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Smart microgels (μGels) made of polymeric particles doped with inorganic nanoparticles have emerged recently as promising multifunctional materials for nanomedicine applications. However, the synthesis of these hybrid materials is still a challenging task with the necessity to control several features, such as particle sizes and doping levels, in order to tailor their final properties in relation to the targeted application. We report herein an innovative modular strategy to achieve the rational design of well-defined and densely filled hybrid particles. It is based on the assembly of the different building blocks, i.e., μGels, dyes, and small gold nanoparticles (4 nm), and the tuning of nanoparticle loading within the polymer matrix through successive incubation steps. The characterization of the final hybrid networks using UV-vis absorption, fluorescence, transmission electron microscopy, dynamic light scattering, and small-angle X-ray scattering revealed that they uniquely combine the properties of hydrogel particles, including high loading capacity and stimuli-responsive behavior, the photoluminescent properties of dyes (rhodamine 6G, methylene blue and cyanine 7.5), and the features of gold nanoparticle assembly. Interestingly, in response to pH and temperature stimuli, the smart hybrid μGels can shrink, leading to the aggregation of the gold nanoparticles trapped inside the polymer matrix. This stimuli-responsive behavior results in plasmon band broadening and red shift toward the near-infrared region (NIR), opening promising prospects in biomedical science. Particularly, the potential of these smart hybrid nanoplatforms for photoactivated hyperthermia, photoacoustic imaging, cellular internalization, intracellular imaging, and photothermal therapy was assessed, demonstrating well controlled multimodal opportunities for theranostics.

We have designed a new Bodipy scaffold for efficient

Volumetric, multimodal imaging with precise spatial and temporal co-registration can provide valuable and complementary information for diagnosis and monitoring. Considerable research has sought to combine 3D photoacoustic (PA) and ultrasound (US) imaging in clinically translatable configurations. However, technical compromises currently result in poor image quality either for photoacoustic or ultrasonic modes. This work aims to provide translatable, high quality, simultaneously co-registered dual-mode PA/US 3D tomography. Volumetric imaging based on a synthetic aperture approach was implemented by interlacing PA and US acquisitions during a rotate-translate scan with a 5-MHz linear array (12 angles and 30-mm translation to image a 21-mm diameter, 19 mm long cylindrical volume within 21 seconds). For co-registration, an original calibration method using a specifically designed thread phantom was developed to estimate 6 geometrical parameters and 1 temporal off-set through global optimization of the reconstructed sharpness and superposition of calibration phantom structures. Phantom design and cost function metrics were selected based on analysis of a numerical phantom, and resulted in a high estimation accuracy for the 7 parameters. Experimental estimations validated the calibration repeatability. The estimated parameters were used for bimodal reconstruction of additional phantoms with either identical or distinct spatial distributions of US and PA contrasts. Superposition distance of the two modes was within < 10% of the acoustic wavelength and a wavelength-order uniform spatial resolution was obtained. This dual-mode PA/US tomography should contribute to more sensitive and robust detection and follow-up of biological changes or the monitoring slower-kinetic phenomena in living systems such as the accumulation of nanoagents., 13 pages, 5 figures

Deterministic control of coherent random light is highly important for information transmission through complex media. However, only a few simple speckle transformations can be achieved through diffusers without prior characterization. As recently shown, spiral wavefront modulation of the impinging beam allows permuting intensity maxima and intrinsic $\pm 1$-charged optical vortices. Here, we study this cyclic-group algebra when combining spiral phase transforms of charge $n$, with $D_3$- and $D_4$-point-group symmetry star-like amplitude modulations. This combination allows statistical strengthening of permutations and controlling the period to be 3 and 4, respectively. Phase saddle-points are shown to complete the cycle. These results offer new tools to manipulate critical points in speckles., Comment: 14 pages, 10 figures, 4 tables

