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Research at the UC Hopland Research and Extension Center (HREC) has improved our understanding of how to reduce sheep depredation while minimizing the impact on coyotes. Analysis of a 14-year data set of HREC coyote-control efforts found that sheep depredation losses were not correlated with the number of coyotes removed in any of three time scales analyzed (yearly, seasonally and monthly) during corresponding intervals for the next 2 years. Field research using radiotelemetry to track coyotes supported and explained this finding. For example, in 1995, dominant “alphas” from four territories were associated with 89% of 74 coyote-killed lambs; “betas” and transients were not associated with any of these kills. Relatively few coyotes were killing sheep, and these animals were difficult to capture by conventional methods at the time of year when depredation was highest. However, selective removal of only the problem alpha coyotes effectively reduced losses at HREC.

Objective. We present the first fully two-dimensional attenuation imaging technique developed for pulse-echo ultrasound systems. Unlike state-of-the-art techniques, which use line-by-line acquisitions, our method uses steered emissions to constrain attenuation values at each location with multiple crossing wave paths, essential to resolve the spatial variations of this tissue property. Approach. At every location, we compute normalized cross-correlations between the beamformed images that are obtained from emissions at different steering angles. We demonstrate that their log-amplitudes provide the changes between attenuation-induced amplitude losses undergone by the different incident waves. This allows us to formulate a linear tomographic problem, which we efficiently solve via a Tikhonov-regularized least-squares approach. Main results. The performance of our tomography technique is first validated in numerical examples and then experimentally demonstrated in custom-made tissue-mimicking phantoms with inclusions of varying size, echogenicity, and attenuation. We show that this technique is particularly good at resolving lateral variations in tissue attenuation and remains accurate in media with varying echogenicity. Significance. Based on a similar principle, this method can be easily combined with computed ultrasound tomography in echo mode for speed-of-sound imaging, paving the way towards a multi-modal ultrasound tomography framework characterizing multiple acoustic tissue properties simultaneously., (Creative Commons Attribution license.)

In recent years, methods estimating the spatial distribution of tissue speed of sound with pulse-echo ultrasound are gaining considerable traction. They can address limitations of B-mode imaging, for instance in diagnosing fatty liver diseases. Current state-of-the-art methods relate the tissue speed of sound to local echo shifts computed between images that are beamformed using restricted transmit and receive apertures. However, the aperture limitation affects the robustness of phase-shift estimations and, consequently, the accuracy of reconstructed speed-of-sound maps. Here, we propose a method based on the Radon transform of image patches able to estimate local phase shifts from full-aperture images. We validate our technique on simulated, phantom and in-vivo data acquired on a liver and compare it with a state-of-the-art method. We show that the proposed method enhances the stability to changes of beamforming speed of sound and to a reduction of the number of insonifications. In particular, the deployment of pulse-echo speed-of-sound estimation methods onto portable ultrasound devices can be eased by the reduction of the number of insonifications allowed by the proposed method.

Background: Non-alcoholic fatty liver disease is rapidly emerging as the leading global cause of chronic liver disease. Efficient disease management requires low-cost, non-invasive techniques for diagnosing hepatic steatosis accurately. Here, we propose quantifying liver speed of sound (SoS) with computed ultrasound tomography in echo mode (CUTE), a recently developed ultrasound imaging modality adapted to clinical pulse-echo systems. CUTE reconstructs the spatial distribution of SoS by measuring local echo phase shifts when probing tissue at varying steering angles in transmission and reception., Methods: In this first-in-human phase II diagnostic study, we evaluated the liver of 22 healthy volunteers and 22 steatotic patients. We used conventional B-mode ultrasound images and controlled attenuation parameter (CAP) to diagnose the presence (CAP≥ 280 dB/m) or absence (CAP < 248 dB/m) of steatosis in the liver. A fully integrated convex-probe CUTE implementation was developed on the ultrasound system to estimate liver SoS. We investigated its diagnostic value via the receiver operating characteristic (ROC) analysis and correlation to CAP measurements., Results: We show that liver CUTE-SoS estimates correlate strongly (r = -0.84, p = 8.27 × 10 -13 ) with CAP values and have 90.9% (95% confidence interval: 84-100%) sensitivity and 95.5% (81-100%) specificity for differentiating between normal and steatotic livers (area under the ROC curve: 0.93-1.0)., Conclusions: Our results demonstrate that liver CUTE-SoS is a promising quantitative biomarker for diagnosing liver steatosis. This is a necessary first step towards establishing CUTE as a new quantitative add-on to diagnostic ultrasound that can potentially be as versatile as conventional ultrasound imaging., (© 2023. The Author(s).)

