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21.02.2019 | Original Article

Along-axon diameter variation and axonal orientation dispersion revealed with 3D electron microscopy: implications for quantifying brain white matter microstructure with histology and diffusion MRI

verfasst von: Hong-Hsi Lee, Katarina Yaros, Jelle Veraart, Jasmine L. Pathan, Feng-Xia Liang, Sungheon G. Kim, Dmitry S. Novikov, Els Fieremans

Erschienen in: Brain Structure and Function | Ausgabe 4/2019

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Abstract

Tissue microstructure modeling of diffusion MRI signal is an active research area striving to bridge the gap between macroscopic MRI resolution and cellular-level tissue architecture. Such modeling in neuronal tissue relies on a number of assumptions about the microstructural features of axonal fiber bundles, such as the axonal shape (e.g., perfect cylinders) and the fiber orientation dispersion. However, these assumptions have not yet been validated by sufficiently high-resolution 3-dimensional histology. Here, we reconstructed sequential scanning electron microscopy images in mouse brain corpus callosum, and introduced a random-walker (RaW)-based algorithm to rapidly segment individual intra-axonal spaces and myelin sheaths of myelinated axons. Confirmed by a segmentation based on human annotations initiated with conventional machine-learning-based carving, our semi-automatic algorithm is reliable and less time-consuming. Based on the segmentation, we calculated MRI-relevant estimates of size-related parameters (inner axonal diameter, its distribution, along-axon variation, and myelin g-ratio), and orientation-related parameters (fiber orientation distribution and its rotational invariants; dispersion angle). The reported dispersion angle is consistent with previous 2-dimensional histology studies and diffusion MRI measurements, while the reported diameter exceeds those in other mouse brain studies. Furthermore, we calculated how these quantities would evolve in actual diffusion MRI experiments as a function of diffusion time, thereby providing a coarse-graining window on the microstructure, and showed that the orientation-related metrics have negligible diffusion time-dependence over clinical and pre-clinical diffusion time ranges. However, the MRI-measured inner axonal diameters, dominated by the widest cross sections, effectively decrease with diffusion time by ~ 17% due to the coarse-graining over axonal caliber variations. Furthermore, our 3d measurement showed that there is significant variation of the diameter along the axon. Hence, fiber orientation dispersion estimated from MRI should be relatively stable, while the “apparent” inner axonal diameters are sensitive to experimental settings, and cannot be modeled by perfectly cylindrical axons.

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Abdollahzadeh A, Belevich I, Jokitalo E, Tohka J, Sierra A (2017) 3D axonal morphometry of white matter. https://doi.org/10.1101/239228

Aboitiz F, Scheibel AB, Fisher RS, Zaidel E (1992) Fiber composition of the human corpus callosum. Brain Res 598:143–153CrossRef

Achanta R, Shaji A, Smith K, Lucchi A, Fua P, Susstrunk S (2012) SLIC superpixels compared to state-of-the-art superpixel methods. IEEE Trans Pattern Anal Mach Intell 34:2274–2282. https://doi.org/10.1109/TPAMI.2012.120 CrossRefPubMed

Adams R, Bischof L (1994) Seeded region growing. IEEE Trans Pattern Anal 16:641–647CrossRef

Alexander DC, Hubbard PL, Hall MG, Moore EA, Ptito M, Parker GJ, Dyrby TB (2010) Orientationally invariant indices of axon diameter and density from diffusion. MRI Neuroimage 52:1374–1389. https://doi.org/10.1016/j.neuroimage.2010.05.043 CrossRefPubMed

Arganda-Carreras I et al (2015) Crowdsourcing the creation of image segmentation algorithms for connectomics. Front Neuroanat 9:142. https://doi.org/10.3389/fnana.2015.00142 CrossRefPubMedPubMedCentral

Anderson AW (2005) Measurement of fiber orientation distributions using high angular resolution diffusion imaging. Magn Reson Med 54(5):1194–1206CrossRefPubMed

