MCA供血区急性脑梗死SWI图像与脑血管反应性的相关性

目的:分析大脑中动脉供血区(MCA)急性脑梗死患者的磁敏感加权成像(SWI),探讨梗死侧侧脑室旁深部髓质静脉(DMV)数量与脑血管反应性(CVR)的相关性。方法:回顾性纳入首次发生患侧MCA供血区卒中患者109例,并已完成TCD CO_2负荷实验和SWI等检查。根据SWI图像将DMV数量分为3级,5条为1级;5-10条为2级;10条为3级,分析DMV分级与CVR的关系。结果:根据排除标准共纳入MCA供血区急性脑梗死患者53例,DMV 1级、2级和3级分别有29、18、6例患者,MCA平均CVR为0.40±0.18。DMV 1级CVR为(0.45±0.22)、2级为(0.35±0.15)和3级为(0.20±0.11),3组患者间CVR存在明显差异(P0.05),且DMV 3级组较DMV 1级组、2级组显著降低(P0.05);Spearman相关分析表明,DMV分级与CVR间存在明显的负性相关关系(P0.001)。结论:MCA供血区脑梗死患者DMV分级与患侧MCA CVR呈负相关关系。     

Islet-selectivity of G-protein coupled receptor ligands evaluated for PET imaging of pancreatic β-cell mass

A critical unmet need exists for methods to quantitatively measure endogenous pancreatic β-cell mass (BCM) for the clinical evaluation of therapies to prevent or reverse loss of BCM and diabetes progression. Our objective was to identify G-protein coupled receptors (GPCRs) that are expressed with a high degree of specificity to islet β-cells for receptor-targeted imaging of BCM. GPCRs enriched in pancreatic islets relative to pancreas acinar and hepatic tissue were identified using a database screen. Islet-specific expression was confirmed by human pancreas immunohistochemistry (IHC). In vitro selectivity assessment was determined from the binding and uptake of radiolabeled ligands to the rat insulinoma INS-1 832/13 cell line and isolated rat islets relative to the exocrine pancreas cell-type, PANC-1. Tail-vein injections of radioligands into rats were used to determine favorable image criteria of in vivo biodistribution to the pancreas relative to other internal organs (i.e., liver, spleen, stomach, and lungs). Database and IHC screening identified four candidate receptors for further in vitro and in vivo evaluation for PET imaging of BCM: prokineticin-1 receptor (PK-1R), metabotropic glutamate receptor type-5 (mGluR5), neuropeptide Y-2 receptor (NPY-2R), and glucagon-like peptide 1 receptor (GLP-1R). In vitro specificity ratios gave the following receptor rank order: PK-1R > GLP-1R > NPY-2R > mGluR5. The biodistribution rank order of selectivity to the pancreas was found to be PK-1R > VMAT2 ∼ GLP-1R > mGluR5. Favorable islet selectivity and biodistribution characteristics suggest several GPCRs as potential targets for PET imaging of pancreatic BCM.     

In Vivo Epithelial Wound Repair Requires Mobilization of Endogenous Intracellular and Extracellular Calcium

We report that a localized intracellular and extracellular Ca²⁺ mobilization occurs at the site of microscopic epithelial damage in vivo and is required to mediate tissue repair. Intravital confocal/two-photon microscopy continuously imaged the surgically exposed stomach mucosa of anesthetized mice while photodamage of gastric epithelial surface cells created a microscopic lesion that healed within 15 min. Transgenic mice with an intracellular Ca²⁺-sensitive protein (yellow cameleon 3.0) report that intracellular Ca²⁺ selectively increases in restituting gastric epithelial cells adjacent to the damaged cells. Pretreatment with U-73122, indomethacin, 2-aminoethoxydiphenylborane, or verapamil inhibits repair of the damage and also inhibits the intracellular Ca²⁺ increase. Confocal imaging of Fura-Red dye in luminal superfusate shows a localized extracellular Ca²⁺ increase at the gastric surface adjacent to the damage that temporally follows intracellular Ca²⁺ mobilization. Indomethacin and verapamil also inhibit the luminal Ca²⁺ increase. Intracellular Ca²⁺ chelation (1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid/acetoxymethyl ester, BAPTA/AM) fully inhibits intracellular and luminal Ca²⁺ increases, whereas luminal calcium chelation (N-(2-hydroxyetheyl)-ethylendiamin-N,N,N′-triacetic acid trisodium, HEDTA) blocks the increase of luminal Ca²⁺ and unevenly inhibits late-phase intracellular Ca²⁺ mobilization. Both modes of Ca²⁺ chelation slow gastric repair. In plasma membrane Ca-ATPase 1^+/− mice, but not plasma membrane Ca-ATPase 4^−/− mice, there is slowed epithelial repair and a diminished gastric surface Ca²⁺ increase. We conclude that endogenous Ca²⁺, mobilized by signaling pathways and transmembrane Ca²⁺ transport, causes increased Ca²⁺ levels at the epithelial damage site that are essential to gastric epithelial cell restitution in vivo.     

