We have utilized a prototype Thermoacoustic Computed Tomography Small Animal Imaging System to acquire images of athymic mice with bilateral tumors implanted in the cranial mammary fat pads. The breast tumor cell lines used in the study, which are MCF7, and MCF7 transfected with Vascular Endothelial Growth Factor (VEGF), exhibit distinctly contrasting levels of vascularization. Three dimensional images of the mice, acquired using pulses of NIR stimulating light, demonstrate the ability of the system to generate high resolution images of the vascular system up to one inch deep in tissue, and at the same time, differentiate tissue types based on the infrared absorption properties of the tissue; a property related in part to blood content and oxygenation levels. We have processed images acquired at different stimulating wavelengths to generate images representative of the distribution of oxygenated and deoxygenated hemoglobin throughout the tumors. The images demonstrate the in vivo capabilities of the imaging system and map system structure as well as the total, oxygenated and deoxygenated hemoglobin components of the blood.

Both digital and physical phantoms are essential to the development of any new imaging modality. Digital phantoms are simply data sets that approximate the signals that would be measured by the imaging equipment. Physical phantoms are objects with similar physical properties to the human body. We compare several mathematical procedures for calculation of digital phantoms for optoacoustic imaging in general and describe convenient ways to construct physical phantoms for optoacoustic breast imaging. LOIS accurately reconstructs the expected images from both.

Photoacoustic imaging is demonstrated in imaging blood vessels of a chicken embryo. Using a weighted sum-and-delay beamforming algorithm we were able to reconstruct two- and three-dimensional images of these blood vessels.

Optoacoustic Tomography (OAT) is a rapidly growing technology that enables noninvasive deep imaging of biological tissues based on their light absorption. In OAT, the interaction of a pulsed laser with tissue increases the temperature of the absorbing components in a confined volume of tissue. Rapid perturbation of the temperature (<1°C) deep within tissue produces weak acoustic waves that easily travel to the surface of the tissue with minor attenuation. Abnormal angiogenesis in a malignant tumor, that increases its blood content, makes a native contrast for optoacoustic imaging; however, the application of OAT for early detection of malignant tumors requires the enhancement of optoacoustic signals originated from tumor by using an exogenous contrast agent. Due to their strong absorption, we have used gold nanoparticles (NP) as a contrast agent. 40nm spherical gold nanoparticles were attached to monoclonal antibody to target cell surface of breast cancer cells. The targeted cancer cells were implanted at depth of 5-6cm within a gelatinous object that optically resembles human breast. Experimental sensitivity measurements along with theoretical analysis showed that our optoacoustic imaging system is capable of detecting a phantom breast tumor with the volume of 0.15ml, which is composed of 25 million NP-targeted cancer cells, at a depth of 5 centimeters in vitro.

Non-intrusive, non-contacting frequency-domain photothermal radiometry (FD-PTR or PTR) and frequency-domain luminescence (FD-LUM or LUM) have been used with 659-nm and 830-nm laser sources to detect artificial and natural sub-surface defects in human teeth. Fifty-two human teeth were examined with simultaneous measurements of PTR and LUM with the 659-nm laser and compared to conventional diagnostic methods including continuous (dc) luminescence (DIAGNOdent), visual inspection and radiographs. To compare each method, sensitivities and specificities were calculated by using histological observations as the gold standard. With the combined criteria of four PTR and LUM signals (two amplitudes and two phases), it was found that the sensitivity of this method was much higher than any of the other methods used in this study, whereas the specificity was comparable to that of dc luminescence diagnostics. Therefore, PTR and LUM, as a combined technique, has the potential to be a reliable tool to diagnose early pit and fissure caries and could provide detailed information about deep lesions with its depth profilometric character. Also, from the experiments with the teeth having natural or aritficial defect, some depth profilometric characteristics were confirmed. The major findings are (i) PTR is sensitive to very deep (>5 mm) defects at low modulation frequencies (5 Hz). Both PTR and LUM amplitudes exhibit a peak at tooth thicknesses ca. 1.4 - 2.7 mm. Furthermore the LUM amplitude exhibits a small trough at ca. 2.5~3.5 mm; (ii) PTR is sensitive to various defects such as a deep carious lesion, a demineralized area, and a crack while LUM exhibits low sensitivity and spatial resolution.

