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Cerenkov luminescence imaging(CLI) is an emerging molecular imaging technology able to optically visualize radioactive decay signals from medical isotopes and has found wide application in tumor diagnose, cancer therapy, drug development, intraoperative guidance, and so on. When Cerenkov luminescence data are collected, the high-energy particles from the radioactive nucleus will be detected by the sensitive CCD camera and lead to impulse noise. To suppress the impulse noise and improve the contrast of the useful signal to the background, the detection-based fuzzy switching median filtering framework is proposed in this paper. Several experiments were conducted respectively to investigate the statistical feature of the noise and to evaluate the performance of the proposed noise removal framework. The results show that the signal-to-noise ratio is improved after noise elimination. The proposed filtering framework outperforms the classical median filter in terms of root mean squared error and the structural similarity index. It also preserves the maximum value and the mean value in the regions of interest better than the median filter does. In addition, compared with the FLICMCDD algorithm, the proposed method works much faster while getting similar results. Graphical abstract.

Objective: In vivo bioluminescence imaging (BLI) is a promising tool for monitoring the growth and metastasis of tumors. However, quantitative BLI research based on intravenous (IV) injection is limited, which greatly restricts its further application. To address this problem, we designed a pharmacokinetic (PK) model which is suitable for applying on IV administration of small amounts of D-Luciferin., Methods: After three weeks of postimplantation, mkn28-luc xenografted mice were subjected to 40-min dynamic BLI immediately following D-Luciferin intravenous injection on days 1, 3, 5, 7, and 9. Furthermore, the PK model was applied on dynamic BLI data to obtain the sum of kinetic rate constants (SKRC)., Results: Results showed that the SKRC values decreased rapidly with the growth of the tumor. There was a statistical difference between the SKRC values measured at different time points, while the time point of luminous intensity peak was unaffected by the growth of the tumor., Conclusion: In short, our results imply that dynamic BLI combined with our PK model can predict tumor growth earlier and with higher sensitivity compared to the conventional method, which is crucial for improving drug evaluation efficacy. In addition, the dynamic BLI may provide a valuable reference for the noninvasive acquiring arterial input function, which may also provide a new application prospect for hybrid PET-optical imaging.

Cancer metastasis is one of the biggest challenges in cancer treatments since it increases the likelihood that a patient will die from the disease. Therefore, the availability of techniques for the early detection and quantification of tumors is very important. We have prepared cyanine 7.5 NHS ester (Cy 7.5 ) and folic acid (FA) conjugated biodegradable mesoporous silica nanoparticles (bMSN@Cy 7.5 -FA NPs) (~100 nm) for visualizing tumors in vivo. The fluorescence spectra revealed that the emission peak of bMSN@Cy 7.5 -FA NPs had a red-shift of 1 nm. Confocal immunofluorescent images showed that bMSN@Cy 7.5 -FA NPs had an excellent targeting ability for visualizing cancer cells. In vivo fluorescence imaging has been conducted using an orthotopic model for pancreatic cancer within 48 h, and the fluorescence intensity reached a maximum at a post injection time-point of 12 h, which demonstrated that the use of bMSN@Cy 7.5 -FA NPs provides an excellent imaging platform for tumor precision therapy in mice., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Multifunctional manganese oxide nanoparticles (NPs) with impressive enhanced T ₁ contrast ability show great promise in biomedical diagnosis. Herein, we developed a dual-modality imaging agent system based on polyethylene glycol (PEG)-coated manganese oxide NPs conjugated with organic dye (Cy 7.5 ), which functions as a fluorescence imaging (FI) agent as well as a magnetic resonance imaging (MRI) imaging agent. The formed Mn₃O₄@PEG-Cy 7.5 NPs with the size of ~10 nm exhibit good colloidal stability in different physiological media. Serial FI and MRI studies that non-invasively assessed the bio-distribution pattern and the feasibility for in vivo dual-modality imaging-guided lymph node mapping have been investigated. In addition, histological and biochemical analyses exhibited low toxicity even at a dose of 20 mg/kg in vivo. Since Mn₃O₄@PEG-Cy 7.5 NPs exhibited desirable properties as imaging agents and good biocompatibility, this work offers a robust, safe, and accurate diagnostic platform based on manganese oxide NPs for tumor metastasis diagnosis., Competing Interests: The authors declare no conflict of interest.

IR-780 iodide, a near-infrared (NIR) fluorescent heptamethine dye, has attracted wide attention in the biomedical community. However, hydrophobicity and toxicity severely limit its further biomedical application. Although many successful efforts have been made to increase its solubility and biocompatibility, a strong fluorescent signal and longer retention time are in high demand in biomedical application in vivo as well as basic science research. In this work, we report the development of novel silica cross-linked micellar core–shell nanoparticles encapsulating IR-780 (NIR-Silica NPs) and their utility for biomedical imaging in vivo. Compared to free IR-780, the solubility of NIR-Silica NPs was not only greatly increased, but there was also a dramatic 5–7-fold enhancement of fluorescence intensity. More importantly, the exceptionally small size (25 nm) and colloidal stability of the NPs are also sufficient to realize the enhanced permeability and retention effect. In vitro cell viability assays further indicated that the NIR-Silica NPs are safer even at the highest concentration tested of 1.0 mg/mL. Finally, sentinel lymph node mapping and long-term tumor imaging in vivo demonstrated that the NIR-Silica NPs have a long circulation time and higher signal-to-noise ratio at a very low dye concentration and short exposure time (0.2 s). Therefore, the NIR-Silica NPs may be a promising fluorescence imaging agent for clinical application.

