Biology subjects

Man, W.

Publications and source records attributed to Man, W..

4 recordsLinked to original sources

bioRxiv2026

Vessel-Resolved Mapping of Perivascular Spaces Reveals Hierarchical Neurofluid Organization In Vivo

Perivascular spaces (PVS) are central to cerebrospinal fluid (CSF)-interstitial fluid (ISF) exchange in the brain, yet their brain-wide organization and in vivo accessibility remain poorly resolved due to limited spatial resolution and contrast specificity of existing imaging approaches. Prior gadolinium (Gd)-enhanced MRI studies demonstrate global tracer distribution but yield spatially diffuse signals that do not resolve PVS at the level of individual vessels. Here we introduce an ultra-high-resolution dual-contrast MRI framework that enables vessel-resolved mapping of PVS across the whole brain in vivo. This approach combines ultra-high-field imaging, an implantable radiofrequency coil for enhanced local sensitivity, and intraventricular Gd delivery to achieve sufficient contrast and spatial specificity for detecting vessel-associated perivascular signal. Using this framework, we show that PVS are hierarchically organized along vascular trees, extending from major surface arteries into deep cortical and subcortical regions. Signal patterns along arterial branches and junctions indicate that PVS follows vascular topology. Quantitative analysis reveals that only a subset of penetrating vessels ([~]6%) exhibits detectable PVS signal, indicating heterogeneous organization across vascular networks independent of vessel caliber. Widespread detection of PVS, including in the hippocampus, further demonstrates that ventricularly delivered tracers access a distributed, vessel-associated perivascular network in vivo. These results establish an anatomical framework for mapping perivascular transport pathways across the brain, bridging global tracer imaging with vessel-resolved organization, and enabling investigation of how vascular architecture and fluid dynamics shape CSF-ISF exchange.

neuroscience↗

bioRxiv2023

Mapping the bioimaging marker of Alzheimer's disease based on pupillary light response-driven brain-wide fMRI in awake mice

Pupil dynamics has emerged as a critical non-invasive indicator of brain state changes. In particular, pupillary-light-responses (PLR) in Alzheimers disease (AD) patients may be used as biomarkers of brain degeneration. To characterize AD-specific PLR and its underlying neuromodulatory sources, we combined high-resolution awake mouse fMRI with real-time pupillometry to map brain-wide event-related correlation patterns based on illumination-driven pupil constriction (Pc) and post-illumination pupil dilation recovery (amplitude, Pd, and time, T). The Pc-driven differential analysis revealed altered visual signal processing coupled with reduced thalamocortical activation in AD mice compared with the wild-type normal mice. In contrast, the post-illumination pupil dilation recovery-based fMRI highlighted multiple brain areas related to AD brain degeneration, including the cingulate cortex, hippocampus, septal area of the basal forebrain, medial raphe nucleus, and pontine reticular nuclei (PRN). Also, brain-wide functional connectivity analysis highlighted the most significant changes in PRN of AD mice, which serves as the major subcortical relay nuclei underlying oculomotor function. This work combined non-invasive pupil-fMRI measurements in preclinical models to identify pupillary biomarkers based on neuromodulatory dysfunction coupled with AD brain degeneration.

neuroscience↗

bioRxiv2023

Millimeter-scale magnetic implants paired with a fully integrated wearable device for wireless biophysical and biochemical sensing

Implantable sensors can directly interface with various organs for precise evaluation of health status. However, extracting signals from such sensors must rely on transcutaneous wires, integrated circuit chips, or cumbersome readout equipment, which increases the risks of infection, reduces the biocompatibility, or limits the portability. Here, we develop a set of millimeter-scale, chip-less and battery-less magnetic implants that can measure biophysical and biochemical signals wirelessly. In particular, the implants form two-way communications with a fully integrated wearable device, where the wearable device can induce a large-amplitude damped vibration of the magnetic implants and capture their subsequent motions in a wireless manner. Such damped vibrations reflect not only the biophysical conditions surrounding the implants movements, but also the concentration of a specific biochemical depending on the surface modification. Experiments in rat models demonstrate the capabilities in measuring cerebrospinal fluid (CSF) viscosity, intracranial pressure (ICP), and CSF glucose levels. This miniaturized system opens possibility for continuous, wireless monitoring of a wide range of biophysical and biochemical conditions within the living organism.

bioengineering↗

bioRxiv2023

Mapping glymphatic solute transportation through the perivascular space of hippocampal arterioles with 14 Tesla MRI

The perivascular space (PVS) plays a crucial role in facilitating the clearance of waste products and the exchange of cerebrospinal fluid and interstitial fluid in the central nervous system. While optical imaging methods identify the glymphatic transport of fluorescent tracers through PVS of surface-diving arteries, their limited depth penetration impedes the study of glymphatic dynamics in deep brain regions. In this study, we introduced a novel high-resolution dynamic contrast-enhanced MRI mapping approach based on single-vessel multi-gradient-echo methods. This technique allowed the differentiation of penetrating arterioles and venules from adjacent parenchymal tissue voxels and enabled the detection of Gd-enhanced signals coupled to PVS of penetrating arterioles in the deep cortex and hippocampus. By directly infusing Gd into the lateral ventricle, we eliminated delays in cerebrospinal fluid flow and focused on PVS Gd transport through PVS of hippocampal arterioles. The study revealed significant PVS-specific Gd signal enhancements, shedding light on glymphatic function in deep brain regions. These findings advance our understanding of brain-wide glymphatic dynamics and hold potential implications for neurological conditions characterized by impaired waste clearance, warranting further exploration of their clinical relevance and therapeutic applications.

neuroscience↗