title: Flow versus permeability weighting in estimating the forward volumetric transfer constant (Ktrans) obtained by DCE-MRI with contrast agents of differing molecular sizes.
abstract: To quantify the differential plasma flow- (Fp-) and permeability surface area product per unit mass of tissue- (PS-) weighting in forward volumetric transfer constant (Ktrans) estimates by using a low molecular (Gd-DTPA) versus high molecular (Gadomer) weight contrast agent in dynamic contrast enhanced (DCE) MRI.
  
  
  
  DCE MRI was performed using a 7T animal scanner in 14 C57BL/6J mice syngeneic for TRAMP tumors, by administering Gd-DTPA (0.9kD) in eight mice and Gadomer (35kD) in the remainder. The acquisition time was 10min with a sampling rate of one image every 2s. Pharmacokinetic modeling was performed to obtain Ktransby using Extended Tofts model (ETM). In addition, the adiabatic approximation to the tissue homogeneity (AATH) model was employed to obtain the relative contributions of Fpand PS.
  
  
  
  The Ktransvalues derived from DCE-MRI with Gd-DTPA showed significant correlations with both PS (r2=0.64, p=0.009) and Fp(r2=0.57, p=0.016), whereas those with Gadomer were found only significantly correlated with PS (r2=0.96, p=0.0003) but not with Fp(r2=0.34, p=0.111). A voxel-based analysis showed that Ktransapproximated PS (<30% difference) in 78.3% of perfused tumor volume for Gadomer, but only 37.3% for Gd-DTPA.
  
  
  
  The differential contributions of Fpand PS in estimating Ktransvalues vary with the molecular weight of the contrast agent used. The macromolecular contrast agent resulted in Ktransvalues that were much less dependent on flow. These findings support the use of macromolecular contrast agents for estimating tumor vessel permeability with DCE-MRI.
authors.affiliation: Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Cheng-He
authors.initials: CH
authors.lastname: Li
authors.affiliation: Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Radiation Biology Research Center, Institute for Radiological Research, Chang Gung University, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Radiation Oncology, Chang Gung Memorial Hospital at Linko, Taoyuan, Taiwan.
authors.forename: Fang-Hsin
authors.initials: FH
authors.lastname: Chen
authors.affiliation: Departments of Diagnostic Radiology and Cancer Systems Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Dawid
authors.initials: D
authors.lastname: Schellingerhout
authors.affiliation: Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Yu-Shi
authors.initials: YS
authors.lastname: Lin
authors.affiliation: Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Radiation Biology Research Center, Institute for Radiological Research, Chang Gung University, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Radiation Oncology, Chang Gung Memorial Hospital at Linko, Taoyuan, Taiwan.
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Hong
authors.affiliation: Department of Imaging Physics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. Electronic address: hlaliu@mdanderson.org.
authors.forename: Ho-Ling
authors.initials: HL
authors.lastname: Liu
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000502:physiology*; D003287:Contrast Media / Q000493:pharmacokinetics*; D005682:Gadolinium / Q000493:pharmacokinetics*; D019786:Gadolinium DTPA / Q000493:pharmacokinetics*; D007089:Image Enhancement / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D008970:Molecular Weight
chemical_list: D003287:Contrast Media; C402765:gadomer 17; D005682:Gadolinium; D019786:Gadolinium DTPA
keywords: Dynamic contrast enhanced; Flow; Forward volumetric transfer constant; MRI; Permeability