编者按: 脑成像与脑网络

揭示脑的奥秘是人类面临的最大挑战之一。神经元是构成神经系统结构与功能的基本单位。神经元与神经元之间通过突触实现信息交互,并构成神经环路或神经网络。神经环路有局部的,也有跨脑区或长程的,甚至全脑尺度的。神经环路则是脑实现神经信息处理的基本单元。若干神经环路构成脑网络。脑网络研究已经成为脑功能与脑疾病研究领域的热点。 在国家自然科学基金委员会和科技部“973计划”等项目的支持下,我国科学家在这一领域已经开展了卓有成效的工作。2011年第393次香山科学会议“脑网络组及其临床应用的前沿科学问题”曾对此进行过比较深入的研讨。为促进对该领域现状及发展的了解,本期汇集了2篇述评和2篇研究论文,作为脑成像与脑网络专题发表,以飨读者。 利用9.4T功能磁共振成像(fMRI)获得轻度麻醉状态下大鼠静息状态及刺激激活的数据,通过互相关分析构建节点之间的相关系数矩阵并计算相应的网络参数,赖永秀等人报道了大鼠感觉运动系统静息态脑网络的研究成果,发现感觉运动系统在静息态时的脑网络具有小世界属性。 扩散磁共振成像(dMRI)的出现为大脑结构与功能研究提供了全新的检测手段,雷皓等报道了小动物高分辨扩散磁共振成像数据分析方法,为小动物脑dMRI研究提供了统一图像模板与完善的计算方法,对于检测神经纤维微观结构的变化,以及临床诊断,将具有极其重要的意义。 神经环路功能变化的实时在体监测是研究脑网络不可或缺的手段,曾绍群等评述了基于声光偏转器的快速无惯性随机扫描双光子显微成像技术的研究进展及发展趋势,指出该技术的进一步发展将为神经活动观测提供一种全新的方法,从而极大地推动脑科学研究的发展。 针对哺乳动物全脑的神经元网络成像,龚辉等从空间分辨率、探测范围、数据配准和成像速度等方面评述了光学显微水平全脑成像方法的研究进展,并讨论所面临的挑战。他们指出,要在全脑尺度获取突起水平分辨率的结构与功能数据,光学成像方法最为成熟。华中科技大学研制的MOST系统,率先获得了一系列高分辨率的完整大脑解剖数据集,该成果将在神经元网络的构建和脑功能与疾病研究中发挥重要作用。 我们期待更多、更好的有关脑成像与脑网络的论文发表,以更广泛和深入地促进我国脑科学研究领域的学术交流。     

Towards the PET radiotracer for p75 neurotrophin receptor: [11C]LM11A-24 shows biological activity in vitro,but unfavorable ex vivo and in vivo profile

Mature neurotrophins as well as their pro forms are critically involved in the regulation of neuronal functions. They are signaling through three distinct types of receptors: tropomyosin receptor kinase family (TrkA/B/C), p75 neurotrophin receptor (p75^NTR) and sortilin. Aberrant expression of p75^NTR in the CNS is implicated in a variety of neurodegenerative diseases, including Alzheimer’s disease. The goal of this work was to evaluate one of the very few reported p75^NTR small molecule ligands as a lead compound for development of novel PET radiotracers for in vivo p75^NTR imaging. Here we report that previously described ligand LM11A-24 shows significant inhibition of carbachol-induced persistent firing (PF) of entorhinal cortex (EC) pyramidal neurons in wild-type mice via selective interaction with p75^NTR. Based on this electrophysiological assay, the compound has very high potency with an EC₅₀ <10 nM. We optimized the radiosynthesis of [¹¹C]LM11A-24 as the first attempt to develop PET radioligand for in vivo imaging of p75^NTR. Despite some weak interaction with CNS tissues, the radiolabeled compound showed unfavorable in vivo profile presumably due to high hydrophilicity.     

