Low perfusion compartments in glioblastoma quantified by advanced magnetic resonance imaging and correlated with patient survival.

BACKGROUND AND PURPOSE: Glioblastoma exhibits profound intratumoral heterogeneity in perfusion. Particularly, low perfusion may induce treatment resistance. Thus, imaging approaches that define low perfusion compartments are crucial for clinical management. MATERIALS AND METHODS: A total of 112 newly diagnosed glioblastoma patients were prospectively recruited for maximal safe resection. The apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV) were calculated from diffusion and perfusion imaging, respectively. Based on the overlapping regions of lowest rCBV quartile (rCBVL) with the lowest ADC quartile (ADCL) and highest ADC quartile (ADCH) in each tumor, two low perfusion compartments (ADCH-rCBVL and ADCL-rCBVL) were identified for volumetric analysis. Lactate and macromolecule/lipid levels were determined from multivoxel MR spectroscopic imaging. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier's and multivariate Cox regression analyses, to evaluate the effects of compartment volume and lactate level on survival. RESULTS: Two compartments displayed higher lactate and macromolecule/lipid levels compared to contralateral normal-appearing white matter (each P < 0.001). The proportion of the ADCL-rCBVL compartment in the contrast-enhancing tumor was associated with a larger infiltration on FLAIR (P < 0.001, rho = 0.42). The minimally invasive phenotype displayed a lower proportion of the ADCL-rCBVL compartment than the localized (P = 0.031) and diffuse phenotypes (not significant). Multivariate Cox regression showed higher lactate level in the ADCL-rCBVL compartment was associated with worsened survival (PFS: HR 2.995, P = 0.047; OS: HR 4.974, P = 0.005). CONCLUSIONS: Our results suggest that the ADCL-rCBVL compartment may potentially indicate a clinically measurable resistant compartment.

Longitudinal Imaging of Tumor Volume, Diffusivity, and Perfusion After Preoperative Endovascular Embolization in Supratentorial Hemispheric Meningiomas.

OBJECTIVE: To describe longitudinal image changes in supratentorial hemispheric meningiomas based on magnetic resonance imaging after preoperative embolization using calibrated microspheres. METHODS: A total of 14 patients with symptomatic supratentorial meningiomas were included in a prospective, mono-centric, mono-arm study. Magnetic resonance imaging changes on diffusion-weighted imaging, dynamic contrast susceptibility-perfusion-weighted imaging, susceptibility-weighted imaging, and magnetization-prepared rapid acquisition gradient-echo sequence T1-weighted postcontrast sequences 6 and 48 hours after embolization were evaluated and correlated with angiographic and clinical data. RESULTS: The mean age of the patients was 63 ± 12.7 years with an equal female/male ratio. Twelve meningiomas were World Health Organization grade I and II tumors. After embolization, baseline apparent diffusion coefficient (901 ± 166 mm2/s) decreased significantly within 6 hours (696 ± 115 mm2/s, P = 0.0008) as well within 48 hours (752 ± 134 mm2/s; P = 0.0147). Baseline mean ratio of relative cerebral blood volume (rCBV)tumor/rCBVwhite matter (3.67 ± 1.83) and relative cerebral blood flow (rCBF)tumor/rCBFwhite matter (2.89 ± 1.57) significantly decreased after embolization within 6 hours (rCBVtumor/rCBVwhite matter of 1.45 ± 0.9; P = 0.0007, rCBF of 1.16 ± 0.68; P = 0.0029) and 48 hours (rCBV of 1.50 ± 1.07; P = 0.0009, rCBFtumor/rCBFwhite matter of 1.19 ± 0.8; P = 0.003). The viable enhanced baseline mean tumor volume (54.3 ± 34.9 mm3) was sustainably and significantly diminished within 6 hours (26.6 ± 20.8 mm3; P = 0.02) and 48 hours (29.7 ± 22.5 mm3; P = 0.035) after embolization. There was a good correlation between angiographic devascularization rate and the embolized tumor volume at 6 hours (r = 0.7; P = 0.03) and 48 hours (r = 0.78; P = 0.041). CONCLUSIONS: Preoperative meningioma embolization with calibrated microspheres is safe and effectively induces a significant and sustainable tissue transformation over 48 hours.

