KEYWORDS: Tumors, Spectroscopy, Photoacoustic spectroscopy, Oxygen, Luminescence, Near infrared, In vivo imaging, Scanners, Data acquisition, Near infrared spectroscopy
Purpose: The purpose of this study is to determine the feasibility of using photacoustic CT spectroscopy(PCT-s) to track
a near infrared dye conjugated with trastuzumab in vivo.
Materials and Methods: An animal model was developed which contained both high and low Her2 expression tumor
xenografts on the same mouse. The tumors were imaged at multiple wavelengths (680- 950nm) in the PCT scanner one
day prior to injection of the near infrared conjugated probe. Baseline optical imaging data was acquired and the probe
was then injected via the tail vein. Fluorescence data was acquired over the next week, PCT spectroscopic data was also
acquired during this timeframe. The mice were sacrificed and tumors were extirpated and sent to pathology for IHC
staining to verify Her2 expression levels. The optical fluorescence images were analyzed to determine probe uptake
dynamics. Reconstructed PCT spectroscopic data was analyzed using IDL routines to deconvolve the probe signal from
endogenous background signals, and to determine oxygen saturation.
Results: The location of the NIR conjugate was able to be identified within the tumor utilizing IDL fitting routines, in
addition oxygen saturation, and hemoglobin concentrations were discernible from the spectroscopic data.
Conclusion: Photacoustic spectroscopy allows for the determination of in vivo tumor drug delivery at greater depths than
can be determined from optical imaging techniques.
Purpose: The purpose of this study is to calibrate the PCT scanner to quantify the hemoglobin status utilizing a blood
flow phantom.
Materials and Methods: A blood circulation system was designed and constructed to control the oxygen saturation and
hemoglobin concentration of blood. As a part of the circulation system, a 1.1mm FEP tube was placed in the center of
imaging tank of PCT scanner as the imaging object. Photoacoustic spectra (690-950 nm) was acquired for different
hemoglobin concentrations (CtHb) and oxygen saturation levels (SaO2), where the formers was formed by diluting
blood samples with PBS and the latter by mixing blood with gases at different oxygen content. Monte Carlo simulations
were performed to calculate the photon energy depositions in the phantom tube, which took into account photon losses in
water and blood. A Kappa value which represents the energy transfer efficiency of hemoglobin molecule was calculated
based on the PCT measurement and simulation result. The final SaO2 value of each blood sample was calculated based
on the PCT spectrum and Kappa value. These oxygen saturation results were compared with co-oximeter measurements
to obtain systematic errors.
Results and Conclusion: The statistic error of calculating Kappa value from hemoglobin concentration experiment was
less than 5%. The systematic error between PCT spectra analysis and co-oximeter analysis for hemoglobin oxygen
saturation was -4.5%. These calibration techniques used to calculate Kappa and hemoglobin absorption spectra would be
used in hypoxia measurements in tumors as well as for endogenous biomarkers studies.
Purpose: The purpose of this study is to use PCT spectroscopy scanner to monitor the hemoglobin concentration and
oxygen saturation change of living mouse by imaging the artery and veins in a mouse tail.
Materials and Methods: One mouse tail was scanned using the PCT small animal scanner at the isosbestic wavelength
(796nm) to obtain its hemoglobin concentration. Immediately after the scan, the mouse was euthanized and its blood was
extracted from the heart. The true hemoglobin concentration was measured using a co-oximeter. Reconstruction
correction algorithm to compensate the acoustic signal loss due to the existence of bone structure in the mouse tail was
developed. After the correction, the hemoglobin concentration was calculated from the PCT images and compared with
co-oximeter result. Next, one mouse were immobilized in the PCT scanner. Gas with different concentrations of oxygen
was given to mouse to change the oxygen saturation. PCT tail vessel spectroscopy scans were performed 15 minutes
after the introduction of gas. The oxygen saturation values were then calculated to monitor the oxygen saturation change
of mouse.
Results: The systematic error for hemoglobin concentration measurement was less than 5% based on preliminary
analysis. Same correction technique was used for oxygen saturation calculation. After correction, the oxygen saturation
level change matches the oxygen volume ratio change of the introduced gas.
Conclusion: This living mouse tail experiment has shown that NIR
PCT-spectroscopy can be used to monitor the oxygen
saturation status in living small animals.
