Tumor-brain Interface Research Articles

Meningiomas with brain edema: Radiological characteristics on MRI and review of the literature

Object: Despite their benign characteristics, meningiomas are often accompanied by perifocal brain edema. The aims of this study are to determine what kind of characteristics on magnetic resonance (MR) image are indicative of a meningioma that produces brain edema and to investigate the mechanism responsible for brain edema accompanying meningiomas. Methods: Fifty-one patients with meningioma were examined by magnetic resonance imaging (MRI), and tumor size, tumor location, shape of tumor margin, peritumoral rim, and signal intensity of tumor on T2-weighted image (T2WI) were compared and correlated with the presence versus absence of brain edema. Surgical histopathology was also examined and correlated with the MRI findings and brain edema. Results: Shape of tumor margin, peritumoral rim, and signal intensity of tumor on T2WI correlated with brain edema on multivariate analyses. Conclusion: Invasive pattern of brain–tumor interface and hyperintensity on T2WI were indicative factors of meningiomas producing brain edema.

Peritumoral brain edema in intracranial meningiomas: effects of radiological and histological factors.

We examined the radiological and histological features influencing the development of peritumoral brain edema (PTBE) among patients with meningiomas. Factors causing PTBE were retrospectively analyzed for 125 patients with primary intracranial meningiomas. These factors included tumor size, tumor location, brain-tumor interface, signal intensity on T2-weighted scans, contrast enhancement, and cyst formation (as observed on magnetic resonance imaging scans), as well as tumor vascularity and blood supply (as observed in digital subtraction angiography studies). We defined the edema/tumor volume ratio as the edema index, and we used this index to evaluate PTBE. A relationship between the tumor size and the volume of PTBE was observed. Convexity and middle fossa meningiomas demonstrated the greatest increases in mean edema indices. Meningothelial, anaplastic, microcystic, and angiomatous subtypes exhibited higher edema indices than did other types. Multivariate analysis demonstrated two significant radiological factors: cortical penetration (as defined by the disappearance of the arachnoid layer on magnetic resonance imaging scans) (relative risk, 2.067; P = 0.0148) and vascular supply from the pial-cortical arteries (as observed on angiograms) (relative risk, 2.087; P = 0.0082). Tumor infiltration into adjacent brain parenchyma and a pial-cortical blood supply are critical factors for the development of PTBE among patients with meningiomas.

Meningiomas of the sellar region presenting with visual impairment: impact of various prognostic factors on surgical outcome in 62 patients.

Meningiomas of the supra- and parasellar region can cause insidious visual loss by optic nerve compression. 62 cases with such tumours affecting the anterior optic pathways were analysed to assess the surgical results and prognostic factors with particular attention to visual outcome. In all patients, visual deterioration was the first clinical manifestation. Eleven lesions had their origin at the anterior clinoid process, 24 at the tuberculum sellae, 10 at the planum sphenoidale, two in the optic canal, 10 in the medial sphenoidal wing, and five in the olfactory groove. All patients underwent microsurgical tumour resection. Median age at the time of operation was 54 years, median duration of symptoms seven months. The mean follow-up time was 5.2 years (range 2 to 8 years). Statistical analysis of prognostic factors (gender, age, tumour location, tumour size, duration of symptoms, brain tumour interface, resection grade, preoperative visual loss, Glascow Outcome Score) was performed using univariate and multivariate analysis. The severe morbidity rate was 6.4%. Two patients died within the first 30 postoperative days. Overall, vision improved in 39 (65%) patients, in 11 (18%) it was unchanged, and worse in 10 (17%). Visual prognosis was favourably affected by age under 54 years (p < 0.025), duration of symptoms of less than seven months (p < 0.037), and the presence of an intact arachnoid membrane around the lesion (p < 0.001). Severe preoperative loss of visual acuity (<0.02) appeared to be an unfavourable prognostic factor (p < 0.047). Possible difficulties and surgical outcome in such patients can be predicted successfully. These facts in connection with new therapeutic modalities (radiosurgery, adjuvant therapies) will demand a careful risk assessment and should influence the treatment strategies and the degree of operative aggressiveness in the future.

