5-ALA induced PpIX fluorescence guided surgery: a clinical study of spectral complexity in healthy tissues and margin boundaries in high and low grade gliomas

Abstract INTRODUCTION Fluorescence-guided surgery can improve tumor identification and extent of surgical resection. 5-ALA is the standard for GBM, but is limited by lack of quantitative fluorescence, a need to work in the dark, and a lack of sensitivity for low grade tumors. We have developed a novel instrument for dye-free tissue autofluorescence lifetime imaging (FLIm) to identify glioma tissue during resection. This approach utilizes time-resolved autofluorescence measurements in narrow-band channels to assess markers of tissue metabolism. Compared to intensity-based imaging of exogenous fluorophores, FLIm has greater sensitivity without dependence on background lighting. The advantages of FLIm include quantitative tissue analysis, the ability to work under full light conditions, sensitivity for high and low grade gliomas, and the potential ability to identify IDH mutational status. In this study, we validated the use of FLIm for identification of glioma tissue at tumor resection margins. METHODS FLIm was used to image tissue margins during glioma resections and compared to microbiopsies from imaged regions to correlate fluorescence with histopathology. RESULTS FLIm was applied intraoperatively to 11 GBM and 5 LGG patients (7 imaged biopsies per patient). In GBM, tumor infiltration of cortex was associated with significantly decreased fluorescence lifetime (FL) in channels 2 (470/28nm;p<0.05) and 3 (542/50nm;p<0.002). In subcortical margins, FL was inversely proportional to the density of tumor in channels 2,3 (p<0.05). When IDH wild-type GBMs were compared to IDH1-mutant tumors, FL was noted to be significantly longer in channel 1 (390/40nm;p<0.05), and trended towards longer FL in channel 2, shorter FL in channel 3. In LGG, FL was significantly correlated with tumor density in channel 2 (p<0.01). CONCLUSIONS FLIm is a dye-free, quantitative alternative to 5-ALA for fluorescence guided glioma resections with sensitivity to high and low-grade tumors, and the ability to predict IDH mutations in GBM. Further validation studies are on-going.

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5-Aminolevulinic Acid–Protoporphyrin IX Fluorescence-Guided Surgery for CNS Tumors

JBNC - JORNAL BRASILEIRO DE NEUROCIRURGIA ◽

10.22290/jbnc.v27i1.783 ◽

2018 ◽

Vol 27 (1) ◽

pp. 13-19

Author(s):

Ricardo Ramina ◽

Erasmo Barros Da Silva Júnior ◽

Maurício Coelho Neto ◽

Leonardo Gilmone Ruschel ◽

Felipe Andrés Constanzo Navarrette

Keyword(s):

Aminolevulinic Acid ◽

Protoporphyrin Ix ◽

High Grade Glioma ◽

Awake Surgery ◽

Histopathological Diagnosis ◽

Low Grade ◽

High Grade ◽

Guided Surgery ◽

Fluorescence Guided Surgery ◽

High Grade Gliomas

Introduction: In the last two decades the 5-aminolevulinic acid (5-ALA) has been utilized in primary brain lesions and metastases surgery to aid the identification of tumor limits and infiltration. Objectives: In this retrospective study, we demonstrate our experience with the first 41 cases Latin America of surgical resection of central nervous system (CNS) lesions with 5-ALA. Methods: In 41 consecutive patients, we recorded age, sex, histopathological diagnosis, intraoperative 5-ALA fluorescence tumor response, 5-ALA post-resection resection grade through magnetic resonance image (MRI) and other concomitantintra-operative techniques utilized (transoperative imaging, awake surgery, electrophysiological stimulation and monitoring). Results: Twenty seven high-grade gliomas and 4 non-glial lesions were 5-ALA fluorescence positive; 6 low-grade gliomas, 1 high-grade glioma and a hippocampal gliosis were 5-ALA fluorescence negative. In one case of a low-grade glioma, the patient developed a cardiac arrhythmia, probably not related to 5-ALA administration, but the surgery was suspended. Conclusions: 5-ALA fluorescence-guided surgery is a safe and easy technique to be used, increasing tumor total gross resection in glioma cases, proving to be an invaluable neurosurgical tool for intracranial tumor surgery. There was no serious side effect in this series. This dye should be utilized in all cases of high-grade gliomas.