重症肺炎患儿suPAR水平对比分析及与影像学表现的相关性

摘要 目的：探讨重症肺炎患儿可溶性尿激酶型纤溶酶原激活物受体（soluble urokinase-type plasminogen activator receptor,suPAR）水平并对比分析及与影像学表现的相关性。方法：选取贵阳市第二人民医院及贵阳市儿童医院2020年1月到2020年12月共收治的70例肺炎患儿作为研究对象,其中重症肺炎患儿35例,男22例、女13例,将其分为重症组,轻症肺炎患儿35例,男20例、女15例,将其分为轻症组。对比两组患儿的suPAR水平、心肌酶水平以及肺部影像学结果,了解suPAR在重症肺炎中是否具有敏感性及特异性,并分析重症肺炎suPAR水平与心肌酶、肺部影像学结果是否存在相关性。结果：重症组suPAR水平较轻症组明显升高,差异具有统计学意义（P＜0.05）,重症组患儿肌酸激酶同工酶（creatine kinase isoenzymes-MB,CK-MB）、肌酸激酶（creatine kinase,CK）、乳酸脱氢酶（lactate dehydrogenase,LDH）、谷草转氨酶（Aspartate aminotransferase,AST）心肌酶相关指标明显高于轻症组,差异具有显著性（P＜0.05）;两组患儿密度增高影、带片絮状影、节段性实变、斑片状影人数对比无明显差异（P＞0.05）,两组患儿肺不张、大片状影、双肺纹增多人数对比差异显著（P＜0.05）;suPAR水平与CK-MB、CK、LDH、AST以及影像学特征呈正相关（P＜0.05）。血清suPAR水平对重症肺炎病情危重程度ROC的AUC为0.897（95%CI：0.819~0.975）,最佳cutoff值为1.9 ng/mL,此时特异度、灵敏度为82.86 %、85.71 %。结论：重症肺炎组suPAR的值与心肌酶呈正相关;suPAR水平与影像学表现具有相关性;suPAR水平越高提示病情越危重,在重症肺炎评估中其敏感性及特异性增高。     

硫化铜纳米粒子应用于肿瘤诊断和治疗的研究进展

癌症是当今威胁人类健康的主要疾病之一。近年来提出的近红外光介导的光热治疗,能够对肿瘤组织进行定点清除并且对正常组织具有较低的毒副作用,为肿瘤的治疗提供了新的方法。开发具有良好生物相容性的高效光热偶联剂是发展光热治疗的首要条件。随着纳米技术的飞速发展,一些金属纳米结构由于具有独特的光学特性作为光热偶联剂被广泛应用到肿瘤的光热治疗中。然而,成本高昂、制备过程繁琐以及光热稳定性较差等不足,限制了这些纳米材料的进一步应用。最新报道的新型光热偶联剂半导体硫化铜纳米粒子(copper sulfide nanoparticles,CuS NPs),由于其具有制备工艺简单、成本低廉、突出的光热稳定性和良好的生物相容性等优势,成为了当今纳米医学领域研究的热点。本文主要综述了CuS纳米粒子在肿瘤光热治疗和影像诊断方面的应用研究,并对CuS纳米粒子在生物医学领域应用中存在的问题和未来的研究方向进行了展望。     

IMp: The customizable LEGO? Pinned Insect Manipulator

We present a pinned insect manipulator (IMp) constructed of LEGO® building bricks with two axes of movement and two axes of rotation. In addition we present three variants of the IMp to emphasise the modular design, which facilitates resizing to meet the full range of pinned insect specimens, is fully customizable, collapsible, affordable and does not require specialist tools or knowledge to assemble.     

Geometric and dosimetric accuracy and imaging dose of the real-time tumour tracking system of a gimbal mounted linac

PurposeTo suggest a comprehensive testing scheme to evaluate the geometric and dosimetric accuracy and the imaging dose of the VERO dynamic tumour tracking (DTT) for its clinical implementation.MethodsGeometric accuracy was evaluated for gantry 0° and 90° in terms of prediction (E_P), mechanical (E_M) and tracking (E_T) errors for sinusoidal patterns with 10 and 20 mm amplitudes, 2–6 s periods and phase shift up to 1 s and for 3 patient patterns. The automatic 4D model update was investigated simulating changes in the breathing pattern during treatment.Dosimetric accuracy was evaluated with gafchromic films irradiated in static and moving phantom with and without DTT. The entrance skin dose (ESD) was assessed using a solid state detector and gafchromic films.ResultsThe RMS of E_P, E_M, and E_T were up to 0.8, 0.5 and 0.9 mm for all non phased-shifted motion patterns while for the phased-shifted ones, E_P and E_T increased to 2.2 and 2.6 mm. Up to 4 updates are necessary to restore a good correlation model, according to type of change.For 100 kVp and 1 mA s X-ray beam, the ESD per portal due to 20 s fluoroscopy was 16.6 mGy, while treatment verification at a frequency of 1 Hz contributed with 4.2 mGy/min.ConclusionsThe proposed testing scheme highlighted that the VERO DTT system tracks a moving target with high accuracy. The automatic update of the 4D model is a powerful tool to guarantee the accuracy of tracking without increasing the imaging dose.