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Labeling Stem Cells with Ferumoxytol, an FDA-Approved Iron Oxide Nanoparticle
Published on: November 4, 2011
Distinguishing Extravascular from Intravascular Ferumoxytol Pools within the Brain: Proof of Concept in Patients with
R F Barajas1,2,3, D Schwartz1,2, H L McConnell4,5
1From the Departments of Radiology (R.F.B. Jr, D.S., B.E.H., J.S., D.R.P., J.P.N., J.M.P., L.S., C.G.V.).
Background And Purpose:
Glioblastoma-associated macrophages are a major constituent of the immune response to therapy and are known to engulf the iron-based MR imaging contrast agent, ferumoxytol. Current ferumoxytol MR imaging techniques for localizing macrophages are confounded by contaminating intravascular signal. The aim of this study was to assess the utility of a newly developed MR imaging technique, segregation and extravascular localization of ferumoxytol imaging, for differentiating extravascular-from-intravascular ferumoxytol contrast signal at a delayed 24-hour imaging time point.
Materials And Methods:
Twenty-three patients with suspected post-chemoradiotherapy glioblastoma progression underwent ferumoxytol-enhanced SWI. Segregation and extravascular localization of ferumoxytol imaging maps were generated as the voxelwise difference of the delayed (24 hours) from the early (immediately after administration) time point SWI maps. Continuous segregation and extravascular localization of ferumoxytol imaging map values were separated into positive and negative components. Image-guided biologic correlation was performed.
Results:
Negative segregation and extravascular localization of ferumoxytol imaging values correlated with early and delayed time point SWI values, demonstrating that intravascular signal detected in the early time point persists into the delayed time point. Positive segregation and extravascular localization of ferumoxytol imaging values correlated only with delayed time point SWI values, suggesting successful detection of the newly developed extravascular signal.
Conclusions:
Segregation and extravascular localization of ferumoxytol MR imaging improves on current techniques by eliminating intrinsic tissue and intravascular ferumoxytol signal and may inform glioblastoma outcomes by serving as a more specific metric of macrophage content compared with uncorrected T1 and SWI techniques.
Insights
A new MR imaging technique, segregation and extravascular localization of ferumoxytol imaging, successfully differentiates ferumoxytol signal from blood vessels. This improves glioblastoma macrophage detection for better outcome prediction.
Area of Science:
- Neuroimaging
- Oncology
- Immunology
Background:
- Glioblastoma-associated macrophages are key players in therapy response.
- Ferumoxytol, an iron-based MRI contrast agent, is taken up by macrophages.
- Current MRI methods for macrophage localization are limited by intravascular signal contamination.
Purpose of the Study:
- To evaluate a novel MRI technique for distinguishing extravascular from intravascular ferumoxytol signal.
- To assess the utility of segregation and extravascular localization of ferumoxytol imaging (SElFI) at a 24-hour delayed time point.
Main Methods:
- Twenty-three patients with suspected glioblastoma progression underwent ferumoxytol-enhanced SWI.
- SElFI maps were generated by subtracting early time point SWI from delayed (24-hour) SWI.
- Image-guided biologic correlation was performed.
Main Results:
- Negative SElFI values correlated with both early and delayed SWI, indicating persistent intravascular signal.
- Positive SElFI values correlated only with delayed SWI, signifying successful detection of extravascular ferumoxytol.
- This suggests SElFI can isolate macrophage-localized ferumoxytol signal.
Conclusions:
- SElFI enhances current ferumoxytol MRI techniques by removing confounding intravascular and intrinsic tissue signals.
- SElFI offers a more specific measure of macrophage content in glioblastoma.
- This improved metric may help inform glioblastoma patient outcomes.
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