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The present study investigates the anti-oxidative effects of D-allose on ischemic damage. Rats were subjected to transient middle cerebral artery occlusion (MCAO) for 1 h under pentobarbital anesthesia. D-allose was intravenously infused during occlusion and a further 1 h after reperfusion (400 mg/kg). The effects of D-allose on focal cerebral ischemia were examined by measuring brain damage (infarction and atrophy volume) and behavioral deficits 7 days after MCAO. In another set of rats, apurnic/apyrimidic abasic sites (AP-sites) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), oxidative stress markers, were investigated 24 h after MCAO to examine the anti-oxidative effects of D-allose. Brain damage and behavioral deficits were significantly decreased by D-allose administration compared to vehicle. The number of AP-sites and 8-OHdG levels were also reduced by D-allose. Thus, the present study suggests that D-allose has anti-oxidative effects and induces neuroprotection in focal cerebral ischemia.

We have developed a novel catheter operating system with danger avoiding method in this paper, which included a highly precise master-slave remote control system. We used micro force sensors to realize haptic feedback, and used web camera and developed algorithm to realize visual feedback, with the help of visual and haptic feedback, surgeons can avoid danger effectively in the process of minimally invasive surgery (MIS). Using the developed mater-slave system, surgeons can avoid being radiated from X-ray. We carried out the operation simulation experiments to prove the efficiency that developed danger avoiding method, the experimental results indicated that the developed danger avoiding method can avoid danger effectively. Using the developed danger avoiding method we can improve the safety of the catheter operating system for medical application.

In this paper, we developed a novel catheter operating system using force sensors and monitor for medical applications, which included a highly precise master-slave remote control system. We designed micro force sensors and used them in the system to ensure the operation security in intravascular neurosurgery applications, using camera to monitor the situation of simulation experiment. We carried out the operation simulation experiments and got the force information by force sensors when the catheter contacted the simulator of blood vessel. The experimental results indicated that the proposed force sensors-based catheter operating system works well and can be controlled remotely, and the force feedback can effectively improve operability, also this system can avoid danger automatically.

Glioblastoma multiforme (GBM) is characterized by tissue hypoxia associated with resistance to radiotherapy and chemotherapy. To clarify the biological link between hypoxia and tumour-induced neovascularization and tumour aggressiveness, we analysed detailed volumetric and spatial information of viable hypoxic tissue assessed by 18F-fluoromisonidazole (FMISO) PET relative to neovascularization in Gd-enhanced MRI and tumour aggressiveness by L-methyl-11C-methionine (MET) PET in newly diagnosed GBMs. Ten patients with newly diagnosed GBMs were investigated with FMISO PET, MET PET and Gd-enhanced MRI before surgery. Tumour volumes were calculated by performing a three-dimensional threshold-based volume of interest (VOI) analysis for metabolically active volume on MET PET (MET uptake indices of ≥1.3 and ≥1.5) and Gd-enhanced volume on MRI. FMISO PET was scaled to the blood FMISO activity to create tumour to blood (T/B) images. The hypoxic volume (HV) was defined as the region with T/B greater than 1.2. PET and MR images of each patient were coregistered to analyse the spatial location of viable hypoxic tissue relative to neovascularization and active tumour extension. Metabolically active tumour volumes defined using MET uptake indices of ≥1.3 and ≥1.5 and the volumes of Gd enhancement showed a strong correlation (r = 0.86, p

We have developed a force display method for a catheter operating system in this paper. We designed micro force sensors and used them in the system to ensure the operation security in intravascular neurosurgery applications. We also used camera to monitor the situation of simulation experiment, and used developed force display system to monitor the changed force that catheter contacted with blood vessel. We carried out the operation simulation experiments and obtained the force information by the force sensors when the catheter contacted the blood vessel. The experimental results indicated that the proposed force display system for a catheter operating system works well and can improve the safety of Master-slave system, and also the force feedback can effectively improve operability, in addition, the developed system can avoid danger automatically.

