Bioheat Model of Spinal Column Heating During High-Density Spinal Cord Stimulation.

INTRODUCTION: High-density (HD) spinal cord stimulation (SCS) delivers higher charge per time by increasing frequency and/or pulse duration, thus increasing stimulation energy. Previously, through phantom studies and computational modeling, we demonstrated that stimulation energy drives spinal tissue heating during kHz SCS. In this study, we predicted temperature increases in the spinal cord by HD SCS, the first step in considering the potential impact of heating on clinical outcomes. MATERIALS AND METHODS: We adapted a high-resolution computer-aided design-derived spinal cord model, both with and without a lead encapsulation layer, and applied bioheat transfer finite element method multiphysics to predict temperature increases during SCS. We simulated HD SCS using a commercial SCS lead (eight contacts) with clinically relevant intensities (voltage-controlled: 0.5-7 Vrms) and electrode configuration (proximal bipolar, distal bipolar, guarded tripolar [+-+], and guarded quadripolar [+--+]). Results were compared with the conventional and 10-kHz SCS (current-controlled). RESULTS: HD SCS waveform energy (reflecting charge per second) governs joule heating in the spinal tissues, increasing temperature supralinearly with stimulation root mean square. Electrode configuration and tissue properties (an encapsulation layer) influence peak tissue temperature increase-but in a manner distinct for voltage-controlled (HD SCS) compared with current-controlled (conventional/10-kHz SCS) stimulation. Therefore, depending on conditions, HD SCS could produce heating greater than that of 10-kHz SCS. For example, with an encapsulation layer, using guarded tripolar configuration (500-Hz, 250-µs pulse width, 5-Vpeak HD SCS), the peak temperature increases were 0.36 °C at the spinal cord and 1.78 °C in the epidural space. CONCLUSIONS: As a direct consequence of the higher charge, HD SCS increases tissue heating; voltage-controlled stimulation introduces special dependencies on electrode configuration and lead encapsulation (reflected in impedance). If validated with an in vivo measurement as a possible mechanism of action of SCS, bioheat models of HD SCS serve as tools for programming optimization.

Tissue Temperature Increases by a 10 kHz Spinal Cord Stimulation System: Phantom and Bioheat Model.

OBJECTIVE: A recently introduced Spinal Cord Stimulation (SCS) system operates at 10 kHz, faster than conventional SCS systems, resulting in significantly more power delivered to tissues. Using a SCS heat phantom and bioheat multi-physics model, we characterized tissue temperature increases by this 10 kHz system. We also evaluated its Implanted Pulse Generator (IPG) output compliance and the role of impedance in temperature increases. MATERIALS AND METHODS: The 10 kHz SCS system output was characterized under resistive loads (1-10 KΩ). Separately, fiber optic temperature probes quantified temperature increases (ΔTs) around the SCS lead in specially developed heat phantoms. The role of stimulation Level (1-7; ideal pulse peak-to-peak of 1-7mA) was considered, specifically in the context of stimulation current Root Mean Square (RMS). Data from the heat phantom were verified with the SCS heat-transfer models. A custom high-bandwidth stimulator provided 10 kHz pulses and sinusoidal stimulation for control experiments. RESULTS: The 10 kHz SCS system delivers 10 kHz biphasic pulses (30-20-30 µs). Voltage compliance was 15.6V. Even below voltage compliance, IPG bandwidth attenuated pulse waveform, limiting applied RMS. Temperature increased supralinearly with stimulation Level in a manner predicted by applied RMS. ΔT increases with Level and impedance until stimulator compliance was reached. Therefore, IPG bandwidth and compliance dampen peak heating. Nonetheless, temperature increases predicted by bioheat multi-physic models (ΔT = 0.64°C and 1.42°C respectively at Level 4 and 7 at the cervical segment; ΔT = 0.68°C and 1.72°C respectively at Level 4 and 7 at the thoracic spinal cord)-within ranges previously reported to effect neurophysiology. CONCLUSIONS: Heating of spinal tissues by this 10 kHz SCS system theoretically increases quickly with stimulation level and load impedance, while dampened by IPG pulse bandwidth and voltage compliance limitations. If validated in vivo as a mechanism of kHz SCS, bioheat models informed by IPG limitations allow prediction and optimization of temperature changes.

Minimal Heating at the Skin Surface During Transcranial Direct Current Stimulation.

