Introducing steady state blood volume mapping using ferumoxytol, a new MRI tool to assess the intravascular space in brain tumors and other intracranial pathologies
Csanad Varallyay1, Daniel Schwartz2, Joao Prola Netto1, Prakash Ambady2, Andrea Horvath2, and Edward Neuwelt2

1Diagnostic Radiology and Neurology, Oregon Health and Science University, Portland, OR, United States, 2Neurology, Oregon Health and Science University, Portland, OR, United States


Steady state blood volume (SS-CBV) mapping using the blood pool agent ferumoxytol as an MRI contrast agent is feasible in brain tumors and other intracranial pathologies. It allows high resolution, distortion free blood volume maps, which can be a useful MRI tool to improve diagnosis and assessment of response to therapy. Ferumoxytol dose and MRI sequences may be optimized for various clinical applications.

Background and Purpose

Ferumoxytol, an iron oxide nanoparticle has been marketed as Feraheme® with the indication of iron replacement in patients with kidney failure. Off label use, as an MR imaging agent has been tested in various parts of the body. Brain imaging is one of the most investigated areas so far with the largest number of cases (~700) in our institution, including subjects with brain tumors and various other intracranial pathologies1.

Based on our previous data, ferumoxytol enhanced MRI may help describe the most vascular/malignant tumor areas for surgical planning; differentiation of progression from treatment related pseudoprogression in primary brain tumors2; advanced visualization of pathologies of vascular origin; visualization of abnormal blood vessels in the tumor, to improve radiological diagnosis; differentiation of extra-axial benign lesions (meningioma) from intraaxial malignant neoplasms (high grade glioma, metastases); assessment of inflammatory components of brain lesions by increased cellular iron uptake.

Due to its large particle size and long plasma half life of 14-21hours, ferumoxytol is considered a blood pool contrast agent early after injection. It uniquely allows high resolution steady state blood volume (SS-CBV) mapping.3 This technique is not feasible with gadolinium based small molecular weight contrast agents.

The purpose of this study was to assess the best acquisition technique and ferumoxytol dose to image the macro and microvasculature.


50 subjects with brain tumors or other intracranial pathologies underwent brain imaging with multiple doses of ferumoxytol injected during the MRI scanning. SS-CBV maps were calculated using T2* weighted sequences before and after 75mg, 225mg, and 510mg Fe doses in protocol eIRB# 1562 (n=43) and 1mg/kg, 3mg/kg and 7mg/kg (not exceeding 510mg total) in eIRB# 9846 (n=7). This latter protocol is a newly launched multicenter study, including 5 US centers aiming to investigate ferumoxytol SS-CBV mapping at various stages of glioblastoma.

Subjects were scanned using 3T Philips scanners. Two types of sequences were used: In both protocols magnitude images of modified susceptibility weighted imaging (SWI) were used to create SS-CBV maps, (3D acquisition, TR/TE/FA: 26/20/15, FOV:210x200mm2, acq matrix 300x300, 2mm thickness, overlap 1mm, scan time: 214s), in protocol eIRB# 9846, multi echo fast field echo (mFFE) were also acquired (2D acquisition, TR 920ms, five echo times between 6.9 and 29 ms were acquired, FA:18, FOV 230x184mm2 acq matrix 384x307, 4mm thickness, 1mm gap, scan time:227s.) The 5 echoes were analyzed separately as well as averaged. Given the intravascular properties of ferumoxytol, SS-CBV maps were created by calculating ΔR2* between coregistered early post and pre contrast scans for each ferumoxytol dose using FSL. T2* weighted images and SS-CBV maps were visually tested and analyzed.


Both SWI and mFFE scans were anatomically correct without major distortions, but both sequences were prone to motion artifacts. (Figure 1) Less susceptibility artifacts were present on the mFFE scans with shorter echo times. Both 3mg/kg and 7mg/kg Fe (225mg and 510mg in study eIRB#1562) doses visualized the abnormal vasculature (Figure 1), and provided clinically sufficient SS-CBV maps. (Figure 2) However, when analyzing lesions within the cortex, higher doses were beneficial. The high spatial resolution and thin slices of SWI allowed good sagittal and coronal reformations, whereas the mFFE sequences allowed calculation of SS-CBV maps with higher signal to noise ratios. Unlike the SWI sequence, the mFFE had no substantial T1 properties.


SS-CBV mapping is feasible using various sequences and various ferumoxytol doses. For surgery planning, SWI magnitude images can be used, with good multi-plane reformations. mFFE may be more beneficial if SS-CBV mapping is used after gadolinium enhanced MRI as an add-on scan, since it lacks T1 weighting. In most cases, lower ferumoxytol dose may be sufficient (3mg/kg), however if thin slices are needed for cortical lesions, 7mg/kg (510mg total) may be beneficial.

This preliminary analysis of data allowed the design of a larger multicenter study, which prospectively analyses SS-CBV during glioblastoma treatment, to further exploit the potentials of this new MRI application.


No acknowledgement found.


1. Neuwelt, E.A., C.G. Varallyay, S. Manninger, et al. The potential of ferumoxytol nanoparticle magnetic resonance imaging, perfusion, and angiography in central nervous system malignancy: a pilot study. Neurosurgery, 2007. 60(4): p. 601-11

2. Gahramanov, S., C. Varallyay, R.M. Tyson, et al. Diagnosis of pseudoprogression using MRI perfusion in patients with glioblastoma multiforme may predict improved survival. CNS Oncol, 2014. 3(6): p. 389-400.

3. Varallyay, C.G., E. Nesbit, R. Fu, et al. High-resolution steady-state cerebral blood volume maps in patients with central nervous system neoplasms using ferumoxytol, a superparamagnetic iron oxide nanoparticle. J Cereb Blood Flow Metab, 2013. 33(5): p. 780-6.


Figure 1 demonstrates the SWI magnitude images as well as the mFFE averaged images at various ferumoxytol doses in a glioblatoma patient. 3mg/kg and 7mg/kg doses show advanced visualization of abnormal vasculature. Note that motion artifacts compromise image quality.

Figure 2 shows SS-CBV maps using SWI vs mFFE sequences at various ferumoxytol doses in the same glioblastoma patient. 3mg/kg and 7mg/kg doses provided clinically sufficient parametric maps.

Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)