High-intensity focused ultrasound (HIFU) has proved to be an effective minimally invasive surgical technology. In this study, we focus on the visualization of HIFU-induced lesions using microwave-induced thermoacoustic tomography (TAT). TAT has high spatial resolution, comparable with ultrasound imaging, and high contrast, which is induced by differences in the microwave absorption rates between tumor tissue and normal tissue. TAT can, in addition, differentiate tumors before and after treatment. A single, spherically focused transducer operating at a center frequency of approximately 4 MHZ was used to generate the focused field. The lesion was generated in porcine muscle. A local-tomography-type reconstruction algorithm was applied to reconstruct the TAT image of the lesions. The lesion shown by gross pathology confirms the corresponding region measured by TAT.

Laser Optoacoustic Imaging System (LOIS) combines high tissue contrast based on the optical properties of tissue and high spatial resolution based on ultrawide-band ultrasonic detection. Patients undergoing thermal or photodynamic therapy of prostate cancer may benefit from capability of LOIS to detect and monitor treatment-induced changes in tissue optical properties and blood flow. The performance of a prototype LOIS was evaluated via 2D optoacoustic images of dye-colored objects of various shapes, small tubes with blood simulating veins and arteries, and thermally coagulated portions of chicken breasts imbedded tissue-mimicking gelatin phantoms. The optoacoustic image contrast was proportional to the ratio of the absorption coefficient between the embedded objects and the surrounding gel. The contrast of the venous blood relative to the background exceeded 250%, and the contrast of the thermally coagulated portions of flesh relative to the untreated tissue ranged between -100% to +200%, dependent on the optical wavelength. We used a 32-element optoacoustic transducer array and a novel design of low-noise preamplifiers and wide-band amplifiers to perform these studies. The system was optimized for imaging at a depth of ~50 mm. The system spatial resolution was better than 1-mm. The advantages and limitations of various signal-processing methods were investigated. LOIS demonstrates clinical potential for non- or minimally-invasive monitoring of treatment-induced tissue changes.

The aim of this study was to use pulsed near infrared photoacoustic spectroscopy to determine the oxygen saturation (SO₂) of a saline suspension of red blood cells in vitro. The photoacoustic measurements were made in a cuvette which formed part of a larger circuit through which the red blood cell suspension was circulated. Oxygen saturation of the red blood cell suspension was altered between 2-3% to 100% in step increments using a membrane oxygenator and at each increment an independent measurement of oxygen saturation was made using a co-oximeter. An optical parametric oscillator laser system provided nanosecond excitation pulses at a number of wavelengths in the near-infrared spectrum (740-1040nm) which were incident on the cuvette. The resulting acoustic signals were detected using a broadband (15MHz) Fabry-Perot polymer film transducer. The optical transport coefficient and amplitude were determined from the acoustic signals as a function of wavelength. These data were then used to calculate the relative concentrations of oxy- and deoxyhaemoglobin, using their known specific absorption coefficients and an empirically determined wavelength dependence of optical scattering over the wavelength range investigated. From this, the oxygen saturation of the suspension was derived with an accuracy of ±5% compared to the co-oximeter SO₂ measurements.

