Fig. 6

In-vivo measurement of brain tissue-displacement suggests that the brain tissue can deform because of pressure changes in the PVS. a Schematic of a thin skulled window. Mice implanted with a thinned-skull window (PoRTS window [49]) were imaged under a two-photon laser scanning microscope (2PLSM). The mice were head-fixed and allowed to run voluntarily on a spherical treadmill. b Experimental setup for two-photon microscopy. Mice were head-fixed and placed on a spherical treadmill. c Schematic of the fluorescent elements in the brain parenchyma (left) surrounding a penetrating arteriole and the expected 2-D images under a 2PLSM (right). A retro-orbital injection of Texas red dye conjugated dextran (40 kDa, 2.5% w/v) makes the vessel lumen fluorescent. The yellow fluorescent protein is expressed by a sparse subset of neuronal processes. d A schematic of the brain tissue deformations expected when pressure changes in the PVS do not deform the brain until PVS collapse. The position of the vessel wall and the PVS are shown on the left. When the arteriole dilates, the brain tissue would not deform until the PVS completely collapses (middle). After the PVS has collapsed completely, the brain tissue would start deforming(right). e Flow chart of the mechanism of brain tissue deformation in a “non-compliant brain” model. f The expected radial displacement in the brain tissue in response to arteriolar dilation when deformability of the brain is initially ignored. The brain tissue does not deform until the PVS has completely collapsed. Note that the expected values are based on the displacement used for our simulations and actual values may vary. g A schematic of the expected brain tissue deformation from a fluid–structure interaction model. Here the pressure changes in the PVS cause the brain tissue to deform. h Flow chart of the mechanism of brain tissue deformation in a fluid–structure interaction model. i The expected radial displacement in the brain tissue in response to arteriolar dilation in the fluid–structure interaction model (also see Additional file 13: Fig S6). Note that the expected values are based on the displacement used for our simulations and actual values may vary. j Median frame of the 2D image collected during in vivo imaging. Example image of penetrating arteriole (magenta) and YFP expressing neurons(green). The arrows show the direction of the displacement measured at the location indicated by the tail of the arrow. k, l Projection in time along a line running through the arrows 1 and 2 respectively shown in (j). The images show that when the vessel dilates (indicated by a widening of the vessel in magenta), there is a corresponding radially-outward deformation in the brain tissue (indicated by the movement of the green line). Time moves forward in the in the vertically downward direction in both images. m The calculated radial displacement in the brain tissue in response to changes in arteriolar radius. The data suggests that the brain tissue deforms due to pressure changes in the PVS before the PVS completely collapses. n The average (7 mice, 21 vessels) peak-normalized impulse response of the radial displacement of the arteriolar wall (magenta) compared to the average peak-normalized impulse response of the radial displacement in the brain tissue (only one data point per vessel was used for this calculation). The data shows that there is no delay between displacement of arteriolar wall and the tissue, suggesting that the brain tissue deforms due to pressure changes in the PVS as predicted by the fluid–structure interaction model