Assaf Y, Basser PJ (2005) Composite hindered and restricted model of diffusion (CHARMED) MR imaging of the human brain. Neuroimage 27:48–58. https://doi.org/10.1016/j.neuroimage.2005.03.042 CrossRefPubMed

Assaf Y, Blumenfeld-Katzir T, Yovel Y, Basser PJ (2008) AxCaliber: a method for measuring axon diameter distribution from diffusion MRI. Magn Reson Med 59:1347–1354. https://doi.org/10.1002/mrm.21577 CrossRefPubMedPubMedCentral

Barazany D, Basser PJ, Assaf Y (2009) In vivo measurement of axon diameter distribution in the corpus callosum of rat brain. Brain 132:1210–1220. https://doi.org/10.1093/brain/awp042 CrossRefPubMedPubMedCentral

Benjamini D, Komlosh ME, Holtzclaw LA, Nevo U, Basser PJ (2016) White matter microstructure from nonparametric axon diameter distribution mapping. Neuroimage 135:333–344. https://doi.org/10.1016/j.neuroimage.2016.04.052 CrossRefPubMedPubMedCentral

Berthold CH, Nilsson I, Rydmark M (1983) Axon diameter and myelin sheath thickness in nerve fibres of the ventral spinal root of the seventh lumbar nerve of the adult and developing cat. J Anat 136:483–508PubMedPubMedCentral

Bingham C (1974) Antipodally symmetric distribution on sphere. Ann Stat 2:1201–1225CrossRef

Budde MD, Frank JA (2010) Neurite beading is sufficient to decrease the apparent diffusion coefficient after ischemic stroke. Proc Natl Acad Sci USA 107:14472–14477. https://doi.org/10.1073/pnas.1004841107 CrossRefPubMed

Burcaw LM, Fieremans E, Novikov DS (2015) Mesoscopic structure of neuronal tracts from time-dependent diffusion. Neuroimage 114:18–37. https://doi.org/10.1016/j.neuroimage.2015.03.061 CrossRefPubMedPubMedCentral

Caminiti R, Ghaziri H, Galuske R, Hof PR, Innocenti GM (2009) Evolution amplified processing with temporally dispersed slow neuronal connectivity in primates. Proc Natl Acad Sci USA 106:19551–19556. https://doi.org/10.1073/pnas.0907655106 CrossRefPubMed

De Santis S, Jones DK, Roebroeck A (2016) Including diffusion time dependence in the extra-axonal space improves in vivo estimates of axonal diameter and density in human. white matter. Neuroimage 130:91–103. https://doi.org/10.1016/j.neuroimage.2016.01.047 CrossRefPubMedPubMedCentral

Dell’Acqua F, Rizzo G, Scifo P, Clarke RA, Scotti G, Fazio F (2007) A model-based deconvolution approach to solve fiber crossing in diffusion-weighted MR imaging. IEEE Trans Biomed Eng 54:462–472. https://doi.org/10.1109/TBME.2006.888830 CrossRefPubMed

Dhital B, Reisert M, Kellner E, Kiselev VG (2019) Intra-axonal diffusivity in brain white matter. NeuroImage 189:543–550CrossRefPubMed

Dorkenwald S, Schubert PJ, Killinger MF, Urban G, Mikula S, Svara F, Kornfeld J (2017) Automated synaptic connectivity inference for volume electron microscopy. Nat Methods 14:435–442. https://doi.org/10.1038/nmeth.4206 CrossRefPubMed

Duval T et al (2015) In vivo mapping of human spinal cord microstructure at 300 mT/m. Neuroimage 118:494–507. https://doi.org/10.1016/j.neuroimage.2015.06.038 CrossRefPubMedPubMedCentral

