Optical Molecular Imaging System Research Articles

Electromagnetic Tracking and Optical Molecular Imaging Guidance for Liver Biopsy and Point-of-Care Tissue Assessment in Phantom and Woodchuck Hepatocellular Carcinoma.

To evaluate an integrated liver biopsy platform that combined CT image fusion, electromagnetic (EM) tracking, and optical molecular imaging (OMI) of indocyanine green (ICG) to target hepatocellular carcinoma (HCC) lesions and a point-of-care (POC) OMIto assessbiopsy cores, allbased on tumor retention of ICGcompared to normal liver, in phantom and animal model. A custom CT image fusion and EM-tracked guidance platform was modified to integrate the measurement of ICG fluorescence intensity signals in targeted liver tissue with an OMI stylet or a POC OMI system. Accuracy was evaluated in phantom and a woodchuck with HCC, 1day after administration of ICG. Fresh biopsy cores and paraffin-embedded formalin-fixed liver tissue blocks were evaluated with the OMI stylet or POC system to identify ICG fluorescence signal and ICG peak intensity. The mean distance between the initial guided needle delivery location and the peak ICG signal was 5.0 ± 4.7mm in the phantom. There was complete agreement between the reviewers of the POC-acquired ICG images, cytology, and histopathology in differentiating HCC-positive from HCC-negative biopsy cores. The peak ICG fluorescence intensity signal in the ex vivo liver blocks was 39 ± 12 and 281 ± 150 for HCC negative and HCC positive, respectively. Biopsy guidance with fused CT imaging, EM tracking, and ICG tracking with an OMI stylet to detect HCC is feasible. Immediate assessment of ICG uptake in biopsy cores with the POC OMI system is feasible and correlates with the presence of HCC in the tissue.

Icariin combined with human umbilical cord mesenchymal stem cells significantly improve the impaired kidney function in chronic renal failure.

At present, the main therapy for chronic renal failure (CRF) is dialysis and renal transplantation, but neither obtains satisfactory results. Human umbilical cord mesenchymal stem cells (huMSCs) are isolated from the fetal umbilical cord which has a high self-renewal and multi-directional differentiation potential. Icariin (ICA), a kidney-tonifying Chinese Medicine can enhance the multipotency of huMSCs. Therefore, this work seeks to employ the use of ICA-treated huMSCs for the treatment of chronic renal failure. Blood urea nitrogen and creatinine (Cr) analyses showed amelioration of functional parameters in ICA-treated huMSCs for the treatment of CRF rats at 3, 7, and 14 days after transplantation. ICA-treated huMSCs can obviously increase the number of cells in injured renal tissues at 3, 7, and 14 days after transplantation by optical molecular imaging system. Hematoxylin-eosin staining demonstrated that ICA-treated huMSCs reduced the levels of fibrosis in CRF rats at 14 days after transplantation. Superoxide dismutase and Malondialdehyde analyses showed that ICA-treated huMSCs reduced the oxidative damage in CRF rats. Moreover, transplantation with ICA-treated huMSCs decreased inflammatory responses, promoted the expression of growth factors, and protected injured renal tissues. Taken together, our findings suggest that ICA-treated huMSCs could improve the kidney function in CRF rats.

Preclinical study of bladder cancer diagnosis using tumor homing peptide fluorescent molecular probe

Objective To evaluate the features of optical molecular imaging of bladder tumor cells labeled by tumor homing peptide fluorescent molecular probe, and to explore the theoretical foundation of optical molecular imaging for bladder cancer diagnosis. Methods After prepared the FITC-CSNRDARRC fluorescent molecular probe, laser scanning confocal microscope, immuno fluorescence and multispectral fluorescence in vivo optical molecular imaging system have been used to evaluate the binding sites, the affecting factors of binding rates, the specificity and the targets. BIU-87 bladder tumor cell line, BIU-87 bladder tumor cell line, 68 cases of paraffin bladder tumor tissue samples, 16 cases of paraffin glandular bladder inflammatory samples, 43 cases of paraffin renal clear cell carcinoma samples, 68 cases of paraffin gastric adenocarcinoma samples, 29 cases of urine exfoliated cells suspected bladder cancer and BIU-87 bladder cancer nude xenograft have been used in this study. Results The binding site of FITC-CSNRDARRC fluorescent molecular probe were at the nucleus of labeled bladder tumor cells. The binding rates were correlated linearly with the dose of probe and the grade of pathology. The in vitro and in vivo studies demonstrate that the probe has a binding specificity with bladder tumor. When the FITC-CSNRDARRC fluorescent molecular probe labeled tumor cells, bright green spots were observed under laser scanning confocal microscope. The bright green spots were more apparent after stained by DAPI again. The tissue samples and tumor cells in the urine can be successful labeled and identified by fluorescence microscope. Optical molecular imaging of in vivo xenograft tumor tissues showed fluorescent spots under EMCCD. Conclusions The labeled loci of single cell by FITC-CSNRDARRC probe have been identified. The spatial resolution of optical molecular image is related to sensitivity of CCD, and the optical molecular imaging cannot be imaged by the conventional endoscope camera. Key words: Urinary bladder neoplasms; Tumor homing peptide; Fluorescent molecular probe; Optical molecular imaging; Molecule diagnosis

