Based on the multi-wavelength laser-based photoacoustic tomography, non-invasive in vivo imaging of functional parameters, including the hemoglobin oxygen saturation and the total concentration of hemoglobin, in small-animal brains was realized. The high sensitivity of this technique is based on the spectroscopic differences between oxy- and deoxy-hemoglobin while its spatial resolution is bandwidth-limited by the photoacoustic signals rather than by the optical diffusion as in optical imaging. The point-by-point distributions of blood oxygenation and blood volume in the cerebral cortical venous vessels, altered by systemic physiological modulations including hyperoxia, normoxia and hypoxia, were visualized successfully through the intact skin and skull. This technique, with its prominent intrinsic advantages, can potentially accelerate the progress in neuroscience and provide important new insights into cerebrovascular physiology and brain function that are of great significance to the neuroscience community.

Reflection-mode photoacoustic microscopy with dark-field laser pulse illumination and high frequency ultrasonic detection is used to non-invasively image blood vessels in the skin in vivo. Dark-field illumination minimizes the interference caused by strong photoacoustic signals from superficial structures. A high numerical-aperture acoustic lens provides high lateral resolution, 45-120 micrometers in this system while a broadband ultrasonic detection system provides high axial resolution, estimated to be ~15-20 micrometers. The optical illumination and ultrasonic detection are in a coaxial confocal configuration for optimal image quality. The system is capable of imaging optical-absorption contrast at up to 3 mm depth in biological tissue.

The new experimental design of an integrated flow cytometry (FC) is presented, combining high-resolution transmission digital microscopy (TDM) with photothermal (PT), photoacoustic (PA), and fluorescence techniques. We used phantom in vitro to verify this concept with moving living cells, and micro- and nanoparticles. The transistion in vivo study was realized by using unique rat mesentery model for real-time detection of circulating red and white blood cells. The adaptation of confocal schematics to PT microscopy to provide 3-D measurement is discussed. We demonstrated that simulataneous transmission, PT and fluorescent imaging provide the basis for nanodiagnostics and nanotherpeutics in vivo with gold nanoparticles as PT probes and sensitizers as well as identification cells with specific absorbing endogenous and exogenous structures. First attempt to use in parallel PA methods with detection PA signals from single live cells are presented. Potential applications of integrated FC are discussed, including identification of selected cells with different natural absorptive properties, characterization of bioflow (e.g., velocity profile), and PT nanotherapeutics and nanodiagnostics of metastatic cells with gold nanoparticles.

Performance studies of a clinical prototype for detecting tumors in the breast based on the photoacoustic effect are presented in terms of sensitivity, frequency response and resolution. Some imaging results on well characterized breast tissue phantoms with embedded tumor simulating inserts are also shown.

Optoacoustic imaging is a promising new tool for the detection and diagnosis of breast cancer. It is progressing from research study to clinical evaluation. We have now built a complete laser optoacoustic imaging system (LOISTM) consisting of a laser illumination system, a 32-element ultrasonic detector probe, signal amplifiers, and a computer with software for image generation. This report describes initial tests to explore the clinical viability of the system. Our results show that the system has sufficient sensitivity to reveal cancerous tumors already identified with X-ray and/or ultrasound imaging, that it has the resolution to show faithfully the size and shape of those tumors, that comparison of images taken at 755 and 1064 nm is indicative of whether or not a suspicious lesion is cancerous, and that the depth of sensitivity of the system is sufficient to detect tumors throughout an average-sized breast.

We report a preliminary study of breast cancer imaging by microwave-induced thermoacoustic tomography. In this study, we built a prototype of breast cancer imager based on a circular scan mode. A 3-GHz 0.3~0.5-μs microwave is used as the excitation energy source. A 2.25-MHz ultrasound transducer scans the thermoacoustic signals. All the measured data is transferred to a personal computer for imaging based on our proposed back-projection reconstruction algorithms. We quantified the line spread function of the imaging system. It shows the spatial resolution of our experimental system reaches 0.5 mm. After phantom experiments demonstrated the principle of this technique, we moved the imaging system to the University of Texas MD Anderson Cancer Center to image the excised breast cancer specimens. After the surgery performed by the physicians at the Cancer Center, the excised breast specimen was placed in a plastic cylindrical container with a diameter of 10 cm; and it was then imaged by three imaging modalities: radiograph, ultrasound and thermoacoustic imaging. Four excised breast specimens have been tested. The tumor regions have been clearly located. This preliminary study demonstrated the potential of microwave-induced thermoacoustic tomography for applications in breast cancer imaging.

