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In Vivo Photoacoustic Imaging: Brain Research Application

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In Vivo Photoacoustic Imaging: Brain Research Application. Vassiliy Tsytsarev, E-mail: [email protected] University of Maryland School of Medicine Most of the presented data have been obtained in: Optical Imaging Laboratory Department of Biomedical Engineering - PowerPoint PPT Presentation

Text of In Vivo Photoacoustic Imaging: Brain Research Application

TitleMost of the presented data have been obtained in:
Optical Imaging Laboratory
In this study, optical-resolution photoacoustic microscopy was used to monitor the somatosensory cortex for vascular responses to direct electrical stimulations through a cranial window. -- *
Photoacoustic imaging - a hybrid biomedical imaging modality, is developed based on the photoacoustic effect
Photoacoustic effect – discovered by Alexander Bell in 1880; he showed that thin discs emitted sound when exposed to a beam of sunlight that was rapidly interrupted with a rotating slotted disk. -- *
PA Imaging: three types of scanning
PACT image of the cortical vasculature in a living adult intact rat
Dark-field AR-PAM -- *
microscopy (OR-PAM)
Hu et al, 2007; (Wang et al., 2003; Stein et al., 2008)
Wavelength-tunable laser system
OR-PAM system employs optical focusing to achieve micrometer-level lateral resolution.
A dye laser pumped by an laser is used as the irradiation source. Laser pulses from the dye laser are spatially filtered by a 25 um diameter pinhole. The optical objective lens and 75 MHz ultrasonic transducer are coaxially and confocally configured.
A combination of time-resolved detection of the photoacoustic waves with a two-dimensional (2D) raster scanning along the x–y plane generates a volumetric
image, or maximum amplitude projection (MAP) images. -- *
(Hu and Wang, 2009)
In vivo PACT image of the cerebral vascular response to right-side whisker stimulation (intact rat)
The hemodynamic response due to whisker stimulation is shown in blue and red and is superimposed on the cortical vascular image shown in gray. -- *
Hu, Maslov, Tsytsarev and Wang, 2009 -- *
Real-time monitoring of photoacoustic signals at specific excitation wavelengths reveals vascular dynamics, such as changes in blood volume and oxygen saturation, in response to electrical or physiological stimulation or epileptic seizures
Although changes in the optical properties of brain tissues, mainly caused by neuron-activity-induced hemodynamic disturbance, were observed within few last decades, it has only been in the last decade that open brain optical imaging techniques have been introduced to illuminate how neurovascular coupling works. -- *
Electrical stimulation may cause neurons to release various neurotransmitters (Glutamate [Glu], GABA, ATP and NO). These reactions drive the vessel to either vasoconstriction or vasodilatation
Blood vessel
Within last couple of decades several studies have hinted that the link between activity and vasomotor responses is highly complex. We still do not have complete understanding of the cellular mechanisms responsible for coupling changes in neuronal activation to changes in cerebra blood flow. Nevertheless,
In the brief words, various cellular processes of neurons, require energy in the form of adenosine triphosphate (ATP), synthesized by oxidative glucose metabolism, which requires oxygen. So, cerebral metabolism depends on a constant supply of both glucose and oxygen. A continuous supply of these two energy substrates is maintained by CBF, which delivers glucose and oxygen to neural tissue. Accordingly, during neural activity, increases in oxygen and glucose consumption are followed by an increase in CBF. Local metabolites such as K+ and protons diffuse from active synapses to the membrane of smooth muscle cells.
Nitric oxide (NO), acting as a retrograde messenger, locally produced by specialized neurons. Glutamate releasing from active excitatory synapses binds to glutamate receptors on the endfeet of astrocytes. This leads to the formation of vasodilatation.
Astrocytes also participate in the re-uptake of K+ (a potent vasodilator) from the synapses.
Smooth muscle cells in the arteriolar wall might also be directly innervated by axon collaterals that control vascular tone. -- *
Photograph of the microelectrode
The oxygen saturation (SO2) mapping is shown as a superposition in color scale. A line-scan monitoring of the vascular response was performed along the dashed yellow line.
400 μm
Optical absorption
Photoacoustic imaging of the mouse microvasculature through the open skull. Maximum amplitude projection (MAP) image acquired at 570 nm is shown in gray scale. The vessel-by-vessel SO2 mapping of a smaller region calculated from dual-wavelength measurements is shown as a superposition in color scale. A line-scan monitoring of the vascular response was performed along the dashed yellow line. -- *
Axial -- *
50 s
130 s
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150 s
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10 s
50 s
126 s
217 s
150 s
280 s
25 µm
50 µm
Optical absorption
Vasoconstriction induced by stimulations at 100 µA. Left, MAP of a line-scan image of an arteriole near the tip of the microelectrode. A line across the vessel diameter was scanned at the rate of 1 Hz. Right, cross-sectional images indicated by the green lines at different time points. The dotted white lines indicate the initial size of the vessel in the horizontal dimension. Red arrows indicate the starting times of the stimulations. (b) Vasodilatation of the same vessel induced by stimulations at 150 µA. -- *
Time courses of the vessel cross-sectional area under various stimulation intensities
Vasoconstriction and vasodilatation are observed, and the response duration is positively correlated with stimulation intensity
Stimulation 1
Stimulation 2
Each stimulation consisted of a train of four 0.3 ms pulses at 300 Hz
150 μA
300 μA
350 μA
110 μA
100 μA
Time characteristics of the stimulation sequence. Two electrical stimulations were executed during one trial, starting at time points 100 s and 200 s, respectively. Each stimulation consisted of a train of four 0.3 ms pulses at 300 Hz. (b) Time courses of the electrical-stimulation-induced vessel cross-sectional area under various stimulation intensities, normalized by the baseline. Two types of responses – vasoconstriction and vasodilatation – were observed. The response duration is positively correlated with stimulation intensity. The two stimulations are indicated by the two vertical dashed lines. -- *
400 μm
Transcranial brain image
(c) -- * -- *
OR-PAM clearly and reliably imaged the vascular response to electrical stimulation at the capillary level with a temporal resolution of one second.
OR-PAM is a promising tool for in vivo studies of neurovascular coupling under a variety of experimental conditions invasively as well as transcranially
Possibly, direct electrical stimulation on smooth muscle cells may cause vessel constriction. Moreover, direct electrical stimulation on astrocytes may result in intracellular calcium waves along the astrocytic syncytium, which may signal the release of various neuromodulators. These neuromodulators can direct the blood vessel to regulate the metabolic supply by increasing or decreasing the local vessel dimension.
Also, electrical stimulation of brain tissue temporally increases extracellular potassium ion (K+) concentration, which has the potential to cause neural hyperactivity. Increasing neural activity requires more blood flow, which may result in vasodilatation. -- *
Vessel 1
Vessel 2
Clinical application: questionable
Perspective: biomarcer hybridozation