Noninvasive molecular imaging makes the observation and comprehensive understanding of complex biological processes possible. Photoacoustic imaging (PAI) is a fast evolving hybrid imaging technology enabling in vivo imaging with high sensitivity and spatial resolution in deep tissue. Among the various probes developed for PAI, genetically encoded reporters attracted increasing attention of researchers, which provide improved performance by acquiring images of a PAI reporter gene's expression driven by disease-specific enhancers/promoters. Here, we present a brief overview of recent studies about the existing photoacoustic reporter genes (RGs) for noninvasive molecular imaging, such as the pigment enzyme reporters, fluorescent proteins and chromoproteins, photoswitchable proteins, including their properties and potential applications in theranostics. Furthermore, the challenges that PAI RGs face when applied to the clinical studies are also examined.

Time-gated (TG) fluorescence imaging (TGFI) has attracted increasing attention within the biological imaging community, especially during the past decade. With rapid development of light sources, image devices, and a variety of approaches for TG implementation, TGFI has demonstrated numerous biological applications ranging from molecules to tissues. The paper presents inclusive TG implementation mainly based on optical choppers and electronic units for synchronization of fluorescence excitation and emission, which also serves as guidelines for researchers to build suited TGFI systems for selected applications. Note that a special focus will be put on TG implementation based on optical choppers for TGFI of long-lived probes (lifetime range from microseconds to milliseconds). Biological applications by TG imaging of recently developed luminescent probes are described.

Based on the energy conversion of light into sound, photoacoustic computed tomography (PACT) is an emerging biomedical imaging modality and has unique applications in a range of biomedical fields. In PACT, image formation relies on a process called acoustic inversion from received photoacoustic signals. While most PACT systems perform this inversion with a basic assumption that biological tissues are acoustically homogeneous, the community gradually realizes that the intrinsic acoustic heterogeneity of tissues could pose distortions and artifacts to finally formed images. This paper surveys the most recent research progress on acoustic heterogeneity correction in PACT. Four major strategies are reviewed in detail, including half-time or partial-time reconstruction, autofocus reconstruction by optimizing sound speed maps, joint reconstruction of optical absorption and sound speed maps, and ultrasound computed tomography (USCT) enhanced reconstruction. The correction of acoustic heterogeneity helps improve the imaging performance of PACT.

As one of the three key components of photodynamic therapy (PDT), photosensitizers (PSs) greatly influence the photodynamic e±ciency in the treatment of tumors. Photosensitizers with tetrapyrrole structure, such as porphyrins, chlorins and phthalocyanines, have been extensively investigated for PDT and some of them have already received clinical approval. However, only a few of porphyrin-based photosensitizers are available for clinical applications, and PDT has not received wide recognition in clinical practice. In this regard, PSs remain a limiting factor. Our research focuses on the rational design of new PSs. Photocyanine, a Zinc (II) phthalocyanine (ZnPc) type photosensitizer with low dark toxicity and high single oxygen quantum yield, is one of the promising PSs candidates and currently being tested in clinical trials. Here, we present an overview on the development of Photocyanine, including its design, synthesis, purification, characterization and preclinical studies, wishing to contribute to the research of more promising PSs.

Adaptive optics has been widely used in biological science to recover high-resolution optical image deep into the tissue, where optical distortion detection with high speed and accuracy is strongly required. Here, we introduce convolutional neural networks, one of the most popular machine learning models, into Shack–Hartmann wavefront sensor (SHWS) to simplify optical distortion detection processes. Without image segmentation or centroid positioning algorithm, the trained network could estimate up to 36th Zernike mode coe±cients directly from a full SHWS image within 1.227 ms on a personal computer, and achieves prediction accuracy up to 97.4%. The simulation results show that the average root mean squared error in phase residuals of our method is 75.64% lower than that with the modal-based SHWS method. With the high detection accuracy and simplified detection processes, this work has the potential to be applied in wavefront sensor-based adaptive optics for in vivo deep tissue imaging.

An integrated optical coherence tomography (OCT) and video rigid laryngoscope have been designed to acquire surface and subsurface tissue images of larynx simultaneously. The dualmodality system that is based on a common-path design with components as few as possible effectively maintains the light transmittance without compromising the imaging quality. In this paper, the field of view (FOV) of the system can reach 70
by use of a gradient index (GRIN) lens as the relay element and a four-lens group as the distal objective, respectively. The simulation showed that the modulation transfer function (MTF) value in each FOV of the rigid video endoscope at 160 lp/mmis greater than 0.1 while the root mean square (RMS) radii of the OCT beamin the center and edge of the FOV are 14.948
m and 73.609
m, respectively. The resolutions of both OCT and video endoscope meet the requirement of clinical application. In addition, all the components of the system are spherical, therefore the system can be of low cost and easy to assemble.

Exact interaction mechanism between Bax and Bcl-XL, two key Bcl-2 family proteins, is an interesting and controversial issue. Partial acceptor photobleaching-based quantitative fluorescence resonance energy transfer (FRET) measurement, PbFRET, is a widely used FRET quantification method in living cells. In this report, we implemented pixel-to-pixel PbFRET imaging on a wide-field microscope to map the FRET e±ciency (ET images of single living HepG2 cells co-expressing CFP-Bax and YFP-Bcl-XL. The E value between CFP-Bax and YFP-Bcl-XL was 4.59% in cytosol and 11.31% on mitochondria, conclusively indicating the direct interaction of the two proteins, and the interaction of the two proteins was strong on mitochondria and modest in cytosol.

Parkinson's disease (PD) is closely related to the oxidative stress induced by excess hydrogen peroxide (H2O2) in organisms. Developing an e±cient method for noninvasive and real-time H2O2 detection is beneficial to investigate the role played by H2O2 in PD. In this work, a novel fluorogenic probe (CBH) for living organisms H2O2 detection has been designed, synthesized and characterized. The emission of CBH in PBS solution is very weak. However, when H2O2 was added, the fluorescence of CBH solution was sharply increased for 12-fold, accompanied by the emission peak blue-shifted from 600 to 530 nm. Moreover, the response of CBH to H2O2 is highly sensitive and selective and is not affected by various ROS/RNS, anions, cations, and amino acids. Based on the good performance of CBH for H2O2 detection, it has been successfully applied to visualizing the H2O2 concentration in living cells, Zebrafish and C. elegans PD models.