Computed ultrasound tomography in echo mode (CUTE) allows real-time imaging of the tissue speed of sound (SoS) using handheld ultrasound. The SoS is retrieved by inverting a forward model that relates the spatial distribution of the tissue SoS to echo shift maps detected between varying transmit and receive angles. Despite promising results, in vivo SoS maps often show artifacts due to elevated noise in echo shift maps. To minimize artifacts, we propose a technique where an individual SoS map is reconstructed for each echo shift map separately, as opposed to a single SoS map from all echo shift maps simultaneously. The final SoS map is then obtained as a weighted average over all SoS maps. Due to the partial redundancy between different angle combinations, artifacts that appear only in a subset of the individual maps can be excluded via the averaging weights. We investigate this real-time capable technique in simulations using two numerical phantoms, one with a circular inclusion and one with two layers. Our results demonstrate that the SoS maps reconstructed using the proposed technique are equivalent to the ones using simultaneous reconstruction when considering uncorrupted data but show significantly reduced artifact level for data that are corrupted by noise.

Introduction: A unique surgical approach - the minimally invasive direct interbody fusion (MIS-DTIF) - was previously introduced in our proof-of-concept study, which included four patients who underwent thoracic interbody fusion below the scapula at the T6/7 vertebral level. However, due to the novelty of this method, a report of associated operative parameters such as pain, function, and clinical outcomes from an expanded patient cohort was needed to assess the validity of our results., Materials and Methods: Following IRB approval, data were analyzed retrospectively from electronic health records between 2014 and 2021. Inclusion criteria were patients ≥18 years old who underwent minimally invasive thoracic interbody fusion using the MIS-DTIF technique for at least one vertebral level. The primary outcomes included demographic/radiographic features (e.g., age). Secondary outcomes included perioperative clinical features (e.g., preoperative and ≥1-year final follow-up (FFU)). Tertiary outcomes included perioperative complications. Both preoperative and FFU patient-reported pain and functional outcomes (ODI scores) were analyzed using t-tests to establish significance.  Results: A total of 13 patients who underwent MIS-DTIF surgery were observed, with eight male patients and five female patients. The average age was 49.2 years, with an average BMI of 30.5 kg/m 2 . Of the surgeries included, the majority (69.23%) were 1-level thoracic vertebrae fusions - with 2-level fusions and ≥ 3-level fusions accounting for 15.38% and 15.38% of cases, respectively. The mean operative time was 58.9 ± 19.9 minutes, with an average fluoroscopy time of 285.7 ± 126.8 seconds and an average actual blood loss volume of 109.0 ± 79.0 mL. The average hospital length of stay was 1.1 (±1.7) days, and no clinically significant perioperative complications were observed in this patient cohort. The average follow-up period was 12.1 ± 9.6 months, with preoperative and FFU back pain visual analog scale (VAS) scores showing highly significant improvement ( p<0.001 ). In addition to pain reduction, quality of life improvements was noted, with significant differences in some of the ODI domains between preoperative and FFU scores ( p<0.05 ), as well as the overall total score between preoperative and FFU ODI assessment ( p<0.001 ) - both of which reflect increased patient function and decreased disability., Conclusion: This study provides further evidence for the safety and efficacy of the MIS-DTIF approach for surgical management of symptomatically refractory patients with thoracic disc herniation or stenosis owing to degenerative disc disease or compression fractures. Additionally, the data gathered suggests that this minimally invasive procedure offers many clinical benefits, including less tissue damage, decreased intraoperative blood loss, shortened surgery time, and shortened hospital length of stay. Finally, in addition to significant pain intensity improvement, this study showed that treated patients highly benefited from 'sleeping' and 'return-to-work' domains and other ODI functional domains in activities of daily living (ADLs). More clinical studies are recommended in larger patient cohorts to ascertain the findings reported in this study., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Abbasi et al.)