Quantitative in vivo imaging of tissue factor expression in glioma using dynamic contrast-enhanced MRI derived parameters.

OBJECTIVE: Tissue Factor (TF) has been well established in angiogenesis, invasion, metastasis, and prognosis in glioma. A noninvasive assessment of TF expression status in glioma is therefore of obvious clinical relevance. Dynamic contrast-enhanced (DCE) MRI parameters have been used to evaluate microvascular characteristics and predict molecular expression status in tumors. Our aim is to investigate whether quantitative DCE-MRI parameters could assess TF expression in glioma. MATERIALS AND METHODS: Thirty-two patients with histopathologically diagnosed supratentorial glioma who underwent DCE-MRI were retrospectively recruited. Extended Tofts linear model was used for DCE-MRI post-processing. Hot-spot, whole tumor cross-sectional approaches, and histogram were used for analysis of model based parameters. Four serial paraffin sections of each case were stained with TF, CD105, CD34 and α-Sooth Muscle Actin, respectively for evaluating the association of TF and microvascular properties. Pearson correlation was performed between percentage of TF expression area and DCE-MRI parameters, multiple microvascular indexes. RESULTS: Volume transfer constant (Ktrans) hot-spot value best correlated with TF (r=0.886, p<0.001), followed by 90th percentile Ktrans value (r=0.801, p<0.001). Moreover, histogram analysis of Ktrans value demonstrated that weak TF expression was associated with less heterogeneous and positively skewed distribution. Finally, pathology analysis revealed TF was associated with glioma grade and significantly correlated with these two dynamic angiogenic indexes which could be used to explain the strong correlation between Ktrans and TF expression. CONCLUSION: Our results indicate that Ktrans may serve as a potential clinical imaging biomarker to predict TF expression status preoperatively in gliomas.

Correlative assessment of tumor microcirculation using contrast-enhanced perfusion MRI and intravoxel incoherent motion diffusion-weighted MRI: is there a link between them?

The purpose of this study was to correlate intravoxel incoherent motion (IVIM) imaging with classical perfusion-weighted MRI metrics in human gliomas. Parametric images for slow diffusion coefficient (D), fast diffusion coefficient (D*), and fractional perfusion-related volume (f) in patients with high-grade gliomas were generated. Maps of Fp (plasma flow), vp (vascular plasma volume), PS (permeability surface-area product), ve (extravascular, extracellular volume), E (extraction ratio), ke (influx ratio into the interstitium), and tc (vascular transit time) from dynamic contrast-enhanced (DCE) and dynamic susceptibility contrast-enhanced (DSC) MRI were also generated. A region-of-interest analysis on the contralateral healthy white matter and on the tumor areas was performed and the extracted parameter values were tested for any significant differences among tumor grades or any correlations. Only f could be significantly correlated to DSC-derived vp and tc in healthy brain tissue. Concerning the tumor regions, Fp was significantly positively correlated with D* and inversely correlated with f in DSC measurements. The D*, f, and f × D* values in the WHO grade III gliomas were non-significantly different from those in the grade IV gliomas. There was a trend to significant negative correlations between f and PS as well as between f × D* and ke in DCE experiments. Presumably due to different theoretical background, tracer properties and modeling of the tumor vasculature in the IVIM theory, there is no clearly evident link between D*, f and DSC- and DCE-derived metrics.

[Preoperative embolization with microspheres of giant supratentorial meningiomas: 5-year experience]. / Embolización preoperatoria con microesferas en meningiomas gigantes supratentoriales: experiencia de 5 años.

