Ultrasound-mediated optical tomography: a review of current methods
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paper_title: A fluorescence confocal endomicroscope for in vivo microscopy of the upper- and the lower-GI tract.

paper_content:

BACKGROUND ::: This report describes the development and the clinical evaluation of a novel confocal endomicroscope for obtaining fluorescence images of cellular morphology of the mucosae of the upper- and the lower-GI tract in vivo. The work assessed the feasibility of performing in vivo microscopy at endoscopic examination and evaluated fluorescence imaging protocols. ::: ::: ::: METHODS ::: Images were collected in real time by using two prototype endoscope configurations, featuring slightly different miniaturized fiber-optic confocal microscopes, fitted integrally into the tips of conventional endoscopes. Confocal scanning was performed at 488 nm illumination for excitation of exogenously applied fluorophores (topical acriflavine and intravenous fluorescein). The images were compared with conventional histology of biopsy specimens and the findings of white-light endoscopy. ::: ::: ::: RESULTS ::: Confocal endomicroscopy enabled imaging of cellular and subcellular structures (i.e., nuclei) of the GI tract. The crypts of the colonic mucosa, the villi of the terminal ileum and duodenum, the gastric pits of the stomach, and the squamous epithelium of the distal esophagus could be clearly visualized. Acriflavine strongly contrasted the cell nuclei of the surface epithelium, including the absorptive epithelial cells and the mucous secreting goblet cells. Fluorescein stained the extracellular matrix of the surface epithelium and also the subepithelial layers of the lamina propria. Images at increasing depth beneath the epithelium showed the mucosal capillary network. The findings correlated with the histology of biopsy specimens. ::: ::: ::: CONCLUSIONS ::: The development of a fluorescence confocal endomicroscope makes it practical to examine the upper- and the lower-GI mucosa in cellular detail during otherwise routine endoscopic examination. The results represent a major technical advance in the development of this new optical imaging modality for the in vivo examination of GI tissue.
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paper_title: Ultrasound-Mediated Biophotonic Imaging: A Review of Acousto-Optical Tomography and Photo-Acoustic Tomography

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This article reviews two types of ultrasound-mediated biophotonic imaging–acousto-optical tomography (AOT, also called ultrasound-modulated optical tomography) and photo-acoustic tomography (PAT, also called opto-acoustic or thermo-acoustic tomography)–both of which are based on non-ionizing optical and ultrasonic waves. The goal of these technologies is to combine the contrast advantage of the optical properties and the resolution advantage of ultrasound. In these two technologies, the imaging contrast is based primarily on the optical properties of biological tissues, and the imaging resolution is based primarily on the ultrasonic waves that either are provided externally or produced internally, within the biological tissues. In fact, ultrasonic mediation overcomes both the resolution disadvantage of pure optical imaging in thick tissues and the contrast and speckle disadvantages of pure ultrasonic imaging. In our discussion of AOT, the relationship between modulation depth and acoustic amplitude is clarified. Potential clinical applications of ultrasound-mediated biophotonic imaging include early cancer detection, functional imaging, and molecular imaging.
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paper_title: Quantitative characterization of turbid media using pressure contrast acousto-optic imaging.

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An acousto-optic imaging technique suitable for the local and quantitative determination of subsurface optical properties in turbid media is presented. Acousto-optic signals elicited by ultrasound pulses at two different peak pressures in turbid media are detected by using photorefractive-crystal-based interferometry. The ratio of the measured signals, once calibrated for a particular set of pressure pulses, is found to give a direct measure of the reduced scattering coefficient of the interaction region between the light and sound. Measurements of the reduced scattering coefficient of inclusions buried in diffuse tissue phantoms are demonstrated.
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paper_title: Biomedical Photonics Handbook

paper_content:

Biomedical Diagnostics. Edited by Tuan Vo-Dinh Edited by Tuan VoDinh. CRC Press 20142014. Pages 311–356. Print ISBN: 978-1-42008514-3. eBook ISBN:. Bjorn Kemper is a senior researcher at the Biomedical Technology Center of the Srirang Manohar is an associate professor of biomedical photonic imaging. This volume discusses biomedical photonics, spectroscopy and microscopy, the basic physical principles underlying the technology and its applications.
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paper_title: Comprehensive approach to breast cancer detection using light: photon localization by ultrasound modulation and tissue characterization by spectral discrimination

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A new technique called Ultrasound Tagging of Light (UTL) for imaging breast tissue is described. In this approach, photon localization in turbid tissue is achieved by cross- modulating a laser beam with focussed, pulsed ultrasound. Light which passes through the ultrasound focal spot is `tagged' with the frequency of the ultrasound pulse. The experimental system uses an Argon-Ion laser, a single PIN photodetector, and a 1 MHz fixed-focus pulsed ultrasound transducer. The utility of UTL as a photon localization technique in scattering media is examined using tissue phantoms consisting of gelatin and intralipid. In a separate study, in vivo optical reflectance spectrophotometry was performed on human breast tumors implanted intramuscularly and subcutaneously in nineteen nude mice. The validity of applying a quadruple wavelength breast cancer discrimination metric (developed using breast biopsy specimens) to the in vivo condition was tested. A scatter diagram for the in vivo model tumors based on this metric is presented using as the `normal' controls the hands and fingers of volunteers. Tumors at different growth stages were studied; these tumors ranged in size from a few millimeters to two centimeters. It is expected that when coupled with a suitable photon localization technique like UTL, spectral discrimination methods like this one will prove useful in the detection of breast cancer by non-ionizing means.© (1993) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
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paper_title: Sentinel lymph node detection ex vivo using ultrasound-modulated optical tomography

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We apply ultrasound-modulated optical tomography (UOT) to image ex-vivo methylene-blue-dyed sentinel lymph nodes embedded in 3.2-cm-thick chicken breast tissues. The UOT system is implemented for the first time using ring-shaped light illumination, intense acoustic bursts, and charge-coupled device (CCD) camera-based speckle contrast detection. Since the system is noninvasive, nonionizing, portable, relatively cost effective, and easy to combine with photoacoustic imaging and single element ultrasonic pulse-echo imaging, UOT can potentially be a good imaging modality for the detection of sentinel lymph nodes in breast cancer staging in vivo.
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paper_title: Nonlinear optical endoscopy based on a double-clad photonic crystal fiber and a MEMS mirror

paper_content:

Two-photon fluorescence and second harmonic generation microscopy have enabled functional and morphological in vivo imaging. However, in vivo applications of those techniques to living animals are limited by bulk optics on a bench top. Fortunately, growing functionality of fiber-optic devices and miniaturization of scanning mirrors stimulate the race to develop nonlinear optical endoscopy. In this paper, we report on a prototype of a nonlinear optical endoscope based on a double-clad photonic crystal fiber to improve the detection efficiency and a MEMS mirror to steer the light at the fiber tip. The miniaturized fiber-optic nonlinear microscope is characterized by rat esophagus imaging. Line profiles from the rat tail tendon and esophagus prove the potential of the technology in in vivo applications.
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paper_title: Ultrasonic modulation of scattered light in turbid media and a potential novel tomography in biomedicine.

paper_content:

Ultrasonic modulation of scattered laser light was used to image objects buried in tissue-simulating turbid media. The ultrasonic wave focused into the turbid media modulated the laser light passing through the ultrasonic field. The modulated laser light collected by a photomultiplier tube reflected primarily the local mechanical and optical properties in the zone of ultrasonic modulation. A raster scanning over a heterogeneous turbid medium yielded an image of the medium based on the ultrasound-modulated optical signal. The detectability of modulated signal was estimated using diffusion theory. The dependence of the modulated signal on the off-axis distance of the detector from the optic axis and on the amplitude of ultrasound was studied. The mechanisms of ultrasonic modulation of scattered light are discussed. A theory based on the field autocorrelation function is reviewed as well.
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paper_title: REAL-TIME MONITORING OF HIGH-INTENSITY FOCUSED ULTRASOUND LESION FORMATION USING ACOUSTO-OPTIC SENSING

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Abstract High-intensity focused ultrasound (HIFU) is a promising modality that is used to noninvasively ablate soft tissue tumors. Nevertheless, real-time treatment monitoring with diagnostic ultrasound still poses a significant challenge since tissue necrosis, in the absence of cavitation or boiling, provides little acoustic contrast with normal tissue. In comparison, the optical properties of tissue are significantly altered accompanying lesion formation. A photorefractive crystal-based acousto-optic (AO) sensing system that uses a single HIFU transducer to simultaneously generate tissue necrosis and pump the AO interaction is used to monitor the real-time optical changes associated with thermal lesions induced in chicken breast ex vivo . It is found that the normalized change in AO response increases proportionally with the volume of necrosis. This study demonstrates AO sensing can identify the onset and growth of lesion formation in real time and, when used as feedback to guide exposures, results in more predictable lesion formation. (E-mails: laipuxiang@gmail.com or ronroy@bu.edu )
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paper_title: Ultrasound-modulated optical computed tomography of biological tissues

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An optical imaging technique called ultrasound-modulated optical computed tomography is demonstrated for tomographic imaging of biological tissues. Ultrasound-modulated optical signals are extracted from scattered light to provide projection data for the image reconstruction. A filtered back-projection algorithm is implemented to reconstruct an image reflecting optical tissue properties from angular and linear scans of an ultrasonic beam across a sample. This reconstruction-based imaging technique provides a way to obtain images of cross sections containing the scanned ultrasonic axis in biological tissues, which enables three-dimensional ultrasound-modulated optical imaging. The technique combines the contrast advantage of optical waves and the resolution advantage of ultrasonic waves.
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paper_title: Non invasive local cerebral oxygenation monitoring using a combination of light and ultrasound.