Photoacoustic imaging, which generates a map of the initial acoustic pressure distribution generated by a short laser pulse, has been demonstrated by several authors. Quantitative photoacoustic imaging takes this one stage further to produce a map of the distribution of an optical property of the tissue, in this case absorption, which can then be related to a physiological parameter. In this technique, the initial pressure distribution is assumed to be proportional to the absorbed laser energy density. A model of light transport in scattering media is then used to estimate the distribution of optical properties that would result in such a pattern of absorbed energy. The light model used a finite element implementation of the diffusion equation (with the delta-E(3) approximation included to improve the accuracy at short distances inside the scattering medium). An algorithm which applies this model iteratively and converges on a quantitative estimate of the optical absorption distribution is described. 2D examples using simulated data (initial pressure maps) with and without noise are shown to converge quickly and accurately.

In this paper, we present first results of a spectral characterisation of doping substances using a resonant optoacoustic cell and a Nd:YAG laser pumped optical parametric generation (OPG) laser source in the mid-infrared wavelength range between 3.0 and 4.0 μm with periodically poled LiNbO₃ as nonlinear medium for the frequency conversion. Single spectra covering a wavelength range of about 220 nm can be conducted within less than 2 hours (3s averaging time, 7s between consecutive data points, about 0.3nm step-width). Despite the large linewidth of the OPG source of 240 GHz (8 cm-1), the laser spectrometer is well suited for the spectral analysis of these large organic molecules as they exhibit structured continuum absorption over a wide spectral range rather than isolated absorption peaks. We present measured spectra of ephedrine, alprenolol, ethacrynic acid, etc. and discuss the potential of laser-based detection of doping substances both as a supplement to existing methods and in view of a fast in situ screening technique at sporting events.

The indicator-dilution theory has been used for flow rate measurements in various imaging modalities, including magnetic resonance imaging, computed tomography and ultrasound. The experimental procedure generally involves the injection of a dose of indicator (i.e., the contrast agent), after which the concentration of the agent is monitored as a function of time; it is therefore also known as the time-intensity method. Although the time-intensity method has been widely applied to other imaging modalities, it has not been demonstrated with optoacoustic imaging. In this study, we experimentally test the hypothesis that quantitative blood flow measurements are feasible with the time-intensity based method in optoacoustic imaging. Gold nanospheres (broad band absorption spectrum peaks at 520 nm) were used as the optoacoustic contrast agent. The imaging system consisted of a frequency-doubled Nd:YAG laser operating at 532 nm for optical illumination, and an ultrasonic single crystal transducer with a center frequency of 3.5 MHz and a focal depth of 7 cm for detection. The volumetric flow rate ranged from 0.23 to 4.29 ml/sec, and the volume of the mixing chamber was from 30 to 80 ml. Results show good agreement between the measured mean transit times and the predicted time constants (correlation coefficient higher than 0.88), thus demonstrating the feasibility of the time-intensity based flow measurement technique. In addition to describing the method and experimental results, issues regarding the system sensitivity and estimation of the dilution transfer function are also discussed.

The sensitivity of optoacoustic (OA) detection in diluted suspensions of gold nanoparticles under irradiation with nanosecond laser pulses was studied as a function of incident laser fluence. The range of moderate values of the laser fluence from 20 mJ/cm² to 2 J/cm² was studied theoretically and experimentally. Under these laser fluences, the usual thermoelastic mechanism of OA generation faces competition from laser-induced cavitation, a statistical process, which leads to considerable fluctuations of the acoustic response from one laser pulse to another. Analytical expressions for the statistical characteristics of the acoustic signal were obtained. A simulation of the statistical characteristics of the cavitation contribution to the signal was performed using the method of Monte Carlo. The experiment utilized the second harmonic pulses (532 nm) of an Nd:YAG laser to irradiate samples of water suspensions of spherical gold nanoparticles (NPs). A series of laser pulses each having from 100 to 2000 pulses were used to iradiate the samples. The statistical rank distributions of the magnitudes of optoacoustic signals recorded by a wide band ultrasonic transducer attached to the measurement cell were used as a tool for sensitive detection of a low concentration of the gold nanoparticles in water.

