced plasticity and pain sensitivity in a mouse model of multiple sclerosis. J Neuroinflammation 13:1–20
doi: 10.1186/s12974-016-0609-4
Riek K, Millward JM, Hamann I, Mueller S, Pfueller CF, Paul F et al (2012) Magnetic resonance elastography reveals altered brain viscoelasticity in experimental autoimmune encephalomyelitis. Neuroimage Clin 1:81–90. https://doi.org/10.1016/j.nicl.2012.09.003
doi: 10.1016/j.nicl.2012.09.003
pubmed: 24179740
pmcid: 3757734
Sack I (2023) Magnetic resonance elastography from fundamental soft-tissue mechanics to diagnostic imaging. Nat Rev Phys 5:25–42. https://doi.org/10.1038/s42254-022-00543-2
doi: 10.1038/s42254-022-00543-2
Sack I, Beierbach B, Hamhaber U, Klatt D, Braun J (2008) Non-invasive measurement of brain viscoelasticity using magnetic resonance elastography. NMR Biomed 21:265–271. https://doi.org/10.1002/nbm.1189
doi: 10.1002/nbm.1189
pubmed: 17614101
Sack I, Beierbach B, Wuerfel J, Klatt D, Hamhaber U, Papazoglou S et al (2009) The impact of aging and gender on brain viscoelasticity. Neuroimage 46:652–657. https://doi.org/10.1016/j.neuroimage.2009.02.040
doi: 10.1016/j.neuroimage.2009.02.040
pubmed: 19281851
Scarlett JM, Hu SJ, Alonge KM (2022) The “loss” of perineuronal nets in Alzheimer’s disease: missing or hiding in plain sight? Front Integr Neurosci 16:896400. https://doi.org/10.3389/fnint.2022.896400
doi: 10.3389/fnint.2022.896400
pubmed: 35694184
pmcid: 9174696
Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T et al (2012) Fiji: an open-source platform for biological-image analysis. Nat Methods 9:676–682. https://doi.org/10.1038/nmeth.2019
doi: 10.1038/nmeth.2019
pubmed: 22743772
Schregel K, Baufeld C, Palotai M, Meroni R, Fiorina P, Wuerfel J et al (2021) Targeted blood brain barrier opening with focused ultrasound induces focal macrophage/microglial activation in experimental autoimmune encephalomyelitis. Front Neurosci 15:665722. https://doi.org/10.3389/fnins.2021.665722
doi: 10.3389/fnins.2021.665722
pubmed: 34054415
pmcid: 8149750
Schregel K, Wuerfel E, Garteiser P, Gemeinhardt I, Prozorovski T, Aktas O et al (2012) Demyelination reduces brain parenchymal stiffness quantified in vivo by magnetic resonance elastography. Proc Natl Acad Sci USA 109:6650–6655. https://doi.org/10.1073/pnas.1200151109
doi: 10.1073/pnas.1200151109
pubmed: 22492966
pmcid: 3340071
Silva RV, Biskup K, Zabala-Jouvin JK, Batzdorf CS, Stellmach C, Morr AS et al (2023) Brain inflammation induces alterations in glycosaminoglycan metabolism and subsequent changes in CS-4S and hyaluronic acid. Int J Biol Macromol 230:123214. https://doi.org/10.1016/j.ijbiomac.2023.123214
doi: 10.1016/j.ijbiomac.2023.123214
pubmed: 36634800
Silva RV, Morr AS, Mueller S, Koch SP, Boehm-Sturm P, Rodriguez-Sillke Y et al (2021) Contribution of tissue inflammation and blood-brain barrier disruption to brain softening in a mouse model of multiple sclerosis. Front Neurosci 15:701308. https://doi.org/10.3389/fnins.2021.701308
doi: 10.3389/fnins.2021.701308
pubmed: 34497486
pmcid: 8419310
Slaker ML, Harkness JH, Sorg BA (2016) A standardized and automated method of perineuronal net analysis using Wisteria floribunda agglutinin staining intensity. IBRO Rep 1:54–60
doi: 10.1016/j.ibror.2016.10.001
pubmed: 28713865
pmcid: 5507617
