Photoacoustic imaging (PAI) is a high-resolution biomedical imaging technology for the non-invasive detection of a broad range of chromophores at multiple scales and depths. However, limited by low chromophore concentration, weak signals in deep tissue, or various noise, the signal-to-noise ratio of photoacoustic images may be compromised in many biomedical applications. Although improvements in hardware and computational methods have been made to address this problem, they have not been readily available due to either high costs or an inability to generalize across different datasets. Here, we present a self-supervised deep learning method to increase the signal-to-noise ratio of photoacoustic images using noisy data only. Because this method does not require expensive ground truth data for training, it can be easily implemented across scanning microscopic and computed tomographic data acquired with various photoacoustic imaging systems. In vivo results show that our method makes the vascular details that were completely submerged in noise become clearly visible, increases the signal-to-noise ratio by up to 12-fold, doubles the imaging depth, and enables high-contrast imaging of deep tumors. We believe this method can be readily applied to many preclinical and clinical applications.

Acoustic-resolution photoacoustic micro- scopy (AR-PAM) system can provide 3-D images of facial tissues. The lateral resolution of AR-PAM depends on the numerical aperture (NA) of the acoustic lens and the central frequency of the ultrasonic transducer. There is a trade-off between resolution enhancement and imaging depth. The acoustic beam is tight in the acoustic focal plane but expands in the out-of-focus regions, deteriorating the resolution. High-NA AR-PAM has depth-variant resolution. Synthetic aperture focusing technique (SAFT) based on a virtual detector (VD) concept can compensate for the beam shape and improve the lateral resolution via beamforming. Although, beamforming can enhance the resolution but the lateral resolution in the focal plane is still limited by acoustic diffraction. Structured-illumination can shift the spatial spectrum of an image to low frequencies hence high-frequency contents can be reserved to overcome the diffraction limit. Conventional structured-illumination via using a three-phase-shifting method can improve the resolution by two folds. Here, a modified phase-shifting method is used to generate the second harmonic of the fringes and double the spectral shift. In this idea, higher frequency information compared to the three-phase shifting method can fall into the band-limited system response. The modified phase-shifting method expands the spatial bandwidth and increases the lateral resolution by five folds. The mathematical relations and the theory are discussed in the context. Tungsten filament result shows resolution improvement from 44.6 [Formula: see text] to 11.3 [Formula: see text] by the modified structured illumination. In vivo and ex vivo experimental results validate the system performance.

Dual-modal ultrasound (US) and photoacoustic (PA) imaging has tremendous advantages in biomedical applications, such as pharmacokinetics, cancer screening, and imaging-guided therapy. Compared with ring-shaped arrays, a linear piezoelectric transducer array applies to more anatomical sites and has been widely used in US/PA imaging. However, the linear array may limit the imaging quality due to narrow bandwidth, partial detection view, or sparse spatial sampling. To meet clinic demand of high-quality US/PA imaging with the linear transducer, we develop dual-modal wide-beam harmonic ultrasound (WBHUS) and photoacoustic computed tomography at video rate. The harmonic US imaging employs pulse phase inversion to reduce clutters and improve spatial resolution. Wide-beam US transmission can shorten the scanning times by 267% and enables a 20-Hz imaging rate, which can minimize motion artifacts in in vivo imaging. The harmonic US imaging does not only provide accurate anatomical references for locating PA features but also reduces artifacts in PA images. The improved image quality allows us to acquire high-resolution anatomical structures in deep tissue without labeling. The fast-imaging speed enables visualizing interventional procedures and monitoring the pulsations of the thoracic aorta and radial artery in real-time. The video-rate dual-modal harmonic US and single-shot PA computed tomography use a clinical-grade linear-array transducer and thus can be readily implemented in clinical US imaging.

