• Proceedings of the KSMRM Conference
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• 2004.09a
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• pp.23-32
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• 2004

The chemotherapy sensitive Lewis lung carcinoma (LLC) and chemotherapy resistant Lewis lung carcinoma (CR-LLC) tumors concurrently implanted in mice, and compare these findings with histological macroscopic observations against 3D reconstruction of Fluorescence Molecular Tomography (FMT) preformed in vivo on the same animals. For the 3D image reconstruction we used 32 laser source images, a flat image and 3D surface rendering that confused for 3D Fluorescence Molecular Imaging (FMI). A minimum of ten tissue sections were analyzed per tumor for quantification of the TUNEL-positive cells, cell-associated Cy5.5-Annexin and vessel-associated Alexa Fluor-Lectin. These are useful apoptosis and angiogenesis markers, and they serve as validation experiments to data obtained in vivousing a Cy5.5-Annexin V conjugate injected intravenously in chemotherapy-treated animals carrying the tumors studied histologically. We detected higher levels of apoptosis and corresponding higher levels of Cy5.5 fluorescence in the LLC vs. the CR-LLC tumors according to tissue depth and these findings confirm that in vivo staining with the Cy5.5-Annexing conjugate correlates well with in vitro TUNEL staining and is consistent with the higher apoptotic index expected from the LLC line. There appeared to be 1.38% more apoptosis for LLC than CR-LLC. Consequently there is good correlation between the histology results and in vivo fluorescence-mediated optical imaging. In conclusion the apoptotic images of 3D FMI were validated by microscopic histological image analysis. This is a significant result for the continuous progress of fluorescence 3D imaging research.

• Korean Journal of Radiology
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• v.25 no.1
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• pp.86-102
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• 2024

Early diagnosis, accurate assessment, and localization of peritoneal metastasis (PM) are essential for the selection of appropriate treatments and surgical guidance. However, available imaging modalities (computed tomography [CT], conventional magnetic resonance imaging [MRI], and 18fluorodeoxyglucose positron emission tomography [PET]/CT) have limitations. The advent of new imaging techniques and novel molecular imaging agents have revealed molecular processes in the tumor microenvironment as an application for the early diagnosis and assessment of PM as well as real-time guided surgical resection, which has changed clinical management. In contrast to clinical imaging, which is purely qualitative and subjective for interpreting macroscopic structures, radiomics and artificial intelligence (AI) capitalize on high-dimensional numerical data from images that may reflect tumor pathophysiology. A predictive model can be used to predict the occurrence, recurrence, and prognosis of PM, thereby avoiding unnecessary exploratory surgeries. This review summarizes the role and status of different imaging techniques, especially new imaging strategies such as spectral photon-counting CT, fibroblast activation protein inhibitor (FAPI) PET/CT, near-infrared fluorescence imaging, and PET/MRI, for early diagnosis, assessment of surgical indications, and recurrence monitoring in patients with PM. The clinical applications, limitations, and solutions for fluorescence imaging, radiomics, and AI are also discussed.

• Molecules and Cells
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• v.45 no.2
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• pp.84-92
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• 2022

To understand the microcircuitry of the brain, the anatomical and functional connectivity among neurons must be resolved. One of the technical hurdles to achieving this goal is that the anatomical connections, or synapses, are often smaller than the diffraction limit of light and thus are difficult to resolve by conventional microscopy, while the microcircuitry of the brain is on the scale of 1 mm or larger. To date, the gold standard method for microcircuit reconstruction has been electron microscopy (EM). However, despite its rapid development, EM has clear shortcomings as a method for microcircuit reconstruction. The greatest weakness of this method is arguably its incompatibility with functional and molecular analysis. Fluorescence microscopy, on the other hand, is readily compatible with numerous physiological and molecular analyses. We believe that recent advances in various fluorescence microscopy techniques offer a new possibility for reliable synapse detection in large volumes of neural circuits. In this minireview, we summarize recent advances in fluorescence-based microcircuit reconstruction. In the same vein as these studies, we introduce our recent efforts to analyze the long-range connectivity among brain areas and the subcellular distribution of synapses of interest in relatively large volumes of cortical tissue with array tomography and superresolution microscopy.

• Toxicological Research
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• v.29 no.1
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• pp.1-6
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• 2013

The process of drug discovery and development requires substantial resources and time. The drug industry has tried to reduce costs by conducting appropriate animal studies together with molecular biological and genetic analyses. Basic science research has been limited to in vitro studies of cellular processes and ex vivo tissue examination using suitable animal models of disease. However, in the past two decades new technologies have been developed that permit the imaging of live animals using radiotracer emission, X-rays, magnetic resonance signals, fluorescence, and bioluminescence. The main objective of this review is to provide an overview of small animal molecular imaging, with a focus on nuclear imaging (single photon emission computed tomography and positron emission tomography). These technologies permit visualization of toxicodynamics as well as toxicity to specific organs by directly monitoring drug accumulation and assessing physiological and/or molecular alterations. Nuclear imaging technology has great potential for improving the efficiency of the drug development process.

