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EXTH-19. WIRELESS INTRACRANIAL FLUORESCENCE MONITOR FOR DRUG DETECTION IN BRAIN TUMOR PATIENTS

Neuro-oncology(2018)

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摘要
Currently, the brain penetration of drugs cannot be adequately evaluated in real-time, making chemotherapy selection for glioblastoma patients an unpredictable and inefficient process. Given recent progress in the microminiaturization of medical devices, our objective was to design and build the prototype of an implantable device allowing immediate quantification of fluorescent agents in vivo. The Wireless Intracranial Fluorescence Monitor (WIFM) was assembled from commercially -purchased electrical and optical components, a custom-made printed circuit board (PCB), and 3D-printed couplers. Parts included a cyan LED, light-filtering lenses, optical fibers, a phototransistor, and a Bluetooth-enabled Arduino microcontroller. The filters prevented overlap of wavelengths from the LED and fluorophore emission spectra, ensuring isolated emission signals. Clinically, the WIFM would fit inside a standard Ommaya Reservoir, surgically implanted into brain parenchyma during craniotomy. The WIFM was tested in vitro in solutions of 0, 0.01, 0.05 and 0.10 mg/mL of fluorescein isothiocyanate (FITC), in PBS. FITC emission signals were converted into millivoltage readings, and transmitted to a laptop computer, allowing instantaneous wireless determinations. Voltage separations occurred 10–90 milliseconds after FITC excitation, were linearly related to FITC concentration, and allowed for FITC quantification by the device. Specifically, FITC concentrations of 0, 0.01, 0.05, and 0.10 mg/mL produced relative mV readings of 0, 30.6 ± 13.4, 99.9 ± 25.9 and 214.3 ± 21.0, respectively (n=15, p<0.05). While animal studies are needed in order to enable discrimination of interstitial fluorophore concentration, WIFM implantation offers the potential for real-time detection and quantification of the delivery of fluorescently-labeled drugs and/or nanoparticles to selected areas of the brain. Further iterations of the WIFM device should allow the administration of therapeutic agents (whether by systemic administration or convection-enhanced delvery) to be optimized, thus prolonging survival for patients with glioblastoma.
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