Biology subjects

Sorelli, M.

Publications and source records attributed to Sorelli, M..

6 recordsLinked to original sources

bioRxiv2025

Anisotropic light propagation in human brain white matter

SignificanceAccurate modeling of light diffusion in the human brain is crucial for applications in optogenetics and spectroscopy diagnostic techniques. White matter tissue is composed of myelinated axon bundles, suggesting the occurrence of enhanced light diffusion along their local orientation direction, which however has never been characterized experimentally. Existing diffuse optics models assume isotropic properties, limiting their accuracy. AimWe aim to characterize the anisotropic scattering properties of human white matter tissue by directly measuring its tensor scattering components along different directions, and to correlate them with the local axon fiber orientation. ApproachUsing a time- and space-resolved setup, we image the transverse propagation of diffusely reflected light across two perpendicular directions in a ex vivo human brain sample. Local fiber orientation is independently determined using light sheet fluorescence microscopy (LSFM). ResultsThe directional dependence of light propagation in organized myelinated axon bundles is characterized via Monte Carlo (MC) simulations accounting for a tensor scattering coefficient, revealing a lower scattering rate parallel to the fiber orientation. The effects of white matter anisotropy are further assessed by simulating a typical time-domain near-infrared spectroscopy measurement in a four-layer human head model. ConclusionsThis study provides a first characterization of the anisotropic scattering properties in ex vivo human white matter, highlighting its direct correlation with axon fiber orientation, and opening to the realization of quantitatively accurate anisotropy-aware human head 3D meshes for diffuse optics applications.

neuroscience↗

bioRxiv2025

Myelinated fiber labeling and orientation mapping of the human brain with light-sheet fluorescence microscopy

The convoluted network of myelinated fibers that supports behavior, cognition, and sensory processing in the human brain is the source of its extraordinary complexity. Advancements in tissue optical clearing, 3D fluorescence microscopy, and automated image analysis have enabled unprecedented insights into the architecture of these networks. Here, we investigate the multiscale organization of myelinated fibers in human brain tissue from the brainstem, Brocas area, hippocampus, and primary visual cortex by exploiting a specific fiber staining method, light-sheet fluorescence microscopy (LSFM), and an advanced spatial orientation analysis tool. Using an optimized protocol that integrates tissue clearing with the lipophilic DiD probe to achieve uniform and deep myelinated fiber labeling, we generate micrometerresolution volumetric reconstructions of multiple brain regions through an inverted LSFM. Automated image processing, employing unsupervised 3D multiscale Frangi filters, provides orientation distribution functions and local orientation dispersion maps. This enables precise characterization of the directionality of white matter bundles, linking mesoscopic structural properties to orientation details computed at the native micrometric resolution of the LSFM apparatus. The presented workflow illustrates a robust platform for large-scale, high-resolution brain mapping, which may facilitate the investigation of pathological alterations with unparalleled spatial resolution and, furthermore, the validation of other neuroimaging modalities.

neuroscience↗

bioRxiv2024

Quantitative cytoarchitectural phenotyping of deparaffinized human brain tissues

Advanced 3D imaging techniques and image segmentation and classification methods can profoundly transform biomedical research by offering deep insights into the cytoarchitecture of the human brain in relation to pathological conditions. Here, we propose a comprehensive pipeline for performing 3D imaging and automated quantitative cellular phenotyping on Formalin-Fixed Paraffin-Embedded (FFPE) human brain specimens, a valuable yet underutilized resource. We exploited the versatility of our method by applying it to different human specimens from both adult and pediatric, normal and abnormal brain regions. Quantitative data on neuronal volume, ellipticity, local density, and spatial clustering level were obtained from a machine learning-based analysis of the 3D cytoarchitectural organization of cells identified by different molecular markers in two subjects with malformations of cortical development (MCD). This approach will grant access to a wide range of physiological and pathological paraffin-embedded clinical specimens, allowing for volumetric imaging and quantitative analysis of human brain samples at cellular resolution. Possible genotype-phenotype correlations can be unveiled, providing new insights into the pathogenesis of various brain diseases and enlarging treatment opportunities.

neuroscience↗

bioRxiv2024

Two-photon all-optical electrophysiology for the dissection of larval zebrafish brain functional connectivity

One of the most audacious goals of modern neuroscience is unraveling the complex web of causal relations underlying the activity of neuronal populations on a whole-brain scale. This endeavor, prohibitive just a couple of decades ago, has recently become within reach owing to the advancements in optical methods and the advent of genetically encoded indicators/actuators. These techniques, applied to the translucent larval zebrafish have enabled recording and manipulation of the activity of extensive neuronal populations spanning the entire vertebrate brain. Here, we present the conception of a custom two-photon optical system, coupling light-sheet imaging and 3D excitation with acousto-optic deflectors for simultaneous high-speed volumetric recording and optogenetic stimulation. By employing a zebrafish line with pan-neuronal expression of both the calcium reporter GCaMP6s and the red-shifted opsin ReaChR, we implemented a crosstalk-free, noninvasive all-optical approach and applied it to the reconstruction of the functional connectivity of the left habenula.

neuroscience↗

bioRxiv2022

Fiber enhancement and 3D orientation analysis inlabel-free two-photon fluorescence microscopy

3D fluorescence microscopy can be profitably used in combination with tissue clearing and myelin labeling techniques for investigating the human brain myeloarchitectonics with sub-micrometric resolution, and for providing detailed histological reference data for the validation of diffusion magnetic resonance imaging (dMRI) tractography. Differently from state-of-the-art polarimetry-based neuroimaging modalities such as 3D polarized light imaging and 3D polarized-sensitive optical coherence tomography, the quantitative histological analysis of cortical and white matter fiber architectures from fluorescence microscopy images requires the estimation of fiber orientations via image processing techniques, as Fourier or structure tensor analysis. However, these can be error-prone as they are not able to detect myelinated fibers in surrounding brain tissue. Here we present a novel image processing pipeline built around a 3D Frangi filter able to enhance fiber structures of varying diameters in tiled brain section reconstructions of arbitrary size, and to produce accurate 3D fiber orientation maps in both grey and white matter regions, while preserving the native resolution of the employed microscopy system. The developed software tool also features the estimation of fiber orientation distribution functions which, in view of their widespread use in the neuroimaging community, may favor a multimodal comparison with brain connectivity data obtained from the aforementioned label-free optical modalities, and the validation of modern dMRI-based tractography. The proposed image processing pipeline was applied to brain samples treated according to a novel label-free preparation technique capable of enhancing the autofluorescence of myelinated fiber axons, thus demonstrating the feasibility of single fiber orientation analyses in fluorescence microscopy without the need for exogenous staining.

bioengineering↗

bioRxiv2020

MAGIC: A label-free fluorescence method for 3D high-resolution reconstruction of myelinated fibers in large volumes

Analyzing the structure of neuronal fibers with single axon resolution, in large volumes, remains an unresolved challenge in connectomics. Here, we propose MAGIC (Myelin Autofluorescence imaging by Glycerol Induced Contrast enhancement), a simple tissue preparation method to perform label-free fluorescence imaging of myelinated fibers. We demonstrate its broad applicability by performing mesoscopic reconstruction at sub-micron resolution of mouse, rat, monkey, and human brain samples and by quantifying the different fiber organization in Control and Reeler mouses hippocampal sections.

neuroscience↗