Application of susceptibility weighted imaging (SWI) for evaluation of draining veins of arteriovenous malformation: utility of magnitude images.

INTRODUCTION: The current study evaluated the signal characteristics of susceptibility weighted imaging (SWI) of arteriovenous malformation (AVM), especially for draining veins. For this purpose, we identified the draining veins of the AVM on angiography and evaluated the signal on magnitude image for SWI (SWI-mag) and minimum intensity projection image (SWI-minIP). METHODS: Subjects were 14 cases with angiographically proven AVM. SWI-mag, SWI-minIP, and time-of-flight (TOF) magnetic resonance angiography were acquired. For the draining veins of the AVM identified on angiography, we analyzed signal intensity on the images listed above, and classified it into hyperintensity (hyper), mixed intensity (mixed), hypointensity (hypo), and no visualization. RESULTS: On the analysis of 27 angiographically proven draining veins, 19 draining veins were classified as hyper, 3 as mixed, 0 as hypo, and 6 as no visualization on SWI-mag. On TOF images, 21 draining veins were classified as hyper, 2 as mixed, 0 as hypo, and 4 as no visualization, while 6 draining veins did not show hyperintensity on TOF, and SWI-mag visualized 3 of these 6 veins as hyper. CONCLUSION: SWI-mag depicted most draining veins of AVM as hyperintensity. We speculate that this is mainly due to the higher concentration of oxygenated hemoglobin (oxy-Hb) and inflow effect of the draining vein. SWI-mag seems to be useful in the analysis and follow-up for AVM as the signal on the image may reflect physiological status.博士（医学）・乙第1316号・平成25年7月22

T1強調像での信号強度が出生後日数と負の相関性を示す新生児・乳児期の脳構造

Purpose: Although the neonatal and infantile brain typically shows sequential T1 shortening according to gestational age as a result of myelination, several structures do not follow this rule. We evaluated the relationship between the signal intensity of various structures in the neonatal and infantile brain on T1-weighted imaging (T1WI) and either postnatal or gestational age. Materials and Methods: We examined magnetic resonance images from 120 newborns and infants without any abnormalities in the central nervous system. Written informed consent was obtained from all parents and the institutional review board approved the study. Gestational age at examination ranged from 35 weeks, 3 days to 46 weeks, 6 days, and postnatal age ranged from 7 days to 127 days. Signal intensity on T1WI was evaluated on a scale from Grade 1 (indistinguishable from surrounding structures) to Grade 4 (higher than cortex and close to fat). We evaluated relationships between the T1 signal grades of various structures in the neonatal brain and postnatal or gestational age using Spearman’s correlation analysis. Results: Significant positive correlations were identified between T1 signal grade and gestational age in the pyramidal tract (P < 0.001). Conversely, significant negative correlations were evident between T1 signal grade and postnatal age (P < 0.001), in structures including the stria medullaris thalami, fornix cerebellar vermis, dentate nucleus and anterior pituitary gland. Conclusion: Significant negative correlations exist between signal intensity on T1WI and postnatal age in some structures of the neonatal and infantile brain. Some mechanisms other than myelination might play roles in the course of signal appearance.博士（医学）・乙第1405号・平成29年6月28日Copyright © 2017 by Japanese Society for Magnetic Resonance in Medicine : This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives International License(https://creativecommons.org/licenses/by-nc-nd/4.0/deed.ja)

急性期虚血性脳卒中患者から機械的血栓回収術で得られた血栓の年齢と組成は血栓回収術転帰および臨床転帰と関連していた

Introduction: Understanding the composition of stroke thrombi retrieved by mechanical thrombectomy is essential to clarify the pathogenesis of stroke. However, it is difficult to evaluate thrombus composition precisely and objectively. Immunohistochemical staining was used to evaluate thrombus composition and age. Materials and methods: Consecutive thrombi (n = 108) retrieved from patients who underwent mechanical thrombectomy for acute large-vessel ischemic stroke were retrospectively analyzed. Lytic features of granulocytes and CD163 were estimated as indicators of the age of the cardioembolic (CE) thrombus. Results: The stroke subtypes were as follows: CE, 74 cases; large artery atherosclerosis, 11; undetermined etiology, 12; and other determined etiology, 11. There were no statistical differences in thrombi composition according to stroke subtypes. The fibrin area was positively correlated with the red blood cell (RBC) and platelet areas. The following analysis was performed using CE only. Regarding age, the thrombus was judged as fresh in 30.0 % and older in 70.0 % based on the lytic features. The RBC areas of older thrombi were smaller than those of fresh thrombi. The puncture-to-reperfusion time of older thrombi was longer than that of fresh thrombi. Platelet-rich thrombi were associated with a greater number of maneuvers, a smaller prevalence of TICI 3, and unfavorable functional outcomes compared to platelet-poor thrombi. The number of CD163 positive cells in thrombi with anticoagulants was higher than in those without anticoagulants. Conclusion: Thrombus composition correlated with revascularization and clinical outcomes. The composition of an acute ischemic thrombus may reflect the pathophysiology of stroke and influence treatment efficacy.博士（医学）・甲第855号・令和4年12月22日Copyright © 2022 Elsevier Ltd. All rights reserved