We are developing new diagnostic and therapeutic technologies for leukemia based on selective targeting of leukemia cells with gold nanoparticles and thermomechanical destruction of the tumor cells with laser-induced microbubbles. Clusters of spherical gold nanoparticles that have strong optical absorption of laser pulses at 532 nm served as nucleation sites of vapor microbubbles. The nanoparticles were targeted selectively to leukemia cells using leukemia-specific surface receptors and a set of two monoclonal antibodies. Application of a primary myeloid-specific antibody to tumor cells followed by targeting the cells with 30-nm nanoparticles conjugated with a secondary antibody (IgG) resulted in formation of nanoparticulate clusters due to aggregation of IgGs. Formation of clusters resulted in substantial decrease of the damage threshold for target cells. The results encourage development of Laser Activated Nanothermolysis as a Cell Elimination Therapy (LANCET) for leukemia. The proposed technology can be applied separately or in combination with chemotherapy for killing leukemia cells without damage to other blood cells. Potential applications include initial reduction of concentration of leukemia cells in blood prior to chemotherapy and treatment of residual tumor cells after the chemotherapy. Laser-induced bubbles in individual cells and cell damage were monitored by analyzing profile of photothermal response signals over the entire cell after irradiation with a single 10-ns long laser pulse. Photothermal microscopy was utilized for imaging formation of microbubbles around nanoparticulate clusters.

Recording of an ultrasonic vibration potential when a burst of ultrasound traverses a body containing a colloidal object can be used as the basis for an imaging method. The fundamentals of the theory of signal production and experimental demonstration of the imaging method are given. In a second imaging method, the use of ultrasound to modify x-ray phase contrast images where the ultrasound acts as a kind of "phase contrast" agent used to translate objects in space is demonstrated.

Optoacoustic binary holography is applied to gain complete spatio-temporal control over ultrasonic beams. For flexible temporal intensity modulation of the sound-inducing laser light, an electro-optic modulator is used. Furthermore, in order to generate the desired spatial intensity distributions of the ultrasound, a spatial light modulator impresses synthetic binary holograms on the modulated light beam. At a light absorbing surface the optoacoustic effect converts the modulated light wave into an ultrasonic beam that propagates into water in the holographically predetermined way. With this approach we have successfully generated amplitude distributions that are difficult to realize with traditional piezo-electric techniques.

We present a dual modality imaging technique by combining photoacoustic tomography (PAT) and near-infrared (NIR) fluorescence imaging for the study of animal model tumors. PAT provides high-resolution structural images of tumor angiogenesis, and fluorescence imaging offers high sensitivity to molecular probes for tumor detection. Coregistration of the PAT and fluorescence images was performed on nude mice with M21 human melanoma cell lines with αvβ3 integrin expression. An integrin αvβ3-targeted peptide-ICG conjugated NIR fluorescent contrast agent was used as the molecular probe for tumor detection. PAT was employed to noninvasively image the brain structures and the angiogenesis associated with tumors in nude mice. Coregistration of the PAT and fluorescence images was used in this study to visualize tumor location, angiogenesis, and brain structure simultaneously.

Angiogenesis in advanced breast cancers is highly distorted and heterogeneous. Non-invasive imaging that can monitor angiogenesis may be invaluable for assessing tumor response to treatment. By combining ultrasound and near infrared optical imaging, a reliable new technique has emerged for predicting tumor angiogenesis within the breast.

Photoacoustic tomography (PAT) in a circular scanning configuration was developed to image the deeply embedded optical heterogeneity in biological tissues. Based on the intrinsic contrast between blood and chicken breast muscle, an embedded blood object that was 5 cm deep in the tissue was detected using pulsed laser light at a wavelength of 1064 nm. Compared with detectors for flat active surfaces, cylindrically focused ultrasonic transducers can reduce the interference generated from the off-plane photoacoustic sources and make the image in the scanning plane clearer. While the optical penetration was optimized with near-infrared laser pulses of 800 nm in wavelength, the optical contrast was enhanced by indocyanine green (ICG) whose absorption peak matched the laser wavelength. This optimized PAT was able to image fine objects embedded at a depth of up to 5.2-cm, which is 6.2 times the 1/e optical penetration depth, in chicken breast muscle, at a resolution of < ~750 microns with a sensitivity of <7 pmol of ICG in blood. The resolution was found to deteriorate slowly with increasing imaging depth.