Thermoacoustic image contrast is dependent on the dielectric and thermoacoustic properties of the tissue being imaged,
its spatial distribution, and the polarization of the incident microwave radiation. We have designed and constructed a
thermoacoustic computed tomography (TCT) test platform to study these effects in phantoms and biologic tissue (e.g.,
beefsteak and mice). Our results indicate that muscle and fat are easily differentiated, but the relative thermoacoustic
absorption is strongly dependent upon the polarization angle of the microwave radiation and the morphology of fat and
muscle tissues.
We have constructed and tested a prototype test bed that allows us to form 3D photoacoustic CT images using
near-infrared (NIR) irradiation (700 - 900 nm), 3D thermoacoustic CT images using microwave irradiation
(434 MHz), and 3D ultrasound images from a commercial ultrasound scanner. The device utilizes a vertically
oriented, curved array to capture the photoacoustic and thermoacoustic data. In addition, an 8-MHz linear array
fixed in a horizontal position provides the ultrasound data. The photoacoustic and thermoacoustic data sets are
co-registered exactly because they use the same detector. The ultrasound data set requires only simple
corrections to co-register its images.
The photoacoustic, thermoacoustic, and ultrasound images of mouse anatomy reveal complementary anatomic
information as they exploit different contrast mechanisms. The thermoacoustic images differentiate between
muscle, fat and bone. The photoacoustic images reveal the hemoglobin distribution, which is localized
predominantly in the vascular space. The ultrasound images provide detailed information about the bony
structures. Superposition of all three images onto a co-registered hybrid image shows the potential of a trimodal
photoacoustic-thermoacoustic-ultrasound small-animal imaging system.
We demonstrate the feasibility of optical angiography on live mice using a new photoacoustic computed tomography
(PCT) scanner. The scanner uses a sparse array of discrete ultrasound detectors geometrically arranged to capture 128
simultaneous radial "projections" through a 25-mm-diameter volume of interest. Denser sets of interleaved radial
projections are acquired by rotating the sparse array continuously about its vertical axis during data acquisition. The
device has been designed specifically for imaging laboratory mice, which remain stationary during data collection.
Angiographic data are acquired at a rate of 1280 radial projections per second following a bolus injection of 2 mg/mL of
indocyanine green (ICG).
We have designed and built a prototype PCT (photoacoustic CT) scanner suitable for small animal imaging that acquires
a sparse set of 128 photoacoustic, radial "projections" uniformly distributed over the surface of a hemisphere in response
to optical absorption from a tunable, pulsed NIR (near-infrared) laser. Acquisition of a denser set of projections is
achieved by rotating the hemispherical array about its vertical axis and acquiring additional, interleaved projections.
Each detector in the array is a 3-mm diameter, piezo-composite with a center frequency of 5 MHz and 70% bandwidth.
Spatial resolution is < 300 μm and nearly isotropic, owing to the array geometry. Preliminary results acquired at half of
the allowable laser power and with no system optimizations show a low contrast sensitivity sufficient to detect a 350 nM
concentration of a NIR-absorbing organic dye embedded in 12.5 mm of soft tissue. This scanner design will allow our
group to take advantage of HYPR (HighlY constrained backPRojection) reconstruction techniques, which can
significantly improve temporal (or spectral) resolution, without sacrificing signal-to-noise or spatial resolution. We will
report how these accelerated reconstruction techniques can be implemented with this PCT scanner design. Using this
approach, we may be able to achieve 100-ms temporal resolution for dynamic studies throughout a 20-mm-diameter
imaging volume.
C. Mistretta, O. Wieben, J. Velikina, Y. Wu, K. Johnson, F. Korosec, O. Unal, G. Chen, S. Fain, B. Christian, O. Nalcioglu, R. Kruger, W. Block, A. Samsonov, M. Speidel, M. Van Lysel, H. Rowley, M. Supanich, P. Turski, Yan Wu, J. Holmes, S. Kecskemeti, C. Moran, R. O'Halloran, L. Keith, A. Alexander, E. Brodsky, J. Lee, T. Hall, J. Zagzebski
KEYWORDS: Signal to noise ratio, Composites, Image processing, X-rays, Magnetic resonance imaging, Medical imaging, Lawrencium, Convolution, Angiography, Positron emission tomography
During the last eight years our group has developed radial acquisitions with angular undersampling
factors of several hundred that accelerate MRI in selected applications. As with all previous
acceleration techniques, SNR typically falls as least as fast as the inverse square root of the
undersampling factor. This limits the SNR available to support the small voxels that these methods
can image over short time intervals in applications like time-resolved contrast-enhanced MR
angiography (CE-MRA). Instead of processing each time interval independently, we have developed
constrained reconstruction methods that exploit the significant correlation between temporal
sampling points. A broad class of methods, termed HighlY Constrained Back PRojection (HYPR),
generalizes this concept to other modalities and sampling dimensions.
