A combined cuff electrode array for organ-specific selective stimulation of vagus nerve enabled by Electrical Impedance Tomography

Previously developed spatially-selective Vagus Nerve Stimulation (sVNS) allows the targeting of specific nerve fascicles through current steering in a multi-electrode nerve cuff but relies on a trial-and-error strategy to identify the relative orientation between electrodes and fascicles. Fast Neural Electrical Impedance Tomography (FN-EIT) has been recently used for imaging neural traffic in the vagus nerves of pigs in a cross-correlation study with sVNS and MicroCT fascicle tracking. FN-EIT has the potential for allowing targeted sVNS; however, up to now, stimulation and imaging have been performed with separate electrode arrays. In this study, different options were evaluated in-silico to integrate EIT and stimulation into a single electrode array without affecting spatial selectivity. The original pig vagus EIT electrode array geometry was compared with a geometry integrating sVNS and EIT electrodes, and with direct use of sVNS electrodes for EIT imaging. Modelling results indicated that both new designs could achieve image quality similar to the original electrode geometry in all tested markers (e.g., co-localisation error <100 µm). The sVNS array was considered to be the simplest due to the lower number of electrodes. Experimental results from testing evoked EIT imaging of recurrent laryngeal activity using electrodes from the sVNS cuff returned a signal-to-noise ratio similar to our previous study (3.9 ± 2.4 vs. 4.1 ± 1.5, N = 4 nerves from 3 pigs) and a lower co-localisation error (≈14% nerve diameter vs. ≈25%, N = 2 nerves from 2 pigs). Performing FN-EIT and sVNS on the same nerve cuff will facilitate translation to humans, simplify surgery and enable targeted neuromodulation strategies

A combined cuff electrode array for organ-specific selective stimulation of vagus nerve enabled by Electrical Impedance Tomography

Previously developed spatially-selective Vagus Nerve Stimulation (sVNS) allows the targeting of specific nerve fascicles through current steering in a multi-electrode nerve cuff but relies on a trial-and-error strategy to identify the relative orientation between electrodes and fascicles. Fast Neural Electrical Impedance Tomography (FN-EIT) has been recently used for imaging neural traffic in the vagus nerves of pigs in a cross-correlation study with sVNS and MicroCT fascicle tracking. FN-EIT has the potential for allowing targeted sVNS; however, up to now, stimulation and imaging have been performed with separate electrode arrays. In this study, different options were evaluated in-silico to integrate EIT and stimulation into a single electrode array without affecting spatial selectivity. The original pig vagus EIT electrode array geometry was compared with a geometry integrating sVNS and EIT electrodes, and with direct use of sVNS electrodes for EIT imaging. Modelling results indicated that both new designs could achieve image quality similar to the original electrode geometry in all tested markers (e.g., co-localisation error &lt;100 µm). The sVNS array was considered to be the simplest due to the lower number of electrodes. Experimental results from testing evoked EIT imaging of recurrent laryngeal activity using electrodes from the sVNS cuff returned a signal-to-noise ratio similar to our previous study (3.9 ± 2.4 vs. 4.1 ± 1.5, N = 4 nerves from 3 pigs) and a lower co-localisation error (≈14% nerve diameter vs. ≈25%, N = 2 nerves from 2 pigs). Performing FN-EIT and sVNS on the same nerve cuff will facilitate translation to humans, simplify surgery and enable targeted neuromodulation strategies

Overcoming temporal dispersion for measurement of activity-related impedance changes in unmyelinated nerves

OBJECTIVE: Fast neural Electrical Impedance Tomography (FnEIT) is an imaging technique that has been successful in visualising electrically evoked activity of myelinated fibres in peripheral nerves by measurement of the impedance changes (dZ) accompanying excitation. However, imaging of unmyelinated fibres is challenging due to temporal dispersion (TP) which occurs due to variability in conduction velocities of the fibres and leads to a decrease of the signal below the noise with distance from the stimulus. To overcome TP and allow EIT imaging in unmyelinated nerves, a new experimental and signal processing paradigm is required allowing dZ measurement further from the site of stimulation than compound neural activity is visible. The development of such a paradigm was the main objective of this study. APPROACH: A FEM-based statistical model of temporal dispersion in porcine subdiaphragmatic nerve was developed and experimentally validated ex-vivo. Two paradigms for nerve stimulation and processing of the resulting data - continuous stimulation and trains of stimuli, were implemented; the optimal paradigm for recording dispersed dZ in unmyelinated nerves was determined. MAIN RESULTS: While continuous stimulation and coherent spikes averaging led to higher signal-to-noise ratios (SNR) at close distances from the stimulus, stimulation by trains was more consistent across distances and allowed dZ measurement at up to 15 cm from the stimulus (SNR = 1.8±0.8) if averaged for 30 minutes. SIGNIFICANCE: The study develops a method that for the first time allows measurement of dZ in unmyelinated nerves in simulation and experiment, at the distances where compound action potentials are fully dispersed