Computed ultrasound tomography in echo mode (CUTE) is a new ultrasound (US)-based medical imaging modality with promise for diagnosing various types of disease based on the tissue's speed of sound (SoS). It is developed for conventional pulse-echo US using handheld probes and can thus be implemented in state-of-the-art medical US systems. One promising application is the quantification of the liver fat fraction in fatty liver disease. So far, CUTE was using linear array probes where the imaging depth is comparable to the aperture size. For liver imaging, however, convex probes are preferred since they provide a larger penetration depth and a wider view angle allowing to capture a large area of the liver. With the goal of liver imaging in mind, we adapt CUTE to convex probes, with a special focus on discussing strategies that make use of the convex geometry in order to make our implementation computationally efficient. We then demonstrate in an abdominal imaging phantom that accurate quantitative SoS using convex probes is feasible, in spite of the smaller aperture size in relation to the image area compared to linear arrays. A preliminary in vivo result of liver imaging confirms this outcome, but also indicates that deep quantitative imaging in the real liver can be more challenging, probably due to the increased complexity of the tissue compared to phantoms., (Creative Commons Attribution license.)

The velocity of ultrasound longitudinal waves (speed of sound) is emerging as a valuable biomarker for a wide range of diseases, including musculoskeletal disorders. Muscles are fiber-rich tissues that exhibit anisotropic behavior, meaning that velocities vary with the wave-propagation direction. Therefore, quantifying anisotropy is essential to improve velocity estimates while providing a new metric related to muscle composition and architecture. For the first time, this work presents a method to estimate speed-of-sound anisotropy in transversely isotropic tissues using pulse-echo ultrasound. We assume elliptical anisotropy and consider an experimental setup with a flat reflector parallel to the linear probe, with the muscle in between. This setup allows us to measure first-arrival reflection traveltimes using multistatic operation. Unknown muscle parameters are the orientation angle of the anisotropy symmetry axis and the velocities along and across this axis. We derive analytical expressions for the nonlinear relationship between traveltimes and anisotropy parameters, including reflector inclinations. These equations are exact for homogeneous media and are useful to estimate the effective average anisotropy in muscles. To analyze the structure of this forward problem, we formulate the inversion statistically using the Bayesian framework. We demonstrate that anisotropy parameters can be uniquely constrained by combining traveltimes from different reflector inclinations. Numerical results from wide-ranging acquisition and anisotropy properties show that uncertainties in velocity estimates are substantially lower than expected velocity differences in the muscle. Thus, our approach could provide meaningful muscle anisotropy estimates in future clinical applications.

Optoacoustic (OA) imaging is a promising modality for quantifying blood oxygen saturation (sO 2 ) in various biomedical applications - in diagnosis, monitoring of organ function, or even tumor treatment planning. We present an accurate and practically feasible real-time capable method for quantitative imaging of sO 2 based on combining multispectral (MS) and multiple illumination (MI) OA imaging with learned spectral decoloring (LSD). For this purpose we developed a hybrid real-time MI MS OA imaging setup with ultrasound (US) imaging capability; we trained gradient boosting machines on MI spectrally colored absorbed energy spectra generated by generic Monte Carlo simulations and used the trained models to estimate sO 2 on real OA measurements. We validated MI-LSD in silico and on in vivo image sequences of radial arteries and accompanying veins of five healthy human volunteers. We compared the performance of the method to prior LSD work and conventional linear unmixing. MI-LSD provided highly accurate results in silico and consistently plausible results in vivo . This preliminary study shows a potentially high applicability of quantitative OA oximetry imaging, using our method., Competing Interests: The authors declare no conflicts of interest., (© 2022 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

