MAP Lab

Optical imaging of blood flow yields critical functional insights into the circulatory system, but its clinical implementation has typically been limited to shallow depths (~1 millimeter) due to light scattering in biological tissue. Here, we present photoacoustic noninvasive Doppler angiography (PANDA) for deep blood flow imaging. PANDA synergizes the photoacoustic and Doppler effects to generate color Doppler velocity and power Doppler blood flow maps of the vascular lumen. Our results demonstrate PANDA's ability to measure blood flow in vivo up to one centimeter in depth, marking approximately an order of magnitude improvement over existing high-resolution pure optical modalities. PANDA enhances photoacoustic flow imaging by increasing depth and enabling cross-sectional blood vessel imaging. We also showcase PANDA's clinical feasibility through three-dimensional imaging of blood flow in healthy subjects and a patient with varicose veins. By integrating the imaging system onto a mobile platform, we have designed PANDA to be a portable modality that is primed for expedient clinical translation. PANDA offers noninvasive, single modality imaging of hemoglobin and blood flow with three-dimensional capability, facilitating comprehensive assessment of deep vascular dynamics in humans.

Imaging the human body's morphological and angiographic information is essential for diagnosing, monitoring, and treating medical conditions. Ultrasonography performs the morphological assessment of the soft tissue based on acoustic impedance variations, whereas photoacoustic tomography (PAT) can visualize blood vessels based on intrinsic hemoglobin absorption. Three-dimensional (3D) panoramic imaging of the vasculature is generally not practical in conventional ultrasonography with limited field-of-view (FOV) probes, and PAT does not provide sufficient scattering-based soft tissue morphological contrast. Complementing each other, fast panoramic rotational ultrasound tomography (RUST) and PAT are integrated for hybrid rotational ultrasound and photoacoustic tomography (RUS-PAT), which obtains 3D ultrasound structural and PAT angiographic images of the human body quasi-simultaneously. The RUST functionality is achieved in a cost-effective manner using a single-element ultrasonic transducer for ultrasound transmission and rotating arc-shaped arrays for 3D panoramic detection. RUST is superior to conventional ultrasonography, which either has a limited FOV with a linear array or is high-cost with a hemispherical array that requires both transmission and receiving. By switching the acoustic source to a light source, the system is conveniently converted to PAT mode to acquire angiographic images in the same region. Using RUS-PAT, we have successfully imaged the human head, breast, hand, and foot with a 10 cm diameter FOV, submillimeter isotropic resolution, and 10 s imaging time for each modality. The 3D RUS-PAT is a powerful tool for high-speed, 3D, dual-contrast imaging of the human body with potential for rapid clinical translation..

Herein we report the first in-human transcranial imaging of brain function using photoacoustic computed tomography. Functional responses to benchmark motor tasks were imaged on both the skull-less and the skull-intact hemispheres of a hemicraniectomy patient. The observed brain responses in these preliminary results demonstrate the potential of photoacoustic computed tomography for achieving transcranial functional imaging.

Ultrasound angiography based on delay-and-sum (DAS) beamforming has enabled mapping of blood flow in soft tissues, e.g., myocardium, brain, and kidney, but its resolution and contrast were suboptimal due to inherent limitations of the DAS beamformer. Adaptive beamformers (data-dependent) show improved resolutions and contrast for B-mode at the expense of increased speckle variations, which degrade the clutter filtering performance. This study thus aims at circumventing the drawback of adaptive beamforming to significantly improve the quality of contrast-agent-free ultrasound angiography.

Recent advances in functional ultrasound imaging (fUS) and photoacoustic tomography (PAT) offer powerful tools for studying brain function. Complementing each other, fUS and PAT, respectively, measure the cerebral blood flow (CBF) and hemoglobin concentrations, allowing synergistic characterization of cerebral hemodynamics. Here, cross-ray ultrasound tomography (CRUST) and its combination with PAT are presented. CRUST employs a virtual point source from a spherically focused ultrasonic transducer (SFUST) to provide widefield excitation at a 4-kHz pulse repetition frequency. A full-ring-shaped ultrasonic transducer array whose imaging plane is orthogonal to the SFUST's acoustic axis receives scattered ultrasonic waves. Superior to conventional fUS, whose sensitivity to blood flow is angle-dependent and low for perpendicular flow, the crossed transmission and panoramic detection fields of CRUST provide omnidirectional sensitivity to CBF. Using CRUST-PAT, the CBF, oxygen saturation, and hemoglobin concentration changes of the mouse brain during sensory stimulation are measured, with a field of view of ≈7 mm in diameter, spatial resolution of ≈170 µm, and temporal resolution of 200 Hz. The results demonstrate CRUST-PAT as a unique tool for studying cerebral hemodynamics.

Imaging deep haemodynamics non-invasively remains a quest. Although optical imaging techniques can be used to measure blood flow, they are generally limited to imaging within ∼1 mm below the skin’s surface. Here we show that such optical diffusion limit can be broken through by leveraging the spatial heterogeneity of blood and its photoacoustic contrast. Specifically, successive single-shot wide-field photoacoustic images of blood vessels can be used to visualize the frame-to-frame propagation of blood and to estimate blood flow speed and direction pixel-wise. The method, which we named photoacoustic vector tomography (PAVT), allows for the quantification of haemodynamics in veins more than 5 mm deep, as we show for regions in the hands and arms of healthy volunteers. PAVT may offer advantages for the diagnosis and monitoring of vascular diseases and for the mapping of the function of the circulatory system.

