Optical measurement of microvascular oxygenation and blood flow responses in awake mouse cortex during functional activation

İkbal Şencan, Tatiana Esipova, Kıvılcım Kılıç, Baoqiang Li, Michèle Desjardins, Mohammad A. Yaseen, Hui Wang, Jason E. Porter, Sreekanth Kura, Buyin Fu, Timothy W. Secomb, David A. Boas, Sergei A. Vinogradov, Anna Devor, Sava Sakadžić

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

The cerebral cortex has a number of conserved morphological and functional characteristics across brain regions and species. Among them, the laminar differences in microvascular density and mitochondrial cytochrome c oxidase staining suggest potential laminar variability in the baseline O2 metabolism and/or laminar variability in both O2 demand and hemodynamic response. Here, we investigate the laminar profile of stimulus-induced intravascular partial pressure of O2 (pO2) transients to stimulus-induced neuronal activation in fully awake mice using two-photon phosphorescence lifetime microscopy. Our results demonstrate that stimulus-induced changes in intravascular pO2 are conserved across cortical layers I–IV, suggesting a tightly controlled neurovascular response to provide adequate O2 supply across cortical depth. In addition, we observed a larger change in venular O2 saturation (ΔsO2) compared to arterioles, a gradual increase in venular ΔsO2 response towards the cortical surface, and absence of the intravascular “initial dip” previously reported under anesthesia. This study paves the way for quantification of layer-specific cerebral O2 metabolic responses, facilitating investigation of brain energetics in health and disease and informed interpretation of laminar blood oxygen level dependent functional magnetic resonance imaging signals.

Original languageEnglish
Pages (from-to)510-525
Number of pages16
JournalJournal of Cerebral Blood Flow and Metabolism
Volume42
Issue number3
DOIs
StatePublished - Mar 2022

Keywords

  • Intravascular partial pressure of oxygen
  • cortical layers
  • neurovascular coupling
  • oxygen extraction fraction
  • two-photon microscopy

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