@article{oai:repo.qst.go.jp:00048785,
 author = {Manami, Takahashi and Urushihata, Takuya and Takuwa, Hiroyuki and Sakata, Kazumi and Takado, Yuhei and Shimizu, Eiji and Suhara, Tetsuya and Higuchi, Makoto and Ito, Hiroshi and 高橋 真奈美 and 漆畑 拓弥 and 田桑 弘之 and 高堂 裕平 and 清水 栄司 and 須原 哲也 and 樋口 真人 and 伊藤 浩},
 issue = {723},
 journal = {Frontiers Neuroscience},
 month = {Jan},
 note = {Green fluorescence imaging (e.g., flavoprotein autofluorescence imaging, FAI) can be
used to measure neuronal activity and oxygen metabolism in living brains without
expressing fluorescence proteins. It is useful for understanding the mechanism of
various brain functions and their abnormalities in age-related brain diseases. However,
hemoglobin in cerebral blood vessels absorbs green fluorescence, hampering accurate
assessments of brain function in animal models with cerebral blood vessel dysfunctions
and subsequent cerebral blood flow (CBF) alterations. In the present study, we developed
a new method to correct FAI signals for hemoglobin-dependent green fluorescence
reductions by simultaneous measurements of green fluorescence and intrinsic optical
signals. Intrinsic optical imaging enabled evaluations of light absorption and scatters
by hemoglobin, which could then be applied to corrections of green fluorescence
intensities. Using thismethod, enhanced flavoprotein autofluorescence by sensory stimuli
was successfully detected in the brains of awake mice, despite increases of CBF,
and hemoglobin interference. Moreover, flavoprotein autofluorescence could be properly
quantified in a resting state and during sensory stimulation by a CO2 inhalation challenge,
which modified vascular responses without overtly affecting neuronal activities. The
flavoprotein autofluorescence signal data obtained here were in good agreement with the
previous findings from a condition with drug-induced blockade of cerebral vasodilation,
justifying the current assaying methodology. Application of this technology to studies on
animal models of brain diseases with possible changes of CBF, including age-related
neurological disorders, would provide better understanding of the mechanisms of
neurovascular coupling in pathological circumstances.},
 title = {Imaging of neuronal activity in awake mice by measurements of flavoprotein autofluorescence corrected for cerebral blood flow},
 volume = {11},
 year = {2018}
}