Achieving real-time photoacoustic (PA) tomography typically requires massive ultrasound transducer arrays and data
acquisition (DAQ) electronics to receive PA waves simultaneously. In this paper, we report the first demonstration of a
photoacoustic tomography (PAT) system using optical fiber-based parallel acoustic delay lines (PADLs). By employing
PADLs to introduce specific time delays, the PA signals (on the order of a few micro seconds) can be forced to arrive at
the ultrasonic transducers at different times. As a result, time-delayed PA signals in multiple channels can be ultimately
received and processed in a serial manner with a single-element transducer, followed by single‐channel DAQ electronics. Our results show that an optically absorbing target in an optically scattering medium can be photoacoustically imaged using the newly developed PADL-based PAT system. Potentially, this approach could be adopted to significantly reduce the complexity and cost of ultrasonic array receiver systems.
Achieving real-time photoacoustic (PA) tomography typically requires multi-element ultrasound transducer arrays and their associated multiple data acquisition (DAQ) electronics to receive PA waves simultaneously. We report the first demonstration of a photoacoustic tomography (PAT) system using optical fiber-based parallel acoustic delay lines (PADLs). By employing PADLs to introduce specific time delays, the PA signals (on the order of a few micro seconds) can be forced to arrive at the ultrasonic transducers at different times. As a result, time-delayed PA signals in multiple channels can be ultimately received and processed in a serial manner with a single-element transducer, followed by single-channel DAQ electronics. Our results show that an optically absorbing target in an optically scattering medium can be photoacoustically imaged using the newly developed PADL-based PAT system. Potentially, this approach could be adopted to significantly reduce the complexity and cost of ultrasonic array receiver systems.
With the increasing use of small animals for human disease studies, small-animal whole-body molecular imaging plays an important role in biomedical research. Currently, none of the existing imaging modalities can provide both anatomical and glucose molecular information, leading to higher costs of building dual-modality systems. Even with image co-registration, the spatial resolution of the molecular imaging modality is not improved. Utilizing a ring-shaped confocal photoacoustic computed tomography system, we demonstrate, for the first time, that both anatomy and glucose uptake can be imaged in a single modality. Anatomy was imaged with the endogenous hemoglobin contrast, and glucose metabolism was imaged with a near-infrared dye-labeled 2-deoxyglucose.
A challenge in photoacoustic tomography (PAT) brain imaging is to compensate for aberrations in the measured photoacoustic data due to their propagation through the skull. By use of information regarding the skull morphology and composition obtained from adjunct x-ray computed tomography image data, we developed a subject-specific imaging model that accounts for such aberrations. A time-reversal-based reconstruction algorithm was employed with this model for image reconstruction. The image reconstruction methodology was evaluated in experimental studies involving phantoms and monkey heads. The results establish that our reconstruction methodology can effectively compensate for skull-induced acoustic aberrations and improve image fidelity in transcranial PAT.
Photoacoustic (PA) microscopy (PAM) can image optical absorption contrast with ultrasonic spatial resolution in the optical diffusive regime. Conventionally, accurate quantification in PAM requires knowledge of the optical fluence attenuation, acoustic pressure attenuation, and detection bandwidth. We circumvent this requirement by quantifying the optical absorption coefficients from the acoustic spectra of PA signals acquired at multiple optical wavelengths. With the acoustic spectral method, the absorption coefficients of an oxygenated bovine blood phantom at 560, 565, 570, and 575 nm were quantified with errors of <3 % . We also quantified the total hemoglobin concentration and hemoglobin oxygen saturation in a live mouse. Compared with the conventional amplitude method, the acoustic spectral method provides greater quantification accuracy in the optical diffusive regime. The limitations of the acoustic spectral method was also discussed.
KEYWORDS: 3D image processing, Imaging systems, Ultrasonography, Data acquisition, In vivo imaging, 3D acquisition, Photoacoustic spectroscopy, Lymphatic system, Photoacoustic imaging, 3D modeling
We present an integrated photoacoustic and ultrasonic three-dimensional (3-D) volumetric imaging system based on a two-dimensional (2-D) matrix array ultrasound probe. A wavelength-tunable dye laser pumped by a Q-switched Nd:YAG laser serves as the light source and a modified commercial ultrasound imaging system (iU22, Philips Healthcare) with a 2-D array transducer (X7-2, Philips Healthcare) detects both the pulse-echo ultrasound and photoacoustic signals. A multichannel data acquisition system acquires the RF channel data. The imaging system enables rendering of co-registered 3-D ultrasound and photoacoustic images without mechanical scanning. The resolution along the azimuth, elevation, and axial direction are measured to be 0.69, 0.90 and 0.84 mm for photoacoustic imaging. In vivo 3-D photoacoustic mapping of the sentinel lymph node was demonstrated in a rat model using methylene blue dye. These results highlight the clinical potential of 3-D PA imaging for identification of sentinel lymph nodes for cancer staging in humans.
