MRI using ferumoxytol improves the visualization of central nervous system vascular malformations

Abstract

Background and purpose: Central nervous system vascular malformations (VMs) result from abnormal vasculo- and/or angiogenesis. Cavernomas and arteriovenous malformations are also sites of active inflammation. The aim of this study was to determine whether MRI detection of VMs can be improved by administration of ferumoxytol iron oxide nanoparticle, which acts as a blood pool agent at early time points and an inflammatory marker when taken up by tissue macrophages.

Methods: Nineteen patients (11 men, 8 women; mean age, 47.5 years) with central nervous system VMs underwent 3-T MRI both with gadoteridol and ferumoxytol. The ferumoxytol-induced signal changes on the T1-, T2-, and susceptibility-weighted images were analyzed at 25 minutes (range, 21 to 30 minutes) and 24 hours (range, 22 to 27 hours).

Results: Thirty-five lesions (capillary telangiectasia, n=6; cavernoma, n=21; developmental venous anomaly, n=7; arteriovenous malformation, n=1) were seen on the pre- and postgadoteridol images. The postferumoxytol susceptibility-weighted sequences revealed 5 additional VMs (3 capillary telangiectasias, 2 cavernomas) and demonstrated further tributary veins in all patients with developmental venous anomalies. The 24-hour T1 and T2 ferumoxytol-related signal abnormalities were inconsistent among patients and within VM types. No additional area of T1 or T2 enhancement was noted with ferumoxytol compared with gadoteridol in any lesion.

Conclusions: Our findings indicate that the blood pool agent ferumoxytol provides important information about the number and true extent of VMs on the susceptibility-weighted MRI. The use of ferumoxytol as a macrophage imaging agent in the visualization of inflammatory cells within and around the lesions warrants further investigation.

Figure 1. Capillary telangiectasia

A–C, Axial T₁- (A), T₂- (B), and susceptibility-weighted images (C) obtained before, after gadoteridol, 25 minutes, and 24 hours after ferumoxytol administration. The gadoteridol and the 24-hour ferumoxytol T₁-weighted MRI show a faint enhancing lesion in the pons (arrow). The capillary telangiectasia is isointense on the T₂-weighted ferumoxytol images at 24 hours. The lesion demonstrates prominent signal loss on the susceptibility-weighted ferumoxytol scans.

Figure 2. Cavernoma and capillary telangiectasia

A–C, Axial T₁- (A), T₂- (B), and susceptibility-weighted images (C) obtained before, after gadoteridol, 25 minutes, and 24 hours after ferumoxytol administration. The gadoteridol MRI shows enhancing lesions: a capillary telangiectasia (arrow) and a cavernoma (arrowhead) in the mesencephalon. The capillary telangiectasia is hyperintense at 25 minutes and hypointense at 24 hours on the T₁-weighted images. The cavernoma, which has a T₁ iso-, T₂ hyperintense core and a T₂ hypointense rim on the precontrast images, shows signal increase at 25 minutes and mixed ferumoxytol-related signal changes at 24 hours on the T₁-weighted scans. Both lesions demonstrate signal loss on the T₂- and susceptibility-weighted ferumoxytol images.

Figure 3. Susceptibility-weighted images of patient 6, 7, and 9

A–C, Axial susceptibility-weighted images of patient 6 (A), 7 (B), and 9 (C) obtained before and 24 hours after ferumoxytol administration. A, The ferumoxytol MRI shows a small capillary telangiectasia in the mesencephalon (arrow), while the precontrast image does not. Areas of decreased signal intensity are observed within the left temporal lobe tumor (arrowheads) 24 hours after ferumoxytol administration. B, The ferumoxytol MRI shows a capillary telangiectasia in the right basal ganglia (arrow), while the precontrast image does not. C, The ferumoxytol MRI shows a small cavernoma in the left anterior frontal lobe (arrow), while the precontrast image does not.

Figure 4. Developmental venous anomaly

A–B, Axial susceptibility-weighted images obtained before (A) and 25 minutes after ferumoxytol administration (B). Albeit the left cerebellar lesion is visible on both the pre- and post-ferumoxytol susceptibility-weighted images, but the ferumoxytol scan demonstrates additional tributary veins (rectangle) compared with the precontrast sequence.

Figure 5. Spinal cord arteriovenous malformation

A–D, Sagittal T₁- (A), T₂-(B), and T₂*-weighted images (C) obtained before and T₂*-weighted images obtained 25 minutes after ferumoxytol administration (D). The T₂-weighted image shows abnormally increased intrinsic cord signal. Dorsal flow voids are visible (arrows). The abnormal tangle of blood vessels on the spinal cord is hypointense with ferumoxytol on the T₂*-weighted images (arrowheads).