Real-time monitoring of human blood-brain barrier disruption.
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.
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.
Vesa
V
Kiviniemi
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.
Vesa
V
Korhonen
Physiological Signal Analysis Team, Center for Machine Vision and Signal Analysis, MRC Oulu, University of Oulu, Oulu, Finland.|Department of Clinical Neurophysiology, MRC, Oulu University Hospital, Oulu, Finland.
Jukka
J
Kortelainen
Department of Clinical Neurophysiology, MRC, Oulu University Hospital, Oulu, Finland.
Seppo
S
Rytky
Oulu Functional NeuroImaging Group, Research Unit of Medical Imaging, Physics and Technology, the Faculty of Medicine, University of Oulu, Oulu, Finland.|Department of Clinical Neurophysiology, MRC, Oulu University Hospital, Oulu, Finland.
Tuija
T
Keinänen
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.
Timo
T
Tuovinen
Department of Diagnostic Radiology, Medical Research Center (MRC), Oulu University Hospital, Oulu, Finland.
Matti
M
Isokangas
Department of Anaesthesiology, MRC, Oulu University Hospital, Oulu, Finland.
Eila
E
Sonkajärvi
Department of Diagnostic Radiology, Medical Research Center (MRC), Oulu University Hospital, Oulu, Finland.
Topi
T
Siniluoto
Department of Oncology, MRC, Oulu University Hospital, Oulu, Finland.
Juha
J
Nikkinen
Department of Anaesthesiology, MRC, Oulu University Hospital, Oulu, Finland.
Seppo
S
Alahuhta
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.
Osmo
O
Tervonen
Department of Oncology, MRC, Oulu University Hospital, Oulu, Finland.
Taina
T
Turpeenniemi-Hujanen
Health & Wellness Measurement Group, Optoelectronics and Measurement Techniques Unit, University of Oulu, Oulu, Finland.
Teemu
T
Myllylä
Department of Oncology, MRC, Oulu University Hospital, Oulu, Finland.
Outi
O
Kuittinen
Department of Biosciences, University of Helsinki, Helsinki, Finland.
Juha
J
Voipio
D000328:Adult; D000368:Aged; D000758:Anesthesia; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology*; D002199:Capillary Permeability / Q000187:drug effects* / Q000502:physiology*; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D016543:Central Nervous System Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology; D004569:Electroencephalography / Q000379:methods; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007261:Infusions, Intra-Arterial; D008223:Lymphoma / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D008353:Mannitol / Q000008:administration & dosage; D008875:Middle Aged; D064926:Neurophysiological Monitoring / Q000379:methods; D010108:Oxyhemoglobins / Q000378:metabolism; D019265:Spectroscopy, Near-Infrared; D014711:Vertebral Artery / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D055815:Young Adult
D000970:Antineoplastic Agents; D006454:Hemoglobins; D010108:Oxyhemoglobins; D008353:Mannitol; C100003:deoxyhemoglobin