We present our findings from a real-time laser optoacoustic imaging system (LOIS). The system utilizes a Q-switched Nd:YAG laser; a standard 128-channel ultrasonic linear array probe; custom electronics and custom software to collect, process, and display optoacoustic (OA) images at 10 Hz. We propose that this system be used during preoperative mapping of forearm vessels for hemodialysis treatment. To demonstrate the real-time imaging capabilities of the system, we show OA images of forearm vessels in a volunteer and compare our results to ultrasound images of the same region. Our OA images show blood vessels in high contrast. Manipulations with the probe enable us to locate and track arteries and veins of a forearm in real time. We also demonstrate the ability to combine a series of OA image slices into a volume for spatial representation of the vascular network. Finally, we use frame-by-frame analysis of the recorded OA video to measure dynamic changes of the crossection of the ulnar artery.
Optoacoustic (OA) tomography has demonstrated utility in identifying blood-rich malignancies in breast tissue. We describe the development and characterization of a laser OA imaging system for the prostate (LOIS-P). The system consists of a fiber-coupled Q-switched laser operating at 757 nm, a commercial 128-channel ultrasonic probe, a digital signal processor, and software that uses the filtered radial back-projection algorithm for image reconstruction. The system is used to reconstruct OA images of a blood-rich lesion induced in vivo in a canine prostate. OA images obtained in vivo are compared to images acquired using ultrasound, the current gold standard for guiding biopsy of the prostate. Although key structural features such as the urethra could be identified with both imaging techniques, a bloody lesion representing a highly vascularized tumor could only be clearly identified in OA images. The advantages and limitations of both forward and backward illumination modes are also evaluated by collecting OA images of phantoms simulating blood vessels within tissue. System resolution is estimated to be 0.2 mm in the radial direction of the acoustic array. The minimum detectable pressure signal is 1.83 Pa. Our results encourage further development toward a dual-modality OA/ultrasonic system for prostate imaging and image-guided biopsy.
In this work we modified light illumination of the laser optoacoustic (OA) imaging system to improve the 3D
visualization of human forearm vasculature. The computer modeling demonstrated that the new illumination design that
features laser beams converging on the surface of the skin in the imaging plane of the probe provides superior OA
images in comparison to the images generated by the illumination with parallel laser beams. We also developed the
procedure for vein/artery differentiation based on OA imaging with 690 nm and 1080 nm laser wavelengths. The
procedure includes statistical analysis of the intensities of OA images of the neighboring blood vessels. Analysis of the
OA images generated by computer simulation of a human forearm illuminated at 690 nm and 1080 nm resulted in
successful differentiation of veins and arteries. In vivo scanning of a human forearm provided high contrast 3D OA
image of a forearm skin and a superficial blood vessel. The blood vessel image contrast was further enhanced after it was
automatically traced using the developed software. The software also allowed evaluation of the effective blood vessel
diameter at each step of the scan. We propose that the developed 3D OA imaging system can be used during
preoperative mapping of forearm vessels that is essential for hemodialysis treatment.
We present results from a clinical case study on imaging breast cancer using a real-time interleaved two laser
optoacoustic imaging system co-registered with ultrasound. The present version of Laser Optoacoustic Ultrasonic
Imaging System (LOUIS) utilizes a commercial linear ultrasonic transducer array, which has been modified to include
two parallel rectangular optical bundles, to operate in both ultrasonic (US) and optoacoustic (OA) modes. In OA mode,
the images from two optical wavelengths (755 nm and 1064 nm) that provide opposite contrasts for optical absorption of
oxygenated vs deoxygenated blood can be displayed simultaneously at a maximum rate of 20 Hz. The real-time aspect of
the system permits probe manipulations that can assist in the detection of the lesion. The results show the ability of
LOUIS to co-register regions of high absorption seen in OA images with US images collected at the same location with
the dual modality probe. The dual wavelength results demonstrate that LOUIS can potentially provide breast cancer
diagnostics based on different intensities of OA images of the lesion obtained at 755 nm and 1064 nm. We also present
new data processing based on deconvolution of the LOUIS impulse response that helps recover original optoacoustic
pressure profiles. Finally, we demonstrate the image analysis tool that provides automatic detection of the tumor
boundary and quantitative metrics of the optoacoustic image quality. Using a blood vessel phantom submerged in a
tissue-like milky background solution we show that the image contrast is minimally affected by the phantom distance
from the LOUIS probe until about 60-65 mm. We suggest using the image contrast for quantitative assessment of an OA
image of a breast lesion, as a part of the breast cancer diagnostics procedure.
