Objective Target selectivity of deep brain stimulation (DBS) therapy is critical, as the precise locus and pattern of the stimulation dictates the degree to which desired treatment responses are achieved and adverse side effects are avoided. There is a clear clinical need to improve DBS technology beyond currently available stimulation steering and shaping approaches. We introduce orientation selective neural stimulation as a concept to increase the specificity of target selection in DBS. Approach This concept, which involves orienting the electric field along an axonal pathway, was tested in the corpus callosum of the rat brain by freely controlling the direction of the electric field on a plane using a three-electrode bundle, and monitoring the response of the neurons using functional magnetic resonance imaging (fMRI). Computational models were developed to further analyze axonal excitability for varied electric field orientation. Main results Our results demonstrated that the strongest fMRI response was observed when the electric field was oriented parallel to the axons, while almost no response was detected with the perpendicular orientation of the electric field relative to the primary fiber tract. These results were confirmed by computational models of the experimental paradigm quantifying the activation of radially distributed axons while varying the primary direction of the electric field. Significance The described strategies identify a new course for selective neuromodulation paradigms in DBS based on axonal fiber orientation.

Recently introduced 3D radial MRI pulse sequence entitled Multi-Band SWeep Imaging with Fourier Transformation (MB-SWIFT) having inherently zero acquisition delay was used to obtain functional MRI (fMRI) contrast in rat’s brain at 9.4 Tesla during deep brain stimulation (DBS). The results demonstrate that MB-SWIFT allows images free of susceptibility artefacts, and provides an excellent fMRI activation contrast in the brain. Flip angle dependence of the MB-SWIFT fMRI signal and elimination of the fMRI contrast while using saturation bands, indicate a blood flow origin of the observed fMRI contrast. MB-SWIFT fMRI modality permits activation studies in the close proximity to the implanted lead, which is not possible to achieve with conventionally used gradient echo and spin echo - echo planar imaging fMRI techniques. We conclude that MB-SWIFT fMRI is a powerful imaging modality for investigations of functional responses during DBS.

Purpose To study in vivo radiofrequency (RF) heating produced due to power deposition from a 3T (Larmour frequency = 123.2 MHz), birdcage, whole-body coil. Methods The RF heating was simulated in a digital swine by solving the mechanistic generic bioheat transfer model (GBHTM) and the conventional, empirical Pennes bioheat transfer equation for the following two cases: (1) when the porcine head was in the isocenter, and (2) when the porcine trunk was in the isocenter. The simulation results were validated by making direct fluoroptic temperature measurements in the skin, brain, simulated hot regions, and rectum of ten swine (Case 1, N= 5, mean animal weight = 84.03 ± 6.85 kg, Whole-body average SAR = 2.65 ± 0.22 W/kg; Case 2, N= 5, mean animal weight = 81.59 ± 6.23 kg, Whole-body average SAR = 2.77 ± 0.26 W/kg) during one hour of exposure to a turbo spin echo sequence. Results The GBHTM simulated the RF heating more accurately compared to the Pennes equation. In vivo temperatures exceeded safe temperature thresholds with allowable SAR exposures. Hot regions may be produced deep inside the body, away from the skin. Conclusion SAR exposures to produce safe temperature thresholds may need re-investigation.