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OBJECTIVES ::: We present a new imaging technology that will allow to obtain three-dimensional maps of oxygen saturation in the brain tissues. This technology is not invasive and not ionizing, and can lead to small, portable device that can be brought to bedside. ::: ::: ::: METHODS ::: The technology uses a combination of near-infrared laser light and ultrasound. Like for other near-infrared spectroscopy techniques, light gives the information on the hemoglobin species present in the tissues. However, since tissues are turbid media, light alone cannot give precise local information. In the technique that we demonstrate, localization is obtained using a focussed ultrasound that locally shifts the laser wavelength, similarly to laser doppler techniques. The frequency-shifted light can be precisely detected and attributed without ambiguities to a specific location. By scanning the ultrasound focus, we can obtain a mapping of the oxygen saturation. ::: ::: ::: RESULTS ::: We present preliminary results on a phantom showing the detection of an absorbing object buried more than two centimeters within the phantom. Scanning the ultrasound on the phantom allows to determine precisely the object position and absorption. Scattering and absorption parameters of the phantom are similar to the brain's. The probe works in the reflection mode, meaning that no transillumination is needed. The ultrasound frequency is 1.25 MHz, ensuring relatively good ultrasound penetration within the skull. ::: ::: ::: CONCLUSIONS ::: The method is very promising for brain imaging of trauma or tumors. It is particularly suited for monitoring, since the use of the ultrasound removes the well-recognized problem of light propagation in the CSF.
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paper_title: Ultrasound-modulated light tomography assessment of osteoporosis.

paper_content:

We present a preliminary series of clinical experiments showing that ultrasound modulation of light in tissues allows tissue properties to be determined well inside the tissue. In this series of clinical experiments the optical scattering coefficient determined by the optical technique is compared with the bone density obtained by dual x-ray absorption. A correlation of 0.84 (p = 0.005) was found for a limited number of patients, showing the potential of this technique for the assessment of osteoporosis.
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paper_title: Photoacoustic imaging in biomedicine

paper_content:

Photoacoustic imaging is a promising method for visualizing biological tissues with optical absorbers. This article provides an overview of the rapidly developing field of photoacoustic imaging. Photoacoustics, the physical basis of photoacoustic imaging, is analyzed briefly. The merits of photoacoustic technology, compared with optical imaging and ultrasonic imaging, are described. Various imaging techniques are also discussed, including scanning tomography, computed tomography and original detection of photoacoustic imaging. Finally, some biomedical applications of photoacoustic imaging are summarized.
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paper_title: Medical Imaging Techniques Combining Light and Ultrasound

paper_content:

The combination of light and ultrasound can lead to new medical imaging techniques combining the spectroscopic capability of light with the spatial resolution of ultrasound. Spectroscopy can be used to measure blood volume and blood oxygen, but because most biological tissues are highly scattering at optical wavelengths, spatial resolution is poor. Ultrasound provides excellent resolution, but not good soft-tissue contrast. There are many techniques for combining light and ultrasound, but the two discussed in this paper have emerged as having the most promise for medical applications. In the first, optoacoustic imaging, an acoustic pulse is generated by a pulse of laser light, and the detected sound is used to produce an image. In the second, acousto-photonic imaging, ultrasound modulates laser light used for diffusive optical tomography. Both of these techniques show promise for a variety of medical applications.
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paper_title: Prospects of photoacoustic tomography

paper_content:

Commercially available high-resolution three-dimensional optical imaging modalities—including confocal microscopy, two-photon microscopy, and optical coherence tomography—have fundamentally impacted biomedicine. Unfortunately, such tools cannot penetrate biological tissue deeper than the optical transport mean free path (∼1mm in the skin). Photoacoustictomography, which combines strong optical contrast and high ultrasonic resolution in a single modality, has broken through this fundamental depth limitation and achieved superdepth high-resolution optical imaging. In parallel, radio frequency-or microwave-induced thermoacoustic tomography is being actively developed to combine radio frequency or microwave contrast with ultrasonic resolution. In this Vision 20/20 article, the prospects of photoacoustictomography are envisaged in the following aspects: (1) photoacoustic microscopy of optical absorption emerging as a mainstream technology, (2) melanoma detection using photoacoustic microscopy, (3) photoacoustic endoscopy, (4) simultaneous functional and molecular photoacoustictomography, (5) photoacoustictomography of gene expression, (6) Doppler photoacoustictomography for flow measurement, (7) photoacoustictomography of metabolic rate of oxygen, (8) photoacoustic mapping of sentinel lymph nodes, (9) multiscale photoacoustic imagingin vivo with common signal origins, (10) simultaneous photoacoustic and thermoacoustic tomography of the breast, (11) photoacoustic and thermoacoustic tomography of the brain, and (12) low-background thermoacoustic molecular imaging.
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paper_title: Recent advances in diffuse optical imaging

paper_content:

We review the current state-of-the-art of diffuse optical imaging, which is an emerging technique for functional imaging of biological tissue. It involves generating images using measurements of visible or near-infrared light scattered across large (greater than several centimetres) thicknesses of tissue. We discuss recent advances in experimental methods and instrumentation, and examine new theoretical techniques applied to modelling and image reconstruction. We review recent work on in vivo applications including imaging the breast and brain, and examine future challenges.
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paper_title: Endoscopic imaging of angiogenesis in vivo.

paper_content:

Angiogenesis has been reported to be an essential step in the progression and development of carcinomas. Numerous growth factors regulate angiogenesis, however, vascular endothelial growth factor (VEGF) has been reported to be most relevant within this context. 1 The endothelium starts to proliferate, vessels migrate into the tumor, and permeability is increased after the VEGF pathway has been started. VEGF is up-regulated in most carcinomas, and its expression correlates positively with tumor progression and negatively with cancer prognosis. Before a tumor can grow beyond 1–2 mm, it requires blood vessels for nutrients and growth. At this size, the production of VEGF by the tumor results in the “angiogenic switch,” where new vasculature is formed in and around the tumor. 2 Of interest, in the colonic mucosa, angiogenesis has been detected as the earliest sign of neoplasia, and microvessel density increases gradually from low-grade to high-grade neoplasia to cancer. 3 Due to the key role of VEGF in carcinogenesis, several drugs have been developed to inhibit angiogenesis by blocking the VEGF receptor. Recently bevacizumab, a monoclonal antibody to VEGF, has been approved for the treatment of patients with metastatic colorectal cancers.
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paper_title: Ultrasonic tagging of photon paths in scattering media:?parallel speckle modulation processing

paper_content:

Tagging of photon trajectories in scattering media is possible by application of a localized ultrasonic field to the sample and by measurement of the induced speckle modulation. Instead of using a single optical detector, which integrates the signal of many speckle grains, we propose a more efficient detection scheme that uses a CCD camera and parallel lock-in detection to record the full modulation of the speckle. The advantage of this multiplex detection is demonstrated, as well as the imaging capabilities of the process for biological tissues.
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paper_title: Imaging optically scattering objects with ultrasound-modulated optical tomography

paper_content:

We show the feasibility of imaging objects having different optical scattering coefficients relative to the surrounding scattering medium using ultrasound-modulated optical tomography (UOT). While the spatial resolution depends on ultrasound parameters, the image contrast depends on the difference in scattering coefficient between the object and the surrounding medium. Experimental measurements obtained with a CCD-based speckle contrast detection scheme are in agreement with Monte Carlo simulations and analytical calculations. This study complements previous UOT experiments that demonstrated optical absorption contrast.
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paper_title: Computations of the acoustically induced phase shifts of optical paths in acoustophotonic imaging with photorefractive-based detection.

paper_content:

Acoustophotonic imaging uses ultrasound-modulated scattered light to improve the quality of optical imaging in diffusive media. Experiments that use photorefractive-crystal-based detection have shown that there is a large dc shift in the acoustically modulated or ac optical signal, which could be utilized to further improve optical imaging resolution. We report that photon paths in a diffusive medium were generated by a Monte Carlo simulation, and the optical phase shifts of the various photons induced by the presence of a realistic focused ultrasound beam were calculated. Quantities that characterize the ac and dc signal components were evaluated by use of the calculated phase shifts. It was confirmed that the dc component dominates owing to coherent summation of the contributions from all the photons.
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paper_title: Detection of the tagged or untagged photons in acousto-optic imaging of thick highly scattering media by photorefractive adaptive holography

paper_content:

We propose an original adaptive wavefront holographic setup based on the photorefractive effect (PR), to make real-time measurements of acousto-optic signals in thick scattering media, with a high flux collection at high rates for breast tumor detection. We describe here our present state of the art and understanding on the problem of breast imaging with PR detection of the acousto-optic signal.
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paper_title: Ultrasonic modulation of multiply scattered light

paper_content:

We report the first observation of ultrasonic modulation of multiple light scattering speckles. The modulation at ƒa = 2 MHz of the temporal field autocorrelation function 〈E(0)E∗(t)〉 of the light scattered from concentrated aqueous suspensions of polystytrene beads was measured. In addition, when using ƒa = 27 MHz, the light intensity spectra measured with a Fabry-Perot interferometer show four inelastic peaks at ƒa and 2ƒa from the principal Rayleigh peak. The modulation amplitudes obtained from both techniques were found to increase with the ultrasonic amplitude and to vary with the mean free path of light in agreement with our simple model.
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paper_title: Diffusing wave spectroscopy.

paper_content:

We obtain useful information from the intensity autocorrelations of light scattered from systems which exhibit strong multiple scattering. A phenomenological model, which exploits the diffusive nature of the transport of light, is shown to be in excellent agreement with experimental data for several different scattering geometries. The dependence on geometry provides an important experimental control over the time scale probed. We call this technique diffusing wave spectroscopy, and illustrate its utility by studying diffusion in a strongly interacting colloidal glass.
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paper_title: Medical Imaging Techniques Combining Light and Ultrasound

paper_content:

The combination of light and ultrasound can lead to new medical imaging techniques combining the spectroscopic capability of light with the spatial resolution of ultrasound. Spectroscopy can be used to measure blood volume and blood oxygen, but because most biological tissues are highly scattering at optical wavelengths, spatial resolution is poor. Ultrasound provides excellent resolution, but not good soft-tissue contrast. There are many techniques for combining light and ultrasound, but the two discussed in this paper have emerged as having the most promise for medical applications. In the first, optoacoustic imaging, an acoustic pulse is generated by a pulse of laser light, and the detected sound is used to produce an image. In the second, acousto-photonic imaging, ultrasound modulates laser light used for diffusive optical tomography. Both of these techniques show promise for a variety of medical applications.
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paper_title: Acousto-optic tomography with multiply scattered light

paper_content:

We have investigated the modulation of the optical field transmitted through a colloid of polystyrene spheres by a narrow quasi-cw ultrasound beam. Measurements of the scale dependence of the heterodyne modulation signal at the acoustic frequency are obtained for samples that are up to 140 scattering lengths thick. A calculation of the modulation signal predicts the possibility of tomographic imaging, which is confirmed experimentally.
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paper_title: Computations of the acoustically induced phase shifts of optical paths in acoustophotonic imaging with photorefractive-based detection.

paper_content:

Acoustophotonic imaging uses ultrasound-modulated scattered light to improve the quality of optical imaging in diffusive media. Experiments that use photorefractive-crystal-based detection have shown that there is a large dc shift in the acoustically modulated or ac optical signal, which could be utilized to further improve optical imaging resolution. We report that photon paths in a diffusive medium were generated by a Monte Carlo simulation, and the optical phase shifts of the various photons induced by the presence of a realistic focused ultrasound beam were calculated. Quantities that characterize the ac and dc signal components were evaluated by use of the calculated phase shifts. It was confirmed that the dc component dominates owing to coherent summation of the contributions from all the photons.
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paper_title: Signal and noise in ultrasound-modulated optical tomography: a Monte Carlo study

paper_content:

Ultrasound-modulated optical tomography in inhomogeneous scattering media was studied using a Monte Carlo modeling technique. The contributions from two different modulation mechanisms were included in the simulation. The differences between embedded absorption and scattering objects in the ultrasound-modulated optical signals were compared. The effects of neighboring inhomogeneity and background optical properties on the ultrasound-modulated optical signals were also studied. We analyzed the signal-to-noise ratio in the experiment and found that the major noise source is the speckle noise caused by small particle movement within the biological tissue sample. This effect was studied by incorporating a Brownian motion factor in the simulation.
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paper_title: In vivo demonstration of the ultrasound-modulated light technique.

paper_content:

We present, to our knowledge for the first time, results of ultrasound-modulated light signals on living tissues. In particular, we analyze, both theoretically and experimentally, the effect of speckle fluctuations on the signal. We find that two different kinds of noise compete--shot noise and speckle noise--and are present at different levels in static phantoms and ex vivo tissue samples on the one hand and in dynamic phantoms and living tissues on the other hand.
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paper_title: Mechanisms of ultrasonic modulation of multiply scattered coherent light: an analytic model.

