We present a photoacoustic tomography-guided diffuse optical tomography approach using a hand-held probe for detection and characterization of deeply-seated targets embedded in a turbid medium. Diffuse optical tomography guided by coregistered ultrasound, MRI, and x ray has demonstrated a great clinical potential to overcome lesion location uncertainty and to improve light quantification accuracy. However, due to the different contrast mechanisms, some lesions may not be detectable by a nonoptical modality but yet have high optical contrast. Photoacoustic tomography utilizes a short-pulsed laser beam to diffusively penetrate into tissue. Upon absorption of the light by the target, photoacoustic waves are generated and used to reconstruct, at ultrasound resolution, the optical absorption distribution that reveals optical contrast. However, the robustness of optical property quantification of targets by photoacoustic tomography is complicated because of the wide range of ultrasound transducer sensitivity, the orientation and shape of the targets relative to the ultrasound array, and the uniformity of the laser beam. We show in this paper that the relative optical absorption map provided by photoacoustic tomography can potentially guide the diffuse optical tomography to accurately reconstruct target absorption maps.
A handheld photoacoustic tomography-guided diffuse optical tomography system for imaging deeply-seated targets in
scattering media is presented. This hybrid imager consists of a probe with an ultrasound transducer in the center and
straddled by two optical fibers for taking photoacoustic images. The diffuse optical tomography component comprises of
9 light-source fibers for delivering light to the imaged tissue, and 14 detector fibers for collecting the light. Single- and
two-phantom targets of high and low optical contrasts were immersed in a scattering intralipid solution to depths of up to
3cm and imaged. The reconstructed absorption coefficients of the targets with guidance from photoacoustic tomography
were compared to those obtained with a-priori depth-only information, and no a-priori information. The reconstructed
absorption maps yielded as much as 2.6-fold improvement in the quantification accuracy compared to the cases with no
guidance from photoacoustic tomography.
KEYWORDS: Acquisition tracking and pointing, Hemodynamics, Imaging systems, Photoacoustic tomography, Brain, Absorption, Photoacoustic spectroscopy, Real time imaging, Image resolution, In vivo imaging
For the first time, the hemodynamics within the entire cerebral cortex of a mouse were studied by using photoacoustic
tomography (PAT) non-invasively and in real time. The PAT system, based on a 512-element full-ring
array with cylindrical focusing, received the PA signal primarily from a slice of about 2 mm thickness. This
system can provide not only high resolution brain vasculature images but also hemodynamic functional images.
We recorded the wash-in process of a photoacoustic contrast agent in a mouse brain in real time. Our results
demonstrated that PAT is a powerful imaging modality to study real-time small animal neurofunctional activities
that cause changes in hemodynamics.
We demonstrate the feasibility of fluorescence imaging of deeply seated tumors using mice injected with an angiogenesis tracer, a vascular endothelial growth factor conjugated with the infrared dye cyanine 7 (VEGF/Cy7). Our optical-only imaging reconstruction method separately estimates the target depth, and then applies this information to reconstruct functional information such as fluorophore concentration. Fluorescence targets with concentrations as low as sub-25 nM are well reconstructed at depths up to 2 cm in both homogeneous and heterogeneous media with this technique.
For the first time, the hemodynamics within the entire cerebral cortex of a mouse were studied by using photoacoustic tomography (PAT) in real time. The PAT system, based on a 512-element full-ring ultrasound array, received photoacoustic signals primarily from a slice of 2-mm thickness. This system can provide high-resolution brain vasculature images. We also monitored the fast wash-in process of a photoacoustic contrast agent in the mouse brain. Our results demonstrated that PAT is a powerful imaging modality that can be potentially used to study small animal neurofunctional activities.
