Visualization of cortical activation in human brain by flavoprotein fluorescence imaging

Daiju MitsuhashiDepartment of Neurosurgery and

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Ryuichi HishidaDepartment of Neurophysiology, Brain Research Institute, Niigata University, Niigata, Japan

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Makoto OishiDepartment of Neurosurgery and

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Tetsuya HiraishiDepartment of Neurosurgery and

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Manabu NatsumedaDepartment of Neurosurgery and

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Katsuei ShibukiDepartment of Neurophysiology, Brain Research Institute, Niigata University, Niigata, Japan

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Yukihiko FujiiDepartment of Neurosurgery and

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OBJECTIVE

To develop an innovative brain mapping and neuromonitoring method during neurosurgery, the authors set out to establish intraoperative flavoprotein fluorescence imaging (iFFI) to directly visualize cortical activations in human brain. The significance of iFFI was analyzed by comparison with intraoperative perfusion-dependent imaging (iPDI), which is considered the conventional optical imaging, and by performing animal experiments.

METHODS

Seven patients with intracerebral tumors were examined by iFFI and iPDI following craniotomy, using a single operative microscope equipped with a laser light source for iFFI and xenon lamp for iPDI. Images were captured by the same charge-coupled device camera. Responses to bipolar stimulation at selected points on the cortical surface were analyzed off-line, and relative signal changes were visualized by overlaying pseudocolor intensity maps onto cortical photographs. Signal changes exceeding 3 SDs from baseline were defined as significant. The authors also performed FFI and PDI on 10 mice using similar settings, and then compared signal patterns to intraoperative studies.

RESULTS

Signals acquired by iFFI exhibited biphasic spatiotemporal changes consisting of an early positive signal peak (F1) and a delayed negative signal peak (F2). In contrast, iPDI signals exhibited only 1 negative peak (P1) that was significantly delayed compared to F1 (p < 0.02) and roughly in phase with F2. Compared to F2 and P1, F1 was of significantly lower amplitude (p < 0.02) and located closer to the bipolar stimulus center (p < 0.03), whereas F2 and P1 were more widespread, irregular, and partially overlapping. In mice, the spatiotemporal characteristics of FFI and PDI resembled those of iFFI and iPDI, but the early positive signal was more robust than F1.

CONCLUSIONS

This is the first report in humans of successful intraoperative visualization of cortical activations by using iFFI, which showed rapid evoked cortical activity prior to perfusion-dependent signal changes. Further technical improvements can lead to establishment of iFFI as a real-time intraoperative tool.

ABBREVIATIONS

CCD = charge-coupled device; FFI = flavoprotein fluorescence imaging; F0 = basal fluorescence; ΔF/F0 = change in fluorescence; iFFI = intraoperative FFI; iOI = intraoperative optical imaging; iPDI = intraoperative PDI; PDI = perfusion-dependent imaging; ROI = region of interest; R0 = basal reflectance; ΔR/R0 = change in reflectance.
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Illustration from Di Somma et al. (pp 1187–1190). Published with permission from Glia Media | Artist: Martha Headworth, MS.

  • 1

    Cannestra AF, Blood AJ, Black KL, Toga AW. The evolution of optical signals in human and rodent cortex. Neuroimage. 1996;3(3 Pt 1):202208.

  • 2

    Cannestra AF, Black KL, Martin NA, et al. Topographical and temporal specificity of human intraoperative optical intrinsic signals. Neuroreport. 1998;9(11):25572563.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Cannestra AF, Pouratian N, Bookheimer SY, Martin NA, Beckerand DP, Toga AW. Temporal spatial differences observed by functional MRI and human intraoperative optical imaging. Cereb Cortex. 2001;11(8):773782.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Nariai T, Sato K, Hirakawa K, et al. Imaging of somatotopic representation of sensory cortex with intrinsic optical signals as guides for brain tumor surgery. J Neurosurg. 2005;103(3):414423.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Sobottka SB, Meyer T, Kirsch M, et al. Intraoperative optical imaging of intrinsic signals: a reliable method for visualizing stimulated functional brain areas during surgery. J Neurosurg. 2013;119(4):853863.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Toga AW, Cannestra AF, Black KL. The temporal/spatial evolution of optical signals in human cortex. Cereb Cortex. 1995;5(6):561565.

  • 7

    Cannestra AF, Bookheimer SY, Pouratian N, et al. Temporal and topographical characterization of language cortices using intraoperative optical intrinsic signals. Neuroimage. 2000;12(1):4154.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Pouratian N, Bookheimer SY, O’Farrell AM, et al. Optical imaging of bilingual cortical representations. Case report. J Neurosurg. 2000;93(4):676681.

  • 9

    Zhou Q, Wang Y, Yi L, Tan Z, Jiang Y. Multisensory interplay within human auditory cortex: new evidence from intraoperative optical imaging of intrinsic signal. World Neurosurg. 2017;98:251257.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Haglund MM, Hochman DW. Optical imaging of epileptiform activity in human neocortex. Epilepsia. 2004;45(4)(suppl 4):4347.

