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A fast scanner of optical-resolution photoacoustic microscopy is inherently vulnerable to perturbation, leading to severe image distortion and significant misalignment among multiple 2D or 3D images. Restoration and registration of these images is critical for accurately quantifying dynamic information in long-term imaging. However, traditional registration algorithms face a great challenge in computational throughput. Here, we develop an unsupervised deep learning based registration network to achieve real-time image restoration and registration. This method can correct artifacts from B-scan distortion and remove misalignment among adjacent and repetitive images in real time. Compared with conventional intensity based registration algorithms, the throughput of the developed algorithm is improved by 50 times. After training, the new deep learning method performs better than conventional feature based image registration algorithms. The results show that the proposed method can accurately restore and register the images of fast-scanning photoacoustic microscopy in real time, offering a powerful tool to extract dynamic vascular structural and functional information.

Alzheimer’s disease (AD), referring to a gradual deterioration in cognitive function, including memory loss and impaired thinking skills, has emerged as a substantial worldwide challenge with profound social and economic implications. As the prevalence of AD continues to rise and the population ages, there is an imperative demand for innovative imaging techniques to help improve our understanding of these complex conditions. Photoacoustic (PA) imaging forms a hybrid imaging modality by integrating the high-contrast of optical imaging and deep-penetration of ultrasound imaging. PA imaging enables the visualization and characterization of tissue structures and multifunctional information at high resolution and, has demonstrated promising preliminary results in the study and diagnosis of AD. This review endeavors to offer a thorough overview of the current applications and potential of PA imaging on AD diagnosis and treatment. Firstly, the structural, functional, molecular parameter changes associated with AD-related brain imaging captured by PA imaging will be summarized, shaping the diagnostic standpoint of this review. Then, the therapeutic methods aimed at AD is discussed further. Lastly, the potential solutions and clinical applications to expand the extent of PA imaging into deeper AD scenarios is proposed. While certain aspects might not be fully covered, this mini-review provides valuable insights into AD diagnosis and treatment through the utilization of innovative tissue photothermal effects. We hope that it will spark further exploration in this field, fostering improved and earlier theranostics for AD.

With the recent advances in nanomaterials, photothermal therapies (PTT) enabled by deep-tissue penetration with novel nanoagents have offered a new hope for treating cancers. Nevertheless, PTT applications in conventional approaches remain translationally restricted due to their non-specificity and collateral pro-inflammatory effects during implementation. To address these drawbacks, we here report Lipo-PTO as the prototype of a new class of liposome-functionalized photothermal theragnostic agents, which can eradicate cancer cells in vivo with high selectivity. Lipo-PTO is activated by low pH and superoxide (O2•–) to specifically deliver and convert preloaded cyanine molecules to release Cy-NH in the tumour microenvironments, eventually enabling the activation of photothermal properties to induce tumour ablation. In further studies on Lipo-PTO for treating breast cancer (BC) in mouse models, Lipo-PTO usage was characterized by a high degree of biocompatibility, optimal retention time pharmacokinetics and tumour regression with minimal collateral damages. This study here thus illustrates an innovative strategy to target intrinsic attributes of tumour microenvironments for improved therapeutic precision and efficacy in PTT applications.

Abstract Photoacoustic microscopy can image many biological molecules and nano‐agents in vivo via low‐scattering ultrasonic sensing. Insufficient sensitivity is a long‐standing obstacle for imaging low‐absorbing chromophores with less photobleaching or toxicity, reduced perturbation to delicate organs, and more choices of low‐power lasers. Here, the photoacoustic probe design is collaboratively optimized and a spectral‐spatial filter is implemented. A multi‐spectral super‐low‐dose photoacoustic microscopy (SLD‐PAM) is presented that improves the sensitivity by ≈33 times. SLD‐PAM can visualize microvessels and quantify oxygen saturation in vivo with ≈1% of the maximum permissible exposure, dramatically reducing potential phototoxicity or perturbation to normal tissue function, especially in imaging of delicate tissues, such as the eye and the brain. Capitalizing on the high sensitivity, direct imaging of deoxyhemoglobin concentration is achieved without spectral unmixing, avoiding wavelength‐dependent errors and computational noises. With reduced laser power, SLD‐PAM can reduce photobleaching by ≈85%. It is also demonstrated that SLD‐PAM achieves similar molecular imaging quality using 80% fewer contrast agents. Therefore, SLD‐PAM enables the use of a broader range of low‐absorbing nano‐agents, small molecules, and genetically encoded biomarkers, as well as more types of low‐power light sources in wide spectra. It is believed that SLD‐PAM offers a powerful tool for anatomical, functional, and molecular imaging.