Since optical contrast is sensitive to functional parameters, including the hemoglobin oxygen saturation and the total concentration of hemoglobin, imaging based on optical contrast has been widely employed for the real-time monitoring of tissue oxygen consumption and hemodynamics in biological tissues. However, due to the overwhelming scattering of light in tissues, traditional optical imaging modalities cannot provide satisfactory spatial resolution. Functional photoacoustic tomography is a novel technique that combines high optical contrast and high ultrasonic resolution. Here, we present our study of a laser-based photoacoustic technique that, for the first time to our knowledge, monitors blood oxygenation in the rat brain in vivo. The cerebral blood oxygenation in the rat brain was imaged by photoacoustic detection at two wavelengths. The change in the hemoglobin oxygen saturation in the brain vessels as a result of the alternation from hyperoxia status to hypoxia status was visualized successfully with satisfactory spatial resolution. This work demonstrates that photoacoustic technique, based on the spectroscopic absorption of oxy- and deoxy-hemoglobin, can provide accurate functional imaging of cerebral blood oxygenation in the small-animal brain non-invasively with the skin and skull intact.

Optical contrast agents, such as indocyanine dyes, nano-particles and their functional derivatives, have been widely applied to enhance the sensitivity and specificity of optical imaging. However, due to the overwhelming scattering of light in biological tissues, the spatial resolution of traditional optical imaging degrades drastically as the imaging depth increases. For the first time to our knowledge, non-invasive in vivo photoacoustic imaging of an optical contrast agent, distributed in the rat brain, was implemented with near-infrared light. Injection of indocyanine green polyethylene glycol, a contrast agent with a high absorption at the 805-nm wavelength, into the circulatory system of a rat enhanced the absorption contrast between the blood vessels and the background brain tissues. Because near-infrared light can penetrate deep into the brain tissues through the skin and skull, we were able to successfully reconstruct the vascular distribution in the rat brain from the detected photoacoustic signals. The dynamic concentration of this contrast agent in the brain blood after the intravenous injection was also studied. This work proved that the distribution of an exogenous contrast agent in biological tissues can be imaged clearly and accurately by photoacoustic tomography. This new technology has high potential for application in dynamic and molecular medical imaging.

Pyrogens being introduced intravenously increase body temperature that leads to hazardous consequences and even to lethal outcome. One of the widespread pyrogen systems is presented by suspensions composed of bacterial endotoxins (or lypopolysaccharides, LPS). The aim of the work is to compare experimentally two methods for the determination of LPS at the submicrogram level and below. Both methods suppose that the LPS suspension is irradiated by a laser pulse. The thermal lens (TL) method (microsecond to millisecond irradiation cycle) detects LPS by a direct pick-up of the transient thermal field. The optoacoustic (OA) method (nanosecond laser pulses) has a potential to use non-thermal constitutents of the LPS response and to provide some selectivity of LPS detection with respect to optically uniform contaminants in the sample. In experiments, the selectivity was enhanced by means of analytical reagents, methylene blue and Stains All dyes. It was shown that both methods are mutually complementary. Then, their detectability potential increases and reaches 10 ppb if there occur ion pairs of LPS and cationic dye.

Adhesion monitoring of grafted skins is very important in successful treatment of severe burns and traumas. However, current diagnosis of skin grafting is usually done by visual observation, which is not reliable and gives no quantitative information on the skin graft adhesion. When the grafted skin adheres well, neovascularities will be generated in the grafted skin tissue, and therefore adhesion may be monitored by detecting the neovascularities. In this study, we attempted to measure photoacoustic signals originate from the neovascularities by irradiating the grafted skins with 532-nm nanosecond light pulses in rat autograft and allograft models. The measurement showed that immediately after skin grafting, photoacoustic signal originate from the blood in the dermis was negligibly small, while 6 - 24 hours after skin grafting, signal was observed from the dermis in the graft. We did not observe a significant difference between the signals from the autograft and the allograft models. These results indicate that neovascularization would take place within 6 hours after skin grafting, and the rejection reaction would make little effect on adhesion within early hours after grafting.

The ultrasonic vibration potential refers to the generation of a potential when ultrasound traverses a colloidal or ionic solution. The vibration potential can be used for imaging of tissue by sending a burst of ultrasound into a body and recording the vibration potential on the surface of the body with a pair of electrodes attached to a preamplifier and signal processing electronics. The theory of imaging in one-dimension is based on an integral of the ultrasound burst over the colloid distribution in space. A complete theory gives the current from the vibration potential as an integral of the product of the pressure with the component of the gradient of the colloid distribution in space in the direction of propagation of the ultrasound.