Diversity of the design and alignment of illumination and ultrasonic transducers empower the fine scalability and versatility of optoacoustic imaging. In this study, we implement an innovative high-resolution optoacoustic mesoscopy for imaging the vasculature and tissue oxygenation within subcutaneous and orthotopic cancerous implants of mice in vivo through acquisition of tomographic projections over 180° at a central frequency of 24 MHz. High-resolution volumetric imaging was combined with multispectral functional measurements to resolve the exquisite inner structure and vascularization of the entire tumor mass using endogenous and exogenous optoacoustic contrast. Evidence is presented for constitutive hypoxemia within the carcinogenic tissue through analysis of the hemoglobin absorption spectra and distribution. Morphometric readouts obtained with optoacoustic mesoscopy have been verified with high-resolution ultramicroscopic studies. The findings described herein greatly extend the applications of optoacoustic mesoscopy toward structural and multispectral functional measurements of the vascularization and hemodynamics within solid tumors in vivo and are of major relevance to basic and preclinical oncological studies in small animal models.

In this work, we experimentally investigate thermal-based nonlinear photoacoustic generation as a mean to discriminate between different types of absorbing particles. The photoacoustic generation from solutions of dye molecules and gold nanospheres (same optical densities) was detected using a high frequency ultrasound transducer (20MHz). Photoacoustic emission was observed with gold nanospheres at low fluence for an equilibrium temperature around 4°C, where the linear photoacoustic effect in water vanishes, highlighting the nonlinear emission from the solution of nanospheres. The photoacoustic amplitude was also studied as a function of the equilibrium temperature from 2°C to 20°C. While the photoacoustic amplitude from the dye molecules vanished around 4°C, the photoacoustic amplitude from the gold nanospheres remained significant over the whole temperature range. Our preliminary results suggest that in the context of high frequency photoacoustic imaging, nanoparticles may be discriminated from molecular absorbers based on nanoscale temperature rises.

Model organisms such as zebrafish play an important role for developmental biologists and experimental geneticists. Still, as they grow into their post-embryonic stage of development it becomes more and more difficult to image them because of high light scattering inside biological tissue. Optoacoustic mesoscopy based on spherically focused, high frequency, ultrasound detectors offers an alternative, where it relies on the focusing capabilities of the ultrasound detectors in generating the image rather than on the focusing of light. Nonetheless, because of the limited numerical aperture the resolution is not isotropic, and many structures, especially elongated ones, such as blood vessels and other organs, are either invisible, or not clearly identifiable on the final image. Herein, based on high frequency ultrasound detectors at 100 MHz and 50 MHz we introduce multi orientation (view) optoacoustic mesoscopy. We collect a rich amount of signals from multiple directions and combine them using a weighted sum in the Fourier domain and a Wiener deconvolution into a single high resolution three-dimensional image. The new system achieves isotropic resolutions on the order of 10 μm in-plane, 40 μm axially, and SNR enhancement of 15 dB compared to the single orientation case. To showcase the system we imaged a juvenile zebrafish ex vivo, which is too large to image using optical microscopic techniques, the reconstructed images show unprecedented performance in terms of SNR, resolution, and clarity of the observed structures. Using the system we see the inner organs of the zebrafish, the pigmentation, and the vessels with unprecedented clarity.

Reliably assessing tissue viability during surgery is of major importance in surgical procedures. The most basic requirement for viability is sufficient oxygen supply to the tissue. Therefore it is highly desirable to visualize in real-time the dynamic process of blood perfusion up to and within the microvasculature. A modality sensitive to structures in the range of few hundred micrometers and offering high contrast to the embedding tissue is then needed. To this end, a number of methods have been developed, but have had no significant impact on the clinical routine due to various deficiencies. In this paper we demonstrate the applicability of optoacoustic imaging, which combines ultrasonic resolution with strong optical contrast. A method for optoacoustic perfusion assessment, based on a local and repeatable injection of saline, was proposed and assessed ex-vivo on large pig bowels and in-vivo in mouse tails. The obtained dynamic perfusion images highlight the method's potential to enable immediate and quantitative assessment of tissue viability during surgery.

In security applications, several methods are used for detection of hidden objects. Metal detectors and palpation are the most common methods. Non-contact acoustic waves imaging of elastic heterogeneities in superficial body tissues could be an interesting alternative.

