Biology subjects

Coronado-Leija, R.

Publications and source records attributed to Coronado-Leija, R..

6 recordsLinked to original sources

bioRxiv2026

RADIAL AND TANGENTIAL FIBER COMPONENTS IN HUMAN SUPERFICIAL WHITE MATTER AND THEIR ASSOCIATIONS WITH MACROSCALE FUNCTION

The superficial white matter (SWM), a thin layer of white matter beneath the cortex, contains a complex arrangement of short- and long-range fiber systems that support communication between cortical regions. These fiber populations include subcortical U-shaped fibers (U-fibers) that predominantly follow a tangential trajectory along the gray matter-white matter interface and long-range fibers that extend more radially through the deeper white matter to connect distant cortical regions. Here, we developed a surface-based framework to dissociate radial and tangential fiber components within the human SWM and investigated their microstructural properties and functional relevance using in-vivo high-field MRI. These components were quantified using apparent fiber density (AFD), fractional anisotropy (FA), and mean diffusivity (MD). We further contextualized SWM fiber architecture by examining depth-dependent microstructural profiles and their relationship with normative patterns of cortical organization and hierarchical specialization. The anatomical assessment of the proposed fiber orientation separation was supported by tractography-based bundle analyses, while the anatomical accuracy of tractography reconstructions was confirmed through comparison with post-mortem white matter dissection data. To assess their functional relevance, the fiber predominance map derived from radial and tangential AFD was related to spatial patterns of functional variability across the cortex. Regions with greater radially oriented fiber contribution exhibited more gradual changes in functional similarity across geodesic distance, whereas tangentially oriented fiber-enriched regions showed more rapid local functional differentiation. These findings reveal distinct structural and functional signatures of radial and tangential SWM fiber components and provide a framework for investigating their contributions to cortical organization and functional specialization. SIGNIFICANCE STATEMENTThe human cerebral cortex is organized into specialized regions that support diverse functions, but the structural principles underlying this organization remain incompletely understood. The superficial white matter (SWM), a thin layer of white matter beneath the cortex, contains intermingled short- and long-range fiber systems that support communication between cortical regions. However, these fiber populations have remained difficult to characterize because they are closely intertwined within the SWM. By developing a reproducible framework for mapping and quantifying distinct SWM fiber systems, this work provides a foundation for systematic investigation of this complex compartment. Integration of multimodal datasets, together with open sharing of analytical tools and standardized features, promotes transparency, reproducibility, enabling future studies of how superficial connectivity supports brain organization.

neuroscience↗

bioRxiv2025

End-to-end evaluation of white matter microstructure of the visual pathway in asymmetric glaucoma

Diffusion magnetic resonance imaging is a non-invasive neuroimaging technique that enables in vivo evaluation of white matter microstructure, providing sensitivity to tissue abnormalities caused by disease. Glaucoma, the second leading cause of blindness worldwide, is characterized by progressive loss of retinal ganglion cells and axonal damage in the optic nerve, leading to degeneration along the entire visual pathway. This degeneration includes secondary effects on fiber crossings within the optic chiasm, which are challenging to characterize with conventional diffusion models. In this study, we evaluated 31 patients with asymmetric glaucoma and 31 healthy controls using advanced diffusion magnetic resonance imaging methods, including Diffusion Tensor Imaging, Constrained Spherical Deconvolution, multi-tensor fit via Multi-Resolution Discrete Search method, and Fixel-Based Analysis. We found significant differences of diffusion metrics in white matter tracts of the visual system, including the optic nerve, optic chiasm, optic tracts, and optic radiations. Moreover, diffusion metrics correlated with clinical ophthalmological parameters such as cup-to-disc ratio, visual field mean deviation, and retinal nerve fiber layer thickness. These findings support the use of advanced diffusion magnetic resonance imaging models as sensitive tools for detecting Wallerian degeneration and resolving complex white matter architecture in the human visual pathway, and demonstrate their utility to study other fiber-crossing regions throughout the brain.

neuroscience↗

bioRxiv2025

3D multimodal histological atlas and coordinate framework for the mouse brain and head

Brain reference atlases are essential for neuroscience experiments and data integration. However, histological atlases of the mouse brain, crucial in biomedical research, have not kept pace. Autofluorescence-based volumetric brain atlases are increasingly used but lack microscopic histological contrast, cytoarchitectonic information, corresponding MRI datasets, and often have truncated brainstems. Here, we present a multimodal, multiscale atlas of the laboratory mouse brain and head. The new reference brains include the whole head with consecutive Nissl and myelin serial section histology in three planes of section with 0.46 {micro}m in-plane resolution, including intact brainstem, cranial nerves, and associated sensors and musculature. We provide reassembled histological volumes with 20mu isotropic resolution in stereotactic coordinates, determined using co-registered in vivo MRI and CT. In addition to conventional MRI contrasts, we provide diffusion MRI-based in vivo and ex vivo microstructural information, adding a valuable co-registered contrast modality that bridges MRI with cell-resolution histological data. We shift emphasis from compartmental annotations to stereotactic coordinates in the reference brains, offering a basis for evolving annotations over time and resolving conflicting neuroanatomical judgments by different experts. This new reference atlas facilitates integration of molecular cell type data and regional connectivity, serves as a model for similar atlases in other species, and sets a precedent for preserving extra-cranial nervous system structures.

