Rapid Label-Free Analysis of Brain Tumor Biopsies by Near Infrared Raman and Fluorescence Spectroscopy—A Study of 209 Patients

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.