A novel super-resolution volumetric photoacoustic microscopy, based on the theory of structured-illumination, is proposed in this paper. The structured-illumination will be introduced in order to surpass the diffraction limit in a photoacoustic microscopy (PAM) structure. Through optical excitation of the targeted object with a sinusoidal spatial fringe pattern, the object's frequency spectrum is forced to shift in the spatial frequency domain. The shifting in the desired direction leads to the passage of the high-frequency contents of the object through the passband of the acoustic diffraction frequency response. Finally, combining the low-frequency image with the high-frequency parts in four regular orientations in the spatial frequency domain is equivalent to imaging the targeted object with an imaging system of two-fold bandwidth and thus half lateral resolution. In order to obtain the image of out-of-focus regions and improve the lateral resolution outside the focal region of a PAM imaging system, Fourier-domain reconstruction algorithm based on the synthetic aperture focusing technique (SAFT) using the virtual detector concept is utilized for reduction in the required computational load and time. The performance of the proposed imaging system is validated with in vivo and ex vivo targets. The experimental results obtained from several tungsten filaments in the depth range of 1.2 mm, show an improvement of -6 dB lateral resolution from 55- [Formula: see text] to 25- [Formula: see text] and also an improvement of signal-to-noise ratio (SNR) from 16-22 dB to 27-33 dB in the proposed system.

Optical-resolution photoacoustic microscopy (OR-PAM) can image blood oxygen saturation (sO2)in vivowith high resolution and excellent sensitivity and offers a great tool for neurovascular study and early cancer diagnosis. OR-PAM ignores the wavelength-dependent optical attenuation in superficial tissue, which cause errors in sO2imaging. Monte Carlo simulation shows that variations in imaging depth, vessel diameter, and focal position can cause up to$\sim 60$% decrease in sO2imaging. Here, we develop a self-fluence-compensated OR-PAM to compensate for the wavelength-dependent fluence attenuation. We propose a linearized model to estimate the fluence attenuations and use three optical wavelengths to compensate for them in sO2calculation. We validate the model in both numerical and physical phantoms and show that the compensation method can effectively reduce the sO2errors. In functional brain imaging, we demonstrate that the compensation method can effectively improve sO2accuracy, especially in small vessels. Compared with uncompensated ones, the sO2values are improved by 10~30% in the brain. We monitor ischemic-stroke-induced brain injury which demonstrates great potential for the pre-clinical study of vascular diseases.

Ultrasonography and photoacoustic tomography provide complementary contrasts in preclinical studies, disease diagnoses, and imaging-guided interventional procedures. Here, we present a video-rate (20 Hz) dual-modality ultrasound and photoacoustic tomographic platform that has a high resolution, rich contrasts, deep penetration, and wide field of view. A three-quarter ring-array ultrasonic transducer is used for both ultrasound and photoacoustic imaging. Plane-wave transmission/receiving approach is used for ultrasound imaging, which improves the imaging speed by nearly two folds and reduces the RF data size compared with the sequential single-channel scanning approach. GPU-based image reconstruction is developed to advance computational speed. We demonstrate fast dual-modality imaging in phantom, mouse, and human finger joint experiments. The results show respiration motion, heart beating, and detailed features in the mouse internal organs. To our knowledge, this is the first report on fast plane-wave ultrasound imaging and single-shot photoacoustic computed tomography in a ring-array system.

We present a fully automated micrograsping methodology that uses a micro-robot and a microgripper to automatically grasp a micropart in three-dimensional (3-D) space. To accurately grasp a micropart in 3-D space, we propose a three-stage micrograsping strategy: (i) coarse alignment of a micropart with a microgripper in the image plane of a video camera system; (ii) alignment of the micropart with the microgripper in the direction normal to the image plane; (iii) fine alignment of the micropart with the microgripper in the image plane, until the micropart is completely grasped. Two different vision-based feedback controllers are employed to perform the coarse and fine alignment in the image plane. The vision-based feedback controller used for the fine alignment employs position feedback signals obtained from two special patterns, which can achieve submicron alignment accuracy. Fully automated micrograsping experiments are conducted on a microassembly robot. The experimental results show that the average alignment accuracy achieved during automated grasping is approximately ± 0.07 μm; the time to complete an automated micrograsping task is as short as 7.9 seconds; and the success rate is as high as 94%.

In this paper, we propose a vision control strategy to perform automatic microassembly tasks in threedimension (3-D), and develop relevant control software. Specifically, using a 6 degree-of-freedom (DOF) robotic workstation to control a passive microgripper to automatically grasp a designated micropart from the chip, pivot the micropart, and then move the micropart to vertically insert into a designated slot on the chip. In the proposed control strategy, the whole microassembly task is divided into two subtasks, micro-grasping and micro-joining, in sequence. To guarantee the success of microassembly and manipulation accuracy, two different two-stage feedback motion strategies, the pattern matching and auto-focus method are employed, with the use of vision-based control system and the vision control software developed. Experiments conducted demonstrate the efficiency and validity of the proposed control strategy.