BACKGROUND: Preoperative embolization of hypervascular tumours such as meningiomas has proven to be a favorable factor for resection of the latter because it diminishes intraoperative bleeding and the need for blood transfusions. OBJECTIVES: Evaluation of surgical outcomes of preoperative embolization with microspheres of giant supratentorial meningiomas. METHODS: We retrospectively analyzed patient records from 2007 to 2012 with the diagnosis of giant supratentorial meningiomas (> 5 cm) (n= 27) and obtained two samples: those with preoperative embolization (n= 14) and patients without any properative embolization (n= 13). We evaluated and compared statistically significant surgical bleeding, surgical time and resection grade (via Simpson scale). Additionally, we evaluated internal/external vascularization rate and the histopathologic diagnosis. RESULTS: According to the Simpson scale, the mean resection grade was 1.21 for embolized meningiomas, whereas for non-embolized meningiomas it was 1.92 . No differences were found in surgical bleeding and operative time. We used microspheres whose diameters were 40-120 µm, and these were easily observed with common microscopy techniques. In all cases we observed predominance in extracranial vascularization. No morbidity and mortality were recorded with the endovascular procedure. CONCLUSIONS: Embolization with microspheres improves resection rate evaluated by the Simpson scale in patients with giant supratentorial meningiomas.

ANTECEDENTES: la embolización preoperatoria de tumores hipervascularizados, como los meningiomas, ha demostrado ser un factor favorable para su resección quirúrgica en términos de menor sangrado transquirúrgico y transfusiones sanguíneas. OBJETIVOS: evaluar el beneficio quirúrgico de la embolización preoperatoria con microesferas en meningiomas gigantes supratentoriales. MATERIAL Y MÉTODOS: estudio retrospectivo de los expedientes de pacientes postoperados entre 2007 y 2012 con diagnóstico de meningiomas gigantes supratentoriales (>5 cm) (n= 27). La muestra se dividió en dos grupos: pacientes embolizados antes de la intervención (n= 14), y pacientes a quienes no se realizó embolización (n= 13). Se comparó la cantidad de sangrado transoperatorio, el tiempo quirúrgico, y el grado de resección evaluado por la escala de Simpson. Además, se evaluó el tamaño tumoral, la tasa de vascularización de la carótida interna y externa y el diagnóstico histopatológico. RESULTADOS: el promedio de resección de acuerdo con la escala de Simpson para meningiomas embolizados fue de 1.21, mientras que para meningiomas no embolizados fue de 1.92 (t de Student, p= < 0.014). No encontramos diferencias significativas en tiempo quirúrgico o en el sangrado transoperatorio. En más de la mitad de los casos utilizamos microesferas de 40-120 µm de diámetro. Las microesferas se observaron fácilmente con los métodos usuales de microscopia y tinción, su existencia se correlacionó con áreas focales de necrosis. En todos los casos se encontró predominio de vascularización extracraneal, sin que el procedimiento endovascular se asociara con mortalidad. CONCLUSIONES: la embolización de meningiomas gigantes supratentoriales con microesferas mejora el grado de resección quirúrgica evaluada por la escala de Simpson.

Three-dimensional reconstruction of the topographical cerebral surface anatomy for presurgical planning with free OsiriX Software.

BACKGROUND: During surgery for intrinsic brain lesions, it is important to distinguish the pathological gyrus from the surrounding normal sulci and gyri. This task is usually tedious because of the pia-arachnoid membranes with their arterial and venous complexes that obscure the underlying anatomy. Moreover, most tumors grow in the white matter without initially distorting the cortical anatomy, making their direct visualization more difficult. OBJECTIVE: To create and evaluate a simple and free surgical planning tool to simulate the anatomy of the surgical field with and without vessels. METHODS: We used free computer software (OsiriX Medical Imaging Software) that allowed us to create 3-dimensional reconstructions of the cerebral surface with and without cortical vessels. These reconstructions made use of magnetic resonance images from 51 patients with neocortical supratentorial lesions operated on over a period of 21 months (June 2011 to February 2013). The 3-dimensional (3-D) anatomic images were compared with the true surgical view to evaluate their accuracy. In all patients, the landmarks determined by 3-D reconstruction were cross-checked during surgery with high-resolution ultrasonography; in select cases, they were also checked with indocyanine green videoangiography. RESULTS: The reconstructed neurovascular structures were confirmed intraoperatively in all patients. We found this technique to be extremely useful in achieving pure lesionectomy, as it defines tumor's borders precisely. CONCLUSION: A 3-D reconstruction of the cortical surface can be easily created with free OsiriX software. This technique helps the surgeon perfect the mentally created 3-D picture of the tumor location to carry out cleaner, safer surgeries.

