Electrical Bioimpedance Cerebral Monitoring : From Hypothesis and Simulation to First Experimental Evidence in Stroke Patients

Sammanfattning: Stroke is amongthe leading causes of death worldwide and requires immediate care to prevent death or permanent disability. Unfortunately, the current stateof stroke diagnosis is limited to fixed neuroimaging facilities that do not allow rapid stroke diagnosis. Hence, a portable stroke-diagnosis device could assist in the pre-hospital triage of patients. Moreover, such a portable device could also be useful for bedside stroke monitoring of patients in the Neuro Intensive Care Unit (Neuro-ICU) to avoid unnecessary neuroimaging. Recent animal studies and numerical simulations have supported the idea of implementing Electrical Bioimpedance (EBI) in a portable device, allowing non-invasive assessment as a useful tool for the pre-hospital triage of stroke and Traumatic Brain Injury (TBI) patients. Unfortunately, these studies have not reported any results from human subjects in the acute phase of the stroke. The numerical simulations are also based on simple models that sometimes lack necessary details.Finite Element Method (FEM) simulations on a realistic numerical head model as well as experimental Bioimpedance Spectroscopy (BIS) measurements from human subjectsin the acute, subacute and chronic phasesof stroke were used to answer the following research questions: (i) Does stroke modify the electrical properties of brain tissue in a way that is detectable via EBI? (ii) Would it be possible to detect stroke via EBI as early as in the acute and sub-acute phase?(iii) Is EBI sensitive enough to monitor changes caused by stroke pathogenesis?Using FEM to simulate electrical current injection on the head and study the resulting distribution of electrical potential on the scalp, it was shown that Intra-Cranial Hemorrhage (ICH) affects the quasi-symmetric scalp potential distribution,creating larger left-right potential asymmetry when compared to the healthy head model. Proof-of-concept FEM simulations were also tested in a small cohort of 6ICH patients and 10 healthy controls, showing that the left-right potential difference in the patients is significantly (p<0.05) larger than in the controls. Using bioimpedance measurements in the acute,  subacute and chronic phasesof stroke and examining simple features, it was also shown that the head EBI measurements of patients suffering stroke are different from controls, enabling the discrimination of healthy controls and stroke patients at any stage of the stroke. The absolute change in test-retest resistance measurements of the control group (~5.33%) was also found to be significantly (p<0.05) smaller than the EBI measurements of patients obtained 24 hours and 72 hours after stroke onset (20.44%). These results suggested that scalp EBI is sensitive to stroke pathogenesis changesand thususeful for bedside monitoring in the Neuro-ICU. These results suggested that EBI is a potentially useful tool for stroke diagnosis and monitoring.Finally, the initial observations based on a small number of patients, addressing the proposed future work of this thesis, suggested that the average head resistance amplitude of hemorrhagic stroke patients is smaller than in healthy controls, while ischemic stroke patients show a larger resistance amplitude than the controls. Scalp potential asymmetry analysis of healthy, hemorrhagic and ischemic stroke subjects also suggests that these three groups can be separated. However, these results are based on a small number of patients and need to be validated using a larger cohort. Initial observations also showed that the resistance of the EBI measurements of controls is robust between test and retest measurements, showing no significant difference (less than 2% and p>0.05). Subject position during EBI recording (supine or sitting) did not seem to affect the resistance of the EBI measurements (p>0.05). However, age, sex and head size showed significant effects on the resistance measurements. These initial observations are encouraging for further research on EBI for cerebral monitoring and stroke diagnosis. However, at this stage, considering the uncertainties in stroke type differentiation, EBI cannot replace CT but has the potential to be used as a consultation tool.