Photoacoustic tomography is a potential and noninvasive medical imaging technology. It combines the advantages of pure optic imaging and pure ultrasound imaging. Photoacoustic signals induced by a short pulse laser cover a wide spectral range. We have explored the frequency spectrum of absorbers with different sizes and the influence of photoacoustic signals with different spectral components on photoacoustic imaging. The simulations and experiments demonstrated that the major frequency ranges of photoacoustic pressures of absorbers with diameters of ~cm, ~mm and hundreds of mm are about 20kHz~300kHz, 70kHz~2.5MHz and 400kHz~20MHz, respectively. The low spectral components of photoacoustic signals contribute to the non-boundary region of absorbers, and the high spectral components contribute to small structures, especially, to boundaries. It suggests that the ultrasonic transducers used to detect photoacoustic pressures should be designed and selected according to the frequency ranges of absorbers.

Photoacoustic imaging combines the contrast advantage of pure optical imaging and the resolution advantage of pure ultrasonic imaging. It has become a popular research subject at present. A fast photoacoustic imaging system based on multi-element linear transducer array and phase-controlled focus method was developed and tested on phantoms and tissues. A Q switched Nd:YAG laser operating at 532nm was used in our experiment as thermal source. The multi-element linear transducer array consists of 320 elements. By phase-controlled focus method, 64 signals, one of which gathered by 11-group element, make up of an image. Experiment results can map the distribution of the optical absorption correctly. The same transducer array also can operate as a conventional phase array and produced ultrasound imaging. Compared to other existing technology and algorithm, the PA imaging based on transducer array was characterize by speediness and convenience. It can provide a new approach for tissue functional imaging in vivo, and may have potentials in developing into an appliance for clinic diagnosis.

Acousto-optical imaging (AOI) in diffuse media is a hybrid technique that is based on the interaction of multiply scattered laser light with a focused ultrasound beam. A phase-modulated optical field emanates from the interaction region and carries with it information about the local opto-mechanical properties of the insonated media. The goal of AOI is to reveal the optically relevant physiological information while maintaining ultrasonic resolution. Among the state-of-the-art optical detection techniques used for AOI, there is a trade-off between the axial resolution (or ultrasound bandwidth) and the signal-to-noise ratio (SNR). In this paper, a photorefractive-crystal (PRC) based interferometry system is employed to detect acousto-optical (AO) signals in highly diffuse media. This system allows for the use of short pulses of focused ultrasound and is capable of imaging mm-scale inhomogeneities imbedded inside tissue-mimicking phantoms. One-dimensional (1-D) AO image along the transducer axis is obtained from a single, time-averaged time-domain acousto-optical signal, and the axial resolution is determined by the acoustic spatial pulse length, rather than the longer axial dimension of the ultrasonic focal region (as is the case when using a continuous-wave (CW) ultrasound source). Two-dimensional (2-D) images can be constructed by scanning the transducer in one dimension, which results in a reduction in imaging acquisition time and makes fast acousto-optical imaging possible.

The acousto-optical sensing (AOS) of a turbid medium is based on the interaction of multiply-scattered coherent laser light with an ultrasonic field. A phase-modulated photon field emanates from the interaction region and carries with it information about the acousto-optical properties of the media. Using a novel technique based on a photorefractive crystal interferometer, it is possible to detect the ultrasound-modulated optical signals generated by short ultrasound pulses. As opposed to continuous-wave (CW) ultrasound, pulsed ultrasound directly provides resolution along the ultrasonic propagation axis. In this work, a commercial ultrasound scanner (Analogic AN2300) was used in pulse mode (5 MHz central frequency) to generate both conventional ultrasound and AO images. Gel-based highly diffusive (μs'=10 cm^-1) tissue-mimicking phantoms were fabricated, with embedded targets possessing acoustical and/or optical contrast. AO images of 26-mm thick phantoms were generated from optical signals averaged in the time-domain, without further signal processing, and were superimposed on the top of the ultrasound images. Good quality AO images of optical absorbers, intrinsically co-registered with the ultrasound images, were obtained within minutes. The axial resolution of the AO images was given by the spatial length of the ultrasound pulse, typically on the order of one mm in the MHz range. These results show that AO signals can be excited in pulse mode using a commercial scanner, and combined to conventional ultrasound images to provide more information related to the optical properties of the medium.

