Changhui Li

Label-free imaging of zebrafish larvae in vivo by photoacoustic microscopy

Zebrafish play an important role in biological and biomedical research. Traditional in vivo imaging methods for studying zebrafish larvae primarily require fluorescence labeling. In this work, relying on tissue intrinsic optical absorption contrast, we acquired high resolution label-free 3D images of zebrafish larvae by using photoacoustic microscopy (PAM) in vivo. The spatial resolution reaches several microns, allowing the study of microstructures in various living organs. We demonstrated that our method has the potential to be a powerful non-invasive imaging method for studying various small animal models, including zebrafish larvae, Caenorhabditis elegans, frogs and drosophila larvae.

High-resolution dual-modality photoacoustic ocular imaging

We have developed a prototype ocular imaging system that integrates optical-resolution photoacoustic microscopy and high-frequency ultrasound imaging. The system can perform high-resolution ocular imaging from the anterior region down to the fundus. It has successfully imaged murine eyes in vivo, including iris, lens, retina, and retinal pigment epithelium. Our results demonstrate that this system shows strong potential for the diagnosis of ophthalmic diseases.

An integrated quad-modality molecular imaging system for small animals.

We developed a novel integrated quad-modality system that included 3 molecular imaging methods (PET, SPECT, and fluorescence molecular imaging [FMI]) and 1 anatomic imaging modality (CT). This system could study various biologic processes in the same animal using multiple molecular tracers. In addition to the technology development, we also discussed the optimization strategy of the imaging protocols. The performance of this system was tested, and the in vivo animal experiment showed its power to trace 3 different molecular probes in living tissues. Our results demonstrated that this system has a great potential for the preclinical study of diseases. Methods: A prototype system integrating PET, SPECT, CT, and a charge-coupled device–based free-space FMI system has been developed. Imaging and fusion capabilities of the system were evaluated by a multimodality phantom. In addition, a mouse disease model with both tumor and inflammation was studied by this system to examine the in vivo performance. The 3 types of molecular probes—18F-FDG, [99mTc(HYNIC-3PRGD2)(tricine)(TPPTS)] (99mTc-3PRG2) (HYNIC = 6-hydrazinonicotinyl; TPPTS = trisodium triphenylphosphine-3,3′,3″-trisulfonate; 3PRGD2 = PEG4-E[PEG4-c(RGDfK)]2), and 3-(triethoxysilyl) propyl-Cy7–entrapped core-cross-linked polymeric micelle (Cy7-entrapped CCPM) nanoparticles—were used to target 3 different biologic processes in the tumor caused by pulmonary adenocarcinoma A549 cells. Moreover, the strategy to optimize multimodal molecular imaging procedure was studied as well, which could significantly reduce the total imaging time. Results: The imaging performance has been validated by both phantom and in vivo animal experiments. With this system and optimized imaging protocol, we successfully differentiated diseases that cannot be distinguished by a single molecular imaging modality. Conclusion: We developed a novel quad-modality molecular imaging system that integrated PET, SPECT, FMI, and CT imaging methods to obtain whole-body multimodality images of small animals. The imaging results demonstrated that this system provides more comprehensive information for preclinical biomedical research. With optimized imaging protocols, as well as novel molecular tracers, this quad-modality system can help in the study of the physiology mechanism at an unprecedented level.

Ultrasonic detection based on polarization-dependent optical reflection

Owing to their extremely wide bandwidths, pure optical ultrasonic detection methods are gaining increasing interest. In this Letter, we proposed a simple ultrasonic detector that is based on the polarization-dependent optical reflection. When the acoustic wave reaches the liquid-glass interface, the acoustic pressure changed the relative refractive index between two media, leading to perturbations in the reflectance of the optical probe beam in glass. Unlike previous studies that detected the modulations in the intensity of the reflected beam, our method, named polarization-dependent reflection ultrasonic detection (PRUD), detects the intensity difference between two polarization components of the same probe beam. The PRUD significantly increased the sensitivity. Besides a phantom study, we also successfully detect weak photoacoustic waves in an in vivo animal experiment. This novel method can provide a simple way for ultrasonic detection, which will have great potential for ultrasound and photoacoustic imaging and sensing.

The Properties and Formation of Cirrus Clouds over the Tibetan Plateau Based on Summertime Lidar Measurements

AbstractAs part of the Tibet Ozone, Aerosol and Radiation (TOAR) project, a micropulse lidar was operated in Naqu (31.5°N, 92.1°E; 4508 m MSL) on the Tibetan Plateau to observe cirrus clouds continuously from 19 July to 26 August 2011. During the experiment, the time coverage of ice clouds only was 15% in the upper troposphere (above 9.5 km MSL). The cirrus top/bottom altitudes (mean values of 15.6/14.7 km) are comparable to those measured previously at tropical sites but relatively higher than those measured at midlatitude sites. The majority of the cloud layers yielded a lidar ratio between 10 and 40 sr, with a mean value of 28 ± 15 sr, characterized by a bimodal frequency distribution. Subvisible, thin, and opaque cirrus formation was observed in 16%, 34%, and 50% of all cirrus cases, respectively. A mean cirrus optical depth of 0.33 was observed over the Tibetan Plateau, slightly higher than those in the subtropics and tropics. With decreasing temperature, the lidar ratio increased slightly, whereas t...

