In vivo monitoring of neural stem cells after transplantation in acute cerebral infarction with dual-modal MR imaging and optical imaging
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The sensitivity and resolution of fluorescence-based imaging in vivo is often limited by autofluorescence and other background noise. To overcome these limitations, we have developed a wide-field background-free imaging technique based on magnetic modulation of fluorescent nanodiamond emission. Fluorescent nanodiamonds are bright, photo-stable, biocompatible nanoparticles that are promising probes for a wide range of in vitro and in vivo imaging applications. Our readily applied background-free imaging technique improves the signal-to-background ratio for in vivo imaging up to 100-fold. This technique has the potential to significantly improve and extend fluorescent nanodiamond imaging capabilities on diverse fluorescence imaging platforms.
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In this paper, we explore the possibility of using ultrasmall near-infrared (NIR) gold nanoclusters (AuNCs) as novel contrast imaging agents for tumor fluorescence imaging in vivo. The fluorescence imaging signal of the tail vein administrated AuNCs in living organisms can spectrally be well distinguished from the background with maximum emission wavelength at about 710 nm, and the high photostability of AuNCs promises continuous imaging in vivo. The uptake of AuNCs by the reticuloendothelial system is relatively low in comparison with other nanoparticle-based contrast imaging agents due to their ultrasmall hydrodynamic size (∼2.7 nm). Through the body weight change analysis, the results show that the body weight of the mice administrated with AuNCs has not been changed obviously in comparison with that of the control mice injected with PBS. Furthermore, using MDA-MB-45 and Hela tumor xenograft models, in vivo and ex vivo imaging studies show that the ultrasmall NIR AuNCs are able to be highly accumulated in the tumor areas, thanks to the enhanced permeability and retention (EPR) effects. And the tumor-to-background ratio is about 15 for 6 h postinjection. The results indicate that the ultrasmall NIR AuNCs appear as very promising contrast imaging agents for in vivo fluorescence tumor imaging.
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There is an increasing interest in the application of fluorescence lifetime imaging (FLIM) for medical diagnosis. Central to the clinical translation of FLIM technology is the development of compact and high-speed clinically compatible systems. We present a handheld probe design consisting of a small maneuverable box fitted with a rigid endoscope, capable of continuous lifetime imaging at multiple emission bands simultaneously. The system was characterized using standard fluorescent dyes. The performance was then further demonstrated by imaging a hamster cheek pouch in vivo, and oral mucosa tissue both ex vivo and in vivo, all using safe and permissible exposure levels. Such a design can greatly facilitate the evaluation of FLIM for oral cancer imaging in vivo.
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The emergence of in vivo molecular imaging probes has provided scientists and clinicians with vital information on the occurrence and development of diseases, guidance of the choices of therapy methods. It also provides the estimation of prognosis as well as evaluation of treatment effects of therapeutic agents. This chapter discusses the recent progress in the development of conjugated polymer (CP)-based fluorescent probes applied for in vivo bioimaging. It focuses on the in vivo fluorescence imaging of CP-based probes. They include in vivo fluorescence imaging of tumors, stimuli-responsive fluorescence imaging, in vivo fluorescence cell tracking, two-photon excited brain vascular imaging, dual-modality imaging of tumors in vivo, as well as other in vivo fluorescence imaging applications. Dual-modality imaging is capable of overcoming the drawbacks of imaging modality when used alone. Fluorescence imaging holds the advantage of high sensitivity; however, it cannot provide 3D information with anatomical resolution.
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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.
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We report here the soft nanomaterial-based targeting polymersomes for near-infrared (NIR) fluorescence imaging to carry out in vivo tumor detection. Two polymersome-based NIR fluorescent probes were prepared through the self-assembly of amphiphilic block copolymers, poly(butadiene-b-ethylene oxide) (PEO-b-PBD). Each of them was encapsulated with distinct hydrophobic near-infrared dyes (DiD and DiR) and modified with different targeting ligands (anti-CEA antibody and anti-EGFR antibody), respectively. After simultaneous injection of these two probes into the tumor-bearing mice via tail vein, multispectral near-infrared fluorescence images were obtained. The results indicate that both probes are successfully directed to the tumor foci, where two distinguishable fluorescent signals were detected through the unmixed fluorescence images. By taking advantage of two targeting polymersome-based probes with distinct fluorescent features, the proposed multispectral near-infrared fluorescence imaging method can greatly improve the specificity and accuracy for in vivo tumor detection.
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Fluorescence-lifetime imaging microscopy
Nanomaterials
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Abstract In vivo fluorescence imaging can perform real‐time, noninvasive, and high spatiotemporal resolution imaging to accurately obtain the dynamic biological information in vivo, which plays significant roles in the early diagnosis and treatment of cancer. However, traditional in vivo fluorescence imaging usually operates in the visible and near‐infrared (NIR)‐I windows, which are severely interfered by the strong tissue absorption, tissue scattering, and autofluorescence. The emergence of NIR‐II imaging at 1000–1700 nm significantly breaks through the imaging limitations in deep tissues, due to less tissue scattering and absorption. Benefiting from the outstanding optical properties of NIR‐II quantum dots (QDs), such as high brightness and good photostability, in vivo fluorescence imaging exhibits excellent temporal‐spatial resolution and large penetration depth, and QDs have become a kind of promising fluorescent biomarkers in the field of in vivo fluorescence imaging. Herein, the authors review NIR‐II QDs from preparation to modification, and summarize recent applications of NIR‐II QDs, including in vivo imaging and imaging‐guided therapies. Finally, they discuss the special concerns when NIR‐II QDs are shifted from in vivo imaging applications to further in‐depth applications.
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