Search

Photoacoustic imaging using a focused, scanning detector in combination with a pulsed light source is a common technique to visualize light-absorbing structures in biological tissue. In the acoustic resolution mode, where the imaging resolution is given by the properties of the transducer, there are various challenges related to the choice of sensors and the optimization of the illumination. These are addressed by linking a Monte Carlo simulation of energy deposition to a time-domain model of acoustic propagation and detection. In this model, the spatial and electrical impulse responses of the focused transducer are combined with a model of acoustic attenuation in a single response matrix, which is used to calculate detector signals from a volumetric distribution of absorbed energy density. Using the radial symmetry of the detector, the calculation yields a single signal in less than a second on a standard personal computer. Various simulation results are shown, comparing different illumination geometries and demonstrating spectral imaging. Finally, simulation results and experimental images of an optically characterized phantom are compared, validating the accuracy of the model. The proposed method will facilitate the design of photoacoustic imaging devices and will be used as an accurate forward model for iterative reconstruction techniques. [ABSTRACT FROM AUTHOR]

Photoacoustic flowmetry (PAF) based on time-domain cross correlation of photoacoustic signals is a promising technique for deep tissue measurement of blood flow velocity. Signal processing has previously been developed for single element transducers. Here, the processing methods for acoustic resolution PAF using a clinical ultrasound transducer array are developed and validated using a 64-element transducer array with a -6 dB detection band of 11 to 17 MHz. Measurements were performed on a flow phantom consisting of a tube (580 µm inner diameter) perfused with human blood flowing at physiological speeds ranging from 3 to 25 mm/s. The processing pipeline comprised: image reconstruction, filtering, displacement detection, and masking. High-pass filtering and background subtraction were found to be key preprocessing steps to enable accurate flow velocity estimates, which were calculated using a cross-correlation based method. In addition, the regions of interest in the calculated velocity maps were defined using a masking approach based on the amplitude of the cross-correlation functions. These developments enabled blood flow measurements using a transducer array, bringing PAF one step closer to clinical applicability. [ABSTRACT FROM AUTHOR]

We investigate the feasibility of photoacoustic (PA) imaging to quantify the concentration of surfacelocalized nanoparticles, using tissue-mimicking phantoms and imaging with a commercial PA instrument at 815 nm and a linear-array transducer at a center frequency of 40 MHz. The nanoparticles were J-aggregating porphysomes (JNP) comprising self-assembling, all-organic porphyrin-lipid micelles with a molar absorption coefficient of 8.7 × 108 cm-1 M-1 at this wavelength. The PA signal intensity versus JNP areal concentration followed a sigmoidal curve with a reproducible linear range of ∼17 fmol/mm2 to 11 pmol/mm2, i.e., ∼3 orders of magnitude with ±34% error. For physiologically-relevant conditions (i.e., optical scattering-dominated tissues: transport albedo >0.8) and JNP concentrations above ∼330 fmol/mm2, the PA signal depends only on the nanoparticle concentration. Otherwise, independent measurement of the optical absorption and scattering properties of the underlying tissue is required for accurate quantification. The implications for surface PA imaging, such as in the use of targeted nanoparticles applied topically to tissue as in endoscopic diagnosis, are considered. [ABSTRACT FROM AUTHOR]

Genetically encoded contrast in photoacoustic imaging (PAI) is complementary to the intrinsic contrast provided by endogenous absorbing chromophores such as hemoglobin. The use of reporter genes expressing absorbing proteins opens the possibility of visualizing dynamic cellular and molecular processes. This is an enticing prospect but brings with it challenges and limitations associated with generating and detecting different types of reporters. The purpose of this review is to compare existing PAI reporters and signal detection strategies, thereby offering a practical guide, particularly for the nonbiologist, to choosing the most appropriate reporter for maximum sensitivity in the biological and technological system of interest. [ABSTRACT FROM AUTHOR]

