R F Barajas1,2,3, D Schwartz1,2, H L McConnell4,5, C N Kersch4,5, X Li2, B E Hamilton1, J Starkey1, D R Pettersson1, J P Nickerson1, J M Pollock1, R F Fu6, A Horvath2, L Szidonya1,4,5,7, C G Varallyay1,4,5, J J Jaboin8, A M Raslan9, A Dogan9, J S Cetas9, J Ciporen9, S J Han9, P Ambady4,5, L L Muldoon4,5, R Woltjer10, W D Rooney2, E A Neuwelt11,9,5,12. 1. From 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.). 2. Advanced Imaging Research Center (R.F.B. Jr, D.S., X.L., A.H., W.D.R.). 3. Knight Cancer Institute Translational Oncology Research Program (R.F.B. Jr). 4. Departments of Neurology (H.L.M., C.N.K., L.S., C.G.V., P.A., L.L.M., E.A.N.). 5. Blood-Brain Barrier Program (H.L.M., C.N.K., L.S., C.G.V., P.A., L.L.M., E.A.N.), Oregon Health & Science University, Portland, Oregon. 6. Medical Informatics and Clinical Epidemiology (R.F.F.). 7. Department of Diagnostic Radiology (L.S.), Heart and Vascular Center, Semmelweis University, Budapest, Hungary. 8. Radiation Medicine (J.J.J.). 9. Neurological Surgery (A.M.R., A.D., J.S.C., J.C., S.J.H., E.A.N.). 10. Pathology (R.W.). 11. Departments of Neurology (H.L.M., C.N.K., L.S., C.G.V., P.A., L.L.M., E.A.N.) neuwelte@ohsu.edu. 12. Portland Veterans Affairs Medical Center (E.A.N.), Portland, Oregon.
Abstract
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.
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.
Authors: Quinn T Ostrom; Haley Gittleman; Jordan Xu; Courtney Kromer; Yingli Wolinsky; Carol Kruchko; Jill S Barnholtz-Sloan Journal: Neuro Oncol Date: 2016-10-01 Impact factor: 12.300
Authors: Ramon F Barajas; Bronwyn E Hamilton; Daniel Schwartz; Heather L McConnell; David R Pettersson; Andrea Horvath; Laszlo Szidonya; Csanad G Varallyay; Jenny Firkins; Jerry J Jaboin; Charlotte D Kubicky; Ahmed M Raslan; Aclan Dogan; Justin S Cetas; Jeremy Ciporen; Seunggu J Han; Prakash Ambady; Leslie L Muldoon; Randy Woltjer; William D Rooney; Edward A Neuwelt Journal: Neuro Oncol Date: 2019-03-18 Impact factor: 12.300
Authors: Ramon F Barajas; J Graeme Hodgson; Jamie S Chang; Scott R Vandenberg; Ru-Fang Yeh; Andrew T Parsa; Michael W McDermott; Mitchel S Berger; William P Dillon; Soonmee Cha Journal: Radiology Date: 2010-02 Impact factor: 11.105
Authors: Heather L McConnell; Daniel L Schwartz; Brian E Richardson; Randall L Woltjer; Leslie L Muldoon; Edward A Neuwelt Journal: Nanomedicine Date: 2016-04-09 Impact factor: 5.307
Authors: Sydney R Gordon; Roy L Maute; Ben W Dulken; Gregor Hutter; Benson M George; Melissa N McCracken; Rohit Gupta; Jonathan M Tsai; Rahul Sinha; Daniel Corey; Aaron M Ring; Andrew J Connolly; Irving L Weissman Journal: Nature Date: 2017-05-17 Impact factor: 49.962