BACKGROUND: The YKL-40 coding chitinase 3-like 1 gene is 1 of the most overexpressed genes in human glioblastomas. The objectives of this study were to explore YKL-40 protein expression status and World Health Organization (WHO) pathologic grades of primary human astrocytoma and to investigate the role of YKL-40 in the proliferation of both established and primary astrocytoma cells in vitro. METHODS: WHO grade 1, 2, 3, and 4 primary astrocytomas (210 patients) were evaluated for YKL-40 protein expression status in immunohistochemical analyses. In addition, after transfection with a plasmid that contained YKL-40 small-interfering RNA (siRNA), cell proliferation and the cell cycle were measured with a cell-viability assay and flow cytometry. Expression levels of phosphorylated, total mitogen-activated protein kinase (MAPK) and protein kinase B (AKT) were detected by Western blot analysis. RESULTS: The percentage of positive cells and the staining intensity differed significantly between different pathologic tumor grades (P < .001). The YKL-40 immunoreactivity score increased markedly with increased pathologic grade (F = 18.89; P < .001). In the in vitro experiment, the cell cycle was arrested in G1 phase. An inhibitor of the p38 MAPK, SB203580, could partially abrogate the cell proliferation inhibition effect by siRNA treatment. The expression levels of phosphorylated extracellular signal-regulated kinase 1/2 and phosphorylated AKT were notably decreased in siRNA-transfected U87 cells. In contrast, the expression levels of phosphorylated p38 and phosphorylated c-jun N-terminal kinase 1 and 2 increased significantly (P < .01). CONCLUSIONS: YKL-40 expression status correlated well with the pathologic grade of primary astrocytomas. The current results also indicted that YKL-40 plays a pivotal role in glioma cell proliferation through activation of the MAPK and AKT pathways. YKL-40 may be an attractive target for glioma therapy. Cancer 2010. © 2010 American Cancer Society.

The prolactin regulatory element-binding protein (PREB) is a transcriptional factor that regulates prolactin (PRL) promoter activity in the anterior pituitary. Prolactinomas are the most common pituitary tumors. Administration of cabergoline, a selective dopamine D2-receptor agonist, has become the initial therapy of choice for most patients with prolactinomas. Although activation of the D2 receptor results in the inhibition of PRL synthesis, the details of the underlying mechanisms remain unknown. Samples of ten prolactinomas and ten nonfunctioning pituitary adenomas were analyzed by immunohistochemistry to detect the expression of PREB. The effect of cabergoline on PREB expression was assessed by western blotting and real-time polymerase chain reaction (PCR) analysis. Reporter gene analysis of PRL was employed to examine the role of PREB on cabergoline-induced suppression of PRL transcription. Immunohistochemical analysis revealed strong positive PREB expression in the prolactinoma tissue, but extremely weak or undetected expression in the nonfunctioning pituitary tumor tissue. Western blots probed with a PREB-specific antiserum revealed that the relative abundance of the PREB protein in the GH3 cells decreased in a dose-dependent manner in response to cabergoline treatment, as did the relative abundance of PREB mRNA. Although cabergoline inhibited the activity of the PRL promoter, mutation of PREB-binding site within the promoter abrogated the ability of cabergoline to inhibit the PRL promoter activity. We have demonstrated that PREB is expressed in prolactinomas and that the suppression of PRL expression by cabergoline requires the transcriptional factor PREB.

Embryonic stem cells (ES cells) differentiate into multiple cell lineages including neural cells. The present study optimized the method to induce differentiation of gamma-aminobutyric acid-producing neurons (GABAergic neurons) from ES cell-derived neural stem/progenitor cells (NS/PCs), and transplanted these ES cell-derived GABAergic neurons producing neural progenitors into kindled epileptic mice, and analyzed the morphological and functional recovery from epilepsy. The response of kindling was evaluated by the modified Racine scale. Following stage 5 kindling, the mice were divided into two groups. Group 1 received NS/PCs derived from the ES cells ubiquitously expressing green fluorescent protein transplanted into the dorsal hippocampal area. Group 2 received microinjections of only the medium. After transplantation, the recovery of seizures was evaluated by the modified Racine scale again. All mice were perfused and fixed for immunohistochemical analysis after finishing the kindling experiment. In Group 1, one mouse was classified as stage 0, five as stage 3, and one as stage 4 recovering from stage 5 at 6 weeks after transplantation. In Group 2, all mice remained in stage 5. The transplanted cells were examined immunohistochemically using neuronal and GABAergic markers. In the transplanted mice, substantial hippocampal GABAergic re-innervation and seizure-suppressing effects were observed. NS/PCs derived from ES cells have high potential for use in transplantation therapy for clinically intractable epilepsies.

