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.
Highlights
Glioblastoma multiforme (GBM) is the most common form of primary malignant brain cancer with an aggressive and infiltrative growth pattern into the normal brain parenchyma [1, 2]
We have demonstrated a system that can quantify several fluorophores in tissue phantoms with highly varying optical properties, and that the system is developed in a way for straight forward miniaturisation to facilitate clinical adaption
This multi-spectral system consisted of eight illumination sources and eight avalanche photodiodes (APD) with variable gain output
Summary
Glioblastoma multiforme (GBM) is the most common form of primary malignant brain cancer with an aggressive and infiltrative growth pattern into the normal brain parenchyma [1, 2]. The use of 5-ALA has been shown to significantly improve the accuracy of tumour resection and increase the patient survival rates [10, 11]. Despite these improvements, definitive delineation between tumour infiltration zone and healthy brain tissue still remains challenging, primarily because the surgeon must make subjective decisions regarding resection margins based on perceived strengths of fluorescence [12,13,14]. 4A shows the effect of increasing background illumination on light intensities collected at high and low gain settings for each illumination source.
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