Kiviniemi Vesa, Korhonen Vesa, Kortelainen Jukka, Rytky Seppo, Keinänen Tuija, Tuovinen Timo, Isokangas Matti, Sonkajärvi Eila, Siniluoto Topi, Nikkinen Juha, Alahuhta Seppo, Tervonen Osmo, Turpeenniemi-Hujanen Taina, Myllylä Teemu, Kuittinen Outi, Voipio Juha
Department of Diagnostic Radiology, Medical Research Center (MRC), Oulu University Hospital, Oulu, Finland.
Oulu Functional NeuroImaging Group, Research Unit of Medical Imaging, Physics and Technology, the Faculty of Medicine, University of Oulu, Oulu, Finland.
PLoS One. 2017 Mar 20;12(3):e0174072. doi: 10.1371/journal.pone.0174072. eCollection 2017.
Chemotherapy aided by opening of the blood-brain barrier with intra-arterial infusion of hyperosmolar mannitol improves the outcome in primary central nervous system lymphoma. Proper opening of the blood-brain barrier is crucial for the treatment, yet there are no means available for its real-time monitoring. The intact blood-brain barrier maintains a mV-level electrical potential difference between blood and brain tissue, giving rise to a measurable electrical signal at the scalp. Therefore, we used direct-current electroencephalography (DC-EEG) to characterize the spatiotemporal behavior of scalp-recorded slow electrical signals during blood-brain barrier opening. Nine anesthetized patients receiving chemotherapy were monitored continuously during 47 blood-brain barrier openings induced by carotid or vertebral artery mannitol infusion. Left or right carotid artery mannitol infusion generated a strongly lateralized DC-EEG response that began with a 2 min negative shift of up to 2000 μV followed by a positive shift lasting up to 20 min above the infused carotid artery territory, whereas contralateral responses were of opposite polarity. Vertebral artery mannitol infusion gave rise to a minimally lateralized and more uniformly distributed slow negative response with a posterior-frontal gradient. Simultaneously performed near-infrared spectroscopy detected a multiphasic response beginning with mannitol-bolus induced dilution of blood and ending in a prolonged increase in the oxy/deoxyhemoglobin ratio. The pronounced DC-EEG shifts are readily accounted for by opening and sealing of the blood-brain barrier. These data show that DC-EEG is a promising real-time monitoring tool for blood-brain barrier disruption augmented drug delivery.
通过动脉内输注高渗甘露醇打开血脑屏障辅助化疗可改善原发性中枢神经系统淋巴瘤的治疗效果。血脑屏障的适当打开对治疗至关重要，但尚无实时监测手段。完整的血脑屏障维持着血液与脑组织之间毫伏级的电势差，从而在头皮产生可测量的电信号。因此，我们使用直流电脑电图（DC-EEG）来表征血脑屏障打开期间头皮记录的慢电信号的时空行为。在通过颈动脉或椎动脉输注甘露醇诱导的47次血脑屏障打开过程中，对9名接受化疗的麻醉患者进行了连续监测。左或右颈动脉输注甘露醇产生强烈的偏向性DC-EEG反应，开始为长达2分钟的高达2000μV的负向偏移，随后是在输注侧颈动脉区域上方持续长达20分钟的正向偏移，而对侧反应极性相反。椎动脉输注甘露醇产生最小偏向且分布更均匀的慢负向反应，具有后-前梯度。同时进行的近红外光谱检测到多相反应，开始于甘露醇推注引起的血液稀释，结束于氧合/脱氧血红蛋白比率的长时间增加。明显的DC-EEG偏移很容易通过血脑屏障的打开和封闭来解释。这些数据表明，DC-EEG是一种有前景的用于监测血脑屏障破坏增强药物递送的实时监测工具。