Supratentorial extraventricular anaplastic ependymoma in an adult with repeated intratumoral hemorrhage.

We report the case of a 61-year-old man with supratentorial extraventricular anaplastic ependymoma who presented with repeated intratumoral hemorrhage. The patient was admitted with headache. Computed tomography and magnetic resonance imaging showed an enhancing mass with intratumoral hemorrhage in the right temporal lobe. Gross total resection was performed. The tumor was well demarcated from the brain tissue, and showed no continuity with the ventricular system. Histopathological examination revealed the features of anaplastic ependymoma. Therefore, additional radiation therapy and adjuvant chemotherapy were administered. Ten months later, the tumor recurred with hemorrhage in the spinal canal. This case showed rapid malignant progression and repeated intratumoral hemorrhage within a short period of time, both of which are characteristics of anaplastic ependymomas. Close observation of the central nervous system and adjuvant radiotherapy are mandatory, even if the ependymoma presents with repeated intratumoral hemorrhage.

Prognostic value of peritumoral edema and angiogenesis in intracranial meningioma surgery.

PURPOSE: In a series of 78 consecutive patients we analyzed the influence of peritumoral edema (PTE) and angiogenesis (vascular endothelial growth factor/ VEGF expression) on the prognosis of morbidity and postoperative complications after intracranial meningioma surgery. METHODS: A retrospective analysis was performed of clinical, neuroradiological and histological data of 78 microsurgically treated patients with intracranial supratentorial meningioma, with follow-up period of at least one year. RESULTS: The severity of PTE showed significant correlation with VEGF expression, and all patients with large PTE (>40 mm) had strong VEGF expression (>50%). Treatment outcome was significantly better in patients with low VEGF expression (p<0.05). All of the monitored postoperative complications were more frequent in the group with PTE.The duration of intensive care treatment in the group with PTE (mean 6.85 days) was significantly longer than in the group without PTE (mean 3.68 days) (p=0.003). In the group without PTE, the outcome was significantly better than in patients with PTE (p<0.01). CONCLUSION: PTE in intracranial meningiomas has significant influence on the prognosis in surgically treated patients in terms of increased risk of morbidity and postoperative complications. VEGF expression is strongly correlated with PTE formation, which also affects the outcome in the management of patients with intracranial meningioma.

Assessment of angiogenesis by CD105 and nestin expression in peritumor tissue of glioblastoma.

Angiogenesis in the peritumor tissue of glioblastoma (GBM) is still an open field of research. This study investigates neovascularization in the tumor surrounding areas by examining CD105 and nestin expression along with microvessel density (MVD) with the aim of establishing their possible prognostic significance. Angiogenesis was also confirmed by investigating, in vessel walls, the presence of pericytes, which are multipotent stem cells, expressing α-smooth muscle actin (α-SMA). In our study, including 40 GBM patients, tissue samples were obtained from tumors (first area) and white matter at a distance <1 cm (second area) and between 1 and 3.5 cm (third area) from the tumor margin. CD105 and nestin were detected by immunohistochemistry in hyperplastic endothelium of GBM and peritumor tissue, and occasionally coexpressed or colocalized. Pericytes encircling hyperplastic endothelium were evident in all three areas. Univariate analysis revealed that patients with a CD105-MVD value ≥8 in the third area have a significantly shorter survival time and Cox analysis indicated an about 3.5-fold increase in death risk in the same patients. These results demonstrate that a tumor neoangiogenesis occurs in GBM peritumor tissue with intimate involvement of pericytes. CD105-MVD in the area located at a greater distance from the tumor margin carries prognostic significance.

