Purpose: To demonstrate in the rat 9L cerebral tumor model that repeated MRI measurements can quantitate acute changes in the blood-brain distribution of Gadomer after dexamethasone administration.
Materials and Methods:A total of 16 Fischer 344 rats were studied at 7T, 15 days after cerebral implantation of a 9L tumor. MRI procedures employed a T-One by Multiple Read Out Pulses (TOMROP) sequence to estimate R 1 (R 1 ϭ 1/T 1 ) at 145-second intervals before and after administration of Gadomer (Bayer), a macromolecular contrast agent (CA). Two baseline studies preceded Gadomer administration and 10 subsequent R 1 maps tracked CA concentration in blood and brain for 25 minutes. Thereafter, either dexamethasone (N ϭ 10) or normal saline (N ϭ 6) was administered intravenously. A total of 90 minutes later a second series of 12 TOMROP measurements of Gadomer distribution was performed. The influx constant, K 1 , plasma distribution volume, v D , backflux constant, k b , and interstitial space, v e , were determined, and the test-retest differences of each of four vascular parameters were calculated.Results: Dexamethasone decreased K 1 approximately 60% (P ϭ 0.02), lowered k b and v D (P ϭ 0.03 and P Ͻ 0.01, respectively), and marginally but insignificantly decreased v e . THE PURPOSE OF THIS STUDY was to develop an MRI technique for evaluating acute drug action (i.e., within one to two hours of administration) upon blood-brain exchange in an experimental cerebral tumor. To accomplish this, a standard cerebral tumor model, the 9L gliosarcoma in Fischer 344 rats (1,2), was employed, and the blood-brain distribution of the macromolecular magnetic resonance contrast agent (MRCA), Gadomer, was assessed quantitatively by MRI both before (test data) and shortly after (retest data) drug administration. Of importance in the selection of this MRCA and the development of this technique, Gadomer is relatively rapidly cleared from the blood (half-life Ϸ 30 minutes (3)). To produce an in vivo change in the bloodbrain distribution system and test the sensitivity in time of this MRI procedure, dexamethasone was administered to the experimental animals after test data acquisition. Postprocessing analyses yielded sets of blood-brain transfer constants-flux rates and distribution spaces-appropriate to one of three models (4). The test-retest differences in the four transfer constants were calculated and used for statistical analysis of drug effects.
ConclusionAs to the choice of drug, the effects of dexamethasone on blood-brain tumor exchange of radioiodinated serum albumin (RISA) has been previously imaged by quantitative autoradiography of a different rat cerebral tumor model, the RG2 glioma (5): The effect of dexa-