Name: a free-breathing fmri method to study human olfactory function
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Het volgende experimentele protocol volgde de richtlijnen van de Institutional Review Board van de Pennsylvania State University College of Medicine, en het menselijk subject gaf schriftelijk geïnformeerde toestemming voor deelname aan de studie. Opmerking: Voor het demonstratieproces wordt een simpel geurstimulatieparadigma gegeven met behulp van een in de handel verkrijgbare, MRI-compatibele olfactometer. Dit paradigma heeft bewezen effectief in het verminderen van het habituation effect ...

<ol>
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Experimentele procedures dienen zorgvuldig te worden overwogen en correct uitgevoerd te worden voor het verzamelen van betrouwbare, activeringsactivering data. De kritieke stappen in het protocol omvatten het implementeren van een ademhaling-triggered paradigma om de geurafgifte te synchroniseren met beeldverwerving, de juiste concentraties geurstoffen op te stellen om psychofysische reacties te regelen, de olfactometer op te zetten met een betrouwbaar stabiel ademhalingssignaal en een constante luchtstroom, en respirat...

Het menselijke olfactorische systeem wordt veel meer begrepen dan een zintuiglijk systeem, omdat olfaction ook een belangrijke rol speelt bij homeostatische regulering en emoties. Klinisch is het menselijk olfactorische systeem bekend om kwetsbaar te zijn tegen aanvallen van veel voorkomende neurologische ziekten en psychiatrische stoornissen, zoals de ziekte van Alzheimer, de ziekte van Parkinson, posttraumatische stressstoornis en depressie 1 , 2 , 3 , 4 , 5 . Momenteel is functionele magnetische resonantiebeeldvorming (fMRI) met bloed-zuurstofgehaltenafhankelijk (BOLD) contrast de meest waardevolle techniek voor het mappen van functies van het menselijke brein. Een aanzienlijke hoeveelheid kennis over specifieke functies van centrale olfactorische structuren ( bijv . Piriforme cortex, orbitofrontale cortex, amygdala en insulaire cortex) is verkregen met deze techniekIque 6 , 7 , 8 , 9 , 10 . De toepassing van fMRI op studies van het menselijke centrale olfactorische systeem en bijbehorende aandoeningen is echter belemmerd door twee belangrijke obstakels: snelle aanwending van het BOLD signaal en variabele modulatie door ademhaling. In het dagelijks leven, wanneer we gedurende een bepaalde tijd aan een geurstof blootgesteld worden, raken we snel aan de geur. In feite, wanneer het met behulp van olfactief fMRI wordt bestudeerd, wordt het geurgeïnduceerde fMRI-signaal snel verzwakt door habituation, wat een uitdaging vormt voor de ontwerpen van stimulatieparadigma 8 , 10 , 11 , 12 , 13 , 14 . Het eerste significante BOLD-signaal in de primaire olfactieve cortex blijft alleen bestaanS enkele seconden na het ontstaan ​​van de geur. Daarom moeten olfactieve fMRI-paradigma&#39;s langdurige of frequente geurstimulaties in een korte periode vermijden. Om het wervingseffect te verminderen, hebben sommige studies geprobeerd alternerende geuren in een fMRI-paradigma te presenteren. Deze aanpak kan echter data-analyse compliceren, aangezien elke geurstof als een onafhankelijke stimulatie-gebeurtenis kan worden behandeld. Een ander technisch probleem is ontstaan ​​met variabiliteit in de ademhalingspatronen van proefpersonen; Inhalatie synchroniseert niet altijd met geuradministratie tijdens een fixed-timing paradigma. Het begin en de duur van de olfactorische stimulatie worden gemoduleerd door de ademhaling van elke individu, waardoor fMRI-data kwaliteit en analyse wordt verstoord. Sommige studies hebben geprobeerd dit probleem te verminderen met visuele of auditieve signalen om het adem- en geurend begin te synchroniseren, maar de naleving van de onderwerpen is variabel, vooral in de klinische populatie. De hersenactivaties geassocieerd met wiDeze cues kunnen ook data-analyse compliceren in bepaalde toepassingen. Zodoende kan synchronisatie van inhalatie met geurstoflevering cruciaal zijn voor olfactieve fMRI studies 15 . Een extra overweging die essentieel is voor olfactorische fMRI, in het bijzonder in het data-analyseproces, is de selectie van geurstoffen. Het vinden van een passende geurstofconcentratie met betrekking tot de waargenomen intensiteit is belangrijk voor kwantificering en vergelijking van activeringsniveaus in de hersenen onder verschillende experimentele aandoeningen of ziekten. De selectie van geurstoffen moet ook rekening houden met geurvalentie of aangename smaak. Dit is bekend dat divergente temporale profielen in olfactisch leren 16 , 17 veroorzaken . Lavendelgeur is voor deze reden voor deze demonstratie gekozen. Afhankelijk van het doel van een specifieke studie kunnen verschillende geurstoffen betere keuzes zijn. Bovendien moet trigeminale stimulatie minimaal worden verminderdE-activering niet direct verband houdend met olfaction 18 . In dit rapport demonstreert we een fMRI techniek om een ​​respiratie-triggered paradigma op te zetten en uit te voeren met behulp van een olfactometer in de magnetische resonantie omgeving. We presenteren ook een postverwerkingshulpmiddel dat bepaalde timingfouten kan verminderen die zich tijdens de acquisitie kunnen voordoen in een poging om de data-analyse verder te verbeteren.

