Yang Liu

The University of Texas Southwestern Medical Center

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Tingfeng Yao

The University of Texas Southwestern Medical Center

Baohong Yuan

The University of Texas Southwestern Medical Center

Shuai Yu

Shandong Academy of Sciences

Liqin Ren

The University of Texas at Arlington

Yi Hong

Zhejiang University

Kytai T. Nguyen

The University of Texas at Arlington

Feng Xu

Suzhou Traditional Chinese Medicine Hospital

Angie L. Bookout

The University of Texas Southwestern Medical Center

Gerhard Knothe

National Center for Agricultural Utilization Research

Laurent Gautron

The University of Texas Southwestern Medical Center

Cooperative Institutions

The University of Texas Southwestern Medical Center

The University of Texas at Arlington

Southwestern Medical Center

Central South University

Nanjing General Hospital of Nanjing Military Command

Nanjing University

Virginia Commonwealth University

Nantong University

Novo Nordisk (United States)

Agricultural Research Service

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Improving sensitivity and imaging depth of ultrasound-switchable fluorescence via an EMCCD-gain-controlled system and a liposome-based contrast agent

Quantitative Imaging in Medicine and Surgery (2020)

Tingfeng Yao Yang Liu Liqin Ren Baohong Yuan

The ultrasound-switchable fluorescence (USF) technique was recently developed to achieve high-resolution fluorescence imaging in centimeters-deep tissue. This study introduced strategies to significantly improve imaging sensitivity and depth using an electron multiplying charge-coupled device (EMCCD) camera-based USF imaging system and a newly developed USF contrast agent of indocyanine green (ICG)-encapsulated liposomes. For a quantitative study, a phantom of a sub-millimeter silicone tube embedded in centimeter-thick chicken breast tissue was adopted in this study as a model.The synthesized ICG-liposome was characterized and compared with the previously reported ICG-nanogel. The exposure of the EMCCD camera was controlled via the MATLAB (The MathWorks, Inc. USA), instead of an external hardware trigger. The stability of the electron multiplying (EM) gain of the EMCCD camera was compared between two trigger modes: the MATLAB trigger mode and the external hardware trigger mode. The signal-to-noise ratio (SNR) of the USF imaging with different EM gain in various thick tissue was studied.The hydrodynamic size of the ICG-liposome was ~181 nm. The ICG-liposome had a sharper temperature switching curve and a better USF performance than the previously reported ICG-nanogel. The EM gain was more stable in MATLAB trigger mode than the external hardware trigger mode. Although, as usual, the SNR decreased quickly with the increase of the tissue thickness, the proposed strategies improved the SNR and the imaging depth significantly by adopting the novel contrast agent and controlling the EM gain.We successfully imaged the sub-millimeter silicone tube with an inner diameter of 0.76 mm and an outer diameter of 1.65 mm in 5.5 cm-thick chicken breast tissue using 808 nm excitation light with a low intensity of 28.35 mW/cm2, the improved EMCCD camera-based USF imaging system and the novel ICG-liposomes.

Indocyanine Green

10.21037/qims-20-796

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Citations (9)

In vivo ultrasound-switchable fluorescence imaging

arXiv (Cornell University) (2018)

Tingfeng Yao Shuai Yu Yang Liu Baohong Yuan

Ultrasound-switchable fluorescence (USF) imaging was recently developed to overcome the limitation of the poor spatial resolution of the conventional fluorescence imaging in centimeter-deep tissue. However, in vivo USF imaging has not been achieved so far because of the lack of stable near-infrared contrast agents in a biological environment and the lack of data about their biodistributions. In this study, for the first time, we achieved in vivo USF imaging successfully in mice with high resolution. USF imaging in porcine heart tissue and mouse breast tumor via local injections were studied and demonstrated. In vivo and ex vivo USF imaging of the mouse spleen via intravenous injections was also successfully achieved. The results showed that the USF contrast agent adopted in this study was very stable in a biological environment, and it was mainly accumulated into the spleen of the mice. All the results of USF imaging were validated by a commercial micro-CT.

