Grand average DC-EEG and average NIRS traces illustrating characteristic responses evoked by intra-arterial mannitol infusion.

<p>Each DC-EEG trace (upper panels; shaded area indicates values within ±1 SD) was generated by first calculating the mean of five electrode signals and then calculating the grand average of each recording. Mannitol infusion starts at time = 0 and lasts 30 s. DC-EEG responses upon carotid or vertebral artery mannitol infusion are shown using the common average montage (CA), however the responses to vertebral artery infusion are shown also after re-referencing to the distant ECG reference electrode (ECG; upper panel on the right). Bottom graphs show corresponding average oxy- and deoxyhemoglobin NIRS traces in arbitrary units (a.u.; ±1 SD). The number of NIRS recordings is less than that of DC-EEG, but all NIRS recordings are paralleled by simultaneously recorded DC-EEG data included in the upper graphs. Left (n = 13) and right (n = 16) carotid artery infusions induce a negative DC-EEG shift in electrodes above the treated arterial territory, which outlasts the infusion and is followed by a slower shift of opposite polarity. Contralateral posterior electrodes record a response that is qualitatively similar but reversed in polarity. A clear fall in the NIRS signals is seen during left (n = 8) and right (n = 8) carotid artery infusions, followed by a pronounced rise in HbO and a transient partial recovery of Hb after which Hb settles down on a level below the original baseline and HbO decreases slowly but does not fully recover. Vertebral artery infusions show a fronto-occipital DC-EEG potential shift (n = 18) without a lateralized effect, as expected. Re-referencing to the distant ECG reference electrode reveals that there is a negative shift throughout the entire scalp. The early transient shifts in the NIRS signals shown for vertebral artery infusions (n = 7) are more delayed and have much smaller amplitudes because NIRS was always measured on the forehead, i.e. they show responses generated in a non-infused brain area.</p

Region of interest analysis of the cbCT following i.a. multi-chemotherapy.

<p>Selected major territories are described using white ellipses marked by numbers 1-5 bilaterally (a). HU-values calculated from these areas and mean of them (named as ‘all’) are illustrated by treated artery; right carotis (b), left carotis (c) and vertebralis (d). In every case right (blue) and left (red) side are separated and also SD bars are represented.</p

Typical spatial distribution of the DC-EEG responses.

<p>Specimen traces recorded during the BBBD procedure with left (a), right (b) and vertebral (c, d) artery infusion of mannitol. On average, carotid artery infusion evoked responses of the kind shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0174072#pone.0174072.g001" target="_blank">Fig 1</a> in electrodes of the 10-10 system located anterior to vertex on the side of the infusion, whereas posterior electrodes on the opposite side showed rather similar responses with opposite polarity (common average reference montage). Therefore, the four subsets of five electrodes shown here were chosen for further characterization of the signals. When using the common average montage, responses evoked by vertebral artery mannitol infusion (c) were strikingly small in amplitude compared to those seen upon carotid artery infusion, suggesting in the former case the presence of a uniformly distributed signal component that cancels out in a differential recording against the common average reference. A reference point distant to the electrodes of the 10-10 system was provided by the ECG reference electrode, and indeed, re-referencing to the low-pass filtered ECG reference electrode signal revealed a prolonged negative shift (d).</p

Spatiotemporal analysis of the DC-EEG data illustrated using heat maps.

<p>(a) Thiopental given at time 0 min generates a weak response in 3 min with slightly positive values along the midline and negative values at lateral electrode locations. Re-referencing the common average (CA) referenced data to the ECG reference renders the entire response slightly more negative. Data from all recordings (47 infusions) were pooled because thiopental was applied intravenously. (b) Temporal evolvement of the spatial distribution of DC-EEG responses to mannitol infusion shown using logarithmically increasing time intervals. The signal level preceding mannitol infusion (0 min) defines the zero level for the average responses calculated for 13 left carotid artery, 16 right carotid artery and 18 vertebral artery infusions. All data are shown using the CA reference montage. In addition, the bottom row of heat plots shows vertebral artery infusion data after re-referencing to the ECG reference.</p

Characteristic EEG and NIRS responses seen during the BBBD procedure.

<p>Specimen traces illustrating simultaneous changes in raw EEG (upper graph) and NIRS signals (lower graph) during right carotid intra-arterial (i.a.) mannitol infusion. Deepening anesthesia with intravenous (i.v.) thiopental bolus (marked with an arrow) induces a baseline shift and suppresses activity at conventional EEG frequencies (insets a to d show 15 s sample traces on a 6 times expanded vertical scale) prior to mannitol infusion. Mannitol infusion (2nd arrow) then induces a multi-phasic potential response that begins with a pronounced negative shift reaching nearly -2000 μV in less than 1 min. The negative peak is followed by a slow potential descent below the pre-bolus level. Note the emerging burst-suppression (c) and subsequent faster EEG activity (d) similar to baseline state (a) as the thiopental effect slowly dissipates over 15 minutes. The simultaneously recorded NIRS graph shows first how the i.v. thiopental bolus produces a minor elevation to both NIRS HbO and Hb signals (red solid line and blue dashed line, respectively). When the 30 s i.a. mannitol infusion starts both NIRS signals plummet due to dilution of blood and they start to increase towards the original levels after the infusion. Subsequently, HbO rises above the baseline and stays there over the 15 minutes. On the other hand, Hb approaches the baseline level but soon starts to fall again obtaining a steady level clearly below the original baseline.</p