Cerebrospinal fluid volume measurements in hydrocephalic rats

Laboratory investigation

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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.

Article Information

Address correspondence to: Andreas Linninger, Ph.D., Department of Bioengineering, University of Illinois at Chicago, Science and Engineering Offices (SEO), Room 218 (M/C 063), 851 South Morgan Street, Chicago, Illinois 60607-7052. email: linninge@uic.edu.

Please include this information when citing this paper: published online August 10, 2012; DOI: 10.3171/2012.6.PEDS11457.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Three-dimensional reconstructions and volume calculation from MRI data in a weanling rat model, in which hydrocephalus (HC) was induced via kaolin injection. The ventricles are shown darker, while the brain is shown as light gray. The images were used to calculate the dimensions of the implanted sensors for rats using Mimics image reconstruction software. Raw images courtesy of M. R. Del Bigio.

  • View in gallery

    Images showing the volume and pressure measurement protocol. A volume sensor (B) was implanted into the lateral ventricles of a hydrocephalic rat (A). An acute procedure of 4 shunting/infusion phases was performed using a syringe pump (A). Volume and pressure were recorded dynamically 10,000 times per second.

  • View in gallery

    Silicone balloon calibration and validation for the rats. The sensor is placed inside a very small silicone balloon (inset, A) whose fluid content can easily be manipulated by adding artificial CSF through a syringe pump. A: Graph shows the raw relationship between sensor output and fluid volume. B: Graph showing sensor-measured volume (solid line) and actual volume (dashed line) after calibration. C: Graph showing the plot of pressure. The relative changes of pressure and volume within the balloon are inherent properties of the balloon compliance.

  • View in gallery

    Average volume and pressure measurements in Phases 1 (A) and 3 (B) of 4 hydrocephalic animals (28 days after induction) due to CSF shunting. The upper row shows measurements and standard deviations with the impedance-based volume sensor. The solid line is the volume removed using the syringe pump. There is an excellent correlation (r = 0.99) between the actual volume and the volume measured during shunting procedures. The pressure measurements are plotted in the lower row. These 4 animals are also represented in Fig. 7B–E.

  • View in gallery

    Bland-Altman Plot. The difference between actual and measured volume are plotted as a function of the amount of CSF removed for Phase 1. The sensor is most accurate for small fluid removal of 0–10 μl and becomes less accurate for large volume changes. The mean measurement difference is 4.6 μl (17.3% maximum measurement error).

  • View in gallery

    Surgical sensor placement. Left: The surgical procedure implant is shown. Right: A lateral radiograph with contrast injected into the hydrocephalic ventricle animal. The sensor and ventricular system are outlined by a dashed line. The skull is outlined in a solid line for better visibility. The electrode contact points of the volume sensor appear to be fully embedded in the CSF fluid.

  • View in gallery

    Coronal cross-sections of a normal rat (A) and hydrocephalic rats with various degrees of ventriculomegaly (B–F). The coronal cuts are made at the same location through the frontal horns. Scale at top = millimeters.

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