Intensity minima and maxima of speckle patterns obtained behind a diffuser are experimentally interchanged by applying a spiral phase delay of charge $\pm 1$ to the impinging coherent beam. This transform arises from the intuitive expectation that a tightly focused beam is so-changed into a vortex beam and vice-versa. The statistics of extrema locations and the intensity distribution of the so-generated "complementary" patterns are characterized by numerical simulations. It is demonstrated experimentally that the incoherent superposition of the three "complementary speckle patterns" yield a synthetic speckle grain size enlarged by a factor $\sqrt{3}$. A cyclic permutation of optical vortices and maxima is unexpectedly observed and discussed., 9 pages, 9 figures

In deep photoacoustic imaging, resolution is inherently limited by acoustic diffraction, and ultrasonic frequencies cannot be arbitrarily increased because of attenuation in tissue. Here we report on the use of multiple speckle illumination to perform super resolution photoacoustic imaging. We show that the analysis of speckle-induced second-order fluctuations of the photoacoustic signal combined with deconvolution enables to resolve optically absorbing structures below the acoustic diffraction limit.

Wavefront control allows controlling interferences of coherent scattered light at depth in scattering tissues. Combined with photoacoustics imaging, I will show it allows photoacoustic-guided focusing in depth, and improved photoacoustic imaging.

This presentation will illustrate how optical speckle patterns, a manifestation of coherent light discarded by the transport theory for energy, may be exploited to enhance photoacoustic imaging, in particular in terms of visibility and super-resolution. Article not available.

Gas nuclei exist naturally in living bodies. Their activation initiates cavitation activity, and is possible using short ultrasonic excitations of high amplitude. However, little is known about the nuclei population in vivo, and therefore about the rarefaction pressure required to form bubbles in tissue. A novel method dedicated to in vivo investigations was used here that combines passive and active cavitation detection with a multi-element linear ultrasound probe (4–7 MHz). Experiments were performed in vivo on the brain of trepanated sheep. Bubble nucleation was induced using a focused single-element transducer (central frequency 660 kHz, f -number = 1) driven by a high power (up to 5 kW) electric burst of two cycles. Successive passive recording and ultrafast active imaging were shown to allow detection of a single nucleation event in brain tissue in vivo. Experiments carried out on eight sheep allowed statistical studies of the bubble nucleation process. The nucleation probability was evaluated as a function of the peak negative pressure. No nucleation event could be detected with a peak negative pressure weaker than −12.7 MPa, i.e. one order of magnitude higher than the recommendations based on the mechanical index. Below this threshold, bubble nucleation in vivo in brain tissues is a random phenomenon. (Some figures in this article are in colour only in the electronic version)

Photoacoustic imaging can achieve high-resolution three-dimensional (3-D) visualization of optical absorbers at penetration depths of ∼1 cm in biological tissues by detecting optically induced high ultrasound frequencies. Tomographic acquisition with ultrasound linear arrays offers an easy implementation of single-side access, parallelized, and high-frequency detection, but usually comes with an image quality impaired by the directionality of the detectors. Indeed, a simple translation of the array perpendicular to its median imaging plane is often used, but results both in a poor resolution in the translation direction and strong limited-view artifacts.To improve the spatial resolution and the visibility of complex structures while retaining a planar detection geometry, we introduce, in this paper, a rotate-translate scanning scheme and investigate the performance ofa scanner implemented at 15 MHz center frequency. The developed system achieved a quasi-isotropic uniform 3-D resolution of ∼170 μm over a cubic volume of side length 8.5 mm, i.e., an improvement in the resolution in the translation direction by almost one order of magnitude. Dual-wavelength imaging was also demonstrated with ultrafast wavelength shifting. The validity of our approach was shown in vitro. We discuss the ability to enable in vivo imaging for preclinical and clinical studies.

