A Free-breathing fMRI Method to Study Human Olfactory Function

Summary

We present the technical challenges and solutions for obtaining reliable functional magnetic resonance imaging (fMRI) data from the human central olfactory system. This includes special considerations in olfactory fMRI paradigm design, descriptions of fMRI data acquisition with an MRI-compatible olfactometer, odorant selection, and a special software tool for data post-processing.

Abstract

The study of human olfaction is a highly complex and valuable field with applications ranging from biomedical research to clinical evaluation. Currently, evaluation of the functions of the human central olfactory system with functional magnetic resonance imaging (fMRI) is still a challenge because of several technical difficulties. There are some significant variables to take into account when considering an effective method for mapping the function of the central olfactory system using fMRI, including proper odorant selection, the interaction between odor presentation and respiration, and potential anticipation of or habituation to odorants. An event-related, respiration-triggered olfactory fMRI technique can accurately administer odorants to stimulate the olfactory system while minimizing potential interference. It can effectively capture the precise onsets of fMRI signals in the primary olfactory cortex using our data post-processing method. The technique presented here provides an efficient and practical means for generating reliable olfactory fMRI results. Such a technique can ultimately be applied in the clinical realm as a diagnostic tool for diseases associated with olfactory degeneration, including Alzheimer's and Parkinson's disease, as we begin to further understand the complexities of the human olfactory system.

Introduction

The human olfactory system is understood to be much more than a sensory system because olfaction also plays an important role in homeostatic regulation and emotions. Clinically, the human olfactory system is known to be vulnerable to attacks of many prevalent neurological diseases and psychiatric disorders, such as Alzheimer's disease, Parkinson's disease, post-traumatic stress disorder, and depression^1,2,3,4,5. Currently, functional magnetic resonance imaging (fMRI) with blood-oxygen-level-dependen....

Protocol

The following experimental protocol followed the guidelines of the Institutional Review Board of the Pennsylvania State University College of Medicine, and the human subject gave written informed consent before participating in the study.

Note: For the purpose of demonstration, a simple odor stimulation paradigm using a commercially available, MRI-compatible olfactometer is presented. This paradigm has proven effective in reducing the habituation effect and has produced reliable olfactory fMRI data¹⁵. Certain steps outlined in this protocol may be specific to the type of olfactometer used. However, any type of equipm....

Results

Figure 1 demonstrates the set-up of olfactory fMRI inside and outside of the magnet room, taking into account MR-compatibility. Figure 2a demonstrates a standard fixed-timing paradigm, while Figure 2b demonstrates a paradigm where the "respiration trigger" allows for the synchronization of odor delivery and inhalation.

A regular respiration.......

Discussion

Experimental procedures should be considered carefully and executed properly for collection of reliable olfactory activation data. The critical steps within the protocol include implementing a respiration-triggered paradigm to synchronize odor delivery with image acquisition, preparing proper concentrations of odorants to control psychophysical responses, setting up the olfactometer with reliable stable respiration signal and constant air flow, and post-processing respiration and odor administration timing data using ONS.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
3T MR scanner	Siemens		Any MR scanner is acceptable.
Olfactometer	Emerging Tech Trans, LLC		Any olfactometer with similar capabilities is acceptable.
6-channel odorant carrier	Emerging Tech Trans, LLC
Nosepiece/applicator	Emerging Tech Trans, LLC
PTFE tubing	Emerging Tech Trans, LLC
TTL convertor box	Emerging Tech Trans, LLC
Respiratory sensor belt	Emerging Tech Trans, LLC
Lavender oil	Givaudan Flavors Corporation
1,2 propanediol	Sigma	P6209
ONSET			www.pennstatehershey.org/web/nmrlab/resources/software/onset
SPM8	Wellcome Trust Center for Neuroimaging, University College London, London, UK