title: Measurement of rat brain tumor kinetics using an intravascular MR contrast agent and DCE-MRI nested model selection.
abstract: OBJECTIVE
  Using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in a rat glioma model, and nested model selection (NMS), to compare estimates of the pharmacokinetic parameters vp , K(trans) , and ve for two different contrast agents (CAs)-gadofosveset, which reversibly binds to human serum albumin, and gadopentetate dimeglumine, which does not.
  
  
  METHODS
  DCE-MRI studies were performed on nine Fisher 344 rats inoculated intracerebrally with 9L gliosarcoma cells using both gadofosveset and gadopentetate. The parameters vp , K(trans) , and ve were estimated using NMS.
  
  
  RESULTS
  K(trans) estimates using gadofosveset, compared to gadopentetate, differed in their means (gadofosveset 0.025 ± 0.008 min(-1) vs. gadopentetate 0.046 ± 0.011 min(-1) ; P = 0.0039). This difference notwithstanding, the intraclass correlation coefficient (ICC) for the two estimates of K(trans) showed nearly perfect linear dependence (ICC = 0.8479 by Pearson's r). Other estimates, ve (gadofosveset 22.7 ± 4.7% vs. gadopentetate 23.6 ± 5.6%; P = 0.4258) and vp (gadofosveset 1.5 ± 0.5% vs. gadopentetate 1.6 ± 0.4%; P = 0.25), were not different in their means between the two CAs, and there was almost perfect agreement for ve (ICC = 0.8798) and substantial agreement for vp (ICC = 0.7981) between the two CAs.
  
  
  CONCLUSIONS
  Estimates of K(trans) were statistically different using gadofosveset and gadopentetate, whereas ve and vp were similar with two CAs. NMS produced robust estimates of pharmacokinetic parameters using DCE-MRI that show promise as important measures of tumor physiology and microenvironment.
authors.affiliation: Department of Radiology, Henry Ford Hospital, Detroit, Michigan, USA.
authors.forename: Wilson B
authors.initials: WB
authors.lastname: Chwang
authors.forename: Rajan
authors.initials: R
authors.lastname: Jain
authors.forename: Hassan
authors.initials: H
authors.lastname: Bagher-Ebadian
authors.forename: Siamak P
authors.initials: SP
authors.lastname: Nejad-Davarani
authors.forename: A S M
authors.initials: AS
authors.lastname: Iskander
authors.forename: Ashley
authors.initials: A
authors.lastname: VanSlooten
authors.forename: Lonni
authors.initials: L
authors.lastname: Schultz
authors.forename: Ali S
authors.initials: AS
authors.lastname: Arbab
authors.forename: James R
authors.initials: JR
authors.lastname: Ewing
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000473:pathology*; D003287:Contrast Media / Q000493:pharmacokinetics*; D005260:Female; D005682:Gadolinium / Q000493:pharmacokinetics*; D019786:Gadolinium DTPA / Q000493:pharmacokinetics*; D018316:Gliosarcoma / Q000473:pathology*; D007089:Image Enhancement / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009368:Neoplasm Transplantation; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D051381:Rats; D011916:Rats, Inbred F344; D013223:Statistics as Topic
chemical_list: D003287:Contrast Media; D009942:Organometallic Compounds; D005682:Gadolinium; D019786:Gadolinium DTPA; C109932:gadofosveset trisodium
keywords: DCE-MRI; contrast agent; gadofosveset; gadopentetate