As electronic devices get smaller, more portable, and smarter, a new approach of realizing electronics in thin, soft, and even stretchable style that could be worn and attached to the skin, which is called skin electronics, has emerged and attracted much attention. To achieve well compliance, extend the maximum stretchability, promote the comfortability of wearing, and make the most use of the skin electronics, researchers are making efforts in different aspects. In this article, we summarized the recent advances in categories of materials science, design strategies and novel applications. Examples of skin electronics using various functional materials including piezoelectric, thermoelectric, etc., and soft conductive materials including PEDOT: PSS-based conductive polymer, carbon nanomaterials, metal-based materials and hydrogels were given. Different mechanics design strategies for enhancing mechanical performance and comfortability design strategies for better wearing experience were introduced. Lastly, practical applications of skin electronics in fields of smart healthcare and human-machine interface were discussed. Research focused on these aspects all boosted the development of skin electronics in different dimensions, with which combined together may help skin electronics take a leap into truly ubiquitous use in our daily life.

The authors developed an optical-fiber-based photoacoustic endoscope for gastroenterology. It can noninvasively view the internal vascular structures and visualize the hemodynamic response in a lesion.

Optical-resolution photoacoustic microscopy offers high-resolution, label-free hemodynamic and functional imaging to many biomedical applications. However, long-standing technical barriers, such as limited field of view, bulky scanning probes, and slow imaging speed, have limited the application of optical-resolution photoacoustic microscopy. Here, we present freehand scanning photoacoustic microscopy (FS-PAM) that can flexibly image various anatomical sites. We develop a compact handheld photoacoustic probe to acquire 3D images with high speed, and great flexibility. The high scanning speed not only enables video camera mode imaging but also allows for the first implementation of simultaneous localization and mapping (SLAM) in photoacoustic microscopy. We demonstrate fast in vivo imaging of some mouse organs, and human oral mucosa. The high imaging speed greatly reduces motion artifacts and distortions from tissue moving, breathing, and unintended handshaking. We demonstrate small-lesion localization in a large region of the brain. FS-PAM offers a flexible high-speed imaging tool with an extendable field of view, enabling more biomedical imaging applications.

Photoacoustic microscopy uses multiple wavelengths to measure concentrations of different absorbers. The speed of sound limits the shortest wavelength switching time to sub-microseconds, which is a bottleneck for high-speed broad-spectrum imaging. Via computational separation of overlapped signals, we can break the sound-speed limit on the wavelength switching time. This paper presents a new signal unmixing algorithm named two-step proximal gradient descent. It is advantageous in separating multiple wavelengths with long overlapping and high noise. In the simulation, we can unmix up to nine overlapped signals and successfully separate three overlapped signals with 12-ns delay and 15.9-dB signal-to-noise ratio. We apply this technique to separate three-wavelength photoacoustic images in microvessels. In vivo results show that the algorithm can successfully unmix overlapped multi-wavelength photoacoustic signals, and the unmixed data can improve accuracy in oxygen saturation imaging.

Full-ring dual-modal ultrasound and photoacoustic computed tomography has unique advantages of nearly isotropic spatial resolution, complementary contrast, deep penetration, and full-view detection. However, the imaging quality may be deteriorated by the inaccurate sound speed estimation. Automatic determining and compensation for sound speed has been a long-standing problem in image reconstruction. Here, we present new adaptive dual-speed ultrasound and photoacoustic computed tomography (ADS-USPACT) to address this challenge. The system features full-view coverage (360°), high-speed dual-modal imaging (10-Hz), automated dual sound speed correction, and synergistic high imaging quality. To correct the sound speed, we develop a two-compartment method that can automatically segment the sample boundary and search for the optimal sound speed based on the rich ultrasonic pulse-echo signals. The method does not require the operator’s intervention. We validate this technique in numerical simulation, phantom study, and in vivo experiments. The ADS-USPACT represents significant progress in dual-modal imaging.

