Fluorescence Lifetime Imaging and Spectroscopic Co-Validation for Protoporphyrin IX-Guided Tumor Visualization in Neurosurgery

Frontiers in Oncology

Marco Wilzbach¹  Christoph Hauger¹  Mikael T. Erkkilae²  Wolfgang Drexler²  Angelika Unterhuber²  Marco Andreana²  Rainer A. Leitgeb³  David Reichert³  Alexandra Lang⁴  Barbara Kiesel⁴  Georg Widhalm⁴  Lisa I. Wadiura⁴  Johanna Gesperger⁵  Adelheid Woehrer⁵  Thomas Roetzer⁵ 

[1] Advanced Development Microsurgery, Carl Zeiss Meditec AG, Oberkochen, Germany;Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria;Christian Doppler Laboratory OPTRAMED, Medical University of Vienna, Vienna, Austria;Department of Neurosurgery, Medical University of Vienna, Vienna, Austria;Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria;

关键词: fluorescence-guided surgery;    fluorescence lifetime imaging (FLIM);    fluorescence spectroscopy;    protoporphyrin IX;    surgical microscope;   

DOI  :  10.3389/fonc.2021.741303

来源: DOAJ

【 摘 要 】

Maximal safe resection is a key strategy for improving patient prognosis in the management of brain tumors. Intraoperative fluorescence guidance has emerged as a standard in the surgery of high-grade gliomas. The administration of 5-aminolevulinic acid prior to surgery induces tumor-specific accumulation of protoporphyrin IX, which emits red fluorescence under blue-light illumination. The technology, however, is substantially limited for low-grade gliomas and weakly tumor-infiltrated brain, where low protoporphyrin IX concentrations are outweighed by tissue autofluorescence. In this context, fluorescence lifetime imaging has shown promise to distinguish spectrally overlapping fluorophores. We integrated frequency-domain fluorescence lifetime imaging in a surgical microscope and combined it with spatially registered fluorescence spectroscopy, which can be considered a research benchmark for sensitive protoporphyrin IX detection. Fluorescence lifetime maps and spectra were acquired for a representative set of fresh ex-vivo brain tumor specimens (low-grade gliomas n = 15, high-grade gliomas n = 80, meningiomas n = 41, and metastases n = 35). Combining the fluorescence lifetime with fluorescence spectra unveiled how weak protoporphyrin IX accumulations increased the lifetime respective to tissue autofluorescence. Infiltration zones (4.1ns ± 1.8ns, p = 0.017) and core tumor areas (4.8ns ± 1.3ns, p = 0.040) of low-grade gliomas were significantly distinguishable from non-pathologic tissue (1.6ns ± 0.5ns). Similarly, fluorescence lifetimes for infiltrated and reactive tissue as well as necrotic and core tumor areas were increased for high-grade gliomas and metastasis. Meningioma tumor specimens showed strongly increased lifetimes (12.2ns ± 2.5ns, p = 0.005). Our results emphasize the potential of fluorescence lifetime imaging to optimize maximal safe resection in brain tumors in future and highlight its potential toward clinical translation.

【 授权许可】

Unknown