Photoacoustic tomography (PAT) is an emerging ultrasound-mediated biophotonic imaging modality that has
great potential for many biomedical imaging applications. In many practical implementations of PAT, the
photoacoustic signals are recorded over an aperture that does not enclose the object, which results in a limitedview
tomographic reconstruction problem. When conventional reconstruction algorithms are applied to limitedview
measurement data, the resulting images can contain severe image artifacts and distortions. To circumvent
such artifacts, we exploit a priori information about the locations of boundaries within the object (optical
absorption function) to improve the fidelity of the reconstructed images. Such boundary information can be
inferred, for example, from a co-registered B-mode ultrasound image or other adjunct imaging study. We develop
and implement an iterative reconstruction algorithm that exploits a priori object information in the form of
support constraints. We demonstrate that the developed iterative reconstruction algorithm produces images
with reduced artifact levels as compared to those produced by a conventional PAT reconstruction algorithm.
It is well documented that photoacoustic imaging has the capability to differentiate tissue based on the spectral
characteristics of tissue in the optical regime. The imaging depth in tissue exceeds standard optical imaging techniques,
and systems can be designed to achieve excellent spatial resolution. A natural extension of imaging the intrinsic optical
contrast of tissue is to demonstrate the ability of photoacoustic imaging to detect contrast agents based on optically
absorbing dyes that exhibit well defined absorption peaks in the infrared. The ultimate goal of this project is to
implement molecular imaging, in which HerceptinTM, a monoclonal antibody that is used as a therapeutic agent in breast
cancer patients that over express the HER2 gene, is labeled with an IR absorbing dye, and the resulting in vivo bio-distribution
is mapped using multi-spectral, infrared stimulation and subsequent photoacoustic detection. To lay the
groundwork for this goal and establish system sensitivity, images were collected in tissue mimicking phantoms to
determine maximum detection depth and minimum detectable concentration of Indocyanine Green (ICG), a common IR
absorbing dye, for a single angle photoacoustic acquisition. A breast mimicking phantom was constructed and spectra
were also collected for hemoglobin and methanol. An imaging schema was developed that made it possible to separate
the ICG from the other tissue mimicking components in a multiple component phantom. We present the results of these
experiments and define the path forward for the detection of dye labeled HerceptinTM in cell cultures and mice models.
Purpose: The purpose of this study is to calibrate the PCT small animal scanner system with a blood phantom and to measure the blood hemoglobin concentration and oxygen saturation level in mouse tail vein and tumors.
Methods and Materials: A blood phantom with variable blood flow and oxygen content was integrated into the PCT scanner with a circulation system. The circulation system consisted of a pump, an oxygen electrode detector and a tonometer. The SaO2 values were determined based on a linear combination model of oxy-hemoglobin and deoxy-hemoglobin absorption spectrum curves. Hemoglobin concentration (CHb) was determined by measuring the linear relationship for different blood dilutions. SaO2 and CHb as measured in vivo for the artery and vein in a mouse tail were also measured.
Results: The PCT spectra of blood phantom samples were measured and compared with hemoglobin optical absorption spectra. The linear relationship between hemoglobin concentration and PCT intensities were observed by phantom study. The hemoglobin concentration of mouse is ~9.7g/dL. The saturation difference between arteries and veins in mouse tail is also measured by PCT scan.
Conclusions: Both the phantom and living mouse tail vessel scans have shown that NIR PCT-spectroscopy can be used to measure the hemoglobin saturation level and hemoglobin concentration in small animal for future tumor hypoxia study.
KEYWORDS: Monte Carlo methods, Tumors, Blood, Photoacoustic spectroscopy, Absorption, Near infrared, Tissue optics, Photon transport, Acoustics, Signal attenuation
Purpose: The purpose of this study is to evaluate the influence of photon propagation on the NIR spectral features associated with photoacoustic imaging.
Introduction: Photoacoustic CT spectroscopy (PCT-S) has the potential to identify molecular properties of tumors while overcoming the limited depth resolution associated with optical imaging modalities (e.g., OCT and DOT). Photoacoustics is based on the fact that biological tissue generates high-frequency acoustic signals due to volume of expansion when irradiated by pulsed light. The amplitude of the acoustic signal is proportional to the optical absorption properties of tissue, which varies with wavelength depending on the molecular makeup of the tissue. To obtain quantifiable information necessitate modeling and correcting for photon and acoustic propagation in tumors.
