High-resolution structural and functional assessments of cerebral microvasculature using 3D Gas ΔR2*-mMRA

Abstract

The ability to evaluate the cerebral microvascular structure and function is crucial for investigating pathological processes in brain disorders. Previous angiographic methods based on blood oxygen level-dependent (BOLD) contrast offer appropriate visualization of the cerebral vasculature, but these methods remain to be optimized in order to extract more comprehensive information. This study aimed to integrate the advantages of BOLD MRI in both structural and functional vascular assessments. The BOLD contrast was manipulated by a carbogen challenge, and signal changes in gradient-echo images were computed to generate ΔR2* maps. Simultaneously, a functional index representing the regional cerebral blood volume was derived by normalizing the ΔR2* values of a given region to those of vein-filled voxels of the sinus. This method is named 3D gas ΔR2*-mMRA (microscopic MRA). The advantages of using 3D gas ΔR2*-mMRA to observe the microvasculature include the ability to distinguish air-tissue interfaces, a high vessel-to-tissue contrast, and not being affected by damage to the blood-brain barrier. A stroke model was used to demonstrate the ability of 3D gas ΔR2*-mMRA to provide information about poststroke revascularization at 3 days after reperfusion. However, this technique has some limitations that cannot be overcome and hence should be considered when it is applied, such as magnifying vessel sizes and predominantly revealing venous vessels.

Figure 1. The BOLD contrast for the inhalation of different gases.

(A) During air inhalation, the vessels exhibited minimal signal intensities relative to nonvessel brain tissues. (B) During the inhalation of 100% O₂, fewer hypointensities were evident in the vessels. (C) During the inhalation of carbogen, few hypointensities remained. (D) Comparison of signal profiles of the sinus (horizontal bars in A to C) in the various inhalation conditions. The BOLD contrast was highest for air, followed by oxygen and then carbogen.

Figure 2. Demonstration of 3D gas ΔR₂*-mMRA.

(A) 3D high-resolution T₂*WI acquired during the inhalation of air. (B) T₂*WI acquired during the inhalation of carbogen. (C) ΔR₂* map computed from the two T₂*WIs. (D) The reconstructed ΔR₂* maps, which can be viewed flexibly in various planes. (E) A 1-mm-thick axial view revealing the microvasculature. (F) A sagittal view. (G) A horizontal view. The cortical penetrating vessels are readily distinguishable in each view, and subcortical vessels are also identified in the striatum and hippocampus.

Figure 3. 3D gas ΔR₂*-mMRA visualization compared with venous and arterial vessels labeled by latex.

(A) 3D gas ΔR₂*-mMRA identifies the superior sagittal sinus, superior cerebral veins, and transverse sinus on the brain surface. (B) Venous vessels labeled by blue latex. (C) Arterial vessels labeled by red latex. Comparison of A with B and C indicates that 3D gas ΔR₂*-mMRA predominately identifies venous vessels.

Figure 4. Comparison of 3D gas ΔR₂*-mMRA and MR venography.

(A) An axial slice from 3D gas ΔR₂*-mMRA. The cortex and white matter are marked by the rectangles and magnified in C. (B) MR venography with identical geometrical settings and ROIs. (C) 3D gas ΔR₂*-mMRA allows the vessels to be readily distinguished at air–tissue interfaces and along the white matter. The arrow, arrowhead, and double-arrowhead indicate the locations of the external capsule, a vein near external capsule, and a vein at air–tissue interfaces, respectively. (D) In MR venography, the signal dephasing near air–tissue interfaces and white matter obscures the blood vessels.

Figure 5. Comparison of 3D gas ΔR₂*-mMRA and 3D ΔR₂-mMRA.

(A) An axial view from 3D gas ΔR₂*-mMRA. (B) An axial view from 3D ΔR₂-mMRA with identical geometrical settings in the same animal. The four sets of arrows label the vessels identified by both methods at the dorsal and ventral portions of the brain. (C, D, E, F) Line profiles, with the positions of vessels indicated by arrows.

Figure 6. Differences in the characterized microvasculature between 3D gas ΔR₂*-mMRA and 3D ΔR₂-mMRA.

(A) A 2×2 mm² cortical slice in the horizontal plane from the ΔR₂* map of 3D gas ΔR₂*-mMRA. (B) The ΔR₂ map of 3D ΔR₂-mMRA. (C) Magnified view of the region of the ΔR₂* map marked by the square in A showing bright signals representing the through-plane cortical penetrating vessels. (D) The bright signals were smaller but more numerous in the ΔR₂ map. (E) Quantification of the sizes of vessels detected by the two methods. (F) Quantification of the densities of vessels detected by the two methods. Data in E and F are mean and SD values.

Figure 7. 3D gas ΔR₂*-mMRA applied to detect poststroke revascularization at 3 days after reperfusion.

(A) 3D gas ΔR₂*-mMRA shows an increased number of cortical vessels in the lesioned cortex (marked by the rectangle) relative to the unlesioned side. (B) 3D ΔR₂-mMRA reveals a different microvasculatural pattern that is very likely confounded by the extravasation of the contrast agent due to the increased vascular permeability.