Functional MRI of the mouse olfactory system

Muir, Eric R.; Biju, K.C.; Cong, Linlin; Rogers, William E.; Hernandez, Enrique Torres; Duong, Timothy Q.; Clark, Robert A.

doi:10.1016/j.neulet.2019.03.055

Cited by 16 publications

(18 citation statements)

References 30 publications

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“…Neuronal activation triggered cerebral blood flow (CBF) increase during odor stimulation has been demonstrated in the rodent OB using two-photon imaging and electrophysiology recordings ( Chaigneau et al, 2007 ). Although functional activities in the OB have been measured in various animal studies ( Xu et al, 2000 , 2003 , 2005 ; Boyett-Anderson et al, 2003 ; Cross et al, 2004 ; Schafer et al, 2005 ; Martin et al, 2007 ; Jia et al, 2014 ; Li et al, 2014 ; Poplawsky and Kim, 2014 ; Berns et al, 2015 ; Zhao et al, 2015 , 2016 , 2017 ; Murphy et al, 2016 ; Muir et al, 2019 ), to our knowledge, this is the first fMRI study to detect functional activation in the OB in human subjects using whole brain BOLD fMRI. Previous reports that detected functional activation in the OB are either animal studies ( Xu et al, 2000 , 2003 , 2005 ; Boyett-Anderson et al, 2003 ; Cross et al, 2004 ; Schafer et al, 2005 ; Martin et al, 2007 ; Jia et al, 2014 ; Li et al, 2014 ; Poplawsky and Kim, 2014 ; Berns et al, 2015 ; Zhao et al, 2015 , 2016 , 2017 ; Murphy et al, 2016 ; Muir et al, 2019 ) or human scans with partial brain coverage ( Fournel et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…It is especially challenging to do fMRI in the OB because of significant susceptibility artifacts and the small size of the bulb. Functional activities in the OB have been reported in rodents using fMRI ( Xu et al, 2000 , 2003 , 2005 ; Schafer et al, 2005 ; Martin et al, 2007 ; Li et al, 2014 ; Poplawsky and Kim, 2014 ; Murphy et al, 2016 ; Zhao et al, 2016 , 2017 ; Muir et al, 2019 ) and manganese enhanced MRI ( Cross et al, 2004 ), in dogs ( Jia et al, 2014 ; Berns et al, 2015 ) using fMRI, and in non-human primates using fMRI ( Boyett-Anderson et al, 2003 ; Zhao et al, 2015 ). A recent human study used a surface coil covering most of the primary olfactory regions to do fMRI in the OB ( Fournel et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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Functional Activities Detected in the Olfactory Bulb and Associated Olfactory Regions in the Human Brain Using T2-Prepared BOLD Functional MRI at 7T

et al. 2021

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Olfaction is a fundamental sense that plays a vital role in daily life in humans, and can be altered in neuropsychiatric and neurodegenerative diseases. Blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) using conventional echo-planar-imaging (EPI) based sequences can be challenging in brain regions important for olfactory processing, such as the olfactory bulb (OB) and orbitofrontal cortex, mainly due to the signal dropout and distortion artifacts caused by large susceptibility effects from the sinonasal cavity and temporal bone. To date, few studies have demonstrated successful fMRI in the OB in humans. T2-prepared (T2prep) BOLD fMRI is an alternative approach developed especially for performing fMRI in regions affected by large susceptibility artifacts. The purpose of this technical study is to evaluate T2prep BOLD fMRI for olfactory functional experiments in humans. Olfactory fMRI scans were performed on 7T in 14 healthy participants. T2prep BOLD showed greater sensitivity than GRE EPI BOLD in the OB, orbitofrontal cortex and the temporal pole. Functional activation was detected using T2prep BOLD in the OB and associated olfactory regions. Habituation effects and a bi-phasic pattern of fMRI signal changes during olfactory stimulation were observed in all regions. Both positively and negatively activated regions were observed during olfactory stimulation. These signal characteristics are generally consistent with literature and showed a good intra-subject reproducibility comparable to previous human BOLD fMRI studies. In conclusion, the methodology demonstrated in this study holds promise for future olfactory fMRI studies in the OB and other brain regions that suffer from large susceptibility artifacts.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Functional Activities Detected in the Olfactory Bulb and Associated Olfactory Regions in the Human Brain Using T2-Prepared BOLD Functional MRI at 7T

