Developing a novel method for rapid assessment of blood flow changes in vivo

A reliable method for real-time blood flow monitoring in vivo is critical for several medical applications, including monitoring cardiovascular diseases, evaluating interventional procedures and surgeries, and increasing the safety and efficacy of neuromodulation procedures. High-speed methods are particularly necessary for neural monitoring, due to the brain's heightened sensitivity to hypoxic and ischemic conditions. High-speed CBF monitoring methods may also provide a useful biomarker for the development of a closed-loop deep brain stimulation (DBS) system. Current methods such as laser Doppler, bold fMRI, and positron emission tomography (PET) often involve cumbersome instrumentation and are therefore not well- suited for chronic microvasculature monitoring. The purpose of this study is to develop a method for real-time measurement of blood flow changes using electrochemical impedance spectra (EIS). Utilizing EIS to measure CBF has the potential to be included in a chronic, closed-loop DBS system that is modulated by fluctuations in CBF, using minimal additional instrumentation. Five experiments in rodents were conducted, with the objective of 1) determining whether electrochemical impedance spectra showed impedance changes correlated with changes in blood flow, assessing the sensitivity, specificity, and limitations of detection of this method, and 2) determining whether cyclic voltammetry-based method could be used to produce EIS more rapidly than current methods. The experimental set-up included electrodes in the femoral artery with the administration of endothelin (ET-1) to induce blood flow changes (N=1), electrodes in the motor cortex using isoflurane variation to induce blood flow changes (N=3), and electrodes in the femoral artery with the administration of nitroglycerin (NTG) to induce blood flow changes (N=1). Preliminary results suggest that impedance changes in the higher frequencies (over 160 Hz) demonstrated higher sensitivity to blood flow changes in the femoral artery model compared to <100 Hz frequencies, with inconclusive results in the motor cortex model. Future in vivo experiments will be conducted using endothelin-1 to further establish the relationship between impedance and cerebral blood flow in the brain.