An Electronic Aerosol Delivery System for Functional Magnetic Resonance Imaging

Abstract

Background: Public health concerns over the addictive potential of electronic cigarettes (e-cigs) have heightened in recent years. Brain function during e-cig use could provide an objective measure of the addictive potential of new vaping products to facilitate research; however, there are limited methods for delivering e-cig aerosols during functional magnetic resonance imaging (fMRI). The current study describes the development and feasibility testing of a prototype to deliver up to four different e-cig aerosols during fMRI. Methods: Standardized methods were used to test the devices’ air flow variability, nicotine yield, and free radical production. MRI scans were run with and without the device present to assess its safety and effects on MRI data quality. Five daily smokers were recruited to assess plasma nicotine absorption from e-liquids containing nicotine concentrations of 8, 11, 16, 24, and 36 mg/ml. Feedback was collected from participants through a semi-structured interview and computerized questionnaire to assess comfort and subjective experiences of inhaling aerosol from the device. Results: Nicotine yield captured from the aerosol produced by the device was highly correlated with the nicotine concentration of the e-liquids used (R2 = 0.965). Nicotine yield was reduced by a mean of 48% and free radical production by 17% after traveling through the device. The e-liquid containing the highest nicotine concentration tested (36 mg/ml) resulted in the highest plasma nicotine boost (6.6 ng/ml). Overall, participants reported that the device was comfortable to use and inhaling the e-cig aerosols was tolerable. The device was determined to be safe for use during fMRI and had insignificant effects on scan quality. Conclusions: With the current project, we were able to design a working prototype that safely and effectively delivers e-cig aerosols during fMRI. The device has the potential to be used to assess brain activation during e-cig use and to compare brain reactivity to varying flavors, nicotine concentrations, and other e-cig characteristics.

The role of flavors in attractiveness of electronic cigarettes

“…Additional support for the interest in flavors moderating differences in individual factors related to vaping is provided by the different patterns of e-liquid flavors used by dual users and exclusive vapers. In line with previous research, both groups mostly used tobacco and menthol/ mint flavored e-cigarettes at initiation, but exclusive vapers currently used more fruit and sweet e-liquid flavors than dual users 5,34,[60][61][62] . This could be interpreted as vapers switching from tobacco to non-tobacco flavors over time, which is supported by a previous study 5 .…”

“…Research showed that flavorings enhance the rewarding and reinforcing effects of nicotine in e-cigarettes in young adult smokers 60,61 . For example, menthol and the green apple flavoring, farnesene, facilitate nicotine dependence through upregulation of nACh receptors in the brain 62,63 .…”

“…For example, activation in reward-related brain areas could be investigated using fMRI in smokers and non-smokers, exposing them to sweet and savory odors in an e-cigarette and a food context. Odors could be presented using an olfactometer 59 , or using an e-cigarette model that is compatible with an MRI scanner such as the one developed and tested in a recent study 60 . Results of such a study could provide further insight in the effects of context (food vs. e-cigarette), flavor category (sweet vs. savory), as well as user group (smokers vs. non-smokers) on reward from e-cigarettes.…”

Evidence from an fMRI study that dessert-flavored e-cigarettes engage taste-related, but not smoking-related, brain circuitry for female daily smokers.

“…The tobacco industry has long understood that trigeminal stimulation enhances the addictive properties of tobacco products (Megerdichian et al, 2007). During testing, we received anectodal reports from participants that 36 mg/ml aerosol irritated their throat, which was likely more salient while inhaling the unflavored aerosol (Hobkirk et al, 2020). Alternatively, reactions to the strawberry-vanilla flavored aerosol varied across participants and some rated it as unpleasant.…”

“…The brain activation we observed was likely elicited by both nicotine and non-nicotine factors during aerosol inhalation. We did not expect to see strong pharmacological effects of nicotine administration in this study since participants were not required to abstain from smoking and our preliminary testing found that our paradigm administers a relatively small (˜4 ng/mL) nicotine boost compared to a combustible cigarette (15–21 ng/mL) (Hobkirk et al, 2020; Williams et al, 2010). However, participants went at least 1 hr without smoking prior to the scan, and therefore were not completely nicotine satiated during the first run.…”