NeuroVu: A Novel Cloud-based Microscope for Remote Neurosurveillance of the Seizure-Brain Tumor Nexus

ABSTRACT Recent clinical and preclinical studies have shown that seizures can adversely interact with brain tumors to sƟmulate tumor cell proliferaƟon and invasion. Moreover, posƟctal hypoperfusion can give rise to hypoxia-driven radiaƟon resistance and convenƟonal anƟ-seizure drugs can limit the efficacy of chemotherapeuƟc agents. CollecƟvely, these factors complicate the clinical management of these paƟents and degrade their quality of life (QOL). Therefore, an understanding of the physiology underlying the “seizure-brain tumor nexus” is crucial for treaƟng brain cancer paƟents and enhancing their QOL. However, brain tumor associated seizures occur at random, creaƟng a major obstacle for studying them with standard imaging technologies (e.g., fMRI/PET) which only offer a few hours of imaging. While EEG can circumvent this problem, it does not provide the spaƟal specificity required to parse the seizure-tumor nexus. AddiƟonally, most imaging technologies also require anesthesia, which confounds the assessment of seizure-induced hemodynamic (i.e. blood flow and oxygenaƟon) abnormaliƟes. These hurdles limit our ability to image the seizure-brain tumor nexus in vivo and elucidate the interacƟons between seizure-induced neuronal hyperexcitaƟons, posƟctal hypoxia, tumor cell proliferaƟon and mobilizaƟon. To address these issues, we propose to develop a new class of remotely controlled, cloud-based, mulƟcontrast miniaturized microscopes called “NeuroVu” for characterizing the seizure-brain tumor nexus without Ɵme constraints in unanestheƟzed or freely behaving animals. NeuroVu will be capable of real-Ɵme dual channel fluorescence (dual-FL), dual intrinsic opƟcal signal (dual-IOS) and laser speckle contrast (LSC) imaging to enable conƟnuous in vivo “neurosurveillance” by imaging both, the seizure-associated hyperexcited neurovascular unit and its interacƟons with proliferaƟng brain tumor cells. A variant of NeuroVu (NeuroVuopto) will be capable of optogeneƟc-based inhibiƟon of neuronal hyperexcitability to directly assess the impact of seizures on brain tumor invasion. QuanƟfying these dynamic interacƟons will provide invaluable insights into the seizure-brain tumor nexus, create a novel platiorm for developing synergisƟc anƟ-seizure and anƟ-cancer therapeuƟcs, and pave the way for more efficacious management of paƟents with brain cancer.