Rapid progress in the development of multispectral optoacoustic tomography techniques has enabled unprecedented insights into biological dynamics and molecular processes in vivo and noninvasively at penetration and spatiotemporal scales not covered by modern optical microscopy methods. Ultrasound imaging provides highly complementary information on elastic and functional tissue properties and further aids in enhancing optoacoustic image quality. We devised the first hybrid transmission–reflection optoacoustic ultrasound (TROPUS) small animal imaging platform that combines optoacoustic tomography with both reflection- and transmission-mode ultrasound computed tomography. The system features full-view cross-sectional tomographic imaging geometry for concomitant noninvasive mapping of the absorbed optical energy, acoustic reflectivity, speed of sound, and acoustic attenuation in whole live mice with submillimeter resolution and unrivaled image quality. Graphics-processing unit (GPU)-based algorithms employing spatial compounding and bent-ray-tracing iterative reconstruction were further developed to attain real-time rendering of ultrasound tomography images in the full-ring acquisition geometry. In vivo mouse imaging experiments revealed fine details on the organ parenchyma, vascularization, tissue reflectivity, density, and stiffness. We further used the speed of sound maps retrieved by the transmission ultrasound tomography to improve optoacoustic reconstructions via two-compartment modeling. The newly developed synergistic multimodal combination offers unmatched capabilities for imaging multiple tissue properties and biomarkers with high resolution, penetration, and contrast.

Implementation of hybrid imaging using optoacoustic tomography (OAT) and ultrasound (US) brings together the important advantages and complementary features of both methods. However, the fundamentally different physical contrast mechanisms of the two modalities may impose significant difficulties in the optimal tomographic data acquisition and image formation strategies. We investigate the applicability of the commonly applied imaging geometries for acquisition and reconstruction of hybrid optoacoustic tomography and pulse-echo ultrasound (OPUS) images. Optimization of the ultrasound image formation strategy using concave array geometry was implemented using a synthetic aperture method combined with spatial compounding. Experimental validation was performed using a custom-made multiplexer unit executing switching between the two modalities employing the same transducer array. A variety of array probes with different angular coverages were subsequently tested, including arrays for clinical hand-held imaging as well as stationary arrays for tomographic small animal imaging. The results demonstrate that acquisition of OAT data by mere addition of an illumination source to the common US linear array geometry may result in significant limited-view artifacts and overall loss of image quality. On the other hand, unsatisfactory US image quality is achieved with tomographic arrays solely optimized for OAT image acquisition without considering the optimal transmit-receive beamforming parameters. Optimal selection of the array pitch size, tomographic coverage and spatial compounding parameters has achieved here an accurate hybrid imaging performance, which was experimentally showcased in tissuemimicking phantoms, post-mortem mice, and hand-held imaging of a healthy volunteer. The efficient combination of the two modalities in a single imaging device reveals the true power of functional and molecular imaging capacities of OAT in addition to the morphological and functional imaging capabilities of US.

Radiology 2019; 00:1-7 • https://doi.org/10.1148/radiol.2019181325 • Content code:Background: Multispectral optical imaging has the capability of resolving hemoglobin, lipid, and water. Volumetric multispectral optoacoustic tomography (MSOT) is a hybrid imaging technique that provides a unique combination of functional and molecular contrast with real-time handheld imaging.Purpose: To investigate whether volumetric MSOT can provide real-time assessment of the anatomic and functional status of the human carotid artery bifurcation noninvasively. Materials and Methods:Imaging of healthy volunteers (n = 16) was performed with a custom-designed handheld volumetric MSOT scanner capable of high-spatial-resolution (approximately 200 µm) and real-time (10 volumes/sec) three-dimensional imaging, while further providing spectroscopic capacity through fast tuning of the excitation light wavelength. For comparison and anatomic cross-validation, volunteers were also scanned with clinical B-mode US.Results: Volumetric MSOT achieved real-time imaging and characterization of the entire carotid bifurcation area across three dimensions simultaneously captured in a single volumetric image frame. Analysis of the acquired data further showed that a higher contrast-to-noise ratio can be achieved for wavelengths corresponding to a high optical absorption of oxygenated hemoglobin. Conclusion:The human carotid artery was visualized by using handheld volumetric multispectral optoacoustic tomography. This imaging approach is less prone to motion artifacts than are the conventional clinical imaging methods, holding promise for providing additional image-based biomarkers for noninvasive label-free assessment of carotid artery disease.