Combination of three complementary imaging technologies - ultrasound imaging, elastography, and optoacoustic imaging - is suggested for detection and diagnostics of tissue pathology including cancer. The fusion of these ultrasound-based techniques results in a novel imaging system capable of simultaneous imaging of the anatomy (ultrasound imaging), cancer-induced angiogenesis (optoacoustic imaging) and changes in mechanical properties (elasticity imaging) of tissue to uniquely identify and differentiate pathology at various stages. To evaluate our approach, analytical and numerical studies were performed using heterogeneous phantoms where ultrasonic, optical and viscoelastic properties of the materials were chosen to closely mimic soft tissue. The results of this study suggest that combined ultrasound-based imaging is possible and can provide more accurate, reliable and earlier detection and diagnosis of tissue pathology. In addition, monitoring of cancer treatment and guidance of tissue biopsy are possible with a combined imaging system.

Frequency-domain correlation and spectral analysis photothermoacoustic (FD-PTA) imaging is a promising new technique, which is being developed to detect tumor masses in turbid biological tissue. Unlike conventional biomedical photoacoustics which uses time-of-flight acoustic information induced by a pulsed laser to indicate the tumor size and location, in this research, a new FD-PTA instrument featuring frequency sweep (chirp) and heterodyne modulation and lock-in detection of a continuous-wave laser source at 1064 nm wavelength is constructed and tested for its depth profilometric capabilities in turbid media imaging. Owing to the linear relationship between the depth of acoustic signal generation and the delay time of signal arrival to the transducer, information specific to a particular depth can be associated with a particular frequency in the chirp signal. Scanning laser-fluence modulation frequencies with a linear frequency sweep method preserves the depth-to-delay time linearity and recovers FD-PTA signals from a range of depths. A report on two-dimensional spatial scans, performed on tissue mimicking control phantoms with various optical, acoustical and geometrical properties will be presented. Combining with the depth information carried by the back-propagated chirp signal at each scanning position, one could rapidly generate sub-surface three-dimensional images of the scanning area, a combination of tasks that is difficult or impossible by use of pulsed photoacoustic detection. It is concluded that frequency domain photothermoacoustics using a linear frequency sweep method and heterodyne lock-in detection has the potential to be a reliable tool for biomedical depth-profilometric imaging.

Spectral optoacoustic imaging uses two or more optical wavelengths for the excitation of ultrasonic waves in order to obtain spectrally resolved images of tissue. We developed a wavelength-multiplexing method that enables the simultaneous generation and detection of optoacoustic waves with two optical wavelengths emitted from a pump laser - optical parametric oscillator system. Two-dimensional images were taken with a linearly scanning optoacoustic transducer from phantoms and from tissue in vivo. The time required for signal acquisition depended solely on the pulse repetition rate of the laser. At presence, with a 10 Hz system, this time was between 10 and 20 seconds. Pairs of images at two wavelengths show an exact overlap of the imaged structures. Wavelength-dependent variations of optical absorption coefficients are visualized by calculating ratio and difference images. The presented experimental results demonstrate the feasibility of the method to generate maps of blood oxygenation.

We present an all-solid-state, transportable photoacoustic spectrometer operated with a continuous-wave optical parametric oscillator. The PPLN-based OPO has a dual cavity configuration (pump-resonant singly-resonant) in order to combine low threshold with good tuning characteristics. A complete spectral coverage between 3.1 and 3.9 μm with a single-frequency output power of 2 x 100 mW is achieved. At 30 seconds lock-in time constant the noise level of the background corresponds to a minimum absorption coefficient of 7.2 x 10^-10 cm^-1, yielding an ethane detection limit of 25 ppt. The OPO based photoacoustic spectrometer including the wavemeter is installed on a 120 cm x 75 cm breadboard. The ethane concentration of ambient air is determined by a multigas analysis. Additionally an online-measurement of biogenic ethane emissions by a freeze-stressed lima bean leaf is presented. The results indicate a high potential of this transportable spectrometer for biological and medical applications.