Material and Methods: A Monte Carlo (MC) algorithm based on MCML (Monte Carlo for Multi-Layered edia) has been developed to simulate photon propagation within objects comprised of a series of complex 3D surfaces (Mcml3D). This code has been used to simulate and correct for the optical attenuation of photons in blood, and for subcutaneous tumors with homogenous and radially heterogeneous vascular distributions.
Results: The NIR spectra for oxygenated and deoxygenated blood as determined from Monte Carlo simulated photoacoustic data matched measured data, and improving oxygen saturation calculations. Subcutaneous tumors with a homogeneous and radially heterogeneous distribution of blood revealed large variations in photon absorption as a function of the scanner projection angle. For select voxels near the periphery of the tumor, this angular profile between the two different tumors appeared similar.
Conclusions: A Monte Carlo code has been successfully developed and used to correct for photon propagation effects in blood phantoms and restoring the integrity of the NIR spectra associated with oxygenated and deoxygenated blood. This code can be used to simulate the influence of intra-tumor heterogeneity on the molecular identification via NIR spectroscopy.
Purpose: To evaluate photoacoustic CT spectroscopy (PCT-S) and dynamic contrast-enhanced CT (DCE-CT) ability to measure parameters - oxygen saturation and vascular physiology - associated with the intra-tumor oxygenation status.
Material and Methods: Breast (VEGF165 enhance MCF-7) and ovarian (SKOV3x) cancer cells were implanted into the fat pads and flanks of immune deficient mice and allowed to grow to a diameter of 8-15 mm. CT was used to determine physiological parameters by acquiring a sequence of scans over a 10 minute period after an i.v. injection of a radio-opaque contrast agent (Isovue). These time-dependent contrast-enhanced curves were fit to a two-compartmental model determining tumor perfusion, fractional plasma volume, permeability-surface area produce, and fractional interstitial volume on a voxel-by-voxel basis. After which, the tumors were imaged using photoacoustic CT (Optosonics, Inc., Indianapolis, IN 46202). The near infrared spectra (700-910 nm) within the vasculature was fit to linear combination of measured oxy- and deoxy-hemoglobin blood samples to obtain oxygen saturation levels (SaO2).
Results: The PCT-S scanner was first calibrated using different samples of oxygenated blood, from which a statistical error ranging from 2.5-6.5% was measured and a plot of the hemoglobin dissociation curve was consistent with empirical formula. In vivo determination of tumor vasculature SaO2 levels were measurably tracked, and spatially correlated to the periphery of the tumor. Tumor depend variations in SaO2 - 0.32 (ovarian) and 0.60 (breast) - and in vascular physiology - perfusion, 1.03 and 0.063 mL/min/mL, and fractional plasma volume, 0.20 and 0.07 - were observed.
Conclusion: Combined, PCT-S and CED-CT has the potential to measure intra-tumor levels of tumor oxygen saturation and vascular physiology, key parameters associated with hypoxia.
Purpose: The purpose of this study is to evaluate PCT Imaging technique to classify tissue and extract kidney cysts in pcy mice model of human adolescent nephronophthisis. Method: Four mice with late stages of nephronophthisis with polycystic kidney disease-PKD and one normal mouse were scanned in the PCT Small Animal Scanner. Both vivo and ex-vivo images of mice kidney were taken at wavelength from 680 nm to 940 nm. The ex-vivo PCT images were compared with histology photographs to check the sensitivity of detecting cysts. Histograms of kidney images were generated over slices and fitted to Gaussian-curve model for volumetric analysis. The portions of cysts in kidneys were estimated and kidney images were segmented by three different colors to present the distribution of different tissues. Result: A good correspondence between PCT imaging findings and PKD histology result was observed. Histogram curves from images of pcy kidneys and normal kidneys were fitted to Gaussian-curve model. Portions of cysts, parenchyma and area of high level hemoglobin were estimated according to the curve fit result. A growth of cysts associated with relatively volume decrease of parenchyma and tissues with high perfusion of hemoglobin was observed. Conclusion: The PCT enabled visualization of renal cysts for mouse model and had the potential for volumetric measurements of kidney.