We report a novel small-animal whole-body imaging system called ring-shaped confocal photoacoustic computed tomography (RC-PACT). RC-PACT is based on a confocal design of free-space ring-shaped light illumination and 512-element full-ring ultrasonic array signal detection. The free-space light illumination maximizes the light delivery efficiency, and the full-ring signal detection ensures a full two-dimensional view aperture for accurate image reconstruction. Using cylindrically focused array elements, RC-PACT can image a thin cross section with 0.10 to 0.25 mm in-plane resolutions and 1.6 s/frame acquisition time. By translating the mouse along the elevational direction, RC-PACT provides a series of cross-sectional images of the brain, liver, kidneys, and bladder.
Speckles have been considered ubiquitous in all scattering-based coherent imaging technologies. However, as an optical-absorption-based coherent imaging technology, photoacoustic (PA) tomography (PAT) suppresses speckles by building up prominent boundary signals. We theoretically study the dependence of PAT speckles on the boundary roughness, which is quantified by the root-mean-squared value and the correlation length of the boundary height. Both the speckle visibility and the correlation coefficient between the reconstructed and actual boundaries are quantified. If the root-mean-squared height fluctuation is much greater than, and the height correlation length is much smaller than the imaging resolution, the reconstructed boundaries become fully developed speckles. In other words, speckle formation requires large uncorrelated height fluctuations within the resolution cell. The first- and second-order statistics of PAT speckles are also studied experimentally. While the amplitude of the speckles follows a Gaussian distribution, the autocorrelation of the speckle patterns tracks that of the system point spread function.
Photoacoustic (PA) tomography (PAT) can image optical absorption contrast with ultrasonic spatial resolution in the
optical diffusive regime. Multi-wavelength PAT can noninvasively monitor hemoglobin oxygen saturation (sO2) with
high sensitivity and fine spatial resolution. However, accurate quantification in PAT requires knowledge of the optical
fluence distribution, acoustic wave attenuation, and detection system bandwidth. We propose a method to circumvent
this requirement using acoustic spectra of PA signals acquired at two optical wavelengths. With the acoustic spectral
method, the absorption coefficients of an oxygenated bovine blood phantom at 560 and 575 nm were quantified with
errors of ><5%.
A photoacoustic tomography (PAT) system using a virtual point ultrasonic transducer was developed for transcranial
imaging of monkey brains. The virtual point transducer provided a 10 times greater field-of-view (FOV) than finiteaperture
unfocused transducers, which enables large primate imaging. The cerebral cortex of a monkey brain was
accurately mapped transcranially, through up to two skulls ranging from 4 to 8 mm in thickness. The mass density and
speed of sound distributions of the skull were estimated from adjunct X-ray CT image data and utilized with a timereversal
algorithm to mitigate artifacts in the reconstructed image due to acoustic aberration. The oxygenation saturation
(sO2) in blood phantoms through a monkey skull was also imaged and quantified, with results consistent with
measurements by a gas analyzer. The oxygenation saturation (sO2) in blood phantoms through a monkey skull was also
imaged and quantified, with results consistent with measurements by a gas analyzer. Our experimental results
demonstrate that PAT can overcome the optical and ultrasound attenuation of a relatively thick skull, and the imaging
aberration caused by skull can be corrected to a great extent.
Photoacoustic tomography (PAT) suppresses speckles by prominent boundary buildups. We theoretically study the
dependence of PAT speckles on the boundary roughness, which is quantified by the root-mean-squared (RMS) value and
the correlation length of the height. The speckle visibility and the correlation coefficient between the reconstructed and
actual boundaries are quantified as a function of the boundary roughness. The statistics of PAT speckles is studied
experimentally.
