Real-time Volumetric Assessment of the Human Carotid Artery: Handheld Multispectral Optoacoustic Tomography.

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. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Mezrich in this issue.

Whole-body live mouse imaging by hybrid reflection-mode ultrasound and optoacoustic tomography.

We present a hybrid preclinical imaging scanner that optimally supports image acquisition in both reflection-mode ultrasonography and optoacoustic (OA) tomography modes. The system comprises a quasi-full-ring tomographic geometry capable of the simultaneous dual-mode imaging through entire cross sections of mice with in-plane spatial resolution in the range of 150 and 350 µm in the respective OA and ultrasound (US) imaging modes with an imaging speed of up to 10 two-dimensional frames per second. Three-dimensional whole-body data is subsequently rendered by rapid scanning of the imaged plane. The system further incorporates rapid laser wavelength tuning for real-time acquisition of multispectral OA data, which enables studies of longitudinal dynamics as well as fast kinetics and biodistribution of contrast agents. In vivo imaging performance is demonstrated by label-free hybrid anatomical scans through living mice, as well as real-time visualization of optical contrast agent perfusion. By setting new standards for whole-body tomographic imaging performance in both the OA and pulse-echo US modes, the developed hybrid imaging approach is expected to benefit numerous applications where the availability of high-quality structural information provided by the tomographic reflection-mode US can ease interpretation of the functional and molecular imaging results attained by the OA modality.

Deep Learning for Automatic Segmentation of Hybrid Optoacoustic Ultrasound (OPUS) Images.

The highly complementary information provided by multispectral optoacoustics and pulse-echo 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.

Noninvasive multiparametric charac-terization of mammary tumors with transmission-reflection optoacoustic ultrasound.

Development of imaging methods capable of furnishing tumor-specific morphological, functional, and molecular information is paramount for early diagnosis, staging, and treatment of breast cancer. Ultrasound (US) and optoacoustic (OA) imaging methods exhibit excellent traits for tumor imaging in terms of fast imaging speed, ease of use, excellent contrast, and lack of ionizing radiation. Here, we demonstrate simultaneous tomographic whole body imaging of optical absorption, US reflectivity, and speed of sound (SoS) in living mice. In vivo studies of 4T1 breast cancer xenografts models revealed synergistic and complementary value of the hybrid imaging approach for characterizing mammary tumors. While neovasculature surrounding the tumor areas were observed based on the vascular anatomy contrast provided by the OA data, the tumor boundaries could be discerned by segmenting hypoechoic structures in pulse-echo US images. Tumor delineation was further facilitated by enhancing the contrast and spatial resolution of the SoS maps with a full-wave inversion method. The malignant lesions could thus be distinguished from other hypoechoic regions based on the average SoS values. The reported findings corroborate the strong potential of the hybrid imaging approach for advancing cancer research in small animal models and fostering development of new clinical diagnostic approaches.

Speed of sound ultrasound transmission tomography image reconstruction based on Bézier curves.

Speed of Sound (SoS) maps from ultrasound tomography (UST) provide valuable quantitative information for soft tissue characterization and identification of lesions, making this technique interesting for breast cancer detection. However, due to the complexity of the processes that characterize the interaction of ultrasonic waves with matter, classic and fast tomographic algorithms such as back-projection are not suitable. Consequently, the image reconstruction process in UST is generally slow compared to other more conventional medical tomography modalities. With the aim of facilitating the translation of this technique into real clinical practice, several reconstruction algorithms are being proposed to make image reconstruction in UST to be a fast and accurate process. The geometrical acoustic approximation is often used to reconstruct SoS with less computational burden in comparison with full-wave inversion methods. In this work, we propose a simple formulation to perform on-the-flight reconstruction for UST using geometrical acoustics with refraction correction based on quadratic Bézier polynomials. Here we demonstrate that the trajectories created with these polynomials are an accurate approximation to reproduce the refracted acoustic paths connecting the emitter and receiver transducers. The method is faster than typical acquisition times in UST. Thus, it can be considered a step towards real-time reconstructions, which may contribute to its future clinical translation.

Transmission-reflection optoacoustic ultrasound (TROPUS) computed tomography of small animals.

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.

Imaging of blood flow and oxygen state with a multi-segment optoacoustic ultrasound array.

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.

Combined Pulse-Echo Ultrasound and Multispectral Optoacoustic Tomography With a Multi-Segment Detector Array.

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.

Hybrid multispectral optoacoustic and ultrasound tomography for morphological and physiological brain imaging.

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 tomography and pulse-echo ultrasonography using concave arrays.

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.