Purpose. To evaluate photoacoustic spectroscopy as a potential imaging modality capable of measuring intra-tumor heterogeneity and spectral features associated with hemoglobin and the molecular probe indocyanine green (ICG). Material and Methods. Immune deficient mice were injected with wildtype and VEGF enhanced MCF-7 breast cancer cells or SKOV3x ovarian cancer cells, which were allowed to grow to a size of 6-12 mm in diameter. Two mice were imaged alive and after euthanasia for (oxy/deoxy)-hemoglobin content. A 0.4 mL volume of 1 μg/mL concentration of ICG was injected into the tail veins of two mice prior to imaging using the photoacoustic computed tomography (PCT) spectrometer (Optosonics, Inc., Indianapolis, IN 46202) scanner. Mouse images were acquired for wavelengths spanning 700-920 nm, after which the major organs were excised, and similarly imaged. A histological study was performed by sectioning the organ and optically imaging the fluorescence distribution. Results. Calibration of PCT-spectroscopy with different samples of oxygenated blood reproduced a hemoglobin dissociation curve consistent with empirical formula with an average error of 5.6%. In vivo PCT determination of SaO2 levels within the tumor vascular was measurably tracked, and spatially correlated to the periphery of the tumor. Statistical and systematic errors associated with hypoxia were estimated to be 10 and 13%, respectively. Measured ICG concentrations determined by contrast-differential PCT images in excised organs (tumor, liver) were approximately 0.8 μg/mL, consistent with fluorescent histological results. Also, the difference in the ratio of ICG concentration in the gall bladder-to-vasculature between the mice was consistent with excretion times between the two mice. Conclusion. PCT spectroscopic imaging has shown to be a noninvasive modality capable of imaging intra-tumor heterogeneity of (oxy/deoxy)-hemoglobin and ICG in vivo, with an estimated error in SaO2 at 17% and in ICG at 0.8 μg/mL in excised tissue. Ongoing development of spectroscopic analysis techniques, probe development, and calibration techniques are being developed to improve sensitivity to both exogenous molecular probes and (oxy/deoxy)-hemoglobin fraction.
We have utilized a prototype Thermoacoustic Computed Tomography Small Animal Imaging System to acquire images of athymic mice with bilateral tumors implanted in the cranial mammary fat pads. The breast tumor cell lines used in the study, which are MCF7, and MCF7 transfected with Vascular Endothelial Growth Factor (VEGF), exhibit distinctly contrasting levels of vascularization. Three dimensional images of the mice, acquired using pulses of NIR stimulating light, demonstrate the ability of the system to generate high resolution images of the vascular system up to one inch deep in tissue, and at the same time, differentiate tissue types based on the infrared absorption properties of the tissue; a property related in part to blood content and oxygenation levels. We have processed images acquired at different stimulating wavelengths to generate images representative of the distribution of oxygenated and deoxygenated hemoglobin throughout the tumors. The images demonstrate the in vivo capabilities of the imaging system and map system structure as well as the total, oxygenated and deoxygenated hemoglobin components of the blood.
We have completed the design and testing of a thermoacoustic computed tomography scanner for whole-breast imaging. We report on the technical changes in this design form our previous TCT scanner, and how these design changes have improved image quality. Improvements to the design include: greater angular coverage of TCT measurements, increased sensitivity of the ultrasound detector array, and improved delivery of radio wave energy. These improvements resulted in higher fidelity 3D reconstructions, reduced scan time, and fewer image artifacts. These improvements were documented by imaging simple, 3D phantoms, formulated from salinated agar spheres. We confirmed improvements in breast image quality by comparing images of patient volunteers taken with our previous TCT scanner and this new TCT scanner.
In order to assess the potential clinical utility of using thermoacoustic computer tomography (TCT) to image the breast, we conducted a retrospective pilot study of 78 patients. We recruited patients in three age groups (<40,40-50,>50 years). The study population was further segregated into normal and suspicious based on the results of the previous x-ray mammography and ultrasound. Image quality was evaluated qualitatively by consensus of two trained mammographers using a 4-point scale. The appearance of normal anatomy, cysts, benign disease and cancer was noted. Patients were also asked to rate the comfort of the TCT exam and to indicate a personal preference for x-ray mammography or TCT. Analysis of the data indicated that TCT image quality was dependent upon both patient age and breast density, improving with both increasing breast density and decreasing patient age. Fibrocystic disease was well seen, cysts appearing as areas of low RF absorption. Fibroadenomas did not demonstrate contrast enhancement with the exception of one patient with associated atypical hyperplasia. Cancer displayed higher RF absorption than surrounding tissues in 4/7 patients in whom cancer was confirmed, including one patient with a 7-mm ductal carcinoma in situ (DCIS).