KEYWORDS: 3D image reconstruction, Transducers, 3D image processing, Reconstruction algorithms, Photoacoustic tomography, 3D modeling, Ultrasonics, Imaging systems, 3D acquisition, Signal to noise ratio
A full ring ultrasonic array-based photoacoustic tomography system was recently developed for small animal brain imaging. The 512-element array is cylindrically focused in the elevational direction, and can acquire a two-dimensional (2D) image in 1.6 s. In this letter, we demonstrate the three-dimensional (3D) imaging capability of this system. A novel 3D reconstruction algorithm was developed based on the focal-line concept. Compared to 3D images acquired simply by stacking a series of 2D images, the 3D focal-line reconstruction method renders images with much less artifacts, and improves the elevational resolution by 30% and the signal-to-noise ratio by two times. The effectiveness of the proposed algorithm was first validated by numerical simulations and then demonstrated with a hair phantom experiment and an ex vivo mouse embryo experiment.
A photoacoustic tomography system (PAT) using virtual point ultrasonic transducers was developed and applied to image a monkey brain. The custom-built transducers provide a 10-fold greater field-of-view (FOV) than finite-aperture unfocused transducers as well as an improved signal-to-noise ratio (SNR) and reduced artifacts rather than negative-lens transducers. Their tangential resolution, radial resolution, and (SNR) improvements were quantified using tissue phantoms. Our PAT system can achieve high uniformity in both resolution (<1 mm) and SNR (>8) within a large FOV of 6 cm in diameter, even when the imaging objects are enclosed by a monkey skull. The cerebral cortex of a monkey brain was accurately mapped transcranially, through a skull ranging from 2 to 4 mm in thickness. This study demonstrates that PAT can overcome the optical and ultrasound attenuation of a relatively thick skull and can potentially be applied to human neonatal brain imaging.
To image beyond the quasi-ballistic photon regime, photoacoustic tomography systems must rely on diffuse photons;
however, there still exists an optimal illumination pattern that results in the largest number of photons reaching a target
at a given depth. Many photoacoustic imaging systems incorporate weak optical focusing through oblique or dark-field
illumination, but these systems are not often optimized for deep light delivery. Multiple parameters and constraints,
particularly for in vivo imaging, need to be considered to determine the optimal illumination scheme for a given system:
beam diameter, incident angle, pulse repetition rate, laser fluence, and target depth. Monte Carlo simulations of varied
beam geometries and incident angles show the best optical illumination schemes for different imaging depths. Further an
analytic model based on the diffusion theory provides a rapid method of determining the optimal beam size and incident
angle for a given target depth and agrees well with the simulations. The results reveal the most efficient optical focal
position to maximize the number of photons delivered to a target depth, therein maximizing the PA signal. The
principles and results discussed here are not limited to the system investigated, but can be applied to other system
configurations to improve the photoacoustic signal strength.
We developed a tri-modal system combining photoacoustic (PA) tomography, thermoacoustic (TA) tomography, and
ultrasound (US) imaging. Acquired images of an excised dog prostate were compared to histology results. All three
modalities can image distinct features. Features like the urethra were shown in both TA and US images, but TA gave a
higher contrast-to-noise ratio. Fibrous tissue was more clearly imaged by TA, while the duct structure was better shown
in PA images. These experimental results demonstrate the potential advantages of our tri-modal imaging system.
KEYWORDS: Photoacoustic spectroscopy, 3D image processing, Ultrasonography, Imaging systems, Photoacoustic imaging, Transducers, Lymphatic system, 3D acquisition, In vivo imaging, Data acquisition
Photoacoustic tomography provides both structural and functional imaging in vivo based on optical absorption contrast.
A novel imaging system that incorporates a two-dimensional matrix ultrasound probe for combined photoacoustic and
ultrasonic three-dimensional (3D) volumetric imaging is presented. The system consists of a tunable dye laser pumped
by a Nd:YAG laser, a commercial ultrasound imaging system (Philips iU22) with a two-dimensional matrix transducer
(Philips X7-2, 2500 elements, 2-7 MHz), and a multichannel data acquisition system which allows us to acquire RF
channel data. Compared with alternative 3D techniques, this system is attractive because it can generate co-registered 3D
photoacoustic and ultrasound images without mechanical scanning. Moreover, the lateral resolution along the azimuth
and elevational directions are measured to be 0.77 ± 0.06 mm and 0.96 ± 0.06 mm, respectively, based on reconstructed
photoacoustic images of phantoms containing individual human hairs. Finally, in vivo 3D photoacoustic sentinel lymph
node mapping using methylene blue dye in a rat model is demonstrated.