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	<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

De studie van menselijke vervloeking is een zeer complex en waardevol gebied met toepassingen, variërend van biomedisch onderzoek naar klinische evaluatie. Momenteel is evaluatie van de functies van het menselijke centrale olfactorische systeem met functionele magnetische resonantiebeeldvorming (fMRI) nog steeds een uitdaging vanwege technische problemen. Er zijn enkele significante variabelen om rekening te houden bij het overwegen van een effectieve methode voor het in kaart brengen van de functie van het centrale olfactorische systeem met behulp van fMRI, met inbegrip van de juiste reukstofselectie, de interactie tussen geurpresentatie en ademhaling, en mogelijke anticipatie of aanpassing aan geurstoffen. Een gebeurtenisgerelateerde, respiratie-geactiveerde olfactieve fMRI-techniek kan geurstoffen nauwkeurig aansturen om het olfactorische systeem te stimuleren, terwijl potentiële interferentie wordt beperkt. Het kan effectief vastleggen van de precieze aanvang van fMRI signalen in de primaire olfactieve cortex met behulp van onze data post-processing methode. De techniek voorafHier verzonden, biedt een efficiënte en praktische manier om betrouwbare olfactieve fMRI resultaten te genereren. Zo&#39;n techniek kan uiteindelijk in het klinische rijk worden toegepast als een diagnostisch hulpmiddel voor ziektes die verband houden met olfactieve degeneratie, met inbegrip van de ziekte van Alzheimer en Parkinson, als we de complexiteit van het menselijke olfactorische systeem verder begrijpen.

Figuur 1 toont de opstelling van olfactorische fMRI binnen en buiten de magneetkamer, rekening houdend met MR-compatibiliteit. Figuur 2a toont een standaard fix-timing paradigma, terwijl Figuur 2b een paradigma demonstreert waarbij de &quot;respiratier trigger&quot; de synchronisatie van geurafgifte en inhalatie mogelijk maakt. Een regelm...

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A Free-breathing fMRI Method to Study Human Olfactory Function

Wij presenteren de technische uitdagingen en oplossingen voor het verkrijgen van betrouwbare functionele magnetische resonantiebeeldvorming (fMRI) data van het menselijke centrale olfactorische systeem. Dit omvat speciale overwegingen in het olfactorisch fMRI-paradigma-ontwerp, beschrijvingen van fMRI-dataverzameling met een MRI-compatibele olfactometer, geurverdeling en een speciaal softwareprogramma voor data post-processing.