Fieremans E, Burcaw LM, Lee HH, Lemberskiy G, Veraart J, Novikov DS (2016) In vivo observation and biophysical interpretation of time-dependent diffusion in human white matter. Neuroimage 129:414–427. https://doi.org/10.1016/j.neuroimage.2016.01.018 CrossRefPubMedPubMedCentral

Frank LR (2002) Characterization of anisotropy in high angular resolution diffusion-weighted MRI. Magn Reson Med 47(6):1083–1099CrossRefPubMed

Giacci MK, Bartlett CA, Huynh M, Kilburn MR, Dunlop SA, Fitzgerald M (2018) Three dimensional electron microscopy reveals changing axonal and myelin morphology along normal and partially injured optic nerves. Sci Rep 8:3979. https://doi.org/10.1038/s41598-018-22361-2 CrossRefPubMedPubMedCentral

Grussu F, Schneider T, Yates RL, Zhang H, Wheeler-Kingshott C, DeLuca GC, Alexander DC (2016) A framework for optimal whole-sample histological quantification of neurite orientation dispersion in the human spinal cord. J Neurosci Methods 273:20–32. https://doi.org/10.1016/j.jneumeth.2016.08.002 CrossRefPubMed

Jespersen SN, Kroenke CD, Ostergaard L, Ackerman JJ, Yablonskiy DA (2007) Modeling dendrite density from magnetic resonance diffusion measurements. Neuroimage 34:1473–1486. https://doi.org/10.1016/j.neuroimage.2006.10.037 CrossRefPubMed

Jespersen SN et al (2010) Neurite density from magnetic resonance diffusion measurements at ultrahigh field: comparison with light microscopy and electron microscopy. Neuroimage 49:205–216. https://doi.org/10.1016/j.neuroimage.2009.08.053 CrossRefPubMed

Jespersen SN, Olesen JL, Hansen B, Shemesh N (2017) Diffusion time dependence of microstructural parameters in fixed spinal cord. Neuroimage. https://doi.org/10.1016/j.neuroimage.2017.08.039 CrossRefPubMedPubMedCentral

Jones DK (2010) Diffusion MRI: theory, methods, and application. Oxford University Press, Oxford

Kaynig V et al (2015) Large-scale automatic reconstruction of neuronal processes from electron microscopy images. Med Image Anal 22:77–88. https://doi.org/10.1016/j.media.2015.02.001 CrossRefPubMedPubMedCentral

Kirschner DA, Hollingshead CJ (1980) Processing for electron microscopy alters membrane structure and packing in myelin. J Ultrastruct Res 73:211–232CrossRefPubMed

Kleinnijenhuis M, Johnson E, Mollink J, Jbabdi S, Miller K (2017) A 3D electron microscopy segmentation pipeline for hyper-realistic diffusion simulations. In: ISMRM 25th annual meeting, Hawaii, USA Proceedings of the ISMRM annual meeting, vol 25, p 1090

Komlosh ME, Ozarslan E, Lizak MJ, Horkayne-Szakaly I, Freidlin RZ, Horkay F, Basser PJ (2013) Mapping average axon diameters in porcine spinal cord white matter and rat corpus callosum using d-PFG. MRI Neuroimage 78:210–216. https://doi.org/10.1016/j.neuroimage.2013.03.074 CrossRefPubMed

Lee H-H, Fieremans E, Novikov DS (2017) What dominates the time dependence of diffusion transverse to axons: intra- or extra-axonal water? NeuroImage. https://doi.org/10.1016/j.neuroimage.2017.12.038 CrossRefPubMedPubMedCentral

Leergaard TB, White NS, de Crespigny A, Bolstad I, D’Arceuil H, Bjaalie JG, Dale AM (2010) Quantitative histological validation of diffusion MRI fiber orientation distributions in the rat brain. PLoS One 5:e8595. https://doi.org/10.1371/journal.pone.0008595 CrossRefPubMedPubMedCentral

