Assessing Metabolic Neuromodulation Induced by Acute Deep Brain Stimulation in Rats Using In Vivo FDG-PET

Abstract

Source: Casquero-Veiga, M. et al. In vivo Positron Emission Tomography to Reveal Activity Patterns Induced by Deep Brain Stimulation in Rats. J. Vis. Exp. (2022).

This video demonstrates the metabolic effects of deep brain stimulation (DBS) using FDG-PET imaging in a rat model. It outlines the steps involved in FDG administration, DBS application, and PET/CT imaging to map brain regions with increased or suppressed metabolic activity.

Protocol

All procedures involving animal models have been reviewed by the local institutional animal care committee and the JoVE veterinary review board.

1. Electrical stimulation administration

NOTE: Electrical stimulation is delivered during the 2-deoxy-2-[¹⁸F]fluoro-D-glucose (FDG) uptake period. For this protocol, the stimulation was delivered with an isolated stimulator, with high-frequency (130 Hz) electrical stimulation in a constant current mode, 150 µA, and a pulse width of 100 µs.

1. DBS stimulator configuration
   1. Prepare the isolated stimulator and the required wires in a wide and quiet room, with enough space for the animal cages and minimal influence of potentially disturbing stimuli.
   2. Connect the stimulation wires to the swivels to allow animals to move freely within their cages and to the stimulator.
   3. Set the stimulation parameters according to the needs of the study.
   4. Use an oscilloscope to check the current mode, frequency, and pulse width. Confirm the biphasic waveform with a rectangular pulse shape.
2. DBS delivery
   1. After the imaging session of the animal without stimulation (D1) and until the session two days later with stimulation (D2), subject animals to a daily habituation protocol (45 min/day) to accustom them to the stimulation system and the operator's handling, avoiding undesirable stress responses in D2. Connect the stimulation system to each animal, but without turning on the stimulation.
   2. Once the stimulator has been set up and the animal has been injected with FDG, connect the swivel to the electrodes and turn on the stimulator.
   3. After 45 min, turn off the stimulator, disconnect the animal from the swivel, and quickly transfer it to an anesthesia induction chamber to begin positron emission tomography (PET) image acquisition.

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Commutator	Plastics One, USA	SL2+2C	4 Channel Commutator for DBS
Concentric bipolar platinum-iridium electrodes	Plastics One, USA	MS303/8-AIU/Spc	Electrodes for DBS
FDG	Curium Pharma Spain S.A., Spain	-----	2-[¹⁸F]fluoro-2-deoxy-D-glucose (PET radiotracer)
MatLab R2021a	The MathWorks, Inc		Support software for SPM12
MRIcro	McCausland Center for Brain Imaging, University of South Carolina, USA	v2.1.58-0	Software for imaging preprocessing and analysis
Multimodality Workstation (MMWKS)	BiiG, Spain		Software for imaging processing and analysis
Statistical Parametric Mapping (SPM12)	The Wellcome Center for Human Neuroimaging, UCL Queen Square Institute of Neurology, UK	SPM12	Software for voxel-wise imaging analysis
STG1004	Multi Channel Systems GmbH, Germany	STG1004	Isolated stimulator
SuperArgus PET/CT scanner	Sedecal, Spain	S0026403	NanoPET/CT scanner for small animal imaging
Wistar rats (Rattus norvergicus)	Charles River, Spain	animal facility	Animal model used