Die Bedeutung von morphologischen Veränderungen der Hirn-Tumor-Grenze für die Pathogenese des Hirnödems bei Meningeomen: Magnetresonanztomographie und intraoperative Untersuchungen

The aim of the study was to verify a possible correlation between macroscopic changes of the brain-tumor interface (BTI) and the development of a peritumoral brain edema in meningiomas. 27 meningiomas were investigated in this prospective study using an optimized inversion-recovery (IR) sequence. After i.v. administration of 0.2 mmol Gd-DTPA/kg axial and coronary images were acquired (slice thickness = 2 mm). The distances of signal altered cortex and obliterations of the subarachnoid space (SAS) were measured at the BTI and related to the pial tumor circumference (cortical-index and SAS-index). Intraoperatively the BTI was divided into the following categories: 0: SAS not obliterated, 1: SAS partially obliterated, 2: direct contact between tumor and white matter, 3: tumor infiltration into brain. Edema-associated meningiomas showed a significantly (p = 0.0001) increased SAS-index (0.47 vs. 0.07) and cortical index (0.45 vs. 0.0) compared to cases without edema. Intraoperatively 95% of meningiomas with brain edema showed SAS-obliterations, compared to 50% of cases without an edema. Arachnoid adhesions at the BTI with obliteration of the SAS seem to play an essential role in the induction of brain edema in meningiomas.

Chordoid glioma of the third ventricle: Confirmatory report of a new entity

The term “chordoid glioma” was recently introduced to denote a circumscribed, apparently low-grade neoplasm arising in or preferentially involving the third ventricle of middle-aged women. We report biopsy and postmortem findings in a 60-year-old woman with symptoms of forgetfulness, headache, and lethargy. Neuroimaging showed a contrast-enhancing third ventricular mass with obstructive hydrocephalus. The tumor was subtotally resected. Microscopically, it consisted of clusters and strands of epithelioid cells in a mucoid matrix. Its margins were remarkably discrete and showed little tendency to infiltrate surrounding brain parenchyma. The majority of neoplastic cells were glial fibrillary acidic protein (GFAP) and vimentin positive, whereas S100 protein labeled only individual cells. Stains for epithelial membrane antigen (EMA) and cytokeratin were nonreactive. There was no evidence of neuroendocrine differentiation or expression of estrogen and progesteron receptors. Lymphoplasmacellular infiltrates were noted throughout the lesion and at the tumor-brain interface. The MIB-1 labeling index averaged 1.5%. At present, chordoid glioma is considered a glial neoplasm of uncertain histogenesis with distinct clinicopathologic features.

Preoperative identification of meningiomas that are highly likely to recur.

Although generally they are well-circumscribed benign tumors, meningiomas recur even after complete removal. The aims of this study are to identify preoperatively groups of patients who have a high risk of meningioma recurrence by reviewing their clinicoradiological features and to plan appropriate treatments. One hundred one patients who underwent macroscopically complete removal of meningiomas were observed postoperatively for at least 5 years or until tumor recurrence. Preoperative radiological findings and clinical characteristics were assessed. Fifteen meningiomas recurred during the follow-up period, which extended to a maximum duration of 18 years. On univariate analysis, tumor size and shape, relation to the major sinuses, calcification, bone changes, and characteristics of the tumor-brain interface were significant predictive factors for recurrence. Patient age and gender were not deemed significant. Multivariate analysis revealed that only the shape of the tumor was significant; both "mushrooming" and lobulated meningiomas were more likely to recur than round ones. Recurrences most frequently occurred at the edge of the dural resection after a Simpson Grade I removal, whereas local recurrences were predominant after a Simpson Grade II or III removal. Meningiomas with mushrooming or lobulated shapes should be treated more aggressively with a wider dural excision. This is not usually necessary for round tumors, although it may be beneficial in younger patients.

Morphometrical characterization of two glioma models in the brain of immunocompetent and immunodeficient rats.

