Dose Optimization for Using the Contrast Agent Gadofosveset in Magnetic Resonance Imaging (MRI) of Domestic Pig Brain

Pigs are useful models in stroke research, and Magnetic Resonance Imaging (MRI) is a useful tool for measurements of brain pathophysiology. Perfusion Weighed Imaging (PWI) with standard Gd-based chelates (i.e. gadobutrol) provides crucial information about breakdown of the Blood-Brain-Barrier (BBB) in patients. Gadofosveset is also a Gd-based contrast agent, but with a higher binding to serum albumin. The prolonged plasma-half life of gadofosveset allows the acquisition of steady state angiographies, which may increase the sensitivity for detection of BBB leakage. We hypothesize that the contrast dosage with gadofosveset can be optimized for PWI and subsequent steady-state Magnetic Resonance Angiography (MRA) in pigs. Anesthetized domestic pigs (females; N=6) were MRI scanned four times in one day: they were initially imaged during a standard gadobutrol bolus injection (0.1 mmol/kg). Then they received three successive gadofosveset bolus injections of varying dosages (0.015-0.09 mmol/kg). Based on projection from our data, we suggest that a bolus injection of 0.0916 mmol/kg gadofosveset would yield contrast similar to that of a standard dose of 0.1 mmol/kg gadobutrol in dynamic susceptibility contrast MRI at 3 T. In conclusion, our results demonstrate the feasibility of gadofosveset based PWI in pig brain research. The relaxation and plasma half-life properties allow detailed steady-state MRA angiographies and may prove useful in detecting subtle BBB disruption of significance in stroke models and human patients

Regional changes in cerebral metabolism during ketone body infusion.

<p>Regional changes in cerebral metabolism during ketone body infusion.</p

Metabolic parameters in the blood.

<p>Results are shown for n = 9 on Control day (CTR) and day with 3-hydroxybuturate (3-OHB) infusion (KET). Two-way repeated measures ANOVA analysis was used to test for differences between the two days. * = <i>p</i> <0.05. Open circles illustrate the mean value (±SE) on the KET day and closed circles illustrate the mean value (±SE) on the CTR day. Plasma 3-OHB (A) was measured every 30 minutes. Plasma free fatty acids (B) and insulin (C) was measured every hour. Plasma glucose (D) was measured every 30 minutes and lactate (E) at 0, 120, 180, and 240 minutes.</p

Flowchart.

<p>The flowchart illustrates the study design and shows the duration of 3-hydroxybuturate (3-OHB)/saline, and the timing of the three different scans and blood sampling.</p