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Multifrequency magnetic resonance elastography of the brain reveals tissue degeneration in neuromyelitis optica spectrum disorder

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Abstract

Objectives

Application of multifrequency magnetic resonance elastography (MMRE) of the brain parenchyma in patients with neuromyelitis optica spectrum disorder (NMOSD) compared to age matched healthy controls (HC).

Methods

15 NMOSD patients and 17 age- and gender-matched HC were examined using MMRE. Two three-dimensional viscoelastic parameter maps, the magnitude |G*| and phase angle φ of the complex shear modulus were reconstructed by simultaneous inversion of full wave-field data in 1.9-mm isotropic resolution at 7 harmonic drive frequencies from 30 to 60 Hz.

Results

In NMOSD patients, a significant reduction of |G*| was observed within the white matter fraction (p = 0.017), predominantly within the thalamic regions (p = 0.003), compared to HC. These parameters exceeded the reduction in brain volume measured in patients versus HC (p = 0.02 whole-brain volume reduction). Volumetric differences in white matter fraction and the thalami were not detectable between patients and HC. However, phase angle φ was decreased in patients within the white matter (p = 0.03) and both thalamic regions (p = 0.044).

Conclusions

MMRE reveals global tissue degeneration with accelerated softening of the brain parenchyma in patients with NMOSD. The predominant reduction of stiffness is found within the thalamic region and related white matter tracts, presumably reflecting Wallerian degeneration.

Key Points

• Magnetic resonance elastography reveals diffuse cerebral tissue changes in patients with NMOSD.

• Premature tissue softening in NMOSD patients indicates tissue degeneration.

• Hypothesis of a widespread cerebral neurodegeneration in form of diffuse tissue alteration.

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Abbreviations

AQP4:

Aquaporin 4 channel

MDEV inversion:

Multifrequency dual elasco-visco inversion

MMRE:

Multifrequency magnetic resonance elastography

NMO:

Neuromyelitis optica

NMOSD:

Neuromyelitis optica spectrum disorder

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Acknowledgement

AF acknowledges a scholarship of the Hanns Seidel Foundation. This work was supported by the German Research Foundation (DFG Exc 257 to FP, DFG 901/17 to IS) and by Bundesministerium für Bildung und Forschung (Competence Network Multiple Sclerosis to FP, FP, KR). The authors thank Susan Pikol and Cynthia Kraut for excellent technical assistance.

The scientific guarantor of this publication is Jens Würfel. The authors of this manuscript declare relationships with the following companies: Alexion, Chugai, Biogen, MedImmune, Teva, MerckSerono, Bayer, Novartis, Roche, SanofiGenzyme, Shire. No complex statistical methods were necessary for this paper. Institutional Review Board approval was obtained. Written informed consent was obtained from all subjects (patients) in this study. Some study subjects or cohorts have been previously reported in Pache F, Zimmermann H, Finke C, et al. (2016) Brain parenchymal damage in neuromyelitis optica spectrum disorder - A multimodal MRI study. Eur Radiol online first: 24 March 2016. DOI 10.1007/s00330-016-4282-x

Methodology: prospective, case-control study, observational, performed at one institution

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    Authors and Affiliations

    1. Department of Radiology, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany

      Kaspar-Josche Streitberger, Andreas Fehlner & Ingolf Sack

    2. Department of Neurology with Experimental Neurology, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany

      Kaspar-Josche Streitberger, Florence Pache, Klemens Ruprecht & Friedemann Paul

    3. NeuroCure Clinical Research Center, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany

      Florence Pache, Anna Lacheta, Sebastian Papazoglou, Alexander Brandt, Friedemann Paul & Jens Wuerfel

    4. Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité – Universitätsmedizin Berlin, Berlin, Germany

      Judith Bellmann-Strobl, Friedemann Paul & Jens Wuerfel

    5. Institute of Medical Informatics, Charité – Universitätsmedizin Berlin, Hindenburgdamm 30, 12203, Berlin, Germany

      Jürgen Braun

    6. Medical Image Analysis Center (MIAC AG), Basel, Switzerland

      Jens Wuerfel

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    1. Kaspar-Josche Streitberger
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    Correspondence to Kaspar-Josche Streitberger.

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    Kaspar-Josche Streitberger and Andreas Fehlner contributed equally to this work.

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    Streitberger, KJ., Fehlner, A., Pache, F. et al. Multifrequency magnetic resonance elastography of the brain reveals tissue degeneration in neuromyelitis optica spectrum disorder. Eur Radiol 27, 2206–2215 (2017). https://doi.org/10.1007/s00330-016-4561-6

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