In vivo monitoring blood-brain barrier permeability using spectral imaging through optical clearing skull window.,Journal of Biophotonics

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In vivo monitoring blood-brain barrier permeability using spectral imaging through optical clearing skull window.
Journal of Biophotonics ( IF 2.0 ) Pub Date : 2018-12-20 , DOI: 10.1002/jbio.201800330
Wei Feng _{1,

2} , Chao Zhang _{1,

2} , Tingting Yu _{1,

2} , Oxana Semyachkina-Glushkovskaya ₃ , Dan Zhu _{1,

2}

Affiliation

The blood‐brain barrier (BBB) plays a key role in the health of the central nervous system. Opening the BBB is very important for drug delivery to brain tissues to enhance the therapeutic effect on brain diseases. It is necessary to in vivo monitor the BBB permeability for assessing drug release with high resolution; however, an effective method is lacking. In this work, we developed a new method that combined spectral imaging with an optical clearing skull window to in vivo dynamically monitor BBB opening caused by 5‐aminolevulinic acid (5‐ALA)‐mediated photodynamic therapy (PDT), in which the Evans blue dye (EBd) acted as an indicator of the BBB permeability. Using this method, we effectively monitored the cerebrovascular EBd leakage process. Moreover, the analysis of changes in the vascular and extravascular EBd concentrations demonstrated that the PDT‐induced BBB opening exhibited spatiotemporal differences in the cortex. This spectral imaging method based on the optical clearing skull window provides a low‐cost and simply operated tool for in vivo monitoring BBB opening process. This has a high potential for the visualization of drug delivery to the central nervous system. Thus, it is of tremendous significance in brain disease therapy. Monitoring the changes in PDT‐induced BBB permeability by evaluating the EBd concentration using an optical clearing skull window. (A) Entire brains and coronal sections following treatment of PDT with/without an optical clearing skull window after injection of EBd. (B) Typical EBd distribution maps before and after laser irradiation captured by the spectral imaging method. (Colorbar represents the EBd concentration).

中文翻译：

使用通过光学清除颅骨窗的光谱成像在体内监测血脑屏障通透性。

血脑屏障（BBB）在中枢神经系统的健康中起关键作用。打开血脑屏障对于将药物输送到脑组织以增强对脑疾病的治疗作用非常重要。有必要在体内监测血脑屏障通透性，以评估药物的高分辨率释放。但是，缺乏有效的方法。在这项工作中，我们开发了一种将光谱成像与光学透明颅骨窗结合起来的新方法，以在体内动态监测由5-氨基乙酰丙酸（5-ALA）介导的光动力疗法（PDT）引起的血脑屏障开放，其中伊文思蓝染料（EBd）充当血脑屏障通透性的指标。使用这种方法，我们有效地监测了脑血管EBd的泄漏过程。而且，血管和血管外EBd浓度变化的分析表明，PDT诱导的BBB开放在皮质中表现出时空差异。这种基于光学透明颅骨窗的光谱成像方法为活体内监测BBB的开放过程提供了一种低成本且操作简单的工具。这对于将药物输送到中枢神经系统的可视化具有很高的潜力。因此，它在脑疾病治疗中具有巨大的意义。通过使用光学透明颅骨窗评估EBd浓度来监测PDT诱导的BBB渗透性的变化。（A）注射EBd后，PDT在有/无光学透明颅骨窗的情况下进行PDT治疗后的整个大脑和冠状切面。（B）通过光谱成像方法捕获的激光辐照前后的典型EBd分布图。（色条表示EBd浓度）。

更新日期：2018-12-20

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