Een vrije ademhaling fMRI methode om menselijke olfactieve functie te bestuderen

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

The overall goal of this video is to present and explain an efficient and easily adaptable method of fMRI in order to effectively explore the mapping of the human olfactory system without interference of natural breathing. One obstacle of using olfactory fMRI to study the brain activation responding to odor and stimulation, is the inconsistency of repetitive odor stimulation, which is caused by the asynchrony of respiration and odor delivery. As illustrated here, when the odor presentation in a fixed timing odor stimulation paradigm is not synchronized with respiration, the repetitive odor stimulation can happen at different phases of respiration.A solution to this problem is to set up a respiration-triggered olfactory fMRI paradigm. Effective olfactory fMRI data collection is accomplished by first designing an event related respiration-triggered olfactory stimulation paradigm on the olfactometer that is resist to habituation and inconsistent inhalation patterns. The second step is to prepare odorants for the olfactory stimulation, taking care to use odorants that minimize trigeminal stimulation and habituation effects.The third step is to set up and run the experiment in the MRI environment by assembling the olfactometer with the capability of running a respiration-triggered paradigm. The final step is to process the data using the program ONSET to define the actual onset and the duration vectors of the stimuli. Ultimately, this technique has the potential to facilitate more sensitive exploration and connections of the human olfactory system.Here, we will demonstrate how to set up a respiration-triggered olfactory fMRI experiment using an ETT Olfactometer. To create a paradigm, assign the odorant channels to specific odorants. There are six odorant channels available in this olfactometer system.Input and edit the sequence and timing of open and close of these channels. Push the Paradigm Setting button on the touchscreen. To input or edit the sequence of the open and close of the odorant channels, push the Edit button for the Valve Sequence.When finished, push the Edit button again to exit the editing mode. To input or edit the timing parameters for the open and close of the odorant channels, push the Set button for Time Sequence. When finished, push the Set button again to exit the editing mode.After finishing the Paradigm Setting, push the Return button to return to the main window. Demonstrated in this video is a simple stimulation paradigm of the same odorant in the same concentration. Each odorant presentation is interleaved with the presentation of fresh air.In this paradigm, the same odor is presented 12 times. Each time, the odorant presentation lasts for six seconds with variable amounts of time between the odor presentations. Set the Valve Open and Valve Close durations, accordingly.In this demonstration, one concentration of lavender oil is prepared. We use lavender oil because of its minimal trigeminal stimulation and activation of certain brain areas. The odorant concentrations can be varied depending on the odorant selected.Choose the concentrations based upon the ideal perception threshold of the odor. By varying the concentration, we lessen the likelihood of habituation to an odorant. To prepare the concentrations, mix the lavender oil with propylene glycol.Propylene glycol is a commonly used solvent for odorants and is stable and nearly odorless. After mixing all solutions as outlined in the paradigm design, pour the same amount of odorants into each container bottle. Then, attach the bottles to the odorant carrier in the correct order.To set up the olfactometer in the MRI, place the odorant carrier in the magnet room next to the machine. Run the tubes through the wave guide to connect to the carrier, taking care that the order of tubes matches the order connecting to the olfactometer. For ease, we color code our tubings to match the odorant channels.Turn the machine on. Adjust the main airflow, as necessary, as well as the individual flow rates for the carrier and flush. Then, connect the respiration belt to the olfactometer and run the belt through the wave guide.The belt will record the subject's respiration activity, as well as the utilization of the respiration trigger. Bring the subject into the magnet room and place the face mask on the subject. When the subject is lying down, place the respiratory belt around their chest or abdomen where there is clear respiration event.Check the respiration pattern on the screen of the olfactometer. If the waves plateau, the belt is fastened too tightly and the respiration trigger will not work properly. Adjust the belt until a complete respiration trace can be seen, as clear respiration peak signals are critical for a successful execution of a respiration-triggered paradigm.Create a data folder on the olfactometer to store the respiration data. The synchrony of the odor presentation with respiration should be tested for accuracy by using the Paradigm Check and adjusting the Trigger Delay time, as necessary. Push the Paradigm Check button on the touchscreen and monitor if odor delivery happens during the inhalation phase of the respiration cycle.The odor delivery period is highlighted in the color pink on the respiration trace. If odor delivery starts during the exhalation phase, to back to Paradigm Setting, adjust the Trigger Delay in the time sequence and then redo the Paradigm Check. Set the paradigm to Trigger In mode so that the execution of the odor stimulation paradigm will be triggered by MRI scanning.Then select the Respiration Trigger Start function. The paradigm is now ready to be run. Once the odor stimulation paradigm is completed, check the respiration data saved in the olfactometer.This file includes the respiration trace and the time stamp of each functional MRI image, respiration trigger, open and close of each odor channel, and the subject response, using a response device. It can be processed using the program ONSET to acquire the actual stimulation onset vectors and durations for fMRI data processing. ONSET can be run in the IDL Virtual Machine.To get the odor stimulation onset vectors and durations, click Respiration Validation. Load the respiration data file that's saved from the olfactometer and set the post processing parameters for ONSET processing. Run ONSET.The actual stimulation onset vectors, the start of each inhalation during odor delivery, will automatically be detected based on the timing of odor presentation and the respiration trace. The results, including the onset and duration vectors, can be utilized in fMRI data processing. Process the fMRI data following standard procedures.Here is an example of data processing using SPM8. Use either the image numbers or the onset vectors and durations in seconds from the onset output, depending on the timing unit chosen for the SPM paradigm design. Generate a statistical parametric map at the individual level by fitting the stimulation paradigm using the actual onset and duration vectors to the functional data with the canonical hemodynamic response function.Here is an example of the primary olfactory cortex activation responding to the odor stimulation. In contrast to the respiration-triggered odor stimulation paradigm, for example, a fixed timing paradigm which we can see here from the same subject, the odor delivery is not triggered by respiration activity. Since there is no control of the subject's respiration, there is significant variability in the amount of odorant that is inhaled.Following the standard procedure to process these fMRI data with the same statistical threshold as that used for the previous respiration-triggered fMRI data, no significant activation was detected in the primary olfactory cortex. However, when a respiration trigger is implemented, odorant presentation is always synchronized with inhalation, improving the consistency and accuracy of odor stimulation. After watching this video, you should have a good understanding of the current practice of olfactory fMRI using an event related respiration-triggered paradigm.Once the technique demonstrated in this video has been mastered, further olfactory stimulation paradigm design and analysis methods can be applied to map the functions of the human central olfactory system and to further explore the olfactory deficits in neurodegenerative diseases.

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