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Fluorescent Guided Surgery in the Surgical Management of Glioma: The Dawn of a New Era

Brain Sciences ◽

10.3390/brainsci10040237 ◽

2020 ◽

Vol 10 (4) ◽

pp. 237

Author(s):

Kostas N. Fountas

Keyword(s):

Surgical Management ◽

Low Grade ◽

New Era ◽

Low Grade Gliomas ◽

Guided Surgery ◽

Growing Body ◽

Supramarginal Resection

A growing body of evidence supports the importance of marginal or even supramarginal resection in cases of high- but also of low-grade gliomas [...]

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Improved Diagnostic Imaging of Brain Tumors by Multimodal Microscopy and Deep Learning

Cancers ◽

10.3390/cancers12071806 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1806

Author(s):

Johanna Gesperger ◽

Antonia Lichtenegger ◽

Thomas Roetzer ◽

Matthias Salas ◽

Pablo Eugui ◽

...

Keyword(s):

Brain Tumor ◽

High Resolution ◽

Tumor Tissue ◽

Intraoperative Imaging ◽

Large Field ◽

Low Grade ◽

Lower Grade ◽

Optical Coherence ◽

Guided Surgery ◽

Fluorescence Guided Surgery

Fluorescence-guided surgery is a state-of-the-art approach for intraoperative imaging during neurosurgical removal of tumor tissue. While the visualization of high-grade gliomas is reliable, lower grade glioma often lack visible fluorescence signals. Here, we present a hybrid prototype combining visible light optical coherence microscopy (OCM) and high-resolution fluorescence imaging for assessment of brain tumor samples acquired by 5-aminolevulinic acid (5-ALA) fluorescence-guided surgery. OCM provides high-resolution information of the inherent tissue scattering and absorption properties of tissue. We here explore quantitative attenuation coefficients derived from volumetric OCM intensity data and quantitative high-resolution 5-ALA fluorescence as potential biomarkers for tissue malignancy including otherwise difficult-to-assess low-grade glioma. We validate our findings against the gold standard histology and use attenuation and fluorescence intensity measures to differentiate between tumor core, infiltrative zone and adjacent brain tissue. Using large field-of-view scans acquired by a near-infrared swept-source optical coherence tomography setup, we provide initial assessments of tumor heterogeneity. Finally, we use cross-sectional OCM images to train a convolutional neural network that discriminates tumor from non-tumor tissue with an accuracy of 97%. Collectively, the present hybrid approach offers potential to translate into an in vivo imaging setup for substantially improved intraoperative guidance of brain tumor surgeries.

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Optical imaging probes and their potential contribution to radiotracer development

Nuklearmedizin ◽

10.1055/s-0037-1616473 ◽

2016 ◽

Vol 55 (02) ◽

pp. 51-62 ◽

Cited By ~ 3

Author(s):

S. Hermann ◽

M. Schäfers ◽

C. Höltke ◽

A. Faust

Keyword(s):

Optical Imaging ◽

Fluorescent Dyes ◽

Great Influence ◽

Potential Contribution ◽

Preclinical Evaluation ◽

Guided Surgery ◽

Fluorescence Guided Surgery ◽

Imaging Probes ◽

Unspecific Binding

SummaryOptical imaging has long been considered a method for histological or microscopic investigations. Over the last 15 years, however, this method was applied for preclinical molecular imaging and, just recently, was also able to show its principal potential for clinical applications (e.g. fluorescence-guided surgery). Reviewing the development and preclinical evaluation of new fluorescent dyes and target-specific dye conjugates, these often show characteristic patterns of their routes of excretion and biodistribution, which could also be interesting for the development and optimization of radiopharmaceuticals. Especially ionic charges show a great influence on biodistribution and netcharge and charge-distribution on a conjugate often determines unspecific binding or background signals in liver, kidney or intestine, and other organs.Learning from fluorescent probe behaviour in vivo and translating this knowledge to radio-pharmaceuticals might be useful to further optimize emerging and existing radiopharmaceuticals with respect to their biodistribution and thereby availability for binding to their targets.

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