Solamen LM, McGarry MDJ, Fried J, Weaver JB, Lollis SS, Paulsen KD (2021) Poroelastic mechanical properties of the brain tissue of normal pressure hydrocephalus patients during lumbar drain treatment using intrinsic actuation MR elastography. Acad Radiol 28:457–466. https://doi.org/10.1016/j.acra.2020.03.009
doi: 10.1016/j.acra.2020.03.009
pubmed: 32331966
Stadelmann C, Albert M, Wegner C, Brück W (2008) Cortical pathology in multiple sclerosis. Curr Opin Neurol 21:229–234. https://doi.org/10.1097/01.wco.0000318863.65635.9a
doi: 10.1097/01.wco.0000318863.65635.9a
pubmed: 18451703
Streitberger K-J, Sack I, Krefting D, Pfüller C, Braun J, Paul F et al (2012) Brain viscoelasticity alteration in chronic-progressive multiple sclerosis. PLoS ONE 7:e29888
doi: 10.1371/journal.pone.0029888
pubmed: 22276134
pmcid: 3262797
Thompson AJ, Baranzini SE, Geurts J, Hemmer B, Ciccarelli O (2018) Multiple sclerosis. Lancet 391:1622–1636. https://doi.org/10.1016/s0140-6736(18)30481-1
doi: 10.1016/s0140-6736(18)30481-1
pubmed: 29576504
Tzschätzsch H, Guo J, Dittmann F, Hirsch S, Barnhill E, Jöhrens K et al (2016) Tomoelastography by multifrequency wave number recovery from time-harmonic propagating shear waves. Med Image Anal 30:1–10
doi: 10.1016/j.media.2016.01.001
pubmed: 26845371
van Horssen J, Bö L, Dijkstra CD, de Vries HE (2006) Extensive extracellular matrix depositions in active multiple sclerosis lesions. Neurobiol Dis 24:484–491. https://doi.org/10.1016/j.nbd.2006.08.005
doi: 10.1016/j.nbd.2006.08.005
pubmed: 17005408
van Olst L, Rodriguez-Mogeda C, Picon C, Kiljan S, James RE, Kamermans A et al (2021) Meningeal inflammation in multiple sclerosis induces phenotypic changes in cortical microglia that differentially associate with neurodegeneration. Acta Neuropathol 141:881–899
doi: 10.1007/s00401-021-02293-4
pubmed: 33779783
pmcid: 8113309
Walton C, King R, Rechtman L, Kaye W, Leray E, Marrie RA et al (2020) Rising prevalence of multiple sclerosis worldwide: insights from the Atlas of MS, third edition. Mult Scler 26:1816–1821. https://doi.org/10.1177/1352458520970841
doi: 10.1177/1352458520970841
pubmed: 33174475
pmcid: 7720355
Wang S, Millward JM, Hanke-Vela L, Malla B, Pilch K, Gil-Infante A et al (2020) MR elastography-based assessment of matrix remodeling at lesion sites associated with clinical severity in a model of multiple sclerosis. Front Neurol 10:1382
doi: 10.3389/fneur.2019.01382
pubmed: 31998225
pmcid: 6970413
Werring DJ, Clark CA, Barker GJ, Thompson AJ, Miller DH (1999) Diffusion tensor imaging of lesions and normal-appearing white matter in multiple sclerosis. Neurology 52:1626–1632. https://doi.org/10.1212/wnl.52.8.1626
doi: 10.1212/wnl.52.8.1626
pubmed: 10331689
Wuerfel J, Paul F, Beierbach B, Hamhaber U, Klatt D, Papazoglou S et al (2010) MR-elastography reveals degradation of tissue integrity in multiple sclerosis. Neuroimage 49:2520–2525
doi: 10.1016/j.neuroimage.2009.06.018
pubmed: 19539039
Yin Z, Romano AJ, Manduca A, Ehman RL, Huston J 3rd (2018) Stiffness and beyond: what MR elastography can tell us about brain structure and function under physiologic and pathologic conditions. Top Magn Reson Imaging 27:305–318. https://doi.org/10.1097/rmr.0000000000000178
doi: 10.1097/rmr.0000000000000178
pubmed: 30289827
pmcid: 6176744