Liewald D, Miller R, Logothetis N, Wagner HJ, Schuz A (2014) Distribution of axon diameters in cortical white matter: an electron-microscopic study on three human brains and a macaque. Biol Cybern 108:541–557. https://doi.org/10.1007/s00422-014-0626-2 CrossRefPubMedPubMedCentral

Little GJ, Heath JW (1994) Morphometric analysis of axons myelinated during adult life in the mouse superior cervical ganglion. J Anat 184(Pt 2):387–398PubMedPubMedCentral

Maco B, Cantoni M, Holtmaat A, Kreshuk A, Hamprecht FA, Knott GW (2014) Semiautomated correlative 3D electron microscopy of in vivo-imaged axons and dendrites. Nat Protoc 9:1354–1366. https://doi.org/10.1038/nprot.2014.101 CrossRefPubMed

Marzan DE, West BL, Salzer JL (2018) Microglia are necessary for toxin-mediated demyelination and activation of microglia is sufficient to induce demyelination. https://doi.org/10.1101/501148

Mason JL, Langaman C, Morell P, Suzuki K, Matsushima GK (2001) Episodic demyelination and subsequent remyelination within the murine central nervous system: changes in axonal calibre. Neuropathol Appl Neurobiol 27:50–58CrossRefPubMed

Mollink J et al (2017) Evaluating fibre orientation dispersion in white matter: comparison of diffusion MRI, histology and polarized light imaging. Neuroimage 157:561–574. https://doi.org/10.1016/j.neuroimage.2017.06.001 CrossRefPubMedPubMedCentral

Neuman C (1974) Spin echo of spins diffusing in a bounded medium. J Chem Phys 60:4508–4511CrossRef

Novikov DS, Jensen JH, Helpern JA, Fieremans E (2014) Revealing mesoscopic structural universality with diffusion. Proc Natl Acad Sci USA 111:5088–5093. https://doi.org/10.1073/pnas.1316944111 CrossRefPubMed

Novikov DS, Fieremans E, Jespersen SN, Kiselev VG (2018a) Quantifying brain microstructure with diffusion MRI: theory and parameter estimation. NMR Biomed. https://doi.org/10.1002/nbm.3998 CrossRefPubMed

Novikov DS, Kiselev VG, Jespersen SN (2018b) On modeling. Magn Reson Med 79:3172–3193. https://doi.org/10.1002/mrm.27101 CrossRefPubMedPubMedCentral

Novikov DS, Veraart J, Jelescu IO, Fieremans E (2018c) Rotationally-invariant mapping of scalar and orientational metrics of neuronal microstructure with diffusion MRI. Neuroimage. https://doi.org/10.1016/j.neuroimage.2018.03.006 CrossRefPubMedPubMedCentral

Perge JA, Koch K, Miller R, Sterling P, Balasubramanian V (2009) How the optic nerve allocates space, energy capacity, and information. J Neurosci 29(24):7917–7928CrossRefPubMedPubMedCentral

Politis A (2016) Microphone array processing for parametric spatial audio techniques. http://urn.fi/URN:ISBN:978-952-60-7037-7

Reisert M, Kellner E, Dhital B, Hennig J, Kiselev VG (2017) Disentangling micro from mesostructure by diffusion MRI: a Bayesian approach. Neuroimage 147:964–975. https://doi.org/10.1016/j.neuroimage.2016.09.058 CrossRefPubMed

Ronen I, Budde M, Ercan E, Annese J, Techawiboonwong A, Webb A (2014) Microstructural organization of axons in the human corpus callosum quantified by diffusion-weighted magnetic resonance spectroscopy of N-acetylaspartate and post-mortem histology. Brain Struct Funct 219:1773–1785. https://doi.org/10.1007/s00429-013-0600-0 CrossRefPubMed

Salo RA, Belevich I, Manninen E, Jokitalo E, Grohn O, Sierra A (2018) Quantification of anisotropy and orientation in 3D electron microscopy and diffusion tensor imaging in injured rat brain. Neuroimage 172:404–414. https://doi.org/10.1016/j.neuroimage.2018.01.087 CrossRefPubMed

