Niloufar Sadeghi

Present and potential future issues in glioblastoma treatment

The treatment of glioblastomas requires a multidisciplinary approach that takes the presently incurable nature of the disease into consideration. Treatments are multimodal and include surgery, radiotherapy and chemotherapy. Current recommendations are that patients with glioblastomas should undergo maximum surgical resection, followed by concurrent radiation and chemotherapy with the novel alkylating drug temozolomide. This is then to be followed by additional adjuvant temozolomide for a period of up to 6 months. Major advances in surgical and imaging technologies used to treat glioblastoma patients are described. These technologies include magnetic resonance imaging and metabolic data that are helpful in the diagnosis and guiding of surgical resection. However, glioblastomas almost invariably recur near their initial sites. Disease progression usually occurs within 6 months and leads rapidly to death. A number of signaling pathways can be activated constitutively in migrating glioma cells, thus rendering these cells resistant to proapoptotic insults, such as conventional chemotherapies. Therefore, the molecular and cellular therapies and local drug delivery that could be used to complement conventional treatments are described, and some of the currently ongoing clinical trials are reviewed, with respect to these new approaches.

Sixty-Four-Row Multisection CT Angiography for Detection and Evaluation of Ruptured Intracranial Aneurysms: Interobserver and Intertechnique Reproducibility

BACKGROUND AND PURPOSE: The purpose of this work was to assess intertechnique and interobserver reproducibility of 64-row multisection CT angiography (CTA) used to detect and evaluate intracranial aneurysms. MATERIALS AND METHODS: From October 2005 to November 2006, 54 consecutive patients with nontraumatic subarachnoid hemorrhage (SAH) underwent both CTA and digital substraction angiography (DSA). Four radiologists independently reviewed CT images, and 2 other radiologists reviewed DSA images. Aneurysm diameter (D), neck width (N), and the presence of a branch arising from the sac were assessed. RESULTS: DSA revealed 67 aneurysms in 48 patients and no aneurysm in 6 patients. Mean sensitivity and specificity of CTA for the detection of intracranial aneurysms were, respectively, 94% and 90.2%. For aneurysms less than 3 mm, CTA had a mean sensitivity of 70.4%. Intertechnique and interobserver agreements were good for the detection of aneurysms (mean κ = 0.673 and 0.732, respectively) and for the measurement of their necks (mean κ = 0.753 and 0.779, respectively). Intertechnique and interobserver agreements were excellent for the measurement of aneurysm diameters (mean κ = 0.847 and 0.876, respectively). In addition, CTA was accurate in determining the N/D ratio of aneurysms and adjacent arterial branches. However, the N/D ratio was overestimated by all of the readers at CTA. CONCLUSION: Sixty-four-row multisection CTA is an imaging method with a good interobserver reproducibility and a high sensitivity and specificity for the detection and the morphologic evaluation of ruptured intracranial aneurysms. It may be used as an alternative to DSA as a first-intention imaging technique in patients with SAH.

Apparent Diffusion Coefficient and Cerebral Blood Volume in Brain Gliomas: Relation to Tumor Cell Density and Tumor Microvessel Density Based on Stereotactic Biopsies

BACKGROUND AND PURPOSE: MR imaging–based apparent diffusion coefficient (ADC) and regional cerebral blood volume (rCBV) measurements have been related respectively to both cell and microvessel density in brain tumors. However, because of the high degree of heterogeneity in gliomas, a direct correlation between these MR imaging–based measurements and histopathologic features is required. The purpose of this study was to correlate regionally ADC and rCBV values with both cell and microvessel density in gliomas, by using coregistered MR imaging and stereotactic biopsies. MATERIALS AND METHODS: Eighteen patients (9 men, 9 women; age range, 19–78 years) with gliomas underwent diffusion-weighted and dynamic susceptibility contrast-enhanced MR imaging before biopsy. Eighty-one biopsy samples were obtained and categorized as peritumoral, infiltrated tissue, or bulk tumor, with quantification of cell and microvessel density. ADC and rCBV values were measured at biopsy sites and were normalized to contralateral white matter on corresponding maps coregistered with a 3D MR imaging dataset. ADC and rCBV ratios were compared with quantitative histologic features by using the Spearman correlation test. RESULTS: The highest correlations were found within bulk tumor samples between rCBV and cell density (r=0.57, P < .001) and rCBV and microvessel density (r=0.46, P < .01). An inverse correlation was found between ADC and microvessel density within bulk tumor (r=−0.36, P < .05), whereas no significant correlation was found between ADC and cell density. CONCLUSION: rCBV regionally correlates with both cell and microvessel density within gliomas, whereas no regional correlation was found between ADC and cell density.

Correlation between dynamic susceptibility contrast perfusion MRI and methionine metabolism in brain gliomas: preliminary results.

To evaluate in brain gliomas the relationship between tumor vascularity measured by MR‐based maximum regional cerebral blood volume (rCBV) and tumor amino‐acid metabolism based on maximum carbon‐11 methionine (MET) uptake on positron emission tomography (PET).

