Subvoxel vascular imaging of the midbrain using USPIO-Enhanced MRI

There is an urgent need for better detection and understanding of vascular abnormalities at the micro-level, where critical vascular nourishment and cellular metabolic changes occur. This is especially the case for structures such as the midbrain where both the feeding and draining vessels are quite small. Being able to monitor and diagnose vascular changes earlier will aid in better understanding the etiology of the disease and in the development of therapeutics. In this work, thirteen healthy volunteers were scanned with a dual echo susceptibility weighted imaging (SWI) sequence, with a resolution of 0.22 ​× ​0.44 ​× ​1 ​mm3 at 3T. Ultra-small superparamagnetic iron oxides (USPIO) were used to induce an increase in susceptibility in both arteries and veins. Although the increased vascular susceptibility enhances the visibility of small subvoxel vessels, the accompanying strong signal loss of the large vessels deteriorates the local tissue contrast. To overcome this problem, the SWI data were acquired at different time points during a gradual administration (final concentration ​= ​4 ​mg/kg) of the USPIO agent, Ferumoxytol, and the data was processed to combine the SWI data dynamically, in order to see through these blooming artifacts. The major vessels and their tributaries (such as the collicular artery, peduncular artery, peduncular vein and the lateral mesencephalic vein) were identified on the combined SWI data using arterio-venous maps. Dynamically combined SWI data was then compared with previous histological work to validate that this protocol was able to detect small vessels on the order of 50 ​μm–100 ​μm. A complex division-based phase unwrapping was also employed to improve the quality of quantitative susceptibility maps by reducing the artifacts due to aliased voxels at the vessel boundaries. The smallest detectable vessel size was then evaluated by revisiting numerical simulations, using estimated true susceptibilities for the basal vein and the posterior cerebral artery in the presence of Ferumoxytol. These simulations suggest that vessels as small as 50 ​μm should be visible with the maximum dose of 4 ​mg/kg. •Low dose Ferumoxytol was used in imaging the midbrain microvasculature.•Multiple timepoints provided useful temporal information and enhanced SWI-SNR.•Novel SWI combination helped reduce blooming artifacts to reveal smaller vessels.•Complex division-based unwrapping helped improve quality of post-contrast QSM.•Histology/simulations we