The Groebke-Blackburn-Bienayme Reaction

Imidazo[1,2a]pyridine is a well‐known scaffold in many marketed drugs, such as Zolpidem, Minodronic acid, Miroprofen and DS‐1 and it also serves as a broadly applied pharmacophore in drug discovery. The scaffold revoked a wave of interest when Groebke, Blackburn and Bienaymé reported independently a new three component reaction resulting in compounds with the imidazo[1,2‐a]‐heterocycles as a core structure. During the course of two decades the Groebke Blackburn Bienaymé (GBB‐3CR) reaction has emerged as a very important multicomponent reaction (MCR), resulting in over a hundred patents and a great number of publications in various fields of interest. Now two compounds derived from GBB‐3CR chemistry received FDA approval. To celebrate the first 20 years of GBB‐chemistry , we present an overview of the chemistry of the GBB‐3CR, including an analysis of each of the three starting material classes, solvents and catalysts. Additionally, a list of patents and their applications and a more in‐depth summary of the biological targets that were addressed, including structural biology analysis, is given

Far-Red and Near-IR AIE-Active Fluorescent Organic Nanoprobes with Enhanced Tumor-Targeting Efficacy:Shape-Specific Effects

The rational design of high-performance fluorescent materials for cancer targeting in vivo is still challenging. A unique molecular design strategy is presented that involves tailoring aggregation-induced emission (AIE)-active organic molecules to realize preferable far-red and NIR fluorescence, well-controlled morphology (from rod-like to spherical), and also tumor-targeted bioimaging. The shape-tailored organic quinoline-malononitrile (QM) nanoprobes are biocompatible and highly desirable for cell-tracking applications. Impressively, the spherical shape of QM-5 nanoaggregates exhibits excellent tumor-targeted bioimaging performance after intravenously injection into mice, but not the rod-like aggregates of QM-2.</p

Design Strategy for a Near-Infrared Fluorescence Probe for Matrix Metalloproteinase Utilizing Highly Cell Permeable Boron Dipyrromethene

Near-infrared (NIR) fluorescence probes are especially useful for simple and noninvasive <i>in vivo</i> imaging inside the body because of low autofluorescence and high tissue transparency in the NIR region compared with other wavelength regions. However, existing NIR fluorescence probes for matrix metalloproteinases (MMPs), which are tumor, atherosclerosis, and inflammation markers, have various disadvantages, especially as regards sensitivity. Here, we report a novel design strategy to obtain a NIR fluorescence probe that is rapidly internalized by free diffusion and well retained intracellularly after activation by extracellular MMPs. We designed and synthesized four candidate probes, each consisting of a cell permeable or nonpermeable NIR fluorescent dye as a Förster resonance energy transfer (FRET) donor linked to the NIR dark quencher BHQ-3 as a FRET acceptor via a MMP substrate peptide. We applied these probes for detection of the MMP activity of cultured HT-1080 cells, which express MMP2 and MT1-MMP, by fluorescence microscopy. Among them, the probe incorporating BODIPY650/665, <b>BODIPY-MMP</b>, clearly visualized the MMP activity as an increment of fluorescence inside the cells. We then applied this probe to a mouse xenograft tumor model prepared with HT-1080 cells. Following intratumoral injection of the probe, MMP activity could be visualized for much longer with <b>BODIPY-MMP</b> than with the probe containing SulfoCy5, which is cell impermeable and consequently readily washed out of the tissue. This simple design strategy should be applicable to develop a range of sensitive, rapidly responsive NIR fluorescence probes not only for MMP activity, but also for other proteases