The nerve fiber bundles constitutive of the white matter in the brain are organized in such a way that they exhibit a certain degree of structural anisotropy and birefringence. The birefringence exhibited by such aligned fibrous tissue is known to be extremely sensitive to small pathological alterations. Indeed, highly aligned anisotropic fibers exhibit higher birefringence than structures with weaker alignment and anisotropy, such as cancerous tissue. In this study, we performed experiments on thick coronal slices of a healthy human brain to explore the possibility of (i) measuring, with a polarimetric microscope the birefringence exhibited by the white matter and (ii) relating the measured birefringence to the fiber orientation and the degree of alignment. This is done by analyzing the spatial distribution of the degree of polarization of the backscattered light and its variation with the polarization state of the probing beam. We demonstrate that polarimetry can be used to reliably distinguish between white and gray matter, which might help to intraoperatively delineate unstructured tumorous tissue and well organized healthy brain tissue. In addition, we show that our technique is able to sensitively reconstruct the local mean nerve fiber orientation in the brain, which can help to guide tumor resections by identifying vital nerve fiber trajectories thereby improving the outcome of the brain surgery., Competing Interests: The authors declare that there are no conflicts of interest related to this article., (© 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

Computed ultrasound tomography in echo mode (CUTE) is a promising ultrasound (US) based multi-modal technique that allows to image the spatial distribution of speed of sound (SoS) inside tissue using hand-held pulse-echo US. It is based on measuring the phase shift of echoes when detected under varying steering angles. The SoS is then reconstructed using a regularized inversion of a forward model that describes the relation between the SoS and echo phase shift. Promising results were obtained in phantoms when using a Tikhonov-type regularization of the spatial gradient (SG) of SoS. In-vivo, however, clutter and aberration lead to an increased phase noise. In many subjects, this phase noise causes strong artifacts in the SoS image when using the SG regularization. To solve this shortcoming, we propose to use a Bayesian framework for the inverse calculation, which includes a priori statistical properties of the spatial distribution of the SoS to avoid noise-related artifacts in the SoS images. In this study, the a priori model is based on segmenting the B-Mode image. We show in a simulation and phantom study that this approach leads to SoS images that are much more stable against phase noise compared to the SG regularization. In a preliminary in-vivo study, a reproducibility in the range of 10 ms -1 was achieved when imaging the SoS of a volunteer's liver from different scanning locations. These results demonstrate the diagnostic potential of CUTE for example for the staging of fatty liver disease.

Computed ultrasound tomography in echo mode (CUTE) allows determining the spatial distribution of speed-of-sound (SoS) inside tissue using handheld pulse-echo ultrasound (US). This technique is based on measuring the changing phase of beamformed echoes obtained under varying transmit (Tx) and/or receive (Rx) steering angles. The SoS is reconstructed by inverting a forward model describing how the spatial distribution of SoS is related to the spatial distribution of the echo phase shift. Thanks to the straight-ray approximation, this forward model is linear and can be inverted in real-time when implemented in a state-of-the art system. Here we demonstrate that the forward model must contain two features that were not taken into account so far: (a) the phase shift must be detected between pairs of Tx and Rx angles that are centred around a set of common mid-angles, and (b) it must account for an additional phase shift induced by the offset of the reconstructed position of echoes. In a phantom study mimicking hepatic and cancer imaging, we show that both features are required to accurately predict echo phase shift among different phantom geometries, and that substantially improved quantitative SoS images are obtained compared to the model that has been used so far. The importance of the new model is corroborated by a preliminary volunteer result., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Interpreting the polarimetric data from fiber-like macromolecules constitutive of tissue can be difficult due to strong scattering. In this study, we probed the superficial layers of fibrous tissue models (membranes consisting of nanofibers) displaying varying degrees of alignment. To better understand the manifestation of membranes' degree of alignment in polarimetry, we analyzed the spatial variations of the backscattered light's Stokes vectors as a function of the orientation of the probing beam's linear polarization. The degree of linear polarization reflects the uniaxially birefringent behavior of the membranes. The rotational (a-)symmetry of the backscattered light's degree of linear polarization provides a measure of the membranes' degree of alignment.

Significance: Quantitative optoacoustic (OA) imaging has the potential to provide blood oxygen saturation (SO2) estimates due to the proportionality between the measured signal and the blood's absorption coefficient. However, due to the wavelength-dependent attenuation of light in tissue, a spectral correction of the OA signals is required, and a prime challenge is the validation of both the optical characterization of the tissue and the SO2., Aim: We propose to assess the reliability of SO2 levels retrieved from spectral fitting by measuring the similarity of OA spectra to the fitted blood absorption spectra., Approach: We introduce a metric that quantifies the trends of blood spectra by assigning a pair of spectral slopes to each spectrum. The applicability of the metric is illustrated with in vivo measurements on a human forearm., Results: We show that physiologically sound SO2 values do not necessarily imply a successful spectral correction and demonstrate how the metric can be used to distinguish SO2 values that are trustworthy from unreliable ones., Conclusions: The metric is independent of the methods used for the OA data acquisition, image reconstruction, and spectral correction, thus it can be readily combined with existing approaches, in order to monitor the accuracy of quantitative OA imaging.

