Wei-Tso Lin

Pain Control on Demand Based on Pulsed Radio-Frequency Stimulation of the Dorsal Root Ganglion Using a Batteryless Implantable CMOS SoC

This paper presents the implementation of a batteryless CMOS SoC with low voltage pulsed radio-frequency (PRF) stimulation. This implantable SoC uses 402 MHz command signals following the medical implanted communication system (MICS) standard and a low frequency (1 MHz) for RF power transmission. A body floating type rectifier achieves 84% voltage conversion ratio. A bi-phasic pulse train of 1.4 V and 500 kHz is delivered by a PRF driver circuit. The PRF parameters include pulse duration, pulse frequency and repetition rate, which are controllable via 402 MHz RF receiver. The minimal required 3 V RF Vin and 2.2 V VDDr is achieved at 18 mm gap. The SoC chip is fabricated in a 0.35 μm CMOS process and mounted on a PCB with a flexible spiral antenna. The packaged PRF SoC was implanted into rats for the animal study. Von Frey was applied to test the mechanical allodynia in a blinded manner. This work has successfully demonstrated that implanted CMOS SoC stimulating DRG with 1.4 V, 500 kHz PRF could significantly reduce spinal nerve ligation (SNL) induced mechanical allodynia for 3-7 days.Although pain is interpreted as the fifth vital sign by many professions, the presence of different degrees of pain significantly affects quality of life for many patients, especially the elderly [1]. Electrical stimulation to the central or peripheral neural conduction paths has been utilized in clinics to achieve effective pain relief [2]. The conventional scheme for pulsed radio-frequency (PRF) pain therapy uses thermal coagulation to permanently damage nerves by heat. This destructive method can cause severe side-effects such as hyper-sensitivity to pain after nerves regenerate. Thus, repeated surgery is needed. Additionally, the conventional design of an implantable system requires a battery for operation, often accounting for over 2/3 of the entire device volume. Therefore, a non-destructive and batteryless method using PRF for pain control is key for implantable systems. This work uses a batteryless implantable pain-control SoC that is effective in pain reduction, using a low stimulation voltage that avoids causing thermal damage to dorsal root ganglion (DRG) tissue. An animal study of neuropathic pain was previously designed with PRF parameters to control tissue temperature at ≪40°C via an external function generator [3]. This work now presents the implementation of this functionality on a CMOS SoC. Its effectiveness is demonstrated by observing the behavior of rats receiving localized bipolar stimulus to the DRG of the lumbar nerve.

Pulsed radiofrequency inhibited activation of spinal mitogen-activated protein kinases and ameliorated early neuropathic pain in rats.

Pulsed radiofrequency (PRF) has been widely used to treat chronic pain, but the effectiveness and mechanisms in preventing early neuropathic pain have not been well explored. Even fewer knowledge is available in its impact on glia‐mediated nociceptive sensitization. This study aims to elucidate the modulation of PRF on nerve injury‐induced pain development and activation of spinal mitogen‐activated protein kinases (MAPKs).

A Dual-Mode Highly Efficient Class-E Stimulator Controlled by a Low-Q Class-E Power Amplifier Through Duty Cycle

This paper presents the design flow of two high-efficiency class-E amplifiers for the implantable electrical stimulation system. The implantable stimulator is a high-Q class-E driver that delivers a sine-wave pulsed radiofrequency (PRF) stimulation, which was verified to have a superior efficacy in pain relief to a square wave. The proposed duty-cycle-controlled class-E PRF driver designed with a high-Q factor has two operational modes that are able to achieve 100% DC-AC conversion, and involves only one switched series inductor and an unchanged parallel capacitor. The measured output amplitude under low-voltage (LV) mode using a 22% duty cycle was 0.98 V with 91% efficiency, and under high-voltage (HV) mode using a 47% duty cycle was 2.95 V with 92% efficiency. These modes were inductively controlled by a duty-cycle detector, which can detect the duty-cycle modulated signal generated from the external complementary low-Q class-E power amplifier (PA). The design methodology of the low-Q inductive interface for a non-50% duty cycle is presented. The experimental results exhibits that the 1.5-V PA that consumes DC power of 14.21 mW was able to deliver a 2.9-V sine wave to a 500 Ω load. The optimal 60% drain efficiency of the system from the PA to the load was obtained at a 10-mm coupling distance.

In Situ Measurement of Tissue Impedance Using an Inductive Coupling Interface Circuit

In this work, a method of an inductive coupling impedance measurement (ICIM) is proposed for measuring the nerve impedance of a dorsal root ganglion (DRG) under PRF stimulation. ICIM provides a contactless interface for measuring the reflected impedance by an impedance analyzer with a low excitation voltage of 7 mV. The paper develops a calibration procedure involving a 50-Ω reference resistor to calibrate the reflected resistance for measuring resistance of the nerve in the test. A de-embedding technique to build the equivalent transformer circuit model for the ICIM circuit is also presented. A batteryless PRF stimulator with ICIM circuit demonstrated good accuracy for the acute measurement of DRG impedance both in situ and in vivo. Besides, an in vivo animal experiment was conducted to show that the effectiveness of pulsed radiofrequency (PRF) stimulation in relieving pain gradually declined as the impedance of the stimulated nerve increased. The experiment also revealed that the excitation voltage for measuring impedance below 25 mV can prevent the excitation of a nonlinear response of DRG.

