Sukhraaj Basati

An Impedance Sensor to Monitor and Control Cerebral Ventricular Volume

This paper presents a sensor for monitoring and controlling the volume of the cerebrospinal fluid-filled ventricles of the brain. The measurement principle of the sensor exploits electrical conductivity differences between the cerebrospinal fluid and the brain tissue. The electrical contrast was validated using dog brain tissue. Experiments with prototype sensors accurately measured the volume content of elastically deformable membranes and gel phantoms with conductivity properties made to match human brain. The sensor was incorporated into a fully automatic feedback control system designed to maintain the ventricular volume at normal levels. The experimental conductivity properties were also used to assess the sensor performance in a simulated case of hydrocephalus. The computer analysis predicted voltage drops over the entire range of ventricular size changes with acceptable positional dependence of the sensor electrodes inside the ventricular space. These promising experimental and computational results of the novel impedance sensor with feedback may serve as the foundation for improved therapeutic options for hydrocephalic patients relying on volume sensing, monitoring or active feedback control.

Dynamic Brain Phantom for Intracranial Volume Measurements

Knowledge of intracranial ventricular volume is important for the treatment of hydrocephalus, a disease in which cerebrospinal fluid (CSF) accumulates in the brain. Current monitoring options involve MRI or pressure monitors (InSite, Medtronic). However, there are no existing methods for continuous cerebral ventricle volume measurements. In order to test a novel impedance sensor for direct ventricular volume measurements, we present a model that emulates the expansion of the lateral ventricles seen in hydrocephalus. To quantify the ventricular volume, sensor prototypes were fabricated and tested with this experimental model. Fluid was injected and withdrawn cyclically in a controlled manner and volume measurements were tracked over 8 h. Pressure measurements were also comparable to conditions seen clinically. The results from the bench-top model served to calibrate the sensor for preliminary animal experiments. A hydrocephalic rat model was used to validate a scaled-down, microfabricated prototype sensor. CSF was removed from the enlarged ventricles and a dynamic volume decrease was properly recorded. This method of testing new designs on brain phantoms prior to animal experimentation accelerates medical device design by determining sensor specifications and optimization in a rational process.

Cerebrospinal fluid volume measurements in hydrocephalic rats

Object Experimental data about the evolution of intracranial volume and pressure in cases of hydrocephalus are limited due to the lack of available monitoring techniques. In this study, the authors validate intracranial CSF volume measurements within the lateral ventricle, while simultaneously using impedance sensors and pressure transducers in hydrocephalic animals. Methods A volume sensor was fabricated and connected to a catheter that was used as a shunt to withdraw CSF. In vitro bench-top calibration experiments were created to provide data for the animal experiments and to validate the sensors. To validate the measurement technique in a physiological system, hydrocephalus was induced in weanling rats by kaolin injection into the cisterna magna. At 28 days after induction, the sensor was implanted into the lateral ventricles. After sealing the skull using dental cement, an acute CSF drainage/infusion protocol consisting of 4 sequential phases was performed with a pump. Implant location was confirmed via radiography using intraventricular iohexol contrast administration. Results Controlled CSF shunting in vivo with hydrocephalic rats resulted in precise and accurate sensor measurements (r = 0.98). Shunting resulted in a 17.3% maximum measurement error between measured volume and actual volume as assessed by a Bland-Altman plot. A secondary outcome confirmed that both ventricular volume and intracranial pressure decreased during CSF shunting and increased during infusion. Ventricular enlargement consistent with successful hydrocephalus induction was confirmed using imaging, as well as postmortem. These results indicate that volume monitoring is feasible for clinical cases of hydrocephalus. Conclusions This work marks a departure from traditional shunting systems currently used to treat hydrocephalus. The overall clinical application is to provide alternative monitoring and treatment options for patients. Future work includes development and testing of a chronic (long-term) volume monitoring system.

Impedance Changes Indicate Proximal Ventriculoperitoneal Shunt Obstruction In Vitro

Extracranial cerebrospinal fluid (CSF) shunt obstruction is one of the most important problems in hydrocephalus patient management. Despite ongoing research into better shunt design, robust and reliable detection of shunt malfunction remains elusive. The authors present a novel method of correlating degree of tissue ingrowth into ventricular CSF drainage catheters with internal electrical impedance. The impedance based sensor is able to continuously monitor shunt patency using intraluminal electrodes. Prototype obstruction sensors were fabricated for in-vitro analysis of cellular ingrowth into a shunt under static and dynamic flow conditions. Primary astrocyte cell lines and C6 glioma cells were allowed to proliferate up to 7 days within a shunt catheter and the impedance waveform was observed. During cell ingrowth a significant change in the peak-to-peak voltage signal as well as the root-mean-square voltage level was observed, allowing the impedance sensor to potentially anticipate shunt malfunction long before it affects fluid drainage. Finite element modeling was employed to demonstrate that the electrical signal used to monitor tissue ingrowth is contained inside the catheter lumen and does not endanger tissue surrounding the shunt. These results may herald the development of “next generation” shunt technology that allows prediction of malfunction before it affects patient outcome.

Modeling and Design of Distributed Systems; Methods and Algorithms

Abstract Mathematical programming techniques to predict cerebrospinal fluid (CSF) flow fields and drug transport in the human brain are presented. In addition, advantageous use of distributed mathematical models to accelerate design and development of a novel volume sensor for hydrocephalus treatment is demonstrated. CSF flow in the brain can be measured analytically in three dimensions, but quantitative interpretation requires a distributed inversion problem. In the example of a volume sensor, medical imaging and rigorous mathematical analysis lead to optimal sensor design and optimal placement for highest sensitivity. Finally, prediction of drug transport in the brain leads to improved treatment options for patients suffering from neurodegenerative disorders such as Parkinsons and Alzheimers. Infusion parameters such as flow rate and drug catheter position need to be optimized in three dimensions to achieve maximal therapeutic thresholds in the desired target area of the soft brain tissue. This example constitutes a three dimensional design problem with partial differential equation constraints. Our systematic modeling approach may improve the simulation and design of disease treatment options.