A unified magnetic resonance imaging pharmacokinetic theory: Intravascular and extracellular contrast reagents

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128 Scopus citations


A fundamental reworking of pharmacokinetic theory for the use of contrast reagents (CRs) in 71,-weighted MRI studies is presented. Unlike the standard model in common use, this derivation starts with the quantities measured, the intravascular, interstitial, and intracellular 1H 2O signals. The time dependences of CR concentrations are introduced as perturbations of the T1 values of these. Since there is an explicit accounting for the equilibrium exchange of water molecules between tissue compartments, the approach here is a new (second) generation of the shutter-speed model (S2M). When the first-order rate constant measuring CR extravasation (Ktrans) is of sufficient magnitude, simulations presented here confirm that neglect of plasma CR, a feature of the first generation of S2M, is a valid approximation. The second S 2M generation (S2M2) also automatically accommodates excursions of either or both of the two major equilibrium water exchange systems (transendothelial and transcytolemmal) into any or all possible exchange conditions, from their fast-exchange limits to their slow-exchange limits. This can happen not because the exchange kinetics themselves vary during the isothermal CR passage, but because the MR shutter speeds for these processes can vary. When Ktrans is sufficiently small, the S2M2 also naturally accounts for the hyperfine blood agent level dependent (BALD) effect that is easily detectable at high magnetic field. This can be seen for virtually all CRs in normal brain tissue and for virtually all tissues with sufficiently intravascular CRs. Thus, S2M2 represents a unified pharmacokinetic theory for intravascular and extracellular T1 contrast reagents.

Original languageEnglish (US)
Pages (from-to)1351-1359
Number of pages9
JournalMagnetic Resonance in Medicine
Issue number6
StatePublished - Dec 2005


  • Longitudinal relaxation
  • Pharmacokinetics
  • Shutter speed
  • Water exchange

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging


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