paper_content:

An analytic model of the ultrasonic modulation of multiply scattered coherent light in scattering media is developed based on two mechanisms: the ultrasonic modulation of the index of refraction and the ultrasonic modulation of the displacements of Rayleigh scatterers. In water solutions, for example, the first mechanism is slightly less important than the second mechanism when the scattering mean free path is less than a critical fraction (0.0890) of the acoustic wavelength, and it becomes increasingly more important beyond this point. This model agrees well with an independent Monte Carlo model.
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paper_title: Mechanisms of ultrasonic modulation of multiply scattered coherent light: a Monte Carlo model

paper_content:

A Monte Carlo model of the ultrasonic modulation of multiply scattered coherent light in scattering media is provided. The model is based on two mechanisms: the ultrasonic modulation of the index of refraction, which causes a modulation of the optical path lengths between consecutive scattering events, and the ultrasonic modulation of the displacements of scatterers, which causes a modulation of optical path lengths with each scattering event. Multiply scattered light accumulates modulated optical path lengths along its path. Consequently, the intensity of the speckles that are formed by the multiply scattered light is modulated. The contribution from the index of refraction is comparable with the contribution from displacement when the acoustic-wave vector is less than a critical fraction of the transport mean free path and becomes increasingly greater than the contribution from displacement beyond this critical point. This Monte Carlo model agrees well with an independent analytical model for isotropically scattering media. Both mechanisms are coherent phenomena, requiring the use of a coherent light source.
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paper_title: Doppler effect's contribution to ultrasonic modulation of multiply scattered coherent light: Monte Carlo modeling.

paper_content:

Modulation of light by ultrasound in turbid media is investigated by modified public domain software based on the Monte Carlo algorithm. Apart from the recognized modulation mechanisms, originating in scatterers' displacements and refractive index modulation, an additional mechanism, evolving from Doppler shift during photon scattering, is considered. Comparison of the relative contributions from all three mechanisms to light modulation by ultrasound is performed for different medium scattering properties and ultrasound frequencies. Refractive index modulation remains the strongest mechanism for light modulation by ultrasound, but for high ultrasound frequencies and for large scattering coefficients the Doppler effect can become dominant.
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paper_title: Parallel detection of amplitude-modulated, ultrasound-modulated optical signals

paper_content:

We investigated the effect of amplitude-modulated (AM) ultrasound (US) on acousto-optic (AO) signals. A phantom was exposed to both AM US and a green laser, and CCD measurements of speckle contrast were made with various exposure times. The results show that the AO signal oscillates at the AM frequency when the CCD exposure time is a fraction of the AM period and stops oscillating when the CCD exposure time is a multiple of the AM period. The AO signal decreases quickly as the AM frequency increases or peak–peak (pk–pk) amplitude decreases. With 4ms exposure time, 250Hz AM frequency and 1.27MPa pk–pk acoustic pressure, there is an ~30% increase in the AO signal compared with that of CW US. The increase in the signal is likely to be due to the particle oscillation and the induced shear wave as a result of the radiation force generated by the AM US.
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paper_title: Fast Monte Carlo simulations of ultrasound-modulated light using a graphics processing unit.

paper_content:

Ultrasound-modulated optical tomography (UOT) is based on "tagging" light in turbid media with focused ultrasound. In comparison to diffuse optical imaging, UOT can potentially offer a better spatial resolution. The existing Monte Carlo (MC) model for simulating ultrasound-modulated light is central processing unit (CPU) based and has been employed in several UOT related studies. We reimplemented the MC model with a graphics processing unit [(GPU), Nvidia GeForce 9800] that can execute the algorithm up to 125 times faster than its CPU (Intel Core Quad) counterpart for a particular set of optical and acoustic parameters. We also show that the incorporation of ultrasound propagation in photon migration modeling increases the computational time considerably, by a factor of at least 6, in one case, even with a GPU. With slight adjustment to the code, MC simulations were also performed to demonstrate the effect of ultrasonic modulation on the speckle pattern generated by the light model (available as animation). This was computed in 4 s with our GPU implementation as compared to 290 s using the CPU.
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paper_title: Theoretical and experimental studies of ultrasound-modulated optical tomography in biological tissue.

paper_content:

Ultrasound-modulated optical tomography in biological tissue was studied both theoretically and experimentally. An ultrasonic beam was focused into biological tissue samples to modulate the laser light passing through the ultrasonic beam inside the tissue. The ultrasound-modulated laser light reflects the local optical and mechanical properties in the ultrasonic beam and permits tomographic imaging of biological tissues by scanning. Parallel detection of the speckle field formed by the transmitted laser light was implemented with the source-synchronous-illumination lock-in technique to improve the signal-to-noise ratio. Two-dimensional images of biological tissues were successfully obtained experimentally with a laser beam at either normal or oblique incidence, which showed that ultrasound-modulated optical tomography depends on diffuse light rather than on ballistic light. Monte Carlo simulations showed that the modulation depth decreased much more slowly than the diffuse transmittance, which indicated the possibility that even thicker biological tissues can be imaged with this technique.
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paper_title: Modulation of multiply scattered coherent light by ultrasonic pulses: an analytical model.

paper_content:

We present an analytical solution for the acousto-optical modulation of multiply scattered light in a medium irradiated with a train of ultrasound pulses. Previous theory is extended to cases where the ultrasound-induced optical phase increments between the different scattering events are strongly correlated, and it is shown that the approximate similarity relation still holds. The relation between the ultrasound induced motions of the background fluid and the optical scatterers is generalized, and it is shown that correlation exists between the optical phase increments that are due to the scatterer movement and the optical phase increments that are due to the modulation of the optical index of refraction. Finally, it is shown that compared with the spectrum of ultrasound pulses, the power spectral density of acousto-optically modulated light is strongly attenuated at the higher ultrasound frequencies.
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paper_title: Correlation transfer equation for multiply scattered light modulated by an ultrasonic pulse.

paper_content:

We develop a temporal correlation transfer equation (CTE) and a Monte Carlo algorithm (MC) for multiply scattered light modulated by an ultrasonic pulse propagating in an optically scattering medium, where the ultrasound field can be nonuniform and the medium can have spatially heterogeneous distribution of optical parameters. The CTE and MC can be used to obtain the time-varying specific intensity and the spatial distribution of the time-dependent power spectral density, respectively, of ultrasound-modulated light. We expect the CTE and MC to be applicable for estimation of contrast and resolution in a wide spectrum of conditions in ultrasound-modulated optical tomography of soft biological tissues.
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paper_title: Heterodyne detection of multiply scattered monochromatic light with a multipixel detector

paper_content:

A new technique is presented for measuring the spectral broadening of light that has been multiply scattered from scatterers in motion. In our method the scattered light is detected by a heterodyne receiver that uses a CCD as a multipixel detector. We obtain the frequency spectrum of the scattered light by sweeping the heterodyne local oscillator frequency. Our detection scheme combines a high optical etendue (product of the surface by the detection solid angle) with an optimal detection of the scattered photons (shot noise). Using this technique, we measure, in vivo, the frequency spectrum of the light scattered through the breast of a female volunteer.
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paper_title: Correlation transfer and diffusion of ultrasound-modulated multiply scattered light

paper_content:

We develop a temporal correlation transfer equation (CTE) and a temporal correlation diffusion equation (CDE) for ultrasound-modulated multiply scattered light, which can be used to calculate the ultrasound-modulated optical intensity in an optically scattering medium with a nonuniform ultrasound field and a heterogeneous distribution of optical parameters. We present an analytical solution based on the CDE for scattering of the temporal autocorrelation function from a cylinder of ultrasound in an optically scattering slab. The CDE is valid for moderate ultrasound pressures on a scale comparable with the optical transport mean free path, which must be greater than the ultrasound wavelength and smaller than or comparable to the sizes of both ultrasonic and optical inhomogeneities. These equations should be applicable to a wide spectrum of conditions for ultrasound-modulated optical tomography of soft biological tissues.
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paper_title: Acousto-optic tomography using amplitude-modulated focused ultrasound and a near-IR laser

paper_content:

A novel tomographic method that can be applied in strongly scattering optical media is proposed. 1-MHz focused ultrasound is used to tag the scattering photons in the biological tissue; it carries a 10-KHz sinusoidal wave to act as a detection wave through amplitude-modulation (AM). The scattering photons that come from the focused zone carry the modulated information. Their optoelectronic signal is demodulated by real-time FFT. By detecting and discriminating ultrasound-modulated information carried by scattered photons, the optical tomographic images of the media simulating biological tissue and of a buried object are reconstructed by the AM spectral intensity. This ultrasound-tagged optical tomography can be applied to tissue structures with different optical parameters. For the first time, by using this method, we obtained the tomographic image of a 5 mm-wide soft rubber cube buried in a biological tissue-simulating media with a detecting depth of 30 mm.
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paper_title: Multi-optical-wavelength ultrasound-modulated optical tomography: a phantom study

paper_content:

We used multiple optical wavelengths to study ultrasound-modulated optical tomography (UOT) in tissue phantoms. By using intense acoustic bursts and a CCD camera-based speckle contrast detection technique, we observed variations of the ultrasound-modulated signal at various optical absorptions. The experimental variations were found to be highly correlated with predictions from Monte Carlo simulations. By irradiating the sample at two optical wavelengths, we quantitatively estimated the total concentration and the concentration ratio of double dyes in objects embedded in tissue phantoms. The results suggest that UOT can potentially provide noninvasive functional imaging of the total concentration and oxygen saturation of hemoglobin in biological tissue.
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paper_title: Ultrasound-modulated optical imaging using a powerful long pulse laser

paper_content:

Ultrasound-modulated optical imaging (or tomography) is an emerging biodiagnostic technique which provides the optical spectroscopic signature and the localization of an absorbing object embedded in a strongly scattering medium. We propose to improve the sensitivity of the technique by using a pulsed single-frequency laser to raise the optical peak power applied to the scattering medium and thereby collect more ultrasonically tagged photons. Moreover, when the detection of tagged photons is done with a photorefractive interferometer, the high optical peak power reduces the response time of the photorefractive crystal below the speckle field decorrelation time. Results obtained with a GaAs photorefractive interferometer are presented for 30- and 60-mm thick scattering media.
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paper_title: Millimeter-resolution acousto-optic quantitative imaging in a tissue model system

paper_content:

We have investigated the application of ultrasound modulated coherent light for quantitative determination of the ratio of dye concentrations and total concentration of absorbers in a blood vessel–mimicking sample. A 3-mm-diam tube containing the mixture of dyes inside an Intralipid-based gel with optical properties similar to tissue was interrogated by two different laser wavelengths in combination with intense microsecond ultrasound bursts. The use of calibration curves allowed us to extract quantitative information on the ratio of dye concentrations with the accuracy of better than 15%, as well as on the total concentration. Furthermore, we demonstrated the feasibility to obtain a quantitative 3-D map of the absorbing structure with a spatial resolution of better than 3 mm. These findings give an outlook to apply this technique for noninvasive 3-D mapping of oxygen saturation and total concentration of hemoglobin in tissue
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paper_title: Optical cross-sectional imaging with pulse ultrasound wave assistance

paper_content:

