Article
Contrast-enhanced MR microangiography (CE-MRA) of cerebral collateralisation during experimental chronic cerebral ischemia
Kontrastmittel-gestützte MR Mikroangiographie der zerebralen Kollateralisierung bei experimenteller chronisch zerebraler Ischämie
Search Medline for
Authors
Published: | May 8, 2019 |
---|
Outline
Text
Objective: Outgrowth of collateral arterioles in the range of 20-50μm in diameter remains one of the most important rescue mechanisms for prevention of hemodynamic stroke. However, robust tools for in vivo assessment of the degree, morphology and dynamics of cerebral arteriogenesis are still lacking. The goal of this study was to develop contrast-enhanced MR microangiography (CE-MRA) as a method to quantify cerebral collateral remodeling during experimental chronic cerebral ischemia in vivo.
Methods: Male C57BL/6 mice underwent permanent unilateral internal carotid artery occlusion (ICAO, n=8) or a sham (n=8) procedures for simulation of chronic cerebral hypoperfusion. 21 days after surgery, a 7T MRI was performed with a cryoprobe. The 1.5-hour protocol consisted of a T2-weighted MRI, CE-MRA (65 μm3resolution) with Ferumoxytol (300 μmol Fe/kg i.v.), and a Dynamic Susceptibility Contrast MRI. In the CE-MRA images, vessel densities were calculated from angiograms by mapping relative cerebral blood volume (rCBV). In order to perform a corresponding histological analysis of the cerebral vasculature, all mice were perfused with 100μL FITC-lectin for either confocal fluorescence microscopy or 3D serial 2-photon tomography. CE-MRA and histology images were then co-registered to the Allen brain atlas.
Results: Co-registration of CE-MRA with fluorescence microscopy showed that vessels as small as 25 μm were directly detectable by CE-MRA. Although an automated CE-MRA vessel counting algorithm was determined non-feasible, a higher CE-MRA contrast signal with corresponding changes of relative CBV (defined as the number of voxels with a blood volume fraction >1%) mirrored spontaneous collateral outgrowth following ICAO in vivo. A quantitative, biophysical model of voxel-wise CE-MRA comparison to 3D histology was successfully established.
Conclusion: Contrast-enhanced MRA permits in vivo visualization of experimental cerebral arteriogenesis. In the future, quantitative CE-MRA will help to investigate mechanisms and explore strategies for therapeutic stimulation of cerebral arteriogenesis and prevention of hemodynamic ischemic stroke.