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Behnam Badie

Publications and source records attributed to Behnam Badie.

13 recordsLinked to original sources

Microglia function in brain tumors.

Microglia play an important role in inflammatory diseases of the central nervous system (CNS). These cells have also been identified in brain neoplasms; however, as of yet their function largely remains unclear. More recent studies designed to characterize further tumor-associated microglia suggest that the immune effector function of these cells may be suppressed in CNS tumors. Furthermore, microglia and macrophages can secrete various cytokines and growth factors that may contribute to the successful immune evasion, growth, and invasion of brain neoplasms. A better understanding of microglia and macrophage function is essential for the development of immune-based treatment strategies against malignant brain tumors.

Animals↗

Impaired capacity for upregulation of MHC class II in tumor-associated microglia.

Immunotherapy for malignant gliomas is being studied as a possible adjunctive therapy for this highly fatal disease. Thus far, inadequate understanding of brain tumor immunology has hindered the design of such therapies. For instance, the role of microglia and macrophages, which comprise a significant proportion of tumor-infiltrating inflammatory cells, in the regulation of the local anti-tumor immune response is poorly understood. To study the response of microglia and macrophages to known activators in brain tumors, we injected CpG oligodeoxynucleotide (ODN), interferon-gamma (IFN-gamma), and IFN-gamma/LPS into normal and intracranial RG2 glioma-bearing rodents. Microglia/macrophage infiltration and their surface expression of MHC class II B7.1 and B7.2 was examined by flow cytometry. Each agent evaluated yielded a distinct microglia/macrophage response: CpG ODN was the most potent inducer of microglia/macrophage infiltration and B7.1 expression, while IFN-gamma resulted in the highest MHC-II expression in both normal and tumors. Regardless of the agent injected, however, MHC-II induction was significantly muted in tumor microglia/macrophage as compared with normal brain. These data suggest that microglia/macrophage responsiveness to activators can vary in brain tumors when compared with normal brain. Understanding the mechanism of these differences may be critical in the development of novel immunotherapies for malignant glioma.

Adjuvants, Immunologic↗

Evaluation of a signal intensity mask in the interpretation of functional MR imaging activation maps.

BACKGROUND AND PURPOSE: The purpose of this study was to determine the incidence of susceptibility artifacts on functional MR imaging (fMRI) studies and their effect on fMRI readings. We hypothesized that the availability of the signal intensity maps (SIMs) changes the interpretation of fMRI studies in which susceptibility artifacts affected eloquent brain regions. METHODS: We reviewed 152 consecutive clinical fMRI studies performed with a SIM. The SIM consisted of the initial echo-planar images (EPI) in each section thresholded to eliminate signal intensity from outside the brain and then overlaid on anatomic images. The cause of the artifact was then determined by examining the images. Cases with a susceptibility artifact in eloquent brain were included in a blinded study read by four readers, first without and then with the SIM. For each reader, the number of times the interpretation changed on viewing the SIM was counted. RESULTS: Of 152 patients, 44% had signal intensity loss involving cerebral cortex and 18% involving an eloquent brain region. Causes of the artifacts were: surgical site artifact, blood products, dental devices, calcium, basal ganglia calcifications, ICP monitors, embolization materials, and air. When provided with the SIM, readers changed interpretations in 8-38% of patient cases, depending on reader experience and size and location of susceptibility artifact. CONCLUSION: Patients referred for clinical fMRI have a high incidence of susceptibility artifacts, whose presence and size can be determined by inspection of the SIM but not anatomic images. The availability of the SIM may affect interpretation of the fMRI.

Artifacts↗

Diffusion tensor imaging of the corticospinal tract before and after mass resection as correlated with clinical motor findings: preliminary data.