Fluorescence-lifetime imaging microscopy

Ex vivo

Molecular Imaging

10.48550/arxiv.1810.04997

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Citations (1)

Ultrasound-Switchable Fluorescence Imaging via an EMCCD Camera and a Z-Scan Method

IEEE Journal of Selected Topics in Quantum Electronics (2018)

Tingfeng Yao Shuai Yu Yang Liu Baohong Yuan

The spatial resolution of the conventional fluorescence imaging in centimeter-deep tissue is limited due to high light scattering. Ultrasound-switchable fluorescence (USF) imaging was recently developed to achieve high resolution in deep tissue. However, previous frequency-domain USF systems adopted a fiber bundle to collect the emitted fluorescence photons, which led to a few limitations, such as, first, low photon-collection efficiency; second, low efficiency for scanning a sample with an uneven surface; third, low imaging speed, because of the adoption of a raster scan and the long wait time for the tissue to cool down before starting the data acquisition at the next location. In this study, we proposed a camera-based USF imaging system to overcome these limitations. Thanks to the spatial information provided by the camera, a new scan method, Z-scan, was developed, and the imaging speed was improved four times over the raster scan. The USF imaging using the Z-scan for tissue samples was realized. The results were validated by a commercial micro-CT system.

Raster scan

Fluorescence-lifetime imaging microscopy

Scan line

10.1109/jstqe.2018.2883892

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Citations (9)

PPARγ mRNA in the adult mouse hypothalamus: distribution and regulation in response to dietary challenges

Frontiers in Neuroanatomy (2015)

Yang Liu Ying Huang Syann Lee Angie L. Bookout Carlos M. Castorena

Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated transcription factor that was originally identified as a regulator of peroxisome proliferation and adipocyte differentiation. Emerging evidence suggests that functional PPARγ signaling also occurs within the hypothalamus. However, the exact distribution and identities of PPARγ-expressing hypothalamic cells remains under debate. The present study systematically mapped PPARγ mRNA expression in the adult mouse brain using in situ hybridization histochemistry. PPARγ mRNA was found to be expressed at high levels outside the hypothalamus including the neocortex, the olfactory bulb, the organ of the vasculosum of the lamina terminalis (VOLT), and the subfornical organ. Within the hypothalamus, PPARγ was present at moderate levels in the suprachiasmatic nucleus (SCh) and the ependymal of the 3rd ventricle. In all examined feeding-related hypothalamic nuclei, PPARγ was expressed at very low levels that were close to the limit of detection. Using qPCR techniques, we demonstrated that PPARγ mRNA expression was upregulated in the SCh in response to fasting. Double in situ hybridization further demonstrated that PPARγ was primarily expressed in neurons rather than glia. Collectively, our observations provide a comprehensive map of PPARγ distribution in the intact adult mouse hypothalamus.

Periventricular nucleus

10.3389/fnana.2015.00120

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Citations (7)

A Biocompatible and Near‐Infrared Liposome for In Vivo Ultrasound‐Switchable Fluorescence Imaging

Advanced Healthcare Materials (2020)

Yang Liu Tingfeng Yao Wenbin Cai Shuai Yu Yi Hong

Abstract Fluorescence imaging is a remarkable tool for molecular targeting and multicolor imaging, but it suffers from low resolution in centimeter‐deep tissues. The recently developed ultrasound‐switchable fluorescence (USF) imaging has overcome this challenge and achieved in vivo imaging in a mouse with help from the indocyanine green (ICG) dye encapsulated poly(N‐isopropylacrylamide) (ICG‐PNIPAM) contrast agent. However, the ICG‐PNIPAM has shortcomings, such as concerns about cytotoxicity and blueshifted excitation and emission spectra. This study introduces a newly developed ICG‐encapsulated liposome to broaden the contrast agent selection for USF imaging and resolve the issues mentioned above. The emission peak of the ICG‐liposome is 836 nm with excellent biostability and USF imaging capability. Furthermore, the cell viability test verifies the low cytotoxicity feature. Eventually, both ex vivo and in vivo USF imaging are successfully achieved and 3D USF images are acquired. The ex vivo result confirms that the ICG‐liposome maintains the thermoresponsive characteristic at the right lobe of the liver and is able to conduct the USF imaging. The further in vivo USF imaging demonstrates that although the whole liver emitted fluorescence, only the right lobe of the liver contains the working ICG‐liposome.

