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分析血脑屏障:医学成像在研究和临床实践中的益处。

Analyzing the blood-brain barrier: the benefits of medical imaging in research and clinical practice.

作者信息

Chassidim Yoash, Vazana Udi, Prager Ofer, Veksler Ronel, Bar-Klein Guy, Schoknecht Karl, Fassler Michael, Lublinsky Svetlana, Shelef Ilan

机构信息

Departments of Physiology & Cell Biology, Cognitive and Brain Sciences, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

Department of Neurophysiology, Charite University of Medicine, Berlin, Germany.

出版信息

Semin Cell Dev Biol. 2015 Feb;38:43-52. doi: 10.1016/j.semcdb.2014.11.007. Epub 2014 Nov 29.

Abstract

A dysfunctional BBB is a common feature in a variety of brain disorders, a fact stressing the need for diagnostic tools designed to assess brain vessels' permeability in space and time. Biological research has benefited over the years various means to analyze BBB integrity. The use of biomarkers for improper BBB functionality is abundant. Systemic administration of BBB impermeable tracers can both visualize brain regions characterized by BBB impairment, as well as lead to its quantification. Additionally, locating molecular, physiological content in regions from which it is restricted under normal BBB functionality undoubtedly indicates brain pathology-related BBB disruption. However, in-depth research into the BBB's phenotype demands higher analytical complexity than functional vs. pathological BBB; criteria which biomarker based BBB permeability analyses do not meet. The involvement of accurate and engineering sciences in recent brain research, has led to improvements in the field, in the form of more accurate, sensitive imaging-based methods. Improvements in the spatiotemporal resolution of many imaging modalities and in image processing techniques, make up for the inadequacies of biomarker based analyses. In pre-clinical research, imaging approaches involving invasive procedures, enable microscopic evaluation of BBB integrity, and benefit high levels of sensitivity and accuracy. However, invasive techniques may alter normal physiological function, thus generating a modality-based impact on vessel's permeability, which needs to be corrected for. Non-invasive approaches do not affect proper functionality of the inspected system, but lack in spatiotemporal resolution. Nevertheless, the benefit of medical imaging, even in pre-clinical phases, outweighs its disadvantages. The innovations in pre-clinical imaging and the development of novel processing techniques, have led to their implementation in clinical use as well. Specialized analyses of vessels' permeability add valuable information to standard anatomical inspections which do not take the latter into consideration.

摘要

血脑屏障功能失调是多种脑部疾病的常见特征,这一事实凸显了需要设计能够在空间和时间上评估脑血管通透性的诊断工具。多年来,生物学研究受益于各种分析血脑屏障完整性的方法。用于检测血脑屏障功能异常的生物标志物种类繁多。向体内注射不能透过血脑屏障的示踪剂,既可以使存在血脑屏障损伤的脑区可视化,也可以对其进行定量分析。此外,在正常血脑屏障功能下受限制的区域中定位分子、生理成分,无疑表明了与脑部病理相关的血脑屏障破坏。然而,对血脑屏障表型的深入研究需要比功能性血脑屏障与病理性血脑屏障更高的分析复杂性;基于生物标志物的血脑屏障通透性分析无法满足这些标准。近期脑科学研究中精确科学和工程科学的参与,带来了该领域的进步,表现为更精确、基于成像的敏感方法。许多成像模式的时空分辨率以及图像处理技术的改进,弥补了基于生物标志物分析的不足。在临床前研究中,涉及侵入性操作的成像方法能够对血脑屏障完整性进行微观评估,具有很高的灵敏度和准确性。然而,侵入性技术可能会改变正常生理功能,从而对血管通透性产生基于模式的影响,需要对此进行校正。非侵入性方法不会影响被检查系统的正常功能,但缺乏时空分辨率。尽管如此,医学成像的益处,即使在临床前阶段,也超过了其缺点。临床前成像的创新和新型处理技术的发展,也使其得以应用于临床。对血管通透性的专门分析为不考虑后者的标准解剖检查增添了有价值的信息。

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