Dyke Award Paper. Kinetics of pathologic blood-brain-barrier permeability in an astrocytic glioma using contrast-enhanced MR.
OBJECTIVE
The feasibility of measuring blood-brain barrier permeability was studied in a 36B-10 brain glioma model in rats.


METHODS
In stage I of our study, sequential MR images of glioma-implanted rats were obtained following intravenous administration of three contrast agents of different molecular sizes--Gd-DTPA, polylysine-(Gd-DTPA), and albumin-(Gd-DTPA). In a second set of experiments, sequential MR imaging with Gd-DTPA, quantitative measurements of plasma Gd-DTPA concentration, and postmortem tumor Gd-DTPA measurements were used to estimate the blood-to-tissue transport coefficient (Ki) in the rat glioma model at 11 and 15 days postimplantation.


RESULTS
In stage I, Gd-DTPA caused rapid and greatest tumor enhancement with a significant washout from the tumor during the 120-min experiment. Tumor enhancement using polylysine-(Gd-DTPA) occurred later and was significantly less compared to Gd-DTPA. Tumor signal intensity increased only slowly over time and the peak level of enhancement was least using albumin-(Gd-DTPA). In stage II, the mean (+/- 1 SD) Ki values were 1.1 +/- .24 at 11 days, and 9.3 +/- .8 at 15 days postimplantation. These results correspond well with published data obtained by autoradiography.


CONCLUSIONS
We believe that the differential enhancement pattern using contrast agents of different molecular sizes reflects a differential permeability of the pathologic blood-brain barrier, and that our studies demonstrate the feasibility of using frequent sequential images and a graphical approach to Ki calculation to determine the blood-to-tissue transport coefficient using contrast-enhanced MR.
Schmiedl
U P
UP
Department of Radiology, University of Washington, Seattle 98195.
Kenney
J
J
Maravilla
K R
KR
D000418:Albumins / Q000493:pharmacokinetics; D000818:Animals; D001254:Astrocytoma / Q000139:chemically induced / Q000503:physiopathology*; D001812:Blood-Brain Barrier / Q000502:physiology*; D001932:Brain Neoplasms / Q000139:chemically induced / Q000503:physiopathology*; D003287:Contrast Media / Q000493:pharmacokinetics*; D005038:Ethylnitrosourea; D005260:Female; D019786:Gadolinium DTPA; D008279:Magnetic Resonance Imaging; D008297:Male; D009368:Neoplasm Transplantation; D009942:Organometallic Compounds / Q000493:pharmacokinetics; D004369:Pentetic Acid / Q000493:pharmacokinetics; D010539:Permeability; D011107:Polylysine / Q000493:pharmacokinetics / Q000031:analogs & derivatives; D051381:Rats; D011916:Rats, Inbred F344
D000418:Albumins; D003287:Contrast Media; D009942:Organometallic Compounds; C058946:albumin-(gadolinium-DTPA); C068674:polylysine-(Gd-DTPA); D011107:Polylysine; D004369:Pentetic Acid; D019786:Gadolinium DTPA; D005038:Ethylnitrosourea