Abstract Ultrasonography is a major medical imaging technique that has been broadly applied in many disease diagnoses. However, due to strong aberration and scattering in the human skull, high-resolution transcranial ultrasonic imaging remains a grand challenge. Here, we explore the rotational-invariant property of ultrasonic speckle and develop high-resolution speckle-scanning ultrasonography to image sub-millimeter-sized features through thick bones. We experimentally validate the rotational invariance of ultrasonic speckle. Based on this property, we scan a random ultrasonic speckle pattern across an object sandwiched between two thick bones so that the object features can be encoded to the ultrasonic waves. After receiving the transmitted ultrasonic waves, we reconstruct the image of the object using an iterative phase retrieval algorithm. We successfully demonstrate imaging of hole and tube features sized as fine as several hundreds of microns between two 0.5 ~ 1-cm-thick bones. With 2.5-MHz excitation and the third-harmonic detection, we measure the spatial resolution as 352 µm. Rotational-invariant speckle-scanning ultrasonography offers a new approach to image through thick bones and paves an avenue towards high-resolution ultrasonic imaging of the human brain.

Current preclinical imaging of intestine in animal models cannot reveal intestinal dynamics in awake condition. Here the authors report a Transillumination Intestine Projection (TIP) imaging system for free-moving mice, and showed the intestine dynamics in conscious animal in natural physiological states.

Optical-resolution photoacoustic microscopy (OR-PAM) enjoys superior spatial resolution and has received intense attention in recent years. The application, however, has been limited to shallow depths because of strong scattering of light in biological tissues. In this work, we propose to achieve deep-penetrating OR-PAM performance by using deep learning enabled image transformation on blurry living mouse vascular images that were acquired with an acoustic-resolution photoacoustic microscopy (AR-PAM) setup. A generative adversarial network (GAN) was trained in this study and improved the imaging lateral resolution of AR-PAM from 54.0 µm to 5.1 µm, comparable to that of a typical OR-PAM (4.7 µm). The feasibility of the network was evaluated with living mouse ear data, producing superior microvasculature images that outperforms blind deconvolution. The generalization of the network was validated with in vivo mouse brain data. Moreover, it was shown experimentally that the deep-learning method can retain high resolution at tissue depths beyond one optical transport mean free path. Whilst it can be further improved, the proposed method provides new horizons to expand the scope of OR-PAM towards deep-tissue imaging and wide applications in biomedicine.

We report fiber-based dual-foci fast-scanning OR-PAM that can double the scanning rate without compromising the imaging resolution, the field of view, and the detection sensitivity. To achieve fast scanning speed, the OR-PAM system uses a single-axis water-immersible resonant scanning mirror that can confocally scan the optical and acoustic beams at 1018 Hz with a 3-mm range. Pulse energies of 45∼100-nJ are sufficient for acquiring vascular and oxygen-saturation images. The dual-foci method can double the B-scan rate to 2036 Hz. Using two lasers and stimulated Raman scattering, we achieve dual-wavelength excitation on both foci, and the total A-line rate is 3.2-MHz. In in vivo experiments, we inject epinephrine and monitor the hemodynamic and oxygen saturation response in the peripheral vessels at 1.7 Hz over 2.5 × 6.7 mm2. Dual-foci OR-PAM offers a new imaging tool for the study of fast physiological and pathological changes.

Optical-resolution photoacoustic microscopy (OR-PAM) is used for in vivo imaging of a variety of albino and pigmented eyes taking advantages of requiring no exogenous dye, performing high-resolution imaging, and achieving morphologic and functional imaging at the same time. However, to accurately diagnose the ophthalmic disease in the OR-PAM images, vascular enhancement algorithms are necessary for extracting vessels and quantifying them correctly. Vascular enhancement algorithms developed for other imaging technologies, are not suitable to be used for OR-PAM, because of the underlying differences in the physics of the formation of images. In this study, a new vascular enhancement algorithm called photoacoustic imaging vasculature enhancement filter (PAIVEF) is proposed, which not only enhances vasculature including micro-vessels signals, suppresses noise signals effectively, but also achieves highly sensitive and accurate enhancement of the vasculature within a large depth range in and out of the system's depth of focus (DOF). Using the PAIVEF, the morphologic and functional 3D images of the whole rat's ocular anterior vasculature segment was displayed simultaneously for a depth range of ~0.6 mm, which was ~7 times of the system's DOF. This study paves the way for the application of OR-PAM technology in ophthalmic disease research.