Ovarian cancer has the highest mortality of all gynecologic cancers, with a five-year survival rate of only 30% or less. Current imaging techniques are limited in sensitivity and specificity in detecting early stage ovarian cancer prior to its widespread metastasis. New imaging techniques that can provide functional and molecular contrasts are needed to reduce the high mortality of this disease. One such promising technique is photoacoustic imaging. We develop a 1280-element coregistered 3-D ultrasound and photoacoustic imaging system based on a 1.75-D acoustic array. Volumetric images over a scan range of 80 deg in azimuth and 20 deg in elevation can be achieved in minutes. The system has been used to image normal porcine ovarian tissue. This is an important step toward better understanding of ovarian cancer optical properties obtained with photoacoustic techniques. To the best of our knowledge, such data are not available in the literature. We present characterization measurements of the system and compare coregistered ultrasound and photoacoustic images of ovarian tissue to histological images. The results show excellent coregistration of ultrasound and photoacoustic images. Strong optical absorption from vasculature, especially highly vascularized corpora lutea and low absorption from follicles, is demonstrated.
We present the application of a curved array photoacoustic tomographic imaging system that can provide rapid, high-resolution photoacoustic imaging of small animal brains. The system is optimized to produce a B-mode, 90-deg field-of-view image at sub-200-µm resolution at a frame rate of ~1 frame/second when a 10-Hz pulse repetition rate laser is employed. By rotating samples, a complete 360-deg scan can be achieved within 15 s. In previous work, two-dimensional (2-D) ex vivo mouse brain cortex imaging has been reported. We report three-dimensional (3-D) small animal brain imaging obtained with the curved array system. The results are presented as a series of 2-D cross-sectional images. Besides structural imaging, the blood oxygen saturation of the animal brain cortex is also measured in vivo. In addition, the system can measure the time-resolved relative changes in blood oxygen saturation level in the small animal brain cortex. Last, ultrasonic gel coupling, instead of the previously adopted water coupling, is conveniently used in near-real-time 2-D imaging.
We present results of investigations of the application of a priori information and sparse
or limited-view algorithms to simultaneously improve imaging quality and timeresolution
in photoacoustic tomography. Modified versions of existing MRI/CT
algorithms such as constrained backprojection and keyhole imaging are evaluated as well
as a new Wiener estimation methods for extrapolation of missing data from reference
data sets. Simulations indicate the effectiveness of the approaches for accurate tracking
of dynamic photoacoustic events for data sets with limited views (< 90 degrees) or
tomographic views with up to 1/64 of the full data set. We present experimental data of
contrast uptake and washout using a 512-element curved transducer with 1:8 electronic
multiplexing that demonstrates high-resolution tomographic imaging with a temporal
resolution of better than 150 milliseconds using these methods.
A 512-element photoacoustic tomography system for small animal imaging using a ring
ultrasound array has been developed. The system features a 5 MHz piezocomposite
transducer array formed into a complete circular aperture. Custom receiver electronics
consisting of dedicated preamplifiers, 8:1 multiplexed post-amplifiers, and a 64-channel
data acquisition module provide full tomographic imaging at up to 8 frames/second. We
present details of the system design along with characterization results of the resolution,
imaging volume, and sensitivity. Small animal imaging performance is demonstrated
through images of mice brain vasculature at different depths and real-time spectroscopic
scans. This system enables real-time tomographic imaging for functional photoacoustic
studies for the first time.
Ovarian cancer has the highest mortality of all gynecologic cancers with a five-year
survival rate of only 30%. Because current imaging techniques (ultrasound, CT, MRI, PET) are
not capable of detecting ovarian cancer early, most diagnoses occur in later stages (III/IV). Thus
many women are not correctly diagnosed until the cancer becomes widely metastatic. On the
other hand, while the majority of women with a detectable ultrasound abnormality do not harbor a
cancer, they all undergo unnecessary oophorectomy. Hence, new imaging techniques that can
provide functional and molecular contrasts are needed for improving the specificity of ovarian
cancer detection and characterization. One such technique is photoacoustic imaging, which has
great potential to reveal early tumor angiogenesis through intrinsic optical absorption contrast
from hemoglobin or extrinsic contrast from conjugated agents binding to appropriate molecular
receptors.