A new concept of acousto-optical imaging is emerging based on an interferometric setup containing a photorefractive crystal as the recombination plate, and a single detector. This wavefront-adaptive holography technique is promising since the measurements are made in real-time with a high flux collection and at a high rate, faster than the speckle decorrelation time. We present here a detailed model that describes correctly the measured signal, whether in a temporal phase or amplitude modulation of the ultrasound.

Ultrasound modulated optical signals from scattered laser light in biological tissue have been investigated in order to improve optical imaging quality, a technique we call acousto-photonic imaging (API). Recent experiments using a photorefractive crystal based detection system have shown that there is a large DC-offset to the acoustically modulated AC optical signal, an effect that is second order in the large acoustically-induced optical phase shifts. We present numerical calculations for the size of the phase shifts of various photons in an API set-up. The calculations use a Monte Carlo simulation for the propagation of laser photons in an optically diffuse medium with properties similar to tissue and a finite-difference time domain simulation of a realistic focused ultrasound beam in that medium. The phase shifts of photons which passed through different regions around the ultrasound focus were compared. Quantities which characterize the AC and DC signal components were evaluated using the calculated phase shifts. It was found that the DC term dominates as it does in experiments, even though it is second order in the phase shifts. This is due to the fact that the contributions to the DC signal from each photon add coherently. In addition, the significant contributions to the DC signal are limited to those photons that passed near the ultrasound focal region, which has important implications for improving the imaging resolution in API.

We present an extension of our work on 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, light absorbing structures placed >3 mm below the surface of chicken breast tissue were imaged with high contrast. The resolutions along the axial and lateral directions with respect to the ultrasound propagation direction were better than 70 um and 120 um, respectively. The resolutions can be scaled down further by using higher ultrasound frequencies. This technology is complementary to other imaging technologies, such as confocal microscopy and optical-coherence tomography, and has potential for broad biomedical applications.

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. The relation between the ultrasound induced motions of the 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 to the modulation of the optical index of refraction. Finally, it is shown that compared with the spectrum of the ultrasound pulses, the power spectral density of the acousto-optically modulated light is strongly attenuated toward the higher ultrasound frequencies.

Ultrasound modulated light tomography (UMLiT) is a very attractive method for optical imaging of turbid media. Different schemes have been developed for effectively discriminating between the non-modulated and modulated photons and locate absorbing inhomogeneities. L. Wang has shown the possibility of using chirped ultrasound as well as Radon transformed-based tomography for three-dimensional imaging, C. Boccara has demonstrated the use of ultrafast cameras in order to increase the signal to noise ratio. Our group has shown the use of pulsed ultrasound for three-dimensional localization. However, although there have been a strong effort towards imaging objects in phantoms, very few experiments have shown quantitative results probing the limits of the technique in terms of resolution and sensitivity. We will present experimental results obtained in a reflection configuration. In a first series of experiments we present results obtained on living mice and rabbits, showing two and three-dimensional representations. In a second series of experiments, we have prepared different Agar-based phantoms in which small absorption inhomogeneities have been introduced. The background effective attenuation was 0.05 cm^-1. Several 5 mm diameter inclusions have been introduced in the phantom in different geometries with an effective absorption varying from twice to ten times the background. These inclusions could be detected up to a depth of 4 cm.

There are many situations in optics (such as heterodyne microscopy and some biomedical imaging applications [1]) where the required information is carried on a modulated component of the received image. When, as frequently is the case, the frequency of modulation exceeds the frame rate of conventional imagers (i.e. CCD or CMOS charge integrating active pixel sensor cameras) this modulated component must be detected by a single detector rather than imaged in parallel by and array or camera. It is for these reasons that there is a pressing need for the development of new imaging technologies. In this paper we present a lock-in pixel for a CMOS modulated light camera (MLC) capable of detecting modulated components in the incident light. The detected frequency is independent of, and is much higher than the frame rate of any conventional commercial camera. The pixel presented here is capable of narrow band lock-in detection of light modulated between 10MHz and 75MHz even when superimposed on a large ambient background. We present the design of this pixel and experimental results that optically image the ultrasound field using a pixel fabricated in a standard 0.35mm CMOS process. We also discuss the current work increasing the frequency response, providing phase sensitive (I and Q) detection and the development of an imaging array leading to a full field modulated light camera.

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 allows to perform tomographies inside several centimeter-thick scattering samples. Test experiments confirm the suitability of this method to perform tomographies inside various types of optically scattering media, including liquids.

