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Investigation of Neurodegenerative Processes in Amyotrophic Lateral Sclerosis Using White Matter Fiber Density

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Abstract

In the current work two novel parameters, fiber density (FD) and mean diffusion signal (MDS) are investigated for evaluating neurodegenerative processes in amyotrophic lateral sclerosis (ALS). The MDS provides a measure of the FD but is derived directly from the diffusion signal. Using tract-based spatial statistics (TBSS), pathological changes across the entire white matter and changes in the parameters over time were evaluated. The results were related to those obtained using the fractional anisotropy (FA) value. A widespread pattern of significantly decreased FD and MDS values was observed. A strong trend towards statistical significance was seen in similar white matter structures using TBSS analysis based on the FA value. Longitudinal analysis of the FD values demonstrated continuing deterioration of the same fiber tracts that were shown to be impaired in the group analysis. The findings suggest that MDS and in particular FD show great promise for evaluating microstructural white matter changes in ALS and may be more sensitive than the more commonly used FA value.

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Funding

This is an EU Joint Programme Neurodegenerative Disease Research (JPND) project. The project is supported through the following funding organizations under the aegis of JPND www.jpnd.eu: France, Agence Nationale de la Recherche; Germany, Bundesministerium für Bildung und Forschung; Ireland, Health Research Board; Italy, Ministero della Salute; The Netherlands, The Netherlands Organisation for Health Research and Development; Poland, Narodowe Centrum Badań i Rozwoju; Portugal, Fundação a Ciência e a Tecnologia; Spain, Ministerio de Ciencia e Innovación; Switzerland, Schweizerischer Nationalfonds zur Förderung der wissenschaftlichen Forschung; Turkey, Tübitak; United Kingdom, Medical Research Council. SNF Grant 31ND30_141622.

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Authors and Affiliations

  1. Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Lenggstrasse 31, 8032, Zurich, Switzerland

    Philipp Stämpfli, Stefan Sommer & Erich Seifritz

  2. MR-Center of the Psychiatric Hospital and the Department of Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland

    Philipp Stämpfli & Stefan Sommer

  3. Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland

    Stefan Sommer, Sebastian Kozerke & Carolin Reischauer

  4. Department of Neurology, Cantonal Hospital Winterthur, Winterthur, Switzerland

    David Czell

  5. Department of Neurology, Spital Linth, Uznach, Switzerland

    David Czell

  6. Neuromoscular Disease Unit/ALS Clinic, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

    Christoph Neuwirth & Markus Weber

  7. Department of Radiology, Cantonal Hospital Winterthur, Winterthur, Switzerland

    Sabine Sartoretti-Schefer

  8. Department of Radiology, Paracelsus Medical University Salzburg, Salzburg, Austria

    Andreas Gutzeit

  9. Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland

    Andreas Gutzeit

  10. Institute of Radiology and Nuclear Medicine, Clinical Research Unit, Hirslanden Hospital St. Anna, Lucerne, Switzerland

    Andreas Gutzeit & Carolin Reischauer

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  1. Philipp Stämpfli
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Correspondence to Philipp Stämpfli.

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Conflict of interest

P. Stämpfli, S. Sommer, D. Czell, S. Kozerke, C. Neuwirth, M. Weber, S. Sartoretti-Schefer, E. Seifritz, A. Gutzeit and C. Reischauer declare that they have no competing interests.

Ethical standards

All procedures described in this article were carried out in accordance with national law and the Helsinki Declaration of 1964 (in its current revised form). Informed consent was obtained from all patients included in the study.

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P. Stämpfli and S. Sommer contributed equally to the manuscript.

Caption Electronic Supplementary Material

62_2018_670_MOESM1_ESM.docx

In the supplementary material section 1, more details about data processing steps and FD computation can be found. Section 2 describes the TBSS analysis steps for analysing FA, FD and MDS maps in more detail. A mathematical derivation of the relationship between the MDS and the FD is provided in section 3.

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Stämpfli, P., Sommer, S., Czell, D. et al. Investigation of Neurodegenerative Processes in Amyotrophic Lateral Sclerosis Using White Matter Fiber Density. Clin Neuroradiol 29, 493–503 (2019). https://doi.org/10.1007/s00062-018-0670-8

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