Brain metastases are secondary intracranial lesions which occur more frequently than primary brain tumors. The four most abundant types of brain metastasis originate from primary tumors of lung cancer, colorectal cancer, breast cancer and renal cell carcinoma. As metastatic cells contain the molecular information of the primary tissue cells and IR spectroscopy probes the molecular fingerprint of cells, IR spectroscopy based methods constitute a new approach to determine the origin of brain metastases. IR spectroscopic images of 4 by 4 mm2 tissue areas were recorded in transmission mode by a FTIR imaging spectrometer coupled to a focal plane array detector. Unsupervised cluster analysis revealed variances within each cryosection. Selected clusters of five IR images with known diagnoses trained a supervised classification model based on the algorithm soft independent modeling of class analogies (SIMCA). This model was applied to distinguish normal brain tissue from brain metastases and to identify the primary tumor of brain metastases in 15 independent IR images. All specimens were assigned to the correct tissue class. This proof-of-concept study demonstrates that IR spectroscopy can complement established methods such as histopathology or immunohistochemistry for diagnosis.

This study applies infrared (IR) spectroscopy to distinguish normal brain tissue from brain metastases and to determine the primary tumor of four frequent brain metastases such as lung cancer, colorectal cancer, breast cancer, and renal cell carcinoma. Standard methods sometimes fail to identify the origin of brain metastases. As metastatic cells contain the molecular information of the primary tissue cells and IR spectroscopy probes the molecular fingerprint of cells, IR spectroscopy based methods constitute a new approach to determine the primary tumor of a brain metastasis. IR spectroscopic images were recorded by a FTIR spectrometer equipped with a macro sample chamber and coupled to a focal plane array detector. Unsu- IntroductionThe metastatic cascade is the process by which the primary tumor detaches and forms deposits at a remote site, e.g., the central nervous system. The primary tumors that have the strongest tendency to form metastases in the brain are lung cancer, breast cancer, renal cell carcinoma, and colorectal cancer. In 10 to 20% of brain metastases patients the primary tumor is initially not known at the time of neurosurgery (1). In 5% of brain metastases patients the primary tumor remains unknown in spite of intensive screening (2). Beside tumor resection, the scope of neurosurgical procedures is to collect tissue specimens for diagnosis (3).Histopathology complemented by immunohistochemistry is the standard method to diagnose brain metastases. Histopathology characterizes cell morphology and tumor differentiation by light microscopic examination of thin tissue sections that are stained by specific dyes such as hematoxylin and eosin (H&E). Unfortunately, most brain metastases are not differentiated in a way that enables histologically unambiguous assignment to the primary tumor.