5-ALA-based fluorescence-guided surgery (FGS) is a state-of-the-art treatment for brain tumors, but may miss areas due to its low sensitivity. To improve the sensitivity we developed dual PpIX and Moxifloxacin Fluorescence Confocal Imaging method that allows simultaneous imaging of 5-ALA and moxifloxacin by excitation with a single light source. This method verified by comparing confocal images in glioblastoma specimen. The distribution of cells expressing 5-ALA and moxifloxacin fluorescence signals showed the same correlation. In large-area tumor sample images, PplX showed differences in signal intensity, but moxifloxacin was constant. These results show the potential to improve sensitivity than with 5-ALA alone.
High-resolution fluorescence imaging using moxifloxacin as a clinically compatible cell labeling agent is described. Moxifloxacin is an antibiotic with good pharmacokinetic properties for tissue penetration and it has intrinsic fluorescence under ultraviolet (UV) excitation. Alternative usage of moxifloxacin as the cell labeling agent was demonstrated in two-photon tissue imaging of various tissues. Cells within tissues were visualized in enhanced contrasts with moxifloxacin. Moxifloxacin based tissue imaging was explored not only in two-photon excitation but also in both single-photon and three-photon excitations. Moxifloxacin based fluorescence imaging is clinically compatible and has potentials for clinical applications where the cellular examination is needed.
Surgical resection is the primary treatment for malignant brain tumors. This procedure has a dilemma—aggressive surgical resection tends to extend patient survival; however, it also increases the risk of neurological deficiencies. Current medical imaging methods are not sensitive and their interpretation largely depend on surgeon’s impression. High-speed cellular imaging method by using clinically applicable moxifloxacin was demonstrated for fast and sensitive tumor-detection. The detailed cytoarchitecture of brain tumor mouse model and malignant human brain tumors was revealed. This study showed the potential and feasibility of moxifloxacin-based confocal microscopy as a surgery-guiding method for tumor removal.
Bone marrow transplantation became the standard choice for treatment of many leukemias, tumors and metabolic diseases. Understanding the dynamic behavior of bone marrow niches, especially in case of bone marrow transplantation is critical to improve the efficiency of the treatment. Intravital microscopy was demonstrated to be a powerful tool to study physiological structure of bone marrow niche. However, current method of intravital microscopy has difficulty in longitudinal monitoring the same bone marrow niche site due to the invasion of the prior-imaging surgery. In this study, we introduce a method to improve the bone marrow niche imaging process and enable the longitudinal imaging of murine calvarium bone marrow. Mouse model for calvarium bone marrow imaging was made by attaching cover glass window to the calvarium bone. Longitudinal imaging of whole bone marrow engraftment process was carried out to demonstrate the advantage of our mouse model. Qualitative and quantitative analysis were also executed on the image data. The result provided a dynamic and full visualization of the bone marrow engraftment process. The study was expected to provide helpful tool for bone marrow studies and useful information for bone marrow transplantation in future.
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