Abstract
Early detection and evaluation of brain tumors during surgery is crucial for accurate resection. Currently cryosections during surgery are regularly performed. Confocal laser endomicroscopy (CLE) is a novel technique permitting in vivo histologic imaging with miniaturized endoscopic probes at excellent resolution. Aim of the current study was to evaluate CLE for in vivo diagnosis in different types and models of intracranial neoplasia. In vivo histomorphology of healthy brains and two different C6 glioma cell line allografts was evaluated in rats. One cell line expressed EYFP, the other cell line was used for staining with fluorescent dyes (fluorescein, acriflavine, FITC-dextran and Indocyanine green). To evaluate future application in patients, fresh surgical resection specimen of human intracranial tumors (n = 15) were examined (glioblastoma multiforme, meningioma, craniopharyngioma, acoustic neurinoma, brain metastasis, medulloblastoma, epidermoid tumor). Healthy brain tissue adjacent to the samples served as control. CLE yielded high-quality histomorphology of normal brain tissue and tumors. Different fluorescent agents revealed distinct aspects of tissue and cell structure (nuclear pattern, axonal pathways, hemorrhages). CLE discrimination of neoplastic from healthy brain tissue was easy to perform based on tissue and cellular architecture and resemblance with histopathology was excellent. Confocal laser endomicroscopy allows immediate in vivo imaging of normal and neoplastic brain tissue at high resolution. The technology might be transferred to scientific and clinical application in neurosurgery and neuropathology. It may become helpful to screen for tumor free margins and to improve the surgical resection of malignant brain tumors, and opens the door to in vivo molecular imaging of tumors and other neurologic disorders.
Highlights
Intracranial neoplasms include a variety of different histopathologic entities, ranging from rather benign tumors, such as meningiomas, to some of the most aggressive types of human cancer
Another key factor with patients undergoing neurosurgical intervention due to intracranial neoplasia is the total removal of the tumor [5], while at the same time minimizing trauma to healthy brain tissue
We demonstrate that confocal laser endomicroscopy with new miniaturized probes allows histological imaging of healthy brain and tumors at microscopic level in vivo in rat allograft models and human tissue
Summary
Intracranial neoplasms include a variety of different histopathologic entities, ranging from rather benign tumors, such as meningiomas, to some of the most aggressive types of human cancer. Studies have shown that - as in almost every other tumor disease - early and precise diagnosis [3] and immediate multi-modal treatment is crucial for improving survival rates and quality of life in patients with brain tumors [2,4]. Another key factor with patients undergoing neurosurgical intervention due to intracranial neoplasia is the total removal of the tumor [5], while at the same time minimizing trauma to healthy brain tissue. Neurosurgeons have recently been equipped with new technologic features, such as neuro-navigation [7] and fluorescence-guided surgery [8], distinction of healthy and tumor cells on a cellular level remains challenging
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