Transvascular and interstitial transport in rat hepatocellular carcinomas: dynamic contrast-enhanced MRI assessment with low- and high-molecular weight agents.
OBJECTIVE
To assess which MRI-derived kinetic parameters reflect decreased transvascular and interstitial transport when low- and high-molecular-weight agents are used in rat hepatocellular carcinomas.


METHODS
Dynamic MRI after injection of a low-molecular-weight contrast agent of 0.56 kDa (Gd-DOTA, gadoterate) and two high-molecular-weight contrast agents of 6.47 kDa (P792, gadomelitol) and 52 kDa (P717, carboxymethyldextran Gd-DOTA) was performed in rats with chemically induced hepatocellular carcinomas. The data were analyzed with the Kety compartmental model, the extended Kety compartmental model in which it is assumed that the tissue voxels contain a vascular component, and the St Lawrence and Lee distributed-parameter model.


RESULTS
The extravascular extracellular space accessible to the contrast agent v(e) and the extraction fraction E decreased with increasing molecular weight of the contrast agent. In contrast, the volume transfer constant Ktrans did not differ significantly when low- or high-molecular-weight agents were used.


CONCLUSIONS
In this animal model the results suggest that the accessible extravascular extracellular space and the extraction fraction are more sensitive indicators of decreased transvascular and interstitial transport with high-molecular-weight agents than the volume transfer constant, which is a lumped representation of blood flow and permeability.
Michoux
Nicolas
N
Diagnostic Radiology Unit, Université Catholique de Louvain, St-Luc University Hospital, Brussels, Belgium. nicolas.michoux@uclouvain.be
Huwart
Laurent
L
Abarca-Quinones
Jorge
J
Dorvillius
Mylène
M
Annet
Laurence
L
Peeters
Frank
F
Van Beers
Bernard E
BE
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000378:metabolism*; D003287:Contrast Media / Q000493:pharmacokinetics*; D006571:Heterocyclic Compounds / Q000493:pharmacokinetics*; D007091:Image Processing, Computer-Assisted; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008970:Molecular Weight; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric
D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate; C435266:contrast agent P792