In this report, we present a novel 3D photoacoustic computed tomography (PACT) system for small-animal whole-body
imaging. The PACT system, based on a 512-element full-ring transducer array, received photoacoustic signals primarily
from a 2-mm-thick slice. The light was generated by a pulse laser, and can either illuminate from the top or be reshaped
to illuminate the sample from the side, using a conical lens and an optical condenser. The PACT system was capable of
acquiring an in-plane image in 1.6 s; by scanning the sample in the elevational direction, a 3D tomographic image could
be constructed. We tested the system by imaging a cylindrical phantom made of human hairs immersed in a scattering
medium. The reconstructed image achieved an in-plane resolution of 0.1 mm and an elevational resolution of 1 mm.
After deconvolution in the elevational direction, the 3D image was found to match well with the phantom. The system
was also used to image a baby mouse in situ; the spinal cord and ribs can be seen easily in the reconstructed image. Our
results demonstrate that the PACT system has the potential to be used for fast small-animal whole-body tomographic
imaging.
Optical absorption is closely associated with many physiologically important parameters, such as the
concentration and oxygen saturation of hemoglobin, and it can be used to quantify the concentrations of non-fluorescent
molecules. We introduce a method to quantify the absolute optical absorption based upon the acoustic spectra of
photoacoustic (PA) signals. This method is self-calibrating and thus insensitive to variations in optical fluence. Factors
such as the detection system bandwidth and acoustic attenuation can affect the quantification but can be canceled by
measuring the acoustic spectra at two optical wavelengths. This method has been implemented on various PA systems,
including optical-resolution PA microscopy, acoustic-resolution PA microscopy, and reconstruction based PA array
systems. We quantified the optical absorption coefficients of phantom samples at various wavelengths. We also
quantified the oxygen saturation of hemoglobin in live mice.
KEYWORDS: Acquisition tracking and pointing, Photoacoustic tomography, In vivo imaging, Data acquisition, Compressed sensing, Sensors, Reconstruction algorithms, Ultrasonics, Tomography, Wavelets
The data acquisition speed in photoacoustic computed tomography (PACT) is limited by the laser repetition rate and the number of parallel ultrasound detecting channels. Reconstructing an image with fewer measurements can effectively accelerate the data acquisition and reduce the system cost. We adapt compressed sensing (CS) for the reconstruction in PACT. CS-based PACT is implemented as a nonlinear conjugate gradient descent algorithm and tested with both phantom and in vivo experiments.
Sentinel lymph node biopsy (SLNB) has become the standard method for axillary staging in breast cancer patients,
relying on invasive identification of sentinel lymph nodes (SLNs) following injection of blue dye and radioactive tracers.
While SLNB achieves a low false negative rate (5-10%), it is an invasive procedure requiring ionizing radiation. As an
alternative to SLNB, ultrasound-guided fine needle aspiration biopsy has been tested clinically. However, ultrasound
alone is unable to accurately identify which lymph nodes are sentinel. Therefore, a non-ionizing and noninvasive
detection method for accurate SLN mapping is needed.
In this study, we successfully imaged methylene blue dye accumulation in vivo in rat axillary lymph nodes using a
Phillips iU22 ultrasound imaging system adapted for photoacoustic imaging with an Nd:YAG pumped, tunable dye
laser. Photoacoustic images of rat SLNs clearly identify methylene blue dye accumulation within minutes following
intradermal dye injection and co-registered photoacoustic/ultrasound images illustrate lymph node position relative to
surrounding anatomy. To investigate clinical translation, the imaging depth was extended up to 2.5 cm by adding
chicken breast tissue on top of the rat skin surface. These results raise confidence that photoacoustic imaging can be used
clinically for accurate, noninvasive SLN mapping.
The data acquisition speed in photoacoustic computed tomography (PACT) is limited by the laser repetition
rate and the number of parallel ultrasound detecting channels. Reconstructing PACT image with a less number of
measurements can effectively accelerate the data acquisition and reduce the system cost. Recently emerged
Compressed Sensing (CS) theory enables us to reconstruct a compressible image with a small number of projections.
This paper adopts the CS theory for reconstruction in PACT. The idea is implemented as a non-linear conjugate
gradient descent algorithm and tested with phantom and in vivo experiments.
Photoacoustic imaging for biomedical applications has seen significant growth during the past few years. Despite its
coherent nature, it possesses a unique advantage to produce images devoid of speckle artifacts. The reason responsible
for this salient feature has not been addressed so far. We found this is a direct result of its extraordinary absorption
contrast. Our discovery is explained using simulations based on a practical photoacoustic imaging system.
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