Real-Time fMRI Brain Mapping in Animals

Summary

Animal brain functional mapping can benefit from the real-time functional magnetic resonance imaging (fMRI) experimental set-up. Using the latest software implemented in the animal MRI system, we established a real-time monitoring platform for small animal fMRI.

Abstract

Dynamic fMRI responses vary largely according to the physiological conditions of animals either under anesthesia or in awake states. We developed a real-time fMRI platform to guide experimenters to monitor fMRI responses instantaneously during acquisition, which can be used to modify the physiology of animals to achieve desired hemodynamic responses in animal brains. The real-time fMRI set-up is based on a 14.1T preclinical MRI system, enabling the real-time mapping of dynamic fMRI responses in the primary forepaw somatosensory cortex (FP-S1) of anesthetized rats. Instead of a retrospective analysis to investigate confounding sources leading to the variability of fMRI signals, the real-time fMRI platform provides a more effective scheme to identify dynamic fMRI responses using customized macro-functions and a common neuroimage analysis software in the MRI system. Also, it provides immediate troubleshooting feasibility and a real-time biofeedback stimulation paradigm for brain functional studies in animals.

Introduction

Functional Magnetic Resonance Imaging (fMRI) is a non-invasive method to measure the hemodynamic responses^{1,2,3,4,5,6,7,8,9}, e.g., the blood-oxygen-level-dependent (BOLD), cerebral blood volume and flow signal, associated with neural activity in the brain. In animal studies, hemodynamic signals can be affected by anesthesia¹⁰, the stress level of....

Protocol

This study was performed in accordance with the German Animal Welfare Act (TierSchG) and Animal Welfare Laboratory Animal Ordinance (TierSchVersV). The experimental protocol described here was reviewed by the ethics commission (§15 TierSchG) and approved by the state authority (Regierungspräsidium, Tübingen, Baden-Württemberg, Germany).

1. Preparing the BOLD-fMRI experimental set-up for small animal study

1. Turn on the console software to control imaging parameters and acquire MRI data.
   NOTE: The proposed real-time fMRI set-up is implemented utilizing macro-functions of the console software (version 6) i....

Results

Figure 3 and Figure 4 show a representative real-time voxel-wise BOLD-fMRI time course and functional maps with electrical forepaw stimulation (3 Hz, 4 s, pulse width 300 us, 2.5 mA). The fMRI design paradigm comprises 10 pre-stimulation scans, 3 stimulation scans, and 12 inter-stimulation scans with a total of 8 epochs (130 scans). The total scan time is 3 min 15 sec (195 sec). Figure 3 shows the voxel-wise time course (black line).......

Discussion

Real-time monitoring of the fMRI signal helps experimenters adjust the physiology of animals to optimize functional mapping. Motion artifacts in awake animals, as well as the anesthetic effect, are major factors that mediate the variability of fMRI signals, confounding the biological interpretation of the signal by itself^{31,32,33,34,35,}

Materials

Name	Company	Catalog Number	Comments
14.1T Bruker MRI system	Bruker BioSpin MRI GmbH	N/A
A365 Stimulus Isolator	World Precision Instruments	N/A
AcqKnowledge Software	Biopac	RRID:SCR_014279, http://www.biopac.com/product/acqknowledge-software/
AFNI	Cox, 1996	RRID:SCR_005927, http://afni.nimh.nih.gov
CO2SMO (ETCO2/SpO2 Monitor), Model 7100	Novametrix Medical Systems Inc	N/A
Isoflurane	CP-Pharma	Cat# 1214
Master-9	A.M.P.I	N/A
Nanoliter Injector	World Precision Instruments	Cat# NANOFIL
Pancuronium Bromide	Inresa Arzneimittel	Cat# 34409.00.00
ParaVision 6	Bruker BioSpin MRI GmbH	RRID:SCR_001964
Phosphate Buffered Saline (PBS)	Gibco	Cat# 10010-023
Rat: Sprague Dawley rat	Charles River Laboratories	Crl:CD(SD)
SAR-830/AP Ventilator	CWE	N/A
α-chloralose	Sigma-Aldrich	Cat# C0128-25G;RRID