The process of translating lab-built innovations into viable tools for clinical applications is complex and costly. Clearing the regulatory processes is the pivotal step that eventually enables these devices to be implemented for the intended clinical applications. Unfortunately this task could be challenging and time-consuming for unprepared academics aiming to translate their inventions/discoveries from bench to bedside. Therefore there is a vital need to educate researchers on adopting the best approach when dealing with regulatory submissions to ensure smoother translation of their respective technologies.
To understand the bench to bedside pathway more clearly, we will utilize the example of the first-ever discovery of near infrared autofluorescence in parathyroid glands at Vanderbilt University. Subsequently a lab-built system was designed for label-free intraoperative parathyroid identification during thyroid and parathyroid surgeries, which was tested across 162 patients with high accuracy. Subsequently Vanderbilt University partnered with AiBiomed (Santa Barbara, California) to develop a clinical prototype called ‘PTeye’ that was user-friendly for surgeons and ready-to-use in operation rooms. The ‘PTeye’ was then evaluated across 81 patients in a single-blinded, multi-centric study that yielded 96% accuracy. Relying on this data, Vanderbilt University and AiBiomed initiated the ‘de novo’ application process with the Food and Drug Administration (FDA) for regulatory clearance of the ‘PTeye’. The ‘de novo’ approach was selected since the instrument design and intended use of ‘PTeye’ did not resemble that of any pre-existing medical devices. Following a successful review, the FDA eventually granted permission to market ‘PTeye’ as an adjunct intraoperative tool for label-free parathyroid identification.
Fluorescence imaging is a well-established optical modality that has been used to localize and track fluorophores in vivo and has demonstrated great potential for surgical guidance. Despite the variety of fluorophores currently being researched, many existing intraoperative fluorescence imaging systems are specifically designed for a limited number of applications. We present a modular wide-field fluorescence overlay tissue imaging system for intraoperative surgical guidance that is comprised of commercially available standardized components. Its modular layout allows for the accommodation of a broad range of fluorophores, fields of view (FOV), and spatial resolutions while maintaining an integrated portable design for intraoperative use. Measurements are automatic and feature a real-time projection overlay technique that intuitively displays fluorescence maps directly onto a 15 × 15 cm2 FOV from a working distance of 35 cm. At a 20-ms exposure time, 10 μM samples of indocyanine green could be measured with high signal-to-noise ratio and was later tested in an in vivo mouse model before finally being demonstrated for intraoperative autofluorescence imaging of human soft tissue sarcoma margins. The system’s modular design and ability to enable naked-eye visualization of wide-field fluorescence allow for the flexibility to adapt to numerous clinical applications and can potentially extend the adoption of fluorescence imaging for intraoperative use.
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