Comprehensive Evaluation of the Anti-Angiogenic and Anti-Neoplastic Effects of Endostar on Liver Cancer through Optical Molecular Imaging

Molecular imaging enables non-invasive monitoring of tumor growth, progression, and drug treatment response, and it has become an important tool to promote biological studies in recent years. In this study, we comprehensively evaluated the in vivo anti-angiogenic and anti-neoplastic effects of Endostar on liver cancer based on the optical molecular imaging systems including micro-computer tomography (Micro-CT), bioluminescence molecular imaging (BLI) and fluorescence molecular tomography (FMT). Firefly luciferase (fLuc) and green fluorescent protein (GFP) dual labeled human hepatocellular carcinoma cells (HCC-LM3-fLuc-GFP cells) were used to establish the subcutaneous and orthotopic liver tumor model. After the tumor cells were implanted 14∼18 days, Endostar (5 mg/kg/day) was administered through an intravenous tail vein injection for continuous 14 days. The computer tomography angiography (CTA) and BLI were carried out for the subcutaneous tumor model. FMT was executed for the orthotopic tumor model. The CTA data showed that tumor vessel formation and the peritumoral vasculature of subcutaneous tumor in the Endostar treatment group was significantly inhibited compared to the control group. The BLI data exhibited the obvious tumor inhibition day 8 post-treatment. The FMT detected the tumor suppression effects of Endostar as early as day 4 post-treatment and measured the tumor location. The above data confirmed the effects of Endostar on anti-angiogenesis and tumor suppression on liver cancer. Our system combined CTA, BLI, and FMT to offer more comprehensive information about the effects of Endostar on the suppression of vessel and tumor formation. Optical molecular imaging system enabled the non-invasive and reliable assessment of anti-tumor drug efficacy on liver cancer.

Lidamycin up-regulates the expression of thymidine phosphorylase and enhances the effects of capecitabine on the growth and pulmonary metastases of murine breast carcinoma

Capecitabine (CAP), a prodrug, needs to be converted to 5-fluorouracil by several key enzymes, including thymidine phosphorylase (TP). To improve the therapeutic index, potentiation of antitumor activity of CAP is required. In this study, we explored whether lidamycin (LDM), an enediyne anticancer antibiotic, can induce synergistic antitumor effects in combination with CAP in murine breast cancer in vitro and in vivo. Using MTT, cell migration and invasion, siRNA knockdown, and Western blot assays, the in vitro synergistic effects of LDM plus CAP on 4T1(LUC) cells were evaluated, and the mechanism of this synergy was explored. For in vivo model of orthotopic implantation model of 4T1(LUC) cells, optical molecular imaging system was utilized to evaluate the growth of primary tumor and metastasis. To further understand the mechanism of action of the LDM/CAP combination, immunohistochemistry analysis was carried out to detect thymidine phosphorylase induction and ERK signaling. As determined by MTT and transwell assay, LDM enhanced the inhibitory effects of CAP on cancer cell proliferation, migration, and invasion. Western blot showed that this synergistic effect was attributed to the up-regulated expression of TP induced by LDM. Knocking down TP impaired the synergistic anti-proliferative effect of LDM and CAP. Furthermore, our data suggested that LDM-induced up-regulation of TP both in vitro and in vivo is associated with ERK activation, because the inhibition of ERK activity by ERK inhibitor U0126 abrogated LDM-induced TP up-regulation. In animal models, LDM plus CAP potently inhibited primary tumor growth as well as lung metastasis compared with control or single-agent-treated group. LDM can potentiate the antitumor effects of CAP on breast cancer line. The synergistic effects suggest that the combination of LDM and CAP is an innovative antitumor strategy for breast cancer therapy.