We report wide-field polygon-scanning functional OR-PAM that for the first time achieves 1-MHz A-line rate of oxygen saturation in vivo. We address two technical challenges. The first is a 1-MHz dual-wavelength pulsed laser that has sufficient pulse energy and ultrafast wavelength switching. The second is a polygon-scanning imaging probe that has a fast scanning speed, a large field of view, and great sensitivity. The OR-PAM system offers a B-scan rate of 477.5 Hz in a 12-mm range and a volumetric imaging rate of ∼1 Hz over a 12 × 5 mm2 scanning area. We image microvasculature and blood oxygen saturation in a 12 × 12 mm2 scanning area in 5 s. Dynamic imaging of oxygen saturation in the mouse ear is demonstrated to monitor fast response to epinephrine injection. The new wide-field fast functional imaging ability broadens the biomedical application of OR-PAM.

Type 1 diabetes (T1D) is an incurable disease that affects 1. 25 million Americans. Diabetic patients typically rely on subcutaneous insulin infusions to regulate their glucose levels. A major contributor to their blood glucose levels is the amount of sugar intake, which cannot be easily tracked. While ultrasound imaging has been used to investigate the relationship between food characteristics and tongue movement, the technique utilized a bulky transducer array that cannot be translated into daily monitoring. Capitalizing on advanced electronics and data processing technologies, we developed a portable system that utilizes only a single ceramic disk to quantify the tongue movement in response to various levels of sweetness. After acquiring 32 subject datasets, we found a significant correlation between food sweetness and tongue movement. Our system can potentially be miniaturized into a wearable device for monitoring sugar intake, which will ultimately help T1D patients to better monitor and control their blood glucose levels and balance their diets accordingly.

We present fast functional optical-resolution photoacoustic microscopy (OR-PAM) that can simultaneously image hemoglobin concentration, blood flow speed, and oxygen saturation with three-pulse excitation. To instantaneously determine the blood flow speed, dual-pulse photoacoustic flowmetry is developed to determine the blood flow speed from photoacoustic signal decay in sub-microseconds. Grueneisen relaxation effect is compensated for in the oxygen saturation calculation. The blood flow imaging is validated in phantom and in vivo experiments. The results show that the flow speed can be measured accurately in sub-microseconds by comparing the dual-pulse flowmetric method with photoacoustic Doppler flowmetry. Wide-field OR-PAM of hemoglobin concentration, blood flow speed, and oxygen saturation are demonstrated in the mouse ear. This technical advance enables more biomedical applications for fast functional OR-PAM. Keywords: Dual-pulse photoacoustic flowmetry, Grueneisen relaxation effect, Multi-functional, Sub-microseconds

Dichroism is a material property that causes anisotropic light-matter interactions for different optical polarizations. Dichroism relates to molecular types and material morphology and thus can be used to distinguish different dichroic tissues. In this paper, we present single-shot dichroism photoacoustic microscopy that can image tissue structure, linear dichroism, and polarization angle with a single raster scanning. We develop a fiber-based laser system to split one laser pulse into three with different polarization angles, sub-microseconds time delay, and identical pulse energy. A dual-fiber optical-resolution photoacoustic microscopy system is developed to acquire three A-lines per scanning step. In such a way, dichroism imaging can achieve the same speed as single-wavelength photoacoustic microscopy. Moreover, the three polarized pulses originate from one laser pulse, which decreases pulse energy fluctuations and reduces dichroism measurement noise by ∼35 %. The new dichroism photoacoustic imaging technique can be used to image endogenous or exogenous polarization-dependent absorption contrasts, such as dichroic tumor or molecule-labeled tissue. Keywords: Linear dichroism, Photoacoustic microscopy, Polarization

The state-of-the-art three-dimensional biomedical imaging often requires specific tissue preparation that may alter the physical properties of the specimen causing loss of information. Here Wong et al. develop a microtomy-assisted photoacoustic microscopy that allows imaging of biological samples without labelling agents and with reduced sectioning.

