Elsevier

Brain Stimulation

Volume 12, Issue 1, January–February 2019, Pages 62-72
Brain Stimulation

Temperature increases by kilohertz frequency spinal cord stimulation

https://doi.org/10.1016/j.brs.2018.10.007Get rights and content

Highlights

  • kHz-SCS deposits significantly more power in tissue compared to conventional SCS frequencies, reflecting increased duty cycle (pulse compression).

  • An experimentally verified bio-heat model shows SCS waveform power determines tissue heating and predicts temperature increases at the spine ~1 °C during kHz-SCS.

  • Tissue heating by kHz-SCS may impact short and long-term outcomes suggesting distinct strategies for waveform optimization and lead placement.

Abstract

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.

Introduction

The emergence of kilohertz frequency (1–10 KHz) spinal cord stimulation (kHz-SCS) [[1], [2], [3], [4], [5], [6], [7]] for the treatment of neuropathic pain has engendered studies on new mechanisms of actions (MoA) [5,[8], [9], [10], [11]]. Divergent clinical observations for conventional rate SCS and kHZ-SCS suggest difference in MoA which could in turn inform distinct programming optimization strategies. Notably, kHZ-SCS can provide an analgesic and side-effects profile distinct from conventional frequency (∼100 Hz) SCS [11,12]. For example, kHz-SCS does not produce the paresthesia associated with dorsal column activation in conventional SCS, and recent studies seemingly rule out direct activation of dorsal column fibers as the primary mechanism of action of kHz-SCS pain relief [13,14] Wash-in time for the therapeutic benefit of conventional rate SCS is on the order of minutes, while responses to wash-in over a longer period [4]. Further indicating distinct MoA, kHz-SCS waveforms involve simultaneous decrease in pulse duration (well below membrane time constants) and increase in pulse frequency (beyond axon refractory periods) that challenge conventional models of stimulation [15,16].

Evidence against traditional neural MoA warrants investigation of other phenomena. We note that since the decrease in interpulse-interval (e.g. from 10 ms at 0.1 KHz to 0.1 ms at 10 KHz) is more drastic than the decrease in pulse duration (e.g. from 100 μS per phase at 0.1 KHz to 40 μS per phase at 10 KHz [5,9]), kHZ stimulation is associated with higher duty cycle – and the RMS power of a rectangular waveform varies positively with the square root of its duty cycle. Through the principle of joule heating, the power of current flow from an implanted lead can produce temperature increases around the lead [10,[17], [18], [19], [20], [21], [22], [23]]. Thus, kHz stimulation deposits more power in the tissue than conventional spinal cord stimulation and is therefore more likely to significantly heat the tissue immediately surrounding the stimulation site. A temperature increase and resultant thermal conduction into the spinal cord can, in turn, affect neuronal function [23] (e.g., via alteration of ion channel or neurotransmitters dynamics) and related biological functions (e.g., via vasodilation [24], heat shock protein expression [25]) depending on the degree of change. Tissue heating further encourages the expression of anti-inflammatory agents, such as heat shock proteins [26], over a period of time consistent with the extended wash-in times of kHz-SCS treatment.

Any form of electrical stimulation produces passive heating and the extent of induced temperature increases are specific to both the stimulation and local tissue properties, with various stimulation and environmental parameters affecting the degree to which heating occurs [19,23,27]. Key stimulation parameters are the stimulation waveform (based on stimulator programming) and electrode montage (based on lead placement), which together with tissue anatomy and electrical conductivity determine joule heat deposition. An implanted stimulator is a constant energy source which will produce unlimited temperature increases without passive (e.g. heat conduction by CSF) or active (e.g. spinal tissue blood perfusion) heat dissipation by the tissue. As such, heating analysis depend on tissue properties such as thermal conductivity, metabolic rate, and blood perfusion; not only of the stimulation target but surrounding tissues. Indeed, we postulate that the local environment around SCS leads is especially conducive to temperature increases, namely the low conductivity of fat and enclosed anatomy of the vertebral canal. If heating due to these factors is sufficient during kHz frequency SCS to shape beneficial responses, then joule heating by SCS may be an adjuvant mechanism underlying therapy. However, the degree of heating during kHz-SCS, including as aggravated by increased power deposition due to pulse compression and/or the enclosed spinal environment, remains unexplored.

The objective of this study was to assess, for the first time, whether an increased duty-cycle (and so power) of High-Rate spinal cord stimulation will produce significant temperature increases in the spinal cord. Prior experimental and modeling studies of conventional non-invasive and invasive forms of brain stimulation has suggested minimal heating under normal device operation (less than 1 °C) [18,[28], [29], [30], [31]]. This study predicts the degree of tissue temperature rises driven by SCS joule heat, and characterizes the role of SCS waveform (including frequency, pulse width, and amplitude) and tissue properties. We measured temperature increases around an experimental SCS lead in a bath to verify a finite-element-model of SCS joule heat. We confirmed the dependence of temperature rise only on the power of the stimulation waveform, independent of other parameters. Finally, we predicted temperature increases during conventional and kHz- SCS at the dorsal spinal cord under passive and active bio-heat conditions in a geometric human spinal cord FEM model.

Section snippets

Saline bath phantom

Thermal and electrical conductivity measurements taken to verify the general heat transfer model were performed in a cylindrical glass container (diameter: 90 mm and height: 130 mm) with three varied NaCl concentrations (154 mmol/L, 34.22 mmol/L, and 3.42 mmol/L (approximating cerebrospinal fluid, meninges, and epidural space respectively). A thermal conductivity meter (Therm Test Inc., Canada) and an electrical conductivity meter (Jenco Instruments, Inc., San Diego, CA) measured the thermal

Phantom measurements and model verification

A specially designed chamber was used to quantify temperature increases around an experimental SCS lead in a saline bath using varied waveforms (Fig. 1A). A micro-manipulator mounted optical temperature probe mapped steady-state temperature increases during stimulation with varied waveforms. As predicted by the FEM, temperature increases when applying a 10 KHz symmetric biphasic pulsed waveform at 5 mA peak intensity in a low conductivity saline phantom was maximal near energized electrodes and

Discussion

Thermoregulation of CNS temperature is complex and depends on a high metabolic activity [46] and both passive (conduction) and active heat exchange (blood flow). Neurostimulation, such as SCS, can challenge this equilibrium in several ways by 1) altering neuronal and so metabolic activity [18,47,48]; with 2) changing the cellular microenvironment [48,49]; 3) changing vascular function as a result of both direct blood vessel stimulation [24,50,51] and secondary to microenvironment changes; and

Conflicts of interest

The City University of New York (CUNY) has IP on neuro-stimulation system and methods with author, Niranjan Khadka and Marom Bikson as inventors. Dr. Marom Bikson has equity in Soterix Medical Inc. Tianhe Zhang, Rosana Esteller, and Brad Hershey are employees of Boston Scientific Inc.

Acknowledgements

This study was partially funded by grants to MB from NIH (NIH-NIMH 1R01MH111896, NIH-NINDS 1R01NS101362, NIH-NCI U54CA137788/U54CA132378, R03 NS054783) New York State Department of Health (NYS DOH, DOH01-C31291GG), RISE Graduate fellowship at CCNY, and Boston Scientific Inc.

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