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Quantitative susceptibility mapping of the normal-appearing white matter as a potential new marker of disability progression in multiple sclerosis

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A Commentary to this article was published on 14 November 2023

Abstract

Objectives

To investigate the normal-appearing white matter (NAWM) susceptibility in a cohort of newly diagnosed multiple sclerosis (MS) patients and to evaluate possible correlations between NAWM susceptibility and disability progression.

Methods

Fifty-nine patients with a diagnosis of MS (n = 53) or clinically isolated syndrome (CIS) (n = 6) were recruited and followed up. All participants underwent neurological examination, blood sampling for serum neurofilament light chain (sNfL) level assessment, lumbar puncture for the quantification of cerebrospinal fluid (CSF) β-amyloid1-42 (Aβ) levels, and brain MRI. T2-weighted scans were used to quantify white matter (WM) lesion loads. For each scan, we derived the NAWM volume fraction and the WM lesion volume fraction. Quantitative susceptibility mapping (QSM) of the NAWM was calculated using the susceptibility tensor imaging (STI) suite. Susceptibility maps were computed with the STAR algorithm.

Results

Primary progressive patients (n = 9) showed a higher mean susceptibility value in the NAWM than relapsing-remitting (n = 44) and CIS (n = 6) (p = 0.01 and p = 0.02). Patients with a higher susceptibility in the NAWM showed increased sNfL concentration (ρ = 0.38, p = 0.004) and lower CSF Aβ levels (ρ = −0.34, p = 0.009). Mean NAWM susceptibility turned out to be a predictor of the expanded disability status scale (EDSS) worsening at follow-up (β = 0.41, t = 2.66, p = 0.01) and of the MS severity scale (MSSS) (β = 0.38, t = 2.43, p = 0.019).

Conclusions

QSM in the NAWM seems to predict the EDSS increment over time. This finding might provide evidence on the role of QSM in identifying patients with an increased risk of early disability progression.

Key Points

• NAWM-QSM is higher in PPMS patients than in RRMS.

• NAWM-QSM seems to be a predictor of EDSS worsening over time.

• Patients with higher NAWM-QSM show increased sNfL concentration and lower CSF Aβ levels.

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Abbreviations

Aβ:

β-Amyloid1-42

CIS:

Clinically isolated syndrome

CSF:

Cerebrospinal fluid

EDSS:

Expanded disability status scale

MRI:

Magnetic resonance imaging

MS:

Multiple sclerosis

MSSS:

Multiple sclerosis severity score

NAWM:

Normal-appearing white matter

NAWM-QSM:

mean QSM value in the NAWM mask

NAWM-VF:

NAWM volume fraction

PPMS:

Primary progressive MS

QSM:

Quantitative susceptibility mapping

RRMS:

Relapsing remitting MS

sNfL:

Serum neurofilament light chain

WM:

White matter

WMLs:

White matter lesions

WMLs-QSM:

Mean QSM value in the lesion mask

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Funding

This study was supported by the Italian Ministry of Health (“Ricerca Corrente” to ES and FT) and Dino Ferrari Center.

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Authors and Affiliations

  1. Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122, Milan, Italy

    Anna M. Pietroboni, Annalisa Colombi, Valeria E. Contarino, Francesco Maria Lo Russo, Giorgio Conte, Silvia Siggillino, Tiziana Carandini, Andrea Arighi, Milena A. De Riz, Marina Arcaro, Giorgio G. Fumagalli, Fabio Triulzi, Elio Scarpini & Daniela Galimberti

  2. University of Milan, Milan, Italy

    Giorgio Conte, Chiara Fenoglio, Luca Sacchi, Fabio Triulzi & Daniela Galimberti

  3. Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy

    Aurelia Morabito

  4. Politecnico di Milano, Milan, Italy

    Anna Maria Bianchi

Authors
  1. Anna M. Pietroboni
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  2. Annalisa Colombi
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  3. Valeria E. Contarino
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Corresponding author

Correspondence to Anna M. Pietroboni.

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The scientific guarantor of this publication is Anna Pietroboni.

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

No complex statistical methods were necessary for this paper.

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

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Institutional Review Board approval was obtained.

Methodology

• prospective

• observational

• cross-sectional study

• performed at one institution

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Pietroboni, A.M., Colombi, A., Contarino, V.E. et al. Quantitative susceptibility mapping of the normal-appearing white matter as a potential new marker of disability progression in multiple sclerosis. Eur Radiol 33, 5368–5377 (2023). https://doi.org/10.1007/s00330-022-09338-6

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  • DOI: https://doi.org/10.1007/s00330-022-09338-6

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