Although the electric impedance of biological tissues is highly sensitive to their physiological and pathological status, pure electrical impedance tomography (EIT) has very poor spatial resolution. We invented acousto-electric tomography (AET) to image the electric impedance properties of biological tissues with high spatial resolution. AET is based on acousto-electric modulation, which is the localized variation in conductivity produced by a focused ultrasonic wave. It combines the contrast advantage of EIT and the resolution advantage of ultrasound imaging. The spatial resolution of AET is primarily defined by the size of the ultrasonic focal spot. Therefore, the resolution is much better than that of EIT, and it is scalable with the acoustic parameters. The contrast of AET is determined by the combination of three factors: the electric impedance, the media dependent modulation coefficient, and the acoustic properties. Unlike EIT, AET forms images directly without resorting to inverse algorithms. And unlike traditional ultrasonography, AET is free of speckles.

We present an implementation of ultrasound-modulated optical tomography that has the potential to provide high resolution images of tissue structures at a penetration depth of several millimeters. Light and pulsed ultrasound are focused on an approximately 100 μm wide area below the sample surface. With this configuration, the length of the ultrasonic pulses determines the axial resolution, and the lateral resolution results from the width of the ultrasonic beam at the focus. Diffuse light reflected from the sample is collected into a fiber and the modulated component is separated from the background by a confocal Fabry-Perot interferometer. Using this setup, high contrast images are obtained of 100 μm wide pieces of hair that are buried one millimeter below the surface of the tissue-mimicking sample. It is the first time, to the authors' knowledge, that images with such high resolution have been obtained using ultrasound-modulated optical tomography in the reflection mode.

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.

Acousto-photonic imaging (API) is a dual-wave sensing technique in which a diffusive photon wave in a turbid medium interacts with an imposed acoustic field that drives scatterers to coherent periodic motion. A phase-modulated photon field emanates from the interaction region and carries with it information about the local opto-mechanical properties of the insonated media. A technological barrier to API has been sensitivity - the flux of phase-modulated photons is very small and the incoherence of the resulting speckle pattern reduces the modulation of the scattered light leading to low sensitivity. We report preliminary results from a new detection scheme in which a photorefractive crystal is used to mix the diffusively scattered laser light with a reference beam. The crystal serves as a dynamic holographic medium where the signal beam interferes with the reference beam, creating a photorefractive grating from which beams diffract. In addition, the phase modulation is converted to an amplitude modulation so that the API signal can be detected. Measurements of the API signal are presented for gel phantoms with polystyrene beads used as scatterers, showing a qualitative agreement with a simple theoretical model developed.

Photoacoustic tomography employs short laser pulses to generate acoustic waves. The photoacoustic image of a test sample can be reconstructed using the detected acoustic signals. The reconstructed image is characterized by the convolution of the sample structure in optical absorption, the laser pulse, and the impulse response of the ultrasonic transducer used for detection. Although laser-induced ultrasonic waves cover a wide spectral range, a single transducer can receive only part of the spectrum because of its limited bandwidth. To systematically analyze this problem, we constructed a photoacoustic tomographic system that uses multiple ultrasonic transducers, each at a different central frequency, to simultaneously receive the induced acoustic waves. The photoacoustic images associated with the different transducers were compared and analyzed. The system was used to detect the vascular system of the rat brain. The vascular vessels in the brain cortex were revealed by all of the transducers, but the image resolutions differed. The higher frequency detectors with wider bandwidths provided better image resolution.

For the first time, proposed is an ultracompact biomedical optical instrument for ultrasound tagged optical tomography that can simultaneously realize an agile ultrasonic probe and an agile optical probe, all in the same fiber-optic package, allowing close proximity in-vivo internal/intracavity imaging. In addition, the same dual probe can be used for external in-vivo imaging of several centimeters thick biological sample. The ultrasound and optical probe utilize the multiwavelength nature of light to provide a compact and fast mechanism to distribute and steer probing beams, thereby reducing motion artifacts and improving imaging contrast detection sensitivity.

