Detecting Bladder Biomarkers for Closed-Loop Neuromodulation: A Technological Review

Abstract

Neuromodulation was introduced for patients with poor outcomes from the existing traditional treatment approaches. It is well-established as an alternative, novel treatment option for voiding dysfunction. The current system of neuromodulation uses an open-loop system that only delivers continuous stimulation without considering the patient's state changes. Though the conventional open-loop system has shown positive clinical results, it can cause problems such as decreased efficacy over time due to neural habituation, higher risk of tissue damage, and lower battery life. Therefore, there is a need for a closed-loop system to overcome the disadvantages of existing systems. The closed-loop neuromodulation includes a system to monitor and stimulate micturition reflex pathways from the lower urinary tract, as well as the central nervous system. In this paper, we reviewed the current technological status to measure biomarker for closed-loop neuromodulation systems for voiding dysfunction.

Keywords: Biomarkers; Implantable neurostimulators; Urinary bladder diseases; Voiding dysfunction.

Fig. 1.

A new cystometry system using a microelectromechanical system (MEMS)-based in-target bladder pressure sensor. (A) Bladder pressures are usually measured from water-filled lines that are connected to externally located transducers. The conventional method uses a catheter through the urethra into the bladder with a transducer in the distal end. This method is implemented with nonphysiological filling state and urethra obstructed by a catheter and produce artefacts by movements and measurement errors. (B) The MEMS-based system is developed in a suprapubic approach to resolve the several limitations of conventional method. It consists of a MEMS sensor (C), custom-made sensor data logger (SDL) (D), and reference sensor probe. This in-target organ pressure sensor is superior in measuring minute pressure pulses. This method is improving the quality of measurements and the option of long-term implantable devices. (E) The clinical trial. MMS, medical measurements systems. Reprinted from Clausen I, et al. Sensors (Basel) 2018 Jul 3;18(7), according to Open Access [51].

Fig. 2.

Piezoelectric catheter-free pressure sensor to detect bladder contractions. The pressure measured in the submucosa correlates with the pressure of the bladder lumen pressures. The correlation coefficient is sufficient enough to measure bladder events such as detrusor contractions or abdominal compressions. Implantable sensor offers the opportunity for chronic monitoring. (A) Illustration of the wired pressure monitor of catheter-free, as implanted within the bladder wall. (B) Photograph of the fabricated implantable pressure monitor prototype. Reprinted from Majerus SJ, et al. PLoS One 2017;12:e0168375, according to Open Access [55].