An Omni-Mesoscope for multiscale high-throughput quantitative phase imaging of cellular dynamics and high-content molecular characterization.

The mesoscope has emerged as a powerful imaging tool in biomedical research, yet its high cost and low resolution have limited its broader application. Here, we introduce the Omni-Mesoscope, a high-spatial-temporal and multimodal mesoscopic imaging platform built from cost-efficient off-the-shelf components. This system uniquely merges the capabilities of label-free quantitative phase microscopy to capture live-cell morphodynamics across thousands of cells with highly multiplexed fluorescence imaging for comprehensive molecular characterization.

An Omni-Mesoscope for multiscale high-throughput quantitative phase imaging of cellular dynamics and high-content molecular characterization.

The mesoscope has emerged as a powerful imaging tool in biomedical research, yet its high cost and low resolution have limited its broader application. Here, we introduce the Omni-Mesoscope, a cost-effective high-spatial-temporal, multimodal, and multiplex mesoscopic imaging platform built from cost-efficient off-the-shelf components. This system uniquely merges the capabilities of quantitative phase microscopy to capture live-cell dynamics over a large cell population with highly multiplexed fluorescence imaging for comprehensive molecular characterization.

Toward drift-free high-throughput nanoscopy through adaptive intersection maximization.

Single-molecule localization microscopy (SMLM) often suffers from suboptimal resolution due to imperfect drift correction. Existing marker-free drift correction algorithms often struggle to reliably track high-frequency drift and lack the computational efficiency to manage large, high-throughput localization datasets. We present an adaptive intersection maximization-based method (AIM) that leverages the entire dataset's information content to minimize drift correction errors, particularly addressing high-frequency drift, thereby enhancing the resolution of existing SMLM systems.

Self-enhancing sono-inks enable deep-penetration acoustic volumetric printing.

Volumetric printing, an emerging additive manufacturing technique, builds objects with enhanced printing speed and surface quality by forgoing the stepwise ink-renewal step. Existing volumetric printing techniques almost exclusively rely on light energy to trigger photopolymerization in transparent inks, limiting material choices and build sizes. We report a self-enhancing sonicated ink (or sono-ink) design and corresponding focused-ultrasound writing technique for deep-penetration acoustic volumetric printing (DAVP).

Epinephrine-induced Effects on Cerebral Microcirculation and Oxygenation Dynamics Using Multimodal Monitoring and Functional Photoacoustic Microscopy.

Background: The administration of epinephrine after severe refractory hypotension, shock, or cardiac arrest restores systemic blood flow and major vessel perfusion but may worsen cerebral microvascular perfusion and oxygen delivery through vasoconstriction. The authors hypothesized that epinephrine induces significant microvascular constriction in the brain, with increased severity after repetitive dosing and in the aged brain, eventually leading to tissue hypoxia.

Methods: The authors investigated the effects of intravenous epinephrine administration in healthy young and aged C57Bl/6 mice on cerebral microvascular blood flow and oxygen delivery using multimodal in vivo imaging, including functional photoacoustic microscopy, brain tissue oxygen sensing, and follow-up histologic assessment.

Multiscale photoacoustic tomography using reversibly switchable thermochromics.

Significance: Based on acoustic detection of optical absorption, photoacoustic tomography (PAT) allows functional and molecular imaging beyond the optical diffusion limit with high spatial resolution. However, multispectral functional and molecular PAT is often limited by decreased spectroscopic accuracy and reduced detection sensitivity in deep tissues, mainly due to wavelength-dependent optical attenuation and inaccurate acoustic inversion.

Aim: Previous work has demonstrated that reversible color-shifting can drastically improve the detection sensitivity of PAT by suppressing nonswitching background signals.

Glassfrogs conceal blood in their liver to maintain transparency.

Transparency in animals is a complex form of camouflage involving mechanisms that reduce light scattering and absorption throughout the organism. In vertebrates, attaining transparency is difficult because their circulatory system is full of red blood cells (RBCs) that strongly attenuate light. Here, we document how glassfrogs overcome this challenge by concealing these cells from view.