The developing realization that acute coronary events, such as myocardial infarctions, can be caused by the sudden disruption of relatively small, rupture-prone plaques has led to increased exploration of clinical techniques that identify "vulnerable plaque" and differentiate it from "stable" plaque. Intravascular optoacoustic imaging promises to be such a technique. It has the capability of measuring the thickness of the plaque cap, the size of the underlying lipid reservoir, and other structural features known to be related to the vulnerability of the plaque. Inside an artery, optoacoustic imaging must necessarily be done in the backward mode, with irradiation and detection close to the same site on the tissue surface. With test phantoms simulating the optical and acoustic properties of the arterial wall, we have been able to show that backward-mode imaging is feasible. Modification of the ultrasonic detector used to allow irradiation and detection at the same point on the same surface affects the signal in a predictable way. The effect of the probe on the signal can reliably be removed by deconvolution of the measured signal to take into account the detector response.

Optoacoustic systems making use of optical detection probes are potentially advantageous over contact transducers for noncontact, noninvasive high-resolution near surface imaging applications. In this work, an interferometer is used for high-frequency optoacoustic microscopy. The limitations of this system in terms of both sensitivity and resolution are discussed. A theoretical model has been developed for two-dimensional excitation source geometries, which can be used to predict the optoacoustic signal from a target material with an arbitrary through-thickness optical absorption distribution. The model incorporates the temporal and spatial profile of the excitation laser pulse, and is used to predict the actual out-of-plane displacement at the target surface. An adaptive, photorefractive crystal-based interferometry system has been used to measure the optically induced displacement on the surface of target materials, and the results show reasonable quantitative agreement with theory. The detection system has a 200 MHz bandwidth allowing for high-resolution imaging, and the use of optical probes for both generation and detection allows for the probes to be easily co-aligned on the sample surface. Preliminary experimental results are presented demonstrating the feasibility of using all-optical optoacoustic microscopy for near surface imaging of small-scale spatial variations in optical absorption.

Photoacoustic signals are usually generated using bulky and expensive Q-switched Nd:YAG lasers, with limited scope for varying the pulse repetition frequency, wavelength and pulse width. An alternative would be to use laser diodes as excitation sources; these devices are compact, relatively inexpensive, and available in a wide variety of NIR wavelengths. Their pulse duration and repetition rates can also be varied arbitrarily enabling a wide range of time and frequency domain excitation methods to be employed. The main difficulty to overcome when using laser diodes for pulsed photoacoustic excitation is their low peak power compared to Q-switched lasers. However, the much higher repetition rate of laser diodes (~ kHz) compared to many Q-switched laser systems (~ tens of Hz) enables a correspondingly greater number of events to be acquired and signal averaged over a fixed time period. This offers the prospect of significantly increasing the signal-to-noise ratio (SNR) of the detected photoacoustic signal. Choosing the wavelength of the laser diode to be lower than that of the water absorption peak at 940nm, may also provide a significant advantage over a system lasing at 1064nm for measurements in tissue. If the output of a number of laser diodes is combined it then becomes possible, in principle, to obtain a SNR approaching that achievable with a Q-switched laser. It is also suggested that optimising the pulse duration of the laser diode may reduce the effects of frequency-dependent acoustic attenuation in tissue on the photoacoustic signal. To investigate this, a numerical model based on the Poisson solution to the wave equation was developed. To validate the model, a high peak power pulsed laser diode system was built. It was composed of a 905nm stacked array laser diode coupled to an optical fibre and driven by a high current laser diode driver. Measurements of the SNR of photoacoustic signals generated in a purely absorbing medium (ink) were made as a function of pulse duration. This preliminary study shows the potential for using laser diodes as excitation sources for photoacoustic applications in the biomedical field.

