Neuronal morphometry directly from bitmap images

Ferreira, Tiago Alves; Blackman, Arne V.; Oyrer, Julia; Jayabal, Sriram; Chung, Andrew; Watt, Alanna J.; Sjöström, P. Jesper; Meyel, Donald J. van

doi:10.1038/nmeth.3125

Cited by 556 publications

(492 citation statements)

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“…We performed Sholl analysis (25) directly from bitmap images by using the Fiji toolbox integrated in ImageJ (imagej.net/Sholl). The plug-in pairs an improved algorithm to retrieve data from bitmap images with curve fitting, regression analysis, and statistical inference so that an automatic estimation of Sholl-based metrics of arborization is possible (36). An example of the Sholl-based analysis is reported in SI Appendix, Fig.…”

Section: Synthetic Tissue Generation and Comparison With A Real Histomentioning

confidence: 99%

New paradigm to assess brain cell morphology by diffusion-weighted MR spectroscopy in vivo

Palombo

Ligneul

Najac

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

131

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The brain is one of the most complex organs, and tools are lacking to assess its cellular morphology in vivo. Here we combine original diffusion-weighted magnetic resonance (MR) spectroscopy acquisition and novel modeling strategies to explore the possibility of quantifying brain cell morphology noninvasively. First, the diffusion of cellspecific metabolites is measured at ultra-long diffusion times in the rodent and primate brain in vivo to observe how cell long-range morphology constrains metabolite diffusion. Massive simulations of particles diffusing in synthetic cells parameterized by morphometric statistics are then iterated to fit experimental data. This method yields synthetic cells (tentatively neurons and astrocytes) that exhibit striking qualitative and quantitative similarities with histology (e.g., using Sholl analysis). With our approach, we measure major interspecies difference regarding astrocytes, whereas dendritic organization appears better conserved throughout species. This work suggests that the time dependence of metabolite diffusion coefficient allows distinguishing and quantitatively characterizing brain cell morphologies noninvasively.cell morphology | noninvasive histology | diffusion-weighted NMR spectroscopy | numerical simulations | metabolites T he brain is one of the most complex organs, and it has defined an inexhaustible field of research over the last centuries. Unfortunately, brain's complexity is paralleled by the difficulty in examining it noninvasively. Some fundamental questions regarding morphological modifications of neurons and astrocytes along brain development, aging, or disease, as well as interspecies differences, can only be investigated postmortem using histology, the current gold standard to study cellular morphology. The development of a noninvasive neuroimaging tool to evaluate and monitor brain cell morphology under normal and pathological conditions in vivo would thus represent a major breakthrough.MRI and magnetic resonance spectroscopy (MRS) techniques have opened new doors for examining brain tissues in vivo at both meso-and macroscales. Diffusion-weighted (DW)-MRI and -MRS, which allow the investigation of the diffusion process of endogenous molecules in biological tissues at these scales (1), have made it clear that cell architecture has a critical influence on molecular displacement (2-5). To quantitatively evaluate the impact of cell structure on measured molecular diffusion, mainly two modeling strategies have been developed. The first approach consists in performing numerical simulations of many particles diffusing in arbitrary geometries (e.g., defined by 3D meshes) mimicking "realistic" cell architectures (6-9). Because these realistic geometries are generally built directly from microscopy data rather than being described and generated by a (small) set of parameters, and because simulations are extremely computationally demanding, this approach does not seem adapted to fit experimental data. The second approach consists in simplifying cell architec...

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Section: Synthetic Tissue Generation and Comparison With A Real Histomentioning

confidence: 99%

New paradigm to assess brain cell morphology by diffusion-weighted MR spectroscopy in vivo

Palombo

Ligneul

Najac

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

131

View full text Add to dashboard Cite

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“…For the in utero electroporation, dendritic branching was analyzed using the Simple Neurite Tracer and the ImageJ plugin for Sholl analysis (Ferreira et al, 2014).…”

Section: Image Collection and Quantitative Analysis Dendritic Numbermentioning

confidence: 99%

Neuronal LRP4 regulates synapse formation in the developing CNS

et al. 2017

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The low-density lipoprotein receptor-related protein 4 (LRP4) is essential in muscle fibers for the establishment of the neuromuscular junction. Here, we show that LRP4 is also expressed by embryonic cortical and hippocampal neurons, and that downregulation of LRP4 in these neurons causes a reduction in density of synapses and number of primary dendrites. Accordingly, overexpression of LRP4 in cultured neurons had the opposite effect inducing more but shorter primary dendrites with an increased number of spines. Transsynaptic tracing mediated by rabies virus revealed a reduced number of neurons presynaptic to the cortical neurons in which LRP4 was knocked down. Moreover, neuron-specific knockdown of LRP4 by in utero electroporation of LRP4 miRNA in vivo also resulted in neurons with fewer primary dendrites and a lower density of spines in the developing cortex and hippocampus. Collectively, our results demonstrate an essential and novel role of neuronal LRP4 in dendritic development and synaptogenesis in the CNS.

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“…Changes of dendritic arbors of OX-A neurons in infected mice vs control ones were analyzed quantitatively with the semiautomated Sholl analysis using the software ImageJ (NIH, Bethesda, MD, USA), as described by Ferreira et al (2014). Briefly, OX-A neurons (10 cells per animal; n = 3 control and infected mice) were randomly sampled in three sections per animal blindedly of the animal group assignment, and individual neurons were analyzed by setting a center point in the soma.…”

Section: Quantitative Analysesmentioning

confidence: 99%