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In Vivo Photoacoustic Imaging:Brain Research Application

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

Washington University, St. Louis


What is Photoacoustic?What is Photoacoustic?

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.


How it works?How it works?

Laser

Ultrasound

Ultrasound trasducer


PA Imaging: three types of scanningPA Imaging: three types of scanning

PACT image of the cortical vasculature in a living adult intact rat

Dark-field AR-PAM OR-PAM (Open Brain)

(Wang et al., 2003; Stein et al., 2008)


Wavelength-tunable laser system

Condenser lens

Pinhole

Microscope objectiveCorrection lens

Ultrasonic transducer

Right-angle prismSilicone oil layer

Water tank

ScannerPolyethylene membrane

Acoustic lens

Scheme of optical-resolution photoacoustic microscopy (OR-PAM)

Scheme of optical-resolution photoacoustic microscopy (OR-PAM)

Hu et al, 2007; (Wang et al., 2003; Stein et al., 2008)


Intact Rat PA ImagingIntact Rat PA Imaging


Open Brain PA ImagingOpen Brain PA Imaging


Functional Brain Imaging: Transcranial ApplicationFunctional Brain Imaging: Transcranial Application

(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.


PA Microscopy: 2-Wavelengths Functional ImagingPA Microscopy: 2-Wavelengths Functional Imaging

Hu, Maslov, Tsytsarev and Wang, 2009


Photoacoustic imaging of the vascular responsePhotoacoustic imaging of the vascular response

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


Neurovascular coupling: response to electrical stimulation

Neurovascular coupling: response to electrical stimulation

AstrocyteNeuron

Electrode

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

GABA

Glu

Glu

K+, NO

ATP

Blood vessel


Photograph of exposed mouse brain surface with introduced microelectrode

Photograph of exposed mouse brain surface with introduced microelectrode

Microelectrode

Cranial opening

5 mm


Photoacoustic imaging of the brain microvasculature

Photoacoustic imaging of the brain microvasculature

Photograph of the microelectrodeMin Max

1.0

SO

2

1mm

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 μmOptical absorption

0.6


Vascular response to electrical stimulationVascular response to electrical stimulation

Transverse

Axi

al

10 μm

Transverse

Axial

Stimulation


Vascular response to electrical stimulationVascular response to electrical stimulation


Vasoconstriction and vasodilatationVasoconstriction and vasodilatation

50 s

130 s

230 s

150 s

250 s

10 s

50 s

126 s

217 s

150 s

280 s

25 µm50 µm Optical absorptionMin Max

Electrical stimulations

150 µA100 µA


Time courses of the vessel cross-sectional area under various stimulation intensities

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 2Each stimulation consisted of a train of four 0.3 ms pulses at 300 Hz

150 μA300 μA

350 μA

110 μA

100 μA


Transcranial imaging of the single blood vesselTranscranial imaging of the single blood vessel

400 μm

Studiedvessel

Stimulation

0 10 20 time (s)

1.6

1.4

1.2

1.0

medial

rostral

Transcranial images of stimulation-induced vasodilatation

a) Transcranial brain imageb) Crossectional monitoringc) Time courses of the electrical-

stimulation-induced vessel size

(a) (b)

(c)


Epileptic Seizures: Single Vessel MonitoringEpileptic Seizures: Single Vessel Monitoring


SummarySummary

Optical-resolution photoacoustic microscopy (OR-PAM) imaged two types of vascular response to electrical stimulation:

Vasoconstriction Vasodilatation

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


Epileptic seizures accompanied by two vessels vasodilatation (PA Imaging)

Epileptic seizures accompanied by two vessels vasodilatation (PA Imaging)

Vessel 1

Vessel 2

EEG

10 s / 2 mV

25 μm


Conlusions and Perspecives:Conlusions and Perspecives:

- Current application: animal experiment- Clinical application: questionable

- Perspective: biomarcer hybridozation