• Molecules and Cells
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• v.44 no.11
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• pp.851-860
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• 2021

Label-free optical diffraction tomography (ODT), an imaging technology that does not require fluorescent labeling or other pre-processing, can overcome the limitations of conventional cell imaging technologies, such as fluorescence and electron microscopy. In this study, we used ODT to characterize the cellular organelles of three different stem cells-namely, human liver derived stem cell, human umbilical cord matrix derived mesenchymal stem cell, and human induced pluripotent stem cell-based on their refractive index and volume of organelles. The physical property of each stem cell was compared with that of fibroblast. Based on our findings, the characteristic physical properties of specific stem cells can be quantitatively distinguished based on their refractive index and volume of cellular organelles. Altogether, the method employed herein could aid in the distinction of living stem cells from normal cells without the use of fluorescence or specific biomarkers.

• Toxicological Research
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• v.34 no.1
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• pp.1-6
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• 2018

The purpose of this study was to detect cell death in the liver of mice treated with thioacetamide (TAA) using fluorescence bioimaging and compare this outcome with that using conventional histopathological examination. At 6 weeks of age, 24 mice were randomly divided into three groups: group 1 (G1), control group; group 2 (G2), fluorescence probe control group; group 3 (G3), TAA-treated group. G3 mice were treated with TAA. Twenty-two hours after TAA treatment, G2 and G3 mice were treated with Annexin-Vivo 750. Fluorescence in vivo bioimaging was performed by fluorescence molecular tomography at two hours after Annexin-Vivo 750 treatment, and fluorescence ex vivo bioimaging of the liver was performed. Liver damage was validated by histopathological examination. In vivo bioimaging showed that the fluorescence intensity was increased in the right upper part of G3 mice compared with that in G2 mice, whereas G1 mice showed no signal. Additionally ex vivo bioimaging showed that the fluorescence intensity was significantly increased in the livers of G3 mice compared with those in G1 or G2 mice (p < 0.05). Histopathological examination of the liver showed no cell death in G1 and G2 mice. However, in G3 mice, there was destruction of hepatocytes and increased cell death. Terminal deoxynucleotidyl transferase dUTP nick end labeling staining confirmed many cell death features in the liver of G3 mice, whereas no pathological findings were observed in the liver of G1 and G2 mice. Taken together, fluorescence bioimaging in this study showed the detection of cell death and made it possible to quantify the level of cell death in male mice. The outcome was correlated with conventional biomedical examination. As it was difficult to differentiate histological location by fluorescent bioimaging, it is necessary to develop specific fluorescent dyes for monitoring hepatic disease progression and to exploit new bioimaging techniques without dye-labeling.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.1 no.1
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• pp.62-73
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• 2015

We developed an evans blue-indocyanine green-$^{99m}Tc$-human serum albumin conjugate for sentinel lymph node mapping and we describe its unique potential usage for clinical implications. This conjugate has combined the strengths of visible blue dye, near-infrared fluorescence and radioisotope into one single conjugate without any additional weakness/disadvantage. All the components of evans blue-indocyanine green-$^{99m}Tc$-human serum albumin are safe and of low cost, and they have already been clinically used. This conjugate was stable in the serum, it showed a long retention time in the lymphatic system and the lymph nodes showed a much higher signal-to-noise ratio after the conjugate was injected intradermally into the paw of mice. Both the single-photon emission computed tomography and near-infrared fluorescent images of the mice were successfully obtained at the same time as the excised sentinel lymph nodes showed blue color. The visual color, near-infrared fluorescence and gamma ray from this agent could be complementary for each other in all the steps of sentinel lymph node sampling: exploring and planning sentinel lymph node before excision with visualization of the exact sentinel lymph node location during an operation. Therefore, the triple modal agent will possibly be very ideal for sentinel lymph node mapping because of the high signal-to-noise ratio for non-invasive imaging and its complementary multimodal nature, easy preparation and safety. It is promising for clinical applications and it may have great advantages over the traditional single modal methods.

• Korean Chemical Engineering Research
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• v.57 no.4
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• pp.445-454
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• 2019

Layered double hydroxides (LDHs) nanoparticles have emerged as novel nanomaterials for bio-imaging applications due to its unique layered structure, physicochemical properties, and good biocompatibility. Bio-imaging is one of the most important fields for medical applications in clinical diagnostics and therapeutics of various diseases. Enhanced diagnostic techniques are needed to realize new paradigm for next-generation personalized medicine through nanoscale materials. When nanotechnology is introduced into bio-imaging system, nanoparticle probes can endow imaging techniques with enhanced ability to obtain information about biological system at the molecular level. In this review, we summarize structural features of LDH nanoparticles with current issues of bio-imaging system. LDH nanoparticle probes are also discussed through in vitro as well as in vivo studies in various bio-imaging techniques including fluorescence imaging, magnetic resonance imaging (MRI), positron emission tomography (PET), and computed X-ray tomography (CT), which will have the potential in the development of the advanced nanoparticles with high sensitivity and selectivity.