Ultra-fast multispectral optical imaging of cortical oxygenation, blood flow, and intracellular calcium dynamics

Bouchard, Michael J.; Chen, Brenda R.; Burgess, Sean A.; Hillman, Elizabeth M. C.

doi:10.1364/oe.17.015670

Cited by 201 publications

(188 citation statements)

References 32 publications

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“…To visualize both neural activity and hemodynamics, awake (Thy1-GCaMP6f) and urethane-anesthetized (Thy1-GCaMP3) mice were imaged using simultaneous fluorescence and multispectral wide-field optical mapping (WFOM) through a thinned-skull cranial window (18,20 (Fig. 1B).…”

Section: Resultsmentioning

confidence: 99%

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Resting-state hemodynamics are spatiotemporally coupled to synchronized and symmetric neural activity in excitatory neurons

Shaik

Kozberg

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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305

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Brain hemodynamics serve as a proxy for neural activity in a range of noninvasive neuroimaging techniques including functional magnetic resonance imaging (fMRI). In resting-state fMRI, hemodynamic fluctuations have been found to exhibit patterns of bilateral synchrony, with correlated regions inferred to have functional connectivity. However, the relationship between resting-state hemodynamics and underlying neural activity has not been well established, making the neural underpinnings of functional connectivity networks unclear. In this study, neural activity and hemodynamics were recorded simultaneously over the bilateral cortex of awake and anesthetized Thy1-GCaMP mice using wide-field optical mapping. Neural activity was visualized via selective expression of the calcium-sensitive fluorophore GCaMP in layer 2/3 and 5 excitatory neurons. Characteristic patterns of resting-state hemodynamics were accompanied by more rapidly changing bilateral patterns of resting-state neural activity. Spatiotemporal hemodynamics could be modeled by convolving this neural activity with hemodynamic response functions derived through both deconvolution and gamma-variate fitting. Simultaneous imaging and electrophysiology confirmed that Thy1-GCaMP signals are well-predicted by multiunit activity. Neurovascular coupling between resting-state neural activity and hemodynamics was robust and fast in awake animals, whereas coupling in urethane-anesthetized animals was slower, and in some cases included lower-frequency (<0.04 Hz) hemodynamic fluctuations that were not well-predicted by local Thy1-GCaMP recordings. These results support that resting-state hemodynamics in the awake and anesthetized brain are coupled to underlying patterns of excitatory neural activity. The patterns of bilaterally-symmetric spontaneous neural activity revealed by widefield Thy1-GCaMP imaging may depict the neural foundation of functional connectivity networks detected in resting-state fMRI. neurovascular coupling | resting state | GCaMP | optical imaging | neural network activity F unctional magnetic resonance imaging (fMRI) measures local changes in deoxyhemoglobin concentration [HbR] as a surrogate for neural activity. In stimulus-evoked studies, the positive fMRI blood oxygen level-dependent (BOLD) signal corresponds to a decrease in [HbR] caused by a local increase in blood flow leading to over-oxygenation of the region. However, a growing number of studies are now using resting-state functional connectivity fMRI (fc-fMRI) in which spontaneous fluctuations in the BOLD signal are recorded in the absence of a task (1). Spatiotemporal correlations in these hemodynamic signals across the brain have been found to be bilaterally symmetric and synchronized in distant brain regions. This synchrony is interpreted as representing the connectivity of intrinsic neural networks (2-6). Many studies have identified changes in these resting-state networks during brain development (7,8) and in neurological and even psychological disorders (9-11). However, understandin...

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Section: Resultsmentioning

confidence: 99%

“…Hemodynamic signals were also used to correct recorded GCaMP fluorescence for the time-varying effects of hemoglobin absorption. All imaging and analysis methods are described in SI Materials and Methods (18,20,21).…”

Section: Resultsmentioning

confidence: 99%

Resting-state hemodynamics are spatiotemporally coupled to synchronized and symmetric neural activity in excitatory neurons

Shaik

Kozberg

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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305

303

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“…See Supplementary Video 3 for a dynamic visualization. In addition, SO 2 changes were analyzed in the same VOIs from Figure 2A, placed outside the major vessel inside the cortex (mouse 1: VOI 3, 4; mouse 2: VOI 7,8). In this case, no threshold was applied to the VOIs.…”

Section: Disclosure/conflict Of Interestmentioning

confidence: 99%

Noninvasive Real-Time Visualization of Multiple Cerebral Hemodynamic Parameters in Whole Mouse Brains Using Five-Dimensional Optoacoustic Tomography

Gottschalk

Fehm

Deán‐Ben

et al. 2015

J Cereb Blood Flow Metab

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Current functional neuroimaging methods are not adequate for high-resolution whole-brain visualization of neural activity in real time. Here, we show imaging of fast hemodynamic changes in deep mouse brain using fully noninvasive acquisition of fivedimensional optoacoustic data from animals subjected to oxygenation stress. Multispectral video-rate acquisition of threedimensional tomographic data enables simultaneous label-free assessment of multiple brain hemodynamic parameters, including blood oxygenation, total hemoglobin, cerebral blood volume, oxygenized and deoxygenized hemoglobin, in real time. The unprecedented results indicate that the proposed methodology may serve as a powerful complementary, and potentially superior, method for functional neuroimaging studies in rodents.

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“…The current fPAM system found shorter time-to-peak HbT and SO 2 changes in MI arterioles than in veins. It is possible that the oxygenated blood flows into the larger MI arterioles first, resulting in the shorter time-to-peak HbT and SO 2 changes in MI arterioles than in veins (Bouchard et al, 2009;Vovenko, 1999) and with studies showing a clear lateralization of unilateral forepaw electrical stimulation (Bouchard et al, 2009;Shih et al, 2009).…”

Section: Functional Changes Of Total Hemoglobin Concentration Cerebrmentioning

confidence: 99%

Transcranial Imaging of Functional Cerebral Hemodynamic Changes in Single Blood Vessels using in vivo Photoacoustic Microscopy

Liao

Lin

Shih

et al. 2012

J Cereb Blood Flow Metab

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Optical imaging of changes in total hemoglobin concentration (HbT), cerebral blood volume (CBV), and hemoglobin oxygen saturation (SO 2 ) provides a means to investigate brain hemodynamic regulation. However, high-resolution transcranial imaging remains challenging. In this study, we applied a novel functional photoacoustic microscopy technique to probe the responses of single cortical vessels to left forepaw electrical stimulation in mice with intact skulls. Functional changes in HbT, CBV, and SO 2 in the superior sagittal sinus and different-sized arterioles from the anterior cerebral artery system were bilaterally imaged with unambiguous 36¾65-lm 2 spatial resolution. In addition, an early decrease of SO 2 in single blood vessels during activation (i.e., 'the initial dip') was observed. Our results indicate that the initial dip occurred specifically in small arterioles of activated regions but not in large veins. This technique complements other existing imaging approaches for the investigation of the hemodynamic responses in single cerebral blood vessels.

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Ultra-fast multispectral optical imaging of cortical oxygenation, blood flow, and intracellular calcium dynamics

Cited by 201 publications

References 32 publications

Resting-state hemodynamics are spatiotemporally coupled to synchronized and symmetric neural activity in excitatory neurons

Resting-state hemodynamics are spatiotemporally coupled to synchronized and symmetric neural activity in excitatory neurons

Noninvasive Real-Time Visualization of Multiple Cerebral Hemodynamic Parameters in Whole Mouse Brains Using Five-Dimensional Optoacoustic Tomography

Transcranial Imaging of Functional Cerebral Hemodynamic Changes in Single Blood Vessels using in vivo Photoacoustic Microscopy

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