Optical detection of ultrasound provides a unique and appealing way of forming detector arrays (1D or 2D) using either raster beam scanning or simultaneous array detection exploiting wide area illumination. Etalon based optical techniques are of particular interest, due to their relatively high sensitivity resulting from multiple optical reflections within the resonance structure. Detector arrays formed by etalon based techniques are characterized by high element density and small element active area, which enables high resolution imaging at high ultrasonic frequencies (typically 10-50 MHz). In this paper we present an application of an optical etalon structure for very high frequency ultrasound detection (exceeding 100 MHz). A thin polymer Fabry-Perot etalon (10 μm thickness) has been fabricated using spin coating of polymer photoresist on a glass substrate and gold evaporation forming partially reflecting mirrors on both faces of the polymer layer. The optical resonator formed by the etalon structure has a measured Q-factor of 300. The characteristic broadband response of the optical signal was demonstrated by insonifying the etalon using two different ultrasound transducers and recording the resulting intensity modulation of optical reflection from the etalon. A focused 10 MHz transducer was used for the low MHz frequency region, and a 50 MHz focused transducer was used for the high frequency region. The optical reflection signal was compared to the pulse/echo signal detected by the same ultrasound transducer. The measured signal to noise ratio of the optically detected signal is comparable to that of the pulse/echo signal in both low and high frequency ranges. The etalon detector was integrated in a photoacoustic imaging system. High resolution images of phantom targets and biological tissue (nerve cord) were obtained. The additional information of optical absorption obtained by photoacoustic imaging, along with the high resolution detection of the etalon, offer unique advantages for intravascular and neurological imaging devices.

We report a universal back-projection formula for three-dimensional photoacoustic computed tomography in three types of imaging geometries: planar, spherical, and cylindrical surfaces. A solid-angle weighting factor is introduced in the back-projection formula to compensate for the variations of detection views. Numerical simulation demonstrates the performance of the algorithm.

Optoacoustic imaging takes advantage of high optical contrast and low acoustical scattering, and has found several biomedical applications. Optoacoustic signals are produced by irradiating laser pulse to a sample, which absorbs light energy and generates ultrasound waves. In the common backward mode optoacoustic imaging, a laser beam illuminates the image object and an acoustic transducer located on the same side as the laser beam. A cross-sectional image is formed by laterally scanning the transducer. Although the laser beam width is generally narrow, strong optical scattering in tissue broadens the optical illumination energy and thus degrades the lateral resolution in optoacoustic image. Therefore, a time-domain delayed and summed technique has been proposed to locate the optoacoustic sources in the tissue. In this study, a combination of synthetic aperture focusing technique and coherence weighting is proposed. Specifically, the focusing quality of the synthetic aperture technique is further improved by using the signal coherence as an image quality index. In this article, we demonstrate the efficacy of the proposed method using numerical simulations and phantom experiments with a phantom comprising hair threads in a 1% milk solution. The results show that the proposed technique improved lateral resolution by 4-8 times and the signal-to-noise ratio by 7-23 dB over the conventional techniques.

Thermoacoustic tomography (TAT) is an ultrasound-mediated biophotonic imaging modality with great potential for a wide range of biomedical imaging applications. In this work, we demonstrate that half-time reconstruction approaches for TAT can mitigate image artifacts due to heterogeneous acoustic properties of an object. We also discuss how half-time reconstruction approaches permit explicit control of statistically complementary information in the measurement data, which can facilitate the reduction of image variances.

The goal of this paper was to evaluate the diagnostic value of integrated photothermal (PT) assay with additional fluorescent and photoacoustic (PA) modules to assess both the "safety limit" of exposure to ionizing γ-radiation and optimal therapeutic doses for cancer treatment. With this assay, the influences of γ irradiation on cancer cells (pancreatic-AR42J and hepatocytes-hepG2) and healthy cells (mouse lymphocytes and erythrocytes) was examined as a function of exposure dose (0.6-5 Gy) and time after irradiation, in vitro and in vivo. Independent verification of data obtained with conventional assays revealed that integrated PT assay allowed us to detect the different stages of radiation impact, including changes in cell metabolism at low dose, or stages related to cell death (apoptosis and necrosis) at high doses with a threshold sensitivity of at least three orders of magnitude better than existing assays. Also, PT assay was capable of quantitatively differentiating the biological action of γ irradiation alone and in combination with drug and nicotine impact. Finally, we demonstrated on an animal model that IPT assay has the potential for use in routine rapid evaluation of biological consequences of low-dose exposure a few days after irradiation.

Two-dimensional micro scale thermal analysis is proposed for the measurement of the latent heat released from the cultured vascular endothelial cells during freezing by use of high-speed infrared focal plane arrays. The thermo graphically observed latent heat spreading over the tissues and the inter- or intracellular thermal diffusion were detected with a spatial resolution of 7.5mm. The temperature distribution in time and space in each endothelial cell was influenced by both the self-release and intercellular diffusion of latent heat. The effect of cryo-protective agent on the cell suspension of bovine fetal aorta endothelial cell (BFAEC) was examined by the observation of latent heat during the repeated freezing processes.

