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In This Article

  • Summary
  • Abstract
  • Introduction
  • Protocol
  • Representative Results
  • Discussion
  • Acknowledgements
  • Materials
  • References
  • Reprints and Permissions

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 responses1,2,3,4,5,6,7,8,9, 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 parameter.......

Representative 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 itself31,32,33,34,35,

Acknowledgements

We thank Dr. D. Chen and Dr. C. Yen for sharing the AFNI script to set up the real-time fMRI for PV 5 and the AFNI team for the software support. This research was supported by NIH Brain Initiative funding (RF1NS113278-01, R01 MH111438-01), and the S10 instrument grant (S10 RR023009-01) to Martinos Center, German Research Foundation (DFG) Yu215/3-1, BMBF 01GQ1702, and the internal funding from Max Planck Society.

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Materials

NameCompanyCatalog NumberComments
14.1T Bruker MRI systemBruker BioSpin MRI GmbHN/A
A365 Stimulus IsolatorWorld Precision InstrumentsN/A
AcqKnowledge SoftwareBiopacRRID:SCR_014279, http://www.biopac.com/product/acqknowledge-software/
AFNICox, 1996RRID:SCR_005927, http://afni.nimh.nih.gov
CO2SMO (ETCO2/SpO2 Monitor), Model 7100Novametrix Medical Systems IncN/A
IsofluraneCP-PharmaCat# 1214
Master-9A.M.P.IN/A
Nanoliter InjectorWorld Precision InstrumentsCat# NANOFIL
Pancuronium BromideInresa ArzneimittelCat# 34409.00.00
ParaVision 6Bruker BioSpin MRI GmbHRRID:SCR_001964
Phosphate Buffered Saline (PBS)GibcoCat# 10010-023
Rat: Sprague Dawley ratCharles River LaboratoriesCrl:CD(SD)
SAR-830/AP VentilatorCWEN/A
α-chloraloseSigma-AldrichCat# C0128-25G;RRID

References

  1. Ogawa, S., Lee, T. M., Kay, A. R., Tank, D. W. Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proceedings of the National Academy of Sciences U.S.A. 87 (24), 9868-9872 (1990).
  2. Belliveau, J. W., et al.

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