The metabolic rate of oxygen consumption is an important metric of tissue oxygen metabolism and is especially critical in the brain, yet few methods are available for measuring it. We use a custom combined photoacoustic-microultrasound system and demonstrate cerebral oxygen consumption estimation in vivo. In particular, the cerebral metabolic rate of oxygen consumption was estimated in a murine model during variation of inhaled oxygen from hypoxia to hyperoxia. The hypothesis of brain autoregulation was confirmed with our method even though oxygen saturation and flow in vessels changed.
In this paper we demonstrate a multi-wavelength optical resolution photoacoustic microscopy system for
both phantom and in vivo imaging. Using a 1ns pulse width, 40-kHz repetition-rate ytterbium-doped fiber laser and
a 3m single-mode polarization maintaining fiber, we produced numerous Raman-shifted wavelength peaks at with
pulse energies between 100 and 400nJ per peak. Peak wavelengths were selected by using 10-nm linewidth bandpass
filters. The capabilities of this system is shown by creating C-scan photoacoustic images of carbon fiber
networks, 200μm dye-filled tubes, and Swiss Webster mouse ears at several wavelengths. Functional imaging
potential was confirmed by assessing tubes filled with varying concentrations of two different dyes.
The metabolic rate of oxygen consumption, an important indicator of tissue metabolism, can be expressed as the change of net blood oxygen flux into and out of a tissue region per 100 g of tissue. In this work, we propose a photoacoustic and Doppler ultrasound method for imaging local blood oxygen flux of a single vessel. An imaging system for combined photoacoustic and high-frequency ultrasound microscopy is presented. This system uses a swept-scan 25-MHz ultrasound transducer with confocal dark-field laser illumination optics. A pulse-sequencer enables ultrasonic and laser pulses to be interlaced so that photoacoustic and Doppler ultrasound images are co-registered. Since the mean flow speed can be measured by color Doppler ultrasound, the vessel cross-sectional area can be measured by power Doppler or structural photoacoustic imaging, and multi-wavelength photoacoustic methods can be used to estimate oxygen saturation (sO2) and total concentration of haemoglobin (CHb), all of the parameters necessary for oxygen flux estimation can be provided. The accuracy of the flow speed and sO2 estimation has been investigated. In vitro sheep blood phantom experiments have been performed at different sO2 levels and mean flow speeds. Blood oxygen flux has been estimated, and the uncertainty of the measurement has been quantified.
The long-term goal of our research is to develop photoacoustic and Doppler ultrasound imaging methods for noninvasive
estimation of the oxygen consumption rate (MRO2) in vivo. Previously, we have demonstrated a combined
photoacoustic and high-frequency Doppler ultrasound system and shown the feasibility of flow velocity and oxygen
saturation (sO2) estimation using double-ink flow phantoms. In this work, the results of in vitro sheep blood experiments
are presented. Blood oxygen flux has been estimated at different sO2 levels and mean flow speeds, and the uncertainty of
the measurement has been quantified. In vivo experiments have been performed on Swiss Webster mice to provide coregistered
photoacoustic and Doppler flow images with imaging depths of ~2mm. Doppler bandwidth broadening
technique has been used to obtain transverse flow velocity. The diameter of the blood vessel is ~500μm and the mean
flow speed is 15cm/s. We are working towards sO2 estimation in vivo and 3D oxygen consumption imaging of tumors at
depths beyond OR-PAM.
Recently, we have developed a combined photoacoustic and high-frequency Doppler ultrasound system with a single
element transducer to estimate the metabolic rate of oxygen consumption in small animal models. However, the long
scanning time due to mechanical motion may be a limitation of our swept-scan system. In this work, the single element
transducer was replaced by a clinical array transducer which may provide more accurate flow velocity estimations,
higher frame rates, improved penetration depth, and improved depth-of-field due to dynamic focusing capabilities. We
used an array system from Verasonics Inc. which enables flexible pulse-sequence programming and parallel channel data
acquisition, along with a pulsed laser and optical parametric oscillator. For flow estimation, we implemented a flash-
Doppler sequence which transmits ensembles of plane-wave excitations. Echo signals are beamformed and subjected to
wall-filtering and Kasai flow estimation algorithms. High frame rates over a wide region can be achieved. Combined
interlaced photoacoustic and Doppler imaging on flow phantoms has been performed on this system. We demonstrate the
ability to image animal blood to depths of 1.5-cm with high signal-to-noise with both modalities. The light penetration is
2-cm. We discuss the performance of Doppler flow estimation and photoacoustic oxygen saturation estimation and their
role in future work of estimating oxygen consumption.
