Large field-of-view movement-compensated intrinsic optical signal imaging for the characterization of the haemodynamic response to spreading depolarizations in large gyrencephalic brains

Abstract

Haemodynamic responses to spreading depolarizations (SDs) have an important role during the development of secondary brain damage. Characterization of the haemodynamic responses in larger brains, however, is difficult due to movement artefacts. Intrinsic optical signal (IOS) imaging, laser speckle flowmetry (LSF) and electrocorticography were performed in different configurations in three groups of in total 18 swine. SDs were elicited by topical application of KCl or occurred spontaneously after middle cerebral artery occlusion. Movement artefacts in IOS were compensated by an elastic registration algorithm during post-processing. Using movement-compensated IOS, we were able to differentiate between four components of optical changes, corresponding closely with haemodynamic variations measured by LSF. Compared with ECoG and LSF, our setup provides higher spatial and temporal resolution, as well as a better signal-to-noise ratio. Using IOS alone, we could identify the different zones of infarction in a large gyrencephalic middle cerebral artery occlusion pig model. We strongly suggest movement-compensated IOS for the investigation of the role of haemodynamic responses to SDs during the development of secondary brain damage and in particular to examine the effect of potential therapeutic interventions in gyrencephalic brains.

Heterogeneous propagation of spreading depolarizations in the lissencephalic and gyrencephalic brain

“…Those anatomical blocks are determined mainly by anatomical structures, such as vessels and sulci, or by hypoperfused or dead tissue, such as after middle cerebral artery occlusion. 15 Moreover, functional blocks can exist. They are determined by temporary refractory periods.…”

Simulation of spreading depolarization trajectories in cerebral cortex: Correlation of velocity and susceptibility in patients with aneurysmal subarachnoid hemorrhage

“…Such double peak DC shifts could be longer than 4 min, though they might not indicate local energy compromise. In the context of branching, we would like to refer previous videos of SDs in the gyrencephalic brain of swine in which this is visualized using IOS imaging ( Santos et al, 2014 , Scholl et al, 2017 ). Neuroimaging excluded in this case that E1, E2 or E3 sampled from two adjacent gyri.…”

“…These findings render it unlikely that changes in SD velocity are useful as an early warning sign of impending ischemia in the individual patient. However, trajectory reconstruction of those SDs failed significantly more often, according to the notion based on animal experiments that their propagation paths can become exceedingly complex ( Bere et al, 2014b , Nakamura et al, 2010 , Scholl et al, 2017 ). In concert with other parameters such as the SD frequency and the durations of depressions and DC shifts ( Dreier et al, 2017 ), this could possibly be used as a tool to monitor alarming development in the individual patient.…”

“…Cycling of SD was moreover observed around electrically stimulated areas, epileptic foci or ischemic zones ( Koroleva and Bures, 1979 , Nakamura et al, 2010 ). It has been advanced as an explanation for the periodicity in clusters of SDs ( Nakamura et al, 2010 , Santos et al, 2017 , Scholl et al, 2017 ).…”

“…In order to reconstruct the potential SD trajectories and velocities based on the TOADs, we chose to restrict the trajectories to the ones for which the following assumptions held: (1) following the typically observed pattern in animal experiments ( Dahlem and Müller, 2004 , Kaufmann et al, 2017 , Kneer et al, 2014 , Santos et al, 2014 , Scholl et al, 2017 ), the shape of the SD wave-front can be approximated by a circular arc that propagates tangentially along the discretized brain surface; (2) the radius of this arc is fairly constant; (3) the velocity of the arc's center is fairly constant; (4) the SD center travels on geodesics (shortest paths) from the point where it reaches one electrode to the point at which it reaches the next electrode in temporal succession.…”