We have constructed a prototype photoacoustic mammography system (PAM-02) capable of simultaneously acquiring photoacoustic (PA) and ultrasound (US) images. Each PA, US, and fused PA/US image can be acquired over a wide area of the breast using the scanning module of a US transducer, a PA detector, and optical prisms. The resolution of the PA images exhibits improvement from 2 to 1 mm compared to images acquired using our previous prototype. The maximum scan area of PAM-02 is 90 mm along the horizontal axis and 150 mm along the vertical axis. In a phantom experiment, the available depth was at least 45 mm. A representative example of the application of the PAM-02 prototype in clinical research at Kyoto University is presented and shows S-factor images, which are considered an approximation parameter related to hemoglobin saturation of tumor-related blood vessels. We confirmed the applicability of the system for anatomical and biological research. [ABSTRACT FROM AUTHOR]

Noninvasive real-time temperature imaging during thermal therapies is able to significantly improve clinical outcomes. An optoacoustic (OA) temperature monitoring method is proposed for noninvasive real-time thermometry of vascularized tissue during cryotherapy. The universal temperature-dependent optoacoustic response (ThOR) of red blood cells (RBCs) is employed to convert reconstructed OA images to temperature maps. To obtain the temperature calibration curve for intensity-normalized OA images, we measured ThOR of 10 porcine blood samples in the range of temperatures from 40°C to -16°C and analyzed the data for single measurement variations. The nonlinearity (ΔTmax) and the temperature of zero OA response (T0) of the calibration curve were found equal to 11.4 ± 0.1°C and -13.8 ± 0.1°C, respectively. The morphology of RBCs was examined before and after the data collection confirming cellular integrity and intracellular compartmentalization of hemoglobin. For temperatures below 0°C, which are of particular interest for cryotherapy, the accuracy of a single temperature measurement was ±1°C, which is consistent with the clinical requirements. Validation of the proposed OA temperature imaging technique was performed for slow and fast cooling of blood samples embedded in tissue-mimicking phantoms. [ABSTRACT FROM AUTHOR]

Laser photocoagulation is an established treatment for a variety of retinal diseases. However, when using the same irradiation parameter, the size and strength of the lesions are unpredictable due to unknown inter- and intraindividual optical properties of the fundus layers. The aim of this work is to investigate a feedback system to generate desired lesions of preselectable strengths by automatically controlling the irradiation time. Optoacoustics were used for retinal temperature monitoring. A 532-nm continuous wave Nd:YAG laser was used for photocoagulation. A 75-ns∕523-nm Q-switched Nd:YLF laser simultaneously excited temperature-dependent pressure transients, which were detected at the cornea by an ultrasonic transducer embedded in a contact lens. The temperature data were analyzed during the irradiation by a LabVIEW routine. The treatment laser was switched off automatically when the required lesion strength was achieved. Five different feedback control algorithms for different lesion sizes were developed and tested on rabbits in vivo. With a laser spot diameter of 133 μm, five different lesion types with ophthalmoscopically visible diameters ranging mostly between 100 and 200 μm, and different appearances were achieved by automatic exposure time control. The automatically controlled lesions were widely independent of the treatment laser power and the retinal pigmentation. [ABSTRACT FROM AUTHOR]

Optical-resolution photoacoustic microscopy (ORPAM) in theory provides lateral resolution equivalent to the optical diffraction limit. Scattering media, such as biological turbid media, attenuates the optical signal and also alters the diffraction-limited spot size of the focused beam. The ORPAM signal is generated only from a small voxel in scattering media with dimensions equivalent to the laser spot size after passing through scattering layers and is detected by an acoustic transducer, which is not affected by optical scattering. Thus, both ORPAM and confocal laser scanning microscopy (CLSM) reject scattered light. A multimodal optical microscopy platform that includes ORPAM and CLSM was constructed, and the lateral resolution of both modes was measured using patterned thin metal film with and without a scattering barrier. The effect of scattering media on the lateral resolution was studied using different scattering coefficients and was compared to computational results based on Monte Carlo simulations. It was found that degradation of lateral resolution due to optical scattering was not significant for either ORPAM or CLSM. The depth discrimination capability of ORPAM and CLSM was measured using microfiber embedded in a light scattering phantom material. ORPAM images demonstrated higher contrast compared to CLSM images partly due to reduced acoustic signal scattering. [ABSTRACT FROM AUTHOR]

