title: Patlak plots of Gd-DTPA MRI data yield blood-brain transfer constants concordant with those of 14C-sucrose in areas of blood-brain opening.
abstract: The blood-to-brain transfer rate constant (K(i)) of Gd-DTPA was determined in MRI studies of a rat model of transient cerebral ischemia. The longitudinal relaxation rate, R(1), was estimated using repeated Look-Locker measurements. A model-independent analysis of deltaR(1), the Patlak plot, produced maps of K(i) for Gd-DTPA and the distribution volume of the mobile protons (V(p)) with intravascular-Gd changed R(1)'s. The K(i)'s of Gd-DTPA were estimated in regions of interest with blood-brain barrier (BBB) opening (regions of interest, ROIs) and compared to those of (14)C-sucrose determined shortly thereafter by quantitative autoradiography. The K(i)'s for both Gd-DTPA and sucrose were much higher than normal within the ROIs (n = 7); linear regression of K(i) for Gd-DTPA vs. K(i) for sucrose yielded a slope of 0.43 +/- 0.11 and r(2) = 0.72 (P = 0.01). Thus, K(i) for Gd-DTPA varied in parallel with, but was less than, K(i) for sucrose. In the ROIs, mean V(p) was 0.071 ml g(-1) and much higher than mean vascular volume estimated by dynamic-contrast-enhancement (0.013 ml g(-1)) or mean V(p) in contralateral brain (0.015 ml g(-1)). This elevated V(p) may reflect increased capillary permeability to water. In conclusion, K(i) can be reliably calculated from Gd-DTPA-MRI data by Patlak plots.
authors.affiliation: Department of Neurology and Center for Stroke Research, Henry Ford Hospital and Health Sciences Center, Detroit, Michigan 48202, USA. jre@neurnis.neuro.hfh.edu
authors.forename: James R
authors.initials: JR
authors.lastname: Ewing
authors.forename: Robert A
authors.initials: RA
authors.lastname: Knight
authors.forename: Tavarekere N
authors.initials: TN
authors.lastname: Nagaraja
authors.forename: John S
authors.initials: JS
authors.lastname: Yee
authors.forename: Vijaya
authors.initials: V
authors.lastname: Nagesh
authors.forename: Polly A
authors.initials: PA
authors.lastname: Whitton
authors.forename: Lian
authors.initials: L
authors.lastname: Li
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Fenstermacher
mesh_terms: D000818:Animals; D001345:Autoradiography; D001812:Blood-Brain Barrier; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics*; D003287:Contrast Media / Q000493:pharmacokinetics; D019786:Gadolinium DTPA / Q000493:pharmacokinetics; D002546:Ischemic Attack, Transient / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D013395:Sucrose / Q000493:pharmacokinetics*
chemical_list: D002250:Carbon Radioisotopes; D003287:Contrast Media; D013395:Sucrose; D019786:Gadolinium DTPA