Many time-difference measurement devices such as time-to-digital converters (TDCs) are designed on the basis of threshold or zero cross detection technology. However, baseline shift, which means that the detected signals may have a shift of amplitude of the whole signal, is common in electronic circuits and has a great influence on the accuracy and stability of the time-difference measured with conventional posedge or negedge detection methods. In general, the baseline shifts can be classified into two cases which are parallel and oblique baseline shifts according to their different origins. Parallel baseline shift means that the baselines of two detected signals are parallel but in different levels, while oblique baseline shift is that the baselines of two detected signals are not parallel and the baselines have a nearly linear relationship with the time in the duration of signals. In this paper, detection methods using multiple edges, namely, double-edge and triple-edge methods, are proposed to reduce the impact of relative baseline shift between two signals for high-precision time-difference measurement because they require more information of the signal waveforms than conventional methods. The simulation results show that the proposed methods have a better performance than conventional posedge or negedge method. The experiment results based on a TDC chip, i.e., TDC-GP21, also demonstrate the validity of proposed methods when baseline shifts exist.

Plane-wave-based ultrafast imaging has become the prevalent technique for non-conventional ultrasound imaging. The image quality, especially in terms of the suppression of artifacts, is generally compromised by reducing the number of transmissions for a higher frame rate. We hereby propose a new ultrafast imaging framework that reduces not only the side lobe artifacts but also the axial lobe artifacts using combined transmissions with a new coherence-based factor. The results from simulations, in vitro wire phantoms, the ex vivo porcine artery, and the in vivo porcine heart show that our proposed methodology greatly reduced the axial lobe artifact by 25±5 dB compared with coherent plane-wave compounding (CPWC), which was considered as the ultrafast imaging standard, and suppressed side lobe artifacts by 15 ± 5 dB compared with CPWC and coherent spherical-wave compounding. The reduction of artifacts in our proposed ultrafast imaging framework led to a better boundary delineation of soft tissues than CPWC.

Ultrafast ultrasound imaging using plane or diverging waves, instead of focused beams, has advanced greatly the development of novel ultrasound imaging methods for evaluating tissue functions beyond anatomical information. However, the sonographic signal-to-noise ratio (SNR) of ultrafast imaging remains limited due to the lack of transmission focusing, and thus insufficient acoustic energy delivery. We hereby propose a new ultrafast ultrasound imaging methodology with cascaded dual-polarity waves (CDWs), which consists of a pulse train with positive and negative polarities. A new coding scheme and a corresponding linear decoding process were thereby designed to obtain the recovered signals with increased amplitude, thus increasing the SNR without sacrificing the frame rate. The newly designed CDW ultrafast ultrasound imaging technique achieved higher quality B-mode images than coherent plane-wave compounding (CPWC) and multiplane wave (MW) imaging in a calibration phantom, ex vivo pork belly, and in vivo human back muscle. CDW imaging shows a significant improvement in the SNR (10.71 dB versus CPWC and 7.62 dB versus MW), penetration depth (36.94% versus CPWC and 35.14% versus MW), and contrast ratio in deep regions (5.97 dB versus CPWC and 5.05 dB versus MW) without compromising other image quality metrics, such as spatial resolution and frame rate. The enhanced image qualities and ultrafast frame rates offered by CDW imaging beget great potential for various novel imaging applications.

The heart is an organ with highly dynamic complexity, including cyclic fast electrical activation, muscle kinematics, and blood dynamics. Although ultrafast cardiac imaging techniques based on pulsed-wave ultrasound (PUS) have rapidly emerged to permit mapping of heart dynamics, they suffer from limited sonographic signal-to-noise ratio (SNR) and penetration due to insufficient energy delivery and inevitable attenuation through the chest wall. We hereby propose ultrafast cascaded-wave ultrasound (uCUS) imaging to depict heart dynamics in higher SNR and larger penetration than conventional ultrafast PUS. To solve the known tradeoff between the length of transmitted ultrasound signals and spatial resolution while achieving ultrafast frame rates (>1000 Hz), we develop a cascaded synthetic aperture (CaSA) imaging method. In CaSA, an array probe is divided into subapertures; each subaperture transmits a train of diverging waves. These diverging waves are weighted in both the aperture (i.e., spatial) and range (i.e., temporal) directions with a coding matrix containing only +1 and -1 polarity coefficients. A corresponding spatiotemporal decoding matrix is designed to recover backscattered signals. The decoded signals are thereafter beamformed and coherently compounded to obtain one high-SNR beamformed image frame. For CaSA with M subapertures and N cascaded diverging waves, sonographic SNR is increased by 10× log10(N×M) (dB) compared with conventional synthetic aperture (SA) imaging. The proposed uCUS with CaSA was evaluated with conventional SA and Hadamard-encoded SA (H-SA) methods in a calibration phantom for B-mode image quality and an invivo human heart in a transthoracic setting for the quality assessment of anatomical, myocardial motion, and chamber blood power Doppler images. Our results demonstrated that the proposed uCUS with CaSA (4 subapertures, 32 cascaded waves) improved SNR (+20.46 dB versus SA, +14.83 dB versus H-SA) and contrast ratio (+8.44 dB versus SA, +7.81 dB versus H-SA) with comparable spatial resolutions to and at the same frame rates as benchmarks.