We have developed instrumentation for measuring the tissue- absorption properties of radio waves in the human body using thermoacoustic interactions. The imaging principles upon which this instrumentation is based are applicable to other irradiation sources, such as visible and IR. We present the imaging reconstruction methodology that we have developed for mapping radiation absorption pattern sin 3D. Both simulated and experimental data are used to illustrate imaging principles.
We have previously developed instrumentation for performing thermoacoustic computed tomography (TCT) of the human breast using 434 MHz radio waves. Recently, we have modified our original TCT scanner design in a number of important ways. We have increased the number of ultrasound detectors and decreased their size, and we have replaced our single RF wave- guide with a phased array of eight wave-guides. These modifications have led to increased spatial resolution, increased imaging field of view, and decreased scan time. Here we report the design considerations that led to these improvements.
Numerical simulations are a valuable tool in the development of complex systems. They provide the ability to determine the effects of individual parameters on system functionality, and in the case of electronic systems, the ability to examine the system without the limitations introduced by electronic noise. The Thermoacoustic Computed Tomography (TACT) system under development was a natural candidate for numerical analysis. Early versions of the system exhibited exceptional promise, but final image quality was limited by a variety of confounding geometrical and electronic factors. The simulations described in this paper were used to generate the transducer signals that would theoretically be collected by the actual TACT imaging system when a sample was exposed to a pulse of electromagnetic radiation. The simulated data streams were then fed into the actual image reconstruction software to provide images of the 'virtual' phantoms. These images were analyzed and quantified to provide a measure of the system parameters responsible for the image blurs that limit system spatial resolution.
Acoustic pressure waves are induced in soft tissue whenever time-varying radiation is absorbed. By recording these time- dependent pressure waves over a sufficient number of angles surrounding the tissue being imaged, it is possible to reconstruct the pattern of radiation absorption within the tissue in three dimensions with spatial resolution that is independent of the carrier frequency of the irradiating energy. We recently constructed the world's first thermoacoustic computed tomography (TACT) scanner, which exploits this physical interaction. Initial in vivo imaging of a human breast was performed using safe levels of 434 MHz radiation. Good soft tissue differentiation with 2 - 5 mm spatial resolution to a depth of 40 mm was achieved. The absorption properties of the breast and the irradiation pattern within the breast determined the TACT image contrast. The length of the RF pulse, the size of the transducers and their frequency response, the geometry of the detector array, and the reconstruction algorithm that was used determined the spatial resolution. We conclude that TACT imaging may have application to breast cancer detection.
Photoacoustic signals generated by breasts irradiated with short microwave, infrared or optical pulses could be used to detect breast cancer. Since radiation at this spectrum is non-ionizing, the photoacoustic approach provides a special safety feature. The purpose of the paper is to present a means to predict photoacoustic pressure signals for different breast phantoms and irradiation conditions. The photoacoustic wave equation was derived for linear, non-viscous liquid media. The equation was solved assuming uniform acoustic properties in an infinite medium. Compressed breast phantoms were used as the objects of simulation. The spatial dependence of electromagnetic energy absorption was given by another research paper of this conference. The time dependence of the absorption was assumed to be either uniform or bell- shaped. Photoacoustic pressure signals received by transducers at different locations were calculated numerically.
The simulation of energy deposition within the compressed human breast following its illumination with a short duration pulse of near-infrared light is examined. Different scattering and absorption conditions are studied: homogeneous scattering with homogeneous absorption, homogeneous scattering with heterogeneous absorption (i.e., the introduction of an abnormality), and heterogeneous scattering with homogeneous absorption. Some of the results were used in a companion paper for the simulation of photoacoustic ultrasonic waves resulting from the quick absorption of energy by a region exhibiting increased differential absorption over that of immediately adjacent areas. A method for simulating heterogenous scattering properties is introduced. It is observed that changes in the scattering coefficient within a region do not influence the absorption patterns of the region.
This investigation describes the design and performance of two, water-immersed, microwave applicators (433 MHz) for use with photoacoustic ultrasonography (PAUS). A cylindrical, open-aperture waveguide was chosen because it could be integrated easily into our PAUS instrumentation. The microwave flux distributions for two microwave applicators were measured using a specially-constructed temperature probe, consisting of an optical fiber with a temperature-sensitive phosphor that was placed inside a thin, polyethylene tube filled with 0.5 M saline. Using this instrumentation, we mapped the microwave flux distribution for each applicator. The physical characteristics of these applicators are discussed.