  • 11

    Zhao M, Suh M, Ma H, Perry C, Geneslaw A, Schwartz TH. Focal increases in perfusion and decreases in hemoglobin oxygenation precede seizure onset in spontaneous human epilepsy. Epilepsia. 2007;48(11):20592067.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Fox PT, Raichle ME. Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects. Proc Natl Acad Sci U S A. 1986;83(4):11401144.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Roy CS, Sherrington CS. On the regulation of the blood-supply of the brain. J Physiol. 1890;11(1-2):85158.17.

  • 14

    Chen-Bee CH, Frostig RD. Variability and interhemispheric asymmetry of single-whisker functional representations in rat barrel cortex. J Neurophysiol. 1996;76(2):884894.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Masino SA, Frostig RD. Quantitative long-term imaging of the functional representation of a whisker in rat barrel cortex. Proc Natl Acad Sci U S A. 1996;93(10):49424947.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Pouratian N, Cannestra AF, Martin NA, Toga AW. Intraoperative optical intrinsic signal imaging: a clinical tool for functional brain mapping. Neurosurg Focus. 2002;13(4):e1.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Duchen MR. Ca(2+)-dependent changes in the mitochondrial energetics in single dissociated mouse sensory neurons. Biochem J. 1992;283(Pt 1):4150.

  • 18

    Mironov SL, Richter DW. Oscillations and hypoxic changes of mitochondrial variables in neurons of the brainstem respiratory centre of mice. J Physiol. 2001;533(Pt 1):227236.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Shibuki K, Hishida R, Murakami H, et al. Dynamic imaging of somatosensory cortical activity in the rat visualized by flavoprotein autofluorescence. J Physiol. 2003;549(Pt 3):919927.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Hishida R, Watanabe K, Kudoh M, Shibuki K. Transcranial electrical stimulation of cortico-cortical connections in anesthetized mice. J Neurosci Methods. 2011;201(2):315321.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Shibuki K, Ono K, Hishida R, Kudoh M. Endogenous fluorescence imaging of somatosensory cortical activities after discrimination learning in rats. Neuroimage. 2006;30(3):735744.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Takao T, Murakami H, Fukuda M, et al. Transcranial imaging of audiogenic epileptic foci in the cortex of DBA/2J mice. Neuroreport. 2006;17(3):267271.

  • 23

    Tohmi M, Kitaura H, Komagata S, Kudoh M, Shibuki K. Enduring critical period plasticity visualized by transcranial flavoprotein imaging in mouse primary visual cortex. J Neurosci. 2006;26(45):1177511785.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Hiraishi T, Kitaura H, Oishi M, et al. Significance of horizontal propagation of synchronized activities in human epileptic neocortex investigated by optical imaging and immunohistological study. Epilepsy Res. 2013;104(1-2):5967.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Kitaura H, Hiraishi T, Murakami H, et al. Spatiotemporal dynamics of epileptiform propagations: imaging of human brain slices. Neuroimage. 2011;58(1):5059.

  • 26

    Kitaura H, Kakita A. Optical imaging of human epileptogenic tissues in vitro. Neuropathology. 2013;33(4):469474.

  • 27

    Kitaura H, Shirozu H, Masuda H, Fukuda M, Fujii Y, Kakita A. Pathophysiological characteristics associated with epileptogenesis in human hippocampal sclerosis. EBioMedicine. 2018;29:3846.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Chance B, Cohen P, Jobsis F, Schoener B. Intracellular oxidation-reduction states in vivo. Science. 1962;137(3529):499508.

  • 29

    Aubin JE. Autofluorescence of viable cultured mammalian cells. J Histochem Cytochem. 1979;27(1):3643.

  • 30

    Benson RC, Meyer RA, Zaruba ME, McKhann GM. Cellular autofluorescence—is it due to flavins?. J Histochem Cytochem. 1979;27(1):4448.

  • 31

    Reinert KC, Dunbar RL, Gao W, Chen G, Ebner TJ. Flavoprotein autofluorescence imaging of neuronal activation in the cerebellar cortex in vivo. J Neurophysiol. 2004;92(1):199211.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32

    Frostig RD, Lieke EE, Ts’o DY, Grinvald A. Cortical functional architecture and local coupling between neuronal activity and the microcirculation revealed by in vivo high-resolution optical imaging of intrinsic signals. Proc Natl Acad Sci U S A. 1990;87(16):60826086.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33

    Malonek D, Grinvald A. Interactions between electrical activity and cortical microcirculation revealed by imaging spectroscopy: implications for functional brain mapping. Science. 1996;272(5261):551554.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34

    Sheth S, Nemoto M, Guiou M, Walker M, Pouratian N, Toga AW. Evaluation of coupling between optical intrinsic signals and neuronal activity in rat somatosensory cortex. Neuroimage. 2003;19(3):884894.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35

    Maniwa K, Yamashita H, Tsukano H, et al. Tomographic optical imaging of cortical responses after crossing nerve transfer in mice. PLoS One. 2018;13(2):e0193017.

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