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Fig. 76: a) Blood vessels and (b) cell clusters impacted the trajectories of the axons. c) Vacuoles were associated with decreases in diameter. d) In a region of fibre crossings with axons projecting in different directions (yellow vs. green), axons

were seen to twist around each other (red and blue).

PRINCIPAL PUBLICATION AND AUTHORS

Axon morphology is modulated by the local environment and impacts the noninvasive investigation of its structure function relationship, M. Andersson (a,b), H.M. Kjer (a,b), J. Rafael-Patino (c), A. Pacureanu (d), B. Pakkenberg (e), J-P. Thiran (c,f,g), M. Ptito (h,i), M. Bech (j), A. Bjorholm Dahl (b), V. Andersen Dahl (b), T.B. Dyrby (a,b). PNAS USA 117(52), 33649-33659 (2020); https:/doi.org/10.1073/pnas.2012533117 (a) Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre (Denmark) (b) Department of Applied Mathematics and Computer Science, Technical University of Denmark, Kongens Lyngby (Denmark) (c) Signal Processing Laboratory (LTS5), Ecole Polytechnique Fédérale de Lausanne (Switzerland) (d) ESRF (e) Research Laboratory for Stereology and Neuroscience, Copenhagen University Hospital, Bispebjerg (Denmark) (f) Radiology Department, Centre Hospitalier Universitaire Vaudois and University of Lausanne (Switzerland) (g) Center for Biomedical Imaging (CIBM), Lausanne (Switzerland) (h) School of Optometry, University of Montreal (Canada) (i) Department of Neuroscience, Faculty of Health Science, University of Copenhagen (Denmark) (j) Department of Medical Radiation Physics, Clinical Science, Lund University (Sweden)

REFERENCES

[1] T.B. Dyrby et al., NeuroImage 182, 62-79 (2018). [2] D.C. Alexander et al., NeuroImage 52, 1374-1389 (2010). [3] T.B. Dyrby et al., Magn. Reson. Med. 70, 711-721 (2013).

The analysis of an XNH volume from a crossing fibre region of the brain showed how the axons also adapt to each other s trajectories, sometimes even twisting and spiralling (Figure 76d).

The discovery that axon morphology can be modulated by extra-axonal structures offers an exciting new avenue for further research. It suggests that axon morphologies may differ in situations where the extra-axonal environment is expected to change, such as in disease. Whether these changes affect the signal conduction process, or if they can be quantified with diffusion MRI, are important questions to pursue.

of the axons obtained from the XNH volumes could act as fingerprints to guide the development and validation of diffusion MRI methods for more accurate in-vivo AD estimation.

By studying the morphological variations of axons against the backdrop of the WM environment in Figure 75a, several trends could be exposed. Large structures such as blood vessels were associated with local trajectory changes of the axons, visible almost as a warping effect (Figure 76a). Similarly, axons were shown to skirt around cell clusters (Figure 76b), while diameter decreases could be associated with the presence of vacuoles (Figure 76c).