BACKGROUND AND PURPOSE: The role of diffusion tensor imaging (DTI) in neurosurgical planning and follow-up is currently being defined and needs clinical validation. To that end, we sought correlations between preoperative and postoperative DTI and clinical motor deficits in patients with space-occupying lesions involving the corticospinal tract (CST). METHODS: DTI findings in four patients with masses near the CST and not involving motor cortex were retrospectively reviewed and compared with contralateral motor strength. CST involvement was determined from anisotropy and eigenvector directional color maps. The CST was considered involved if it was substantially deviated or had decreased anisotropy. Interpretations of the DTIs were blinded to assessments of motor strength, and vice versa. RESULTS: Of the four patients with potential CST involvement before surgery, DTI confirmed CST involvement in three, all of whom had preoperative motor deficits. The patient without CST involvement on DTI had no motor deficit. After surgery, DTI showed CST preservation and normalization of the position and/or anisotropy in two of the three patients with preoperative deficits, and both of those patients had improvement in motor strength. The other patient with preoperative deficits had evidence of wallerian degeneration on DTI and had only equivocal clinical improvement. CONCLUSION: Preoperative CST involvement, as determined on DTI, was predictive of the presence or absence of motor deficits, and postoperative CST normalization on DTI was predictive of clinical improvement. Further study is warranted to define the role of DTI in planning tumor resections and predicting postoperative motor function.

Adult↗

Diffusion tensor eigenvector directional color imaging patterns in the evaluation of cerebral white matter tracts altered by tumor.

PURPOSE: To categorize the varied appearances of tumor-altered white matter (WM) tracts on diffusion tensor eigenvector directional color maps. MATERIALS AND METHODS: Diffusion tensor imaging (DTI) was obtained preoperatively in 13 patients with brain tumors ranging from benign to high-grade malignant, including primary and metastatic lesions, and maps of apparent diffusion coefficient (ADC), fractional anisotropy (FA), and major eigenvector direction were generated. Regions of interest (ROIs) were drawn within identifiable WM tracts affected by tumor, avoiding grossly cystic and necrotic regions, known fiber crossings, and gray matter. Patterns of WM tract alteration were categorized on the basis of qualitative analysis of directional color maps and correlation analysis of ADC and FA. RESULTS: Four basic patterns of WM alteration were identified: 1) normal or nearly normal FA and ADC, with abnormal tract location or tensor directions attributable to bulk mass displacement, 2) moderately decreased FA and increased ADC with normal tract locations and tensor directions, 3) moderately decreased FA and increased ADC with abnormal tensor directions, and 4) near isotropy. FA and ADC were inversely correlated for Patterns 1-3 but did not discriminate edema from infiltrating tumor. However, in the absence of mass displacement, infiltrating tumor was found to produce tensor directional changes that were not observed with vasogenic edema, suggesting the possibility of discrimination on the basis of directional statistics. CONCLUSION: Tumor alteration of WM tracts tends to produce one of four patterns on FA and directional color maps. Clinical application of these patterns must await further study.

Adult↗

Microglia cyclooxygenase-2 activity in experimental gliomas: possible role in cerebral edema formation.

PURPOSE: Cerebral edema is responsible for significant morbidity and mortality in patients harboring malignant gliomas. To examine the role of inflammatory cells in brain edema formation, we studied the expression cyclooxygenase (COX)-2, a key enzyme in arachidonic acid metabolism, by microglia in the C6 rodent glioma model. EXPERIMENTAL DESIGN: The expression of COX-2 in primary microglia cultures obtained from intracranial rat C6 gliomas was examined using reverse transcription-PCR, Western analysis, and prostaglandin E(2) (PGE(2)) enzyme immunoassay. Blood-tumor barrier permeability was studied in the same tumor model using magnetic resonance imaging. RESULTS: In contrast to C6 glioma cells, microglia isolated from intracranial C6 tumors produced high levels of PGE(2) through a COX-2-dependent pathway. To test whether the observed microglia COX-2 activity played a role in brain edema formation in gliomas, tumor-bearing rats were treated with rofecoxib, a selective COX-2 inhibitor. Rofecoxib was as effective as dexamethasone in decreasing the diffusion of contrast material into the brain parenchyma (P = 0.01, rofecoxib versus control animals), suggesting a reduction in blood-tumor barrier permeability. CONCLUSIONS: These findings suggest that glioma-infiltrating microglia are a major source of PGE(2) production through the COX-2 pathway and support the use of COX-2 inhibitors as possible alternatives to glucocorticoids in the treatment of peritumoral edema in patients with malignant brain tumors.