We have developed an optical cross-sectional imaging method for turbid media with the aid of a pulse ultrasound wave. Observation of deep regions in turbid media, such as tissue samples, is difficult owing to the rapid dispersion of an incoming laser beam by scattering. A pulse ultrasound wave, which is less scattered in tissues, can indicate the measuring point on the basis of the change of the optical scattering properties in a localized region. A depth-resolving capability can be achieved from the time-dependent measurement of the scattered-light intensity as the pulse ultrasound wave propagates in the sample. We verified the method by observing absorptive objects embedded in silicone rubber and by obtaining the cross-sectional image of an absorbing object surrounded by a strong scattering medium.
---
paper_title: Continuous-wave ultrasonic modulation of scattered laser light to image objects in turbid media

paper_content:

Continuous-wave ultrasonic modulation of scattered laser light has been used to image objects in tissue-simulating turbid media for what is to our knowledge the first time. The ultrasound wave focused into the turbid media modulates the laser light passing through the ultrasonic focal zone. The modulated laser light collected by a photomultiplier tube reflects the local mechanical and optical properties in the focal zone. Buried objects are located with millimeter resolution by scanning and detecting alterations of the modulated optical signal. This technique has the potential to provide a noninvasive, nonionizing, inexpensive diagnostic tool for diseases such as breast cancer.
---
paper_title: Transmission- and side-detection configurations in ultrasound-modulated optical tomography of thick biological tissues

paper_content:

Ultrasound-modulated optical tomography of thick biological tissues was studied based on speckle-contrast detection. Speckle decorrelation was investigated with biological tissue samples of various thicknesses. Images of optically absorbing objects buried in biological tissue samples with thicknesses up to 50 mm were obtained in a transmission-detection configuration. The image contrast was more than 30%, and the spatial resolution was approximately 2 mm. In addition, a side-detection scheme along with two specific configurations were examined, and the advantages were demonstrated. Experimental results implied feasibility of applying the ultrasound-modulation technique to characterize optical properties in inhomogeneous biological tissues.
---
paper_title: Ultrasound tagged light imaging in turbid media in a reflectance geometry.

paper_content:

A combination of light and focused ultrasound waves provides a unique way to obtain directly three-dimensional absorption data in a turbid medium. We present the combination of an ultrasound wave and light in which both the input and the output optodes are on the same side of the sample (reflectance geometry). This technique permits local detection in depth of the presence of a purely absorbing object, without further mathematical processing. It is a promising technique for medical imaging and monitoring of tissues.
---
paper_title: Theoretical and experimental studies of ultrasound-modulated optical tomography in biological tissue.

paper_content:

Ultrasound-modulated optical tomography in biological tissue was studied both theoretically and experimentally. An ultrasonic beam was focused into biological tissue samples to modulate the laser light passing through the ultrasonic beam inside the tissue. The ultrasound-modulated laser light reflects the local optical and mechanical properties in the ultrasonic beam and permits tomographic imaging of biological tissues by scanning. Parallel detection of the speckle field formed by the transmitted laser light was implemented with the source-synchronous-illumination lock-in technique to improve the signal-to-noise ratio. Two-dimensional images of biological tissues were successfully obtained experimentally with a laser beam at either normal or oblique incidence, which showed that ultrasound-modulated optical tomography depends on diffuse light rather than on ballistic light. Monte Carlo simulations showed that the modulation depth decreased much more slowly than the diffuse transmittance, which indicated the possibility that even thicker biological tissues can be imaged with this technique.
---
paper_title: Detection of inhomogeneities with ultrasound tagging of light

paper_content:

Ultrasound modulated light for optical tomography is very useful, since it can provide three-dimensional data with minimal mathematical processing. Although several experimental studies have shown the potential of this method, the link between the ultrasound location and the modulated signal intensity at the detector is not yet fully understood. We derive an analytical formula relating the position of the ultrasound transducer and the optical signal at the detector. We also derive an expression for the signal-to-shot-noise ratio as a function of the transducer position. We show that in certain conditions this ratio is only slowly decreasing as a function of the light penetration depth, which makes this technique attractive for optical tomography.
---
paper_title: Ultrasonic tagging of photon paths in scattering media:?parallel speckle modulation processing

paper_content:

Tagging of photon trajectories in scattering media is possible by application of a localized ultrasonic field to the sample and by measurement of the induced speckle modulation. Instead of using a single optical detector, which integrates the signal of many speckle grains, we propose a more efficient detection scheme that uses a CCD camera and parallel lock-in detection to record the full modulation of the speckle. The advantage of this multiplex detection is demonstrated, as well as the imaging capabilities of the process for biological tissues.
---
paper_title: Ultrasound-modulated optical tomography of absorbing objects buried in dense tissue-simulating turbid media.

paper_content:

Continuous-wave ultrasonic modulation of scattered laser light was used to image objects buried in tissue-simulating turbid media. The buried object had an absorption coefficient greater than the background turbid medium. The ultrasonic wave that was focused into the turbid media modulated the laser light that passed through the ultrasonic field. The modulated laser light that was collected by a photomultiplier tube reflected the local mechanical and optical properties in the zone of ultrasonic modulation. Objects buried in the middle plane of 5-cm-thick dense turbid media were imaged with millimeter resolution through the scanning and detecting alterations of the ultrasound-modulated optical signal. The optical properties of the dense turbid media included an absorption coefficient of 0.1 cm(-1) and a reduced scattering coefficient of 10 cm(-1) and were comparable with those of biological tissues in the visible and near-IR ranges. The dependence of the ultrasound-modulated optical signal on the off-axis distance of the detector from the optic axis and the area of the detector was studied as well.
---
paper_title: Comprehensive approach to breast cancer detection using light: photon localization by ultrasound modulation and tissue characterization by spectral discrimination

paper_content:

A new technique called Ultrasound Tagging of Light (UTL) for imaging breast tissue is described. In this approach, photon localization in turbid tissue is achieved by cross- modulating a laser beam with focussed, pulsed ultrasound. Light which passes through the ultrasound focal spot is `tagged' with the frequency of the ultrasound pulse. The experimental system uses an Argon-Ion laser, a single PIN photodetector, and a 1 MHz fixed-focus pulsed ultrasound transducer. The utility of UTL as a photon localization technique in scattering media is examined using tissue phantoms consisting of gelatin and intralipid. In a separate study, in vivo optical reflectance spectrophotometry was performed on human breast tumors implanted intramuscularly and subcutaneously in nineteen nude mice. The validity of applying a quadruple wavelength breast cancer discrimination metric (developed using breast biopsy specimens) to the in vivo condition was tested. A scatter diagram for the in vivo model tumors based on this metric is presented using as the `normal' controls the hands and fingers of volunteers. Tumors at different growth stages were studied; these tumors ranged in size from a few millimeters to two centimeters. It is expected that when coupled with a suitable photon localization technique like UTL, spectral discrimination methods like this one will prove useful in the detection of breast cancer by non-ionizing means.© (1993) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
---
paper_title: Continuous-wave ultrasonic modulation of scattered laser light to image objects in turbid media

paper_content:

Continuous-wave ultrasonic modulation of scattered laser light has been used to image objects in tissue-simulating turbid media for what is to our knowledge the first time. The ultrasound wave focused into the turbid media modulates the laser light passing through the ultrasonic focal zone. The modulated laser light collected by a photomultiplier tube reflects the local mechanical and optical properties in the focal zone. Buried objects are located with millimeter resolution by scanning and detecting alterations of the modulated optical signal. This technique has the potential to provide a noninvasive, nonionizing, inexpensive diagnostic tool for diseases such as breast cancer.
---
paper_title: Theoretical and experimental studies of ultrasound-modulated optical tomography in biological tissue.

paper_content:

Ultrasound-modulated optical tomography in biological tissue was studied both theoretically and experimentally. An ultrasonic beam was focused into biological tissue samples to modulate the laser light passing through the ultrasonic beam inside the tissue. The ultrasound-modulated laser light reflects the local optical and mechanical properties in the ultrasonic beam and permits tomographic imaging of biological tissues by scanning. Parallel detection of the speckle field formed by the transmitted laser light was implemented with the source-synchronous-illumination lock-in technique to improve the signal-to-noise ratio. Two-dimensional images of biological tissues were successfully obtained experimentally with a laser beam at either normal or oblique incidence, which showed that ultrasound-modulated optical tomography depends on diffuse light rather than on ballistic light. Monte Carlo simulations showed that the modulation depth decreased much more slowly than the diffuse transmittance, which indicated the possibility that even thicker biological tissues can be imaged with this technique.
---
paper_title: High-resolution ultrasound-modulated optical tomography in biological tissues

paper_content:

We present a novel implementation of high-resolution ultrasound-modulated optical tomography that, based on optical contrast, can image several millimeters deep into soft biological tissues. A long-cavity confocal Fabry-Perot interferometer, which provides a large etendue and a short response time, was used to detect the ultrasound-modulated coherent light that traversed the scattering biological tissue. Using 15-MHz ultrasound, we imaged with high-contrast light-absorbing structures placed >3 mm below the surface of chicken breast tissue. The resolution along the axial and the lateral directions with respect to the ultrasound propagation direction was better than 70 and 120 microm, respectively. The resolution can be scaled down further by use of higher ultrasound frequencies. This technology is complementary to other imaging technologies, such as confocal microscopy and optical-coherence tomography, and has the potential for broad biomedical applications.
---
paper_title: Acousto-optic tomography with multiply scattered light

paper_content:

We have investigated the modulation of the optical field transmitted through a colloid of polystyrene spheres by a narrow quasi-cw ultrasound beam. Measurements of the scale dependence of the heterodyne modulation signal at the acoustic frequency are obtained for samples that are up to 140 scattering lengths thick. A calculation of the modulation signal predicts the possibility of tomographic imaging, which is confirmed experimentally.
---
paper_title: Ex vivo blood vessel imaging using ultrasound-modulated optical microscopy

paper_content:

Recently we developed ultrasound-modulated optical microscopy (UOM) based on a long-cavity confocal Fabry-Perot interferometer (CFPI). This interferometer is used for real-time detection of multiply scattered light modulated by high frequency (30to75MHz) ultrasound pulses propagating in an optically, strongly scattering medium. In this work, we use this microscope to study the dependence of ultrasound-modulated optical signals on the optical absorption and scattering properties of objects embedded about 3mm deep in tissue mimicking phantoms. These results demonstrate that UOM has the potential to map both optical absorption and scattering contrast. Most importantly, for the first time in the field of ultrasound-modulated optical imaging, we image blood vasculature in highly scattering tissue samples from a mouse and a rat. Therefore, UOM could be a promising tool to study the morphology of blood vasculature and blood-associated functional parameters, such as oxygen saturation.
---
paper_title: Sentinel lymph node detection ex vivo using ultrasound-modulated optical tomography

paper_content:

We apply ultrasound-modulated optical tomography (UOT) to image ex-vivo methylene-blue-dyed sentinel lymph nodes embedded in 3.2-cm-thick chicken breast tissues. The UOT system is implemented for the first time using ring-shaped light illumination, intense acoustic bursts, and charge-coupled device (CCD) camera-based speckle contrast detection. Since the system is noninvasive, nonionizing, portable, relatively cost effective, and easy to combine with photoacoustic imaging and single element ultrasonic pulse-echo imaging, UOT can potentially be a good imaging modality for the detection of sentinel lymph nodes in breast cancer staging in vivo.
---
paper_title: Optical detection of ultrasound at a distance using a confocal Fabry–Perot interferometer

paper_content:

