Imaging ex vivo healthy and pathological human brain tissue with ultra-high-resolution optical coherence tomography

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Abstract
In neurosurgery, the goal of any intracranial intervention is to provide accurate localization, diagnosis, and an appropriate treatment of intracranial abnormalities, while causing minimal damage to the intact brain. During open-skull surgery, the boundaries of some lesions, in particular some gliomas, as well as the presence and location of small brain tumors may be difficult to determine by means of visual inspection or microscopic imaging of the tissue surface. In the past a number of nonoptical imaging methods1 2 3 4 5 6 7 8 9 such as magnetic resonance imaging (MRI), ultrasound, and computed tomography (CT) have been used to identify the margins of large brain tumors and to locate clusters of tumor cells positioned farther away. Although these imaging modalities enable noninvasive tumor diagnostics, they suffer from two major disadvantages: poor spatial resolution (hundreds of micrometers to a few millimeters), insufficient for resolving small brain tumors, and misalignment between the imaged and actual positions of the tumor due to tissue movement during surgery.10 Recently, there has been a constant demand for the development of noninvasive or minimally invasive optical imaging techniques that can be applied in neurosurgery as guiding tools and as an alternative to standard excisional biopsy. Imaging methods such as diffuse optical tomography, reflectance imaging, near-IR and Raman spectroscopy, fluorescence, and confocal microscopy11 12 13 14 15 have enabled visualization of single tumor cells as well as better delineation of brain tumor borders. Despite all these advantages, each of these imaging modalities possesses some inherent limitation related to image resolution, acquisition time, specificity, and accuracy of the acquired image/information, etc., which motivates the constant search for novel more precise and less invasive imaging modalities.

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