Biology subjects

Mezer, A.

Publications and source records attributed to Mezer, A..

6 recordsLinked to original sources

bioRxiv2026

Postnatal maturation of putamen microstructure accompanies topographic white matter connectivity and altered circuits in autism

The putamen is a major hub of the basal ganglia that emerges early in gestation. However, whether its mature organization is established before birth or emerges postnatally remains unknown. Using cross-sectional and longitudinal quantitative MRI (R1 and R2*, related to tissue density and iron, respectively) and diffusion MRI, we characterized the development of putamen's microstructure and its white matter connectivity with cortex from birth to 12 months and compared their trajectories with those in adults. Despite its prenatal emergence, the putamen undergoes substantial postnatal development. R1 increases from birth to 12 months, producing a prominent anterior-posterior gradient, whereas R2* increases primarily between age one and adulthood, producing a medial-lateral gradient. Cortico-putamen white matter connectivity is diffuse in infants but becomes topographic in adults, with anterior putamen linked to frontal cortex and posterior putamen to sensorimotor cortex. In autism spectrum disorder, this organization is largely preserved and accompanied by increased anterior putamen-prefrontal connectivity. Our findings reveal distinct spatial developmental trajectories of putamen microstructure and cortical connectivity providing a developmental framework for understanding the organization of the putamen in infancy, which has implications for assessing neurodevelopmental disorders of the basal ganglia.

neuroscience↗

bioRxiv2025

Loss of Brain Structural qMRI Signatures in Aging

The human brain undergoes significant changes during aging, affecting its macrostructure and microstructure features and impacting its functionality. These aging-related changes are oftentimes linked to different neurodegenerative diseases. Previous studies using MRI and molecular analyses have proposed that aging in each individual brain leads to increased similarity between different brain regions, whereas on the population level, they show greater variability. We investigated these hypotheses using multi-parametric, microstructural, quantitative MRI (qMRI) approaches. Using seven qMRI parametric methods in data from young and older adults, we created unique microstructural signatures of 128 brain regions. Our results supported both hypotheses: First, that inter-regional microstructural similarity is stronger within older individuals; and second, that the variability in microstructural signatures across individuals is also greater in older than in younger adults. Our findings provide new insights into the brains microstructural changes during aging and demonstrate the potential of using multi-parameter qMRI techniques in neuroscience research.

neuroscience↗

bioRxiv2022

Uncovering molecular iron compounds in the living human brain.

Strict iron regulation is essential for normal brain function. The iron homeostasis, determined by the milieu of available iron compounds, is impaired in aging, neurodegenerative diseases and cancer. However, non-invasive assessment of different molecular iron environments implicating brain tissues iron homeostasis remains a challenge. We present a novel magnetic resonance imaging (MRI) technology sensitive to the iron homeostasis of the living brain (the r1-r2* relaxivity). In vitro, our MRI approach reveals the distinct paramagnetic properties of ferritin, transferrin and ferrous iron. In the in vivo human brain, we validate our approach against ex vivo iron compounds quantification and gene expression. Our approach varies with the iron mobilization capacity across brain regions and in aging. It reveals brain tumors iron homeostasis, and enhances the distinction between tumor tissue and non-pathological tissue without contrast agents. Therefore, our approach may allow for non-invasive research and diagnosis of iron homeostasis in living human brains. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=133 SRC="FIGDIR/small/490254v2_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@17e2722org.highwire.dtl.DTLVardef@13b646aorg.highwire.dtl.DTLVardef@3d9bfeorg.highwire.dtl.DTLVardef@cc5b7d_HPS_FORMAT_FIGEXP M_FIG Non-invasive assessment of normal and impaired iron homeostasis in living human brains. C_FIG

neuroscience↗

bioRxiv2021

Myelin contributes to microstructural growth in human sensory cortex during early infancy.