Recent theoretical calculations by our group (2134-14) indicate that regional optical absorption of radiation within highly scattering media, such as biologic tissue, can be localized by detecting photo-acoustic waves that are produced during regional, optical absorption. This paper reports our initial experimental verification that measurable ultrasonic waves are produced when differential optical absorption takes place within turbid media simulating biologic tissue. For these experiments, an aquarium filled with a 0.5% intralipid solution was used to simulate the scattering properties of biologic tissue. Regional, optical absorption was produced by suspending black, latex spheres (3 - 10 mm diameter) within the intralipid bath. A broadband, xenon flash lamp (1 microsecond(s) ec rise time) was used for one set of experiments and a Nd:YAG laser ((lambda) equals 1064 nm, pulse width < 10 ns) was used for another set. A variety of focused, ultrasound transducers (0.5 - 2.5 MHz) were used successfully to detect and localize photo-acoustic waves. Lateral scanning of the transducers was used to localize the position of the absorption cells with a spatial resolution approximately 1 mm.
Localizing optical absorption within biologic tissue is compromised by the ubiquitous scattering of light that takes place within such tissues. As an alternative to purely optical detection schemes, regional absorption of optical radiation can be detected and localized within highly scattering tissues by detecting the acoustic waves that are produced whenever differential absorption of radiation takes place within such tissues. When the source of optical radiation is delivered in pulses of <EQ 1 microsecond(s) ec duration, the acoustic waves that are produced lie in the medical ultrasonic frequency range, and can be localized using conventional ultrasonic transducers and reconstruction methodology. Localizing such acoustic waves is not adversely affected by optical scattering. This paper introduces a simplistic theory of acoustic wave production within turbid media. The relationships among the irradiating optical pulse power, regional absorption, and strength of acoustic wave production are developed. Estimates of contrast and spatial resolution are presented, assuming a conventional, focused ultrasound transducer and translational scanning are used. Initial theoretical work indicates that optical absorption can be localized with millimeter spatial resolution for 10% absorption or less in biologic tissues as thick as 6.0 cm using safe levels of optical radiation.
A new approach to solve the radiative transport equation for time-resolved spectroscopy is presented. A new phase function that shows much better agreement with Mie theory than Henyey-Greenstein's phase function is introduced. Initial laser beams are properly modeled. For every small time increment, precise and analytical solutions are found to satisfy the radiative transport equation for the uniform field, wide beam, and narrow beam. Computer simulations give promising results. Different conditions of initial beams, media, and medium abnormalities are discussed. A strategy for using the semianalytical solutions to reconstruct the regional distribution of the scattering attenuation coefficient and future work are described.
A computerized scheme for the automated segmentation of contrast enhanced arteries is developed for computerized tomographic angiography (CTA) data. Segmentation is performed with two-dimensional (2D) images on a slice-by-slice base. Image processing techniques include gray-level thresholding, eight-point connectivity tracking, region growing, moment analysis and morphological erosion. The results enable the generation of separated three-dimensional (3D) displays of both vascular and non-vascular structures. The method has been applied to several clinical cases and has shown great promises.
This article proposes a new approach to the `forward problem' by directly solving the radiative transport equation. A new phase function introduced by the authors' previous work has been used in the new approach in a simplified form. A function modeling the spatial, directional and temporal distributions of the incident laser pulse is proposed. For every small time increment, analytical approximation solutions to the time-dependent radiative transport equation are formulated. Preliminary results of computer simulation of the approach are provided.
A method is presented for simulating the paths traced by photons traveling through a homogenous isotropically scattering medium. An initial photon path is defined with a string of characters that represent the most direct path between a source pixel and a detection pixel. This string then is expanded systematically in unit increments using well-defined rules. In two dimensions using a hexagonal lattice, these rules assume that only six possible directions of scatter are allowed. In three dimensions using a Cartesian lattice, there also are only six directions. The method is tractable and lends itself to computational implementation. Because the method is deterministic, it is more efficient than Monte Carlo methods when investigating paths between specific source and detection pixels. When boundaries are imposed on an object, it is possible to investigate millions of photon paths of a given specified length and to determine probabilistically the pixels visited by the photons within the object.
A mathematical model is proposed describing time-resolved output measurements obtained on the surface of a diffusely scattering body due to an input pulse of near-IR light at a different location also on the surface. Such measurements can be obtained using a pulsed near-IR laser coupled with a CCD streak camera. The scattering body is assumed to exhibit homogenous scattering and spatially varying absorption. Using this model, an iterative algorithm is derived using maximum likelihood methods that allows the reconstruction of the spatial absorption pattern from a set of time-resolved tomographic measurements. The methodology places no restrictions upon the time-of-arrival of the detected photons, thus permitting the entire time-resolved signal to be used in the reconstruction process. The reconstruction algorithm is easily initialized and preliminary results indicate that stable reconstructions can be performed.