OBJECTIVE: To assess if transcranial direct current stimulation (tDCS) produces a temperature change at the skin surface, if any change is stimulation polarity (anode or cathode) specific, and the contribution of passive heating (joule heat) or blood flow on such change. MATERIAL AND METHODS: Temperature differences (ΔTs) in an agar phantom study and an in vivo study (forearm stimulation) including 20 volunteers with both experimental measures and finite element method (FEM) multiphysics prediction (current flow and bioheat) models of skin comprising three tissue layers (epidermis, dermis, and subcutaneous layer with blood perfusion) or of the phantom for active stimulation and control cases were compared. Temperature was measured during pre, post, and stimulation phases for both phantom and subject's forearms using thermocouples. RESULTS: In the phantom, ΔT under both anode and cathode, compared to control, was not significantly different and less than 0.1°C. Stimulation of subjects resulted in a gradual increase in temperature under both anode and cathode electrodes, compared to control (at t = 20 min: ΔTanode = 0.9°C, ΔTcathode = 1.1°C, ΔTcontrol = 0.05°C). The FEM phantom model predicted comparable maximum ΔT of 0.27°C and 0.28°C (at t = 20 min) for the control and anode/cathode cases, respectively. The FEM skin model predicted a maximum ΔT at t = 20 min of 0.98°C for control and 1.36°C under anode/cathode electrodes. CONCLUSIONS: Taken together, our results indicate a moderate and nonhazardous increase in temperature at the skin surface during 2 mA tDCS that is independent of polarity, and results from stimulation induced blood flow rather than joule heat.

Development and Clinical Validation of a Finite Element Method Model Mapping Focal Intracranial Cooling.

Therapeutic hypothermia (TH) is a common and effective technique to reduce inflammation and induce neuroprotection across a variety of diseases. Focal TH of the brain can avoid the side effects of systemic cooling. The degree and extent of focal TH are a function of cooling probe design and local brain thermoregulation processes. To refine focal TH probe design, with application-specific optimization, we develop precise computational models of brain thermodynamics under intense local cooling. Here, we present a novel multiphysics in silico model that can accurately predict brain response to focal cooling. The model was parameterized from previously described values of metabolic activity, thermal conductivity, and temperature-dependent cerebral perfusion. The model was validated experimentally using data from clinical cases where local cooling was induced intracranially and brain temperatures monitored in real-time with MR thermometry. The validated model was then used to identify optimal design probe parameters to maximize volumetric TH, including considering three stratifications of cooling (mild, moderate, and profound) to produce Volume of Tissue Cooled (VOTC) maps. We report cooling radius increases in a nearly linear fashion with probe length and decreasing probe surface temperature.

Adaptive current tDCS up to 4 mA.

BACKGROUND: Higher tDCS current may putatively enhance efficacy, with tolerability the perceived limiting factor. OBJECTIVE: We designed and validated electrodes and an adaptive controller to provide tDCS up to 4 mA, while managing tolerability. The adaptive 4 mA controller included incremental ramp up, impedance-based current limits, and a Relax-mode where current is transiently decreased. Relax-mode was automatically activated by self-report VAS-pain score >5 and in some conditions by a Relax-button available to participants. METHODS: In a parallel-group participant-blind design with 50 healthy subjects, we used specialized electrodes to administer 3 daily session of tDCS for 11 min, with a lexical decision task as a distractor, in 5 study conditions: adaptive 4 mA, adaptive 4 mA with Relax-button, adaptive 4 mA with historical-Relax-button, 2 mA, and sham. A tablet-based stimulator with a participant interface regularly queried VAS pain score and also limited current based on impedance and tolerability. An Abort-button provided in all conditions stopped stimulation. In the adaptive 4 mA with Relax-button and adaptive 4 mA with historical-Relax-button conditions, participants could trigger a Relax-mode ad libitum, in the latter case with incrementally longer current reductions. Primary outcome was the average current delivered during each session, VAS pain score, and adverse event questionnaires. Current delivered was analyzed either excluding or including dropouts who activated Abort (scored as 0 current). RESULTS: There were two dropouts each in the adaptive 4 mA and sham conditions. Resistance based current attenuation was rarely activated, with few automatic VAS pain score triggered relax-modes. In conditions with Relax-button option, there were significant activations often irrespective of VAS pain score. Including dropouts, current across conditions were significantly different from each other with maximum current delivered during adaptive 4 mA with Relax-button. Excluding dropouts, maximum current was delivered with adaptive 4 mA. VAS pain score and adverse events for the sham was only significantly lower than the adaptive 4 mA with Relax-button and adaptive 4 mA with historical-Relax-button. There was no difference in VAS pain score or adverse events between 2 mA and adaptive 4 mA. CONCLUSIONS: Provided specific electrodes and controllers, adaptive 4 mA tDCS is tolerated and effectively blinded, with acceptability likely higher in a clinical population and absence of regular querying. Indeed, presenting participants with overt controls increases rumination on sensation.

