Determination of the MRI contrast agent concentration time course in vivo following bolus injection: Effect of equilibrium transcytolemmal water exchange

For bolus‐tracking studies, it is commonly assumed that CR concentration bears a linear relationship with the measured (usually longitudinal) 1H2O relaxation rate constant, R*1 ≡(T1 *)–1. This requires that equilibrium transcytolemmal water exchange be in the fast exchange limit (FXL). However, though systems remain in fast exchange, the FXL will not usually obtain. Here, the consequences are considered: 1) the measurement of R1 * itself can be affected, 2) the resultant non‐linear [CR]‐dependence causes significant error by assuming FXL, 3) the thermodynamic [CR] (based on the space in which CR is actually distributed) can be determined, 4) transcytolemmal water permeability may be estimated, and 5) the pharmacokinetic parameters can be factored. For a 30‐sec, 0.17 mmol/kg dose of GdDTPA2–, the FXL assumption underestimates the [CR] maximum in rat thigh muscle by a factor of almost two. Similar results are obtained for a rat brain GS‐9L gliosarcoma tumor model. Magn Reson Med 44:563–574, 2000. Published 2000 Wiley‐Liss, Inc.

[1]  S B Reeder,et al.  Effects of water exchange on the measurement of myocardial perfusion using paramagnetic contrast agents , 1999, Magnetic resonance in medicine.

[2]  B R Rosen,et al.  Dynamic Gd‐DTPA enhanced MRI measurement of tissue cell volume fraction , 1995, Magnetic resonance in medicine.

[3]  J. Kalef-Ezra,et al.  Boron neutron capture therapy of intracerebral rat gliosarcomas. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[4]  G S Karczmar,et al.  A new method for imaging perfusion and contrast extraction fraction: Input functions derived from reference tissues , 1998, Journal of magnetic resonance imaging : JMRI.

[5]  M. Knopp,et al.  Estimating kinetic parameters from dynamic contrast‐enhanced t1‐weighted MRI of a diffusable tracer: Standardized quantities and symbols , 1999, Journal of magnetic resonance imaging : JMRI.

[6]  G S Karczmar,et al.  In vivo imaging of extraction fraction of low molecular weight mr contrast agents and perfusion rate in rodent tumors , 1997, Magnetic resonance in medicine.

[7]  J S Fowler,et al.  Intimate combination of low‐ and high‐resolution image data: I. real‐space PET and 1H2O MRI, PETAMRI , 1999, Magnetic resonance in medicine.

[8]  H. Weinmann,et al.  Pharmacokinetics of GdDTPA/dimeglumine after intravenous injection into healthy volunteers. , 1984, Physiological chemistry and physics and medical NMR.

[9]  E. Rostrup,et al.  Quantification of gadolinium-DTPA concentrations for different inversion times using an IR-turbo flash pulse sequence: a study on optimizing multislice perfusion imaging. , 1998, Magnetic resonance imaging.

[10]  Weitekamp,et al.  Quantum statistical corrections to dynamic nuclear magnetic resonance , 1999, Science.

[11]  C. Springer,et al.  Using flow relaxography to elucidate flow relaxivity. , 1999, Journal of magnetic resonance.

[12]  C. Westin,et al.  Multi‐component apparent diffusion coefficients in human brain † , 1999, NMR in biomedicine.

[13]  C. Patlak,et al.  Susceptibility changes following bolus injections , 1993, Magnetic resonance in medicine.

[14]  C. S. Springer,et al.  Physicochemical Principles Influencing Magnetopharmaceuticals , 1994 .

[15]  Xin Li,et al.  Equilibrium transcytolemmal water‐exchange kinetics in skeletal muscle in vivo , 1999, Magnetic resonance in medicine.

[16]  J C Djurhuus,et al.  In vivo measurement of T1 and T2 relaxivity in the kidney cortex of the pig--based on a two-compartment steady-state model. , 1998, Magnetic resonance imaging.

[17]  P. Gowland,et al.  Dynamic studies of gadolinium uptake in brain tumors using inversion‐recovery echo‐planar imaging , 1992, Magnetic resonance in medicine.

[18]  Hellmut Merkle,et al.  Quantitative measurements of cerebral blood flow in rats using the FAIR technique: Correlation with previous lodoantipyrine autoradiographic studies , 1998, Magnetic resonance in medicine.

[19]  C. Springer,et al.  Relaxographic imaging. , 1994, Journal of magnetic resonance. Series B.

[20]  K. Schulten,et al.  Theory of heterogeneous relaxation in compartmentalized tissues , 1997, Magnetic resonance in medicine.

[21]  C. Lorenz,et al.  Regional measurement of the Gd‐DTPA tissue partition coefficient in canine myocardium , 1997, Magnetic resonance in medicine.

[22]  Scott Fields,et al.  Mapping pathophysiological features of breast tumors by MRI at high spatial resolution , 1997, Nature Medicine.

[23]  E. Rostrup,et al.  Myocardial perfusion modeling using MRI , 1996, Magnetic resonance in medicine.

[24]  D. Burstein,et al.  Gd‐DTPA2− as a measure of cartilage degradation , 1996, Magnetic resonance in medicine.

[25]  A. Schiller,et al.  Morphological studies of rat brain tumors induced by N-nitrosomethylurea. , 1971, Journal of neurosurgery.

[26]  R M Weisskoff,et al.  Water diffusion and exchange as they influence contrast enhancement , 1997, Journal of magnetic resonance imaging : JMRI.

[27]  H. Lyng,et al.  Measurement of perfusion rate in human melanoma xenografts by contrast‐enhanced magnetic resonance imaging , 1998, Magnetic resonance in medicine.

[28]  W C Eckelman,et al.  Pharmacokinetic analysis of blood distribution of intravenously administered 153Gd-labeled Gd(DTPA)2- and 99mTc(DTPA) in rats. , 1990, Magnetic resonance imaging.

[29]  P. Tofts Modeling tracer kinetics in dynamic Gd‐DTPA MR imaging , 1997, Journal of magnetic resonance imaging : JMRI.

[30]  R. Shprintzen,et al.  What's in a name? , 1990, The Cleft palate journal.

[31]  M. Botta,et al.  1H and 17O-NMR relaxometric investigations of paramagnetic contrast agents for MRI. Clues for higher relaxivities , 1999 .