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Real-time Brain Tumor imaging with endogenous fluorophores: a diagnosis proof-of-concept study on fresh human samples
Fanny Poulon1, Johan Pallud2,3,4, Pascale Varlet5,3,4
1IMNC Laboratory, UMR 8165-CNRS/IN2P3, Paris-Saclay university, 91405, Orsay, France.
Abstract:
The primary line of therapy for high-grade brain tumor is surgical resection, however, identifying tumor margins in vivo remains a major challenge. Despite the progress in computer-assisted imaging techniques, biopsy analysis remains the standard diagnostic tool when it comes to delineating tumor margins. Our group aims to answer this challenge by exploiting optical imaging of endogenous fluorescence in order to provide a reliable and reproducible diagnosis close to neuropathology. In this study, we first establish the ability of two-photon microscopy (TPM) to discriminate normal brain tissue from glioblastomas and brain metastasis using the endogenous fluorescence response of fresh human brain sample. Two-photon fluorescence images were compared to gold standard neuropathology. "Blind" diagnosis realized by a neuropathologist on a group of TPM images show a good sensitivity, 100%, and specificity, 50% to discriminate non tumoral brain tissue versus glioblastoma or brain metastasis. Quantitative analysis on spectral and fluorescence lifetime measurements resulted in building a scoring system to discriminate brain tissue samples.
Insights
This study demonstrates two-photon microscopy (TPM) can accurately distinguish brain tumors from healthy tissue using natural fluorescence. This optical imaging technique offers a promising alternative for precise tumor margin delineation in neurosurgery.
Area of Science:
- Neuro-oncology
- Optical Imaging
- Medical Diagnostics
Background:
- Surgical resection is the primary treatment for high-grade brain tumors, but precise tumor margin identification in vivo remains a significant challenge.
- Current methods rely on biopsy analysis, which is time-consuming and may not always accurately delineate tumor boundaries.
- Advanced imaging techniques are needed to provide real-time, reliable margin assessment during surgery.
Purpose of the Study:
- To evaluate the efficacy of two-photon microscopy (TPM) in discriminating between normal brain tissue and brain tumors (glioblastomas and metastases) using endogenous fluorescence.
- To establish TPM as a reliable and reproducible diagnostic tool for intraoperative tumor margin delineation.
- To develop a quantitative scoring system based on spectral and fluorescence lifetime measurements for improved tissue discrimination.
Main Methods:
- Two-photon microscopy (TPM) was used to image fresh human brain tissue samples.
- Endogenous fluorescence properties of normal brain tissue, glioblastomas, and brain metastases were analyzed.
- TPM images were compared with gold-standard neuropathology, and a neuropathologist performed blind diagnoses.
- Quantitative spectral and fluorescence lifetime measurements were performed.
Main Results:
- TPM successfully discriminated between normal brain tissue and high-grade brain tumors (glioblastomas and metastases) based on endogenous fluorescence.
- Blind diagnosis by a neuropathologist using TPM images achieved 100% sensitivity and 50% specificity in differentiating non-tumoral tissue from tumors.
- Quantitative analysis of spectral and fluorescence lifetime data enabled the development of a scoring system for tissue discrimination.
Conclusions:
- Two-photon microscopy (TPM) utilizing endogenous fluorescence is a viable optical imaging modality for distinguishing brain tumors from normal brain tissue.
- TPM offers a potentially rapid and accurate method for intraoperative tumor margin assessment, complementing existing diagnostic tools.
- Further development of TPM-based quantitative analysis could significantly enhance surgical precision in neuro-oncology.
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