Image reconstruction in optoacoustic imaging is often based on a delay-and-sum (DAS) or a frequency domain (FD) algorithm. In this study, we performed a comprehensive comparison of these two algorithms together with coherence factor (CF) weighting using phantom and in-vivo mouse data obtained with optoacoustic microscopy. For this purpose we developed an FD based definition of the CF. Our results reveal the equivalence of DAS and FD, with and without CF weighting, in terms of spatial resolution and contrast-to-noise ratio (CNR) but highlight the clear advantage of FD in terms of computational cost, making it preferable for 3D reconstruction or real-time applications. An important additional result of this research is that, contradictory to previous studies, CF weighting does not lead to any improvement in lateral resolution., (© 2019 The Author(s).)

In vivo imaging of tissue/vasculature oxygen saturation levels is of prime interest in many clinical applications. To this end, the feasibility of combining two distinct and complementary imaging modalities is investigated: optoacoustics (OA) and near-infrared optical tomography (NIROT), both operating noninvasively in reflection mode. Experiments were conducted on two optically heterogeneous phantoms mimicking tissue before and after the occurrence of a perturbation. OA imaging was used to resolve submillimetric vessel-like optical absorbers at depths up to 25 mm, but with a spectral distortion in the OA signals. NIROT measurements were utilized to image perturbations in the background and to estimate the light fluence inside the phantoms at the wavelength pair (760 nm, 830 nm). This enabled the spectral correction of the vessel-like absorbers' OA signals: the error in the ratio of the absorption coefficient at 830 nm to that at 760 nm was reduced from 60%-150% to 10%-20%. The results suggest that oxygen saturation (SO 2 ) levels in arteries can be determined with <10% error and furthermore, that relative changes in vessels' SO 2 can be monitored with even better accuracy. The outcome relies on a proper identification of the OA signals emanating from the studied vessels., (© 2018 The Authors. Journal of Biophotonics published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Epi-style optoacoustic (OA) imaging provides flexibility by integrating the irradiation optics and ultrasound receiver, yet clutter generated by optical absorption near the probe obscures deep OA sources. Localised vibration tagging (LOVIT) retrieves OA signal from images that are acquired with and without a preceding ultrasonic pushing beam: Radiation force leads to a phase shift of signals coming from the focal area resulting in their visibility in a difference image, whereas clutter from outside the pushing beam is eliminated. Disadvantages of a single-focus approach are residual clutter from inside the pushing beam above the focus, and time-intensive scanning of the focus to retrieve a large field-of-view. To speed up acquisition, we propose to create multiple foci in parallel, forming comb-shaped ARF patterns. By subtracting OA images obtained with interleaved combs, this technique moreover results in greatly improved clutter reduction in phantoms mimicking optical, acoustic and elastic properties of breast tissue.

Reflection artifacts caused by acoustic inhomogeneities constitute a major problem in epi-mode biomedical photoacoustic imaging. Photoacoustic transients from the skin and superficial optical absorbers traverse into the tissue and reflect off echogenic structures to generate reflection artifacts. These artifacts cause difficulties in the interpretation of images and reduce contrast and imaging depth. We recently developed a method called PAFUSion (photoacoustic-guided focused ultrasound) to circumvent the problem of reflection artifacts in photoacoustic imaging. We already demonstrated that the photoacoustic signals can be backpropagated using synthetic aperture pulse-echo data for identifying and reducing reflection artifacts in vivo . In this work, we propose an alternative variant of PAFUSion in which synthetic backpropagation of photoacoustic signals is based on multi-angled plane-wave ultrasound measurements. We implemented plane-wave and synthetic aperture PAFUSion in a handheld ultrasound/photoacoustic imaging system and demonstrate reduction of reflection artifacts in phantoms and in vivo measurements on a human finger using both approaches. Our results suggest that, while both approaches are equivalent in terms of artifact reduction efficiency, plane-wave PAFUSion requires less pulse echo acquisitions when the skin absorption is the main cause of reflection artifacts.