Organotopic organization of the porcine mid-cervical vagus nerve

Introduction: Despite detailed characterization of fascicular organization of somatic nerves, the functional anatomy of fascicles evident in human and large mammal cervical vagus nerve is unknown. The vagus nerve is a prime target for intervention in the field of electroceuticals due to its extensive distribution to the heart, larynx, lungs, and abdominal viscera. However, current practice of the approved vagus nerve stimulation (VNS) technique is to stimulate the entire nerve. This produces indiscriminate stimulation of non-targeted effectors and undesired side effects. Selective neuromodulation is now a possibility with a spatially-selective vagal nerve cuff. However, this requires the knowledge of the fascicular organization at the level of cuff placement to inform selectivity of only the desired target organ or function. / Methods and results: We imaged function over milliseconds with fast neural electrical impedance tomography and selective stimulation, and found consistent spatially separated regions within the nerve correlating with the three fascicular groups of interest, suggesting organotopy. This was independently verified with structural imaging by tracing anatomical connections from the end organ with microCT and the development of an anatomical map of the vagus nerve. This confirmed organotopic organization. / Discussion: Here we show, for the first time, localized fascicles in the porcine cervical vagus nerve which map to cardiac, pulmonary and recurrent laryngeal function (N = 4). These findings pave the way for improved outcomes in VNS as unwanted side effects could be reduced by targeted selective stimulation of identified organ-specific fiber-containing fascicles and the extension of this technique clinically beyond the currently approved disorders to treat heart failure, chronic inflammatory disorders, and more

Optical and electrical characterization of biocompatible polymeric lines for hemodialysis applications

During hemodialysis (HD), blood is circulated through an extracorporeal tubing system (bloodline) made of medical-grade polymeric material. Sensors of various types that do not come into contact with blood (optical, electromagnetic, etc.) are applied directly across the bloodline for clinical purposes and for therapy customization. Thus, a detailed knowledge of the bloodline's physical properties is useful for the development of next-generation HD sensors. In this work, we performed a novel comparative analysis of the materials used by the manufacturers of the bloodlines. We focused on signals and characterization techniques matching those of the abovementioned sensors; consequently, this is an application-specific study of the optical and electrical characterization of bloodline material. Such properties are analyzed and compared for bloodlines from seven different manufacturers by optical absorbance spectroscopy and electrical impedance spectroscopy (EIS). Absorbance spectrum measurements are carried out in the VIS-NIR range. Absorbance spectra are pre-processed and data from both types of analyses are normalized with respect to sample thickness. Optical analysis shows that all bloodlines except one have similarly shaped spectra with slight quantitative differences. In all optical spectra, we find a decreasing trend of specific absorption from 0.14 mm??1 at 400 nm to 0.06 mm-1 at 1000 nm, with an absorption peak at 915 nm. In one case, a large absorption peak centered at 43600 nm is found. Electrical analysis shows that all bloodlines have the electrical properties of a constant-phase element (CPE), with statistically significant differences in parameters' values. Estimation of electrical CPE parameters for all bloodline returns a range of 0.942-0.957 for parameter n and a range of 12.41-16.64 for parameter Q0'. In conclusion, we find that, although some statistically significant differences are present, bloodlines from a representative group of manufacturers share similar electrical and optical properties. Therefore, contactless sensing devices developed for HD will work on different bloodlines if a simple recalibration is performed

Sensor Technologies for On-line Monitoring of Biological Parameters During Hemodialysis

Modern hemodialysis machines make use of sensors to monitor the proper functioning of the machine, the safety of the treatment and the intra-session alterations of the hematic properties of the patient. The real-time stream of sensor data is also crucial for the implementation of biofeedback algorithms. Non-invasive sensing techniques have the advantages of avoiding contact with the patient’s blood, thus increasing safety and avoiding the use of disposable elements. The primary aim of this doctoral thesis was the development of non-invasive sensing techniques for the measurement of physiological parameters during the hemodialysis session. An additional activity concerning mathematical modeling of the dialysis process was also carried out. The thesis is composed of four chapters. Chapter 1 serves as an introduction to the field of hemodialysis, giving the reader an overview of the different aspects of this medical therapy. In Chapter 2, a new method for the contactless estimation of plasmatic conductivity is described. High-frequency impedance measurement and model fitting are used to estimate electrical conductivity of the liquid contained inside the bloodline. Good results were obtained with measurements on saline solution and a blood-mimicking fluid. In Chapter 3, a system for continuous estimation of relative blood volume loss and plasmatic sodium concentration is described. The system integrates information from multiple sensors, among which is a new fiber-optic sensor, to estimate these two variables with satisfying accuracy. In Chapter 4, a model of sodium diffusion across the hemodialysis filter is reported. The innovative aspect of the presented model is that it interconnects mathematical descriptions of both the patient and the dialyzer, at different abstraction levels, in order to give a more realistic representation of sodium exchange during the treatment. The thesis closes with some final remarks and an outlook for the possible future developments

The effect of osmolarity on optical blood volume sensors for hemodialysis applications

Optical sensors are commonly used in hemodialysis (HD) for the continuous estimation of relative blood volume (RBV) during the session. Recently, the reliability of these devices was put into question due to the possible influence of osmolarity on this type of measurements. In this work, we investigated this issue with an experimental setup which expands on traditional optical sensor designs for HD. With the new setup, we were able to confirm the presence of the osmolarity artifact, and to collect data in an extended domain, compared to traditional sensors. However, the extended measurements only gave hints about possible solutions for the osmolarity issue