Brain imaging is an important technique in cognitive neuroscience. In this article, we designed a stereotaxic-apparatus-compatible photoacoustic microscope for the studies of rat cortical hemodynamics. Compared with existing optical resolution photoacoustic microscopy (ORPAM) systems, the probe owns feature of fast, light and miniature. In this microscope, we integrated a miniaturized ultrasound transducer with a center frequency of 10 MHz to detect photoacoustic signals and a 2-dimensional (2D) microelectromechanical system (MEMS) scanner to achieve raster scanning of the optical focus. Based on phantom evaluation, this imaging probe has a high lateral resolution of 3.8 μm and an effective imaging domain of 2 × 2 mm2. Different from conventional ORPAMs, combining with standard stereotaxic apparatus enables broad studies of rodent brains without any motion artifact. To show its capability, we successfully captured red blood cell flow in the capillary, monitored the vascular changes during bleeding and blood infusion and visualized cortical hemodynamics induced by middle cerebral artery occlusion.

Heng Guo, Qian Chen, Weizhi Qi, Xingxing Chen, Lei Xi*, Journal of Biophotonics, 2018, DOI: 10.1002/jbio.201800067.

Optical resolution photoacoustic microscopy (ORPAM),benefiting from rich optical contrast, scalable acoustic resolution,and deep penetration depth, is of great importancefor the fields of biology and medicine. However, limitedby the size and performance of reported optical/acousticscanners, existing portable/handheld ORPAMs are bulkyand heavy, and suffer from low imaging quality/speed.Here, we present an ultracompact ORPAM probe, whichis miniature and light, and has high imaging quality.The probe only weighs 20 grams and has an outer sizeof 22 mm × 30 mm × 13 mm, a high lateral resolution of3.8 μm, and an effective imaging domain of 2 mm × 2 mm.To show its advantages over existing ORPAMs, we applythis probe to image vasculatures of internal organs in arat abdominal cavity and inspect the entire human oralcavity.[pdf]‍

Qian Chen, Heng Guo, Tian Jin, Weizhi Qi, Huikai Xie, Lei Xi*, Optics Letters, 2018, 46, 1615-1618,

The use of existing optical resolution photoacoustic microscopy (ORPAM) has been limited to small organs or part of large organs due to the millimeter-scale field of view (FOV) in both lateral and axial directions. Here, we report a large-field-of-view ORPAM (L-ORPAM) using a combination of a new scanning mechanism and an ultrafast pulsed laser. Phantom and in vivo experiments show that L-ORPAM has a spatial FOV of 40 mm in lateral and 12 mm in axial, which expends the effective imaging domain to one order that of existing ORPAMs. To show the advantages of L-ORPAM, we apply it to imaging vasculatures of both brain and ears simultaneously in mice, and visualizing intestinal vasculatures in rats. The result suggests that L-ORPAM has sufficient contrast, resolution and spatial FOV to carry out studies of large rodents.[pdf]

Wei Qin,^# Tian Jin,^# Heng Guo, Lei Xi* , Optics Express, 2018, 26, 4271-4278.

Here, wedescribe a portable optical resolution photoacoustic microscopy (pORPAM) systemfor threedimensional (3D) imaging of smalltolarge rodents and humans with ahigh spatiotemporal resolution and a large field of view (FOV). We showextensive applications of pORPAM to multiscale animals including mice andrabbits. In addition, we image the 3D vascular networks of human lips, anddemonstrate the feasibility of pORPAM to observe the recovery process of oralulcer and cancerassociated capillary loops in human oral cavities. Thistechnology is promising for broad biomedical studies from fundamental biologyto clinical diseases.[pdf]

Tian Jin, Heng Guo, Lei Yao, Huikai Xie, HuabeiJiang, Lei Xi*, Journal of Biophotonics, 2017, DOI: 10.1002/jbio.201700250

In this Letter, we present the design and evaluation of a portable ORPAM with a highspatiotemporal resolution and a large field of view. In this system, we utilizea rotatory scanning mechanism instead of the conventional raster scanning toachieve translationless imaging of the probe/samples, making it accessible tothe human oral lip and tongue. After phantom evaluation, we applied this systemto monitor longitudinal neo-angiogenesis of tumor growth and, for the firsttime, to the best of our knowledge, image the oral vascular network of humansto show its potential in clinical detection of early-stage oral cancer.[pdf]

Jin T, Guo H,Jiang H, Ke B, Xi L*, Optics Letters. 2017 Nov 1;42(21):4434-4437.

Zebrafish play an important role in biology, pharmacology, toxicology, andmedicine. The cardio-cerebrovascular development of zebrafish is particularly critical tounderstand both brain disorders and cardiovascular diseases in human. In this paper, weapplied optical resolution photoacoustic microscopy (ORPAM) to image the whole-bodyvasculature of the embryonic zebrafish with a special focus on the development of the cardiocerebrovascularsystem. Using the intrinsic optical absorption contrast of the embryo, wesuccessfully visualized the formation of the cardio-cerebrovascular network in highresolutionusing a 10 × objective, and monitored the whole-body vascular development usinga 4 × objective. In addition, we evaluated the impact of the eggshell and pigment inhibitor onthe image quality. Our results suggest that ORPAM is capable of studying the cardiocerebrovasculardevelopment of zebrafish in the embryonic stage, and thus has the potentialto investigate the cardiovascular and cerebrovascular diseases of human in the future.[pdf]

Qian Chen, Tian Jin, Weizhi Qi, Xianming Mo, Lei Xi*, Biomedical Optics Express, 2017，8: 2359-2367.

In this study, we report an inverted multiscale (IM)-ORPAM that utilizesa two-dimensional galvanometric scanner integratedwith two microscopic imaging lenses to achieve rotaryscanning-basedmultiscale imaging. A 15 MHz cylindricallyfocused ultrasonic transducer is mounted on a motorizedrotator to synchronously follow the optical scanningpaths. To minimize the loss of signal-to-noise ratio,the acoustic focal line is precisely adjusted confocal withthe optical focal plane. Black tapes, carbon fibers, andsharp blades are imaged to evaluate the performance ofthe system, and in vivo multiscale imaging of vasculaturesinside the ears and brains of mice is demonstrated usingthis system.[pdf]

Weizhi Qi#, Tian Jin#, Jian Rong, Huabei Jiang, Lei Xi*, Journal of Biophotonics, 2017, 1-6 (DOI 10.1002/jbio.201600246).