TAQ

TAQ

[Name of the Writer]

[Name of the Institution]

Abstract

In pharmacological magnetic resonance imaging (phMRI) with anesthetized animals, there is usually only a single time window to observe the dynamic signal change to an acute drug administration since subsequent drug injections are likely to result in altered response properties (e.g., tolerance). Unlike the block-design experiments in which fMRI signal can be elicited with multiple repetitions of a task, these single-event experiments require stable baseline in order to reliably identify drug-induced signal changes. Such factors as subject motion, scanner instability and/or alterations in physiological conditions of the anesthetized animal could confound the baseline signal. The unique feature of such functional MRI (fMRI) studies necessitates a technique that is able to monitor MRI signal in a real-time fashion and to interactively control certain experimental procedures. In the present study, an approach for real-time MRI on a Bruker scanner is presented. The custom software runs on the console computer in parallel with the scanner imaging software, and no additional hardware is required. The utility of this technique is demonstrated in manganese-enhanced MRI (MEMRI) with acute cocaine challenge, in which temporary disruption of the blood-brain barrier (BBB) is a critical step for MEMRI experiments. With the aid of real-time MRI, we were able to assess the outcome of BBB disruption following bolus injection of hyperosmolar mannitol in a near real-time fashion prior to drug administration, improving experimental success rate. It is also shown that this technique can be applied to monitor baseline physiological conditions in conventional fMRI experiments using blood oxygenation level-dependent (BoLD) contrast, further demonstrating the versatility of this technique.

Keywords: Real-time MRI; Manganese-enhanced MRI; Functional MRI; phMR; Cocaine

Table of Contents

1. Introduction4

2. Methods6

2.1. RTMRI on a Bruker scanner6

2.2. Interactive MEMRI experiments using RTMRI9

2.3. MRI Scan10

2.4. Experimental paradigm10

2.5. Data analysis11

2.6. Monitoring BoLD signal changes resulting from perturbations of baseline physiological condition11

3. Results13

3.1. Monitoring the effect of BBB disruption using RTMRI13

3.2. Monitoring BoLD response following transient blood gas perturbations using RTMRI17

4. Discussion18

References20

TAQ

1. Introduction

Functional magnetic resonance imaging (fMRI) has been widely used to investigate the sensory, motor and cognitive functions of the brain. Most of these studies used the so-called blood oxygenation level-dependent (BoLD) contrast. More recently, this technique has been applied to investigate the effects of pharmacological agents in the brain. The noninvasive nature of this technique, coupled with its high spatial and temporal resolution, has made it an attractive tool for drug research. The application of fMRI techniques to neuropharmacology, termed pharmacological MRI (phMRI) , has been successfully used to identify regional brain responses to such pharmacological agents as cocaine and nicotine, providing information about neural substrates and pharmacodynamics of drug actions.

phMRI has been traditionally conducted by bolus administrations of drug and identification of brain regions that exhibit alterations in hemodynamic responses corresponding with the dynamic change of drug concentration in the brain. Due to such limitations as the pharmacokinetics of drug actions, neuronal adaptations and drug tolerance, etc., subjects usually receive only one drug administration in a session. Such single-event experiments require stable baseline in order ...