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Imaging the Cerebral Vasculature Using Ferumoxytol Enhanced Susceptibility Weighted Imaging and Quantitative Susceptibility Mapping at 3T1Department of Radiology, Wayne State University, Detroit, MI, United States, 2The MRI Institute for Biomedical Research, Bingham Farms, MI, United States, 3Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, NY, United States
Synopsis
Imaging the major arteries in the brain is straightforward using MR angiography either with or without a contrast agent. However, imaging vessels at the 250μm level is challenging and imaging vessels at the 50μm to 100μm level is essentially impossible even with high field systems. One potential approach to bring them to life is using an iron-based contrast agent to enhance SWI. In this work, we extend the use of Ferumoxytol to image the small cerebral arteries and veins to 3T and show that within a reasonable scanning time, one can obtain superb images of the vasculature of the brain.
Introduction
Imaging the major arteries in the brain is straightforward using MR angiography either with or without a contrast agent. However, imaging vessels at the 250μm level is challenging and imaging vessels at the 50μm to 100μm level is essentially impossible with even high field systems today. Thanks to the presence of deoxyhemoglobin in veins, imaging the veins using susceptibility weighted imaging (SWI) has made it possible to visualize 50μm venules at 7T and 250μm medullary veins at 3T [1–6]. The problem is that arteries do not have a susceptibility difference with the surrounding tissue. Recently, a novel approach to image every macro-vessel (non-capillaries) in the human brain was introduced. [2] The concept behind this was to change the susceptibility of the arteries to be similar to that for veins with 70% oxygen saturation. This became possible thanks to the use of an FDA approved iron-based contrast agent, Ferumoxytol. In this work, we extend the use of Ferumoxytol to image the small cerebral arteries to 3T and show that within a reasonable scanning time, one can obtain superb images of the vasculature of the brain.Methods
Data acquisition: SWI data were collected on three healthy subjects and one patient with metastases on a 3T Siemens Verio. This study was approved by the local IRB and written consent was obtained from each subject. Ferumoxytol was injected manually through intravenous infusion controlled slowly over a 15-minute window. A dose of 3mg/kg was used. Pre- and post-contrast high-resolution SWI was acquired with: TR/TE=30/15ms; FA=10o; BW=80Hz/pixel; resolution=0.25x0.25x1.5mm3; 64 slices; TA=11-minute. To observe the clearance of Ferumoxytol, one subject was scanned four different days: the day of the injection, post-1-day, post-1-week and post-2-weeks.
Data processing: For quantitative susceptibility mapping (QSM) reconstruction, BET [7] was used for brain extraction, 3DSRNCP [8] for phase unwrapping, SHARP [9] for background phase removal and iSWIM [10] for resolving the inverse problem and reducing streaking artifacts. A homodyne high-pass filter with a kernel size of 64x64 was used for conventional SWI [5] and a susceptibility mask for true-SWI [11]. The ratio of co-registered (rigid registration using Elastix, http://elastix.isi.uu.nl) pre/post-contrast magnitude images was computed to reveal the capillary density for regions with no visible macro vessels on post-contrast images.
Results
The signal-to-noise and image quality for a resolution of 0.25x0.25x1.5mm3 was sufficient for imaging very small arteries (Figure 1). The measured SNR for internal cerebral veins had a mean value of 22.5:1 per ppm on the four post-contrast QSM data. Cerebral arteries are known to be roughly 100μm in size and several of these can be seen in these images (Figure 1 and 3). Large vessels show a susceptibility of roughly 600ppb as expected with this dose (Figure 1) [2]. The small vessels infiltrating metastases can be visualized in the capillary density map (Figure 2). The follow-up data revealed that 3mg/kg Ferumoxytol had obvious T2* effect at post-1-week and reached close to the pre-contrast level at post-2-weeks (Figure 3).Discussion and Conclusion
The introduction of an iron-based contrast agent has made it possible to image very small arteries at 3T. [1] The original work at 7T gave a CNR of 20:1 while here we found similar results but with a larger voxel size [2]. It is expected that noise will drop linearly with the change in field strength, but it also turns out that Ferumoxytol is saturated at low fields. Therefore, the effective susceptibility will increase as field strength decreases and we expect that the CNR will therefore remain roughly constant despite going to lower field strengths. The visibility of small vessels with SWI also depends on the partial volume of the vessel. Small veins that are one quarter of a voxel in size provide the optimal signal loss and visibility with SWI. [2] Therefore, in terms of vessel size, one expects to be able to see 125μm sized vessels. Since the SNR is so high it may be possible to reduce the slice thickness further to 1mm or even 0.5mm to reveal even smaller vessels. One problem with this method is the presentation of arteries and veins. We propose using pre-contrast SWI to remove the major veins and reveal mostly arteries. Using this approach and vessel tracking it should be possible to segment the arteries and veins to calculate venous to arterial volume ratios. In conclusion, it is possible to evaluate the microvasculature of the brain using SWI and Ferumoxytol. Clinical applications could include any microvascular disease as well as the study of tumors as shown in this paper.Acknowledgements
This work was supported in part by the following grants from NIH/NIA: R56AG060822 and R01NS108491.References
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