title: Improved perfusion MR imaging assessment of intracerebral tumor blood volume and antiangiogenic therapy efficacy in a rat model with ferumoxytol.
abstract: OBJECTIVE
  To evaluate the consistency of tumor blood volume measurements and antiangiogenic therapy efficacy assessments with a low-molecular-weight gadolinium-based contrast agent (GBCA, gadodiamide) versus an iron oxide nanoparticle (ferumoxytol) in the presence or absence of a loading dose of contrast agent before perfusion magnetic resonance (MR) imaging (preload method).
  
  
  METHODS
  The protocol was approved by the institutional animal care and use committee. U87MG tumor cells were implanted intracerebrally in 13 rats. All 13 rats underwent 11.75-T MR imaging with gadodiamide (60 μL) 13 days after tumor implantation. The next day, nine rats underwent MR imaging with ferumoxytol (60 μL). Immediately after ferumoxytol imaging, six rats received bevacizumab (45 mg/kg). MR imaging was repeated 48 hours after bevacizumab treatment with gadodiamide and 72 hours after treatment with ferumoxytol. Each study included three consecutive dynamic susceptibility-weighted contrast material-enhanced (DSC) MR acquisitions, which were performed without preload, with single-dose preload, and with double-dose preload. Tumor relative cerebral blood volume (rCBV) was estimated from each DSC MR acquisition. Two-way repeated measures analysis of variance was performed to test for differences between groups with both contrast agents.
  
  
  RESULTS
  DSC MR imaging with gadodiamide and without preload showed low rCBV (≤ 1.75) in nine of the 13 tumors; estimated rCBV increased progressively with both single- and double-dose preloads (P < .001). Conversely, rCBVs obtained with ferumoxytol were high (>1.75) and remained constant with all three acquisitions. The magnitude of rCBV decrease after bevacizumab administration was dependent on the dose of gadodiamide preload, whereas the magnitude of rCBV decrease with ferumoxytol was constant regardless of whether contrast agent preload was used.
  
  
  CONCLUSIONS
  With GBCA, tumor rCBV can be underestimated without preload and becomes dose dependent with preload correction. Conversely, ferumoxytol provides consistent assessment of tumor rCBV and antiangiogenic therapy efficacy.
authors.affiliation: Department of Neurology and Neurosurgery, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd, Room L603, Portland, OR 97239-3098, USA.
authors.forename: Seymur
authors.initials: S
authors.lastname: Gahramanov
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Muldoon
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Edward A
authors.initials: EA
authors.lastname: Neuwelt
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D000068258:Bevacizumab; D001810:Blood Volume; D001932:Brain Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000473:pathology; D002560:Cerebrovascular Circulation; D003287:Contrast Media; D052203:Ferrosoferric Oxide; D019786:Gadolinium DTPA; D005910:Glioma / Q000098:blood supply* / Q000188:drug therapy / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051381:Rats; D011923:Rats, Nude; D014183:Transplantation, Heterologous
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003287:Contrast Media; D000068258:Bevacizumab; C064925:gadodiamide; D019786:Gadolinium DTPA; D052203:Ferrosoferric Oxide