Schilling K, Janve V, Gao Y, Stepniewska I, Landman BA, Anderson AW (2016) Comparison of 3D orientation distribution functions measured with confocal microscopy and diffusion. MRI Neuroimage 129:185–197. https://doi.org/10.1016/j.neuroimage.2016.01.022 CrossRefPubMed

Schilling KG, Janve V, Gao Y, Stepniewska I, Landman BA, Anderson AW (2018) Histological validation of diffusion MRI fiber orientation distributions. and dispersion. Neuroimage 165:200–221. https://doi.org/10.1016/j.neuroimage.2017.10.046 CrossRefPubMed

Schneider R, Weil W (2008) Stochastic and integral geometry. Springer, BerlinCrossRef

Sepehrband F, Alexander DC, Clark KA, Kurniawan ND, Yang Z, Reutens DC (2016a) Parametric probability distribution functions for axon diameters of corpus callosum. Front Neuroanat 10:59. https://doi.org/10.3389/fnana.2016.00059 CrossRefPubMedPubMedCentral

Sepehrband F, Alexander DC, Kurniawan ND, Reutens DC, Yang Z (2016b) Towards higher sensitivity and stability of axon diameter estimation with diffusion-weighted MRI. NMR Biomed 29:293–308. https://doi.org/10.1002/nbm.3462 CrossRefPubMedPubMedCentral

Shepherd GM, Raastad M, Andersen P (2002) General and variable features of varicosity spacing along unmyelinated axons in the hippocampus and cerebellum. Proc Natl Acad Sci USA 99:6340–6345. https://doi.org/10.1073/pnas.052151299 CrossRefPubMed

Sommer C, Straehle C, Koethe U, Hamprecht FA (2011) Ilastik: interactive learning and segmentation toolkit. In: Biomedical imaging: from nano to macro, 2011 IEEE international symposium on IEEE, pp 230–233

Sotiropoulos SN, Behrens TE, Jbabdi S (2012) Ball and rackets: inferring fiber fanning from diffusion-weighted. MRI Neuroimage 60:1412–1425. https://doi.org/10.1016/j.neuroimage.2012.01.056 CrossRefPubMed

Stikov N, Perry LM, Mezer A, Rykhlevskaia E, Wandell BA, Pauly JM, Dougherty RF (2011) Bound pool fractions complement diffusion measures to describe white matter micro and macrostructure. Neuroimage 54:1112–1121. https://doi.org/10.1016/j.neuroimage.2010.08.068 CrossRefPubMed

Stikov N et al (2015) In vivo histology of the myelin g-ratio with magnetic resonance imaging. Neuroimage 118:397–405. https://doi.org/10.1016/j.neuroimage.2015.05.023 CrossRefPubMed

Straehle CN, Kothe U, Knott G, Hamprecht FA (2011) Carving: scalable interactive segmentation of neural volume electron microscopy images. Med Image Comput Comput Assist Interv 14:653–660PubMed

Sturrock RR (1980) Myelination of the mouse corpus callosum. Neuropathol Appl Neurobiol 6:415–420CrossRefPubMed

Sun D, Roth S, Black MJ (2010) Secrets of optical flow estimation and their principles. In: Computer vision and pattern recognition (CVPR), 2010 IEEE conference on IEEE, pp 2432–2439

Sun D, Roth S, Black MJ (2014) A quantitative analysis of current practices in optical flow estimation and the principles behind them. Int J Comput Vis 106:115–137CrossRef

Tang-Schomer MD, Johnson VE, Baas PW, Stewart W, Smith DH (2012) Partial interruption of axonal transport due to microtubule breakage accounts for the formation of periodic varicosities after traumatic axonal injury. Exp Neurol 233:364–372. https://doi.org/10.1016/j.expneurol.2011.10.030 CrossRefPubMed

