Breakthrough brain imaging technology reveals neurovascular dynamics at cellular resolution
Chinese researchers have developed a revolutionary hybrid microscope that simultaneously captures brain blood flow and neuronal activity across the entire mouse cortex with unprecedented detail. The LiTA-HM system achieves subcellular resolution over a 6mm field of view, opening new frontiers in neurovascular coupling research and brain-computer interface development.
Revolutionary microscope transforms brain imaging capabilities
Researchers from the Chinese Academy of Sciences have engineered a groundbreaking imaging system that solves a fundamental challenge in neuroscience: simultaneously monitoring brain blood vessels and neuronal activity across the entire cortex with cellular-level precision.
The Linear Transducer Array-based Hybrid Microscope (LiTA-HM) represents a major technological leap forward, combining photoacoustic microscopy with confocal fluorescence microscopy to achieve what the authors describe as “simultaneous cortex-wide microvascular dynamics, blood oxygenation metabolism, and neuronal activities with high spatiotemporal resolution.”
Published in Science Advances on 23 July 2025, the research demonstrates the system’s remarkable capabilities: 6-micrometre spatial resolution across a 6mm × 5mm field of view, capturing images at 1.25 frames per second. This performance represents a significant advancement over existing technologies, which typically sacrifice either resolution for field of view or imaging speed for comprehensive coverage.
Technical innovations enable unprecedented brain monitoring
The breakthrough lies in LiTA-HM’s sophisticated engineering, particularly its custom-designed linear array of eight miniature ultrasound transducers. These components, each measuring just 0.47mm × 0.57mm with a 40 MHz centre frequency, dramatically expand the detection range whilst maintaining exceptional sensitivity for photoacoustic signals.
Professor Hairong Zheng, who led the research team, explained that the system “enables simultaneous, dynamic, high-resolution imaging of neuronal activity and microvascular behaviour across the entire cortex of awake mice.” The researchers developed a novel weighted averaging image reconstruction algorithm that enhances signal-to-noise ratio by 1.6 times, ensuring consistent image quality across the entire field of view.
A key innovation is the high-speed polygon scanning system, featuring a custom 16-facet configuration that achieves ultrafast line scanning at 1.33 kHz whilst maintaining mechanical stability. This design eliminates interference from ultrasonic coupling media whilst preserving inherent speed advantages.
Neurovascular coupling insights transform disease understanding
The research team demonstrated LiTA-HM’s capabilities through comprehensive experiments examining neurovascular coupling (NVC) – the critical relationship between brain activity and blood supply. In hypoxia experiments, they observed distinct neuronal response patterns, with the authors noting: “Four distinguished groups of neurons were observed by performing K-means clustering of their calcium dynamics in the hypoxia experiment.”
Particularly significant were the temporal dynamics revealed during different physiological states. In hypoxia conditions, vascular responses preceded neuronal activity by approximately 10.8 seconds, whilst anaesthesia experiments showed inverse correlations between fluorescence intensity and blood oxygen saturation across multiple cortex regions.
The epilepsy studies proved especially revealing, with the system successfully tracking spreading depolarisation waves across hemispheres. As the authors reported: “During the seizure phase, global epilepsy was observed across the entire cortex, followed by propagation of spreading depolarizations in the left hemisphere and the right hemisphere.”
Clinical applications promise enhanced brain disease research
LiTA-HM’s unprecedented capabilities offer substantial advantages for neurological research and potential clinical applications. The system’s ability to simultaneously monitor thousands of individual neurons and capillary-level blood vessels provides comprehensive insights into brain function previously impossible to achieve.
The research has particular relevance for brain-computer interface development, as the authors noted that NVC “plays a critical role in non-invasive brain-computer interfaces –such as systems for controlling robotic arms or cursors.” The technology’s high spatiotemporal resolution could significantly enhance the precision of neural signal detection for therapeutic applications.
For epilepsy research specifically, the findings suggest that “the timing and brain region location of epileptic events can be determined by monitoring the hemodynamic changes,” potentially revolutionising seizure prediction and localisation methods.
Future directions in neuroscience imaging
The research team anticipates broad applications across neurological disorders, including stroke, Alzheimer’s disease, and cerebral small vessel disease. The authors suggest that “future investigations could help decode NVC mechanisms by integrating optogenetic manipulation in LiTA-HM and combining excitatory/inhibitory neuron-specific fluorescent labelling techniques.”
This technological advancement represents a significant step towards understanding the complex interplay between neuronal populations and cerebrovascular networks at unprecedented scale and resolution. The system’s ability to provide real-time, cortex-wide monitoring could accelerate discoveries in neurovascular coupling mechanisms and advance therapeutic interventions for brain diseases.
The research demonstrates how innovative engineering solutions can overcome longstanding technical limitations, opening new possibilities for neuroscience research and clinical applications.
Reference
Liu, L., Xu, Z., Lai, Z., Xu, B., Wu, T., Ma, G., … & Liu, C. (2025). Photoacoustic and fluorescence hybrid microscope for cortex-wide imaging of neurovascular dynamics with subcellular resolution. Science Advances, 11(30), eadw5275. https://doi.org/10.1126/sciadv.adw5275