High levels of cellular proliferation predict pseudoprogression in glioblastoma patients

Radiochemotherapy (RT) with concomitant followed by monthly temozolomide (TMZ) chemotherapy is the gold standard for the treatment of glioblastoma (GBM) patients. GBM patients can experience transient radiological deterioration after concurrent RT/TMZ that stabilizes or even resolves after additional cycles of adjuvant TMZ, a phenomenon defined as radiological pseudoprogression. The aim of this retrospective study was to identify a reliable marker associated with pseudoprogression processes. Patients with histologically proven newly diagnosed GBM were identified from a retrospective database between 2005 and 2009. Predictive factors for pseudoprogression were analyzed from clinical, radiological and biological data. Of the 130 analyzed patients, 63 underwent RT/TMZ treatment followed by cycles of TMZ and were evaluated for radiological responses every two months by magnetic resonance imaging. Early progression was confirmed in 52% (33/63) of the patients, and, within this group, 21% (7/33) displayed evidence of pseudo-progression. The predictive factors were evidenced in terms of clinical or radiological findings. In GBM patients, the level of cellular proliferation (Ki67 indices) emerged as a statistically significant prognostic marker for distinguishing pseudoprogression from actual progression. Our observation, suggesting that GBM associated with a high level of cellular proliferation may differentiate tumor progression from pseudoprogression, warrants further investigation in a large multi-center prospective study.

Semi-quantification of methionine uptake and flair signal for the evaluation of chemotherapy in low-grade oligodendroglioma.

Abstract11C-Methionine (MET) is a useful positron emission tomography (PET) tracer for the evaluation of low-grade gliomas. Among these tumors, a high percentage of low-grade oligodendrogliomas (ODG) are sensitive to chemotherapy with procarbazine, CCNU, and vincristine (PCV). We aimed at: (1) objectively assessing ODG response to PCV by a metabolic index (the Activity Volume Index or AVI) generated from an automated semi-quantification of PET with MET (PET-MET); (2) comparing AVI and quantitative magnetic resonance imaging (MRI) measurements of response to PCV.Methods: seven patients with ODG were followed for a period of 19.9±6.6months after the completion of PCV chemotherapy. Regions of interest (ROI) were generated by covering all voxels with count values above a threshold level set at 120% of the mean cerebellar activity. On each slice, ROI volume and mean count values were calculated. AVI was calculated as the sum over all ROI of tumor volume×(tumor mean count/cerebellum count). Tumor volume measurements on MRI, were based on signal abnormalities visually detected on fluid-attenuated inversion recovery (FLAIR) sequences.Results: PCV therapy was associated with a drastic decrease in AVI (mean±SD, cm3): AVI post-PCV=0.80±1.45 vs. AVI prior PCV=12.94±11.46 (P=0.03). Likewise, we observed a decrease in tumor volume estimated from the FLAIR signal (31.37±11.99 post-PCV vs. 67.95±39.96 prior PCV, P=0.03) although AVI decrease after PCV was significantly more pronounced (P=0.015).Conclusion: This study, based on limited number of patients and follow-up period indicates that AVI may be a sensitive and observer-independent method applicable to the assessment of ODG responsiveness to PCV treatment and may offer a major added value to both clinical assessment and MRI evaluation of chemotherapeutic outcomes.

TIMP-4 and CD63: new prognostic biomarkers in human astrocytomas.

Based on the molecular profiling of astrocytomas, we previously identified a series of genes involved in astrocytoma invasion. Of these, tissue inhibitor of metalloproteinase-4 (TIMP-4) was found to be overexpressed in pilocytic astrocytomas relative to diffuse astrocytomas of any histological grade. Although some data suggest that TIMP-4 may be an anti-tumoral actor in astrocytomas, recent findings challenge this concept. The present study aims to investigate the diagnostic and prognostic values of TIMP-4 and its putative partner CD63 in human astrocytomas. Tissue microarray and image analysis were first carried out to quantitatively analyze the immunohistochemical expression of these proteins in 471 gliomas including 354 astrocytomas. Pathological semi-quantitative scores of both markers’ expression were then established and correlated to astrocytoma diagnosis and patient prognosis. TIMP-4 and CD63 expressions were both overexpressed in astrocytomas compared with oligodendrogliomas (P<0.001) and in pilocytic astrocytomas compared with grade II diffuse astrocytomas (P<0.001). In glioblastomas, high TIMP-4/CD63 co-expression scores were identified as independent prognostic factors associated with progression and shorter survival. In conclusion, this work provides the first evidence of a TIMP-4/CD63 association in astrocytoma tumor cells. It identifies TIMP-4 and CD63 as markers of the astrocytic phenotype in patients with gliomas. In addition, this work highlights the contribution of high TIMP-4/CD63 co-expression to the adverse outcomes of patients with glioblastomas.

Right diaphragmatic rupture and hepatic hernia: An indirect sign on computed tomography

Abstract. We report a case of blunt traumatic right diaphragm rupture with hepatic hernia. The diagnosis was first suggested by an abnormal hepatic location depicted on axial CT. This finding can be considered as a potentially new indirect sign of right diaphragm rupture in patients with blunt trauma. The diagnosis was then confirmed by reformatted CT and MR images.

Hereditary angio-edema involving the gastrointestinal tract: CT findings

Abstract We report a case of hereditary angio-edema in a young man presenting with recurrent abdominal pain for many years. The diagnosis was suspected on the basis of abdominal CT performed during an abdominal attack and was then confirmed by the measurement of serum concentration of C1 esterase inhibitor (C1-INH). To our knowledge, this is the first case reported of the hereditary form of angio-edema with isolated abdominal pain and in which the diagnosis was suggested by abdominal CT findings.

Intracranial tuberculoma: is diffusion-weighted imaging useful in the diagnosis?

Revised: 24 September 2002 Accepted: 1 October 2002 Published online: 12 November 2002