Objective: Cerebral edema characterized as 4 an abnormal accumulation of interstitial fluid has not been 5 treated effectively. We propose a novel edema treatment 6 approach to drive edematous fluid out of the brain by di-7 rect current utilizing brain tissue's electroosmotic property. 8 Methods: A finite element (FE) head model is developed 9 and employed to assess the feasibility of the approach. 10 First, the capacity of the model for electric field predic-11 tion is validated against human experiments. Second, two 12 electrode configurations (S and D-montage) are designed 13 to evaluate the distribution of the electric field, electroos-14 motic flow (EOF), current density, and temperature across 15 the brain under an applied direct current. Results: The 16 S-montage is shown to induce an average EOF velocity 17 of 7e-4 mm/s underneath the anode by a voltage of 15 V, 18 and the D-montage induces a velocity of 9e-4 mm/s by a 19 voltage of 5 V. Meanwhile, the brain temperature in both 20 configurations is below 38°C, which is within the safety 21 range. Further, the magnitude of EOF is proportional to 22 the electric field, and the EOF direction follows the current 23 flow from anode to cathode. The EOF velocity in the white 24 matter is significantly higher than that in the gray matter 25 under the anode where the fluid is to be drawn out. Conclu-26 sion: The proposed electroosmosis based approach allows 27 alleviating brain edema within the critical time window by 28 direct current. Significance: The approach may be further 29 developed as a new treatment solely or as a complement to 30 existing conventional treatments of edema. 31 Index Terms-Cerebral edema, Electroosmotic flow, 32 Electric field, FE head model. 33 I. INTRODUCTION 34 C EREBRAL edema is defined as the accumulation of water 35 in extracellular and intracellular spaces, leading to high 36 morbidity and mortality [1], [2]. Among a variety of pathogenic 37 factors, traumatic brain injuries (TBIs) constitute the primary 38 cause for brain swelling that could also lead to other serious

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Background Hyperosmotic therapy is a mainstay treatment for cerebral edema. Although often effective, its disadvantages include mainly acting on the normal brain region with limited effectiveness in eliminating excess fluid in the edema region. This study investigates how to configure our previously proposed novel electroosmosis based edema treatment as a complement to hyperosmotic therapy. Methods Three electrode configurations are designed to drive the excess fluid out of the edema region, including 2-electrode, 3-electrode, and 5-electrode designs. The focality and directionality of the induced electroosmotic flow (EOF) are then investigated using the same patient-specific head model with localized edema. Results The 5-electrode design shows improved EOF focality with reduced effect on the normal brain region than the other two designs. Importantly, this design also achieves better directionality driving excess edema tissue fluid to a larger region of surrounding normal brain where hyperosmotic therapy functions better. Thus, the 5-electrode design is suggested to treat edema more efficiently via a synergic effect: the excess fluid is first driven out from the edema to surrounding normal brain via EOF, where it can then be treated with hyperosmotic therapy. Meanwhile, the 5-electrode design drives 2.22 mL excess fluid from the edema region in an hour comparable to the other designs, indicating a similar efficiency of EOF. Conclusions The results show that the promise of our previously proposed novel electroosmosis based edema treatment can be designed to achieve better focality and directionality towards a complement to hyperosmotic therapy.