The feasibility of photoacoustic imaging (PAI) application was evaluated to map punctured blood vessels thermally treated by high-intensity focused ultrasound (HIFU) for hemostasis. A single-element HIFU transducer with a central frequency of 2.0 MHz, was used to induce thermal hemostasis on the punctured arteries. The HIFU-treated lesion was imaged and localized by high-contrast PAI guidance. The results showed that complete hemostasis was achieved after treatment of the damaged blood vessels within 25 to 52 s at the acoustic intensity of 3600 W/cm². The coagulation time for the animal artery was ~20% longer than that of the phantom possibly due to a lower Young's modulus. The reconstructed PA images were able to distinguish the treated area from the surrounding tissue in terms of augmented signal amplitudes (up to three times). Spectroscopic studies demonstrated that the optimal imaging wavelength was found to be 700 nm in order to reconstruct high-contrast photoacoustic images on HIFU-treated lesions. The proposed PAI integrated with HIFU treatment can be a feasible application to obtain safe and rapid hemostasis for acute arterial bleeding. [ABSTRACT FROM AUTHOR]

Photoacoustic tomography (PAT) detects ultrasound signals generated by the objects after absorbing illuminating photons. However, the widely used piezoelectric ultrasound transducers are generally not optically transparent, which would cause conflicts between the light illumination and the ultrasonic detection in PAT. We report a different acoustically penetrable optical reflector (APOR) concept to provide a solution to this conflict. We measured the properties of an APOR and experimentally tested its performance in a PAT system. The results demonstrated that the APOR successfully allowed the transducer to detector photoacoustic signals without affecting the light illumination. Moreover, the APOR concept can be readily implemented in various PAT systems. [ABSTRACT FROM AUTHOR]

We introduce a needle probe based on photoacoustics (PA) to extend the scope of optical needle methods in guiding biopsies. Pulsed light is coupled to an optical fiber in a needle to be inserted in tissue, and PA signals are detected using an ultrasound imager used for needle guidance. This PA needle samples large volumes and possesses an imaging component so that sites forward and offaxis of the fiber are surveyed. This allows navigation of those regions for optical characterization and direct biopsy in a subsequent step. The concept is explored on simple phantoms and biological specimens. [ABSTRACT FROM AUTHOR]

We develop a system for three-dimensional whole-body optoacoustic tomography of small animals for applications in preclinical research. The tomographic images are obtained while the objects of study (phantoms or mice) are rotated within a sphere outlined by a concave arc-shaped array of 64 piezocomposite transducers. Two pulsed lasers operating in the near-IR spectral range (755 and 1064 nm) with an average pulsed energy of about 100 mJ, a repetition rate of 10 Hz, and a pulse duration of 15 to 75 nsare used as optical illumination sources. During the scan, the mouse is illuminated orthogonally to the array with two wide beams of light from a bifurcated fiber bundle. The system is capable of generating images of individual organs and blood vessels through the entire body of a mouse with spatial resolution of ∼0.5 mm. [ABSTRACT FROM AUTHOR]

Complete and continuous imaging of microvascular networks is crucial for a wide variety of biomedical applications. Photoacoustic tomography can provide high resolution microvascular imaging using hemoglobin within red blood cells (RBCs) as an endogenic contrast agent. However, intermittent RBC flow in capillaries results in discontinuous and fragmentary capillary images. To overcome this problem, we use Evans blue (EB) dye as a contrast agent for in vivophotoacoustic imaging. EB has strong optical absorption and distributes uniformly in the blood stream by chemically binding to albumin. With the help of EB, complete and continuous microvascular networks—especially capillaries—are imaged. The diffusion dynamics of EB leaving the blood stream and the clearance dynamics of the EB-albumin complex are also quantitatively investigated. [ABSTRACT FROM AUTHOR]

