MRI measures of changes in the transfer constant of gadomer after dexamethasone in 9L rat cerebral tumor

Introduction

We used Gadomer (Schering AG), a magnetic resonance contrast agent (MRCA), and magnetic resonance imaging (MRI) measures of T₁ to estimate changes in tumor vascular permeability after the administration of dexamethasone.

Methods

Five male Fischer 344 rats weighing 250 to 300 g were implanted with 10,000 9L tumor cells using methods previously described^{2, 3}; the resultant population of animals with cerebral tumor was studied about 14 days post-implantation using MRI and Gadomer, a dendritic gadolinium (Gd) chelate with an effective molecular weight of about 33 kD. MRI studies were carried out at 7 Tesla, using a Bruker console. Following established procedures ⁴ , a TOMROP ⁵ sequence was used to measure R₁ (R₁ = 1/T₁) at baseline, and at 145 s intervals following injection of the MRCA. Matrix size was 128×64, FOV 32 mm, three 2 mm slices. Changes in R₁ were assumed to reflect changes in MRCA concentration.

Prior to the administration of MRCA, two baseline TOMROP studies were obtained, after which the next TOMROP sequence was started and Gadomer was administered in a slow push (250 μmol/kg in a 0.3 ml volume in about 1 minute). During and after the administration of Gadomer, 10 iterations of TOMROP were run to follow the tissue concentration of MRCA across a 25 min period. Intravascular dexamethasone (2.4 mg/kg in 0.15 ml) was administered, and, after an interval of about 90 minutes, a second series of TOMROP images was run. Using a standard analysis^{1, 2}, the parameters vascular volume (v_d), transfer constant (K₁) and efflux constant, k_b were computed. The extravascular, extracellular space (v_EES) was estimated from the ratio K^trans/k_b. Both region-of-interest (tumor), as well as pixel-by-pixel whole brain estimates, were generated.

Results and Discussion

Changes in permeability parameters are summarized in the table 1 and compared to the work of Nakagawa et al ⁶ , in which Radioiodinated serum albumin (RISA) was used to study the effect of dexamethasone on the RG-2 cerebral tumor. In every animal, the transfer constant decreased after the administration of dexamethasone. Gadomer should approximate RISA when used as a measure of vascular permeability. Despite the differences in tumor type, administration schedule, and measurement technique, the agreement between these two studies is striking, particularly the numerical agreement in the change of V_EES.

Table 1

Mean Vascular Leakage Parameters, pre- and post-dexamethasone

Parameter*	Pre-Dex	Post-Dex	Paired t-test p-value	RISA Values **6
				Pre	Post
Vd[ml/ml]	0.0261±0.00724	0.0191±0.0242	NS	0.030±0.24	0.018±0.0091
Kl[min−1]	0.0122±0.00724	0.00591±0.00429	p=0.001	0.0236±0.0089	0.0083±0.0029
VEES=Ktrans/kb	0.110±0.0291	0.0765±0.0555	P<0.05	0.140±0.02	0.08±0.02

*

MRI units

**

‘Radiological’ units, scaled to MRI units by tissue density