A novel scheme to detect ultrasonic motion at the surface of a solid sample is presented. The surface of the sample is illuminated by a laser and the light scattered by the surface is received by a confocal Fabry–Perot interferometer which demodulates the Doppler shift produced by ultrasound. Experimental results, obtained at a distance of 1.5 m from a machined but not polished steel plate, and excited by ultrasound produced by a laser pulse, are presented.
---
paper_title: Ultrasound-modulated optical microscopy.

paper_content:

We demonstrate that microscopic imaging is feasible in ultrasound-modulated optical tomography (UOT) of soft biological tissues, using a high-frequency focused ultrasound transducer with a 75-MHz central frequency. Our experiments in tissue mimicking phantoms show that at an imaging depth of about 2 mm, an axial resolution better than 30 microm can be achieved, whereas the lateral resolution is 38 microm. A long-cavity scanning confocal Fabry-Perot interferometer (CFPI) is used for real-time detection of multiply scattered light modulated by high-frequency ultrasound pulses propagating in an optically scattering medium. We also compare the performances of various high-frequency focused ultrasound transducers with central frequencies of 15 MHz, 30 MHz, 50 MHz, and 75 MHz. The comparison is based on two-dimensional (2-D) images of optically absorbing objects positioned at a few millimeters depth below the surface of both optically scattering phantoms and soft biological tissue samples. Our experimental results show that modulation depth and image contrast decrease with an increase in ultrasound frequency. In addition, we use analytical calculations to show that modulation depth decreases with increasing ultrasound frequency.
---
paper_title: High-resolution ultrasound-modulated optical tomography in biological tissues

paper_content:

We present a novel implementation of high-resolution ultrasound-modulated optical tomography that, based on optical contrast, can image several millimeters deep into soft biological tissues. A long-cavity confocal Fabry-Perot interferometer, which provides a large etendue and a short response time, was used to detect the ultrasound-modulated coherent light that traversed the scattering biological tissue. Using 15-MHz ultrasound, we imaged with high-contrast light-absorbing structures placed >3 mm below the surface of chicken breast tissue. The resolution along the axial and the lateral directions with respect to the ultrasound propagation direction was better than 70 and 120 microm, respectively. The resolution can be scaled down further by use of higher ultrasound frequencies. This technology is complementary to other imaging technologies, such as confocal microscopy and optical-coherence tomography, and has the potential for broad biomedical applications.
---
paper_title: Pulsed ultrasound-modulated optical tomography using spectral-hole burning as a narrowband spectral filter

paper_content:

We applied a submegahertz nonlinear optical filter afforded by a cryogenically cooled spectral-hole burning crystal to ultrasound-modulated optical tomography. Our experimental results show that this technique, having the largest etendue among all available ultrasound-modulated optical tomography techniques and being immune to speckle decorrelation, offers potential for imaging in vivo and forming high resolution optical tomograms in real time. It opens an opportunity for the development of a clinically applicable high resolution optical imaging modality.
---
paper_title: Detection of ultrasound-modulated diffuse photons using spectral-hole burning

paper_content:

The lack of efficient detection techniques has so far prevented ultrasound-modulated optical tomography from achieving maturity. By applying a quantum spectral filter based on spectral-hole burning, one modulation sideband of the ultrasound-modulated diffuse photons can be efficiently selected while the DC and the other sidebands are blocked. This technique features a large etendue as well as the capability of processing numerous speckles in parallel. It is also immune to speckle decorrelation, potentially allowing real-time in vivo imaging. Both theory and experiments are presented.
---
paper_title: Shot-noise detection of ultrasound-tagged photons in ultrasound-modulated optical imaging

paper_content:

We propose a new detection method for ultrasound-modulated optical tomography that allows us to perform parallel speckle detection with optimum shot-noise sensitivity, using a CCD camera. Moreover, we show that making use of a spatial filter system allows us to fully filter out speckle decorrelation noise. This method is confirmed by a test experiment
---
paper_title: Acousto-optic tomography with multiply scattered light

paper_content:

We have investigated the modulation of the optical field transmitted through a colloid of polystyrene spheres by a narrow quasi-cw ultrasound beam. Measurements of the scale dependence of the heterodyne modulation signal at the acoustic frequency are obtained for samples that are up to 140 scattering lengths thick. A calculation of the modulation signal predicts the possibility of tomographic imaging, which is confirmed experimentally.
---
paper_title: Ultrasound-modulated optical tomography of absorbing objects buried in dense tissue-simulating turbid media.

paper_content:

Continuous-wave ultrasonic modulation of scattered laser light was used to image objects buried in tissue-simulating turbid media. The buried object had an absorption coefficient greater than the background turbid medium. The ultrasonic wave that was focused into the turbid media modulated the laser light that passed through the ultrasonic field. The modulated laser light that was collected by a photomultiplier tube reflected the local mechanical and optical properties in the zone of ultrasonic modulation. Objects buried in the middle plane of 5-cm-thick dense turbid media were imaged with millimeter resolution through the scanning and detecting alterations of the ultrasound-modulated optical signal. The optical properties of the dense turbid media included an absorption coefficient of 0.1 cm(-1) and a reduced scattering coefficient of 10 cm(-1) and were comparable with those of biological tissues in the visible and near-IR ranges. The dependence of the ultrasound-modulated optical signal on the off-axis distance of the detector from the optic axis and the area of the detector was studied as well.
---
paper_title: Ultrasonic modulation of multiply scattered light

paper_content:

We report the first observation of ultrasonic modulation of multiple light scattering speckles. The modulation at ƒa = 2 MHz of the temporal field autocorrelation function 〈E(0)E∗(t)〉 of the light scattered from concentrated aqueous suspensions of polystytrene beads was measured. In addition, when using ƒa = 27 MHz, the light intensity spectra measured with a Fabry-Perot interferometer show four inelastic peaks at ƒa and 2ƒa from the principal Rayleigh peak. The modulation amplitudes obtained from both techniques were found to increase with the ultrasonic amplitude and to vary with the mean free path of light in agreement with our simple model.
---
paper_title: Theoretical and experimental studies of ultrasound-modulated optical tomography in biological tissue.

paper_content:

Ultrasound-modulated optical tomography in biological tissue was studied both theoretically and experimentally. An ultrasonic beam was focused into biological tissue samples to modulate the laser light passing through the ultrasonic beam inside the tissue. The ultrasound-modulated laser light reflects the local optical and mechanical properties in the ultrasonic beam and permits tomographic imaging of biological tissues by scanning. Parallel detection of the speckle field formed by the transmitted laser light was implemented with the source-synchronous-illumination lock-in technique to improve the signal-to-noise ratio. Two-dimensional images of biological tissues were successfully obtained experimentally with a laser beam at either normal or oblique incidence, which showed that ultrasound-modulated optical tomography depends on diffuse light rather than on ballistic light. Monte Carlo simulations showed that the modulation depth decreased much more slowly than the diffuse transmittance, which indicated the possibility that even thicker biological tissues can be imaged with this technique.
---
paper_title: Acousto-optic tomography with multiply scattered light

paper_content:

We have investigated the modulation of the optical field transmitted through a colloid of polystyrene spheres by a narrow quasi-cw ultrasound beam. Measurements of the scale dependence of the heterodyne modulation signal at the acoustic frequency are obtained for samples that are up to 140 scattering lengths thick. A calculation of the modulation signal predicts the possibility of tomographic imaging, which is confirmed experimentally.
---
paper_title: Flow visualization by means of single-exposure speckle photography

paper_content:

Abstract A photograph of a flow field is taken under laser illumination. If the exposure is short enough, the velocity distribution in the field will be mapped on the photograph as variations in speckle contrast. These contrast variations can be converted to intensity variations by means of a simple spatial filtering technique, to give a direct picture of the velocity distribution in the flow field. A potential application of this technique to the mapping of retinal blood flow is described.
---
paper_title: Picometric profilometry. II. Multidetector approach and multiplexed lock-in detection

paper_content:

In a first paper [Journal of Optics, vol.25, p.207, 1994] we described a surface profilometer using a single detector and a sample scanning procedure. We have developed a multidetector version of this setup using a CCD linear array (256 pixels) and an original multiplexed lockin detection procedure.
---
paper_title: Ultrasonic tagging of photon paths in scattering media:?parallel speckle modulation processing

paper_content:

Tagging of photon trajectories in scattering media is possible by application of a localized ultrasonic field to the sample and by measurement of the induced speckle modulation. Instead of using a single optical detector, which integrates the signal of many speckle grains, we propose a more efficient detection scheme that uses a CCD camera and parallel lock-in detection to record the full modulation of the speckle. The advantage of this multiplex detection is demonstrated, as well as the imaging capabilities of the process for biological tissues.
---
paper_title: Numerical heterodyne holography with two-dimensional photodetector arrays

paper_content:

We present an original heterodyne holography method for digital holography that relies on two-dimensional heterodyne detection to record the phase and the amplitude of a f ield. The technique has been tested on objects as much as 13 mm in size. Consistency checks were performed, and high-resolution images were computed. We show the requirement for a spatial f ilter to select properly sampled near-axis photons. Heterodyne holography is superior to off-axis digital holography for both f ield of view and resolution.
---
paper_title: Shot-noise detection of ultrasound-tagged photons in ultrasound-modulated optical imaging

paper_content:

We propose a new detection method for ultrasound-modulated optical tomography that allows us to perform parallel speckle detection with optimum shot-noise sensitivity, using a CCD camera. Moreover, we show that making use of a spatial filter system allows us to fully filter out speckle decorrelation noise. This method is confirmed by a test experiment
---
paper_title: Phase-shifting digital holography.

paper_content:

A new method for three-dimensional image formation is proposed in which the distribution of complex amplitude at a plane is measured by phase-shifting interferometry and then Fresnel transformed by a digital computer. The method can reconstruct an arbitrary cross section of a three-dimensional object with higher image quality and a wider viewing angle than from conventional digital holography using an off-axis configuration. Basic principles and experimental verification are described.
---
paper_title: Shot-noise detection of ultrasound-tagged photons in ultrasound-modulated optical imaging

paper_content:

We propose a new detection method for ultrasound-modulated optical tomography that allows us to perform parallel speckle detection with optimum shot-noise sensitivity, using a CCD camera. Moreover, we show that making use of a spatial filter system allows us to fully filter out speckle decorrelation noise. This method is confirmed by a test experiment
---
paper_title: Pulsed ultrasound-modulated optical tomography using spectral-hole burning as a narrowband spectral filter

paper_content:

We applied a submegahertz nonlinear optical filter afforded by a cryogenically cooled spectral-hole burning crystal to ultrasound-modulated optical tomography. Our experimental results show that this technique, having the largest etendue among all available ultrasound-modulated optical tomography techniques and being immune to speckle decorrelation, offers potential for imaging in vivo and forming high resolution optical tomograms in real time. It opens an opportunity for the development of a clinically applicable high resolution optical imaging modality.
---
paper_title: Computations of the acoustically induced phase shifts of optical paths in acoustophotonic imaging with photorefractive-based detection.