Although several glioma models exist, systematic morphometrical studies on such experimental tumors are lacking. The purpose of this study was the quantitative assessment of how rat strains, cell lines, injection techniques and location affect tumors reproducibility and histopathological features. Glioma cells were implanted in 3 brain locations, with different injection techniques (free hand, stereotactic, water-tight device), variable volumes, cell concentrations and infusion rates. Tumors were developed from 2 rat glioma cell lines (9L and C6) in immunocompetent (Wistar and Fischer 344) and immunodeficient rats (New Zealand). Animals underwent daily neurological examination. At the scheduled time the tumors were macro and microscopically evaluated and a quantitative morphometrical analysis was performed. C6 gliomas appeared very infiltrative and irregularly shaped; 9L gliomas showed, by using the same injection technique, a grossly regular shape. Margins at the tumor-brain interface were macroscopically demarcated in the immunocompetent rats. In the nude rats, 9L tumors appeared microscopically more infiltrative, although regularly shaped, with a closer morphological resemblance to human gliomas. The implantation in the frontal area, anterior to the nucleus caudatus (3 mm anterior the coronal suture) gave reproducible tumor shape and size, no hydrocephalus and no early neurological deterioration. The use of a stereotactic technique or of a water-tight device, small volume (< 10 microl) of cell suspension, low infusion rate were useful to reduce morbidity and to improve data reproducibility. No difference in morbidity and mortality were observed in immunocompetent and immunodeficient rats. The 9L glioma model with stereotactic implantation constitutes a good option for reliable morphometrical evaluation of tumor growth. We propose a location for tumor implantation anterior to the nucleus caudatus. This produced the longest symptom-free survival.

Tumor Cell Endocytosis Imaging Facilitates Delineation of the Glioma–Brain Interface

We describe a method for measuring tumor cell endocytosisin vivoand provide the anatomic correlate of this tumor cell function using a superparamagnetic and histologically detectable marker for cell uptake (MION). Rats (n=22) were intrahemispherically implanted with a thymidine kinase (TK)-positive 9L gliosarcoma cell line, where TK served as the tumor marker. Twenty-four hours after intravenous injection of 10 mg Fe/kg of MION, rat brains were removed and underwent MR imagingex vivoat near-microscopic resolution (isotropic voxel size of 86 μm, 9.4 T) prior to histologic processing. The imaging probe accumulated within tumor cells adjacent to the hyperpermeable tumor–brain interface including microscopic deposits and along finger-like invasions of the tumor into brain, facilitating the demarcation of the true histologic tumor border in three dimensions by MR microscopy. The method has potential research and clinical implications for delineating the tumor–brain interface prior to therapy and/or for providing a rational basis for imaging nanocolloid drug delivery to solid tumors.

Nitric oxide synthase is expressed in experimental malignant glioma and influences tumour blood flow.

The distribution and function of nitric oxide synthase (NOS) was studied in the rodent C6 implantation glioma model. Using a histochemical stain for NADPH diaphorase, which colocalises with NOS, morphological studies revealed non homogenous staining of the constituent tumour cells and the neoplastic endothelium. Immunocytochemical staining for macrophages (ED1, ED2) showed dense positivity at the tumour brain interface with more patchy positivity within the tumour mass. This finding suggests that both macrophages, which are known to produce large amounts of NO, and the C6 cells contribute to the NADPH diaphorase positivity. Administration of the NOS inhibitor Ng-nitro-L-argine methyl ester (L-NAME) significantly reduced both tumour (40%) and contralateral local cerebral blood flow (20%) compared to control animals. These findings demonstrate that (i) NOS is present in experimental malignant glioma; (ii) NO mediated mechanisms contribute to tumour blood vessel dilatation and blood flow regulation; and (iii) using this model there is a significant differential sensitivity of the tumour and brain parenchymal vascular beds to a NOS inhibitor. Further investigations are required to determine the potential therapeutic and biological relevance of these findings and the relative contributions of tumour cells, neoplastic endothelium and reactive macrophages to NO mechanism in gliomas.

Invasive meningioma: a tumour with high proliferating and "recurrence" potential.