The tumour-associated carbonic anhydrases CA II, CA IX and CA XII in a group of medulloblastomas and supratentorial primitive neuroectodermal tumours: an association of CA IX with poor prognosis.

BACKGROUND: Medulloblastomas (MBs) and supratentorial primitive neuroectodermal tumours (PNETs) are the most common highly aggressive paediatric brain tumours. In spite of extensive research on these tumours, there are only few known biomarkers or therapeutic target proteins, and the prognosis of patients with these tumours remains poor. Our aim was to investigate whether carbonic anhydrases (CAs), enzymes commonly overexpressed in various tumours including glioblastomas and oligodendrogliomas, are present in MBs and PNETs, and whether their expression can be correlated with patient prognosis. METHODS: We determined the expression of the tumour-associated carbonic anhydrases CA II, CA IX and CA XII in a series of MB/PNET specimens (n = 39) using immunohistochemistry. RESULTS: Endothelial CA II, cytoplasmic CA II, CA IX and CA XII were expressed in 49%, 73%, 23% and 11% of the tumours, respectively. CA II was detected in the neovessel endothelium and the tumour cell cytoplasm. CA IX was mainly expressed in the tumour cells located in perinecrotic areas. CA XII showed the most homogenous distribution within the tumours. Importantly, CA IX expression predicted poor prognosis in both univariate (p = 0.041) and multivariate analyses (p = 0.016). CONCLUSIONS: We suggest that CA IX should be considered a potential prognostic and therapeutic target in MBs and PNETs.

Indomethacin-loaded nanocapsules treatment reduces in vivo glioblastoma growth in a rat glioma model.

Multimodal combinations of target agents with radiation and chemotherapy may enhance cancer treatment efficacy; however, despite these treatments, gliomas recur early due to their highly proliferative, infiltrative and invasive behaviors. Nanoparticles of biodegradable polymers for anticancer drug delivery have attracted intensive interest in recent years since they may provide a sustained, controlled and targeted delivery. In the present study, we investigated the effect of indomethacin-loaded nanocapsules in an experimental glioma model. The rats treated with indomethacin-loaded nanocapsules demonstrated a significant reduction in tumor size and half of these animals presented just cells with characteristics of a residual tumor, as shown by immunostaining for nestin. Pathological analyses showed that the treated gliomas presented a significant reduction in the mitotic index and other histological characteristics that indicate a less invasive/proliferative tumor. An important finding of the present study is that indomethacin carried by polymeric nanocapsules achieved higher intracerebral drug concentrations than those of indomethacin in solution. Furthermore, indomethacin achieved a greater concentration in the hemisphere where the glioma was implanted, compared with the contralateral healthy hemisphere. Indomethacin-loaded nanocapsule treatment did not cause characteristics of toxicity and increased the survival of animals. Thus, our results show that polymeric nanocapsules are able to increase the intratumoral bioavailability of indomethacin and reduce the growth of implanted gliomas. Data suggest that indomethacin-loaded nanocapsules could offer new and potentially highly effective strategies for the treatment of malignant gliomas.

Low-grade gliomas: do changes in rCBV measurements at longitudinal perfusion-weighted MR imaging predict malignant transformation?