We have developed an epi-illumination raster-scan optoacoustic mesoscopy system (RSOM), the new system is capable of imaging model organisms, and vasculature. The newly developed system is based on a custom designed; spherically focused detector with a Characterization of the system shows an isotropic lateral resolution of 18 μm, and an axial resolution of 4 μm. The scan times are on the order of 8 minutes for a field of view of 10×10 mm2. The achieved resolution is slightly degraded up to a depth of 5 mm. After characterizing the system we showcase it's performance on a zebrafish ex vivo, and an excised mouse ear. Additionally, to improve the visibility of small structures we have reconstructed the high frequencies, and the low frequencies separately, and at the end overplayed the two reconstructions using different colors, this way the high frequencies are not masked by the low frequencies which have a higher signal to noise ratio.

International audience; We study the potential of photoacoustic guidance for light focusing through scattering samples via wavefront-shaping and iterative optimization. We experimentally demonstrate that the focusing efficiency on an extended absorber can be improved by iterative optimization of the high frequency components of the broadband photoacous-tic signal detected with a spherically focused transducer. We demonstrate more than 12-fold increase in the photoacoustic signal generated by a 30 μm wire using a narrow frequency band around 60 MHz. By monitoring the speckle pattern evolution during the optimization process with a CCD camera, we experimentally confirm that such optimization leads to a smaller optical focus than what would be obtained by optimizing lower frequencies of the photoacoustic feedback.

Optoacoutic mesoscopy aims to bridge the gap between optoacoustic microscopy and optoacoustic tomography. We have developed a setup for optoacoustic mesoscopy where we use a high frequency, high numerical aperture spherically focused ultrasound transducer, with a wide bandwidth of 25-125 MHz. The excitation is performed using a diode laser capable of >500 μJ/pulse, 1.8ns pulse width, 1.4 kHz pulse repetition rate, at 515 nm. The system is capable to penetrate more than 5 mm with a resolution of 7 μm axially and 30 μm transversally. Using high-speed stages and scanning the transducer in a quasi-continuous mode, a field of view of 2×2 mm2 is scanned in less than 2 minutes. The system is suitable for imaging biological samples that have a diameter of 1-5 mm; zebrafish, drosophila melanogaster, and thin biological samples such as the mouse ear and mouse extremities. We have used our mesoscopic setup to generate 3- dimensional images of genetically modified drosophila fly, and drosophila pupae expressing GFP from the wings, high resolution images were generated in both cases, in the fly we can see the wings, the legs, the eyes, and the shape of the body. In the pupae the outline of the pupae, the spiracles at both ends and a strong signal corresponding to the location of the future wings are observed.

We investigate experimentally the use of speckle illumination for photoacoustic imaging. In particular, we demonstrate that otherwise invisible features are revealed through high-frequency signals fluctuations from different speckle realizations.

International audience; We implement the photoacoustic transmission matrix approach on a two-dimensional photoacoustic imaging system, using a 15 MHz linear ultrasound array. Using a black leaf skeleton as a complex absorbing structure, we demonstrate that the photoacoustic transmission matrix approach allows to reveal structural features that are invisible in conventional photoacoustic images, as well as to selectively control light focusing on absorbing targets, leading to a local enhancement of the photoacoustic signal.

Image quality in 3-D optoacoustic (photoacoustic) tomography is greatly influenced by both the measurement system, in particular the number and spatial arrangement of ultrasound sensors, and the ability to account for the spatio-temporal response of the sensor element(s) in the reconstruction algorithm. Herein we present a reconstruction procedure based on the inversion of a time-domain forward model incorporating the spatial impulse response due to the shape of the transducer, which is subsequently applied in a tomographic system based on a translation-rotation scan of a linear detector array. The proposed method was also adapted to cope with the data-intensive requirements of high-resolution volumetric optoacoustic imaging. The processing of 2 · 10 (4) individual signals resulted in well-resolved images of both ~ 200 μm absorbers in phantoms and complex vascular structures in biological tissue. The results reported herein demonstrate that the introduced model-based methodology exhibits a better contrast and resolution than standard back-projection and model-based algorithms that assume point detectors. Moreover, the capability of handling large datasets anticipates that model-based methods incorporating the sensor properties can become standard practice in volumetric opto acoustic image formation.

