title: Tumor blood volume determination by using susceptibility-corrected DeltaR2* multiecho MR.
abstract: OBJECTIVE
  To evaluate a susceptibility-corrected multiecho magnetic resonance (MR) relaxometry technique for an accurate and robust determination of DeltaR2* as a noninvasive surrogate parameter of the perfused tumor blood volume.
  
  
  METHODS
  All experiments were approved by the institutional animal care committee. In a glass tube phantom with different superparamagnetic iron oxide (SPIO) particle concentrations and at tumor mice xenografts with DU-4475, HT-1080, and MDA-MB-435 tumors (n = 15 total, n = 5 per model) with different degrees of neovascularization after injection of different ultrasmall SPIO (USPIO) doses changes of the transverse relaxation rate (DeltaR2*) were determined by using a fixed echo time (TE) of 22 msec and a susceptibility-corrected multigradient-echo technique. The mean DeltaR2* value and the vascular volume fraction (VVF) of each tumor was determined and compared with independent in vivo fluorescent tumor perfusion measurements and histologic analysis helped determine microvessel density (MVD). Statistical differences were tested by using analysis of variance and linear correlations.
  
  
  RESULTS
  For the phantom study, DeltaR2* maps calculated with a fixed TE of 22 msec showed a higher standard deviation of the noise index compared with the susceptibility-corrected multiecho technique. For the xenograft model, mean tumor DeltaR2* values (+/- standard error of the mean) showed significant differences between the various tumors (eg, DU-4475: 12.3 sec(-1) +/- 2.67, HT-1080: 36.47 sec(-1) +/- 5.84, and MDA-MB-435: 64.01 sec(-1) +/- 8.87 at 80 mumol of iron per kilogram; P < .05). DeltaR2* values increased dose dependently and in a linear fashion, resulting in reproducibly stable VVF measurements. Fluorescent tumor perfusion measurements and MVD counts corroborated the MR results.
  
  
  CONCLUSIONS
  Susceptibility-corrected multiecho MR relaxometry allows a highly accurate and robust determination of DeltaR2* and VVF with an excellent dynamic range for tumor characterization at clinically relevant doses of USPIO.
authors.affiliation: Department of Clinical Radiology, University Hospital Muenster, Albert-Schweitzer-Str. 33, D-48149 Münster, Germany. tpersi@uni-muenster.de
authors.forename: Thorsten
authors.initials: T
authors.lastname: Persigehl
authors.forename: Alexander
authors.initials: A
authors.lastname: Wall
authors.forename: Julia
authors.initials: J
authors.lastname: Kellert
authors.forename: Janine
authors.initials: J
authors.lastname: Ring
authors.forename: Stefanie
authors.initials: S
authors.lastname: Remmele
authors.forename: Walter
authors.initials: W
authors.lastname: Heindel
authors.forename: Hannes
authors.initials: H
authors.lastname: Dahnke
authors.forename: Christoph
authors.initials: C
authors.lastname: Bremer
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003911:Dextrans; D052203:Ferrosoferric Oxide; D007089:Image Enhancement / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D051379:Mice; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000098:blood supply*; D009389:Neovascularization, Pathologic / Q000175:diagnosis*; D019047:Phantoms, Imaging; D014407:Tumor Cells, Cultured
chemical_list: D003911:Dextrans; D058185:Magnetite Nanoparticles; C065507:ferumoxides; D052203:Ferrosoferric Oxide