Biology subjects

Lin, B.-Z.

Publications and source records attributed to Lin, B.-Z..

5 recordsLinked to original sources

bioRxiv2026

Stabilizing gas in aqueous liquids with metal-organic frameworks for persistent acoustic transduction

Gas is the most efficient mediator of acoustic energy owing to its high compressibility, yet its thermodynamic instability in aqueous environments makes it inherently transient, limiting sustained ultrasound-biological interfacing. Here, we show that gas can be stabilized, confined, and manipulated in the liquid phase to function as a persistent acoustic transducer. By trapping gas within designed microporous metal-organic framework (MOF) nanocrystals, interfacial forces establish a stable ternary-phase equilibrium that suppresses water intrusion and prevents gas collapse, enabling reversible, non-destructive oscillations under ultrasound stimulation and providing design principles for stabilizing gas in liquid environments. By leveraging high-resolution ultra-high-speed digital image correlation (DIC), we unveil the previously inaccessible spatiotemporal dynamics of confined gas oscillations within these nanotransducers under ultrasound stimulation, revealing localized amplification of the surrounding acoustic field and establishing a quantitative structure-function relationship for programmable acoustic transduction. These aqueous-phase gas nanotransducers exhibit sustained acoustic amplification over millions of excitation cycles and remain functional after prolonged storage (>2 years) under physiological conditions. In vitro and in vivo, this platform enables long-term ultrasound imaging and sustained, non-invasive neuromodulation by converting confined gas oscillations into persistent and amplified mechanical actuation. Our findings establish a generalizable design framework for stabilizing gas in liquid environments to achieve persistent and programmable acoustic transduction, thereby enabling sustained ultrasound-biological interfacing and opening opportunities for gas-based therapeutics.

bioengineering↗

bioRxiv2026

Longitudinal Awake Mouse Brain Imaging Using Functional Ultrasound and Functional Ultrasound Localization Microscopy

Ultrafast ultrasound offers a unique route to cross-scale neurovascular phenotyping by integrating functional ultrasound (fUS), ultrasound localization microscopy (ULM), and functional ULM (fULM). Yet the baseline variability, longitudinal stability, and biological safety of such multimodal imaging in awake animals remain insufficiently defined, limiting its use for detecting subtle disease-associated neurovascular changes. Here, an awake longitudinal fUS-ULM-fULM framework is established and validated in mice over five months. Structural vascularity, microvascular flow velocity, mesoscale hemodynamic responses, and microvascular functional responses are repeatedly quantified in the same animals during monthly imaging sessions. Across all metrics, no significant longitudinal drift is detected (p > 0.60). Structural and flow-derived measures are markedly more reproducible than functional readouts, with within-subject coefficients of variation of 5.1% for mean flow velocity and 7.3% for vascularity, compared with 25.0% for fUS-derived cerebral blood volume responses and 53.2% for fULM-derived microvascular functional responses. Mean flow velocity shows the strongest longitudinal consistency (ICC = 0.70) and the lowest detection threshold. Behavioral testing and GFAP/Iba1 staining further reveal no memory impairment or chronic neuroinflammation. This study defines quantitative baselines, reproducibility limits, and safety evidence for awake cross-scale ultrasound imaging, providing a reference framework for longitudinal neurovascular phenotyping in preclinical disease models.

neuroscience↗

bioRxiv2025

Microbubble Track-based Functional Ultrasound Localization Microscopy in Awake Mice

Functional neuroimaging with ultrafast ultrasound is an emerging neuroimaging tool for studying neural activities in the rodent brain. Existing methods, however, are challenged by the compromise between functional imaging sensitivity (i.e., sensitivity in detecting neural responses) and spatial resolution. For example, functional ultrasound (fUS) uses native red blood cells (RBCs) as imaging targets, which offers high functional imaging sensitivity but limited spatial resolution that is confined by the diffraction limit of ultrasound. On the other hand, functional ultrasound localization microscopy (fULM) employs intravenously injected microbubble (MB) as contrast agent to achieve super-resolved spatial resolution but at the cost of functional imaging sensitivity. This study aims to address this challenge by developing a novel, MB track-based hemodynamic activity estimation method to enhance the functional imaging sensitivity of fULM. Our approach involves conducting functional correlation analysis using the MB signals acquired from the entire MB movement track rather than individual MB centroid locations, which overcomes the signal sparsity issue in fULM. To further boost the functional sensitivity of fULM, we developed a novel approach based on indwelling jugular vein catheters to achieve fULM imaging in awake mice. The in vivo imaging results demonstrate that the proposed techniques successfully enhanced the functional imaging sensitivity of fULM without compromising its high spatial resolution. In the whisker stimulation experiments, the proposed technique enabled detection of significantly activated brain regions within fewer than five stimulation cycles (5 minutes of acquisition), reducing the required time by over 50% compared to conventional fULM.

bioengineering↗

bioRxiv2025

Microbubble Backscattering Intensity Improves the Sensitivity of Three-dimensional (3D) Functional Ultrasound Localization Microscopy (fULM)

Functional ultrasound localization microscopy (fULM) enables brain-wide mapping of neural activity at micron-scale resolution but suffers from limited sensitivity due to sparse and noisy microbubble (MB) detections. Extending fULM into three dimensions (3D) further exacerbates these challenges because of low-frequency matrix arrays, reduced localization efficiency, and severe data sparsity. To address these limitations, we developed a statistical framework that models MB arrivals in 3D as a Poisson process accounting for localization efficiency, detection probability, and backscattered amplitude. This analysis predicts that integrating amplitude with count-based fULM improves functional sensitivity, particularly under high MB concentrations where localization saturates. Three-dimensional MB advection simulations confirmed these predictions, showing that backscattering fULM (B-fULM) maintains sensitivity at higher MB concentrations where conventional fULM fails. In rat brain experiments, B-fULM yielded stronger and more robust stimulus-evoked responses, with SNR gains of 18% in the somatosensory cortex and 61% in the thalamus, while preserving super-resolved spatial detail (33.4 m for B-fULM vs 35.7 m for fULM). These results establish B-fULM as a practical and sensitive approach for super-resolved 3D functional neuroimaging

bioengineering↗

bioRxiv2023

Longitudinal Awake Imaging of Deep Mouse Brain Microvasculature with Super-resolution Ultrasound Localization Microscopy

Ultrasound localization microscopy (ULM) is an emerging imaging modality that resolves microvasculature in deep tissues with high spatial resolution. However, existing preclinical ULM applications are largely constrained to anesthetized animals, introducing confounding vascular effects such as vasodilation and altered hemodynamics. As such, ULM quantifications (e.g., vessel diameter, density, and flow velocity) may be confounded by the use of anesthesia, undermining the usefulness of ULM in practice. Here we introduce a method to address this limitation and achieve ULM imaging in awake mouse brain. Pupillary monitoring was used to support the presence of the awake state during ULM imaging. Vasodilation induced by isoflurane was observed by ULM. Upon recovery to the awake state, reductions in vessel density and flow velocity were observed across different brain regions. In the cortex, the effects induced by isoflurane are more pronounced on venous flow than on arterial flow. In addition, serial in vivo imaging of the same animal brain at weekly intervals demonstrated the highly robust longitudinal imaging capability of the proposed technique. The consistency was further verified through quantitative analysis on individual vessels, cortical regions of arteries and veins, and subcortical regions. This study demonstrates longitudinal ULM imaging in the awake mouse brain, which is crucial for many ULM brain applications that require awake and behaving animals.

biophysics↗