Integrated optical molecular imaging system for four-dimensional real-time detection in living single cells

A novel, multifunctional optical imaging system was developed by integrating four-dimensional (4D) real-time confocal microscopy (RT-CM), multicolor total internal reflection microscopy (TIRFM), and Nomarski differential interference contrast (DIC) microscopy based on an epifluorescence microscope platform. A microcell incubator was combined with the imaging system for extended, real-time monitoring of living cells. The 4D images were generated by a combination of 3D images and multiple spatial or time images of a specimen, obtained at 10nm intervals. Optical sectioning was accomplished with a z-motor, which obtained 4D information with sequential layered sections. The integrated imaging system showed excellent detection sensitivity at the single-molecule level and 3D-spatial resolution (20nm x–y and 10nm z-axis) without moving the cell sample. This could be a tool for obtaining crucial information needed to develop approaches for characterizing and understanding the dynamics of biomolecules and nanoparticles in individual living cells and molecular interactions at the single-molecule level.

New Optical Molecular Imaging Systems

Molecular imaging has become a research focus in recent years, which provides an effective information acquisition, analysis and processing methodology at cellular and molecular levels for biomedical study. As an important molecular imaging technique, optical molecular imaging, especially fluorescence and bioluminescence imaging, has attracted remarkable attention in tumor study and drug development for its excellent performance, non-radiativity and high cost-effectiveness in comparison with conventional imaging modalities. Generally speaking, optical molecular imaging is regarded as the combination of traditional medical imaging technology and modern molecular biology, in which the advanced optics, biology, information, medicine, and other techniques are being married to non-invasively obtain in vivo physiological and pathological information sensitively, quantitatively, and specifically. Further, with the research of imaging theories, algorithms and molecular probes, optical imaging systems have been rapidly developed for biomedical study in molecular imaging discipline, including planar imaging systems, tomographic imaging systems, and multimodality fusion systems, and so on. This review focuses on some typical optical molecular imaging systems, especially for in vivo small animal use. It also provides a brief discussion on the future development and application of the optical molecular imaging systems.

Optical contrast agents and imaging systems for detection and diagnosis of cancer.

Molecular imaging has rapidly emerged as a discipline with the potential to impact fundamental biomedical research and clinical practice. Within this field, optical imaging offers several unique capabilities, based on the ability of cells and tissues to effect quantifiable changes in the properties of visible and near-infrared light. Beyond endogenous optical properties, the development of molecularly targeted contrast agents enables disease-specific morphologic and biochemical processes to be labeled with unique optical signatures. Optical imaging systems can then provide real-time visualization of pathophysiology at spatial scales from the subcellular to whole organ levels. In this article, we review fundamental techniques and recent developments in optical molecular imaging, emphasizing laboratory and clinical systems that aim to visualize the microscopic and macroscopic hallmarks of cancer.

Po-Thur Eve General-17: Design and Characterization of a CT Scanner for Small Animal Imaging

A prototype cone beam computed tomographyscanner has been designed for use in small animal imaging. The system consists of a small air‐cooled microfocus x‐ray source, a flat‐panel CMOS (complimentary metal‐oxide semiconductor) x‐ray detector, a motorized rotation stage and a personal computer. The scanner will ultimately be integrated into a planned quantitative optical molecular imagingsystem. Some initial performance characterization of the x‐ray detector has been performed. The detector response curve was found to be non‐linear at both low and high exposures. The response curve was “linearized” by using a polynomial gain correction technique involving fitting the response of the detector with a 3rd order polynomial function. The MTF of the detector was also measured using the angled edge technique. The MTF had a value of approximately 8.6 cycles/mm at 10% contrast. A transaxial slice of an acrylic phantom reconstructed using a Feldkamp back‐projection algorithm is also presented.

Optical Molecular Imaging: Overview and Technological Aspects

Summary Optical Molecular Imaging (OMI) is an in vivo procedure for early detection of pathologically changed tissue, such as tumours and inflammatory rheumatoid finger joints. Combining the advantages of optical diagnostics with the potential of genetic research, it employs specific markers to enhance the contrast of diseased tissue areas. These so-called optical markers can be both fluorescent and absorbent. The purpose of OMI is to activate the markers exclusively in the pathologically changed areas by means of specific enzyme reactions thus obtaining high contrast. The detection system must be highly sensitive and tailored to the marker's mechanism and field of application. Procedures such as diffuse optical tomography (DOT) and laser-induced fluorescence spectroscopy (LIF) are suitable for OMI systems. One out of many suppositions for the application of OMI is the accessibility of light penetration (cm range) in pathological changes, provided appropriate markers are found. The OMI principle is another challenging field of research, which offers a wide range of applications and a huge potential for the development of cost-favourable and efficient diagnostic methods.