paper_content:

Acoustophotonic imaging uses ultrasound-modulated scattered light to improve the quality of optical imaging in diffusive media. Experiments that use photorefractive-crystal-based detection have shown that there is a large dc shift in the acoustically modulated or ac optical signal, which could be utilized to further improve optical imaging resolution. We report that photon paths in a diffusive medium were generated by a Monte Carlo simulation, and the optical phase shifts of the various photons induced by the presence of a realistic focused ultrasound beam were calculated. Quantities that characterize the ac and dc signal components were evaluated by use of the calculated phase shifts. It was confirmed that the dc component dominates owing to coherent summation of the contributions from all the photons.
---
paper_title: Detection of ultrasonic motion of a scattering surface by two‐wave mixing in a photorefractive GaAs crystal

paper_content:

The performance of an interferometric system based on two‐wave mixing at 1.06 μm in undoped GaAs crystal, for the remote detection of transient motion of a scattering surface, is described. In this system, the wave scattered by the surface is mixed inside the photorefractive crystal with a pump wave directly derived from the laser to provide the reference wave of the interferometer. The system shows several features appropriate to industrial applications, although its sensitivity is less than passive interferometric systems of the confocal Fabry–Perot type presently in use, except in the low frequency range (below 1 MHz).
---
paper_title: Photorefractive detection of tagged photons in ultrasound modulated optical tomography of thick biological tissues

paper_content:

We present a new and simple method to obtain ultrasound modulated optical tomography images in thick biological tissues with the use of a photorefractive crystal. The technique offers the advantage of spatially adapting the output speckle wavefront by analysing the signal diffracted by the interference pattern between this output field and a reference beam, recorded inside the photorefractive crystal. Averaging out due to random phases of the speckle grains vanishes, and we can use a fast single photodetector to measure the ultrasound modulated optical contrast. This technique offers a promising way to make direct measurements within the decorrelation time scale of living tissues.
---
paper_title: Detection of the tagged or untagged photons in acousto-optic imaging of thick highly scattering media by photorefractive adaptive holography

paper_content:

We propose an original adaptive wavefront holographic setup based on the photorefractive effect (PR), to make real-time measurements of acousto-optic signals in thick scattering media, with a high flux collection at high rates for breast tumor detection. We describe here our present state of the art and understanding on the problem of breast imaging with PR detection of the acousto-optic signal.
---
paper_title: Ultrasound-modulated optical imaging using a powerful long pulse laser

paper_content:

Ultrasound-modulated optical imaging (or tomography) is an emerging biodiagnostic technique which provides the optical spectroscopic signature and the localization of an absorbing object embedded in a strongly scattering medium. We propose to improve the sensitivity of the technique by using a pulsed single-frequency laser to raise the optical peak power applied to the scattering medium and thereby collect more ultrasonically tagged photons. Moreover, when the detection of tagged photons is done with a photorefractive interferometer, the high optical peak power reduces the response time of the photorefractive crystal below the speckle field decorrelation time. Results obtained with a GaAs photorefractive interferometer are presented for 30- and 60-mm thick scattering media.
---
paper_title: Theoretical description of the photorefractive detection of the ultrasound modulated photons in scattering media.

paper_content:

Acousto-optic imaging of thick biological tissues can be obtained in real-time with an adaptive-wavefront holographic setup, where the holographic media is a self-developping photorefractive crystal. As a consequence, the interference signal resulting from the acousto-optic effect can be easily collected with a high etendue and fast single photodetector. We present a statistical model of the field propagating through the scattering media and show why the various acoustic frequency components contained in the speckle output pattern are uncorrelated. We then give a detailed description of the signal measured through the photorefractive effect, in order to explain the quadratic pressure response observed for the two commonly used configurations setup e.g an amplitude or a phase modulation of the ultrasound.
---
paper_title: Detection of ultrasound-modulated photons in diffuse media using the photorefractive effect

paper_content:

Ultrasound-modulated optical tomography is a dual-wave sensing technique in which diffusive light in a turbid medium interacts with an imposed acoustic field. A phase-modulated photon field emanates from the interaction region and carries with it information about the optomechanical properties of the medium. We present a technique for detection of ultrasound-induced optical phase modulation using an adaptive, photorefractive-crystal-based interferometry system. Experimental results are presented demonstrating detection of ultrasound-modulated signals in highly scattering media by use of pulsed ultrasound insonation.
---
paper_title: Photorefractive acousto-optic imaging in thick scattering media at 790 nm with a Sn(2)P(2)S(6):Te crystal.

paper_content:

Acousto-optic imaging is based on ultrasound modulation of multiply scattered light in thick media. We experimentally demonstrate the possibility to perform a self-adaptive wavefront holographic detection at 790nm, within the optical therapeutic window where absorption of biological tissues is minimized. A high-gain Te-doped Sn(2)P(2)S(6) crystal is used for this purpose. Optical absorbing objects embedded within a thick scattering phantom are imaged by use of pulsed ultrasound to get a dynamic millimetric axial resolution. Our technique represents an interesting approach for breast cancer detection.
---
paper_title: In situ monitoring of the photorefractive response time in a self-adaptive wavefront holography setup developed for acousto-optic imaging

paper_content:

The measurement of optical contrasts within thick biological tissues can be performed with the hybrid technique of acousto-optic imaging, but it has been shown that an acquisition rate in the 1 - 10kHz range is required for a good efficiency. This comes from the interferometric nature of the signal, blurred by speckle decorrelation in a time τc, due to a decrease of the speckle pattern contrast at the exit of the sample. An holographic setup that associates a fast and large area single photodetector and a photorefractive crystal, can measure in real-time the acousto-optic signal: this is the so-called self-adaptive wavefront holography technique. Nevertheless, it is essential to size the photorefractive response time (τPR) of the crystal with τc in order to optimize the signal-to-noise ratio of the measurement. This time mainly depends on the overall light intensity within the crystal. We have developed an original in situ method to determine τPR with the combination of acoustic pulses and a frequency de-tuning of the reference beam. We can measure precisely this time but also monitor it according to a theoretical model that we have previously described. We are able to adapt the response time of the setup to the decorrelation time of the medium under study.
---
paper_title: Ultrasound-modulated optical tomography of absorbing objects buried in dense tissue-simulating turbid media.

paper_content:

Continuous-wave ultrasonic modulation of scattered laser light was used to image objects buried in tissue-simulating turbid media. The buried object had an absorption coefficient greater than the background turbid medium. The ultrasonic wave that was focused into the turbid media modulated the laser light that passed through the ultrasonic field. The modulated laser light that was collected by a photomultiplier tube reflected the local mechanical and optical properties in the zone of ultrasonic modulation. Objects buried in the middle plane of 5-cm-thick dense turbid media were imaged with millimeter resolution through the scanning and detecting alterations of the ultrasound-modulated optical signal. The optical properties of the dense turbid media included an absorption coefficient of 0.1 cm(-1) and a reduced scattering coefficient of 10 cm(-1) and were comparable with those of biological tissues in the visible and near-IR ranges. The dependence of the ultrasound-modulated optical signal on the off-axis distance of the detector from the optic axis and the area of the detector was studied as well.
---
paper_title: Continuous-wave ultrasonic modulation of scattered laser light to image objects in turbid media

paper_content:

Continuous-wave ultrasonic modulation of scattered laser light has been used to image objects in tissue-simulating turbid media for what is to our knowledge the first time. The ultrasound wave focused into the turbid media modulates the laser light passing through the ultrasonic focal zone. The modulated laser light collected by a photomultiplier tube reflects the local mechanical and optical properties in the focal zone. Buried objects are located with millimeter resolution by scanning and detecting alterations of the modulated optical signal. This technique has the potential to provide a noninvasive, nonionizing, inexpensive diagnostic tool for diseases such as breast cancer.
---
paper_title: Detection and discrimination of optical absorption and shear stiffness at depth in tissue-mimicking phantoms by transient optoelastography

paper_content:

This work investigates the ability of transient optoelastography to detect both shear stiffness contrasts and optical absorption contrasts embedded deep in tissuelike media. The technique consists of a camera-based optical detection scheme designed to detect selectively the transient shear motion created at depth by the acoustic radiation force in optically turbid media. It is demonstrated on tissue-mimicking phantoms that transient optoelastography is not only sensitive to both optical absorption and shear stiffness contrasts, but also provides discrimination between these two types of contrasts.
---
paper_title: Ultrasonic tagging of photon paths in scattering media:?parallel speckle modulation processing

paper_content:

Tagging of photon trajectories in scattering media is possible by application of a localized ultrasonic field to the sample and by measurement of the induced speckle modulation. Instead of using a single optical detector, which integrates the signal of many speckle grains, we propose a more efficient detection scheme that uses a CCD camera and parallel lock-in detection to record the full modulation of the speckle. The advantage of this multiplex detection is demonstrated, as well as the imaging capabilities of the process for biological tissues.
---
paper_title: Frequency-swept ultrasound-modulated optical tomography in biological tissue by use of parallel detection.

paper_content:

A frequency-swept ultrasonic beam was focused into a biological tissue sample to modulate the laser light passing through the ultrasonic beam inside the tissue. Parallel detection of the speckle field formed by the transmitted laser light was implemented with the source-synchronous-illumination lock-in technique to improve the signal-to-noise ratio. The ultrasound-modulated laser light reflects the local optical and mechanical properties in the ultrasonic beam and can be used for tomographic imaging of the tissue. Sweeping the ultrasonic frequency provides spatial resolution along the ultrasonic axis, which is scalable with the frequency span of the sweep. Two-dimensional images of biological tissue with buried objects were successfully obtained experimentally.
---
paper_title: Ultrasound-modulated optical tomography of absorbing objects buried in dense tissue-simulating turbid media.

paper_content:

Continuous-wave ultrasonic modulation of scattered laser light was used to image objects buried in tissue-simulating turbid media. The buried object had an absorption coefficient greater than the background turbid medium. The ultrasonic wave that was focused into the turbid media modulated the laser light that passed through the ultrasonic field. The modulated laser light that was collected by a photomultiplier tube reflected the local mechanical and optical properties in the zone of ultrasonic modulation. Objects buried in the middle plane of 5-cm-thick dense turbid media were imaged with millimeter resolution through the scanning and detecting alterations of the ultrasound-modulated optical signal. The optical properties of the dense turbid media included an absorption coefficient of 0.1 cm(-1) and a reduced scattering coefficient of 10 cm(-1) and were comparable with those of biological tissues in the visible and near-IR ranges. The dependence of the ultrasound-modulated optical signal on the off-axis distance of the detector from the optic axis and the area of the detector was studied as well.
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paper_title: High-contrast fast Fourier transform acousto-optical tomography of phantom tissues with a frequency-chirp modulation of the ultrasound

paper_content:

We report new results on acousto-optical tomography in phantom tissues using a frequency chirp modulation and a CCD camera. This technique allows quick recording of three-dimensional images of the optical contrast with a two-dimensional scan of the ultrasound source in a plane perpendicular to the ultrasonic path. The entire optical contrast along the ultrasonic path is concurrently obtained from the capture of a film sequence at a rate of 200 Hz. This technique reduces the acquisition time, and it enhances the axial resolution and thus the contrast, which are usually poor owing to the large volume of interaction of the ultrasound perturbation.
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paper_title: Ultrasonic modulation of scattered light in turbid media and a potential novel tomography in biomedicine.