A study was undertaken to investigate the correlation between histological invasiveness and proliferating potential and clinical recurrence in meningioma. In 39 meningiomas, the histological findings at the tumour-brain interface zone were classified into 3 types, consisting of 29 cases of non-invasion (NON). 7 cases of nodular invasion (NOD), and 3 cases of intermingled invasion (INT). Proliferating cell nuclear antigen (PCNA) and argyrophilic nucleolar organizer region (AgNOR) indices were studied. PCNA indices (mean +/- standard error) of NON, NOD. and INT were 1.7 +/- 0.1%, 5.2 +/- 0.5%, and 7.5 +/- 0.7%. respectively, and the AgNOR indices (dot number/nucleus) were 1.50 +/- 0.03, 2.00 +/- 0.04, and 2.22 +/- 0.07, respectively. Significant differences were found among the three types in both parameters. Clinically, tumour recurrence was observed in 1/29 NON, 4/7 NOD, and 2/2 INT cases, indicating a higher incidence of recurrence in invasive meningiomas (NOD plus INT). Four of 32 patients who underwent gross total removal of the tumours showed recurrence, and all of these four tumours were invasive meningiomas. The results of the present study showed that tumour invasiveness as measured by PCNA + AgNOR indices correlated well with high proliferative potential and clinical recurrence.

Frameless stereotaxy and interactive neurosurgery with the ISG viewing wand.

Preliminary experience with the ISG wand for frameless stereotaxy is presented. The wand is a multijointed mechanical arm with a range of 25 inch radius sphere. The arm has a analog/digital hybrid transducers to locate the spatial position of the probe tip. The real time displays of triplanar 2D images with an optional 2D/3D image helps in surgical planning and interactive surgery. Seventeen patients underwent neurosurgical procedures with the help of wand. The wand was used to place minimal craniotomies, localise the brain-tumour interface and excise the lesions. The wand had an accuracy of 1.8 mm (SEM +/- 0.36 mm) in localising the lesions. Thus, the use of frameless stereotaxy has made easier and more precise surgical planning in several applications.

Invasion of experimental rat brain tumor: early morphological changes following microinjection of C6 glioma cells.

We present morphological data of the early stage of tumor invasion in the central nervous system. C6 rat glioma cells were injected into the caudate-putamen of rat brain using glass micropipettes to minimize traumatic reactions. Four days after the inoculation, we examined the tumor-brain interface using light and electron microscopy. Ultrastructurally the tumor processes were attached to the perivascular basement membrane instead of the astroglial end-feet. At the tumor periphery, the vessel walls were in contact with both tumor processes and astroglial end-feet. Astrocytes withdrew their processes from the vascular walls and changed into a reactive phenotype, while the neuronal cells remained virtually intact, even when surrounded by tumor cells. Immunohistochemical study using C6 cells labeled with bromodeoxyuridine showed migration of the cells toward the perivascular space that was distant from the site of injection. These observations represent the earliest morphologically detectable changes of the tumor-brain interface, and suggest that the C6 cells possess the characteristics of high affinity to the endothelial basement membrane and invade along the preexisting blood vessels with brain parenchymal infiltration.

Peritumoral cerebral edema in meningiomas: the role of the tumor-brain interface

We investigated the role of the tumor-brain interface in the production of peritumoral cerebral edema in meningiomas by analysing the size, shape, histological type and location of the tumor, and radiological and operative findings. Our results suggest that changes of the boundary zone between the tumor and the brain such as the disappearance of the subarachnoid space, cortical thinning or loss, and possibly partial loss of the arachnoid membrane are the most important factors in edema production, and that multiple other factors determine the morphological changes which occur at the tumor-brain interface.

Anticopper Treatment Inhibits Pseudopodial Protrusion and the Invasive Spread of 9L Gliosarcoma Cells in the Rat Brain

Abstract The copper ion, a cofactor of angiogenesis, is sequestered in human brain tumors and the adjacent brain. The invasive spread of neoplastic cells has been linked to angiogenesis and involves similar mechanisms of migration and tumormatrix interaction. In this report, copper depletion inhibited the infiltrative spread of the normally invasive 9L gliosarcoma. Twenty male Fischer 344 rats were each injected with 1 x 1059L cells; 10 rats were treated with a lowcopper diet and penicillamine. In the normocupremic control rats, a “diffuse” invasive pattern was observed in all 10 animals. In the hypocupremic group, a “nodular” pattern, with a discrete border between tumor and brain, was found in 7 of 10 rats (P&amp;lt; 0.01). In a second experiment, the brains of 16 tumor-bearing rats were studied by electron microscopy. In the 8 normocupremic control rats, cytoplasmic extensions and pseudopodial protrusions, cytological markers of invasive cells, were prominent at the tumor-brain interface. In striking contrast, pseudopodia were absent along the border of the tumors in the 8 hypocupremic rats. These findings suggest a biological role of copper in the neoplastic spread of brain tumor cells. Pharmacological and metabolic alteration of the cellular microenvironment to inhibit invasiveness represents a novel therapeutic approach, especially for tumors of the brain in which malignancy is a function of regional invasiveness.