Chordoid meningioma (CM) is characterized by a striking histologic resemblance to chordoma and propensity for aggressive behavior or recurrence (WHO grade II designation). Orbital intraosseous CM is extremely uncommon and only one case report has been documented. A case is presented here in which squash smears of a left orbital tumor in a 53-year-old male revealed small clusters or cord-like structures of bland tumor cells embedded in a myxoid or mucinous background. Whorl-like structures were also identified. The tumor cells possessed uniformly round nuclei with a smooth nuclear outline, fine granular chromatin, and small nucleoli. Occasional intranuclear inclusions, coarse collageneous cytoplasmic filaments were observed. Many spindle-shaped cells with similar nuclear findings were also seen. A cytologic diagnosis of a chordoid meningioma was suggested and histochemical and immunohistochemical studies were conducted on formalin-fixed, paraffin-embedded material. Immunohistochemically, the tumor cells showed diffuse and strong membranous and cytoplasmic staining for vimentin, epithelial membrane antigen (EMA) and faintly reactive with S-100 protein but negative for pan-neuroendocrine markers (i.e., NSE, chromogranin A, synaptophysin), cytokeratin AE1/AE3, smooth muscle actin, D2-40, brachyury or class III beta-tubulin. The proliferative index with MIB-1 was less than 1%. The diagnosis of orbital intraosseous CM was confirmed based on cytopathologic, histopathological, immunohistochemical results, location of the tumor, and the lack connection to the duramater. We demonstrated here for the first time the cytopathological features of intraosseous CM with emphasis on differential diagnostic considerations. Diagn. Cytopathol. 2010; 38:818–821. © 2010 Wiley-Liss, Inc.

The purpose of this retrospective study was to evaluate the prognostic value of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in immunocompetent patients with primary central nervous system lymphoma (PCNSL). We also investigated whether FDG uptake was related to angiogenesis in the tumors. Seventeen patients with newly diagnosed and histologically confirmed PCNSL were investigated with FDG-PET before the treatment. FDG uptake was assessed by standardized uptake value of the tumor showing the maximum uptake (SUVmax). The Kaplan–Meier method was used to estimate the overall and the progression-free survival times. The difference of the survival curves between the low to moderate FDG uptake (SUVmax

We report the case of an 18-year-old woman with suprasellar germinoma masquerading as lymphocytic hypophysitis, which was associated with central diabetes insipidus, delayed sexual development, and hypopituitarism. Magnetic resonance imaging revealed an enlarged pituitary gland, thickened pituitary stalk, and a mass lesion in the inferior hypothalamus; these findings are typical of lymphocytic hypophysitis. Despite the administration of prednisolone therapy for 3 months, an enlarged irregular cystic mass lesion developed in the pituitary stalk and inferior hypothalamus. Open cranial surgery of the posterior pituitary revealed the presence of a germinoma. Therefore, chemotherapy and stereotactic radiation therapy were administered, resulting in complete remission of the germinoma. This case illustrates that the presence of an intrasellar mass lesion in association with pituitary stalk thickening can often cause difficulties in differential diagnosis. We believe that lymphocytic hypophysitis in pubertal children may be the first sign of a host reaction to an occult germinoma.

L-type amino acid transporter 1 (LAT1) is a neutral amino acid transport system and is a major route for the transport of large neutral amino acids, including methionine, through the plasma membrane. LAT1 requires the heavy chain of 4F2 cell surface antigen (4F2hc) for its functional expression. Positron emission tomography (PET) with L-[methyl-(11)C] methionine (MET) provides information about amino acid metabolism in brain tumors. We conducted a clinicopathologic study to elucidate the correlation of LAT1 and 4F2hc expression with MET uptake in patients with newly diagnosed human gliomas. Thirty-three newly diagnosed glioma patients were enrolled in this study. Uptake of MET in the tumor was evaluated with the maximum standardized uptake value (SUVmax). Expression of the LAT1, 4F2hc, and CD34, and Ki-67 labeling index of the tumor were analyzed by immunohistochemical staining, and the correlation with the SUVmax in the tumors was examined. Expression of LAT1 and 4F2hc was higher in high-grade gliomas than in low-grade gliomas. The grade of LAT1 immunostaining increased with glioma grade. LAT1 was mainly expressed in the tumor cytoplasm and vascular endothelium and 4F2hc was mainly expressed in the tumor cytoplasm and plasma membrane. Expression of LAT1 but not 4F2hc was significantly correlated with MET SUVmax. Expression of LAT1 in the tumor vascular endothelium is significantly correlated with CD34 positive microvessel density. In conclusion, MET SUVmax correlates with LAT1 expression in the tumor in newly diagnosed gliomas. MET transport may be increased by an increased number of microvessels combined with a higher density or activity of LAT1 in the tumor endothelial cells in high-grade gliomas. Use of MET-PET as a molecular target combined with anti-angiogenesis in glioma therapy should be addressed in future studies.