To better understand the cancer disease process of ovarian tissue using photoacoustic
imaging, it is necessary to first characterize the properties of normal ovarian tissue. We have
imaged ex-vivo ovarian tissue using a 3D co-registered ultrasound and photoacoustic imaging
system. The system is capable of volumetric imaging by means of electronic focusing. Detecting
and visualizing small features from multiple viewing angles is possible without the need for any
mechanical movement. The results show strong optical absorption from vasculature, especially
highly vascularized corpora lutea, and low absorption from follicles. We will present correlation
of photoacoustic images from animals with histology. Potential application of this technology
would be the noninvasive imaging of the ovaries for screening or diagnostic purposes.
We report experimental investigations of photoacoustic guidance of diffusive optical
tomography for detection and characterization of optical contrast targets. The hybrid
system combined an 8-source, 10-detector frequency domain DOT with a clinical
reflection geometry probe. For the photoacoustic tomography (PAT) functionality, a
high-energy 1×7 optical fiber delivery system illuminated a 2 cm central region for
localization of absorptive targets. Two-dimensional PAT images along one central axis
of the probe defined of regions of interest for a dual-zone mesh DOT imaging algorithm.
PVC Plastisol phantom absorbers, 1 cm on a side, with absorption coefficients ranging
from 0.075 to 0.23 cm-1 were imaged at depths up to 2.5 cm. Pairs of absorbers
simulating a multi-lobed heterogeneous tumor were also investigated. Without PAT
guidance, the absorber location was not clear and lower contrast targets in the twoabsorber
configurations were not distinguishable. With PAT guidance, the two targets
were well resolved and the reconstructed absorption coefficients improved to within 15%
of the true values.
We present a robust technique for diffuse optical fluorescence imaging of tumors in mice and tissue
simulating fluorescence phantoms. The detection optics, which is a crucial part of a frequency domain
fluorescence imaging system, with appropriate optical filters for efficient rejection of the excitation light, is
demonstrated. The image reconstruction is divided into two parts; i.e. reconstructing the target locations
such as size and position, and reconstructing the functional information such as fluorophore concentration
and image reconstruction. The structural parameters i.e. tumor size and locations of the targets are
recovered by a chi-square fitting technique by fitting the experimental data into analytically generated data.
Having the structural information beforehand, the images are reconstructed by using our dual-mesh
technique. The fluorescence images of targets of few tens of nanomolar fluorophore concentrations in both
homogeneous and heterogeneous media are reconstructed in this study.
We present the application of an optimized curved array photoacoustic tomographic imaging system, which can provide
rapid, high-resolution photoacoustic imaging of small animal brains. The system can produce a B-mode, 90-degree
field-of-view image at sub-200 μm resolution at a frame rate of ~1 frame/second when a 10-Hz pulse repetition rate
laser is employed. By rotating samples, a complete 360-degree scan can be achieved within 15 seconds. In previous
work, two-dimensional ex vivo mouse brain cortex imaging has been reported. In the current work, we report three-dimensional
small animal brain imaging obtained with the curved array system. The results are presented as a series of
two-dimensional cross-sectional images. Besides structural imaging, the blood oxygen saturation of the animal brain
cortex is also measured in vivo. In addition, the system can measure the time-resolved relative changes in blood oxygen
saturation level in the small animal brain cortex. Finally, ultrasonic gel coupling, instead of the previously adopted
water coupling, is conveniently used in near-real-time 2D imaging.