The in vivo capabilities of a new, integrated optical system for studying lymph and blood flow were explored, including imaging of moving red and white blood cells. This system combined transmission microscopy with different dual-beam photothermal (PT) techniques, such as PT imaging, PT thermolens method, and PT deflection velocimetry. All of these PT techniques are based on irradiation of rat mesenteric microvessels with a short laser pulse and on detection of temperature-dependent variations of the refractive index with a second, probe laser beam. In general, the concept of in vivo PT flow cytometry was developed, with a focus on real-time monitoring of moving blood cells in their natural states without labeling (e.g., fluorescent), including obtaining PT images of the cells and determining their flow velocity and response to different interventions. Preliminary experiments revealed many potential applications of this integrated system: (1) quantitation of lymph and blood flow without probes; (2) imaging of moving red and white blood cells; (3) visualization and tracking of PT nanoprobes and sensitizers; (4) comparison of laser-tissue interactions in vivo and in vitro, especially optimization of laser treatment of vascular lesions (port-wine stains, lymphatic malformations, etc.); and (5) determination of the link between in vitro and in vivo cytotoxicity studies.

This short review presents findings from a recent evaluation of the diagnostic capabilities of a new experimental design of the advanced photothermal (PT) imaging system; specifically, its performance in studying the impact of nicotine, a combination of antitumor drugs, and radiation on the absorbing structures of various cells. We used this imaging system to test our hypothesis that low doses of chemicals or drugs lead to changes in cell metabolism, that these changes are accompanied by the shrinking of cellular absorbing zones (e.g. organelles), and that these reactions cause increased local absorption. Conversely, high (toxic) doses may lead to swelling of organelles or release of chromophores into the intracellular space, causing decreased local absorption. In this study, we compared PT images and PT responses of the pancreatic exocrine tumor cell line AR42J resulting from exposure to various concentrations of nicotine versus those of control cells. We found that responses were almost proportional to the drug concentration in concentrations ranging from 1 nM-100 μM, reached saturation at a maximum of approximately 100 μM-1 mM, and then fell rapidly at concentrations ranging from 1-50 mM. We also examined the influence of antitumor drugs (vinblastine and paclitaxel) on KB3 carcinoma cells, with drug concentrations ranging from 10^-10 nM to 10 nM. In this instance, exposure initially led to slight cell activation, which was then followed by decreased cellular PT response. Drug administration led to corresponding changes in the amplitude and spatial intracellular localization of PT responses, including bubble formation, as an indicator of local absorption level. Additionally, it was shown that, depending on cell type, x-ray radiation may produce effects similar to those resulting from exposure to drugs. Independent verification with a combined PT-fluorescence assay and conventional staining kits (trypan blue, Annexin V-propidium iodide [PI]) revealed that this new PT assay has the potential to detect different stages of environmental impact, including changes in cell metabolism and apoptotic- and toxic-related phenomena, at a concentration threshold sensitivity at least three orders of magnitude better than existing assays. This assay may also help optimize combined cancer therapies.

Ultrasound can be used in order to locally modulate, or tag, light in a turbid medium. This tagging process is made possible due to the extreme sensitivity of laser speckle distribution to minute changes within the medium. This hybrid technique presents several advantages compared to all-optical tomographic techniques, in that the image resolution is fixed by the ultrasound focus diameter. To our best knowledge, only in vitro experiments have been performed, either on tissue-like phantoms or meat. However a strong difference exists between these sample and living tissues. In living tissues, different kind of liquids flow through the capillaries, strongly reducing the sspeckle autocorrelation time. We have performed experiments on both mice and humans, showing that the autocorrelation time is much shorter than what was previously thought. We show however that it is possible to obtain signal with acceptable signal to noise ratio down to a few cm depth. We will also discuss the origin and characteristics of the speckle noise.