We develop a system for three-dimensional whole-body optoacoustic tomography of small animals for applications in preclinical research. The tomographic images are obtained while the objects of study (phantoms or mice) are rotated within a sphere outlined by a concave arc-shaped array of 64 piezocomposite transducers. Two pulsed lasers operating in the near-IR spectral range (755 and 1064 nm) with an average pulsed energy of about 100 mJ, a repetition rate of 10 Hz, and a pulse duration of 15 to 75 ns are used as optical illumination sources. During the scan, the mouse is illuminated orthogonally to the array with two wide beams of light from a bifurcated fiber bundle. The system is capable of generating images of individual organs and blood vessels through the entire body of a mouse with spatial resolution of ~0.5 mm.
We describe early stage experiments to test the feasibility of an ultrasound brain helmet to produce multiple
simultaneous real-time 3D scans of the cerebral vasculature from temporal and suboccipital acoustic windows of the
skull. The transducer hardware and software of the Volumetrics Medical Imaging real-time 3D scanner were modified to
support dual 2.5 MHz matrix arrays of 256 transmit elements and 128 receive elements which produce two simultaneous
64° pyramidal scans. The real-time display format consists of two coronal B-mode images merged into a 128° sector,
two simultaneous parasagittal images merged into a 128° × 64° C-mode plane, and a simultaneous 64° axial image.
Real-time 3D color Doppler images acquired in initial clinical studies after contrast injection demonstrate flow in several
representative blood vessels. An offline Doppler rendering of data from two transducers simultaneously scanning via the
temporal windows provides an early visualization of the flow in vessels on both sides of the brain. The long-term goal is
to produce real-time 3D ultrasound images of the cerebral vasculature from a portable unit capable of internet
transmission, thus enabling interactive 3D imaging, remote diagnosis and earlier therapeutic intervention. We are
motivated by the urgency for rapid diagnosis of stroke due to the short time window of effective therapeutic intervention.
KEYWORDS: Transducers, Acoustics, Sensors, Calibration, Wavefronts, Ultrasonography, Signal attenuation, Pulsed laser operation, Image restoration, Signal to noise ratio
Comprehensive characterization of optoacoustic transducers is achieved through the analysis of their frequency
response using a procedure of measuring angular dependence of the transducer sensitivity to the ultrawide-band
delta pulse. The testing was performed under standard repeatable operating conditions. Back-illumination of a
blackened, acoustically matched, planar surface with a short laser pulse creates an acoustic impulse which was used
as an ultrawide-band ultrasonic source. The bandwidth of such a source extends well over 10 MHz (6dB point at 16
MHz for illumination with a 16 ns pulse) and the low frequency
roll-off is around 300 kHz. Analysis of the angular
dependence of the frequency response yields invaluable directivity information about the detector under study,
which in turn permits accurate forward and inverse problem models.
We developed a 3D whole-body optoacoustic tomography system for applications in preclinical research on mice. The
system is capable of generating images with resolution better than 0.6 mm. Two pulsed lasers, an Alexandrite laser
operating at 755 nm and a Nd:YAG laser operating at 532 nm and 1064nm were used for light delivery. The
tomographic images were obtained while the objects of study (phantoms or mice) were rotated within a sphere outlined
by a concave arc-shaped array of 64 piezo-composite transducers. During the scan, the mouse was illuminated
orthogonally to the array with two wide beams of light from a bifurcated fiber bundle. Illumination at 532 nm showed
superficial vasculature, but limited penetration depth at this wavelength prevented the detection of deeper structures.