Temperature increases by kilohertz frequency spinal cord stimulation.

INTRODUCTION: Kilohertz frequency spinal cord stimulation (kHz-SCS) deposits significantly more power in tissue compared to SCS at conventional frequencies, reflecting increased duty cycle (pulse compression). We hypothesize kHz-SCS increases local tissue temperature by joule heat, which may influence the clinical outcomes. METHODS: To establish the role of tissue heating in KHZ-SCS, a decisive first step is to characterize the range of temperature changes expected during conventional and KHZ-SCS protocols. Fiber optic probes quantified temperature increases around an experimental SCS lead in a bath phantom. These data were used to verify a SCS lead heat-transfer model based on joule heat. Temperature increases were then predicted in a seven-compartment (soft tissue, vertebral bone, fat, intervertebral disc, meninges, spinal cord with nerve roots) geometric human spinal cord model under varied parameterization. RESULTS: The experimentally constrained bio-heat model shows SCS waveform power (waveform RMS) determines tissue heating at the spinal cord and surrounding tissues. For example, we predict temperature increased at dorsal spinal cord of 0.18-1.72 °C during 3.5 mA peak 10 KHz stimulation with a 40-10-40 µs biphasic pulse pattern, 0.09-0.22 °C during 3.5 mA 1 KHz 100-100-100 µs stimulation, and less than 0.05 °C during 3.5 mA 50 Hz 200-100-200 µs stimulation. Notably, peak heating of the spinal cord and other tissues increases superlinearly with stimulation power and so are especially sensitive to incremental changes in SCS pulse amplitude or frequency (with associated pulse compression). Further supporting distinct SCS intervention strategies based on heating; the spatial profile of temperature changes is more uniform compared to electric fields, which suggests less sensitivity to lead position. CONCLUSIONS: Tissue heating may impact short and long-term outcomes of KHZ-SCS, and even as an adjunct mechanism, suggests distinct strategies for lead position and programming optimization.

Dry tDCS: Tolerability of a novel multilayer hydrogel composite non-adhesive electrode for transcranial direct current stimulation.

BACKGROUND: The adoption of transcranial Direct Current Stimulation (tDCS) is encouraged by portability and ease-of-use. However, the preparation of tDCS electrodes remains the most cumbersome and error-prone step. Here, we validate the performance of the first "dry" electrodes for tDCS. A "dry electrode" excludes 1) any saline or other electrolytes, that are prone to spread and leaving a residue; 2) any adhesive at the skin interface; or 3) any electrode preparation steps except the connection to the stimulator. The Multilayer Hydrogel Composite (MHC) dry-electrode design satisfied these criteria. OBJECTIVE/HYPOTHESIS: Over an exposed scalp (supraorbital (SO) regions of forehead), we validated the performance of the first "dry" electrode for tDCS against the state-of-the-art conventional wet sponge-electrode to test the hypothesis that whether tDCS can be applied with a dry electrode with comparable tolerability as conventional "wet" techniques? METHODS: MHC dry-electrode performance was verified using a skin-phantom, including mapping voltage at the phantom surface and mapping current inside the electrode using a novel biocompatible flexible printed circuit board current sensor matrix (fPCB-CSM). MHC dry-electrode performance was validated in a human trial including tolerability (VAS and adverse events), skin redness (erythema), and electrode current mapping with the fPCB-CSM. Experimental data from skin-phantom stimulation were compared against a finite element method (FEM) model. RESULTS: Under the tested conditions (1.5 mA and 2 mA tDCS for 20 min using MHC-dry and sponge-electrode), the tolerability was improved, and the erythema and adverse-events were comparable between the MHC dry-electrode and the state-of-the-art sponge electrodes. CONCLUSION: Dry (residue-free, non-spreading, non-adhesive, and no-preparation-needed) electrodes can be tolerated under the tested tDCS conditions, and possibly more broadly used in non-invasive electrical stimulation.