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In vivo quantification of brain soma and neurite density abnormalities in multiple sclerosis

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Abstract

Background

Soma and neurite density imaging (SANDI) is a new biophysical model that incorporates soma in addition to neurite density, thus possibly providing more specific information about the complex pathological processes of multiple sclerosis (MS).

Purpose

To discriminate the pathological abnormalities of MS white matter (WM) lesions, normal-appearing (NA) WM and cortex and to evaluate the associations among SANDI-derived measures, clinical disability, and conventional MRI variables.

Methods

Twenty healthy controls (HC) and 23 MS underwent a 3 T brain MRI. Using SANDI on diffusion-weighted sequence, the fractions of neurite (fneurite) and soma (fsoma) were assessed in WM lesions, NAWM, and cortex.

Results

Compared to HC WM, MS NAWM showed lower fneurite (false discovery rate [FDR]-p = 0.011). In MS patients, WM lesions showed lower fneurite and fsoma compared to both HC and MS NAWM (FDR-p < 0.001 for all). In the cortex, MS patients had lower fneurite and fsoma compared to HC (FDR-p ≤ 0.009). Compared to both HC and RRMS, PMS patients had lower fneurite in NAWM (vs HC: FDR-p < 0.001; vs RRMS: FDR-p = 0.003) and cortex (vs HC: FDR-p < 0.001; vs RRMS: p = 0.031, not surviving FDR correction), and lower cortical fsoma (vs HC: FDR-p < 0.001; vs RRMS: FDR-p = 0.009). Compared to HC, PMS also showed a higher fsoma in NAWM (FDR-p = 0.015). Fneurite and fsoma in the different brain compartments were correlated with age, phenotype, disease duration, disability, WM lesion volumes, normalized brain, cortical, and WM volumes (r from − 0.761 to 0.821, FDR-p ≤ 0.4).

Conclusions

SANDI may represent a clinically relevant model to discriminate different neurodegenerative phenomena that gradually accumulate through MS disease course.

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Data availability

The dataset used and analyzed during the current study is available from the corresponding author on reasonable request.

Abbreviations

DMT:

Disease-modifying treatment

EDSS:

Expanded disability status scale

NBV:

Normalized brain volume

NCV:

Normalized cortical volume

NWMV:

Normalized white matter volume

SANDI:

Soma and neurite density imaging

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Funding

MP is supported by UKRI Future Leaders Fellowship grant no. MR/T020296/2.

Author information

Authors and Affiliations

  1. Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Monica Margoni, Elisabetta Pagani, Paolo Preziosa, Mor Gueye, Matteo Azzimonti, Massimo Filippi & Maria Assunta Rocca

  2. Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Monica Margoni, Paolo Preziosa, Mor Gueye, Matteo Azzimonti, Massimo Filippi & Maria Assunta Rocca

  3. Neurorehabilitation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Massimo Filippi

  4. Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Massimo Filippi

  5. Vita-Salute San Raffaele University, Milan, Italy

    Massimo Filippi & Maria Assunta Rocca

  6. Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, Cardiff, UK

    Marco Palombo

  7. School of Computer Science and Informatics, Cardiff University, Cardiff, UK

    Marco Palombo

Authors
  1. Monica Margoni
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Corresponding author

Correspondence to Maria Assunta Rocca.

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Conflicts of interest

M. Margoni reports grants and personal fees from Almiral. She was awarded a MAGNIMS-ECTRIMS fellowship in 2020. E. Pagani received speakers’ honoraria from Biogen Idec. P. Preziosa received speaker honoraria from Roche, Biogen, Novartis, Merck Serono, Bristol Myers Squibb and Genzyme. He has received research support from Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla. M. Palombo, M. Azzimonti and M. Gueye have nothing to disclose. M. Filippi is Editor-in-Chief of the Journal of Neurology, Associate Editor of Human Brain Mapping, Associate Editor of Radiology, and Associate Editor of Neurological Sciences; received compensation for consulting services from Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi; speaking activities from Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA; participation in Advisory Boards for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, Takeda; scientific direction of educational evens for Biogen, Merck, Roche, Celgene, Bristol-Myers Squibb, Lilly, Novartis, Sanofi-Genzyme; he receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).M.A. Rocca received speakers’ honoraria from Bayer, Biogen, Bristol Myers Squibb, Celgene, Genzyme, Merck Serono, Novartis, Roche, and Teva, and receives research support from the MS Society of Canada and Fondazione Italiana Sclerosi Multipla.

Ethical statement

Approval was obtained from the institutional ethical standards committee on human experimentation of IRCCS Ospedale San Raffaele for any experiments using human subjects (protocol number 2015–33). Written informed consent was obtained from all subjects prior to study participation according to the Declaration of Helsinki.

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Margoni, M., Pagani, E., Preziosa, P. et al. In vivo quantification of brain soma and neurite density abnormalities in multiple sclerosis. J Neurol 270, 433–445 (2023). https://doi.org/10.1007/s00415-022-11386-3

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  • DOI: https://doi.org/10.1007/s00415-022-11386-3

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