Animal studies in clinical MRI scanners: A custom setup for combined fMRI and deep-brain stimulation in awake rats

Maik Derksen,Valerie Rhemrev,Marijke Van Der Veer,Linda Jolink,Birte Zuidinga,Tosca Mulder,Liesbeth Reneman,Aart Nederveen,Matthijs Feenstra,Ingo Willuhn,Damiaan Denys

doi:10.1016/j.jneumeth.2021.109240

Abstract

BackgroundIn humans, functional magnetic resonance imaging (fMRI) cannot be used to its full potential to study the effects of deep-brain stimulation (DBS) on the brain due to safety reasons. Application of DBS in small animals is an alternative, but was hampered by technical limitations thus far. New MethodWe present a novel setup that extends the range of available applications by studying animals in a clinical scanner. We used a 3 T-MRI scanner with a custom-designed receiver coil and a restrainer to measure brain activity in awake rats. DBS electrodes made of silver were used to minimize electromagnetic artifacts. Before scanning, rats were habituated to the restrainer. ResultsUsing our novel setup, we observed minor DBS-electrode artifacts, which did not interfere with brain-activity measurements significantly. Movement artifacts were also minimal and were not further reduced by restrainer habituation. Bilateral DBS in the dorsal part of the ventral striatum (dVS) resulted in detectable increases in brain activity around the electrodes tips. Comparison with Existing MethodsThis novel setup offers a low-cost alternative to dedicated small-animal scanners. Moreover, it can be implemented in widely available clinical 3 T scanners. Although spatial and temporal resolution was lower than what is achieved in anesthetized rats in high-field small-animal scanners, we obtained scans in awake animals, thus, testing the effects of bilateral DBS of the dVS in a more physiological state. ConclusionsWith this new technical setup, the neurobiological mechanism of action of DBS can be explored in awake, restrained rats in a clinical 3 T-MRI scanner.

Highlights

Deep-brain stimulation (DBS) is an intervention that relies on implanted electrodes delivering high-frequency currents into targeted brain areas
Stimulation electrodes were custom-made from either platinum/ iridium wires (90 % platinum, 10 % iridium, 75 μm bare diameter, 18 μm PFTE insulation coating, Advent Research Materials LTD, Oxford, United Kingdom), a paramagnetic alloy commonly used for electrodes in animal research with a magnetic susceptibility of 27 × 10− 5 at 20 de grees Celsius, or silver wires (99.99 % pure silver, 125 μm bare diameter, 26 um PFTE insulation coating, Advent Research Materials LTD, Oxford, United Kingdom), a diamagnetic alloy with a relatively lower magnetic susceptibly of -2.6 × 10-5
Visual inspection of the T2-weighted images of the custom-made, two-channel electrodes of different materials, indicates that electrodes made of silver induce smaller MRI artifacts than electrodes made of the commonly used platinum/iridium (Fig. 1)

Summary

Introduction

Deep-brain stimulation (DBS) is an intervention that relies on implanted electrodes delivering high-frequency currents into targeted brain areas. Comparison with Existing Methods: This novel setup offers a low-cost alternative to dedicated small-animal scanners. It can be implemented in widely available clinical 3 T scanners. Spatial and temporal resolution was lower than what is achieved in anesthetized rats in high-field small-animal scanners, we obtained scans in awake animals, testing the effects of bilateral DBS of the dVS in a more physiological state. Conclusions: With this new technical setup, the neurobiological mechanism of action of DBS can be explored in awake, restrained rats in a clinical 3 T-MRI scanner

Methods

Results

Conclusion