PURPOSE: To prospectively perform longitudinal magnetic resonance (MR) perfusion imaging of conservatively treated low-grade gliomas to determine whether relative cerebral blood volume (rCBV) changes precede malignant transformation as defined by conventional MR imaging and clinical criteria. MATERIALS AND METHODS: All patients gave written informed consent for this institutional ethics committee-approved study. Thirteen patients (seven men, six women; age range, 29-69 years) with biopsy-proved low-grade glioma treated only with antiepileptic drugs were examined longitudinally with susceptibility-weighted perfusion, T2-weighted, fluid-attenuated inversion recovery, and high-dose contrast material-enhanced T1-weighted MR imaging at 6-month intervals to date or until malignant transformation was diagnosed. Student t tests were used to determine differences in rCBV values between "transformers" and "nontransformers" at defined time points throughout study follow-up. RESULTS: Seven patients showed progression to high-grade tumors between 6 and 36 months (mean, 22.3 months), and disease in six patients remained stable over a period of 12-36 months (mean, 23 months). Transformers had a slightly (but not statistically significantly) higher group mean rCBV than nontransformers at the point of study entry (1.93 vs 1.31). In nontransformers, the rCBV remained relatively stable and increased to only 1.52 over a mean follow-up of 23 months. In contrast, transformers showed a continuous increase in rCBV up to the point of transformation, when contrast enhancement became apparent on T1-weighted images. The group mean rCBV was 5.36 at transformation but also showed a significant increase from the initial study at 12 months (3.14, P = .022) and at 6 months (3.65, P = .049) before transformation. Rates of rCBV change between two successive time points were also significantly higher in transformers than in nontransformers. CONCLUSION: In transforming low-grade glioma, susceptibility-weighted MR perfusion imaging can demonstrate significant increases in rCBV up to 12 months before contrast enhancement is apparent on T1-weighted MR images.

Dysembryoplastic neuroepithelial tumors: proton MR spectroscopy, diffusion and perfusion characteristics.

INTRODUCTION: We describe the magnetic resonance (MR) imaging characteristics of dysembryoplastic neuroepithelial tumors (DNT) and discuss their differential diagnosis. MATERIAL AND METHODS: Proton MR spectroscopy (TE 30 and 136 ms), diffusion-weighted and perfusion images were retrospectively evaluated in 22 patients with pathologically proven DNT (17 male and 5 female, mean age 18.7 years) and 14 control subjects (10 male and 4 female, mean age 16.9 years). The results from the DNT patients and from the control subjects were compared using an independent sample t-test and the degree of correlation was tested by Pearson's correlation. RESULTS: All DNTs were solitary and in a supratentorial cortical or subcortical location (ten temporal, eight frontal and four parietal). They had low-signal on T1-weighted images and high-signal on T2-weighted images without a prominent mass effect. Additionally a cystic appearance (six patients, 27.3%), cortical dysplasia (six patients, 27.3%) and contrast enhancement (four patients, 18.2%) were also noted. No significant differences were detected in NAA/Cho, NAA/Cr, NAA/Cho+Cr or Cho/Cr ratios between DNT and normal brain. DNTs had a significantly higher mI/Cr ratio and apparent diffusion coefficient (ADC) values and lower cerebral blood values than normal parenchyma (P < 0.001). ADC had the highest correlation with the diagnosis of DNT (r = 0.996) followed by relative cerebral blood volume (rCBV) (r = -0.883) and mI/Cr ratio (r = 0.663). CONCLUSION: Proton MR spectroscopy, diffusion-weighted and perfusion imaging characteristics of DNTs provide additional information to their MR imaging findings. The MR spectrum showing a slight increase in mI/Cr ratio, and higher ADC and lower rCBV values than normal parenchyma help to differentiate DNTs from other cortical tumors, which had higher rCBV and lower ADC values than DNTs.

Usefulness of diffusion/perfusion-weighted MRI in patients with non-enhancing supratentorial brain gliomas: a valuable tool to predict tumour grading?

22 patients with non-enhancing supratentorial gliomas on contrast-enhanced MRI underwent both diffusion- and perfusion-weighted MRI (DWI/PWI) before surgical resection. 14 low-grade gliomas (WHO Grade I and II) and 8 anaplastic gliomas were verified histologically. Both apparent diffusion coefficient (ADC) values and relative cerebral blood volume (rCBV) ratios were calculated on the solid portion of the tumour, on peritumoural area, as well as on the contralateral normal white matter, respectively. The results showed that lower ADC values were present in the solid portions of anaplastic gliomas, but not in low grade (p < 0.01). All ADC values in peritumoural regions of tumours were decreased compared with the contralateral normal white matter. However, there was no significant difference between anaplastic gliomas and low-grade gliomas. Meanwhile, higher rCBV ratios were present in both solid portions and peritumoural regions of anaplastic gliomas, but not in low grade gliomas (p < 0.01). In conclusion, non-enhancing brain gliomas with lower ADC values in the solid portions and higher rCBV ratios in both solid portions and peritumoural regions of tumours are significantly correlated with anaplasia. Therefore, DWI and PWI should be integrated in the diagnostic work-up of non-enhancing gliomas in order to predict grading.