For real-time optoacoustic imaging of the human body, a linear array transducer and reflection mode optical irradiation is preferably used. Experimental outcomes however revealed that such a setup results in significant image background, which prevents imaging structures at the ultimate depth limited only by the optical attenuation of the irradiating light and the signal noise level. Various sources of image background, such as bulk tissue absorption, reconstruction artifacts, and backscattered ultrasound, could be identified. To overcome these limitations, we developed a novel method that results in significantly reduced background and increased imaging depth. For this purpose, we acquire, in parallel, a series of optoacoustic and echo-ultrasound images while the tissue sample is gradually deformed by an externally applied force. Optoacoustic signals and background signals are differently affected by the deformation and can thus be distinguished by image processing. This method takes advantage of a combined optoacoustic/echo-ultrasound device and has a strong potential for improving real-time optoacoustic imaging of deep tissue structures. [ABSTRACT FROM AUTHOR]

The hearing performance with conventional hearing aids and cochlear implants is dramatically reduced in noisy environments and for sounds more complex than speech (e. g. music), partially due to the lack of localized sensorineural activation across different frequency regions with these devices. Laser light can be focused in a controlled manner and may provide more localized activation of the inner ear, the cochlea. We sought to assess whether visible light with parameters that could induce an optoacoustic effect (532 nm, 10-nspulses) would activate the cochlea. Auditory brainstem responses (ABRs) were recorded preoperatively in anesthetized guinea pigs to confirm normal hearing. After opening the bulla, a 50-mcore-diameter optical fiber was positioned in the round window niche and directed toward the basilar membrane. Optically induced ABRs (OABRs), similar in shape to those of acoustic stimulation, were elicited with single pulses. The OABR peaks increased with energy level (0.6 to 23 J/pulse) and remained consistent even after 30 minutesof continuous stimulation at 13 J, indicating minimal or no stimulation-induced damage within the cochlea. Our findings demonstrate that visible light can effectively and reliably activate the cochlea without any apparent damage. Further studies are in progress to investigate the frequency-specific nature and mechanism of green light cochlear activation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The optoacoustic technique is a noninvasive imaging method with high spatial resolution. It potentially can be used to monitor anatomical and physiological changes. Photodynamic therapy (PDT)-induced vascular damage is one of the important mechanisms of tumor destruction, and real-time monitoring of vascular changes can have therapeutic signicance. A unique optoacoustic system is developed for neovascular imaging during tumor phototherapy. In this system, a single-pulse laser beam is used as the light source for both PDT and for concurrently generating ultrasound signals for optoacoustic imaging. To demonstrate its feasibility, this system is used to observe vascular changes during PDT treatment of chicken chorioallantoic membrane (CAM) tumors. The photosensitizer used in this study is protoporphyrin IX (PpIX) and the laser wavelength is 532 nm. Neovascularization in tumor angiogenesis is visualized by a series of optoacoustic images at different stages of tumor growth. Damage of the vascular structures by PDT is imaged before, during, and after treatment. Rapid, real-time determination of the size of targeted tumor blood vessels is achieved, using the time difference of positive and negative ultrasound peaks during the PDT treatment. The vascular effects of different PDT doses are also studied. The experimental results show that a pulsed laser can be conveniently used to hybridize PDT treatment and optoacoustic imaging and that this integrated system is capable of quantitatively monitoring the structural change of blood vessels during PDT. This method could be potentially used to guide PDT and other phototherapies using vascular changes during treatment to optimize treatment protocols, by choosing appropriate types and doses of photosensitizers and doses of light. [ABSTRACT FROM AUTHOR]