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

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O seguinte protocolo experimental seguiu as diretrizes do Conselho de Revisão Institucional da Faculdade de Medicina da Universidade Estadual da Pensilvânia, e o sujeito humano deu o consentimento informado por escrito antes de participar do estudo. Nota: Para fins de demonstração, é apresentado um paradigma de estimulação de odor simples usando um olfactômetro compatível com MRI comercialmente disponível. Este paradigma mostrou-se efetivo na redução do efeito de habituação e p...

<ol>
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Os procedimentos experimentais devem ser cuidadosamente considerados e executados corretamente para a coleta de dados confiáveis ​​de ativação olfativa. Os passos críticos dentro do protocolo incluem a implementação de um paradigma desencadeado pela respiração para sincronizar o fornecimento de odor com a aquisição da imagem, preparando concentrações adequadas de odorantes para controlar as respostas psicofísicas, estabelecendo o olfatômetro com sinal de respiração estável confiável e fluxo de ar c...

O sistema olfativo humano é entendido como muito mais do que um sistema sensorial porque o olfato também desempenha um papel importante na regulação homeostática e nas emoções. Clinicamente, o sistema olfativo humano é conhecido por ser vulnerável a ataques de muitas doenças neurológicas prevalentes e transtornos psiquiátricos, como doença de Alzheimer, doença de Parkinson, transtorno de estresse pós-traumático e depressão 1 , 2 , 3 , 4 , 5 . Atualmente, a ressonância magnética funcional (fMRI) com contraste dependente do nível de oxigênio no sangue (BOLD) é a técnica mais valiosa para mapear funções do cérebro humano. Uma quantidade significativa de conhecimento sobre funções específicas das estruturas olfativas centrais ( por exemplo , córtex piriforme, córtex orbitofrontal, amígdala e córtex insular) foi adquirida com este tecnológicoIque 6 , 7 , 8 , 9 , 10 . A aplicação de fMRI aos estudos do sistema olfativo central humano e doenças associadas, no entanto, tem sido dificultada por dois grandes obstáculos: aceleração rápida do sinal BOLD e modulação variável pela respiração. No cotidiano, quando exposto a um odorante por um período de tempo, habitamos rapidamente o aroma. De fato, quando estudado usando fMRI olfatório, o sinal fMRI induzido por odor é rapidamente atenuado pela habituação, o que representa um desafio nos projetos de paradigma de estimulação 8 , 10 , 11 , 12 , 13 , 14 . O sinal BOLD significativo inicial no córtex primário olfativo só persisteS por vários segundos após o início do odor. Portanto, os paradigmas olfativos de fMRI devem evitar estimulações de odor prolongadas ou freqüentes em um curto período de tempo. Para reduzir o efeito de habituação, alguns estudos tentaram apresentar odores alternados em um paradigma de IRMF. No entanto, essa abordagem pode complicar a análise de dados, pois cada odorante pode ser tratado como um evento de estimulação independente. Outra questão técnica surge com a variabilidade nos padrões de respiração dos sujeitos; A inalação nem sempre se sincroniza com a administração de odorantes durante um paradigma de temporização fixa. O início ea duração da estimulação olfativa são modulados pela respiração de cada indivíduo, o que confunde a qualidade e a análise dos dados do fMRI. Alguns estudos tentaram mitigar esse problema com pistas visuais ou auditivas para sincronizar o início da respiração e odorantes, mas a conformidade dos sujeitos é variável, especialmente na população clínica. As ativações cerebrais associadas wiEssas dicas também podem complicar a análise de dados em determinadas aplicações. Assim, a sincronização da inalação com entrega odorante pode ser crucial para os estudos olfativos de fMRI 15 . Uma consideração adicional vital para o fMRI olfativo, especialmente no processo de análise de dados, é a seleção de odorantes. Encontrar uma concentração apropriada de odorantes em relação à intensidade percebida é importante para quantificação e comparação de níveis de ativação no cérebro em várias condições experimentais ou doenças. A seleção de odorantes também deve levar em consideração valência de odor ou prazeres. Isso é conhecido por causar perfis temporais divergentes na aprendizagem olfativa 16 , 17 . O odor de lavanda foi escolhido para esta demonstração parcialmente por esse motivo. Dependendo da finalidade de um estudo específico, diferentes odorantes podem ser melhores escolhas. Além disso, a estimulação trigeminal deve ser minimizada para reduçãoE ativação não diretamente relacionada ao olfato 18 . Neste relatório, demonstramos uma técnica fMRI para configurar e executar um paradigma desencadeado pela respiração usando um olfatômetro no ambiente de ressonância magnética. Também apresentamos uma ferramenta de pós-processamento que pode diminuir alguns erros de temporização que podem ter ocorrido durante a aquisição de dados na tentativa de melhorar ainda mais a análise de dados.

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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

O estudo da olfação humana é um campo altamente complexo e valioso com aplicações que vão desde a pesquisa biomédica até a avaliação clínica. Atualmente, a avaliação das funções do sistema olfativo central humano com ressonância magnética funcional (fMRI) ainda é um desafio devido a várias dificuldades técnicas. Existem algumas variáveis ​​significativas a serem consideradas quando se considera um método efetivo para mapear a função do sistema olfativo central usando fMRI, incluindo a seleção adequada de odorantes, a interação entre apresentação de odor e respiração, e potencial antecipação ou habituação de odorantes. Uma técnica de fMRI olfactiva desencadeada por eventos, relacionada ao evento, pode administrar com precisão odorantes para estimular o sistema olfativo, minimizando a interferência potencial. Ele pode efetivamente capturar os ataques precisos de sinais de fMRI no córtex olfativo primário usando nosso método de pós-processamento de dados. A técnica préAqui, fornece um meio eficiente e prático para gerar resultados confiáveis ​​de fMRI olfativos. Tal técnica pode, em última instância, ser aplicada no campo clínico como uma ferramenta de diagnóstico para doenças associadas à degeneração olfativa, incluindo a doença de Alzheimer e Parkinson, à medida que começamos a compreender melhor as complexidades do sistema olfativo humano.

A Figura 1 demonstra a instalação da fMRI olfativa dentro e fora da sala de ímã, levando em consideração a compatibilidade de MR. A Figura 2a demonstra um paradigma de sincronismo fixo padrão, enquanto a Figura 2b demonstra um paradigma onde o &quot;gatilho de respiração&quot; permite a sincronização de entrega de odor e inalação. <p class="jove_content" fo:keep-together.within-page...

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

Apresentamos os desafios técnicos e as soluções para a obtenção de dados confiáveis ​​de imagem por ressonância magnética funcional (fMRI) do sistema olfativo central humano. Isso inclui considerações especiais no projeto olfativo de paradigma de fMRI, descrições de aquisição de dados fMRI com um olfactômetro compatível com MRI, seleção de odorantes e uma ferramenta de software especial para pós-processamento de dados.

Um método de fmRI de respiração livre para estudar a função olfativa humana

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.

Research

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Neuroscience

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Neurociência

Lentivirus-mediated Genetic Manipulation and Visualization of Olfactory Sensory Neurons in vivo

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The Olfactory System as a Model to Study Axonal Growth Patterns and Morphology In Vivo

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O Sistema Olfativo como um modelo para estudar os padrões de crescimento axonal e Morfologia<em&gt; In Vivo</em

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