Acoustical monitoring of laser-induced optical breakdown can be used as an important tool for diagnostics and therapeutics in living cells. Laser-induced intracellular microbubbles provide measurable contrast when detected with high-frequency ultrasound, and the bioeffects of these bubbles can be controlled to be within two distinct regimes. In the nondestructive regime, a single, transient, detectable bubble can be generated within a cell, without affecting its viability. In the destructive regime, the induced photodisruption can kill a target cell. To generate and monitor this range of effects in real time, we have developed a system integrating a femtosecond pulsed laser source with optical and acoustical microscopy. Experiments were performed on monolayers of Chinese hamster ovary cells. A Ti:Sapphire laser (793 nm wavelength, 100 fs pulse duration) was pulsed at 3.8 kHz and tightly focused to a 1 μm spot within each cell, and a high-frequency (50 MHz) ultrasonic transducer monitored the generated bubble with continuous pulse-echo recordings. The photodisruption was also observed with bright field optical microscopy, and cell viability was assessed after laser exposure using a colorimetric live/dead stain. By controlling laser pulse fluence, exposure duration, and the intracellular location of the laser focus, either nondestructive or destructive bubbles could be generated.

A novel application of polymer waveguide microring resonator for high-frequency ultrasound detection is presented. The device consists of a microring optical resonator that is coupled to a straight optical waveguide which serves as both input and output ports. Acoustic waves irradiating the ring waveguide induce strain that causes a change in the effective refractive index of optical waves propagating along the ring. The sharp wavelength dependence of the high Q-factor resonator enhances the optical response to the acoustic strain. High sensitivity has been demonstrated experimentally in the detection of broadband ultrasound pulses from a 10MHz transducer. WDM methods are proposed to extend the technique into an array of microrings for ultrasound imaging applications.

We report on the further development of our previously described spectroscopic imaging technique based on time-resolved interferometric measurements of laser-induced thermoelastic expansion (POISe: Pulsed Optoelastic Interferometric Spectroscopy and Imaging). We show the capability of POISe to form tomographic images of tissue phantoms and live animal tissues. By performing image reconstruction on data sets acquired from several tissue-like phantoms we demonstrate the ability of POISe to provide better than 200 microns spatial resolution in a strongly scattering medium (μ_s'=1.5/mm). Additionally we demonstrate the ability of POISe to image chicken chorio-allantoic membrane (CAM) blood vessels through a 6-10 mm layer of Intralipid with μ_s'=0.75/mm.

A new approach to the detection of opto-acoustic signals with the use of single-scattered optical fields in low scattering media is presented with the ultimate goal of performing opto-acoustic confocal microscopy in human skin. The method is based on the generation of heterodyne optical signals using opto-acoustic generated signals as a source of particle displacement. A focused, pulsed laser is used to generate an opto-acoustic signal and the particle displacement detection is performed with a coherent confocal microscope. The goal is to improve the depth of imaging obtained by confocal microscopy while maintaining its resolution. The use of optical coherent detection of teh Doppler shifts generated by teh ultrasound filed positioned at the optical focus gives us information about the amplitude and phase of the the scattered optical field. The results of interferometric measurements at different depths into scattering phantoms are presented.

An ultrasound field mapping system has been developed for high resolution photoacoustic imaging applications. This operates by optically scanning a Fabry-Perot (FP) ultrasound sensor with a wavelength tuned, single focused spot of interrogating CW light at 850nm. By rapidly tuning the wavelength of the interrogating light source, the interferometer transfer function (ITF) can be obtained at each addressed point on the FP sensor. This enables the optimal bias wavelength point to be located prior to recording the photoacoustic signal. The FP sensors used have dichroic designs which allow the transmission of excitation laser pulses at 1064nm through the sensor into the underlying target. Such optical designs enable the photoacoustic sensor system to operate in backward mode. The area over which the photoacoustic signals can be mapped by the present system is 3.6cm × 2.5cm with an optically defined element size of 50μm. Images obtained (using a 12MHz bandwidth sensor) of phantoms consisting of India ink filled, 12μm bore tubes immersed in Intralipid, show lateral and depth resolutions of 110μm and 70μm, respectively at depths up to 7mm. It is considered that this system has the potential to be used for backward mode imaging of superficial structures such as the dermal and sub-dermal microvasculature.