Tariq M, Schneider T, Alexander DC, Gandini Wheeler-Kingshott CA, Zhang H (2016) Bingham-NODDI: mapping anisotropic orientation dispersion of neurites using diffusion. MRI Neuroimage 133:207–223. https://doi.org/10.1016/j.neuroimage.2016.01.046 CrossRefPubMed

Tournier JD, Calamante F, Connelly A (2007) Robust determination of the fibre orientation distribution in diffusion MRI: non-negativity constrained super-resolved spherical deconvolution. Neuroimage 35:1459–1472. https://doi.org/10.1016/j.neuroimage.2007.02.016 CrossRefPubMed

Veraart J, Fieremans E, Novikov DS (2018a) On the scaling behavior of water diffusion in human brain white matter. Neuroimage. https://doi.org/10.1016/j.neuroimage.2018.09.075 CrossRefPubMedPubMedCentral

Veraart J, Novikov DS, Fieremans E (2018b) TE dependent diffusion imaging (TEdDI) distinguishes between compartmental T-2 relaxation times. Neuroimage 182:360–369. https://doi.org/10.1016/j.neuroimage.2017.09.030 CrossRefPubMed

West KL, Kelm ND, Carson RP, Does MD (2015) Quantitative analysis of mouse corpus callosum from electron microscopy images. Data Brief 5:124–128. https://doi.org/10.1016/j.dib.2015.08.022 CrossRefPubMedPubMedCentral

West KL, Kelm ND, Carson RP, Does MD (2016) A revised model for estimating g-ratio from MRI. Neuroimage 125:1155–1158. https://doi.org/10.1016/j.neuroimage.2015.08.017 CrossRefPubMed

Wilke SA et al (2013) Deconstructing complexity: serial block-face electron microscopic analysis of the hippocampal mossy fiber synapse. J Neurosci 33:507–522. https://doi.org/10.1523/JNEUROSCI.1600-12.2013 CrossRefPubMedPubMedCentral

Womersley RS (2017) Efficient spherical designs with good geometric properties. Contemporary computational mathematics - A celebration of the 80th birthday of Ian Sloan. Springer, Cham, pp 1243–1285

Yang HJ, Vainshtein A, Maik-Rachline G, Peles E (2016) G protein-coupled receptor 37 is a negative regulator of oligodendrocyte differentiation and myelination. Nat Commun 7:10884. https://doi.org/10.1038/ncomms10884 CrossRefPubMedPubMedCentral

Zaimi A, Wabartha M, Herman V, Antonsanti PL, Perone CS, Cohen-Adad J (2018) AxonDeepSeg: automatic axon and myelin segmentation from microscopy data using convolutional neural networks. Sci Rep 8:3816. https://doi.org/10.1038/s41598-018-22181-4 CrossRefPubMedPubMedCentral

Zhang H, Schneider T, Wheeler-Kingshott CA, Alexander DC (2012) NODDI: practical in vivo neurite orientation dispersion and density imaging of the human brain. Neuroimage 61:1000–1016. https://doi.org/10.1016/j.neuroimage.2012.03.072 CrossRefPubMed

Titel: Along-axon diameter variation and axonal orientation dispersion revealed with 3D electron microscopy: implications for quantifying brain white matter microstructure with histology and diffusion MRI
verfasst von: Hong-Hsi Lee
Katarina Yaros
Jelle Veraart
Jasmine L. Pathan
Feng-Xia Liang
Sungheon G. Kim
Dmitry S. Novikov
Els Fieremans
Publikationsdatum: 21.02.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Brain Structure and Function / Ausgabe 4/2019
Print ISSN: 1863-2653
Elektronische ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-019-01844-6

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Along-axon diameter variation and axonal orientation dispersion revealed with 3D electron microscopy: implications for quantifying brain white matter microstructure with histology and diffusion MRI

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