Multi-parametric quantitative microvascular imaging with optical-resolution photoacoustic microscopy in vivo

Many diseases involve either the formation of new blood vessels (e.g., tumor angiogenesis) or the damage of existing ones (e.g., diabetic retinopathy) at the microcirculation level. Optical-resolution photoacoustic microscopy (OR-PAM), capable of imaging microvessels in 3D in vivo down to individual capillaries using endogenous contrast, has the potential to reveal microvascular information critical to the diagnosis and staging of microcirculation-related diseases. In this study, we have developed a dedicated microvascular quantification (MQ) algorithm for OR-PAM to automatically quantify multiple microvascular morphological parameters in parallel, including the vessel diameter distribution, the microvessel density, the vascular tortuosity, and the fractal dimension. The algorithm has been tested on in vivo OR-PAM images of a healthy mouse, demonstrating high accuracy for microvascular segmentation and quantification. The developed MQ algorithm for OR-PAM may greatly facilitate quantitative imaging of tumor angiogenesis and many other microcirculation related diseases in vivo

A miniature multi-functional photoacoustic probe

Photoacoustic technology is a promising tool to provide morphological and functional information in biomedical research. To enhance the imaging efficiency, the reported photoacoustic probes have been designed coaxially involving complicated optical/acoustic prisms to bypass the opaque piezoelectric layer of ultrasound transducers, but this has led to bulky probes and has hindered the applications in limited space. Though the emergence of transparent piezoelectric materials helps to save effort on the coaxial design, the reported transparent ultrasound transducers were still bulky. In this work, a miniature photoacoustic probe with an outer diameter of 4 mm was developed, in which an acoustic stack was made with a combination of transparent piezoelectric material and a gradient-index lens as a backing layer. The transparent ultrasound transducer exhibited a high center frequency of ~47 MHz and a −6 dB bandwidth of 29.4%, which could be easily assembled with a pigtailed ferrule of a single-mode fiber. The multi-functional capability of the probe was successfully validated through experiments of fluid flow sensing and photoacoustic imaging

Miniature intravascular photoacoustic endoscopy with coaxial excitation and detection

Recent research pointed out that the degree of inflammation in the adventitia could correlate with the severity of atherosclerotic plaques. Intravascular photoacoustic endoscopy can provide the information of arterial morphology and plaque composition, and even detecting the inflammation. However, most reported work used a non-coaxial configuration for the photoacoustic catheter design, which formed a limited light-sound overlap area for imaging so as to miss the adventitia information. Here we developed a novel 0.9 mm-diameter intravascular photoacoustic catheter with coaxial excitation and detection to resolve the aforementioned issue. A miniature hollow ultrasound transducer with a 0.18 mm-diameter orifice in the center was successfully fabricated. To show the significance and merits of our design, phantom and ex vivo imaging experiments were conducted on both coaxial and non-coaxial catheters for comparison. The results demonstrated that the coaxial catheter exhibited much better photoacoustic/ultrasound imaging performance from the intima to the adventitia

Multi-parametric quantitative microvascular imaging with optical-resolution photoacoustic microscopy in vivo

Many diseases involve either the formation of new blood vessels (e.g., tumor angiogenesis) or the damage of existing ones (e.g., diabetic retinopathy) at the microcirculation level. Optical-resolution photoacoustic microscopy (OR-PAM), capable of imaging microvessels in 3D in vivo down to individual capillaries using endogenous contrast, has the potential to reveal microvascular information critical to the diagnosis and staging of microcirculation-related diseases. In this study, we have developed a dedicated microvascular quantification (MQ) algorithm for OR-PAM to automatically quantify multiple microvascular morphological parameters in parallel, including the vessel diameter distribution, the microvessel density, the vascular tortuosity, and the fractal dimension. The algorithm has been tested on in vivo OR-PAM images of a healthy mouse, demonstrating high accuracy for microvascular segmentation and quantification. The developed MQ algorithm for OR-PAM may greatly facilitate quantitative imaging of tumor angiogenesis and many other microcirculation related diseases in vivo