Indocyanine Green

Ex vivo

Fluorescence-lifetime imaging microscopy

Molecular Imaging

10.1002/adhm.201901457

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Citations (26)

Evaluating the efficiency of a photoelectrochemical electrode constructed with photosystem II-enriched thylakoid membrane fragments

Bioelectrochemistry (2018)

Yang Liu John Daye David L. Jenson Stephen S. Fong

Photoelectrochemical cell

Indium tin oxide

Photoelectrochemistry

10.1016/j.bioelechem.2018.06.007

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Citations (3)

In vivo ultrasound-switchable fluorescence imaging using a camera-based system

Biomedical Optics Express (2020)

Shuai Yu Tingfeng Yao Yang Liu Baohong Yuan

Ultrasound-switchable fluorescence (USF) is a novel imaging technique that provides high spatial resolution fluorescence images in centimeter-deep biological tissue. Recently, we successfully demonstrated the feasibility of in vivo USF imaging using a frequency-domain photomultiplier tube-based system. In this work, for the first time we carried out in vivo USF imaging via a camera-based USF imaging system. The system acquires a USF signal on a two-dimensional (2D) plane, which facilitates the image acquisition because the USF scanning area can be planned based on the 2D image and provides high USF photon collection efficiency. We demonstrated in vivo USF imaging in the mouse's glioblastoma tumor with multiple targets via local injection. In addition, we designed the USF contrast agents with different particle sizes (70 nm and 330 nm) so that they could bio-distribute to various organs (spleen, liver, and kidney) via intravenous (IV) injections. The results showed that the contrast agents retained stable USF properties in tumors and some organs (spleen and liver). We successfully achieved in vivo USF imaging of the mouse's spleen and liver via IV injections. The USF imaging results were compared with the images acquired from a commercial X-ray micro computed tomography (micro-CT) system.

Fluorescence-lifetime imaging microscopy

Ultrasound imaging

10.1364/boe.385996

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Citations (9)

Direct transesterification of spent coffee grounds for biodiesel production

Fuel (2017)

Yang Liu Qingshi Tu Gerhard Knothe Mingming Lu

10.1016/j.fuel.2017.02.094

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Citations (132)

In vivo ultrasound-switchable fluorescence imaging

Scientific Reports (2019)

Tingfeng Yao Shuai Yu Yang Liu Baohong Yuan

The conventional fluorescence imaging has limited spatial resolution in centimeter-deep tissue because of the tissue's high scattering property. Ultrasound-switchable fluorescence (USF) imaging, a new imaging technique, was recently proposed to realize high-resolution fluorescence imaging in centimeter-deep tissue. However, in vivo USF imaging has not been achieved so far because of the lack of stable near-infrared contrast agents in a biological environment and the lack of data about their biodistributions. In this study, for the first time, we achieved in vivo USF imaging successfully in mice with high resolution. USF imaging in porcine heart tissue and mouse breast tumor via local injections were studied and demonstrated. In vivo and ex vivo USF imaging of the mouse spleen via intravenous injections was also successfully achieved. The results showed that the USF contrast agent adopted in this study was very stable in a biological environment, and it was mainly accumulated into the spleen of the mice. By comparing the results of CT imaging and the results of USF imaging, the accuracy of USF imaging was proved.

Fluorescence-lifetime imaging microscopy

Ex vivo

Molecular Imaging

10.1038/s41598-019-46298-2

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Citations (19)

Size effect of liposomes on centimeter-deep ultrasound-switchable fluorescence imaging and ultrasound-controlled release

Journal of Materials Chemistry B (2022)

Yang Liu Tingfeng Yao Liqin Ren Baohong Yuan

Liposomes have been widely used in both medical imaging and drug delivery fields due to their excellent biocompatibility and easy surface modification. Recently our lab reported for the first-time the implementation of temperature-sensitive and indocyanine green (ICG)-encapsulated liposome microparticles for in vivo ultrasound-switchable fluorescence (USF) imaging. A previous study showed that liposome microparticles achieved USF imaging in centimeter-deep tissue. This study aimed to control the size of liposomes at the nanoscale and study the size effect on the USF imaging depth. Also, we explored the feasibility of combining USF imaging with ultrasound-controlled release. Liposomes were synthesized via the hydration method and the size was controlled by an extruding process. Characterization parameters, including fluorescence profile, spectra, size, stability, encapsulation efficiency, and ultrasound-controlled release, were evaluated. USF imaging in blood serum was conducted successfully in a phantom model, and an imaging depth study was conducted at 1.0 cm and 2.5 cm and confirmed that nano-sized liposomes had a stronger USF signal than micron-sized liposomes. Additionally, releasing tests indicated that both ultrasound power and exposure time affected the release efficiency in that increasing the power and extending the exposure time led to higher release efficiency. Above all, this study shows the potential for using liposomes for USF imaging and ultrasound-controlled release.

Fluorescence-lifetime imaging microscopy

Biocompatibility

Indocyanine Green

10.1039/d2tb01343f

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Citations (3)