et al. 2021

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“…New experimental approaches including genome-wide association studies (GWAS) [ 188 , 191 , 192 ], CRISPR-Cas9 technology [ 193 , 194 , 195 ], high throughput screening (HTS) [ 196 ], organ-on-chip technologies [ 197 , 198 ], functional MRI (fMRI) techniques [ 199 , 200 ], and positron emission tomography (PET) [ 201 ] may lead to new drug targets for NDs, which can feed into future CADD projects.…”

Section: A Roadmap For Implementing Cadd In Nd Drug Designmentioning

confidence: 99%

Advances in Applying Computer-Aided Drug Design for Neurodegenerative Diseases

Salman

Al-Obaidi

Kitchen

et al. 2021

IJMS

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Neurodegenerative diseases (NDs) including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease are incurable and affect millions of people worldwide. The development of treatments for this unmet clinical need is a major global research challenge. Computer-aided drug design (CADD) methods minimize the huge number of ligands that could be screened in biological assays, reducing the cost, time, and effort required to develop new drugs. In this review, we provide an introduction to CADD and examine the progress in applying CADD and other molecular docking studies to NDs. We provide an updated overview of potential therapeutic targets for various NDs and discuss some of the advantages and disadvantages of these tools.

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“…Alternative to medetomidine anesthesia, we previously developed an intermittent intraperitoneal ketamine/xylazine (K/X) anesthesia protocol for mouse fMRI 43 with several subsequent mouse fMRI studies utilizing ketamine or the cocktail 9 , 16 , 41 , 44 . The cocktail is commonly used during animal surgery, but when applied with fMRI, we found it to have robust, longitudinal cortical response to forepaw stimulation at 9.4 Tesla.…”

Section: Introductionmentioning

confidence: 99%

Characterization of brain-wide somatosensory BOLD fMRI in mice under dexmedetomidine/isoflurane and ketamine/xylazine

You

Kim

2021

Sci Rep

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Mouse fMRI under anesthesia has become increasingly popular due to improvement in obtaining brain-wide BOLD response. Medetomidine with isoflurane has become well-accepted for resting-state fMRI, but whether this combination allows for stable, expected, and robust brain-wide evoked response in mice has yet to be validated. We thus utilized intravenous infusion of dexmedetomidine with inhaled isoflurane and intravenous infusion of ketamine/xylazine to elucidate whether stable mouse physiology and BOLD response are obtainable in response to simultaneous forepaw and whisker-pad stimulation throughout 8 h. We found both anesthetics result in hypercapnia with depressed heart rate and respiration due to self-breathing, but these values were stable throughout 8 h. Regardless of the mouse condition, brain-wide, robust, and stable BOLD response throughout the somatosensory axis was observed with differences in sensitivity and dynamics. Dexmedetomidine/isoflurane resulted in fast, boxcar-like, BOLD response with consistent hemodynamic shapes throughout the brain. Ketamine/xylazine response showed higher sensitivity, prolonged BOLD response, and evidence for cortical disinhibition as significant bilateral cortical response was observed. In addition, differing hemodynamic shapes were observed between cortical and subcortical areas. Overall, we found both anesthetics are applicable for evoked mouse fMRI studies.

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Functional MRI of the mouse olfactory system

Cited by 16 publications

References 30 publications

Functional Activities Detected in the Olfactory Bulb and Associated Olfactory Regions in the Human Brain Using T2-Prepared BOLD Functional MRI at 7T

Functional Activities Detected in the Olfactory Bulb and Associated Olfactory Regions in the Human Brain Using T2-Prepared BOLD Functional MRI at 7T

Advances in Applying Computer-Aided Drug Design for Neurodegenerative Diseases

Characterization of brain-wide somatosensory BOLD fMRI in mice under dexmedetomidine/isoflurane and ketamine/xylazine

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