In high-frequency photoacoustic imaging with uniform illumination, homogeneous photo-absorbing structures may be invisible because of their large size or limited-view issues. Here we show that, by exploiting dynamic speckle illumination, it is possible to reveal features which are normally invisible with a photoacoustic system comprised of a 20MHz linear ultrasound array. We demonstrate imaging of a 5 mm diameter absorbing cylinder and a 30 micrometer black thread arranged in a complex shape. The hidden structures are directly retrieved from photoacoustic images recorded for different random speckle illuminations of the phantoms by assessing the variation in the value of each pixel over the illumination patterns., Comment: 4 pages, 3 figures, Accepted in Optics letters

International audience; Bubbles can form in biological tissues through ultrasonic activation of natural gas nuclei. The damaging aftereffects raise safety concerns. However, the population of nuclei is currently unknown, and bubble nucleation is stochastic and thus unpredictable. This study investigates the statistical behavior of bubble nucleation experimentally and introduces a model-based analysis to determine the distribution of nuclei in biological samples-two pig blood samples in vitro. Combined ultra-fast passive and active cavitation detection with a linear array was used to detect nucleation from pulsed ultrasound excitations at 660 kHz. Single nucleation events were detected at peak rarefaction pressures from -3.6 to -24 MPa, and the nucleation probability over the range 0 to 1 was estimated from more than 330 independent acquisitions per sample. Model fitting of the experimental probability revealed that the distribution of nuclei is most likely continuous, and nuclei are rare in comparison to blood cells.

Broadband optoacoustic waves generated by biological tissues excited with nanosecond laser pulses carry information corresponding to a wide range of geometrical scales. Typically, the frequency content present in the signals generated during optoacoustic imaging is much larger compared to the frequency band captured by common ultrasonic detectors, the latter typically acting as bandpass filters. To image optical absorption within structures ranging from entire organs to microvasculature in three dimensions, we implemented optoacoustic tomography with two ultrasound linear arrays featuring a center frequency of 6 and 24 MHz, respectively. In the present work, we show that complementary information on anatomical features could be retrieved and provide a better understanding on the localization of structures in the general anatomy by analyzing multi-bandwidth datasets acquired on a freshly excised kidney.

Whole-body optical imaging of post-embryonic stage model organisms is a challenging and long sought-after goal. It requires a combination of high-resolution performance and high-penetration depth. Optoacoustic (photoacoustic) mesoscopy holds great promise, as it penetrates deeper than optical and optoacoustic microscopy while providing high-spatial resolution. However, optoacoustic mesoscopic techniques only offer partial visibility of oriented structures, such as blood vessels, due to a limited angular detection aperture or the use of ultrasound frequencies that yield insufficient resolution. We introduce 360° multi orientation (multi-projection) raster scan optoacoustic mesoscopy (MORSOM) based on detecting an ultra-wide frequency bandwidth (up to 160 MHz) and weighted deconvolution to synthetically enlarge the angular aperture. We report unprecedented isotropic in-plane resolution at the 9–17 μm range and improved signal to noise ratio in phantoms and opaque 21-day-old Zebrafish. We find that MORSOM performance defines a new operational specification for optoacoustic mesoscopy of adult organisms, with possible applications in the developmental biology of adulthood and aging. An optoacoustic technique has been used to realize whole-body imaging of post-embryonic zebrafish by researchers in Germany and France. The whole-body imaging of biological specimens beyond the embryonic stage is highly desired for biological studies. While showing promise, raster-scan optoacoustic mesoscopy (RSOM) is limited by the low numerical aperture of the ultrasonic detectors used. Now, Murad Omar at the Technical University of Munich and co-workers have demonstrated a Multi Orientation RSOM technique that, similar to X-ray computed tomography, collects projections over 360 degrees. As it uses broad-field illumination and its resolution is limited only by ultrasound diffraction, the new method can achieve a high resolution and wide range of spatial frequencies. The team demonstrated it by obtaining high-resolution whole-body images of 21-day-old zebrafish, which cannot be obtained by optical microscopy or conventional optoacoustic mesoscopy.

