Multi-Spectral Clinical Prototype for Fluorophore Detection

Abstract

Identification of tumour margins during resection of the brain is critical for improving the post-operative outcomes. Current methods of tumour identification use 5-ALA, an exogenous precursor, metabolized to fluorescent PpIX in tumour tissue. Although visible under fluorescent microscope, PpIX is easily photo-bleached and tumour tagging is subjective, resulting in tumour under-resection and accelerated recurrence. To address this issue, photo-bleaching resistant and quantitative method is required. This study describes the characterization of a pulsed, multi-wavelengths system designed to measure diffuse reflectance and auto-fluorescence under strong ambient illumination conditions. The performance was tested on n = 400 liquid tissue phantoms containing a wide concentration range of absorber, scatterer and two fluorophores as well as on ex-vivo samples of gray and white matter. The background subtraction technique was shown to be efficient for a range of ambient illumination intensities. A linear relationship was observed between system response and predicted fluorophore concentrations as well as 97.8% accuracy of tissue classification by 5-fold cross-correlation, linear SVM.

Silicon Photomultiplier—A High Dynamic Range, High Sensitivity Sensor for Bio-Photonics Applications

“…In this section, a bio-photonics tissue-recognition biopsy device is discussed. A previous version of the work by Lu et al [ 4 ] is presented, and its adaptation into a board with SiPMs is demonstrated.…”

“…Aiming to develop a bio-photonics tissue-recognition device for surgical guidance in vivo, Lu et al investigated the introduction of multiple illumination and detection bands [ 4 ]. Specifically, eight illumination sources and eight APDs were used to simultaneously collect DRS and AF spectra to distinguish between healthy and cancerous tissue.…”

“…Designing a high-sensitivity, wide dynamic range and low-noise application-specific integrated circuit (ASIC) for silicon photomultipliers (SiPMs) with the potential for device heterogeneous integration, miniaturisation and surgical tool integration will enhance clinical utility. This integrated ASIC and SiPM will have particular application for brain tumour margin resection using auto-fluorescence (AF) [ 3 , 4 , 5 ]. Additionally, use of multispectral and hyperspectral optical source techniques for deep tissue measurements and AF measurements for biomarker detection further challenges the sensitivity and dynamic range requirements of detectors and their supporting electronics [ 2 , 4 , 6 ].…”

“…This integrated ASIC and SiPM will have particular application for brain tumour margin resection using auto-fluorescence (AF) [ 3 , 4 , 5 ]. Additionally, use of multispectral and hyperspectral optical source techniques for deep tissue measurements and AF measurements for biomarker detection further challenges the sensitivity and dynamic range requirements of detectors and their supporting electronics [ 2 , 4 , 6 ].…”

“…However, some published works contain detailed discussion of the photodetectors employed. Some of the research listed here used photodiodes (PDs) [ 8 , 9 ], avalanche photodiodes (APDs) [ 2 , 4 , 10 , 11 , 12 , 13 , 14 ], single photon avalanche photodiodes (SPADs) [ 15 ], and silicon photomultipliers [ 16 , 17 , 18 , 19 , 20 ]. These works primarily focus on the specific bio-photonics applications rather than discussing the specifications of the photo detection devices.…”