Animals↗

Supplementary motor area activation in patients with frontal lobe tumors and arteriovenous malformations.

BACKGROUND AND PURPOSE: Some patients who undergo surgical resection of portions of the supplementary motor area (SMA) have severe postoperative motor and language deficits, whereas others have no deficits. We tested the hypothesis that in some patients with lesions affecting the SMA, the contralateral SMA exhibits some of the activation normally associated with the ipsilateral SMA. METHODS: Functional MR imaging studies in seven healthy volunteers and 19 patients with frontal lobe tumors or arteriovenous malformations were reviewed retrospectively. The hemisphere in which the SMA activation predominated was tabulated for right and left motor tasks. The relative hemispheric dominance in the SMA for the right and left motor tasks was compared in the healthy and patient groups and with the location of the lesion in the patient group. RESULTS: None of the control subjects performing a right hand motor task activated predominantly the right SMA. Fifty percent of the patients with lesions overlapping the left SMA performing the right motor task activated predominantly the right SMA. Fifty-seven percent of control subjects performing the left hand motor task activated the left SMA predominantly. One hundred percent of patients with lesions overlapping the right frontal SMA performing the left motor task activated the left SMA predominantly. Differences between patients and controls were statistically significant. CONCLUSION: A lesion that contacts or overlaps the SMA is associated with an increased functional MR imaging response within the contralateral SMA.

Adolescent↗

Differential expression of MHC class II and B7 costimulatory molecules by microglia in rodent gliomas.

To assess the immune function of microglia and macrophages in brain tumors, the expression of MHC class II and B7 costimulatory molecules in three rodent glioma models was examined. Microglia and macrophages, which accounted for 5-12% of total cells, expressed B7.1 and MHC class II molecules in the C6 and 9L tumors, but not RG2 gliomas. Interestingly, the expression of B7.1 and MHC class II molecules by microglia and macrophage was associated with an increase in the number of tumor-infiltrating lymphocytes in C6 and 9L tumors. B7.2 expression, which was present at low levels on microglia and macrophages in normal brain, did not significantly change in tumors. Interestingly, the expression of all three surface antigens increased after microglia were isolated from intracranial C6 tumors and cultured for a short period of time. We conclude that microglia immune activity may be suppressed in gliomas and directly correlates to the immunogenecity of experimental brain tumors.

Animals↗

Drug-induced iatrogenic intraparenchymal hemorrhage.

Intracerebral hemorrhage is bleeding into the brain parenchyma with possible extension into the ventricles and subarachnoid space. Each year, approximately 37,000 to 52,400 people suffer from intraparenchymal hemorrhage (IPH) in the United States. This rate is expected to rise dramatically in the next few decades as a result of the increasing age of the population and a change in racial demographics. IPH accounts for 8% to 13% of all stroke cases and is associated with the highest mortality rate.

Brain↗

Correlation between auditory function and internal auditory canal pressure in patients with vestibular schwannomas.

OBJECT: Hearing loss is the most common presenting symptom in patients who harbor a vestibular schwannoma (VS). Although mechanical injury to the cochlear nerve and vascular compromise of the auditory apparatus have been proposed, the exact mechanism of this hearing loss remains unclear. To test whether pressure on the cochlear nerve from tumor growth in the internal auditory canal (IAC) is responsible for this clinical finding, the authors prospectively evaluated intracanalicular pressure (ICaP) in patients with VS and correlated this with preoperative brainstem response. METHODS: In 40 consecutive patients undergoing a retrosigmoid-transmeatal approach for tumor excision, ICaP was measured by inserting a pressure microsensor into the IAC before any tumor manipulation. Pressure recordings were correlated with tumor size and preoperative auditory evoked potential (AEP) recordings. The ICaP, which varied widely among patients (range 0-45 mm Hg), was significantly elevated in most patients (median 16 mm Hg). Although these pressure measurements directly correlated to the extension of tumor into the IAC (p = 0.001), they did not correlate to total tumor size (p = 0.2). In 20 patients in whom baseline AEP recordings were available, the ICaP directly correlated to wave V latency (p = 0.0001), suggesting that pressure from tumor growth in the IAC may be responsible for hearing loss in these patients. CONCLUSIONS: Tumor growth into the IAC results in elevation of ICaP and may play a role in hearing loss in patients with VS. The relevance of these findings to the surgical treatment of these tumors is discussed.