Expression of cathepsin B and microvascular density increases with higher grade of astrocytomas.

Samples were taken from supratentorial gliomas border and normal brain autopsy which were divided into four groups, these including eight cases normal brain tissues, 30 cases of astrocytomas, 25 cases of anaplastic astrocytomas and 22 cases of glioblastomas. Cathepin B (CB) expression and microvessel density (MVD) were determined with immunohistochemical studies. Staining results of CB was scored according to the percentage of positive cells, graded as negative (-), weak (+), moderate (++), and strong (+ + +). MVD was analyzed by Weidner's revised technique. CB positive staining was negative in eight cases of normal brain tissue. Only 9 out of 30 cases of astrocytomas showed a low percentage of positive cells that were stained in a light, diffuse cytoplasmic pattern (score +). Twenty-two out of 35 cases of anaplastic astrocytomas showed positive light, granular staining pattern, it including five samples (score +), and 17 samples (score + +). In contrast, all 22 cases of glioblastomas were stained all, and it was present in a course, granular staining pattern with an intensity of score (+ +) of two sample, and score (+ + +) of 20 samples. Positive staining tumor cells were found in extracellular matrix (ECM), basement membrane (BM), and the endothelial cells of blood vessels were also positive stained. Along with elevating glioma grade, CB expression and MVD value were both increased. Therefore, it showed MVD value was positive correlated with expression of CB. It highly suggested that CB and angiogenesis plays an important role in glioma progression.

Effects of dexamethasone on peritumoural oedematous brain: a DT-MRI study.

OBJECTIVES: Glucocorticoids (dexamethasone) are thought to reduce peritumoural brain oedema by decreasing the permeability of neoplastic capillaries and/or enhancing the clearance of extracellular water. Diffusion tensor magnetic resonance imaging (DT-MRI) was used to measure the water diffusion parameters of oedematous and normal brain in a group of patients with intracranial tumours before and after steroid treatment. METHODS: Fifteen patients with intracranial tumours (seven with high-grade glioma, four with metastatic carcinoma and four with meningioma) were examined before and 48-72 h after dexamethasone treatment (16 mg/day). The mean diffusivity () and fractional anisotropy (FA) were measured for oedematous brain and apparently normal contralateral white matter before and after steroid therapy. RESULTS: In all three patient groups there was a significant decrease in of oedematous brain after steroid treatment (p<0.01). There was no significant change in FA of oedematous brain after treatment in any of the three groups. There was also no significant change in either or FA of apparently normal contralateral white matter after treatment. CONCLUSION: These data indicate that dexamethasone produces a localised reduction in the magnitude of extracellular water molecule mobility, and hence water content, in peritumoural oedematous brain. Furthermore, the magnitude of these changes is similar for both intra- and extra-axial tumours.

Distinguishing of primary cerebral lymphoma from high-grade glioma with perfusion-weighted magnetic resonance imaging.

To assess the usefulness of perfusion-weighted echo-planar magnetic resonance imaging in the differential diagnosis of primary supratentorial lymphoma (PCNSL) and glioblastoma (GBM), 12 patients with a PCNSL and 12 with a GBM were examined using a 1.5 T magnetic resonance (MR) imager. With dynamic-susceptibility contrast MR imaging the intensity-time curves of each tumor were analyzed, and we determined the relative regional cerebral blood volume ratios (rrCBV [tumor/contralateral white matter (WM)]) to find out whether these parameters could be used to separate PCNSL from GBM. The maximum rrCBV ratio in the PCNSL was significantly lower than that of the GBM (P<0.0001). Comparing the intensity-time curves for the two tumor groups, the PCNSL showed a characteristic type of curve with a significant increase in signal intensity above the baseline due to massive leakage of contrast media into the interstitial space. PCNSL tend to have low maximum CBV ratios and typical intensity-time curves. These two parameters may be useful in distinguishing PCNSL from GBM.

