Poster Z8 - A Novel Non-Invasive Nasal Stimulation Device for Use in Ischemic Stroke Care

Introduction: Ischemic stroke is the second leading cause of death worldwide with an annual mortality rate of 5.5 million [1]. When ischemic stroke occurs the blood vessels supplying the brain are occluded, cutting off oxygen to affected brain regions [2]. Acute ischemic stroke is treated by restoring cerebral blood flow using tissue plasminogen activators or thrombectomy, but these must be administered within a few hours of stroke onset to be effective [3]. Reducing time-to-treatment during pre-hospital transportation settings can lead to lower mortality rates and better functional outcomes for patients [4]. Recent studies have shown that stimulation of the sphenopalatine ganglion (SPG) leads to increased collateral blood flow [5,6]. However, current devices that stimulate the SPG are invasive, therefore they cannot be used in pre-hospital settings. Here, we have developed a nasopharyngeal device capable of non-invasive SPG stimulation. Our proof-of-concept experiments show that our device can noninvasively simulate the SPG in a phantom model using synthetic mucosal fascia. Additionally, these tests characterize the stimulation and electrode placement parameters that will inform further prototype development.

Materials and

Methods: The nasal mucosa was modeled using 1mm synthetic mucosal fascia tissue plates (SynDaver). Fixtures were designed in Fusion360 (Autodesk) and 3D printed in white polylactic acid using the Ultimaker S5 (Figure 1). The prototype is controlled using an Arduino Uno R3 with code that creates a square pulse wave based on user input pulse width and frequency. A noninverting operational amplifier (TL061IP, DigiKey) amplifies the signal from the Arduino based on a combination of resistors ranging from 1 to 3.3kOhm (SparkFun) to achieve amplitudes up to 16V (Figure 2). Two electrodes (stimulating and ground) were applied to the layered mucosal tissue to administer stimulation, and the output voltage was measured on the other side of the tissue using an oscilloscope as a recording electrode (DS1054, Rigol) (Figure 3). Parameters tested included: mucosal tissue thickness, distance from recording electrode to stimulating and ground electrodes, distance between stimulating and ground electrodes, pulse width, and pulse frequency. Input voltages were increased by adjusting the gain on the operational amplifier to determine the parameters required to reach an output of 10V.

Results, Conclusions, and Discussions: Our proof of concept experiments showed that an input pulse with an amplitude of 15.7V is sufficient to produce 10V through 6mm of mucosal tissue, roughly the average depth at which the SPG sits in the nasal cavity [7]. Increasing mucosal tissue thickness decreased the ability of the electrodes to transmit voltage. Data collection on output voltages across tissue with varying thickness demonstrated an average voltage drop of 15% of voltage at 1mm (SD: 5%), 35% at 4mm (SD: 2%), 36% at 6mm (SD: 3%), 37% at 8mm (SD: 7%), 55% at 10mm (SD: 7%), and 65% at 12mm (SD: 8%). Increasing the distance from the recording electrode to the stimulating or ground electrodes was not associated with changes in output voltage. However, placement of the stimulating electrode closer to the recording electrode resulted in an average increase in output voltage of 0.9V, compared to when the ground electrode was placed closer. Distance between stimulating and ground electrodes also did not impact output voltages. Output voltages remained consistent across pulse widths ranging from 100 to 400 µs and frequencies from 5 to 100 Hz.

The observed voltage drop increases with increasing tissue thickness, suggesting a decline in conductive efficiency. However, preliminary data indicate that variables such as pulse width, frequency and distance between recording and stimulating or ground electrodes do not impact simulation efficacy. While 10V was achieved at 6mm, higher amplitudes will be required to reach this threshold across the range of 4-12mm, accounting for the anatomical variation of SPG depth. These findings support the feasibility of developing a noninvasive and effective SPG stimulation device with the potential for blind placement in pre-hospital settings. Additionally, these results provide guidance for developing future prototypes that will be tested in vivo in large animal models.

Acknowledgements (Optional):

References:
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