Raman spectroscopic imaging for in vivo detection of cerebral brain metastases

Abstract

We report for the first time a proof-of-concept experiment employing Raman spectroscopy to detect intracerebral tumors in vivo by brain surface mapping. Raman spectroscopy is a non-destructive biophotonic method which probes molecular vibrations. It provides a specific fingerprint of the biochemical composition and structure of tissue without using any labels. Here, the Raman system was coupled to a fiber-optic probe. Metastatic brain tumors were induced by injection of murine melanoma cells into the carotid artery of mice, which led to subcortical and cortical tumor growth within 14 days. Before data acquisition, the cortex was exposed by creating a bony window covered by a calcium fluoride window. Spectral contributions were assigned to proteins, lipids, blood, water, bone, and melanin. Based on the spectral information, Raman images enabled the localization of cortical and subcortical tumor cell aggregates with accuracy of roughly 250 μm. This study demonstrates the prospects of Raman spectroscopy as an intravital tool to detect cerebral pathologies and opens the field for biophotonic imaging of the living brain. Future investigations aim to reduce the exposure time from minutes to seconds and improve the lateral resolution.

Raman spectroscopy as a promising noninvasive tool in brain cancer detection

“…They created a bony window in the mice skull to enable in vivo studies using a¯ber-optic probe. Cortical and subcortical tumor cell aggregates could be localized with an accuracy of 250 m. 20 In vivo studies were also carried out by Beljebbar et al, however, they used a microprobe coupled to their spectrometer instead of a¯-beroptic probe. A glioblastoma Wistar rat model was used in this study, obtained after injecting a C6 glioma cell suspension into brain cortex, and sequential progression was monitored at days 4, 6, 8, 11, 13, 15, and 20 post tumor injection.…”

Molecular pathology via IR and Raman spectral imaging

“…Another example was a murine model where brain metastases were induced by injection of tumor cells of malignant melanoma into the carotid artery. A fiber optic probe Raman setup was applied to collect Raman images of murine brains [90] and brain regions in living mice through a cranial window [91]. Recent work studied human brain metastases by Raman and FTIR microscopic imaging [92,93].…”

Biological and Medical Applications of Multivariate Curve Resolution Assisted Raman Spectroscopy

“…[56][57][58][59][60][61] Raman spectroscopy has been successfully employed to both in vivo and in vitro, and one can easily find its application in various fields of medicine including pathology, 62,63 physiology, 64 virology, 65 urology, 66,67 and dentistry. [68][69][70] Either by using cells, dissected tissues or real time monitoring during surgery, researchers have demonstrated the utility of Raman spectroscopy, particularly in cancers related to brain, 71,72 83,84 Additionally, by analyzing biofluids such as blood and urine, non-invasive diagnostic assays are also being actively developed for many diseases such as diabetes (glucose level monitoring), 85,86 cancer, 87,88 asthma, 89 and malaria. 90,91 Most of these studies relied on univariate analysis (one or two marker bands used for biomolecular identification).…”