A comparison between pulsed radiofrequency and electro-acupuncture for relieving pain in patients with chronic low back pain.

Many treatment options for chronic low back pain are available, including varied forms of electric stimulation. But little is known about the electricity effect between electro-acupuncture and pulsed radiofrequency. The objective of this study is to assess the difference in effectiveness of pain relief between pulsed radiofrequency and electro-acupuncture. Visual analog score (VAS) pain score, the Oswestry disability index (ODI) to measure a patients permanent functional disability, and Short form 36 (SF-36) which is a survey used in health assessment to determine the cost-effectiveness of a health treatment, were used as rating systems to measure the pain relief and functional improvement effect of pulsed radiofrequency and electro-acupuncture, based on the methodological quality of the randomized controlled trials, the relevance between the study groups, and the consistency of the outcome evaluation. First, the baseline status before therapy shows no age and gender influence in the SF-36 and VAS score but it is significant in the ODI questionnaire. From ANOVA analyses, it is apparent that radiofrequency therapy is a significant improvement over electro-acupuncture therapy after one month. But electro-acupuncture also showed functional improvement in the lumbar spine from the ODI. This study provides sufficient evidence of the superiority of pulsed radiofrequency (PRF) therapy for low back pain relief compared with both electro-acupuncture (EA) therapy and the control group. But the functional improvement of the lumbar spine was proved under EA therapy only. Both therapies are related to electricity effects.

Effects of low amplitude pulsed radiofrequency stimulation with different waveform in rats for neuropathic pain

Pulsed-radiofrequency (PRF) electrical stimulation has been widely used for chronic pain treatment. It has been demonstrated with advantages of low temperature over traditional continuous radiofrequency (CRF) lesions with higher amplitude and mono polar electrode to treat pain in clinics (frequency 500 KHz, Pulse duration 20 msec, Amplitude 45 V, Treatment 2 min). We compare the effects of different pulse waveforms and PRF parameters (Pulse duration 25 ms, Treatment duration 5 min, low amplitude of 2.5/1.25 V) with a miniature bi-polar electrode on Dorsal root ganglion (DRG). The pain relief effect due to PRF is evaluated by using Von Frey method for the pain threshold index based on behavior response to mechanical stimulus of various strengths. Experimental results of Von Frey Score show that the sinusoidal group has higher responses than the square wave one. Both fast and secondary expressed proteins of c-fos and pp38 are measured from spinal cord tissue sectioning slides to characterize the pain associated inflammatory responses and their responses due to PRF stimulation.

Using Radio Frequency Electrical Stimulation to Block External Urethral Sphincter Contraction and Improved Voiding Efficiency

Block of the external urethral sphincter contractions by using high frequency electrical stimulation of the pudendal nerves is a potential method for inhibiting detrusor sphincter dyssynergia. Most researchers use high frequency electrical stimulation at frequencies between 2kHz to 20kHz, but the parameters and mechanism of this block are not well understood. This paper demonstrated the use of radio frequency electrical stimulation (500kHz) as a method to block the external urethral sphincter contractions and improved voiding efficiency by electrical stimulation of unilateral pudendal nerve efferent axons. The most efficient waveform for conduction was 500kHz (with 0.2 to 1mA) constant-current biphasic sinusoidal, voiding efficiency increased from 53 to 71-92%. These results raise the possibility that using radio frequency electrical stimulation to block external urethral sphincter contraction may provide a new approach for improving voiding in spinal cord injured patients.

Chaotic phase space differential algorithm for real-time detection of ventricular arrhythmias: Application in animal model

Life-threatening ventricular arrhythmias remain the main cause of death among patients with cardiovascular diseases. Efforts have been spent on early detection of such fatal cardiac signs. We have previously reported a novel chaotic phase space differential (CPSD) algorithm in discriminating VPC, VT, and VF from normal sinus rhythm with both good sensitivity and specificity. In this article, we apply this algorithm on the rat model of calcium induced ventricular tachycardia. Peaked CPSD values can be observed along with the occurrence of ventricular tachycardia. In addition, minor ECG changes such as new onset S wave or sinus arrhythmia can also be noted on CPSD tracing. We believe that the CPSD algorithm not only is capable of detecting lethal ventricular arrhythmias, but also is potentially a good tool for long-term monitoring the change of ECG signals.

An implantable bipolar spine stimulation probe with bio-inspired adhesive microtubes

This paper presents a bipolar electrical probe for implantable nerve stimulation treatment. This probe features bio-inspired microtubes to enhance the adhesion with tissues and to extrude out a tissue adhesive. The probe has a hollow chamber to store the tissue adhesive, and the adhesive can flow outside through a seal which is dissolved when exposed to water in tissues. The probe is fabricated from a designed 4-layer flexible printed circuit (FPC) substrate. The FPC is composed of polyimide and patterned coppers layers adhered together by a glue. In addition to the electrical conduction, the copper circuit on the FPC can be used as sacrificial material for making the microtubes and the chamber. Polyurethane (PU) is used to cover the chamber, and parylene C is deposited for biocompatibility. Polyethylene glycol (PEG) is chosen to seal the microtubes due to its water solubility and biodegradability. By combining FPC structure design with post process, an adhesive implantable stimulating probe was fabricated.