International audience; The activation of natural gas nuclei to induce larger bubbles is possible using short ultrasonic excitations of high amplitude, and is required for ultrasound cavitation therapies. However, little is known about the distribution of nuclei in tissues. Therefore, the acoustic pressure level necessary to generate bubbles in a targeted zone and their exact location are currently difficult to predict. To monitor the initiation of cavitation activity, a novel all-ultrasound technique sensitive to single nucleation events is presented here. It is based on combined passive detection and ultrafast active imaging over a large volume using the same multi-element probe. Bubble nucleation was induced using a focused transducer (660 kHz, f-number = 1) driven by a high-power electric burst (up to 300 W) of one to two cycles. Detection was performed with a linear array (4 to 7 MHz) aligned with the single-element focal point. In vitro experiments in gelatin gel and muscular tissue are presented. The synchronized passive detection enabled radio-frequency data to be recorded, comprising high-frequency coherent wave fronts as signatures of the acoustic emissions linked to the activation of the nuclei. Active change detection images were obtained by subtracting echoes collected in the unnucleated medium. These indicated the appearance of stable cavitating regions. Because of the ultrafast frame rate, active detection occurred as quickly as 330 μs after the high-amplitude excitation and the dynamics of the induced regions were studied individually.

International audience; Brain treatment through the skull with high-intensity focused ultrasound can be achieved with multichannel arrays and adaptive focusing techniques such as time reversal. This method requires a reference signal to be either emitted by a real source embedded in brain tissues or computed from a virtual source, using the acoustic properties of the skull derived from computed tomography images. This noninvasive computational method focuses with precision, but suffers from modeling and repositioning errors that reduce the accessible acoustic pressure at the focus in comparison with fully experimental time reversal using an implanted hydrophone. In this paper, this simulation-based targeting has been used experimentally as a first step for focusing through an ex vivo human skull at a single location. It has enabled the creation of a cavitation bubble at focus that spontaneously emitted an ultrasonic wave received by the array. This active source signal has allowed 97 +/- 1.1% of the reference pressure (hydrophone-based) to be restored at the geometrical focus. To target points around the focus with an optimal pressure level, conventional electronic steering from the initial focus has been combined with bubble generation. Thanks to step-by-step bubble generation, the electronic steering capabilities of the array through the skull were improved.

Brain treatment with High Intensity Focused Ultrasound (HIFU) can be achieved by multichannel arrays through the skull using time-reversal focusing. Such a method requires a reference signal either sent by a real source embedded in brain tissues or computed from a virtual source, using the acoustic properties of the skull deduced from CT images. This non-invasive computational method allows precise focusing, but is time consuming and suffers from unavoidable modeling and repositioning errors which reduce the accessible acoustic pressure at the focus in comparison with real experimental time-reversal using an implanted hydrophone. Ex vivo simulations with a half skull immersed in a water tank allow us to reach at low amplitude levels a pressure ratio of 83% of the reference pressure (real time-reversal) at 1 MHz. Using this method to transcranially focus a pulse signal in an agar gel (model for in vivo bubble formation), we induced a cavitation bubble that generated an ultrasonic wave received by the array. Selecting the 1 MHz component, the signal was time reversed and re-emitted, allowing 97%plusmn1.1% of pressure ratio to be restored. To target points in the vicinity of the geometrical focus, conventional electronic steering from the reference signal has been achieved. Skull aberrations severely degrade the accessible pressure while moving away from the focus ( ~90% at 11 mm in the focal plane). Nevertheless, inducing cavitation bubbles close to the limit of the primary accessible zone allowed us to acquire multiple references signal to increase the electronic steering area by 50%.

Optical mesoscopy extends the capabilities of biological visualization beyond the limited penetration depth achieved by microscopy. However, imaging of opaque organisms or tissues larger than a few hundred micrometers requires invasive tissue sectioning or chemical treatment of the specimen for clearing photon scattering, an invasive process that is regardless limited with depth. We developed previously unreported broadband optoacoustic mesoscopy as a tomographic modality to enable imaging of optical contrast through several millimeters of tissue, without the need for chemical treatment of tissues. We show that the unique combination of three-dimensional projections over a broad 500 kHz–40 MHz frequency range combined with multi-wavelength illumination is necessary to render broadband multispectral optoacoustic mesoscopy (2B-MSOM) superior to previous optical or optoacoustic mesoscopy implementations.