VPS35 haploinsufficiency increases Alzheimer’s disease neuropathology

The retromer complex component VPS35 prevents activation of the BACE1 and Aβ production and thus plays an essential role in limiting Alzheimer’s disease neuropathology

Characterization of AcMNPV with a deletion of ac69 gene

<p>ORF69 (Ac69) of <em>Autographa californica</em> multiple nucleopolyhedrovirus (Ac<em>M</em>NPV) is conserved in some baculovirus genomes. Although it has been shown that Ac69 has cap 0-dependent methyltransferase activity and is not required for budded virus production in <em>Spodoptera frugiperda</em> Sf-9 cells, its role in occlusion-derived virus synthesis and virus oral infectivity is not known. This paper describes generation of an <em>ac69</em> knockout Ac<em>M</em>NPV bacmid mutant and analyses of the influence of <em>ac69</em> deletion on the viral infectivity in Sf-9 cells and <em>Trichoplusia ni</em> larvae so as to investigate the role of <em>ac69 in the viral life cycle. Results indicated that ac69</em> deletion has little effect on the production rates and morphogenesis of budded virus and occlusion-derived virus in Sf-9 cells. In addition, animal experiment revealed that the deletion mutant did not affect Ac<em>M</em>NPV infectivity for <em>Trichoplusia ni</em> larvae in LD₅₀ and LT₅₀ bioassay when administered orally. These results suggest that <em>ac69</em> may be dispensable for viral infectivity both in vitro and in vivo.</p

Solid‐State NMR and MRI Spectroscopy for Li/Na Batteries: Materials, Interface, and In Situ Characterization

Enhancing the electrochemical performance of batteries, including the lifespan, energy, and power densities, is an everlasting quest for the rechargeable battery community. However, the dynamic and coupled (electro)chemical processes that occur in the electrode materials as well as at the electrode/electrolyte interfaces complicate the investigation of their working and decay mechanisms. Herein, the recent developments and applications of solid-state nuclear magnetic resonance (ssNMR) and magnetic resonance imaging (MRI) techniques in Li/Na batteries are reviewed. Several typical cases including the applications of NMR spectroscopy for the investigation of the pristine structure and the dynamic structural evolution of materials are first emphasized. The NMR applications in analyzing the solid electrolyte interfaces (SEI) on the electrode are further concluded, involving the identification of SEI components and investigation of ionic motion through the interfaces. Beyond, the new development of in situ NMR and MRI techniques are highlighted, including their advantages, challenges, applications and the design principle of in situ cell. In the end, a prospect about how to use ssNMR in battery research from the perspectives of materials, interface, and in situ NMR, aiming at obtaining deeper insight of batteries with the assistance of ssNMR is represented

Intravascular optical-resolution photoacoustic tomography with a 1.1 mm diameter catheter.

Photoacoustic imaging is an emerging technology that can provide anatomic, functional, and molecular information about biological tissue. Intravascular spectroscopic and molecular photoacoustic imaging can potentially improve the identification of atherosclerotic plaque composition, the detection of inflammation, and ultimately the risk stratification of atherosclerosis. In this study, a first-of-its-kind intravascular optical-resolution photoacoustic tomography (OR-PAT) system with a 1.1 mm diameter catheter is developed, offering optical-diffraction limited transverse resolution as fine as 19.6 μm, ∼ 10-fold finer than that of conventional intravascular photoacoustic and ultrasonic imaging. To offer complementary imaging information and depth, the system also acquires co-registered intravascular ultrasound images in parallel. Imaging of an iliac stent and a lipid phantom shows that the high resolution and contrast of OR-PAT can enable improved stent implantation guidance and lipid identification. In the future, these capabilities may ultimately improve the diagnosis and interventional treatment of vulnerable atherosclerotic plaques, which are prone to cause thrombotic complications such as myocardial infarction and stroke