The metabolic rate of oxygen consumption (MRO2) quantifies tissue metabolism, which is important for diagnosis of
many diseases. For a single vessel model, the MRO2 can be estimated in terms of the mean flow velocity, vessel crosssectional
area, total concentration of hemoglobin (CHB), and the difference between the oxygen saturation (sO2) of blood
flowing into and out of the tissue region. In this work, we would like to show the feasibility to estimate MRO2 with our
combined photoacoustic and high-frequency ultrasound imaging system. This system uses a swept-scan 25-MHz
ultrasound transducer with confocal dark-field laser illumination optics. A pulse-sequencer enables ultrasonic and laser
pulses to be interlaced so that photoacoustic and Doppler ultrasound images are co-registered. Since the mean flow
velocity can be measured by color Doppler ultrasound, the vessel cross-sectional area can be measured by power
Doppler or photoacoustic imaging, and multi-wavelength photoacoustic methods can be used to estimate sO2 and CHB,
all of these parameters necessary for MRO2 estimation can be provided by our system. Experiments have been performed
on flow phantoms to generate co-registered color Doppler and photoacoustic images. To verify the sO2 estimation, two
ink samples (red and blue) were mixed in various concentration ratios to mimic different levels of sO2, and the result
shows a good match between the calculated concentration ratios and actual values.
Both photoacoustic imaging and power Doppler ultrasound are capable of producing images of the vasculature of living subjects, however, the contrast mechanisms of the two modalities are very different. We present a quantitative and objective comparison of the two methods using phantom data, highlighting relative merits and shortcomings. An imaging system for combined photoacoustic and high-frequency power Doppler ultrasound microscopy is presented. This system uses a swept-scan 25-MHz ultrasound transducer with confocal dark-field laser illumination optics. A pulse-sequencer enables ultrasonic and laser pulses to be interlaced so that photoacoustic and power Doppler ultrasound images can be coregistered. Experiments are performed on flow phantoms with various combinations of vessel size, flow velocity, and optical wavelength. For the task of blood volume detection, power Doppler is seen to be advantageous for large vessels and high flow speeds. For small vessels with low flow speeds, photoacoustic imaging is seen to be more effective than power Doppler at the detection of blood as quantified by receiver operating characteristic analysis. A combination of the two modes could provide improved estimates of fractional blood volume in comparison with either mode used alone.
Photoacoustic imaging has emerged as a promising technique for visualizing optically absorbing structures with
ultrasonic spatial resolution. Since it relies on optical absorption of tissues, photoacoustic imaging is particularly
sensitive to vascular structures even at the micro-scale. Power Doppler ultrasound can be used to detect moving blood
irrespective of Doppler angles. However, the sensitivity may be inadequate to detect very small vessels with slow flow
velocities. In this work, we merge these two synergistic modalities and compare power Doppler ultrasound images with
high-contrast photoacoustic images. We would like to understand the advantages and disadvantages of each technique
for assessing microvascular density, an important indicator of disease status. A combined photoacoustic and highfrequency
ultrasound system has been developed. The system uses a swept-scan 25 MHz ultrasound transducer with
confocal dark-field laser illumination optics. A pulse-sequencer enables ultrasonic and laser pulses to be interlaced so
that photoacoustic and Doppler ultrasound images are co-registered. Experiments have been performed on flow
phantoms to test the capability of our system and signal processing methods. Work in progress includes in vivo color
flow mapping. This combined system will be used to perform blood oxygen saturation and flow estimations, which will
provide us with the parameters to estimate the local rate of metabolic oxygen consumption, an important indicator for
many diseases.
Recently a realtime photoacoustic microscopy system has been demonstrated. Unfortunately, however, displayed B-scan
images were sometimes difficult to interpret as there was little structural context. In this work, we provide structural
context for photoacoustic microscopy images by adding ultrasound biomicroscopy as a complementary and synergistic
modality. Our system uses a voice-coil translation stage capable of 1" lateral translation, and can operate in excess of 15
Hz for 1-cm translations, providing up to 30 ultrasound frames per second. The frame-rate of the photoacoustic
acquisitions is limited by the 20-Hz pulse-repetition rate of the laser, but can be increased with a faster-repetition-rate
laser. Data from the system is streamed in real time from a 2GS/s PCI data acquisition card to the host PC at rates as
high as 200 MB/s. The system should prove useful for various in vivo studies, including combined ultrasound Doppler
and photoacoustic imaging.
Photoacoustic microscopy and tomography are hybrid biomedical imaging technologies that provide optical absorption
contrast with ultrasonic spatial resolution. To date, photoacoustic methods have provided little information about the
optical scattering properties of tissues. Yet scattering is a key tissue parameter with diagnostic potential for a number of
diseases. Moreover, quantitative knowledge of the optical scattering coefficient may prove valuable for improving
quantitative estimates of blood oxygen saturation and other functional parameters. We present a new photoacoustic
method that shows promise for sensing the local reduced scattering coefficient of tissues.
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