Biology subjects

Zeineh, M.

Publications and source records attributed to Zeineh, M..

5 recordsLinked to original sources

bioRxiv2025

Precise MRI-Histology Coregistration of Paraffin-Embedded Tissue with Blockface Imaging

Magnetic resonance imaging (MRI) provides 3D spatial information on tissue, yet it lacks at the molecular level. In contrast, histology provides cellular and molecular information, but it lacks the 3D spatial context and direct in vivo translation. Coregistering the two is key for the 3D-embedding of histological details, validating pathological MRI findings, and finding quantitative imaging biomarkers of neurodegenerative diseases. However, coregistration is challenging due to non-linear distortions of the tissue from histological processing and sectioning leading to microscopic and macroscopic nonlinear 3D deformations between specimen MRI and stained histology sections. To address this, we developed a novel pipeline, named Brewsters Blockface Quantification (BBQ), integrating robust optical approaches with innovative 2D and 3D registration algorithms to achieve precise volumetric alignment of specimen MRI data with histological images. On a variety of brain tissue specimens from distinct anatomical regions and across multiple species, our methodology generated blockface volumes with minimal distortion and artifacts. Using these blockface volumes as an intermediary, we achieve a precise alignment between MRI and histology slides, yielding registration results with an overlapping Dice score of [~]90% for whole tissue alignment between MRI and blockface volumes, and >95% for 2D MRI-histology registration. This correlative MRI-histology pipeline with robust 2D and 3D coregistration methods promises to enhance our understanding of neurodegenerative diseases and aid the development of MRI-based disease biomarkers.

bioengineering↗

bioRxiv2022

Microstructural alterations in tract development in college football: a longitudinal diffusion MRI study

Background and ObjectivesRepeated concussive and sub-concussive impacts in high-contact sports can affect the brains microstructure, which can be studied using diffusion MRI. Most prior imaging studies, however, employ a cross-sectional design, do not include low-contact players as controls, or use traditional diffusion tensor imaging without investigating novel tractspecific microstructural metrics. MethodsWe examined brain microstructure in 63 high-contact (American football) and 34 low-contact (volleyball) collegiate athletes with up to 4 years of follow-up (315 total scans) using advanced diffusion MRI, a comprehensive set of multi-compartment models, and automated fiber quantification tools. We investigated diffusion metrics along the length of tracts using nested linear mixed-effects models to ascertain the acute and chronic effects of sub-concussive and concussive impacts, as well as associations between diffusion changes with clinical, behavioral, and sports-related measures. ResultsSignificant longitudinal increases in fractional anisotropy and axonal water fraction were detected in volleyball players, but not in football players, along with decreases in radial and mean diffusivity as well as orientation dispersion index (all findings absolute T-statistic > 3.5, p < .0001). This pattern was present in the callosum forceps minor, left superior longitudinal fasciculus, left thalamic radiation, and right cingulum hippocampus. Longitudinal group differences were more prominent and observed in a larger number of tracts in concussed (previously or in-study) football players (p < .0001), while smaller effects were noted in un-concussed players. An analysis of immediate-post concussion scans in football players demonstrated a transient localized increase in axial diffusivity, mean and radial kurtosis in the left uncinate and right cingulum hippocampus (p < .0001). Finally, football players with high position-based sub-concussive risk demonstrated increased orientation dispersion index over time (p < .0001). DiscussionThe observed longitudinal changes in our volleyball cohort likely reflect normal development in this age range, while the relative attenuation of these effects seen in football, and especially concussed athletes, could possibly reveal diminished myelination, altered axonal calibers, or depressed pruning processes leading to a static, non-decreasing axonal dispersion. This prospective longitudinal study demonstrates significantly divergent tract-specific trajectories of brain microstructure, possibly reflecting a concussive and/or repeated sub-concussive impact-related alteration of normal white matter development in football athletes.

neuroscience↗

bioRxiv2021

The Presence of the Temporal Horn Exacerbates the Vulnerability of Hippocampus during Head Impacts

Hippocampal injury is common in traumatic brain injury (TBI) patients, but the underlying pathogenesis remains elusive. In this study, we hypothesize that the presence of the adjacent fluid-containing temporal horn exacerbates the biomechanical vulnerability of the hippocampus. Two finite element models of the human head were used to investigate this hypothesis, one with and one without the temporal horn, and both including a detailed hippocampal subfield delineation. A fluid-structure interaction coupling approach was used to simulate the brain-ventricle interface, in which the intraventricular cerebrospinal fluid was represented by an arbitrary Lagrangian-Eulerian multi-material formation to account for its fluid behavior. By comparing the response of these two models under identical loadings, the model that included the temporal horn predicted increased magnitudes of strain and strain rate in the hippocampus with respect to its counterpart without the temporal horn. This specifically affected cornu ammonis (CA) 1 (CA1), CA2/3, hippocampal tail, subiculum, and the adjacent amygdala and ventral diencephalon. These computational results suggest that the presence of the temporal horn exacerbate the vulnerability of the hippocampus, highlighting the mechanobiological dependency of the hippocampus on the temporal horn.

bioengineering↗

bioRxiv2020

White matter tract-oriented deformation is dependent on real-time axonal fiber orientation

Traumatic axonal injury (TAI) is a critical public health issue with its pathogenesis remaining largely elusive. Finite element (FE) head models are promising tools to bridge the gap between mechanical insult, localized brain response, and resultant injury. In particular, the FE-derived deformation along the direction of white matter (WM) tracts (i.e., tract-oriented strain) has been shown to be an appropriate predictor for TAI. However, the evolution of fiber orientation in time during the impact and its potential influence on the tract-oriented strain remains unknown. To address this question, the present study leveraged an embedded element approach to track real-time fiber orientation during impacts. A new scheme to calculate the tract-oriented strain was proposed by projecting the strain tensors from pre-computed simulations along the temporal fiber direction instead of its static counterpart directly obtained from diffuse tensor imaging. The results revealed that incorporating the real-time fiber orientation not only altered the direction but also amplified the magnitude of the tract-oriented strain, resulting in a generally more extended distribution and a larger volume ratio of WM exposed to high deformation along fiber tracts. These effects were exacerbated with the impact severities characterized by the acceleration magnitudes. Results of this study provide insights into how best to incorporate fiber orientation in head injury models and derive the WM tract-oriented deformation from computational simulations, which is important for furthering our understanding of the underlying mechanisms of TAI.

bioengineering↗

bioRxiv2018

Anticorrelated inter-network electrophysiological activity varies dynamically with attentional performance and behavioral states

The default mode network (DMN) is thought to exhibit infraslow anticorrelated activity with dorsal attention (DAN) and salience (SN) networks across various behavioral states. To investigate the dynamics of activity across these networks on a finer timescale, we used human intracranial electroencephalography with simultaneous recordings within core nodes of the three networks. During attentional task performance, the three sites showed dissociable profiles of high-frequency broadband activity. Anticorrelated infraslow fluctuations of this activity were found across networks during task performance but also intermittently emerged during rest and sleep in concert with the expression of task-like network-level topographic patterns. Critically, on a finer timescale, DAN and SN activations preceded DMN deactivations by hundreds of milliseconds. Moreover, greater lagged, but not zero-lag, anticorrelation between DAN and DMN activity was associated with better attentional performance. These findings have implications for interpreting antagonistic network relationships and confirm the behavioral importance of time-lagged inter-network interactions.

neuroscience↗