This PDF file contains the front matter associated with SPIE Proceedings Volume 8800, including the Title Page, Copyright information, Table of Contents, Introduction (if any), and Conference Committee listing.

Acoustic line detectors have been shown to be capable of providing accurate signals for three-dimensional photoacoustic tomography. Free and guided beam optical Mach-Zehnder interferometers (MZI) have been used as well as a waveguide Fabry-Perot interferometer (FPI). The ultimate sensitivity is expected from a FPI where the optical field in the resonator propagates in the acoustic coupling medium (water) surrounding the imaged object. Such a free-beam FPI is completely optically and acoustically transparent, while providing a higher sensitivity compared to the MZI due to the multiple beam interference. In this work the performance of a FPI for measurement of ultrasound waves is compared to a MZI. It is shown that an at least 4.5-fold higher signal to noise ratio is achieved compared to a MZI. The resolution of the FPI is simulated and measured, showing a constant diameter of the interferometer beam. Verification of the stability of the free beam FPI over longer time periods is demonstrated by acquiring a two-dimensional tomography image of a phantom. The sensitivity and stability of the setup makes it suitable for tomographic imaging.

In optoacoustic imaging absorbing structures excited with short laser pulses generate broadband ultrasound waves, which tomographically detected outside the sample enable reconstruction of initial pressure distribution. As light scatters in biological tissues, the excitation has a three-dimensional (3D) pattern allocation. Accurate reconstruction of the 3D distribution of optical absorption requires a large solid angle of detection of the ultrasonic field. Moreover, the center frequency and bandwidth of a given detector define the range of structure sizes it is able to resolve. Therefore, detectors with different frequency bandwidths record different subsets of information. A volumetric optoacoustic system using linear ultrasound arrays with different central frequencies, 6MHz and 24MHz, is introduced. By employing a novel scanning geometry that takes advantage of the high sensitivity on the transversal dimension of these linear probes, high resolution optoacoustic signals are being recorded. Resolution performance and biological capabilities are demonstrated with a 20um crossed-suture phantom and an excised mouse liver lobe.

Breast cancer is the most common form of cancer and the leading cause of cancer death among females. Early diagnosis improves the survival chances for the disease and that is why there is an ongoing search for improved methods for visualizing breast cancer. One of the hallmarks of breast cancer is the increase in tumor vascularization that is associated with angiogenesis: a crucial factor for survival of malignancies. Photoacoustic imaging can visualize the malignancyassociated increased hemoglobin concentration with optical contrast and ultrasound resolution, without the use of ionizing radiation or contrast agents and is therefore theoretically an ideal method for breast imaging. Previous clinical studies using the Twente Photoacoustic Mammoscope (PAM), which works in forward mode using a single wavelength (1064 nm), showed that malignancies can indeed be identified in the photoacoustic imaging volume as high contrast areas. However, the specific appearance of the malignancies led to questions about the contrast mechanism in relation to tumor vascularization. In this study, the photoacoustic lesion appearance obtained with an updated version of PAM is compared with the lesion appearance on Magnetic Resonance Imaging (MRI), both in general (19 patients) and on an individual basis (7 patients). Further, in 3 patients an extended histopathology protocol is being performed in which malignancies are stained for vascularity using an endothelial antibody: CD31. The correspondence between PAM and MRI and between PAM and histopathology makes it likely that the high photoacoustic contrast at 1064 nm is indeed largely the consequence of the increased tumor vascularization.

A purely optical setup for simultaneous photoacoustic (PA) and laser-ultrasound (US) tomography is presented. It is shown that combined imaging can be achieved by using the same laser pulse for photoacoustic generation and for launching a broadband ultrasound pulse from an optically absorbing target. Detection of the laser-generated plane waves that have been scattered at the imaging object and of the photoacoustic signals emitted from the sample is done interferometrically. This way data for PA and US imaging are acquired within one single measurement. Distinction between the signals is possible due to their different times of flight. After data separation, image reconstruction is done using standard back-projection algorithms. The resolution of the setup was estimated and images of a zebra fish are shown, demonstrating the complementary information of the two imaging modalities.

