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

Quanyu Zhou, Chaim Glück, Lin Tang, Lukas Glandorf, Jeanne Droux, Mohamad El Amki, Susanne Wegener, Bruno Weber, Daniel Razansky, Zhenyue Chen

Research output: Contribution to journalArticlepeer-review


Large-scale imaging of brain activity with high spatio-temporal resolution is crucial for advancing our understanding of brain function. The existing neuroimaging techniques are largely limited by restricted field of view, slow imaging speed, or otherwise do not have the adequate spatial resolution to capture brain activities on a capillary and cellular level. To address these limitations, we introduce fluorescence localization microscopy aided with sparsely-labeled red blood cells for cortex-wide morphological and functional cerebral angiography with 4.9 µm spatial resolution and 1 s temporal resolution. When combined with fluorescence calcium imaging, the proposed method enables extended recordings of stimulus-evoked neuro-vascular changes in the murine brain while providing simultaneous multiparametric readings of intracellular neuronal activity, blood flow velocity/direction/volume, and vessel diameter. Owing to its simplicity and versatility, the proposed approach will become an invaluable tool for deciphering the regulation of cortical microcirculation and neurovascular coupling in health and disease.

Original languageEnglish
Article number3526
JournalNature Communications
Issue number1
StatePublished - Dec 2024
Externally publishedYes


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