Adult↗

Diffusion-tensor imaging of white matter tracts in patients with cerebral neoplasm.

OBJECT: Preserving vital cerebral function while maximizing tumor resection is a principal goal in surgical neurooncology. Although functional magnetic resonance imaging has been useful in the localization of eloquent cerebral cortex, this method does not provide information about the white matter tracts that may be involved in invasive, intrinsic brain tumors. Recently, diffusion-tensor (DT) imaging techniques have been used to map white matter tracts in the normal brain. The aim of this study was to demonstrate the role of DT imaging in preoperative mapping of white matter tracts in relation to cerebral neoplasms. METHODS: Nine patients with brain malignancies (one pilocytic astrocytoma, five oligodendrogliomas, one low-grade oligoastrocytoma, one Grade 4 astrocytoma, and one metastatic adenocarcinoma) underwent DT imaging examinations prior to tumor excision. Anatomical information about white matter tract location, orientation, and projections was obtained in every patient. Depending on the tumor type and location, evidence of white matter tract edema (two patients), infiltration (two patients), displacement (five patients), and disruption (two patients) could be assessed with the aid of DT imaging in each case. CONCLUSIONS: Diffusion-tensor imaging allowed for visualization of white matter tracts and was found to be beneficial in the surgical planning for patients with intrinsic brain tumors. The authors' experience with DT imaging indicates that anatomically intact fibers may be present in abnormal-appearing areas of the brain. Whether resection of these involved fibers results in subtle postoperative neurological deficits requires further systematic study.

Adenocarcinoma↗

Preoperative mapping of the supplementary motor area in patients harboring tumors in the medial frontal lobe.

OBJECT: Injury to the supplementary motor area (SMA) is thought to be responsible for transient motor and speech deficits following resection of tumors involving the medial frontal lobe. Because direct intraoperative localization of SMA is difficult, the authors hypothesized that functional magnetic resonance (fMR) imaging might be useful in predicting the risk of postoperative deficits in patients who undergo resection of tumors in this region. METHODS: Twelve patients who had undergone fMR imaging mapping while performing speech and motor tasks prior to excision of their tumor, that is, based on anatomical landmarks involving the SMA, were included in this study. The distance between the edge of the tumor and the center of SMA activation was measured and was correlated with the risk of incurring postoperative neurological deficits. In every patient, SMA activation was noted in the superior frontal gyrus on preoperative fMR imaging. Two speech and two motor deficits typical of SMA injury were observed in three of the 12 patients. The two speech deficits occurred in patients with tumors involving the dominant hemisphere, whereas one of the motor deficits occurred in a patient with a tumor in the nondominant hemisphere. The risk of developing a postoperative speech or motor deficit was 100% when the distance between the SMA and the tumor was 5 mm or less. When the distance between SMA activation and the lesion was greater than 5 mm, the risk of developing a motor or a speech deficit was 0% (p = 0.0007). CONCLUSIONS: Early data from this study indicated that fMR imaging might be useful in localizing the SMA and in determining the risk of postoperative deficits in patients who undergo resection of tumors located in the medial frontal lobe.

Adult↗

Endoscopic and minimally invasive microsurgical approaches for treating brain tumor patients.

Recent developments in neuroendoscopy and minimally invasive procedures have greatly impacted the diagnosis and treatment of brain tumors. In this paper, we will review these innovations and discuss how they have influenced our approach to the treatment of intraventricular and pituitary tumors. Finally, the concept of keyhole neurosurgery is illustrated by discussing 'eyebrow orbitotomy' approach as an example. As noninvasive therapeutic alternative become available, future neurosurgeons will be challenged to develop effective and less invasive surgical approaches for the diagnosis and treatment of patients will brain tumors.

Brain Neoplasms↗