Quantitative photoacoustic tomography is an emerging imaging technique aiming at estimating the distribution of optical parameters inside tissue from photoacoustic image which is formed by combining optical information and ultrasound propagation. In this paper reconstruction of absorption and scattering distributions using the radiative transfer equation and the diffusion approximation as forward models for light propagation is investigated. Data is simulated using Monte Carlo method and different size target domains are considered. The results show that the radiative transfer equation can estimate both absorption and scattering distributions with good accuracy. Furthermore, in the simulated test cases, the diffusion approximation can produce as good estimates for absorption as the radiative transfer equation.

An innovative very fast non-contact imaging technique for Photoacoustic Tomography is introduced. It is based on holographic optical speckle detection of a transiently altering surface topography for the reconstruction of absorbing targets. The surface movement is obtained by parallel recording of speckle phase changes known as Electronic Speckle Pattern Interferometry. Due to parallelized 2-D camera detection and repetitive excitation with variable delay with respect to the image acquisition, data recording of whole volumes for Photoacoustic Imaging can be completed in times far below one second. The size of the detected area is scalable by optical magnification. As a proof of concept, an interferometric setup is realized, capable of surface displacement detection with an axial resolution of less than 3 nm. The potential of the proposed method for in vivo Photoacoustic Imaging is discussed.

Photoacoustic tomography (PAT) is ideally suited to image tissue vasculature and is therefore able to provide functional response data for the pharmacodynamic time course of vascular targeted therapies. We show in a preclinical model of colorectal carcinoma that 40mg/kg of the vascular disrupting agent OXi4503 causes central tumour blood vessel destruction that can be assessed by PAT at 48 hours. This is confirmed with histological haematoxylin and eosin staining. Outward growth of solid tumours is then static until 16 days post-dose whilst vessel regrowth occurs inwardly to repopulate the necrotic core.

Retinal photocoagulation lacks objective dosage in clinical use, thus the commonly applied lesions are too deep and strong, associated with pain reception and the risk of visual field defects and induction of choroidal neovascularisations. Optoacoustics allows real-time non-invasive temperature measurement in the fundus during photocoagulation by applying short probe laser pulses additionally to the treatment radiation, which excite the emission of ultrasonic waves. Due to the temperature dependence of the Grüneisen parameter, the amplitudes of the ultrasonic waves can be used to derive the temperature of the absorbing tissue. By measuring the temperatures in real-time and automatically controlling the irradiation by feedback to the treatment laser, the strength of the lesions can be defined. Different characteristic functions for the time and temperature dependent lesion sizes were used as rating curves for the treatment laser, stopping the irradiation automatically after a desired lesion size is achieved. The automatically produced lesion sizes are widely independent of the adjusted treatment laser power and individual absorption. This study was performed on anaesthetized rabbits and is a step towards a clinical trial with automatically controlled photocoagulation.

Frequency domain optoacoustics relates to stimulation of optoacoustic signals using intensity modulated continuous wave light instead of pulsed laser light employed in time domain optoacoustic imaging. We present a method to generate frequency domain tomographic images of optical absorbers and cross sectional in-vivo mouse images, showing the changes of optical absorption before and after injection of indocyanine green (ICG). OCIS codes: 170.6960, 170.3880, 170.5220

The discrepancy between optoacoustic reconstruction algorithms assuming point-like and realistic finite-size transducers causes severe artifacts. Two model-based algorithms accounting for finite-size of cylindrically focused detectors are presented and its performance tested in simulations and experiments.

We have generated high resolution images of RF-Contrast in small animals using nearfield thermoacoustic system. This enables us to see some anatomical features of a mouse such as the heart, the spine and the boundary. OCIS codes: (000.0000) General; (000.0000) General [8-pt. type. For codes, see www.opticsinfobase.org/submit/ocis.]

Gold nanorods exhibit intense optical absorbance in the near-infrared window of principal interest for applications in biomedical optics making them appealing as contrast agents in photoacoustic imaging and selective photothermolysis of cancer. However their photoinstability under laser irradiation remains a drawback of practical concern. In particular, when GNRs are irradiated with nanosecond laser pulses in resonance with their plasmon oscillations, there may occur phenomena like reshaping into spherical particles, as well as fragmentation at higher optical fluences, which result into modifications of their optical absorption bands and substantial loss of photoacoustic conversion efficiency.

