Purpose: To develop a method for body magnetic resonance imaging (MRI) of conscious mice and investigate the effect of isoflurane anesthesia and hypothermia on the hepatic kinetics of gadoxetate disodium (Gd-EOB-DTPA).
Materials and Methods:Conscious or anesthetized mice were restrained on a holder and the rectal temperature was measured serially. Serial MRI of the liver was performed after intravenous injection of Gd-EOB-DTPA with or without temperature control. Three mice were studied for each condition.
Results:The temperature dropped rapidly in anesthetized mice beside the MR unit. The decline was less prominent in conscious mice. The temperature decreased less in anesthetized mice and remained constant in conscious mice in the radiofrequency (RF) coil. The washout of Gd-EOB-DTPA was slower in anesthetized hypothermic mice than in conscious normothermic mice. Warmed anesthetized mice showed faster washout, and cooled conscious mice showed delayed washout. Severer hypothermia in anesthetized mice resulted in weaker initial enhancement and slower washout.Conclusion: By separately manipulating the presence or absence of anesthesia and hypothermia, we demonstrated that washout of Gd-EOB-DTPA was delayed under hypothermia, regardless of anesthesia. Serial body MRI of conscious mice was feasible and allowed the evaluation of kinetics of a contrast agent, while excluding the possible effects of anesthesia. MAGNETIC RESONANCE IMAGING (MRI) is a noninvasive technique that provides 3D information about both anatomy and function and is accepted as a powerful modality for small animal experiments as well as for clinical practice (1-4). Small animal MRI is usually performed under anesthesia, which may change physiological conditions and affect the experimental results including the pharmacokinetics of a contrast agent. The kinetics of a hepatobiliary contrast agent reflects liver function in humans and small animals (5,6) and is important to determine the optimal timing of imaging. It has been suggested that the kinetics of two hepatobiliary contrast agents, gadobenate dimeglumine (Gd-BOPTA) (7) and gadoxetate disodium (Gd-EOB-DTPA) (8), differ between anesthetized and conscious mice, and that anesthesia using isoflurane or pentobarbital prolongs contrast enhancement in the liver. Although the body temperature in mice decreases under anesthesia (9,10), the kinetics of contrast agents was evaluated without warming or measurement of body temperature in the previous studies. Therefore, hypothermia, other than the direct action of anesthetic, might have affected the kinetics.We developed a method for acquiring body MR images in conscious mice and evaluated the kinetics of Gd-EOB-DTPA in mouse liver under conditions of isoflurane anesthesia and consciousness. Furthermore, we manipulated the body temperature to separately assess the direct action of the anesthetic and the effect of hypothermia. The aim of this study was to determine the feasibility and potential usefulness of serial body MRI in conscious mice and to investigat...