Anticopper treatment inhibits pseudopodial protrusion and the invasive spread of 9L gliosarcoma cells in the rat brain

The copper ion, a cofactor of angiogenesis, is sequestered in human brain tumors and the adjacent brain. The invasive spread of neoplastic cells has been linked to angiogenesis and involves similar mechanisms of migration and tumor-matrix interaction. In this report, copper depletion inhibited the infiltrative spread of the normally invasive 9L gliosarcoma. Twenty made Fischer 344 rats were each injected with 1 X 10(5) 9L cells; 10 rats were treated with a low-copper diet and penicillamine. In the normocupremic control rats, a "diffuse" invasive pattern was observed in all 10 animals. In the hypocupremic group, a "nodular" pattern, with a discrete border between tumor and brain, was found in 7 of 10 rats (P less than 0.01). In a second experiment, the brains of 16 tumor-bearing rats were studied by electron microscopy. In the 8 normocupremic control rats, cytoplasmic extensions and pseudopodial protrusions, cytological markers of invasive cells, were prominent at the tumor-brain interface. In striking contrast, pseudopodia were absent along the border of the tumors in the 8 hypocupremic rats. These findings suggest a biological role of copper in the neoplastic spread of brain tumor cells. Pharmacological and metabolic alteration of the cellular microenvironment to inhibit invasiveness represents a novel therapeutic approach, especially for tumors of the brain in which malignancy is a function of regional invasiveness.

Interface between the meningioma and the brain on magnetic resonance imaging

Magnetic resonance imaging of 31 meningiomas in 29 patients was retrospectively reviewed and compared with pathologic specimens in 25 tumors to investigate how magnetic resonance imaging could delineate a tumor-brain interface. The thick, collagenous connective tissue, which was seen around four tumors, was shown as a low signal intensity rim on both a T1-weighted image and a T2-weighted image. A rim of low signal intensity on a Tl-weighted image and high signal intensity on a T2-weighted image most likely represented cerebrospinal fluid space: this finding was seen around eight tumors. No distinct rim could be identified in five tumors. Of these five, two tumors grew invasively into the brain. Although mixed features predominated in meningiomas, magnetic resonance imaging could well delineate a tumor-brain relationship in most of the cases.

A new glioma model in rat: the C6 spheroid implantation technique permeability and vascular characterization.

The C6 spheroid implantation glioma model is a simple, easily reproduced model for primary gliomas in which C6 astrocytoma cells are grown in vitro as spheroids and subsequently implanted into the brains of Sprague Dawley rat hosts. This report describes the growth, histology, vessel architecture and vascular permeability of the resulting tumors. The appearance of the tumor was investigated by light and electron microscopy, and by using the alkaline phosphatase technique. The leakage of tracer was measured from vessels in the tumor and peritumoral area at various times during tumor development. The spheroid implant produces a fully vascularized, rapidly growing tumor with many of the characteristics of glioblastoma multiforme, from an avascular focus of neoplastic cells. The major advantage of this model is that the tumors grow in a spheroidal fashion and the tumor-brain interface can be easily located. Many of the important events in the process of vascularization take place at the tumor-brain interface. Two distinctive vascular events appear to occur simultaneously: proliferation of blood vessels and their growth into the tumor mass so that they develop into typical, permeable tumor vessels, and migration of tumor cells along normal vessels into the surrounding brain. Tumor vessels were permeable to the tracer Evans Blue (EB) from the earliest days of ingrowth. Leakage of the EB increased as the tumors increased in size, but eventually leakage plateaued as tumors developed necrotic centers. It is well known that the structural and permeability characteristics of vessels associated with the tumor affect tumor growth. This model will be useful for a number of proposed studies including assessment of various clinical therapies on tumor growth and development, and more specifically, quantitative analysis of the vascularization process in tumors.