[Correlation between vascular endothelial growth factor and peritumoural edema in meningiomas].

OBJECTIVE: To study the relationship between the expression of vascular endothelial growth factor (VEGF) and peritumoural brain edema (PTBE) in meningiomas. METHODS: The expression of VEGF was investigated in 40 specimens of intracranial supratentorial meningioma resected during operation, using immunohistochemical techniques. The expression of factor VIII-related antigen (VIII-R Ag) was examined by immunohistochemistry so as to calculate the microvascular density (MVD). The formulae V = 4/3pi x abc and EI = V(edema) + V(tumor)/V(tumor) were used to determine the edema index (EI). The results of staining were compared with the data by MRI and neuroradiology in double blind fashion. RESULTS: Compared to VEGF-negative meningiomas, tumours with striking VEGF staining revealed a significantly higher mean EI (4.6 vs. 1.5, P = 0.003), higher edema incidence (88.2% vs. 41.7%, P = 0.023 68), and higher MVD (53.0 vs. 26.5, P = 0.018). Equally, meningiomas with pial supply revealed a significantly higher mean EI than meningiomas with only dural supply (4.4 vs. 1.8, P = 0.044). Meningiomas severely adhered to brain revealed a higher edema incidence than those with milder adhesion (88.9% vs. 45.5%, P = 0.004 17). The tumour volume did not correlate with EI (P > 0.05). CONCLUSION: The VEGF expression and tumour angiogenesis are correlated with peritumoural brain edema. The rate of brain edema is higher in the tumors with pial supply and severe adhesion with brain. There is no a significant correlation between the tumour volume and edema degree.

Ki-67 immunoreactivity, basic fibroblastic growth factor (bFGF) expression, and microvessel density as supplementary prognostic tools in low-grade astrocytomas. An immunohistochemical study with special reference to the reliability of different Ki-67 antibodies.

Low-grade diffuse astrocytomas are generally slow-growing tumors; however, they may progress to anaplastic astrocytomas or glioblastomas. As existing grading systems fail to distinguish these tumors, ongoing research strives to identify new prognostic markers. In this study, 22 adult patients with supratentorial diffuse astrocytomas, WHO grade II, were investigated to clarify whether proliferative activity, assessed by different Ki67 antibodies (MIB-1, NC-MM1, NC-Ki67p, rahKi67), expression of basic fibroblast growth factor (bFGF) or microvessel density have prognostic power. The Ki67 antibodies revealed low proliferation indices (PI); however, there was a wide spread of values, ranging from 0.1% to about 10%. In general, a positive correlation between the different Ki67 PIs was found. In 12 of 22 cases, bFGF immunoreactivity was recorded. Microvessel density was generally low. MIB-1 PI was the only prognostic factor of statistical significance. Ki67 PI, obtained by using the monoclonal antibody MIB-1, can thus serve as a prognostic factor capable of identifying subsets of low-grade diffuse astrocytomas with a potentially more aggressive clinical behavior.

[Arterial aneurysm within a tumor in a pediatric patient]. / Anévrisme artériel intra-tumoral chez l'enfant.

A middle cerebral artery aneurysm, completely enclosed in a large frontotemporal anaplastic astrocytoma, is demonstrated in a 11-month-old girl admitted for intracranial hypertension. Clipping of the aneurysm along with radical resection was successfully performed. Five years later, follow-up neurological examination is normal, aneurysm occlusion and no evidence of tumor recurrence are demonstrated by angiogram and MRI. The association of brain tumor and aneurysm is discussed, and documented with the only two cases of a neoplasm surrounding on aneurysm reported in the literature.