We developed a reflection-mode optoacoustic mesoscopy system, based on raster-scanning of a custom designed spherically focused ultrasound detector, enabling seamless epi-illumination of the volume imaged. We study the performance of acoustic-resolution mesoscopy operating at an ultrawideband bandwidth of 20-180 MHz. i.e., a frequency band spreading over virtually an order of magnitude. Using tomographic reconstruction we showcase previously unreported, to our knowledge, axial resolutions of 4 μm and transverse resolutions of 18 μm reaching depths of up to 5 mm. We further investigate the frequency-dependence of features seen on the images to understand the implications of ultrawideband measurements. We show the overall imaging performance and the frequency ranges that contribute to observable resolution improvements from phantoms and animals.

We developed a raster-scan acoustic resolution broadband optoacoustic mesoscopy system and investigated the imaging performance using ultrasonic frequencies up to 125 MHz. The developed system achieves 7 μm axial resolution and transverse resolution of 30 μm reaching depths of at least 5 mm. This unprecedented performance is achieved by operating at out-of-focus ultrasonic detection and tomographic reconstruction. We demonstrate the limits reached due to the width of the laser pulse employed and showcase the technique on drosophila fly and drosophila pupae ex vivo.

Purpose: Optoacoustic imaging relies on the detection of ultrasonic waves induced by laser pulse excitations to map optical absorption in biological tissue. A tomographic geometry employing a conventional ultrasound linear detector array for volumetric optoacoustic imaging is reported. The geometry is based on a translate-rotate scanning motion of the detector array, and capitalizes on the geometrical characteristics of the transducer assembly to provide a large solid angular detection aperture. A system for three-dimensional whole-body optoacoustic tomography of small animals is implemented. Methods: The detection geometry was tested using a 128-element linear array (5.0/7.0 MHz, Acuson L7, Siemens), moved by steps with a rotation/translation stage assembly. Translation and rotation range of 13.5 mm and 180°, respectively, were implemented. Optoacoustic emissions were induced in tissue-mimicking phantoms andex vivo mice using a pulsed laser operating in the near-IR spectral range at 760 nm. Volumetric images were formed using a filtered backprojection algorithm. Results: The resolution of the optoacoustic tomography system was measured to be better than 130μm in-plane and 330 μm in elevation (full width half maximum), and to be homogenous along a 15 mm diameter cross section due to the translate-rotate scanning geometry. Whole-body volumetric optoacoustic images of mice were performed ex vivo, and imaged organs and blood vessels through the intact abdominal and head regions were correlated to the mouse anatomy. Conclusions: Overall, the feasibility of three-dimensional and high-resolution whole-body optoacoustic imaging of small animal using a conventional linear array was demonstrated. Furthermore, the scanning geometry may be used for other linear arrays and is therefore expected to be of great interest for optoacoustic tomography at macroscopic and mesoscopic scale. Specifically, conventional detector arrays with higher central frequencies may be investigated.

Optoacoustic (photoacoustic) mesoscopic and microscopic imaging is often implemented by linearly scanning a spherically focused ultrasound transducer. In this case, the resolution and sensitivity along the scan direction are limited by diffraction and therefore degrade rapidly for imaging depths away from the focal point. Partial restoration of the lost resolution can be achieved by using data-processing techniques, such as the virtual detector delay-and-sum method. However, these techniques are based on an approximate description of the detector properties, which limits the improvement in image quality they achieve. Herein we propose a reconstruction method based on an exact model of the optoacoustic generation and propagation that incorporates the spatial response of the sensor. The proposed method shows superior imaging performance over previously considered techniques.

We present optical and atomic force microscopy measurements of the roughness of the inner surfaces within glass capillary tubes and Hollow Core Photonic Bandgap Fibers over the [3×10−2 μηm-1–30 μm-1] spatial frequency range.

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.