Reflection artifacts caused by acoustic inhomogeneities are a critical problem in epi-mode biomedical photoacoustic imaging. High light fluence beneath the probe results in photoacoustic transients, which propagate into the tissue and reflect back from echogenic structures. These reflection artifacts cause problems in image interpretation and significantly impact the contrast and imaging depth. We recently proposed a method called PAFUSion (Photoacoustic-guided focused ultrasound) to identify such reflection artifacts in photoacoustic imaging. In its initial version, PAFUSion mimics the inward-travelling wavefield from small blood vessel-like PA sources by applying ultrasound pulses focused towards these sources, and thus provides a way to identify the resulting reflection artifacts. In this work, we demonstrate reduction of reflection artifacts in phantoms and in vivo measurements on human volunteers. In view of the spatially distributed PA sources that are found in clinical applications, we implemented an improved version of PAFUSion where photoacoustic signals are backpropagated to imitate the inward travelling wavefield and thus the reflection artifacts. The backpropagation is performed in a synthetic way based on the pulse-echo acquisitions after transmission on each single element of the transducer array. The results provide a direct confirmation that reflection artifacts are prominent in clinical epi-photoacoustic imaging, and that PAFUSion can strongly reduce these artifacts to improve deep-tissue photoacoustic imaging.

Spectral optoacoustic (OA) imaging enables spatially-resolved measurement of blood oxygenation levels, based on the distinct optical absorption spectra of oxygenated and de-oxygenated blood. Wavelength-dependent optical attenuation in the bulk tissue, however, distorts the acquired OA spectrum and thus makes quantitative oxygenation measurements challenging. We demonstrate a correction for this spectral distortion without requiring a priori knowledge of the tissue optical properties, using the concept of multiple irradiation sensing: recording the OA signal amplitude of an absorbing structure ( e.g. blood vessel), which serves as an intrinsic fluence detector, as function of irradiation position. This permits the reconstruction of the bulk effective optical attenuation coefficient μ eff , λ . If performed at various irradiation wavelengths, a correction for the wavelength-dependent fluence attenuation is achieved, revealing accurate spectral information on the absorbing structures. Phantom studies were performed to show the potential of this technique for handheld clinical combined OA and ultrasound imaging.

Computed ultrasound tomography in echo-mode (CUTE) allows imaging the speed of sound inside tissue using hand-held pulse-echo ultrasound. This technique is based on measuring the changing local phase of beamformed echoes when changing the transmit beam steering angle. Phantom results have shown a spatial resolution and contrast that could qualify CUTE as a promising novel diagnostic modality in combination with B-mode ultrasound. Unfortunately, the large intensity range of several tens of dB that is encountered in clinical images poses difficulties to echo phase tracking and results in severe artefacts. In this paper we propose a modification to the original technique by which more robust echo tracking can be achieved, and we demonstrate in phantom experiments that dynamic range artefacts are largely eliminated. Dynamic range artefact reduction also allowed for the first time a clinical implementation of CUTE with sufficient contrast to reproducibly distinguish the different speed of sound in different tissue layers of the abdominal wall and the neck., (Copyright © 2015. Published by Elsevier B.V.)

Aberrations of the acoustic wave front, caused by spatial variations of the speed-of-sound, are a main limiting factor to the diagnostic power of medical ultrasound imaging. If not accounted for, aberrations result in low resolution and increased side lobe level, over all reducing contrast in deep tissue imaging. Various techniques have been proposed for quantifying aberrations by analysing the arrival time of coherent echoes from so-called guide stars or beacons. In situations where a guide star is missing, aperture-based techniques may give ambiguous results. Moreover, they are conceptually focused on aberrators that can be approximated as a phase screen in front of the probe. We propose a novel technique, where the effect of aberration is detected in the reconstructed image as opposed to the aperture data. The varying local echo phase when changing the transmit beam steering angle directly reflects the varying arrival time of the transmit wave front. This allows sensing the angle-dependent aberration delay in a spatially resolved way, and thus aberration correction for a spatially distributed volume aberrator. In phantoms containing a cylindrical aberrator, we achieved location-independent diffraction-limited resolution as well as accurate display of echo location based on reconstructing the speed-of-sound spatially resolved. First successful volunteer results confirm the clinical potential of the proposed technique.