POISe is a spectroscopic imaging technique based on the measurement of surface motion resulting from thermoelastic stress waves produced by short pulse laser irradiation of optically heterogeneous turbid samples. Here we show the capability of POISe to form tomographic images of tissue phantoms using surface displacement measurements taken at several locations following irradiation of a sample with a Q-switched Nd:YAG laser λ=1064 nm. The principal component of POISe is a modified Mach-Zehnder interferometer that provides surface displacement measurements with a temporal resolution of 4 ns and a displacement sensitivity of 0.2 nm. By performing simple image reconstructions on data sets acquired from several tissue-like phantoms, we demonstrate the ability of POISe to provide better than 250 μm spatial resolution at depths of 6 to 8 mm in a strongly scattering medium (μ^'_s=1/mm). This technique shows great promise for high-resolution non-invasive imaging of superficial (< 1 cm) tissue structures.

A high sensitivity, wideband ultrasound sensor based on a high finesse Fabry-Perot (FP) polymer film interferometer has been demonstrated with a bandwidth of 20 MHz and a 50μm diameter active area. Used in conjunction with a balanced photodetector to enable the use of a high intensity interrogating light beam of up to 36mW, the sensor system provided a noise equivalent pressure (NEP) of 0.35kPa over a 20 MHz measured bandwidth. It is shown further that this NEP could, in principle, be reduced to 0.16 kPa by using an interrogating source with a wider wavelength tuning range than was available in the current study to track drift in the phase bias of the FP sensor. The sensitivity achieved is an order of magnitude higher than previously demonstrated with this type of sensors, and is comparable to that of a 1mm diameter PVDF element. The combination of high sensitivity and the small active area (<50μm diameter) makes the FP sensor scheme particularly suitable for photoacoustic imaging applications.

A novel optical ultrasound sensor has been developed for backward-mode photoacoustic imaging. The sensor is based on a Fabry Perot polymer film interferometer, the mirrors of which are transparent to 1064nm, but highly reflective at 850nm. When illuminated by a CW interrogating laser source at the latter wavelength, the system acts as a resonant Fabry Perot (FP) sensing cavity, the reflected intensity output of which is dependent upon acoustically-induced changes in the optical thickness of the polymer film. By optically addressing different regions of the sensor, a notional ultrasound array of arbitrary aperture and dimensionality can be synthesised. The system was demonstrated in backward mode by transmitting 1064nm excitation laser pulses through the sensor into an Intralipid scattering solution (μ_a=0.03mm^-1, μ_s^'=1mm^-1) containing various absorbing structures and detecting the resulting photoacoustic signals over a line. A 1D depth profile of a 1.3mm thick absorbing polymer sheet (µ_a=0.8mm^-1) immersed to a depth of 12mm in the Intralipid solution was obtained by performing an 11mm linescan. In another experiment, a 3-layer structure consisting of 0.076mm thick line absorbers was immersed in Intralipid and a 2D image reconstructed from the detected photoacoustic signals using an inverse k-space reconstruction algorithm. Lateral resolution was 0.4mm and the vertical resolution 0.1mm. The ability of this system to map wideband photoacoustic signals with high sensitivity in backward mode may provide a useful tool for high resolution imaging of superficial tissue structures such as the skin microvasculature.

Propagation models to predict the temporal output of a sensor in response to an arbitrary photoacoustically generated initial pressure distribution have been developed. k-space (frequency-wavenumber) implementations have been studied with the aim of producing fast and accurate predictions. The k-space models have several advantages. They may be implemented using the Fast Fourier transform, which makes them efficient, and the impulse response of the sensor may be straightforwardly included, which makes them more accurate. Also, there is a closely related inverse scheme - a 3D photoacoustic imaging algorithm. Studying the forward problem provides insight into the inverse problem and may indicate ways in which the imaging can be improved. For instance, a validated model of the detector response may be used to improve the spatial resolution of an image reconstructed from measurements via deconvolution. The propagation models were experimentally validated. Broadband (30 MHz) ultrasonic pulses were generated in water by illuminating thin polymer sheets and other optically-absorbent targets with a Q switched Nd:YAG laser (1064 nm, 6 ns pulse duration). The output of the Fabry Perot polymer film sensor was compared to the models' predictions.

