title: Misleading early blood volume changes obtained using ferumoxytol-based magnetic resonance imaging perfusion in high grade glial neoplasms treated with bevacizumab.
abstract: BACKGROUND
  Neovascularization, a distinguishing trait of high-grade glioma, is a target for anti-angiogenic treatment with bevacizumab (BEV). This study sought to use ferumoxytol-based dynamic susceptibility contrast magnetic resonance imaging (MRI) to clarify perfusion and relative blood volume (rCBV) changes in glioma treated with BEV and to determine potential impact on clinical management.
  
  
  METHODS
  16 high grade glioma patients who received BEV following post-chemoradiation radiographic or clinical progression were included. Ferumoxytol-based MRI perfusion measurements were taken before and after BEV. Lesions were defined at each timepoint by gadolinium-based contrast agent (GBCA)-enhancing area. Lesion volume and rCBV were compared pre and post-BEV in the lesion and rCBV "hot spot" (mean of the highest rCBV in a 1.08 cm2area in the enhancing volume), as well as hypoperfused and hyperperfused subvolumes within the GBCA-enhancing lesion.
  
  
  RESULTS
  GBCA-enhancing lesion volumes decreased 39% (P = 0.01) after BEV. Mean rCBV in post-BEV GBCA-enhancing area did not decrease significantly (P = 0.227) but significantly decreased in the hot spot (P = 0.046). Mean and hot spot rCBV decreased (P = 0.039 and 0.007) when post-BEV rCBV was calculated over the pre-BEV GBCA-enhancing area. Hypoperfused pixel count increased from 24% to 38 (P = 0.007) and hyperperfused decreased from 39 to 28% (P = 0.017). Mean rCBV decreased in 7/16 (44%) patients from >1.75 to <1.75, the cutoff for pseudoprogression diagnosis.
  
  
  CONCLUSIONS
  Decreased perfusion after BEV significantly alters rCBV measurements when using ferumoxytol. BEV treatment response hinders efforts to differentiate true progression from pseudoprogression using blood volume measurements in malignant glioma, potentially impacting patient diagnosis and management.
authors.affiliation: Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.|Department of Neuroradiology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.
authors.forename: Joao Prola
authors.initials: JP
authors.lastname: Netto
authors.affiliation: Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.|Advanced Imaging Research Center, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Schwartz
authors.affiliation: Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.
authors.forename: Csanad
authors.initials: C
authors.lastname: Varallyay
authors.affiliation: School of Public Health, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.|Emergency Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.
authors.forename: Rongwei
authors.initials: R
authors.lastname: Fu
authors.affiliation: Department of Neuroradiology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.
authors.forename: Bronwyn
authors.initials: B
authors.lastname: Hamilton
authors.affiliation: Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA. neuwelte@ohsu.edu.|Department of Veterans Affairs Medical Center, 3710 SW U.S. Veterans Hospital Road, Portland, OR, 97239, USA. neuwelte@ohsu.edu.|Department of Neurosurgery, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, L603, Portland, OR, 97239, USA. neuwelte@ohsu.edu.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Neuwelt
mesh_terms: D000328:Adult; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use*; D001810:Blood Volume / Q000187:drug effects; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000503:physiopathology; D003287:Contrast Media; D018450:Disease Progression; D005260:Female; D052203:Ferrosoferric Oxide; D005682:Gadolinium; D005910:Glioma / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D018810:Magnetic Resonance Angiography / Q000379:methods*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D012189:Retrospective Studies; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D003287:Contrast Media; D000068258:Bevacizumab; D005682:Gadolinium; D052203:Ferrosoferric Oxide
keywords: Bevacizumab; Ferumoxytol; High grade glioma; Perfusion MRI