The limitations of diagnostic echo ultrasound have motivated research into novel modalities that complement ultrasound in a multimodal device. One promising candidate is speed of sound imaging, which has been found to reveal structural changes in diseased tissue. Transmission ultrasound tomography shows speed of sound spatially resolved, but is limited to the acoustically transparent breast. We present a novel method by which speed-of-sound imaging is possible using classic pulse-echo equipment, facilitating new clinical applications and the combination with state-of-the art diagnostic ultrasound. Pulse-echo images are reconstructed while scanning the tissue under various angles using transmit beam steering. Differences in average sound speed along different transmit directions are reflected in the local echo phase, which allows a 2-D reconstruction of the sound speed. In the present proof-of-principle study, we describe a contrast resolution of 0.6% of average sound speed and a spatial resolution of 1 mm (laterally) × 3 mm (axially), suitable for diagnostic applications., (Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

In combined clinical optoacoustic (OA) and ultrasound (US) imaging, epi-mode irradiation and detection integrated into one single probe offers flexible imaging of the human body. The imaging depth in epi-illumination is, however, strongly affected by clutter. As shown in previous phantom experiments, the location of irradiation plays an important role in clutter generation. We investigated the influence of the irradiation geometry on the local image contrast of clinical images, by varying the separation distance between the irradiated area and the acoustic imaging plane of a linear ultrasound transducer in an automated scanning setup. The results for different volunteers show that the image contrast can be enhanced on average by 25% and locally by more than a factor of two, when the irradiated area is slightly separated from the probe. Our findings have an important impact on the design of future optoacoustic probes for clinical application.

This paper investigates a novel method which allows clutter elimination in deep optoacoustic imaging. Clutter significantly limits imaging depth in clinical optoacoustic imaging, when irradiation optics and ultrasound detector are integrated in a handheld probe for flexible imaging of the human body. Strong optoacoustic transients generated at the irradiation site obscure weak signals from deep inside the tissue, either directly by propagating towards the probe, or via acoustic scattering. In this study we demonstrate that signals of interest can be distinguished from clutter by tagging them at the place of origin with localised tissue vibration induced by the acoustic radiation force in a focused ultrasonic beam. We show phantom results where this technique allowed almost full clutter elimination and thus strongly improved contrast for deep imaging. Localised vibration tagging by means of acoustic radiation force is especially promising for integration into ultrasound systems that already have implemented radiation force elastography.

For clinical optoacoustic imaging, linear probes are preferably used because they allow versatile imaging of the human body with real-time display and free-hand probe guidance. The two-dimensional (2-D) optoacoustic image obtained with this type of probe is generally interpreted as a 2-D cross-section of the tissue just as is common in echo ultrasound. We demonstrate in three-dimensional simulations, phantom experiments, and in vivo mouse experiments that for vascular imaging this interpretation is often inaccurate. The cylindrical blood vessels emit anisotropic acoustic transients, which can be sensitively detected only if the direction of acoustic radiation coincides with the probe aperture. Our results reveal for this reason that the signal amplitude of different blood vessels may differ even if the vessels have the same diameter and initial pressure distribution but different orientation relative to the imaging plane. This has important implications for the image interpretation, for the probe guidance technique, and especially in cases when a quantitative reconstruction of the optical tissue properties is required.

