The objective of this effort was to demonstrate the feasibility of using ultrasound induced neuromodulation (UNMOD) to manage pain. Pain management for acute trauma is generally accomplished with narcotics, which is less than ideal in a battlefield scenario. The technology of peripheral ultrasound neuromodulation (PUNMOD) offers several advantages over narcotics and current methods of neurostimulation. PUNMOD has the potential to be highly portable as a battlefield analgesic, and has the advantage of leaving the patient’s cognitive abilities intact. In addition, PUNMOD does not carry with it the risk of abuse or the need for the surveillance that is associated with pharmaceutical analgesics.

Fig. 1 – The Ultrasound Neuromodulation Handheld Probe. In order for the transducer to couple with skin, it was decided that at the tip of the transducer housing, a flexible “ravioli” interface containing acoustic gel would be used.

The initial goal was to develop a modular software package for applying UNMOD. The software package addressed a need for a systematic, combinatorial approach for testing new waveforms in different phantom, animal, and human models. A software platform was developed using National Instruments LabVIEW and the PXI control system.

A sinusoidal voltage waveform was generated, and the resulting current and voltage were recorded using the software platform. The use of waveform generators allows the measurement of the electrical responses of transducers to clean sinusoidal as well as other multifrequency waveforms. This technique can be applied to any transducer and used to measure the impedance and total electrical power through the system. Spectral analysis can also be performed to see how these signals undergo transformations through each stage. This can be used for the characterization of waveform generators, amplifiers, and transducers.

In order to produce the optimal sets of parameters for pain modulation using ultrasound stimulation, the appropriate ultrasound pulse duration (PD), acoustic frequency of the ultrasound waveforms (Af), and the pulse repetition frequency (PRF) of the pulses must be discovered. A program was developed that can generate complex waveforms while being able to record important experimental data such as acoustic intensity, temperature changes, and neural activation levels.

The overall goal was to develop an alpha-prototype for modulating pain circuits with UNMOD. The prototype should be able to deliver sufficient acoustic intensity to modulate peripheral somatosensory nerves based on previous studies. The overall system should not weigh more than ten pounds and the ultrasound stimulation should be delivered with a handheld probe (See Figure 1).

For the alpha prototype, it was important to develop an evaluation system that makes it easy to test in a broad range of contexts. In order for the transducer to couple with skin, it was decided that at the tip of the transducer housing, a flexible “ravioli” interface containing acoustic gel would be used. For the electronics housing, the design was based on wanting to adjust four parameters using uncomplicated controls: ultrasound frequency, pulse repetition frequency, pulse length/duration, and stimulus length. For the initial prototype, there were three defined points for these parameters that were achieved using adjustable potentiometers for each parameter. The electronics housing has a simple design with a power cord, on/off master power switch, coax transducer attachment, and a “deliver therapy” button.

The initial testing conducted with Neurotrek V1.0 was to determine the acoustic power and temperature increases delivered by the prototype using a soft tissue phantom. For this testing, a Blatek 300-kHz transducer and a 2" piece of beef muscle were used for the phantom. Hydrophone measurements directly over the center of the transducer showed that the maximum spatial-peak pulse average acoustic intensity (ISPPA) that can be delivered by the prototype is 87.1W/cm2, which is significantly higher than what is needed for UNMOD. The ultrasound field through a 2" piece of muscle had an ISPPA of 8.0 W/cm2, which shows that the prototype can deliver more than sufficient energy to deep tissues.

A FLIR E60BX infrared thermal imaging camera and thermister probes were used to measure temperature changes in the soft tissue phantom and the transducer itself. Using waveform parameters that are consistent with what has been used for UNMOD in previous studies elicited no detectable temperature changes in the transducer itself and minimal changes in the phantom. Artificially high parameters were used to model the temperature changes in soft tissue as it relates to total energy delivered. Raising the intensity and duration to deliver a stimulus with roughly 9,000 times the energy of a single UNMOD stimulus led to significant heating of the transducer and an 8.5 °C change at the surface of the phantom. Modeling the heat increase showed that the increase in temperature was quite linear, indicating that each acoustic cycle has a thermal dose.

Minor skin burns do not start to occur until 44 °C, and heat dissipation will be better in tissue with active circulation. These results indicate there is ample safety margin for delivering enough UNMOD energy while keeping the risk of burns through ultrasound-mediated tissue heating low. The temperature change in the opposite side of the 2" phantom was approximately 1.5 °C, in line with approximately a 10-fold energy attenuation through the tissue.

This work was done by Sumon K. Pal of Synsonix, LLC for the U.S. Army Research Office. ARL-0144