title: Variation of the relaxographic "shutter-speed" for transcytolemmal water exchange affects the CR bolus-tracking curve shape.
abstract: Contrast reagents (CRs) may enter the tissue interstitium for a period after a vascular bolus injection. As the amount of interstitial CR increases, the longitudinal relaxographic NMR "shutter-speed" (T(-1)) for the equilibrium transcytolemmal water exchange process increases. The quantity T(-1) is given by |r(1o)[CR(o)] + R(1o0) - R(1i)| (where r(1o) and [CR(o)] represent the interstitial (extracellular) CR relaxivity and concentration, respectively, and R(1o0) and R(1i) are the extra- and intracellular (1)H(2)O relaxation rate constants, respectively, in the absence of exchange). The increase of T(-1) with [CR(o)] causes the kinetics of the water exchange equilibrium to appear to decrease. Here, analytical theory for two-site-exchange processes is combined with that for pharmacokinetic CR delivery, extraction, and distribution in a method termed BOLus Enhanced Relaxation Overview (BOLERO(Copyright )). The shutter-speed effect alters the shape of the bolus-tracking (B-T) time-course. It is shown that this is mostly accounted for by the inclusion of only one additional parameter, which measures the mean intracellular lifetime of a water molecule. Simulated and real data demonstrate that the effect of shutter-speed variation on pharmacokinetic parameters can be very significant: neglecting this effect can lead to an underestimation of the parameter values by 50%. This phenomenon can be heterogeneous. Within a tiny gliosarcoma implanted in the rat brain, the interstitial CR in the tumor core never rises to a level sufficient to cause apparent slowing of the exchange process. However, within the few microns needed to reach the proliferating rim, this occurs to a significant degree. Thus, even relative pharmacokinetic quantities can be incorrectly represented in a parametric map that neglects this effect. The BOLERO analysis shows promise for in vivo vascular phenotyping in pathophysiology. It also includes a provision for approximating the separation of the perfusion and permeability contributions to CR extravasation.
authors.affiliation: Chemistry Department, Brookhaven National Laboratory, Upton, New York, USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Yankeelov
authors.forename: William D
authors.initials: WD
authors.lastname: Rooney
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Charles S
authors.initials: CS
authors.lastname: Springer
mesh_terms: D000818:Animals; D001834:Body Water / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism*; D003287:Contrast Media / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019786:Gadolinium DTPA / Q000008:administration & dosage / Q000493:pharmacokinetics; D018316:Gliosarcoma / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D009368:Neoplasm Transplantation; D051381:Rats
chemical_list: D003287:Contrast Media; D019786:Gadolinium DTPA