Development of cortical tissue during infancy is critical for the emergence of typical brain functions in cortex. However, how cortical microstructure develops during infancy remains unknown. We measured the longitudinal development of cortex from newborns to six-months-old infants using multimodal quantitative imaging of cortical microstructure. Here we show that infants cortex undergoes profound microstructural tissue growth during the first six months of human life. Comparison of postnatal to prenatal transcriptomic gene expression data demonstrates that myelination and synaptic processes are dominant contributors to this postnatal microstructural tissue growth. Using visual cortex as a model system, we find hierarchical microstructural growth: higher-level visual areas have less mature tissue at birth than earlier visual areas but grow at faster rates. This overturns the prevailing view that visual areas that are most mature at birth develop fastest. Together, in vivo, longitudinal, and quantitative measurements, which we validated with ex vivo transcriptomic data, shed new light on the rate, sequence, and specific biological mechanisms of developing cortical systems. Importantly, our findings propose a new hypothesis that cortical myelination is a key factor in cortical development during early infancy, which has significant implications for diagnosis of neurodevelopmental disorders and delays in infants.

neuroscience↗

bioRxiv2020

Neurobiological underpinnings of rapid white matter plasticity during intensive reading instruction

Diffusion MRI is a powerful tool for imaging brain structure, but it is challenging to discern the biological underpinnings of plasticity inferred from these and other non-invasive MR measurements. Biophysical modeling of the diffusion signal aims to render a more biologically rich image of tissue microstructure, but the application of these models comes with important caveats. A separate approach for gaining biological specificity has been to seek converging evidence from multi-modal datasets. Here we use metrics derived from diffusion kurtosis imaging (DKI) and the white matter tract integrity (WMTI) model along with quantitative MRI measurements of T1 relaxation to characterize changes throughout the white matter during an 8-week, intensive reading intervention (160 total hours of instruction). Behavioral measures, multi-shell diffusion MRI data, and quantitative T1 data were collected at regular intervals during the intervention in a group of 33 children with reading difficulties (7-12 years old), and over the same period in an age-matched non-intervention control group. Throughout the white matter, mean extra-axonal diffusivity was inversely related to intervention time. In contrast, model estimated axonal water fraction (AWF), overall diffusion kurtosis, and T1 relaxation time showed no significant change over the intervention period. Both diffusion and quantitative T1 based metrics were correlated with pre-intervention reading performance, albeit with distinct anatomical distributions. These results are consistent with the view that rapid changes in diffusion properties reflect phenomena other than widespread changes in myelin density. We discuss this result in light of recent work highlighting non-axonal factors in experience-dependent plasticity and learning. HighlightsO_LIDiffusion MRI measurements in white matter show changes linked to an educational intervention. C_LIO_LITissue modeling results point to changes within the extra-axonal space. C_LIO_LIComplementary MRI measurements fail to suggest a widespread change in white matter in myelination over the intervention period. C_LIO_LIBoth diffusion and quantitative T1 measures correlate with pre-intervention reading skill. C_LI

neuroscience↗

bioRxiv2018

A Phantom System Designed to Assess the Effects of Membrane Lipids on Water Proton Relaxation

PurposeQuantitative magnetic resonance imaging (qMRI) provides a method for the non-invasive study of brain structure and associated changes, expressed in physical units. qMRI parameters have been shown to reflect brain tissue composition such as myelin. Nevertheless, it remains a major challenge to identify and quantify the contributions of specific molecular components to the MRI signal. Here, we describe a phantom system that can be used to evaluate the contribution of human brain lipids to qMRI parameters.\n\nMethodsA thin layer evaporation-hydration technique was used to formulate liposomes that mimic the physiological bi-layered membrane lipid environment. We then applied quantitative clinical MRI techniques with adjusted bias corrections in order to test the ability of the phantom system to estimate multiple qMRI parameters such as proton density (PD), T1, T2, T2* and magnetization transfer (MT).\n\nResultsThe results indicated that phantoms composed of various lipids could provide a stable and reliable estimation of qMRI parameters. In addition, the calculated water fraction (WF) maps for the phantoms were found to accurately represent the true WF volumes.\n\nConclusionWe have successfully created a biologically relevant liposome phantom system whose lipid composition can be fully controlled. This system can be used to measure the contributions of lipids to qMRI parameters under conditions that are relevant to in-vivo human scans.

neuroscience↗