Abstract
In brain surgery, novel technologies are continuously developed to achieve better tumor delineation and maximize the extent of resection. Raman spectroscopy is an optical method that enables to retrieve a molecular signature of tissue biochemical composition in order to identify tumor and normal tissue. Here, the translation of Raman spectroscopy to the surgical practice for discerning a variety of different tumor entities from non-neoplastic brain parenchyma was investigated. Fresh unprocessed biopsies obtained from brain tumor surgery were analyzed over 1.5 years including all patients that gave consent. Measurements were performed with a Raman microscope by medical personnel as routine activity. The Raman and fluorescence signals of the acquired spectra were analyzed by principal component analysis, followed by supervised classification to discriminate non-tumor tissue vs. tumor and distinguish tumor entities. Histopathology of the measured biopsies was performed as reference. Classification led to the correct recognition of all non-neoplastic biopsies (7/7) and of 97% of the investigated tumor biopsies (195/202). For instance, GBM was recognized as tumor with a correct rate of 94% if primary, and of 100% if recurrent. Astrocytoma and oligodendroglioma were recognized as tumor with correct rates of 86 and 90%, respectively. All brain metastases, meningioma and schwannoma were correctly recognized as tumor and distinguished from non-neoplastic brain tissue. Furthermore, metastases were discerned from glioma with correct rate of 90%. Oligodendroglioma and astrocytoma IDH1-mutant, which differ in the presence of 1p/19q codeletion, were discerned with a correct rate of 81%. These results demonstrate the feasibility of rapid brain tumors recognition and extraction of diagnostic information by Raman spectroscopy, using a protocol that can be easily included in the routine surgical workflow.
Highlights
During the last decades, advances in imaging, functional mapping, neuronavigation as well as fluorescence-based technologies for identification of malignant tissue have increased the ability of neurosurgeons to optimize tumor removal and preserve normal brain [1]
Fresh unprocessed biopsies of 210 patients undergoing brain surgery at the Dresden University Hospital were collected in the operating room (OR) immediately after resection and transported to the Raman spectroscopic system inside a tube filled with isotonic NaCl solution
Several studies have already shown that Raman spectroscopy is a very powerful and sensitive technique to highlight subtle aspects of brain tumor biochemistry [12, 17, 18, 22] and to monitor tumor metabolism [9, 31]
Summary
Advances in imaging, functional mapping, neuronavigation as well as fluorescence-based technologies for identification of malignant tissue have increased the ability of neurosurgeons to optimize tumor removal and preserve normal brain [1]. Optical molecular imaging techniques emerged in the recent years as innovative methods for retrieving diagnostic information and provide real-time histopathologic images of tumors [4]. Among those techniques, Raman spectroscopy has attracted increasing attention in oncology as non-invasive and label-free method, with the aim to provide new tools for the detection of malignant and pre-malignant lesions in a variety of cancer entities [5]. Raman band intensity is correlated with the concentration of those groups, thereby providing the possibility to probe the biochemistry of cancerous tissue without markers and to perform molecular pathology [6,7,8]
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