University of Oulu

Kiviniemi V, Korhonen V, Kortelainen J, Rytky S, Keinänen T, Tuovinen T, et al. (2017) Real-time monitoring of human blood-brain barrier disruption. PLoS ONE 12(3): e0174072.

Real-time monitoring of human blood-brain barrier disruption

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Author: Kiviniemi, Vesa1,2; Korhonen, Vesa1,2; Kortelainen, Jukka3,4;
Organizations: 1Department of Diagnostic Radiology, Medical Research Center (MRC), Oulu University Hospital, Oulu, Finland, Oulu
2Oulu Functional NeuroImaging group, Research Unit of Medical Imaging, Physics and Technology, the Faculty of Medicine, University of Oulu, Oulu, Finland
3Physiological Signal Analysis Team, Center for Machine Vision and Signal Analysis, MRC Oulu, University of Oulu, Oulu, Finland
4Department of Clinical Neurophysiology, MRC, Oulu University Hospital, Oulu, Finland
5Department of Anaesthesiology, MRC, Oulu University Hospital, Oulu, Finland
6Department of Oncology, MRC, Oulu University Hospital, Oulu, Finland
7Health & Wellness Measurement Group, Optoelectronics and Measurement Techniques Unit, University of Oulu, Oulu, Finland
8Department of Biosciences, University of Helsinki, Helsinki, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.5 MB)
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Language: English
Published: Public Library of Science, 2017
Publish Date: 2017-05-29


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.

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Series: PLoS one
ISSN: 1932-6203
ISSN-E: 1932-6203
ISSN-L: 1932-6203
Volume: 12
Issue: 3
Article number: e0174072
DOI: 10.1371/journal.pone.0174072
Type of Publication: A1 Journal article – refereed
Field of Science: 3112 Neurosciences
Funding: CSTI/SHOK Salwe WP302 grant (VKi), JAES grant (VKi), MRC Oulu DP-grant (VKo), Oulu University Scholarship Foundation (VKo), Tauno Tönning Foundation (VKo) and Academy of Finland grant # 275352 (VKi) is cordially acknowledged in this study.
Academy of Finland Grant Number: 275352
Detailed Information: 275352 (Academy of Finland Funding decision)
Dataset Reference: A fully anonymized minimal data set, as defined by PLOS, can be made available upon request. Due to ethical restrictions related to protecting individual patients’ privacy and Finnish legislation, data requests may be subject to individual consent and/or evaluation by the Ethical Committee of Northern Ostrobothnia Hospital District in Oulu, Finland. Data requests should be directed to the Research Coordinator, Esa Liukkonen, Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland, E-mail:
Copyright information: © 2017 Kiviniemi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.