Direct imaging of macrovascular and microvascular contributions to BOLD fMRI in layers IV-V of the rat whisker-barrel cortex - PubMed (original) (raw)
Direct imaging of macrovascular and microvascular contributions to BOLD fMRI in layers IV-V of the rat whisker-barrel cortex
Xin Yu et al. Neuroimage. 2012.
Abstract
The spatiotemporal characteristics of the hemodynamic response to increased neural activity were investigated at the level of individual intracortical vessels using BOLD-fMRI in a well-established rodent model of somatosensory stimulation at 11.7 T. Functional maps of the rat barrel cortex were obtained at 150 × 150 × 500 μm spatial resolution every 200 ms. The high spatial resolution allowed separation of active voxels into those containing intracortical macro vessels, mainly vein/venules (referred to as macrovasculature), and those enriched with arteries/capillaries and small venules (referred to as microvasculature) since the macro vessel can be readily mapped due to the fast T2 decay of blood at 11.7 T. The earliest BOLD response was observed within layers IV-V by 0.8s following stimulation and encompassed mainly the voxels containing the microvasculature and some confined macrovasculature voxels. By 1.2s, the BOLD signal propagated to the macrovasculature voxels where the peak BOLD signal was 2-3 times higher than that of the microvasculature voxels. The BOLD response propagated in individual venules/veins far from neuronal sources at later times. This was also observed in layers IV-V of the barrel cortex after specific stimulation of separated whisker rows. These results directly visualized that the earliest hemodynamic changes to increased neural activity occur mainly in the microvasculature and spread toward the macrovasculature. However, at peak response, the BOLD signal is dominated by penetrating venules even at layers IV-V of the cortex.
Copyright © 2011 Elsevier Inc. All rights reserved.
Figures
Figure 1
The spatial pattern of hemodynamic response in the coronal EPI slice. A coronal EPI slice covering the barrel cortex was acquired in rats with bilateral whisker pad stimulation. The intracortical macro vessels (white arrowhead) are visualized in the averaged 2D EPI image (A) and the uniformity corrected image (B). The spatial pattern of BOLD response at every 200ms is represented in gray-scale beta maps(C). BOLD responses first appeared at 0.8–1.0s after stimulation (red arrow) and peaked at macro vessels (bright stripes) in the later time. The undershoot of BOLD responses appeared at 8s after stimulation (green arrow). BOLD responses in a single macro vessel penetrating the white matter appeared at 1.6s after stimulation (yellow arrow). BOLD responses in macro vessels penetrating the white matter were observed in another two rats (D, yellow arrow).
Figure 2
The hemodynamic response of representative single voxels. One voxel is located in the center of a macro vessel (red) and the other in the tissue (blue) surrounding the macro vessel at Layer IV–V of the barrel cortex (A, EPI). Gray-scale beta maps at 0.8s and 1.4s are shown to highlight the early BOLD signal response of the two voxels (A). The time-course of BOLD response (4s on / 16s off, 8 epochs) and the HRF of the two voxels are shown in B and C. The baseline signal intensity of vessel voxel is much lower than that of the tissue voxel (B). In the HRF, the BOLD signal of the tissue voxel (blue) is higher than that of the vessel voxel at 0.8s after stimulation, which becomes opposite at 1.4s after stimulation (C).
Figure 3
The spatial pattern of BOLD response from 0.8 to 1.4s from multiple subjects. Intracortical macro vessels are highlighted in EPI images (A, white arrowhead). Beta maps at 0.8, 1.0, 1.2, and 1.4s after stimulation are shown in B. C is the color-coded onset delay map. D is the averaged HRF of macro vessel (red) and tissue (blue) ROIs(inset). E is the enlarged figure of the BOLD response from 0s to 1.6s, showing the higher BOLD signal in tissue ROIs than the macro vessel ROI at 0.8s after stimulation (* mean paired t-test, p=0.009, n=7, error bar is the standard deviation of 7 rats). Mean beta values of tissue and macro vessel ROIs at 0.8s from individual rats are shown in the inset.
Figure 4
Layer-specific group ROI analysis of HRF. A is the HRF of ROIs at different cortical layers (I–III in purple, IV–V in yellow, VI in green, inset). The HRF from 0 to 1.4s after stimulation is shown in the enlarged figure (B, error bar is the standard deviation of 7 rats). Mean beta values at 0.8s from individual animals are shown across different layers (C, n=7).
Figure 5
The spatial pattern of BOLD response in Layer IV–V barrel cortex. The horizontal EPI slice was positioned to cover the layer IV–V of the barrel cortex (A). In the EPI image, the intracortical macro vessel can be visualized as dark dots (B). The HRF of representative single voxels on macro vessel (B, red circle) and adjacent tissue (B, blue circle) is shown in C with the scaled time-courses (inset, dotted line). D shows beta maps at every 200ms from 0s to 1.6s after stimulation with macro vessels highlighted by red squares (D).
Figure 6
Group analysis of the early BOLD response in Layer IV–V barrel cortex. A is EPI images across Layer IV–V barrel cortex with uniformity corrected images to show the macro vessels in dotted blue circle. Enlarged beta maps at 0.8s and 1.4s after stimulation are shown to examine the BOLD response in macro vessels (B). C is the overlapped macro vessel (green) with beta maps with active voxels colored in red. The activated macro vessel voxels appeared in yellow (C). D shows the HRF of macro vessel (red) and tissue (blue) ROIs (inset, representative ROIs from rat #2). The enlarged 0–1.6s HFR shows the higher BOLD signal in tissue ROIs than the macro vessel ROI at 0.8s after stimulation (D, * means paired t-test, p=0.0088, n=6, error bar is the standard deviation of 6 rats). Mean beta values of tissue and macro vessel ROIs at 0.8s from individual rats are shown in the inset
Figure 7
Mapping the whisker row-B and row-D barrel areas. The orientation of whisker row-B and row-D is shown in the schematic drawing of whisker maps in the barrel cortex and the EPI slice (A). Gray-scale beta maps of row-B and row-D were derived from the linear regression of the total period of the hemodynamic response (B). The two beta maps were overlapped (row-B in red, row-D in green, overlapped active voxels in yellow) and a macro vessel in the overlapped area is highlighted by a red rectangle. Two ROIs were drawn on the centroid of active barrel area for row-B and row-D (B, blue rectangle) to match the macro vessel ROI. The BOLD signal changes of the three ROIs (error bar is the standard deviation of 6 voxels of each ROI) are shown in the lower panel of B. Color-coded beta maps for row-B (C, right) and row-D (C, left) are shown at every 0.8s after stimulation. The macro vessel draining both row-B and row-D barrel area is highlighted by red arrowhead (C).
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