The high complementarity of ultrasonography and optoacoustic tomography has prompted the development of combined approaches that utilize the same transducer array for detecting both optoacoustic and pulse-echo ultrasound responses from tissues. Yet, due to the fundamentally different physical contrast and image formation mechanisms, the development of detection technology optimally suited for image acquisition in both modalities remains a major challenge. Herein, we introduce a multi-segment detector array approach incorporating array segments of linear and concave geometry to optimally support both ultrasound and optoacoustic image acquisition. The various image rendering strategies are tested and optimized in numerical simulations and calibrated tissue-mimicking phantom experiments. We subsequently demonstrate real-time hybrid optoacoustic ultrasound image acquisition in a healthy volunteer. The new approach enables the acquisition of high-quality anatomical data by both modalities complemented by functional information on blood oxygenation status provided by the multispectral optoacoustic tomography.

Changes in hemodynamic parameters are directly linked to biological function and physiological activity. Characterization of hemodynamics is commonly performed by Doppler ultrasound, which provides accurate measurements of blood flow velocity. Multi-spectral optoacoustic tomography is rapidly undergoing clinical translation fostered by its unique and complementary capacity for label-free mapping of the blood volume and the distribution of oxy- and deoxy-hemoglobin in blood. Here we report on a hybrid optoacoustic and ultrasound imaging approach that enables multi-modal imaging of blood flow and oxygen state using a multi-segment detector array. We further demonstrate rendering of multi-modal pulse-echo ultrasound, multi-spectral optoacoustic tomography, and color Doppler images from carotid artery of a healthy subject.

The highly complementary information provided by multispectral optoacoustics and pulseecho ultrasound have recently prompted development of hybrid imaging instruments bringing together the unique contrast advantages of both modalities. In the hybrid optoacoustic ultrasound (OPUS) combination, images retrieved by one modality may further be used to improve the reconstruction accuracy of the other. In this regard, image segmentation plays a major role as it can aid improving the image quality and quantification abilities by facilitating modeling of light and sound propagation through the imaged tissues and surrounding coupling medium. Here, we propose an automated approach for surface segmentation in whole-body mouse OPUS imaging using a deep convolutional neural network (CNN). The method has shown robust performance, attaining accurate segmentation of the animal boundary in both optoacoustic and pulse-echo ultrasound images, as evinced by quantitative performance evaluation using Dice coefficient metrics.

Expanding usage of small animal models in biomedical research necessitates development of technologies for structural, functional, or molecular imaging that can be readily integrated in the biological laboratory. Herein, we consider dual multispectral optoacoustic (OA) and ultrasound tomography based on curved ultrasound detector arrays and describe the performance achieved for hybrid morphological and physiological brain imaging of mice in vivo. We showcase coregistered hemodynamic parameters resolved by OA tomography under baseline conditions and during alterations of blood oxygen saturation. As an internal reference, we provide imaging of abdominal organs. We illustrate the performance advantages of hybrid curved detector ultrasound and OA tomography and discuss immediate and long-term implications of our findings in the context of animal and human studies.

Hybrid optoacoustic and pulse-echo ultrasound imaging is an attractive multi-modal combination owing to the highly complementary contrast of the two techniques. Efficient hybridization is often hampered by significant dissimilarities between their optimal data acquisition and image formation strategies. Herein, we introduce an approach for combined optoacoustic and ultrasound imaging based on a plano-concave detector array design with a non-uniform pitch distribution. The hybrid design optimized for both modalities allows for maintaining an extended field of view for efficient ultrasound navigation while simultaneously providing broad tomographic coverage for optimal optoacoustic imaging performance. Imaging sessions performed in tissue-mimicking phantoms and healthy volunteers demonstrate that the suggested approach renders an enhanced imaging performance as compared with the previously reported hybrid optoacoustic and ultrasound imaging approaches. Thus, it can greatly facilitate clinical translation of the optoacoustic imaging technology by means of its efficient combination with ultrasonography, a well-established clinical imaging modality.