High-speed wide-field photoacoustic microscopy using a cylindrically focused transparent high-frequency ultrasound transducer.

Combining focused optical excitation and high-frequency ultrasound detection, optical-resolution photoacoustic microscopy (OR-PAM) can provide micrometer-level spatial resolution with millimeter-level penetration depth and has been employed in a variety of biomedical applications. However, it remains a challenge for OR-PAM to achieve a high imaging speed and a large field of view at the same time. In this work, we report a new approach to implement high-speed wide-field OR-PAM, using a cylindrically-focused transparent ultrasound transducer (CFT-UT).

Intraperitoneal administration for sustained photoacoustic contrast agent imaging.

Photoacoustic (PA) imaging at 1064 nm in the second near-infrared (NIR-II) has attracted recent attention. We recently reported a surfactant-based formulation of a NIR-II dye (BIBDAH) for NIR-II PA contrast. Here, we investigated BIBDAH as a NIR-II PA contrast agent for longitudinal preclinical PA imaging.

Detection of weak optical absorption by optical-resolution photoacoustic microscopy.

Optical-resolution photoacoustic microscopy (OR-PAM) is one of the major implementations of photoacoustic (PA) imaging. With tightly focused optical illumination and high-frequency ultrasound detection, OR-PAM provides micrometer-level resolutions as well as high sensitivity to optical absorption contrast. Traditionally, it is assumed that the detected PA signal in OR-PAM has a linear dependence on the target's optical absorption coefficient, which is the basis for quantitative functional and molecular PA imaging.

Photoacoustic imaging of 3D-printed vascular networks.

Thrombosis in the circulation system can lead to major myocardial infarction and cardiovascular deaths. Understanding thrombosis formation is necessary for developing safe and effective treatments. In this work, using digital light processing (DLP)-based 3D printing, we fabricated sophisticatedmodels of blood vessels with internal microchannels that can be used for thrombosis studies.

High-speed functional photoacoustic microscopy using a water-immersible two-axis torsion-bending scanner.

Optical-resolution photoacoustic microscopy (OR-PAM) can provide functional, anatomical, and molecular images at micrometer level resolution with an imaging depth of less than 1 mm in tissue. However, the imaging speed of traditional OR-PAM is often low due to the point-by-point mechanical scanning and cannot capture time-sensitive dynamic information. In this work, we demonstrate a recent effort in improving the imaging speed of OR-PAM, using a newly developed water-immersible two-axis scanner.

Structural and Functional Imaging of the Retina in Central Retinal Artery Occlusion - Current Approaches and Future Directions.

Central retinal artery occlusion (CRAO) is a form of acute ischemic stroke which affects the retina. Intravenous thrombolysis is emerging as a compelling therapeutic approach. However, it is not known which patients may benefit from this therapy because there are no imaging modalities that adequately distinguish viable retina from irreversibly infarcted retina.

Deep image prior for undersampling high-speed photoacoustic microscopy.

Photoacoustic microscopy (PAM) is an emerging imaging method combining light and sound. However, limited by the laser's repetition rate, state-of-the-art high-speed PAM technology often sacrifices spatial sampling density (, undersampling) for increased imaging speed over a large field-of-view. Deep learning (DL) methods have recently been used to improve sparsely sampled PAM images; however, these methods often require time-consuming pre-training and large training dataset with ground truth.

Photoacoustic imaging of in vivo hemodynamic responses to sodium nitroprusside.

The in vivo hemodynamic impact of sodium nitroprusside (SNP), a widely used antihypertensive agent, has not been well studied. Here, we applied functional optical-resolution photoacoustic microscopy (OR-PAM) to study the hemodynamic responses to SNP in mice in vivo. As expected, after the application of SNP, the systemic blood pressure (BP) was reduced by 53%.

A near-infrared genetically encoded calcium indicator for in vivo imaging.

