Name: a free-breathing fmri method to study human olfactory function
Uploaded: 2017-07-30T13:00:00
Description: Watch this Scientific Journal Video about A Free-breathing fMRI Method to Study Human Olfactory Function at JoVE.com

The authors have no acknowledgements.

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...

<ol>
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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...

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&#39;s disease, Parkinson&#39;s disease, post-traumatic stress disorder, and depression1,2,3,4,5. Currently, functional magnetic resonance imaging (fMRI) with blood-oxygen-level-dependent (BOLD) contrast is the most valuable technique for mapping functions of the human brain. A significant amount of knowledge about specific functions of central olfactory structures (e.g., piriform cortex, orbitofrontal cortex, amygdala, and insular cortex) has been acquired with this technique6,7,8,9,10.
The application of fMRI to studies of the human central olfactory system and associated diseases, however, has been hindered by two major obstacles: rapid habituation of BOLD signal and variable modulation by respiration. In everyday life, when exposed to an odorant for a period of time, we quickly habituate to the scent. In fact, when studied using olfactory fMRI, the odor-induced fMRI signal is rapidly attenuated by habituation, which poses a challenge on stimulation paradigm designs8,10,11,12,13,14. The initial&#160;significant BOLD signal in the primary olfactory cortex only persists for several seconds after odorant onset. Therefore, olfactory fMRI paradigms should avoid prolonged or frequent odor stimulations in a short period of time. To reduce the habituation effect, some studies have attempted to present alternating odors in an fMRI paradigm. However, this approach may complicate data analysis since each odorant can be treated as an independent stimulation event.
Another technical issue arises with variability in subjects&#39; respiration patterns; inhalation does not always synchronize with odorant administration during a fixed-timing paradigm. The onset and duration of olfactory stimulation are modulated by each individual&#39;s respiration, which confounds fMRI data quality and analysis. Some studies have attempted to mitigate this problem with visual or auditory cues to synchronize breathing and odorant onset, but the compliance of subjects is variable, especially in the clinical population. The brain activations associated with these cues could also complicate data analysis in certain applications. Thus, synchronizing inhalation with odorant delivery can be crucial for olfactory fMRI studies15.
An additional consideration vital to olfactory fMRI, especially in the data analysis process, is odorant selection. Finding an appropriate odorant concentration with respect to perceived intensity is important for quantification and comparison of activation levels in the brain under various experimental conditions or diseases. Odorant selection must also take into consideration odor valence, or pleasantness. This is known to cause divergent temporal profiles in olfactory learning16,17. Lavender odor was chosen for this demonstration partially for this reason. Depending on the purpose of a specific study, different odorants may be better choices. In addition, trigeminal stimulation must be minimized to reduce activation not directly related to olfaction18.
In this report, we demonstrate an fMRI technique to set up and run a respiration-triggered paradigm using an olfactometer in the magnetic resonance environment. We also present a post-processing tool that can diminish some timing errors that may have occurred during data acquisition in an attempt to further improve data analysis.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>3T MR scanner</td>
			<td>Siemens</td>
			<td></td>
			<td>Any MR scanner is acceptable.&#160;</td>
		</tr>
		<tr>
			<td>Olfactometer</td>
			<td>Emerging Tech Trans, LLC</td>
			<td></td>
			<td>Any olfactometer with similar capabilities is acceptable.</td>
		</tr>
		<tr>
			<td>6-channel odorant carrier</td>
			<td>Emerging Tech Trans, LLC</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Nosepiece/applicator</td>
			<td>Emerging Tech Trans, LLC</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>PTFE tubing</td>
			<td>Emerging Tech Trans, LLC</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>TTL convertor box</td>
			<td>Emerging Tech Trans, LLC</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Respiratory sensor belt</td>
			<td>Emerging Tech Trans, LLC</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Lavender oil</td>
			<td>Givaudan Flavors Corporation</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>1,2 propanediol</td>
			<td>Sigma</td>
			<td>P6209</td>
			<td></td>
		</tr>
		<tr>
			<td>ONSET</td>
			<td></td>
			<td></td>
			<td>www.pennstatehershey.org/web/nmrlab/resources/software/onset</td>
		</tr>
		<tr>
			<td>SPM8&#160;</td>
			<td>Wellcome Trust Center for Neuroimaging, University College London, London, UK&#160;</td>
			<td></td>
			<td></td>
		</tr>
	</tbody>
</table>

a free-breathing fmri method to study human olfactory function

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&#39;s and Parkinson&#39;s disease, as we begin to further understand the complexities of the human olfactory system.

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 &#34;respiration trigger&#34; allows for the synchronization of odor delivery and inhalation.
A regular res...

Watch this Scientific Journal Video about A Free-breathing fMRI Method to Study Human Olfactory Function at JoVE.com

A Free-breathing fMRI Method to Study Human Olfactory Function

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.

The study of human olfaction is a highly complex and valuable field with applications ranging from biomedical research to clinical evaluation. Currently, ...

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