We propose an approach allowing significant reduction or even complete removal of artifacts that can appear in optoacoustic images acquired with limited number of transducers (missing detectors) due to incomplete data. In optoacoustic tomography the image is reconstructed from a set of acoustic transducers located on the surface of tissue irradiated by a laser. The rigorous solution of the tomographic problem requires covering of the entire surface of the illuminated volume by an array of transducers. However, in practice, only portion of the surface is available. As a result of data incompleteness, artifacts (usually looking like arc-shaped shadows extending from the bright objects) can appear. These artifacts limit the spatial resolution, degrade the image contrast and distort shapes of the reconstructed objects. The results of the numerical simulation, presented in this work, show that the intensity and the shape of the “arc-shadow” artifacts depend on the surface area of uncovered by the acoustic detectors. The cause of the artifacts appearance is the violation of the absorbed energy conservation by the image reconstruction algorithm. Such explanation of this fact represents a key for removal of these artifacts. As presented in the paper, the intensity of the artifacts could be reduced by partial restoration of the missed transducers. In case of sufficient a priori information about number of objects, the proposed algorithm can be considered as the interpolation/extrapolation of the data or substitution of the missed signal by averaged real signal taking into account energy conservation. In a common case, the signals of virtual transducers are restored from the distorted image using the solution of the wave equation. Then the cleaned image is reconstructed from the complete set of signals combining real and virtual transducers. These operations can be repeated iteratively until artifacts become weak. The accuracy of the image reconstruction depends on the number of absent transducers, i.e. portion of the surface area uncovered by the detectors.

Reconstruction for thermoacoustic tomography in an arbitrary detection geometry is proposed by time-reversing the measured field back to the time when the thermoacoustic sources are excited. Time reversal of the field can be implemented efficiently by applying the delay-and-sum algorithm. The theoretical conclusions are supported by a numerical simulation of three-dimensional thermoacoustic tomography.

We present an analytic explanation of the spatial resolution in three-dimensional photo-acoustic (also called opto-acoustic or thermo-acoustic) reconstruction. Based on rigorous reconstruction formulas, we analytically derive the point-spread functions (PSFs) for three types of specific recording geometries, including spherical, planar, and cylindrical surfaces. The PSFs as a function of the bandwidth of the measurement system and the finite size of the detector aperture, as well as the discrete sampling effect on the reconstruction, are investigated. The analyses clearly reveal that the dependence of the PSFs on the bandwidth of all of the recording geometries shares the same space-invariant expression while the dependence on the aperture size of the detector differs. The bandwidth affects both axial and lateral resolution; in contrast, the detector aperture blurs the lateral resolution greatly but the axial resolution only slightly. Under-sampling in the measurement causes significant aliasing artifacts in the reconstruction. A general sampling strategy to avoid aliasing is proposed

We present an image reconstruction technique for ultrasound-modulated optical tomography. It is the first time, to the authors' knowledge, that a reconstruction technique is developed for such tomography. In analogy to X-ray computed tomography, an ultrasonic beam is scanned linearly and angularly across a biological-tissue sample. Ultrasound-modulated optical signals, reflecting the optical properties of the sample inside the ultrasonic column, are detected and taken as the projection data for the reconstruction, where a filtered back-projection algorithm is implemented. With the technique, two-dimensional images of biological tissues in cross-sections containing the scanned ultrasonic axis are obtained. The image resolution is determined by the diameter of the ultrasonic focal zone. The technique can be implemented with any standard signal-detection scheme for ultrasonic modulation of coherent light in scattering media and can be applied directly to achieve three-dimensional images of biological tissues.