Researchers in biomedical optics use either the photon diffusion model or the Monte Carlo simulation to approach the `forward problem' of image reconstruction of the optical diffusion tomography for turbid media. Solving the photon transport equation is an alternate method to solve the `forward problem,' and might be more accurate because light propagation in turbid media is supposed to be better depicted by the photon transport equation than the other two methods. A solution to the time-dependent integro-differential equation has been found, using a hybrid (finite-difference and analytic) method. When the spatial and directional distributions of the initial light beam are given, analytical solutions to the photon transport equation are obtained for following discrete instances. This new approach has potential application to the time-resolved optical diffusion tomography as a more accurate solution to the `forward problem.'
A method of imaging through highly scattering media has been applied to the reconstruction
of a transaxial slice across a cylindrical phantom containing a low absorbing, high scattering
solution. The imaging method involves recording anddiscriminating between the times-of-flight of
transmitted photons. Images of the phantom are presented which were generated using light
transmitted through the phantom with the shortest flight times.
A digital angiographic system has been modified into a prototype of an image intensifier-based volume CT imager for angiography. The modified system has been tested by a vascular phantom. The system consists of two x-ray tubes and two image intensifiers that are separately mounted on a gantry. The two tube-detector sets can be rotated over 360 degree(s) in the gantry. To explore the imaging performance of the system for reconstructing a three-dimensional (3D) vascular structure a set of nonsubtraction projections of a vascular phantom, acquired over 36 projection angles, were digitized. These data were reconstructed using an iterative algorithm specially designed for 3D vascular structures. The quality of the reconstructed vascular images indicates that the system can offer adequate signal-to-noise ratio (SNR) for direct 3D vascular reconstruction when only a few projections are used without subtraction procedure, assuming intra-arterial injection of contrast. Also, a pincushion distortion correction algorithm has been developed and the results suggest that the algorithm works well for the image intensifier-based volume CT imager.
Preliminary results are presented of a study of the spatial resolution performance of a system which produces transmission images of highly scattering objects by recording and discriminating between the times-of- flight of transmitted photons. This system is being developed as a possible means of screening for breast cancer using harmless doses of visible or near-infrared radiation.
A series of simulations have been performed in order to investigate the feasibility of constructing a time-of-flight breast imaging system capable of achieving clinically useful resolution using state-of-the-art picosecond laser pulse generation and detection technology. Simulated images are presented which demonstrate the likely performance of such a system, based on the attenuation and scattering characteristics of breast tissue measured in the laboratory.
A prototype voluiie CT irnager has been tested using a vascular phantom. This systen consists of a fixed x-ray tube a conventional image intensifier coupled to a chargecoupled device (CCD) camera a computer-controlled turntable on which phantons are placed and a digital computer with a graphics station. To explore the imaging performance of the system for reconstructing a three-dimensional (3D) vascular structure a set of subtraction projections of a vascular phantom acquired over 25 projection angles with two different sizes of image intensifiers were digitized. Then these data were reconstructed using two iterative algorithms specially designed for 3D vascular structures. The quality of the reconstructed vascular images indicates that the system can offer adequate signal-to-noise ratio (SNR) for direct 3D vascular reconstruction when only a few subtraction projections are used assuming intraarterial injection of contrast. The results also suggest that the iterative vascular reconstruction algorithms work well for direct 3D vascular reconstruction. 1.
The feasibility of a new diagnostic imaging technique is investigated that potentially might be
used for breast cancer screening with millimeter resolution, but without using ionizing radiation. It
is suggested that acoustic pulses of sufficient intensity may produce small density changes within
tissue which result in small but detectable changes in electrical current flowing through the tissue.
The magnitude of this current fluctuation is shown to be inversely proportional to the conductivity
of the tissue within the region occupied by the pulse. Measurement of the current modulation may
enable small resistive inhomogeneities, such as tumors, to be detected. If the position of a pulse's
wavefront can be predicted with sufficient precision at any given instant, measurement of the
current modulation could be used to reconstruct the unknown electrical impedance distribution
within the tissue. The rudiments of the technique are discussed and, using some simplifying
assumptions, a rough estimate is made of the magnitude of the current modulation, and of the
timescale necessary to obtain useful diagnostic information.
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