Objective: The existence of void regions and the complexity of structural heterogeneity and optical specificity are two challenges encountered in three-dimensional (3-D) optical imaging of in situ gastric cancer. An adaptively alternative light-transport-model-based 3-D optical imaging method was developed for addressing these challenges., Methods: In this newly developed imaging method, both the anatomical structure and optical properties are considered as a priori information, which makes the full use of the specificity of the biological tissues and improves both the quality and efficiency of the reconstructed images. The soul of the adaptively alternative technique is technique is configured to first classify the tissues based on the anatomical structure and optical properties and then select various equations to specifically characterize the light transport in different categories of tissues., Results: A series of rigorous simulations were conducted to demonstrate the performance of the hybrid light transport model, and the quality of the reconstructed images was then evaluated using a digital-mouse-based gastric cancer mimicing simulation, which showed that the localization error was less than 1 mm and the quantification error was approximately 10%. Finally, the applicability of the proposed method for in vivo imaging of gastric cancer was illustrated using groups of gastric cancer-bearing mice, which demonstrated the ability of the proposed method for longitudinal and quantitative monitoring of gastric cancer., Conclusion: The developed method offers improved probability and great potential in the applications of earlier detecting in situ gastric cancer and longitudinal and quantitative observation of its development.

The aim of this article is to investigate the influence of a tracer injection dose (ID) and camera integration time (IT) on quantifying pharmacokinetics of Cy5.5-GX1 in gastric cancer BGC-823 cell xenografted mice. Based on three factors, including whether or not to inject free GX1, the ID of Cy5.5-GX1, and the camera IT, 32 mice were randomly divided into eight groups and received 60-min dynamic fluorescence imaging. Gurfinkel exponential model (GEXPM) and Lammertsma simplified reference tissue model (SRTM) combined with a singular value decomposition analysis were used to quantitatively analyze the acquired dynamic fluorescent images. The binding potential (Bp) and the sum of the pharmacokinetic rate constants (SKRC) of Cy5.5-GX1 were determined by the SRTM and EXPM, respectively. In the tumor region, the SKRC value exhibited an obvious trend with change in the tracer ID, but the Bp value was not sensitive to it. Both the Bp and SKRC values were independent of the camera IT. In addition, the ratio of the tumor-to-muscle region was correlated with the camera IT but was independent of the tracer ID. Dynamic fluorescence imaging in conjunction with a kinetic analysis may provide more quantitative information than static fluorescence imaging, especially for a priori information on the optimal ID of targeted probes for individual therapy.

The third-order simplified harmonic spherical approximation (SP3) and diffusion approximation (DA) equations have been widely used in the three-dimensional (3D) whole-body optical imaging of small animals. With different types of tissues, which were classified by the ratio of µ s'/µ ɑ, the two equations have their own application scopes. However, the classification criterion was blurring and unreasonable, and the scope has not been systematically investigated until now. In this study, a new criterion for classifying tissues was established based on the absolute value of absorption and reduced scattering coefficients. Using the newly defined classification criterion, the performance and applicability of the SP3 and DA equations were evaluated with a series of investigation experiments. Extensive investigation results showed that the SP3 equation exhibited a better performance and wider applicability than the DA one in most of the observed cases, especially in tissues of low-scattering-low-absorption and low-scattering-high-absorption range. For the case of tissues with the high-scattering-low-absorption properties, a similar performance was observed for both the SP3 and the DA equations, in which case the DA was the preferred option for 3D whole-body optical imaging. Results of this study would provide significant reference for the study of hybrid light transport models.

Natural products (NPs) are an important source for new drug discovery over the past decades, which have been demonstrated to be effectively used in cancer prevention, treatment, and adjuvant therapy. Many methods, such as the genomic and metabolomic approaches, immunochemistry, mass spectrometry, and chromatography, have been used to study the effects of NPs on cancer as well as themselves. Because of the advantages in specificity, sensitivity, high throughput, and cost-effectiveness, optical imaging (OI) approaches, including optical microscopic imaging and macroscopic imaging techniques have also been applied in the studies of NPs. Optical microscopic imaging can observe NPs as cancer therapeutics at the cellular level and analyze its cytotoxicity and mechanism of action. Optical macroscopic imaging observes the distribution, metabolic pathway, and target lesions of NPs in vivo , and evaluates NPs as cancer therapeutics at the whole-body level in small living animals. This review focuses on the recent advances in NPs as cancer therapeutics, with particular emphasis on the powerful use of optical microscopic and macroscopic imaging techniques, including the studies of observation of ingestion by cells, anticancer mechanism, and in vivo delivery. Finally, we prospect the wider application and future potential of OI approaches in NPs as cancer therapeutics. [ABSTRACT FROM AUTHOR]