neuroscience↗

bioRxiv2024

Longitudinal Multi-Tensor Analysis of Neocortical Microstructure in an Animal Model of Cortical Dysplasia

The neocortex is a highly organized structure, with region-specific spatial patterns of cells and fibers constituting cyto- and myelo-architecture, respectively. These architectural features are modulated during neurodevelopment, aging, and disease. While invasive techniques have contributed significantly to our understanding of cortical patterning, the task remains challenging through non-invasive methods. Structural magnetic resonance imaging (MRI) has advanced to improve sensitivity in identifying cortical features, yet most methods focus on capturing macrostructural characteristics, often overlooking critical microscale components. Diffusion-weighted MRI (dMRI) offers an opportunity to extract quantitative information reflecting microstructural changes. Here we investigate how different dMRI modalities contribute to the detection of microstructural characteristics and whether per-bundle approaches can disentangle characteristics related to the orientational organization of the myelo- and cyto-architecture in an animal model of cortical dysplasia, a malformation of cortical development. We scanned 32 animals (n=16 experimental; n=16 control) at four different time points (30, 60, 120, and 150 post-natal days) using both structural and multi-shell diffusion-weighted MRI. All dMRI metrics were sampled using a 2D curvilinear system of coordinates as a common anatomical descriptor across animals. Per-bundle metrics were labeled according to their orientation with respect to the cortical surface, and analyzed separately. Experimental animals showed diffusion abnormalities of the tangential and radial fiber components in deeper cortical areas, consistent with histological findings of neuronal and fiber disorganization. The ability of dMRI to detect abnormalities in an animal model of cortical dysplasia is indicative of the clinical potential of advanced dMRI methods to study cortical microstructure in neurological disorders.

neuroscience↗

bioRxiv2023

The influence of axonal beading and undulation on axonal diameter mapping

We consider the effect of non-cylindrical axonal shape on axonal diameter mapping with diffusion MRI. Practical sensitivity to axon diameter is attained at strong diffusion weightings b, where the deviation from the [Formula] scaling yields the finite transverse diffusivity, which is then translated into axon diameter. While axons are usually modeled as perfectly straight, impermeable cylinders, the local variations in diameter (caliber variation or beading) and direction (undulation) have been observed in microscopy data of human axons. Here we quantify the influence of cellular-level features such as caliber variation and undulation on axon diameter estimation. For that, we simulate the diffusion MRI signal in realistic axons segmented from 3-dimensional electron microscopy of a human brain sample. We then create artificial fibers with the same features and tune the amplitude of their caliber variations and undulations. Numerical simulations of diffusion in fibers with such tunable features show that caliber variations and undulations result in under- and over-estimation of axon diameters, correspondingly; this bias can be as large as 100%. Given that increased axonal beading and undulations have been observed in pathological tissues, such as traumatic brain injury and ischemia, the interpretation of axon diameter alterations in pathology may be significantly confounded.

neuroscience↗

bioRxiv2019

Histological validation of per-bundle water diffusion metrics within a region of fiber crossing following axonal degeneration

Micro-architectural characteristics of white matter can be inferred through analysis of diffusion-weighted magnetic resonance imaging (dMRI). The diffusion-dependent signal can be analyzed through several methods, with the tensor model being the most frequently used due to its straightforward interpretation and relaxed acquisition parameters. While valuable information can be gained from the tensor-derived metrics in regions of homogeneous tissue organization, this model does not provide reliable microstructural information at crossing fiber regions, which are pervasive throughout human white matter. Several multiple fiber models have been proposed that seem to overcome the limitations of the tensor, with few providing per-bundle dMRI-derived metrics. However, biological interpretations of such metrics are limited by the lack of histological confirmation. To this end, we developed a straightforward biological validation framework. Unilateral retinal ischemia was induced in ten rats, which resulted in axonal (Wallerian) degeneration of the corresponding optic nerve, while the contralateral was left intact; the intact and injured axonal populations meet at the optic chiasm as they cross the midline, generating a fiber crossing region in which each population has different diffusion properties. Five rats served as controls. High-resolution ex vivo dMRI was acquired five weeks after experimental procedures. We correlated and compared histology to per-bundle descriptors derived from three novel methodologies for dMRI analysis (constrained spherical deconvolution and two multi-tensor representations). We found a tight correlation between axonal density (as evaluated through automatic segmentation of histological sections) with per-bundle apparent fiber density and fractional anisotropy (derived from dMRI). The multi-fiber methods explored were able to correctly identify the damaged fiber populations in a region of fiber crossings (chiasm). Our results provide validation of metrics that bring substantial and clinically useful information about white-matter tissue at crossing fiber regions. Our proposed validation framework is useful to validate other current and future dMRI methods.

neuroscience↗