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Electroosmosis Based Treatment Approach for Cerebral Edema

Time: Mon 2021-09-20 10.00

Location:, Huddinge (English)

Subject area: Technology and Health

Doctoral student: Teng Wang , Neuronik

Opponent: Professor Tiit Illimar Mathiesen, University of Copenhagen

Supervisor: Universitetslektor Xiaogai Li, Neuronik; Professor Svein Kleiven, Neuronik

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Cerebral edema characterized as an abnormal accumulation of excess fluid in the intracellular or extracellular spaces has not been treated effectively despite aggressive treatments. As a result, cerebral edema often leads to intracranial pressure (ICP) elevation with potentially severe consequences unless treated effectively. Hyperosmotic therapy is a mainstay of pharmacologic treatment for cerebral edema by drawing fluid out of the brain into the vascular system by osmotic gradient between the two; however, it usually causes side effects such as decreased cerebral perfusion and renal failure. For patients with severe cerebral edema, decompressive craniectomy (DC) is commonly considered a last resort to reduce raised ICP, although DC causes stretching of the brain tissue, which has been suggested to contribute to unfavorable patient outcomes, vegetative state, and even death. Therefore, cerebral edema treatment is still an arduous task and new innovative therapies are to be sought to improve patient outcomes.

This thesis attempts to develop a novel edema treatment approach to drive edematous fluid out of the brain parenchyma by applying an external direct current utilizing the brain’s electroosmotic property. Given the advantage of the finite element (FE) method to handle complex geometries and solve partial differential equations within neuroscience, FE head models were employed to explore the distribution of electric field, current density, temperature, and electroosmotic flow (EOF) across the brain during the electroosmosis based treatment. 

The electroosmosis based treatment was first proposed and evaluated systematically via a baseline head model in the first study. The proposed approach was verified to allow alleviating brain edema within a critical time window by a direct current, in which the excess fluid was driven from the edema region to subarachnoid space (SAS) along the direction of electric current flow. In the second study, three representative anisotropic conductivity algorithms were employed for the white matter (WM) and compared with isotropic WM. The extent of EOF velocity variation was highly correlated with the degree of the anisotropic ratio of the WM regions, and EOF in anisotropic models tended to move along the principal fiber direction. The results suggested the importance of incorporating WM anisotropic conductivity for a more reliable prediction of electric field and EOF inside the brain. In the third study, the capability of the electroosmosis based approach for edema treatment was further evaluated with three patient-specific head models with various types of edema. The electroosmosis based treatment was shown to reduce excess fluid at a rate of 1.8, 2.38, 0.73 mL/hour for patients with diffuse, localized, and expanded edema, respectively; thus, the estimated treatment time for the respective patient was around 15.4, 2.0, and 26 hours. In the fourth study, the application of electroosmosis based treatment in different age groups was investigated. The results demonstrated that anatomical structure (e.g., fontanel, brain volume, and brain atrophy) significantly affected the EOF distribution across the brain, suggesting that special attention should be paid to select appropriate treatment dosage for infants and adults with relatively smaller brains to avoid brain injury caused by high current density. The final study aimed at investigating the possibility of configuring the proposed approach as a complement to hyperosmotic therapy for cerebral edema. Through redesigning electrode configuration, the proposed approach improved EOF focality with a reduced effect on normal brain regions, and better directionality allowing driving the fluid from the edema region into the surrounding tissues more evenly where it could be absorbed by a larger volume of tissue during hyperosmotic therapy.

In conclusion, this thesis describes a novel edema treatment approach to alleviate the abnormal accumulation of excess fluid in brain parenchyma by applying an external direct current, and then demonstrates its capacity utilizing FE head models. It is hoped that this research has made a valuable and lasting contribution to cerebral edema treatment.