We present systematic characterization of a photoacoustic imaging system optimized for rapid, high-resolution tomographic imaging of small animals. The system is based on a 128-element ultrasonic transducer array with a 5-MHz center frequency and 80% bandwidth shaped to a quarter circle of 25 mm radius. A 16-channel data-acquisition module and dedicated channel detection electronics enable capture of a 90-deg field-of-view image in less than 1 s and a complete 360-deg scan using sample rotation within 15 s. Measurements on cylindrical phantom targets demonstrate a resolution of better than 200 µm and high-sensitivity detection of 580-µm blood tubing to depths greater than 3 cm in a turbid medium with reduced scattering coefficient µ=7.8 cm−1. The system is used to systematically investigate the effects of target size, orientation, and geometry on tomographic imaging. As a demonstration of these effects and the system imaging capabilities, we present tomographic photoacoustic images of the brain vasculature of an ex vivo mouse with varying measurement aperture. For the first time, according to our knowledge, resolution of sub-200-µm vessels with an overlying turbid medium of greater than 2 cm depth is demonstrated using only intrinsic biological contrast.
We report experimental imaging results with mice using an array-based photoacoustic tomography system designed for small animal imaging. The system features a 128-element curved transducer array with stage rotation to enable complete two-dimensional tomographic
imaging in less than 15 seconds. High fidelity imaging of ex vivo mouse brain vasculature was achieved with resolution of vessels less than 200 microns in diameter in the cortex as well as the
cerebellum. Images obtained using varying measurement surface angular spans clearly illustrate the impact on feature definition with orientation. The high sensitivity of the system was
demonstrated by images of the brain vasculature with an overlying turbid medium (μa=0.03 cm-1 and μs'~7 cm-1 at 780 nm) of over 2 cm depth. In phantom experiments, high-quality images of blood tubing in a turbid medium were achieved at depths greater than 3 cm for incident fluences of less than 15 mJ/cm2. These results illustrate the suitability for near real-time small animal imaging of deep tissue with high definition.
We report the first experimental investigations of photoacoustic guidance of diffusive optical
tomography for detection and characterization of optical contrast targets. The hybrid system
combined an 8-source, 10-detector reflection mode frequency domain DOT imager with either
orthogonal and reflection-geometry photoacoustic systems. The PAT subsystems imaged two-dimensional
cross-sections to define centers and radii of regions of interest for a dual-zone mesh
DOT imaging algorithm. Phantom absorbers, 1 cm in diameter, of high and low contrast, were
spaced 1.5 to 2.5 cm apart at depths ranging from 1 to 2 cm in a turbid medium. Without PAT
guidance, the absorber DOT images in many cases were merged and indistinguishable. With
PAT guidance, the two targets were well resolved and the reconstructed absorption coefficients
improved to 86-130% of the true values. In addition, using both pulse-echo and photoacoustic
image detection, the photoacoustic guidance correctly distinguished mechanical from optical
contrast providing more specific target information and reconstruction accuracy.
Three-dimensional imaging is very valuable in detecting and visualizing lesions from
multiple viewing angles. In addition, co-registered 3D imaging combining conventional
ultrasound and photoacoustic tomography allows visualization of tissue structures with
simultaneous structural and functional information.
We have developed a 1280 element 3D ultrasound imaging system based on a 1.75D
acoustic array. Complete volumetric images over the full scanning range can be achieved in a few
minutes. In conjunction with a Ti:Sapphire laser, the system has been used for photoacoustic
imaging. We present 3D co-registered images obtained with the system. Ultrasound and
photoacoustic co-registered images of phantoms with different optical and acoustical properties
are shown to demonstrate its advantage in cancer detection.
In principle, absorbed energy profiles can be exactly reconstructed from photoacoustic measurements on a
closed surface. Clinical applications, however, involve compromises due to transducer focus, frequency
characteristics, and incomplete measurement apertures. These tradeoffs introduce artifacts and errors in
reconstructed absorption distributions that affect quantitative interpretations as well as qualitative contrast
between features. The quantitative effects of target geometry, limited measurement surfaces, and bandpass
transducer frequency response have been investigated using a ring transducer system designed for small
animal imaging. The directionality of photoacoustic radiation is shown to increase with target aspect ratio,
producing proportionate overestimates of absorption values for two-dimension apertures less than
approximately 150 degrees. For all target geometries and orientations, mean absorption values approach
the full view values for hemicircular measurement surfaces although the true spatial uniformity is
recovered only with the complete surface. The bandpass transducer frequency spectrum produces a peaked
amplitude response biased toward spatial features ranging from 1 to 8 times the system resolution. We
discuss the implications of these results for design of clinical systems.
