Cortex-wide transcranial localization microscopy with fluorescently labeled red blood cells

Area of Science:

• Neuroscience
• Biomedical Engineering
• Microscopy

Background:

• High spatio-temporal resolution brain imaging is essential for understanding brain function.
• Current neuroimaging methods face limitations in field of view, speed, and spatial resolution for capillary-level analysis.

Purpose of the Study:

• To introduce a novel fluorescence localization microscopy technique for cortex-wide cerebral angiography.
• To overcome limitations of existing methods for visualizing microcirculation and neuronal activity.

Main Methods:

• Utilized fluorescence localization microscopy with sparsely-labeled red blood cells.
• Achieved 4.9 µm spatial resolution and 1 s temporal resolution for cerebral angiography.
• Combined with fluorescence calcium imaging for simultaneous multiparametric recordings.

Main Results:

• Enabled cortex-wide morphological and functional cerebral angiography.
• Provided simultaneous recordings of neuronal activity, blood flow (velocity, direction, volume), and vessel diameter.
• Facilitated extended recordings of stimulus-evoked neuro-vascular changes in the murine brain.

Conclusions:

• The proposed method offers a versatile tool for studying cortical microcirculation.
• It is invaluable for deciphering neurovascular coupling in both healthy and diseased states.
• Advances the understanding of brain function through detailed imaging capabilities.