While calcium imaging has become a mainstay of modern neuroscience, the spectral properties of current fluorescent calcium indicators limit deep-tissue imaging as well as simultaneous use with other probes. Using two monomeric near-infrared (NIR) fluorescent proteins (FPs), we engineered an NIR Förster resonance energy transfer (FRET)-based genetically encoded calcium indicator (iGECI). iGECI exhibits high levels of brightness and photostability and an increase up to 600% in the fluorescence response to calcium.

Reconstructing Undersampled Photoacoustic Microscopy Images Using Deep Learning.

One primary technical challenge in photoacoustic microscopy (PAM) is the necessary compromise between spatial resolution and imaging speed. In this study, we propose a novel application of deep learning principles to reconstruct undersampled PAM images and transcend the trade-off between spatial resolution and imaging speed. We compared various convolutional neural network (CNN) architectures, and selected a Fully Dense U-net (FD U-net) model that produced the best results.

photoacoustic imaging dynamically monitors the structural and functional changes of ischemic stroke at a very early stage.

Ischemic stroke (IS) is one of the leading causes of death and accounts for 85% of stroke cases. Since the symptoms are not obvious, diagnosis of IS, particularly at an early stage, is a great challenge. Photoacoustic imaging combines high sensitivity of optical imaging and fine resolution of ultrasonography to non-invasively provide structural and functional information of IS.

Simultaneous photoacoustic imaging of intravascular and tissue oxygenation.

Hypoxia, a low tissue oxygenation condition caused by insufficient oxygen supply, leads to potentially irreversible tissue damage, such as brain infarction during stroke. Intravascular oxygenation has long been used by photoacoustic imaging, among other imaging modalities, to study hypoxia. However, intravascular oxygenation describes only the oxygen supply via microcirculation, which does not directly reflect the amount of free oxygen available for metabolism in the interstitial fluid.

Ag-Hybridized plasmonic Au-triangular nanoplates: highly sensitive photoacoustic/Raman evaluation and improved antibacterial/photothermal combination therapy.

Core-shell metal nanostructures with versatile functions have attracted extensive attention and are highly desirable for imaging and therapeutic purposes. Among them, gold and silver nanomaterials are widely explored for biological applications due to their unique properties. Despite a wide range of applications, limited enhancement ability and insufficient photothermal performance have hampered their further development.

Noninvasive photoacoustic and fluorescent tracking of optical dye labeled T cellular activities of diseased sites at new depth.

The migration of immune cells is crucial to the immune response. Visualization of these processes has previously been limited because of the imaging depth. We developed a deep-penetrating, sensitive and high-resolution method to use fast photoacoustic tomography (PAT) to image the dynamic changes of T cells in lymph node and diseases at new depth (up to 9.

Potential tumor suppressing role of microRNA-545 in epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is the most common type of ovarian cancer, which exhibits invasive traits. MicroRNAs (miRNAs/miRs) have been demonstrated to serve important functions in the pathogenesis of EOC. However, the function of miR-545 in EOC remains unknown.

Whole-genome analyses of human adenovirus type 55 emerged in Tibet, Sichuan and Yunnan in China, in 2016.

Three outbreaks of acute respiratory disease occurred at military camps in 2016 at Tibet, Sichuan and Yunnan province, China. The pathogen induced these three outbreaks were all confirmed as HAdV-55 by genotype-specific PCR. The outbreak in Tibet was the first report that HAdV-55 occurred in the high altitude (HA, above sea level 3658 m).

Self-prior strategy for organ reconstruction in fluorescence molecular tomography.

The purpose of this study is to propose a strategy for organ reconstruction in fluorescence molecular tomography (FMT) without prior information from other imaging modalities, and to overcome the high cost and ionizing radiation caused by the traditional strategy. The proposed strategy is designed as an iterative architecture to solve the inverse problem of FMT. In each iteration, a short time Fourier transform (STFT) based algorithm is used to extract the information in the space-frequency energy spectrum with the assumption that the regions with higher fluorescence concentration have larger energy intensity, then the cost function of the inverse problem is modified by the self-prior information, and lastly an iterative Laplacian regularization algorithm is conducted to solve the updated inverse problem and obtains the reconstruction results.