Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology, Wuhan, Hubei, China.
MOE Key Laboratory for Biomedical Photonics, Collaborative Innovation Center for Biomedical Engineering, School of Engineering Sciences, Huazhong University of Science and Technology, Wuhan, Hubei, China.
J Biophotonics. 2019 Apr;12(4):e201800330. doi: 10.1002/jbio.201800330. Epub 2018 Dec 20.
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).
血脑屏障（BBB）在中枢神经系统的健康中起着关键作用。打开 BBB 对于将药物递送到脑组织中以增强对脑部疾病的治疗效果非常重要。有必要通过体内监测 BBB 的通透性，以高分辨率评估药物释放；然而，缺乏有效的方法。在这项工作中，我们开发了一种新的方法，该方法将光谱成像与光学透明颅骨窗相结合，以体内动态监测 5-氨基乙酰丙酸（5-ALA）介导的光动力疗法（PDT）引起的 BBB 开放，其中 Evans 蓝染料（EBd）作为 BBB 通透性的指示剂。使用这种方法，我们有效地监测了脑血管 EBd 泄漏过程。此外，血管内和血管外 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体内监测 BBB 开放过程提供了一种低成本且易于操作的工具。这对于药物递送到中枢神经系统的可视化具有很高的潜力。因此，它在脑部疾病治疗中具有重要意义。通过使用光学透明颅骨窗评估 EBd 浓度来监测 PDT 诱导的 BBB 通透性变化。(A) 在注射 EBd 后，进行 PDT 治疗并用/不用光学透明颅骨窗的整个大脑和冠状切片。(B) 通过光谱成像方法捕获的激光照射前后 EBd 典型分布图谱。（颜色条表示 EBd 浓度）。
