**5. Definition of histological borders**

392 Advances in the Biology, Imaging and Therapies for Glioblastoma

Fig. 6. Representative NLM images from patients with histologically proven meningeoma (n=3, bar = 100 µm). a: tumor center with a high density of pleomorphic tumor cells in grade II meningeoma, b: undirected tumor cells with a pathological blood vessel (in between the spotted line) and neoangiogenesis (arrows) in the same patient; c: typical onion-shaped tumor cell configuration in grade I meningeoma (circle), d: single apoptotic cells (arrows) in

Neurolasermicroscopy (NLM) was shown to recognize malignant brain tumor characteristics in patients with histologically proven GBM in our pilot feasibility study (Schlosser et al., 2009 (Epub)). There was a good accordance of the NLM images compared to the histopathological findings with respect to the WHO classification (Louis et al., 2007). The differentiation of more specific tumor entities by NLM should be performed after this promising technique is transferred into the intraoperative situation. Our ex vivo approach opened the door for a neurosurgical in vivo diagnosis on a cellular and subcellular level. Moreover, the combination of confocal laser microscopy and flexible video systems may promote a variety of potential developments eligible for neurosurgical procedures. This ranges from process optimization in the operating room (OR) to new ways to corroborate regenerative therapy (Wessels et al., 2007). Current research data showed the same technique we use in our pilot study to be useful in patients during neurosurgery (Sanai et al., 2011 (Epub), Schlosser, H.G., Bojarski, C. (2011 (Epub)). Confocal Neurolasermicroscopy

the tumor border in the same patient.

(NLM). Neurosurgery, Epub,).

**4. Discussion** 

Realizing in vivo histology during neurosurgery would contribute to a better definition of the histological borders of the tumor. This would improve the definition of the resection margins significantly. However, due to the infiltrative growth of many primary brain tumours it is not possible to clearly define the exact margins of a tumor mass in all cases, neither by conventional histology nor by NLM. The in vivo look on these areas from tumor to intact brain tissue (probably by using a histopathological NLM classification) could provide new insights towards a standardized diagnosis during neurosurgery.

On a cellular basis the excision could be performed as much as necessary but as little as possible which could be beneficial for patients suffering from a brain tumor (Lacroix et al., 2001) (Ammirati et al., 1987). The amount of residual tumor mass after surgery is one of the most important prognostic factors (Burger and Green, 1987) (Wood et al., 1988). NLM scans on a cellular and subcellular level could be more accurate than performing the whole investment of brain navigation even with shift correction (Asthagiri et al., 2007).

Regarding those aspects one has to focus on the appearance of the NLM scans depicting tumor pathologies. Cell types, cell division, neovascularisation and boarder zones have to become acquainted to the observer as well as th possibility for dynamic investigation. This histology is different from the appearance in classical histopathology. So neurosurgeon and pathologist have to share their insight and practically an atlas for defining all pathologies seen in NLM with regard for the process in the theatre has to be developed in the near future.
