Functional lung imaging with synchrotron radiation: Methods and preclinical applications

Many lung disease processes are characterized by structural and functional heterogeneity that is not directly appreciable with traditional physiological measurements. Experimental methods and lung function modeling to study regional lung function are crucial for better understanding of disease mechanisms and for targeting treatment. Synchrotron radiation offers useful properties to this end: coherence, utilized in phase-contrast imaging, and high flux and a wide energy spectrum which allow the selection of very narrow energy bands of radiation, thus allowing imaging at very specific energies. K-edge subtraction imaging (KES) has thus been developed at synchrotrons for both human and small animal imaging. The unique properties of synchrotron radiation extend X-ray computed tomography (CT) capabilities to quantitatively assess lung morphology, and also to map regional lung ventilation, perfusion, inflammation and biomechanical properties, with microscopic spatial resolution. Four-dimensional imaging, allows the investigation of the dynamics of regional lung functional parameters simultaneously with structural deformation of the lung as a function of time. This review summarizes synchrotron radiation imaging methods and overviews examples of its application in the study of disease mechanisms in preclinical animal models, as well as the potential for clinical translation both through the knowledge gained using these techniques and transfer of imaging technology to laboratory X-ray sources.     

Sensing cellular biochemistry with fluorescent chemical–genetic hybrids

Fluorescent biosensors are powerful tools for the detection of biochemical events inside cells with high spatiotemporal resolution. Biosensors based on fluorescent proteins often suffer from issues with photostability and brightness. On the other hand, hybrid, chemical–genetic systems present unique opportunities to combine the strengths of synthetic, organic chemistry with biological macromolecules to generate exquisitely tailored semisynthetic sensors.     

CT与MRI对肝硬化背景下小肝癌检出率的比较

目的:分析比较CT与MR对肝硬化背景下小肝癌检出情况,探究CT与MR在肝硬化背景下小肝癌的诊断价值。方法:选择2010年6月~2015年6月期间,我院收治确诊为肝硬化背景下小肝癌患者91例为研究对象,病理及临床相关方法确诊102个病灶,其中小肝癌69个和微小肝癌33个,患者均在不同时期或序列下行多排螺旋CT与MRI检查,分析比较两者对小肝癌和微小肝癌的检出率。结果:多排螺旋CT检查发现肝癌小病灶91个,其中66个小肝癌,25个微小肝癌;MRI检查发现95个病灶,小肝癌67个,微小肝癌28个;69个小肝癌病灶,检出率最高的为CT动脉期(92.75%)与LAVA动脉期(92.75%),检出率最低的为CT平扫(76.81%);33个微小肝癌病灶,检出率最高为LAVA动脉期(75.76%),检出率最低的为LAVA平衡期(36.36%);CT平扫、门静脉期、动脉期、平衡期、MRI-IN-PHASE、LAVA平衡期、LAVA平扫对小肝癌的检出率显著高于对微小肝癌的检出率(P0.05);CT对小肝癌的检出率显著高于微小肝癌的检出率(P0.05),MRI对小肝癌与微小肝癌的检出率无显著差异(P0.05);MRI与CT对小肝癌的检出率不存在差异(P0.05),但MRI对微小肝癌的检出率显著高于CT(P0.05)。结论:MRI-LAVA的动脉期序列对小肝癌病灶与微小肝癌病灶的检出率最高;CT与MRI在对小肝癌的检出率不存在差异,但MRI对微小肝癌的检出具有更明显的优势。     

Telomere Recognition and Assembly Mechanism of Mammalian Shelterin

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Somatic and Dendritic Encoding of Spatial Variables in Retrosplenial Cortex Differs during 2D Navigation

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Comparison of label-free and GFP multiphoton imaging of hair follicle-associated pluripotent (HAP) stem cells in mouse whiskers

Hair-follicle-associated pluripotent (HAP) stem cells can differentiate into many cell types, including neurons and heart muscle cells, and have been shown to repair peripheral nerves and the spinal cord in mice. HAP stem cells can be obtained from each individual patient for regenerative medicine which overcomes problems with immune rejection. Previously, we have demonstrated that genetically-encoded protein markers such as GFP in transgenic mice can be used to visualize HAP stem cells in vivo by multiphoton tomography. Detection and visualization of stem cells in vivo without exogenous labels such as GFP would be important for human application. In the present report, we demonstrate label-free visualization of hair follicle stem cells in mouse whiskers by multiphoton tomography due to the intrinsic fluorophores such as NAD(P)H/flavins. We compared multiphoton tomography of GFP-labeled HAP stem cells and unlabeled stem cells in isolated mouse whiskers. We show that observation of HAP stem cells by label-free multiphoton tomography is comparable to detection using GFP-labeled stem cells. The results described here have important implications for detection and isolation of human HAP stem cells for regenerative medicine.     

99mTc标记BmK CT及其胶质瘤荷瘤裸鼠的SPECT成像研究

目的:通过放射性核素~(99m)Tc标记BmK CT多肽制备靶向胶质瘤的显像剂,探讨~(99m)?Tc-BmK CT用于胶质瘤显像的可行性。方法:采用BmK CT多肽游离的氨基与DTPA酸酐反应得到BmK CT-DTPA,经99m Tc标记后通过柱层析分离纯化制备~(99m)?Tc-BmK CT。测定标记物在PBS溶液和血清中不同时间点放射性化学纯度,评价BmK CT-~(99m)?Tc体外稳定性。新西兰白兔耳缘静脉注射~(99m)Tc-BmK CT进行SPECT显像,观察不同时间点体内的放射性分布。皮下胶质瘤裸鼠经尾静脉注射~(99m)Tc-BmK CT,观察不同时间点肿瘤的摄取情况;注射后4 h处死裸鼠,分离肿瘤和主要器官进行离体SPECT显像,并用勾画感兴趣区法分析相对放射性计数。结果:~(99m)Tc标记BmK CT多肽标记率大于80%,经柱层析分离纯化后放射性化学纯度大于99%。标记物在PBS和血清稳定性良好,6 h内放射性化学纯度均大于95%,12 h内放射性化学纯度大于90%。正常白兔SPECT显像表明~(99m)Tc-BmK CT主要浓聚在肝脏、脾脏和肾脏,软组织持续显影微弱,甲状腺区及胃肠未见核素浓聚;显像剂主要通过泌尿系统排泄,24 h肾脏与肝脏显影接近。胶质瘤裸鼠SPECT显像表明,注射后4 h肿瘤显像清楚,ROI分析结果显示肿瘤/肌肉比4.26±0.25,标记物在肿瘤内代谢缓慢,8 h肿瘤部位仍有较高摄取。结论:本研究成功制备了~(99m)Tc标记BmK CT多肽,标记物主要被肝、脾和肾摄取,经泌尿系统排泄;~(99m)Tc-BmK CT能够在皮下胶质瘤中浓聚,注射后4 h肿瘤显影清晰,瘤内代谢缓慢,有潜力成为一种新型胶质瘤分子探针。     

Prefrontal deep projection neurons enable cognitive flexibility via persistent feedback monitoring

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