paper_content:

Ultrasonic modulation of scattered laser light was used to image objects buried in tissue-simulating turbid media. The ultrasonic wave focused into the turbid media modulated the laser light passing through the ultrasonic field. The modulated laser light collected by a photomultiplier tube reflected primarily the local mechanical and optical properties in the zone of ultrasonic modulation. A raster scanning over a heterogeneous turbid medium yielded an image of the medium based on the ultrasound-modulated optical signal. The detectability of modulated signal was estimated using diffusion theory. The dependence of the modulated signal on the off-axis distance of the detector from the optic axis and on the amplitude of ultrasound was studied. The mechanisms of ultrasonic modulation of scattered light are discussed. A theory based on the field autocorrelation function is reviewed as well.
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paper_title: Optical cross-sectional imaging with pulse ultrasound wave assistance

paper_content:

We have developed an optical cross-sectional imaging method for turbid media with the aid of a pulse ultrasound wave. Observation of deep regions in turbid media, such as tissue samples, is difficult owing to the rapid dispersion of an incoming laser beam by scattering. A pulse ultrasound wave, which is less scattered in tissues, can indicate the measuring point on the basis of the change of the optical scattering properties in a localized region. A depth-resolving capability can be achieved from the time-dependent measurement of the scattered-light intensity as the pulse ultrasound wave propagates in the sample. We verified the method by observing absorptive objects embedded in silicone rubber and by obtaining the cross-sectional image of an absorbing object surrounded by a strong scattering medium.
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paper_title: Ultrasound-modulated optical computed tomography of biological tissues

paper_content:

An optical imaging technique called ultrasound-modulated optical computed tomography is demonstrated for tomographic imaging of biological tissues. Ultrasound-modulated optical signals are extracted from scattered light to provide projection data for the image reconstruction. A filtered back-projection algorithm is implemented to reconstruct an image reflecting optical tissue properties from angular and linear scans of an ultrasonic beam across a sample. This reconstruction-based imaging technique provides a way to obtain images of cross sections containing the scanned ultrasonic axis in biological tissues, which enables three-dimensional ultrasound-modulated optical imaging. The technique combines the contrast advantage of optical waves and the resolution advantage of ultrasonic waves.
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paper_title: Fusion of conventional ultrasound imaging and acousto-optic sensing by use of a standard pulsed-ultrasound scanner

paper_content:

Acousto-optic sensing (AOS) is a dual-wave sensing technique based on the ultrasound modulation of diffuse light in a turbid medium. We experimentally demonstrate the feasibility of combining AOS and conventional ultrasound imaging by use of a commercially available pulsed-ultrasound scanner coupled with a photorefractive crystal-based optical interferometry system. Optically absorbing targets embedded in highly diffusive phantoms (?s?=10?cm?1) are imaged through a thickness of 27?mm with millimeter resolution. The acousto-optic images are intrinsically coregistered with the ultrasound images.
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paper_title: Pulsed acousto-optic imaging in dynamic scattering media with heterodyne parallel speckle detection.

paper_content:

We present a new detection scheme for acousto-optic tomography based on pulsed-wave ultrasound and illumination combined with heterodyne parallel speckle detection. This setup can perform tomographies inside several-centimeter-thick scattering samples. Test experiments confirm the suitability of this method for performing tomographies inside various types of optically scattering media, including liquids.
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paper_title: Continuous-wave ultrasonic modulation of scattered laser light to image objects in turbid media

paper_content:

Continuous-wave ultrasonic modulation of scattered laser light has been used to image objects in tissue-simulating turbid media for what is to our knowledge the first time. The ultrasound wave focused into the turbid media modulates the laser light passing through the ultrasonic focal zone. The modulated laser light collected by a photomultiplier tube reflects the local mechanical and optical properties in the focal zone. Buried objects are located with millimeter resolution by scanning and detecting alterations of the modulated optical signal. This technique has the potential to provide a noninvasive, nonionizing, inexpensive diagnostic tool for diseases such as breast cancer.
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paper_title: Nonlinear effects in acousto-optic imaging.

paper_content:

Acousto-optic (AO) imaging is a promising technique that is able to reveal optical properties in the millimeter range inside scattering media by tagging the photon paths with an ultrasonic beam. To increase both the contrast and the resolution of the AO images, we have explored the possibility of using the nonlinear response of the speckle modulation. Variation of the second-harmonic signal as the square of the ultrasonic amplitude has been found, and strong reduction of the tagged zone size has been demonstrated.
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paper_title: Theoretical and experimental studies of ultrasound-modulated optical tomography in biological tissue.

paper_content:

Ultrasound-modulated optical tomography in biological tissue was studied both theoretically and experimentally. An ultrasonic beam was focused into biological tissue samples to modulate the laser light passing through the ultrasonic beam inside the tissue. The ultrasound-modulated laser light reflects the local optical and mechanical properties in the ultrasonic beam and permits tomographic imaging of biological tissues by scanning. Parallel detection of the speckle field formed by the transmitted laser light was implemented with the source-synchronous-illumination lock-in technique to improve the signal-to-noise ratio. Two-dimensional images of biological tissues were successfully obtained experimentally with a laser beam at either normal or oblique incidence, which showed that ultrasound-modulated optical tomography depends on diffuse light rather than on ballistic light. Monte Carlo simulations showed that the modulation depth decreased much more slowly than the diffuse transmittance, which indicated the possibility that even thicker biological tissues can be imaged with this technique.
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paper_title: Acousto-optic tomography with multiply scattered light

paper_content:

We have investigated the modulation of the optical field transmitted through a colloid of polystyrene spheres by a narrow quasi-cw ultrasound beam. Measurements of the scale dependence of the heterodyne modulation signal at the acoustic frequency are obtained for samples that are up to 140 scattering lengths thick. A calculation of the modulation signal predicts the possibility of tomographic imaging, which is confirmed experimentally.
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paper_title: Acousto-optic tomography using amplitude-modulated focused ultrasound and a near-IR laser

paper_content:

A novel tomographic method that can be applied in strongly scattering optical media is proposed. 1-MHz focused ultrasound is used to tag the scattering photons in the biological tissue; it carries a 10-KHz sinusoidal wave to act as a detection wave through amplitude-modulation (AM). The scattering photons that come from the focused zone carry the modulated information. Their optoelectronic signal is demodulated by real-time FFT. By detecting and discriminating ultrasound-modulated information carried by scattered photons, the optical tomographic images of the media simulating biological tissue and of a buried object are reconstructed by the AM spectral intensity. This ultrasound-tagged optical tomography can be applied to tissue structures with different optical parameters. For the first time, by using this method, we obtained the tomographic image of a 5 mm-wide soft rubber cube buried in a biological tissue-simulating media with a detecting depth of 30 mm.
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paper_title: The role of viscosity in the impulse diffraction field of elastic waves induced by the acoustic radiation force

paper_content:

Several ultrasound-based techniques for the estimation of soft tissue elasticity are currently being investigated. Most of them study the medium response to dynamic excitations. Such responses are usually modeled in a purely elastic medium using a Green's function solution of the motion equation. However, elasticity by itself is not necessarily a discriminant parameter for malignancy diagnosis. Modeling viscous properties of tissues could also be of great interest for tumor characterization. We report in this paper an explicit derivation of the Green's function in a viscous and elastic medium taking into account shear, bulk, and coupling waves. From this theoretical calculation, 3D simulations of mechanical waves in viscoelastic soft tissues are presented. The relevance of the viscoelastic Green's function is validated by comparing simulations with experimental data. The experiments were conducted using the supersonic shear imaging (SSI) technique which dynamically and remotely excites tissues using acoustic radiation force. We show that transient shear waves generated with SSI are modeled very precisely by the Green's function formalism. The combined influences of out-of-plane diffraction, beam shape, and shear viscosity on the shape of transient waves are carefully studied as they represent a major issue in ultrasound-based viscoelasticity imaging techniques.
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paper_title: Ultrasound-stimulated vibro-acoustic spectrography.

paper_content:

An ultrasound method based on radiation force is presented for imaging the acoustic response of a material to mechanical excitation. Acoustic energy was emitted from solids and tissues in response to an oscillatory radiation force produced by interfering focused beams of ultrasound. Frequency spectra of ultrasound-stimulated acoustic emission exhibited object resonances. Raster-scanning the radiation force over the object and recording the amplitude and phase of the emitted sound resulted in data from which images related to the elastic compositions of the acoustically emitting objects could be computed. Acoustic emission signals distinguished tuning-fork resonances, submillimeter glass spheres, and calcification in excised arteries and detected object motions on the order of nanometers.
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paper_title: Assessment of ultrasound modulation of near infrared light on the quantification of scattering coefficient

paper_content:

Purpose: To assess the effect of ultrasound modulation of near infrared (NIR) light on the quantification of scattering coefficient in tissue-mimicking biological phantoms.Methods: A unique method to estimate the phase of the modulated NIR light making use of only time averaged intensity measurements using a charge coupled device camera is used in this investigation. These experimental measurements from tissue-mimicking biological phantoms are used to estimate the differential pathlength, in turn leading to estimation of optical scattering coefficient. A Monte-Carlo model base numerical estimation of phase in lieu of ultrasound modulation is performed to verify the experimental results. Results: The results indicate that the ultrasound modulation of NIR light enhances the effective scattering coefficient. The observed effective scattering coefficient enhancement in tissue-mimicking ::: viscoelastic phantoms increases with increasing ultrasound drive voltage. The same trend is noticed as the ultrasound modulation frequency approaches the natural vibration frequency of the phantom material. The contrast enhancement is less for the stiffer (larger storage modulus) tissue, mimicking tumor necrotic core, compared to the normal tissue. Conclusions: The ultrasound modulation of the insonified region leads to an increase in the effective number of scattering events experienced by NIR light, increasing the measured phase, causing the enhancement in ::: the effective scattering coefficient. The ultrasound modulation of NIR light could provide better estimation of scattering coefficient. The observed local enhancement of the effective scattering coefficient, in the ultrasound focal region, is validated using both experimental measurements and Monte-Carlo simulations. (C) 2010 American Association of Physicists in Medicine. [DOI: 10.1118/1.3456441]
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paper_title: Acoustic radiation force impulse imaging: in vivo demonstration of clinical feasibility.

paper_content:

Abstract The clinical viability of a method of acoustic remote palpation, capable of imaging local variations in the mechanical properties of soft tissue using acoustic radiation force impulse (ARFI) imaging, is investigated in vivo . In this method, focused ultrasound (US) is used to apply localized radiation force to small volumes of tissue (2 mm 3 ) for short durations (less than 1 ms) and the resulting tissue displacements are mapped using ultrasonic correlation-based methods. The tissue displacements are inversely proportional to the stiffness of the tissue and, thus, a stiffer region of tissue exhibits smaller displacements than a more compliant region. Due to the short duration of the force application, this method provides information about the mechanical impulse response of the tissue, which reflects variations in tissue viscoelastic characteristics. In this paper, experimental results are presented demonstrating that displacements on the order of 10 μm can be generated and detected in soft tissues in vivo using a single transducer on a modified diagnostic US scanner. Differences in the magnitude of displacement and the transient response of tissue are correlated with tissue structures in matched B-mode images. The results comprise the first in vivo ARFI images, and support the clinical feasibility of a radiation force-based remote palpation imaging system. (E-mail: kathy.nightingale@duke.edu)
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paper_title: Parallel detection of amplitude-modulated, ultrasound-modulated optical signals

paper_content:

We investigated the effect of amplitude-modulated (AM) ultrasound (US) on acousto-optic (AO) signals. A phantom was exposed to both AM US and a green laser, and CCD measurements of speckle contrast were made with various exposure times. The results show that the AO signal oscillates at the AM frequency when the CCD exposure time is a fraction of the AM period and stops oscillating when the CCD exposure time is a multiple of the AM period. The AO signal decreases quickly as the AM frequency increases or peak–peak (pk–pk) amplitude decreases. With 4ms exposure time, 250Hz AM frequency and 1.27MPa pk–pk acoustic pressure, there is an ~30% increase in the AO signal compared with that of CW US. The increase in the signal is likely to be due to the particle oscillation and the induced shear wave as a result of the radiation force generated by the AM US.
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paper_title: Intense acoustic bursts as a signal-enhancement mechanism in ultrasound-modulated optical tomography

paper_content:

Biophotonic imaging with ultrasound-modulated optical tomography (UOT) promises ultrasonically resolved imaging in biological tissues. A key challenge in this imaging technique is a low signal-to-noise ratio (SNR). We show significant UOT signal enhancement by using intense time-gated acoustic bursts. A CCD camera captured the speckle pattern from a laser-illuminated tissue phantom. Differences in speckle contrast were observed when ultrasonic bursts were applied, compared with when no ultrasound was applied. When CCD triggering was synchronized with burst initiation, acoustic-radiation-force-induced displacements were detected. To avoid mechanical contrast in UOT images, the CCD camera acquisition was delayed several milliseconds until transient effects of acoustic radiation force attenuated to a satisfactory level. The SNR of our system was sufficiently high to provide an image pixel per acoustic burst without signal averaging. Because of the substantially improved SNR, the use of intense acoustic bursts is a promising signal enhancement strategy for UOT.
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paper_title: Transient optoelastography in optically diffusive media

paper_content:

The authors present a camera-based optical detection scheme designed to detect the transient motion created by the acoustic radiation force in soft elastic media. An optically diffusive tissue-mimicking phantom was illuminated with coherent laser light, and a high speed camera (2kHz frame rate) was used to acquire and cross-correlate consecutive speckle patterns. Time-resolved transient decorrelation of the optical speckle was measured as the result of localized motion induced by the radiation force and the associated propagating shear waves. The proposed technique is sensitive only to the low frequency transient motion induced in the medium by the radiation force.
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paper_title: The acoustic radiation force

paper_content:

The physical origin of the radiation force exerted by an ultrasonic beam on an absorbing target is explained. It is shown that the force may have two sources—a nonzero time‐averaged sound pressure in the ultrasonic beam, and the momentum transported by the beam—but that there is a movement of material out of the ultrasonic beam to prevent a nonzero time‐averaged sound pressure from being established. Consequently, the transfer of wave momentum is the sole cause of the force. The assumptions made in evolving this explanation are discussed, and the resulting change in mean density within the ultrasonic beam is considered. It is pointed out that the acoustic radiation force is but one example of a universal phenomenon associated with all forms of wave motion.
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paper_title: Ultrasound-modulated optical tomography with intense acoustic bursts

paper_content:

Ultrasound-modulated optical tomography (UOT) detects ultrasonically modulated light to spatially localize multiply scattered photons in turbid media with the ultimate goal of imaging the optical properties in living subjects. A principal challenge of the technique is weak modulated signal strength. We discuss ways to push the limits of signal enhancement with intense acoustic bursts while conforming to optical and ultrasonic safety standards. A CCD-based speckle-contrast detection scheme is used to detect acoustically modulated light by measuring changes in speckle statistics between ultrasound-on and ultrasound-off states. The CCD image capture is synchronized with the ultrasound burst pulse sequence. Transient acoustic radiation force, a consequence of bursts, is seen to produce slight signal enhancement over pure ultrasonic-modulation mechanisms for bursts and CCD exposure times of the order of milliseconds. However, acoustic radiation-force-induced shear waves are launched away from the acoustic sample volume, which degrade UOT spatial resolution. By time gating the CCD camera to capture modulated light before radiation force has an opportunity to accumulate significant tissue displacement, we reduce the effects of shear-wave image degradation, while enabling very high signal-to-noise ratios. Additionally, we maintain high-resolution images representative of optical and not mechanical contrast. Signal-to-noise levels are sufficiently high so as to enable acquisition of 2D images of phantoms with one acoustic burst per pixel.
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paper_title: Breast lesions: quantitative elastography with supersonic shear imaging--preliminary results.

paper_content:

PURPOSE ::: To determine the appearance of breast lesions at quantitative ultrasonographic (US) elastography by using supersonic shear imaging (SSI) and to assess the correlation between quantitative values of lesion stiffness and pathologic results, which were used as the reference standard. ::: ::: ::: MATERIALS AND METHODS ::: This study was approved by the French National Committee for the Protection of Patients Participating in Biomedical Research Programs. All patients provided written informed consent. Conventional US and SSI quantitative elastography were performed in 46 women (mean age, 57.6 years; age range, 38-71 years) with 48 breast lesions (28 benign, 20 malignant; mean size, 14.7 mm); pathologic results were available in all cases. Quantitative lesion elasticity was measured in terms of the Young modulus (in kilopascals). Sensitivity, specificity, and area under the curve were obtained by using a receiver operating characteristic curve analysis to assess diagnostic performance. ::: ::: ::: RESULTS ::: All breast lesions were detected at SSI. Malignant lesions exhibited a mean elasticity value of 146.6 kPa +/- 40.05 (standard deviation), whereas benign ones had an elasticity value of 45.3 kPa +/- 41.1 (P < .001). Complicated cysts were differentiated from solid lesions because they had elasticity values of 0 kPa (no signal was retrieved from liquid areas). ::: ::: ::: CONCLUSION ::: SSI provides quantitative elasticity measurements, thus adding complementary information that potentially could help in breast lesion characterization with B-mode US.
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paper_title: Pulsed ultrasound-modulated light tomography.

paper_content:

Ultrasound-modulated light tomography is a new technique that combines laser light and ultrasound to provide a representation of the light density inside turbid media. We present a method that can produce two- or three-dimensional light density representations with standard ultrasonic pulses. This technique should allow simple, direct fusion of ultrasonic images with optical tomography.
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paper_title: Imaging optically scattering objects with ultrasound-modulated optical tomography

paper_content:

We show the feasibility of imaging objects having different optical scattering coefficients relative to the surrounding scattering medium using ultrasound-modulated optical tomography (UOT). While the spatial resolution depends on ultrasound parameters, the image contrast depends on the difference in scattering coefficient between the object and the surrounding medium. Experimental measurements obtained with a CCD-based speckle contrast detection scheme are in agreement with Monte Carlo simulations and analytical calculations. This study complements previous UOT experiments that demonstrated optical absorption contrast.
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paper_title: Detection and discrimination of optical absorption and shear stiffness at depth in tissue-mimicking phantoms by transient optoelastography

paper_content:

This work investigates the ability of transient optoelastography to detect both shear stiffness contrasts and optical absorption contrasts embedded deep in tissuelike media. The technique consists of a camera-based optical detection scheme designed to detect selectively the transient shear motion created at depth by the acoustic radiation force in optically turbid media. It is demonstrated on tissue-mimicking phantoms that transient optoelastography is not only sensitive to both optical absorption and shear stiffness contrasts, but also provides discrimination between these two types of contrasts.
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paper_title: Effects of acoustic radiation force and shear waves for absorption and stiffness sensing in ultrasound modulated optical tomography

paper_content:

Ultrasound-modulated optical tomography (UOT) combines optical contrast with ultrasound spatial resolution and has great potential for soft tissue functional imaging. One current problem with this technique is the weak optical modulation signal, primarily due to strong optical scattering in diffuse media and minimal acoustically induced modulation. The acoustic radiation force (ARF) can create large particle displacements in tissue and has been shown to be able to improve optical modulation signals. However, shear wave propagation induced by the ARF can be a significant source of nonlocal optical modulation which may reduce UOT spatial resolution and contrast. In this paper, the time evolution of shear waves was examined on tissue mimicking-phantoms exposed to 5 MHz ultrasound and 532 nm optical radiation and measured with a CCD camera. It has been demonstrated that by generating an ARF with an acoustic burst and adjusting both the timing and the exposure time of the CCD measurement, optical contrast and spatial resolution can be improved by ~110% and ~40% respectively when using the ARF rather than 5 MHz ultrasound alone. Furthermore, it has been demonstrated that this technique simultaneously detects both optical and mechanical contrast in the medium and the optical and mechanical contrast can be distinguished by adjusting the CCD exposure time.
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Title: Ultrasound-mediated Optical Tomography: A Review of Current Methods

Section 1: INTRODUCTION
Description 1: This section provides an overview of the diagnostic potential of optical imaging in tissues, the challenges associated with light absorption and scattering, and the principles of ultrasound-mediated optical tomography (UOT).

Section 2: THE ORIGIN OF THE ULTRASOUND-MEDIATED OPTICAL TOMOGRAPHY SIGNAL
Description 2: This section describes the physical mechanisms of how ultrasound affects light propagation in tissue, including modifications to the local refractive index and the displacement of scatterers.

Section 3: MODELLING AND SIMULATION OF ULTRASOUND-MEDIATED OPTICAL TOMOGRAPHY SIGNALS
Description 3: This section discusses analytical and simulation methods used to model the impact of ultrasound on optical signals, highlighting different approaches and their limitations.

Section 4: METHODS FOR DETECTING LIGHT MODULATED BY ULTRASOUND
Description 4: This section reviews various detection methods for ultrasound-modulated light, including single-point detection, Fabry-Perot interferometers, spectral hole burning, parallel detection, and photorefractive crystals.

Section 5: TISSUE PHANTOMS
Description 5: This section outlines different simulated biological tissues used in UOT studies to approximate the optical absorption and scattering properties of actual tissue.

Section 6: METHODS OF SCANNING THE OBJECT
Description 6: This section covers different scanning methodologies to create three-dimensional UOT images, including physical scanning, frequency-swept ultrasound, and techniques employing computer tomography methods.

Section 7: ATTEMPTS TO INCREASE THE ULTRASOUND-MEDIATED OPTICAL TOMOGRAPHY SIGNAL USING THE ACOUSTIC RADIATION FORCE
Description 7: This section discusses the use of acoustic radiation force (ARF) to enhance the UOT signal by achieving larger scatterer displacements, thereby increasing modulation depth.

Section 8: USE OF THE ACOUSTIC RADIATION FORCE TO DETECT OPTICAL AND MECHANICAL CONTRAST
Description 8: This section presents studies on utilizing ARF for simultaneous sensitivity to optical and mechanical properties of tissues, describing experimental results and the trade-offs between signal strength and spatial resolution.

Section 9: CONCLUSIONS
Description 9: This section summarizes the diagnostic potential of UOT, the effectiveness of various detection techniques, the promise of UOT in clinical applications, and the future outlook for the field.