In this contribution we present an investigation of the photostability of gold nanorods embedded in biomimetic scaffolds by means of photoacustic experiments.

A method for determining the Grüneisen parameter of absorbing liquids is presented. An integrating sphere is used as a platform for accurate and simultaneous detection of optical and photoacoustic signals. Calibration of the setup is done using aqueous ink solutions. The method is validated using human blood.

Photoacoustic/thermoacoustic imaging is an emerging hybrid imaging modality combining optical/microwave imaging with ultrasound imaging. The photoacoustic/thermoacoustic signal generated are affected by the nature of excitation pulse waveform, pulse width, target object size, transducer size etc. In this study k-wave was used to simulate various configurations of excitation pulse, transducer types, and target object sizes and to see their effect on the photoacoustic/thermoacoustic signals. Numerical blood vessel phantom was also used to see the effect of various pulse waveform and excitation pulse width on the reconstructed images. This study will help in optimizing transducer design and reconstruction methods to obtain the superior reconstructed image.

Quantification of extrinsically administered contrast agents in optoacoustic (photoacoustic) tomography is a challenging task, mainly due to spectrally-dependent contributions from absorbing background tissue chromophores leading to strong changes in the light fluence for different positions and wavelengths. Herein we present a procedure capable of self-calibrating light fluence variations for quantitative imaging of the distribution of photo-absorbing agents. The method makes use of a logarithmic representation of the images taken at different wavelengths assisted with a blind unmixing approach. It is shown that the serial expansion of the logarithm of an image contains a term representing the ratio between absorption of the probe of interest and other background components. Provided the background variations are not very high, this term can be isolated with an unmixing algorithm, so that the concentration of the probe can subsequently be resolved.

Back-projection algorithms are probably the fastest approach to reconstruct an image from a set of optoacoustic (photoacoustic) data set. However, standard implementations of back-projection formulae are still not adequate for real-time (greater than 5 frames per second) visualization of three-dimensional structures. This is due to the fact that the number of voxels one needs to reconstruct in three-dimensions is orders of magnitude larger than the number of pixels in two dimensions. Herein we describe a parallel implementation of optoacoustic signal processing and back-projection reconstruction in an attempt to achieve real-time visualization of structures with three-dimensional optoacoustic tomographic systems. For this purpose, the parallel computation power of a graphics processing unit (GPU) is utilized. The GPU is programmed with OpenCL, a programming language for heterogenous platforms. We showcase that with the implementation suggested in this work imaging at frame rates up to 50 high-resolution three-dimensional images per second is achievable.

Some biological samples contain strongly mismatched tissues such as bones or lungs that generally produce acoustic reflections and scattering, leading to consequent image distortion if the reconstruction is performed by assuming an acoustically homogeneous medium. A weighted optoacoustic reconstruction procedure based on statistical principles is presented herein to tomographically image tissues with strong acoustic mismatch. The procedure is based on weighting the contribution of the collected optoacoustic signals to the reconstruction with the probability that they are not affected by reflections or scattering. Since such probability depends on the available information about the distribution of optical absorbers, an iterative procedure in which the reconstructted images are used to recalculate the weighting values is presented in this work. The benefit of the reconstruction procedure described herein is showcased by reconstructing a phantom containing a straw filled with air, which mimicks air-gaps in actual biological samples.

Reconstruction in multispectral optoacoustic tomography has become an critical area of importance, given the development of real-time imaging and visualization techniques. Speed of sound calibration is an intrinsic problem associated with the reconstruction process. Traditionally, the calibration has been user mediated, making it a tedious and offline affair. In this manuscript, we aim to introduce autofocusing and wavelet based measures to automatically calibrate the speed of sound. Further, it is observed that the temperature of the coupling medium (water) often drift during the signal acquisition, severely straining the image quality. The measures address these problems by iteratively determining the speeds with the changing boundary conditions with time.