In vivo study of endometriosis in mice by photoacoustic microscopy.

Endometriosis (EM) impacts the healthcare and the quality of life for women of reproductive age. However, there is no reliable noninvasive diagnosis method for either animal study or clinical use. In this work, a novel imaging method, photoacoustic microscopy (PAM) was employed to study the EM on the mouse model. Our results demonstrated the PAM noninvasively provided the high contrast and 3D imaging of subcutaneously implanted EM tissue in the nude mouse in vivo. The statistical study also indicated PAM had high sensitivity and specificity in the diagnosis of EM in this animal study. In addition, we also discussed the potential clinical application for PAM in the diagnosis of EM.

Slip-ring-based multi-transducer photoacoustic tomography system

Although the transducer array-based photoacoustic tomography (PAT) system provides fast imaging speed, its high cost and system complexity hinder its implementations. In this Letter, for the first time, to the best of our knowledge, the electrical slip ring was used to develop a PAT system that compromises the cost and the imaging speed. This system enables using multiple transducers to image the target simultaneously and continuously. In addition, it is versatile to use different transducers. The performance of this PAT system has been demonstrated by both phantom and in vivo animal experiments.

Photoacoustic/ultrasound dual imaging of human thyroid cancers: an initial clinical study

We reported an initial clinical study of in vivo human thyroid by a photoacoustic/ultrasound handheld probe. Our dual-modality system is based on a high-end clinical ultrasound machine. Both healthy and cancerous thyroids were imaged non-invasively, and we compared the photoacoustic imaging with color Doppler ultrasound. The results of photoacoustic thyroid imaging could reveal many blood vessels that were not sensitive for Doppler ultrasound. Our study demonstrated that photoacoustic imaging could provide important complementary information for traditional ultrasound thyroid examination, which has a great potential for clinical diagnosis.

Optical fluence compensation for handheld photoacoustic probe: An in vivo human study case

Integrating photoacoustic (PA) and ultrasound (US) into a handheld probe to perform PA/US dual-modal imaging has been widely studied over the past few years. However, optical fluence decreases quickly in deeper tissue due to light scattering and absorption, which would significantly affect the quantitative PA imaging. In this paper, we performed a fluence compensation for a PA imaging study of human breast. The comparison of PA/US image with and without optical fluence compensation demonstrated that the fluence compensation could effectively improve imaging quality for handheld probe.

Establishment of an mKate2-Expressing Cell Line for Non-Invasive Real-Time Breast Cancer In Vivo Imaging

PurposeNon-invasive real-time in vivo imaging experiments using mice as animal models have become crucial for understanding cancer development and treatment. In this study, we have developed and validated a new breast cancer cell line MDA-MB-435s that stably express a far-red fluorescence protein (mKate2) and that could serve as a highly valuable cell model for studying breast cancer detection and therapy using in vivo fluorescence imaging in nude mice.ProceduresThe new cell line (MDA-MB-435s-mKate2) was constructed by plasmid transfection. The stability and sensitivity of mKate2, and the cell biological activities, were tested in vitro using different experimental approaches. For its potential use in tumor growth research and drug therapy in vivo, MDA-MB-435s-mKate2 was validated using the immunocompromised Balb/c nude mice tumor model. In addition, the new cell line has been characterized as a luteinizing hormone-releasing hormone receptor (LHRHR) positive cell line.ResultsFirstly, MDA-MB-435s-mKate2 has shown a stable chromosomal integration of the amplified mKate2 gene and good fluorescence sensitivity for detection using a fluorescence reflectance imaging (FRI) device. Compared to its parental cell line, no significant difference in cell migration, proliferation, and clone formation was observed in vitro. Secondly, using the quantification of tumor-fluorescence surface area in live animals, we were able to monitor and detect the tumor progress or tumor inhibition rate (by Paclitaxel treatment) non-invasively and in real-time. Furthermore, MDA-MB-435s-mKate2 has been positively tested for LHRHR; these findings open the possibility to use this cell line for future studies of breast cancer therapy based on LHRH analogs in vivo.ConclusionIn the present research, we have successfully built the MDA-MB-435s-mKate2 cell line that can be used as a suitable cell model for breast cancer therapy and anti-cancer drug evaluation by non-invasive fluorescence imaging in mice.