Abstract
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. 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. 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. 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.
Highlights
BACKGROUND AND PURPOSEGlioblastoma-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
Following CRT, some patients undergo an inflammatory response that manifests as transiently progressive gadoliniumbased contrast agent (GBCA) enhancement on MR imaging, Received August 16, 2019; accepted after revision April 2, 2020
The normalized signal intensity of GBCA T1 enhancement was not correlated with delayed time point SWI maps or SELFI measures (r(21) 1⁄4 0.33, 0.33, and À0.13, P . .1; Fig 3B, bottom left), suggesting that the functional significance of the magnitude patients with isocitrate dehydrogenase (IDH) wild-type disease progression (5 pseudoprogressions, 14 disease recurrences) was nonsignificant for the delayed time point metric (B 1⁄4 –0.13, Wald 1⁄4 0.017, P . .8), though it approached significance for the tumor-wide SELFI1 metric (B 1⁄4 2.98, Wald 1⁄4 2.57, P 1⁄4 .1)
Summary
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
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