Illumination at 755 and 1064 nm showed organs and blood vessels, respectively. Filtering of the optoacoustic signals
using high frequency enhancing wavelets further emphasized the smaller blood vessels.
We describe two laser optoacoustic imaging systems for breast cancer detection based on arrays of acoustic detectors
operated manually in a way similar to standard ultrasonic breast imaging. The systems have the advantages of standard
light illumination (regardless of the interrogated part of the breast), the ability to visualize any part of the breast, and
convenience in operation. The first system could work in both ultrasonic and optoacoustic mode, and was developed
based on a linear ultrasonic breast imaging probe with two parallel rectangular optical bundles. We used it in a pilot
clinical study to provide for the first time demonstration that the boundaries of the tumors visualized on the optoacoustic
and ultrasonic images matched. Such correlation of coregistered images proves that the objects on both images
represented indeed the same tumor. In the optoacoustic mode we were also able to visualize blood vessels located in the
neighborhood of the tumor. The second system was proposed as a circular array of acoustic transducers with an axisymmetric
laser beam in the center. It was capable of 3D optoacoustic imaging with minimized optoacoustic artifacts
caused by the distribution of the absorbed optical energy within the breast tissue. The distribution of optical energy
absorbed in the bulk tissue of the breast was removed from the image by implementing the principal component analysis
on the measured signals. The computer models for optoacoustic imaging using these two handheld probes were
developed. The models included three steps: (1) Monte Carlo simulations of the light distribution within the breast
tissue, (2) generation of optoacoustic signals by convolving
N-shaped pressure signals from spherical voxels with the
shape of individual transducers, and (3) back-projecting processed optoacoustic signals onto spherical surfaces for image
reconstruction. Using the developed models we demonstrated the importance of the included spatial impulse response of
the optoacoustic imaging system.
A three-dimensional laser optoacoustic imaging system was developed, which combines the advantages of optical
spectroscopy and high resolution ultrasonic detection, to produce high contrast maps of optical absorbance in tissues.
This system was tested in a nude mouse model of breast cancer and produced tissue images of tumors and vasculature.
The imaging can utilize either optical properties of hemoglobin and oxyhemoglobin, which are the main endogenous
tissue chromophores in the red and near-infrared spectral ranges, or exogenous contrast agent based on gold nanorods.
Visualization of tissue molecules targeted by the contrast agent provides molecular information. Visulization of blood at
multiple colors of light provides functional information on blood concentration and oxygen saturation. Optoacoustic
imaging, using two or more laser illumination wavelengths, permits an assessment of the angiogenesis-related
microvasculature, and thereby, an evaluation of the tumor stage and its metastatic potential.
The optoacoustic imaging system was also used to generate molecular images of the malignancy-related receptors
induced by the xenografts of BT474 mammary adenocarcinoma cells in nude mice. The development of the latter images
was facilitated by the use of an optoacoustic contrast agent that utilizes gold nanorods conjugated to monoclonal
antibody raised against HER2/neu antigens. These nanorods possess a very strong optical absorption peak that can be
tuned in the near-infrared by changing their aspect ratio. The effective conversion of the optical energy into heat by the
gold nanorods, followed by the thermal expansion of the surrounding water, makes these nanoparticles an effective
optoacoustic contrast agent. Optical scattering methods and x-ray tomography may also benefit from the application of
this contrast agent. Administration of the gold nanorod bioconjugates to mice resulted in an enhanced contrast of breast
tumors relative the background of normal tissues in the nude mouse model. The combination of this novel contrast agent
and optoacoustic imaging has the potential to become a useful imaging modality, for preclinical research in murine
models of cancer and other human diseases.
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