High-resolution whole-cortex imaging reveals neurovascular dynamics in awake mice

Neurovascular coupling (NVC) is the dynamic regulation of cerebral blood flow in response to neural activity. Specifically, when neurons become active, nearby blood vessels dilate to increase blood supply, thereby meeting the heightened energy demands associated with neural activity.

NVC is essential for maintaining normal brain function and plays a critical role in non-invasive brain-computer interfaces (BCIs)-such as systems for controlling robotic arms or cursors.

Unfortunately, conventional technologies have limited detection range or insufficient spatiotemporal resolution for high-precision analyzing the dynamic changes in neurons and vasculature across the whole cortex, thereby hindering research into the potential of NVC.

In a study published in Science Advances on July 23, a research team led by Prof. ZHENG Hairong, Prof. LIU Chengbo, and Prof. ZHENG Wei from the Shenzhen Institute of Advanced Technology of the Chinese Academy of Sciences has developed a linear transducer-array-based hybrid microscope (LiTA-HM) that enables simultaneous, dynamic, high-resolution imaging of neuronal activity and microvascular behavior across the entire cortex of awake mice.

The researchers first developed a high-speed polygon scanning system for optical-resolution photoacoustic microscopy, which significantly increases imaging speed while maintaining system stability. This system, together with optimized optical pathways that provide uniform 6-μm resolution across a 6.5-mm range and a flat imaging plane, lays the foundation for high-resolution, rapid multimodal imaging.

To expand the imaging field of view, LiTA-HM has an 8-channel transducer array with a 6-mm detection range while maintaining high sensitivity. Importantly, this design allows the polygon scanner to operate in air, eliminating interference from ultrasonic coupling media without compromising its inherent speed or mechanical stability.

To enhance the performance of LiTA-HM, the researchers developed a novel image reconstruction algorithm that employs weighted averaging and adaptive stripe filtering. The algorithm effectively suppresses transducer-induced artifacts and significantly improves the signal-to-noise ratio.

With its combined imaging modalities and technical innovations, LiTA-HM enables high-speed, large-field-of-view visualization of neurovascular activity in awake mice. It captures capillary-scale vascular networks and single-neuron soma details across the entire cortex, achieving 6-μm spatial resolution across a 6 mm × 5 mm field of view at 1.25 frames per second. This capability allows real-time, full-cortex monitoring of neurovascular dynamics.

Using LiTA-HM, the researchers successfully performed awake mouse experiments in models of brain disease and functional imaging, highlighting the technology's potential for advancing brain research and its practical applications. The LiTA-HM system provides a new tool for non-invasive BCI data acquisition.