KEYWORDS: Ultrasonography, 3D image processing, Photoacoustic imaging, Imaging systems, Photoacoustic spectroscopy, 3D scanning, Data acquisition, Tissue optics, Acoustics, 3D acquisition
Photoacoustic imaging is a promising non-invasive imaging technology due to its ability to combine the enhanced contrast of optical absorption with the spatial resolution of acoustic imaging. Co-registered three-dimensional (3-D) ultrasound and photoacoustic imaging takes advantage of both modalities to allow visualization of tissue structures within a volume using simultaneous structural and functional information. 1.75D acoustic arrays are well-suited for this application due to their ability to scan in 3-D volumes rapidly and accurately while maintaining a reasonable system complexity and cost. We have designed, fabricated, and tested a 1.75D 1280-ch ultrasound system for co-registered 3-D ultrasound and photoacoustic imaging. The system features a 1.75D 1280-channel ultrasound array with a center frequency of 5MHz and 80% bandwidth. The electronics includes 1280 high-voltage pulsers, 40 32-to-1 multiplexers, amplification circuitry, and a 40-channel data acquisition circuit. The system is able to drive the entire array simultaneously, and each array element independently, to scan a 3-D volume within +/- 40 degrees in azimuth direction and +/- 10 degrees in elevation respectively. System performance including axial and lateral resolution has been characterized and compared with simulations. Co-registered 3-D ultrasound and photoacoustic imaging has been successfully performed on phantoms with different geometries and contrast.
We have developed and tested a photoacoustic imaging system based on a 128 element curved-phased
ultrasonic array, which spans a quarter of a complete circle with a radius of curvature equal to 25mm. The center
frequency of the array is 5 MHz with 60% bandwidth. The physical dimensions of the elements are 10x0.3mm (elevation
x azimuth) with an elevation focus of 19mm. Earlier we reported acoustic measurements of the axial and lateral
resolutions of the system that were limited by the impulse response of the narrowband source used in the test. In this
paper we discuss photoacoustic characterization of the system including resolution and sensitivity. The array forms the
building block for a 512-element ring designed for complete tomographic imaging of small animals. Imaging results of
phantoms will be compared with simulations.
We report stabilization of self-pulsating laser diodes using a combination of self-injection locking and frequency locked loops. Short term frequency stability better than 1 part in 106 (3ffl linewidth <1 kHz at 1 .3 GHz) was readily achieved with continuous tunability from 600 MHz to over 3 GHz using inexpensive commercial devices. Experimental results illustrating the effects of loop operation on error performance in subcarrier multiplexed (SCM)
systems are presented.
A massively parallel simulation program TEMPEST is used to investigate the role of topography in generating reflective notching and to study the possibility of reducing effects through the introduction of special properties of resists and antireflection coating materials. The emphasis is on examining physical scattering mechanisms such as focused specular reflections resist thickness interference effects reflections from substrate grains and focusing of incident light by the resist curvature. Specular reflection from topography can focus incident radiation causing a 10-fold increase in effective exposure. Further complications such as dimples in the surface of positive resist features can result from a second reflection of focused energy by the resist/air interface. Variations in line-edge exposure due to substrate grain structure are primarily specular in nature and can become significant for grains larger than )tresi Local exposure variations due to vertical standing waves and changes in energy coupling due to changes in resist thickness are displaced laterally and are significant effects even though they are slightly less severe than vertical wave propagation theory suggests. Focusing effects due to refraction by the curved surface of the resist produce only minor changes in exposure. Increased resist contrast and resist absorption offer some improvement in reducing notching effects though minimizing substrate reflectivity is more effective. CPU time using 32 virtual nodes to simulate a 4 pm by 2 pm isolated domain with 13 bleaching steps was 30 minutes
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