Purpose: To assess differences in the simultaneous management of pharmacy and medical benefits by analyzing the health care utilization and costs associated with managed care patients who received oral linezolid as a pharmacy benefit or intravenous (IV) daptomycin or IV vancomycin as medical benefits for skin and soft tissue infections (SSTIs)., Methodology: The first medical or pharmacy claim from 03/01/2007 to 03/01/2010 was defined as the index date. Patients 18-64 years of age, with an inpatient SSTI diagnosis and > or = 1 target antibiotic claim(s), were included. Follow-up was 45 days; hospitalizations, emergency room (ER) visits, outpatient medical services, prescription fills, and total health care costs were compared for the treatments using univariate generalized linear modeling (GLM) analyses. Total health care costs were compared with GLM multivariate analyses adjusting for baseline covariate values., Results: Of the 8,905 patients included, 2,123 received linezolid, 5,503 vancomycin, and 1,279 daptomycin therapy; 14.4% of linezolid, 37.7% of vancomycin, and 22.8% of daptomycin patients were re-hospitalized (p < 0.001). A smaller proportion of linezolid patients (8.6%) required emergency services, versus 11.6% of vancomycin and 10.8% of daptomycin patients (p < 0.001). Multivariate analyses showed vancomycin costs to be significantly lower than daptomycin costs, -$5,425 (95% CI, -$1,535 to -$9,315), and a significantly higher mean cost difference for vancomycin, $11,182 (95% CI, $6,255 to $16,108), and daptomycin, $16,607 (95% CI, $9,426 to $23,788), versus linezolid., Conclusion: Patients treated with oral linezolid had fewer re-hospitalizations and emergency room visits and lower total costs compared with patients who received vancomycin or daptomycin therapy, suggesting that oral linezolid, which is covered under members' pharmacy benefits, may be more cost-effective than the two intravenous treatments for SSTIs.

Photoacoustic imaging, based on ultrasound detected after laser irradiation, is an extension to diagnostic ultrasound for imaging the vasculature, blood oxygenation and the uptake of optical contrast media with promise for cancer diagnosis. For versatile scanning, the irradiation optics is preferably combined with the acoustic probe in an epi-style arrangement avoiding acoustically dense tissue in the acoustic propagation path from tissue irradiation to acoustic detection. Unfortunately epiphotoacoustic imaging suffers from strong clutter, arising from optical absorption in tissue outside the image plane, and from acoustic backscattering. This limits the imaging depth for useful photoacoustic image contrast to typically less than one centimeter. Deformation-compensated averaging (DCA), which takes advantage of clutter decorrelation induced by palpating the tissue with the imaging probe, has previously been proposed for clutter reduction. We demonstrate for the first time that DCA results in reduced clutter in real-time freehand clinical epiphotoacoustic imaging. For this purpose, combined photoacoustic and pulse-echo imaging at 10-Hz frame rate was implemented on a commercial scanner, allowing for ultrasound-based motion tracking inherently coregistered with photoacoustic frames. Results from the forearm and the neck confirm that contrast is improved and imaging depth increased by DCA.

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.

In optoacoustic imaging, short laser pulses irradiate highly scattering human tissue and adiabatically heat embedded absorbing structures, such as blood vessels, to generate ultrasound transients by means of the thermoelastic effect. We present an optoacoustic vascular imaging system that records these transients on the skin surface with an ultrasound transducer array and displays the images online. With a single laser pulse a complete optoacoustic B-mode image can be acquired. The optoacoustic system exploits the high intrinsic optical contrast of blood and provides high-contrast images without the need for contrast agents. The high spatial resolution of the system is determined by the acoustic propagation and is limited to the submillimeter range by our 7.5-MHz linear array transducer. A Q-switched alexandrite laser emitting short near-infrared laser pulses at a wavelength of 760 nm allows an imaging depth of a few centimeters. The system provides real-time images at frame-rates of 7.5 Hz and optionally displays the classically generated ultrasound image alongside the optoacoustic image. The functionality of the system was demonstrated in vivo on human finger, arm and leg. The proposed system combines the merits and most compelling features of optics and ultrasound in a single high-contrast vascular imaging device.

An optoacoustic detection method suitable for depth profiling of optical absorption of layered or continuously varying tissue structures is presented. Detection of thermoelastically induced pressure transients allows reconstruction of optical properties of the sample to a depth of several millimeters with a spatial resolution of 24 mum. Acoustic detection is performed using a specially designed piezoelectric transducer, which is transparent for optical radiation. Thus, ultrasonic signals can be recorded at the same position the tissue is illuminated. Because the optoacoustical sound source is placed in the pulsed-acoustic near field of the pressure sensor, signal distortions commonly associated with acoustical diffraction are eliminated. Therefore, the acoustic signals mimic exactly the depth profile of the absorbed energy. This is illustrated by imaging the absorption profile of a two-layered sample with different absorption coefficients, and of a dye distribution while diffusing into a gelatin phantom., (Copyright 2005 Society of Photo-Optical Instrumentation Engineers.)