abbreviatioNs CS = cavernous sinus; ER = endocrinological remission; GTR = gross-total resection; ICA = internal carotid artery. submitted May 22, 2014. accepted December 2, 2014. iNclude wheN citiNg Published online February 6, 2015; DOI: 10.3171/2014.12.JNS141083. disclosure The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. obJect An important prognostic factor for the surgical outcome and recurrence of a pituitary adenoma is its invasiveness into parasellar tissue, particularly into the space of the cavernous sinus (CS). The aims of this study were to reevaluate the existing parasellar classifications using an endoscopic technique and to evaluate the clinical and radiological outcomes associated with each grade. methods The authors investigated 137 pituitary macroadenomas classified radiologically at least on one side as Grade 1 or higher (parasellar extension) and correlated the surgical findings using an endoscopic technique, with special reference to the invasiveness of the tumor into the CS. In each case, postoperative MRI was performed to evaluate the gross-total resection (GTR) rate and the rate of endocrinological remission (ER) in functioning adenomas. results The authors found a 16% rate of CS invasion during surgery for these macroadenomas. Adenomas radiologically classified as Grade 1 were found to be invasive in 1.5%, and the GTR/ER rate was 83%/88%. For Grade 2 adenomas, the rate of invasion was 9.9%, and the GTR/ER rate was 71%/60%. For Grade 3 adenomas, the rate of invasion was 37.9%, and the GTR/ER rate was 75%/33%. When the superior compartment of the CS (Grade 3A) was involved, the authors found a rate of invasion that was lower (p < 0.001) than that when the inferior compartment was involved (Grade 3B). The rate of invasion in Grade 3A adenomas was 26.5% with a GTR/ER rate of 85%/67%, whereas for Grade 3B adenomas, the rate of surgically observed invasion was 70.6% with a GTR/ER rate of 64%/0%. All of the Grade 4 adenomas were invasive, and the GTR/ER rate was 0%. A comparison of microscopic and endoscopic techniques revealed no difference in adenomas with Grade 1 or 4 parasellar extension. In Grade 2 adenomas, however, the CS was found by the endoscopic technique to be invaded in 9.9% and by microscopic evaluation to be invaded in 88% (p < 0.001); in Grade 3 adenomas, the difference was 37.9% versus 86%, respectively (p = 0.002). Grade 4 adenomas had a statistically significant lower rate of GTR than those of all the other grades. In case of ER only, Grade 1 adenomas had a statistically significant higher rate of remission than did Grade 3B and Grade 4 adenomas. coNclusioNs The proposed classification proved that with increasing grades, the likelihood of surgically observed invasion rises and the chance of GTR and ER decreases. The direct endoscopic view confirmed the low rate of invasion of Grade 1 adenomas but showed significantly lower rates of invasion in Grade 2 and 3 adenomas than those previousl...

BACKGROUND: Because of intratumoral heterogeneity, diffusely infiltrating gliomas that lack significant contrast enhancement on magnetic resonance imaging are prone to tissue sampling error. Subsequent histologic undergrading may delay adjuvant treatments. 5-Aminolevulinic acid (5-ALA) leads to accumulation of fluorescent porphyrins in malignant glioma tissue, and is currently used for resection of malignant gliomas. The aim of this study was to clarify whether 5-ALA might serve as marker for visualization of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement for precise intraoperative tissue sampling. METHODS: 5-ALA was administered in 17 patients with diffusely infiltrating gliomas with nonsignificant contrast enhancement. During glioma resection, positive fluorescence was noted by a modified neurosurgical microscope. Intraoperative topographic correlation of focal 5-ALA fluorescence with maximum 11 C-methionine positron emission tomography uptake (PET max ) was performed. Multiple tissue samples were taken from areas of positive and/or negative 5-ALA fluorescence. Histopathological diagnosis was established according to World Health Organization (WHO) 2007 criteria. Cell proliferation was assessed for multiregional samples by MIB-1 labeling index (LI). RESULTS: Focal 5-ALA fluorescence was observed in 8 of 9 patients with WHO grade III diffusely infiltrating gliomas. All 8 of 8 WHO grade II diffusely infiltrating gliomas were 5-ALA negative. Focal 5-ALA fluorescence correlated topographically with PET max in all patients. MIB-1 LI was significantly higher in 5-ALA-positive than in nonfluorescent areas within a given tumor. CONCLUSIONS: The data indicate that 5-ALA is a promising marker for intraoperative visualization of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement. Unaffected by intraoperative brain shift, 5-ALA may increase the precision of tissue sampling during tumor resection for histopathological grading, and therefore optimize allocation of patients to adjuvant treatments. Cancer 2010;116:1545-52.

BackgroundIntraoperative identification of anaplastic foci in diffusely infiltrating gliomas (DIG) with non-significant contrast-enhancement on MRI is indispensible to avoid histopathological undergrading and subsequent treatment failure. Recently, we found that 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX) fluorescence can visualize areas with increased proliferative and metabolic activity in such gliomas intraoperatively. As treatment of DIG is predominantely based on histopathological World Health Organisation (WHO) parameters, we analyzed whether PpIX fluorescence can detect anaplastic foci according to these criteria.MethodsWe prospectively included DIG patients with non-significant contrast-enhancement that received 5-ALA prior to resection. Intraoperatively, multiple samples from PpIX positive and negative intratumoral areas were collected using a modified neurosurgical microscope. In all samples, histopathological WHO criteria and proliferation rate were assessed and correlated to the PpIX fluorescence status.ResultsA total of 215 tumor specimens were collected in 59 patients. Of 26 WHO grade III gliomas, 23 cases (85%) showed focal PpIX fluorescence, whereas 29 (91%) of 33 WHO grade II gliomas were PpIX negative. In intratumoral areas with focal PpIX fluorescence, mitotic rate, cell density, nuclear pleomorphism, and proliferation rate were significantly higher than in non-fluorescing areas. The positive predictive value of focal PpIX fluorescence for WHO grade III histology was 85%.ConclusionsOur study indicates that 5-ALA induced PpIX fluorescence is a powerful marker for intraoperative identification of anaplastic foci according to the histopathological WHO criteria in DIG with non-significant contrast-enhancement. Therefore, application of 5-ALA optimizes tissue sampling for precise histopathological diagnosis independent of brain-shift.

Surgical approaches tailored to an individual patient's anatomy and pathology have become standard in neurosurgery. Precise preoperative planning of these procedures, however, is necessary to achieve an optimal therapeutic effect. Therefore, multiple radiological imaging modalities are used prior to surgery to delineate the patient's anatomy, neurological function, and metabolic processes. Developing a three-dimensional perception of the surgical approach, however, is traditionally still done by mentally fusing multiple modalities. Concurrent 3D visualization of these datasets can, therefore, improve the planning process significantly. In this paper we introduce an application for planning of individual neurosurgical approaches with high-quality interactive multimodal volume rendering. The application consists of three main modules which allow to (1) plan the optimal skin incision and opening of the skull tailored to the underlying pathology; (2) visualize superficial brain anatomy, function and metabolism; and (3) plan the patient-specific approach for surgery of deep-seated lesions. The visualization is based on direct multi-volume raycasting on graphics hardware, where multiple volumes from different modalities can be displayed concurrently at interactive frame rates. Graphics memory limitations are avoided by performing raycasting on bricked volumes. For preprocessing tasks such as registration or segmentation, the visualization modules are integrated into a larger framework, thus supporting the entire workflow of preoperative planning.