title: Incorporating the effects of transcytolemmal water exchange in a reference region model for DCE-MRI analysis: theory, simulations, and experimental results.
abstract: Models have been developed for the analysis of dynamic contrast-enhanced MRI (DCE-MRI) data that do not require direct measurements of the arterial input function; such methods are referred to as reference region models. These models typically return estimates of the volume transfer constant (K(trans)) and the extravascular extracellular volume fraction (v(e)). To date such models have assumed a linear relationship between the measured R(1) ( identical with 1/T(1)) and the concentration of contrast agent, a transformation referred to as the fast exchange limit, but this assumption is not valid for all concentrations of an agent. A theory for DCE-MRI reference region models which accounts for water exchange is presented, evaluated in simulations, and applied in tumor-bearing mice. Using reasonable parameter values, simulations show that the assumption of fast exchange can underestimate K(trans) and v(e) by up to 82% and 46%, respectively. By analyzing a large region of interest and a single voxel the new model can return parameters within approximately +/-10% and +/-25%, respectively, of their true values. Analysis of experimental data shows that the new approach returns K(trans) and v(e) values that are up to 90% and 73%, respectively, greater than conventional fast exchange analyses.
authors.affiliation: Institute of Imaging Science, Vanderbilt University, 1161 21st Avenue South, Nashville, TN 37232, USA. thomas.yankeelov@vanderbilt.edu
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Yankeelov
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Luci
authors.forename: Laura M
authors.initials: LM
authors.lastname: DeBusk
authors.forename: P Charles
authors.initials: PC
authors.lastname: Lin
authors.forename: John C
authors.initials: JC
authors.lastname: Gore
mesh_terms: D000465:Algorithms; D000818:Animals; D001834:Body Water / Q000378:metabolism*; D003198:Computer Simulation; D003287:Contrast Media / Q000493:pharmacokinetics*; D005260:Female; D019786:Gadolinium DTPA / Q000493:pharmacokinetics*; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism*; D051379:Mice; D008962:Models, Theoretical
chemical_list: D003287:Contrast Media; D019786:Gadolinium DTPA