We present a new spatial compounding method to improve the contrast of ultrasonic images for non-delayed sequential beamforming (NDSB). Sequential beamforming adopts more than one beamformer to reconstruct B-mode images which has the advantage of simple front-end electronics and fast data transfer rate. Via field pattern analysis, we propose a compounding method where two more sub-images can be reconstructed along with the NDSB sub-image. These sub-images can be seen as being produced with different transmit origins; thus, their summation enhances image contrast. Image quality was analyzed in terms of spatial resolution, contrast ratio (CR), and contrast-to-noise ratio (CNR). The proposed compounding method improves the lateral resolution up to 41%. In vitro results confirm a 13.0-dB CR and 4.0-dB CNR improvement. In vivo results reveal 10.9-dB and 6.0-dB improvement in CR and CNR for cross-section jugular vein and 8.0-dB and 4.5-dB improvement in CR and CNR for the longitudinal-section carotid artery.

Hemostasis is vital to save lives, reducing risks of organ failure and hemorrhagic shock. Exploring novel hemostatic materials and precise monitoring of the hemostatic status is of great importance for efficient hemostasis. We present the development of chitosan–graphene oxide-based hemostatic composite and multi-scale photoacoustic evaluation of the hemostatic performance. The hemostatic sponge can quickly and efficiently absorb the blood with its porous cavity and specific surficial property. We inspect the hemostatic performance via an in vitro blood absorption test and in vivo mouse bleeding injury experiments. Results show that the synthesized hemostatic sponge can not only absorb plasma in blood fast with its interior porous structure but also stimulate the interfacial reaction with erythrocytes and platelets. The superiority of multi-scale photoacoustic imaging for guiding, monitoring, and evaluating the hemostatic stages of sponges is demonstrated with high spatial resolution and great sensitivity at depths. Photoacoustic evaluation of a chitosan–graphene oxide-based hemostatic sponge has the potential to be transferred toward the clinical assessment of wound healing.

Optical resolution photoacoustic microscopy (OR-PAM) provides high-resolution, label-free and non-invasive functional imaging for broad biomedical applications. Dual-polarized fiber laser sensors have high sensitivity, low noise, a miniature size, and excellent stability; thus, they have been used in acoustic detection in OR-PAM. Here, we review recent progress in fiber-laser-based ultrasound sensors for photoacoustic microscopy, especially the dual-polarized fiber laser sensor with high sensitivity. The principle, characterization and sensitivity optimization of this type of sensor are presented. In vivo experiments demonstrate its excellent performance in the detection of photoacoustic (PA) signals in OR-PAM. This review summarizes representative applications of fiber laser sensors in OR-PAM and discusses their further improvements.

This study investigates the heat dissipation mechanism of the insulation layer and other plane insulation layers in the polar drilling rig system. Combining the basic theory of heat transfer with the environmental requirements of polar drilling operations and the characteristics of polar drilling processes, we analyze the factors that affect the insulation effect of the drilling rig system. These factors include the thermal conductivity of the insulation material, the thickness of the insulation layer, ambient temperature, and wind speed. We optimize the thermal insulation material of the polar drilling rig system using a steady-state method to measure solid thermal conductivity. By analyzing the distribution of temperature in space after heating, we optimize the distribution and air outlet angle of the heater using Fluent hydrodynamics software. The results demonstrate that under polar conditions, polyisocyanurate with stable thermodynamic properties is selected as the thermal insulation material. The selection of thermal insulation material and thickness significantly affects the thermal insulation effect of the system but has little effect on its heating effect. Moreover, when the air outlet angle of the heater is set to 32.5°, the heating efficiency of the system can be effectively improved. According to heat transfer equations and heat balance theory, we determine that the heating power required for the system to reach 5°C is close to numerical simulation. [ABSTRACT FROM AUTHOR]