Our previous studies have demonstrated that thrombin plays an important role in intracerebral hemorrhage (ICH)-induced brain injury and edema formation. We, therefore, examined whether nafamostat mesilate (FUT), a serine protease inhibitor, can reduce ICH-induced brain injury. Anesthetized male Sprague-Dawley rats received an infusion of autologous whole blood (100 microL), thrombin (5U/50 microL) or type VII collagenase (0.4 U/2 microL) into the right basal ganglia, the three ICH models used in the present study. FUT (10 mg/kg) or vehicle was administered intraperitoneally 6 h after ICH (or immediately after thrombin infusion) and then at 12-h intervals (six treatments in total, n = 5 in each group). All rats were sacrificed 72 h later. We also examined whether FUT promotes rebleeding in a model in which ICH was induced by intracerebral injection of collagenase. Systemic administration of FUT starting 6 h after ICH reduced brain water content in the ipsilateral basal ganglia 72 h after ICH compared with vehicle. FUT attenuated ICH-induced changes in 8-OHdG and thrombin-reduced brain edema. FUT did not increase collagenase-induced hematoma volume. FUT attenuates ICH-induced brain edema and DNA injury suggesting that serine protease inhibitor may be potential therapeutic agent for ICH.

Positron emission tomography (PET) with [18F]-fluoro-3'-deoxy-3'-L-fluoro-'thymidine (FLT) provides information on cellular proliferation activity and has been used in malignant brain tumors. FLT-PET is sensitive in detecting malignant glioma due to the very low background uptake in the normal brain tissue. However, the ability to detect low grade glioma and tumor extension appears to be lower for FLT than for methionine (MET). Recent studies have found a correlation between WHO tumor grade and FLT uptake in gliomas. Our recent experience demonstrated a significant difference in the maximum standardized uptake value (SUVmax) of FLT between grade II (0.27 +/- 0.06, n=6) and grade IV (2.18 +/- 0.93, n=10) glioma (P0.0001), and grade III (0.70 +/- 0.45, n=7) and grade IV glioma (P0.001). FLT uptake correlated significantly better with the Ki-67 index (r = 0.86, P0.0001) than did MET uptake in gliomas. Studies have also reported the use of FLT-PET to investigate the effectiveness of therapy and prognosis of glioma. Increased FLT accumulation is also observed in other brain tumors including malignant lymphoma and metastatic brain tumor. Further studies are necessary to validate the usefulness of FLT-PET in brain tumor diagnosis and treatment.

The aim of the present study was to evaluate cerebral metabolism monitoring during therapeutic hypothermia for global ischemic brain damage after cardiopulmonary resuscitation (CPR).Jugular venous sampling and positron emission tomography (PET) were used. Seven comatose patients with cardiopulmonary arrest underwent hypothermia treatment as soon as possible after CPR. The body temperature of these patients was maintained at 34 degrees C for 72 h. Rewarming was performed at a rate of 1 degrees C/day. To monitor jugular venous saturation (SjO2) and lactate (lac-JV), a fiberoptic catheter was inserted into the jugular bulb. Oxygen extraction fraction (OEF) was calculated using the difference between arterial oxygen saturation (SaO2) and SjO2. 18F-fluorodeoxyglucose (FDG) PET was performed to investigate cerebral glucose metabolism at the end of therapeutic hypothermia.The OEF was significantly increased at the end of hypothermia in four patients with favorable outcome on the Glasgow Outcome Scale (hypothermia onset 15.3 +/- 2.0% vs. hypothermia end 30.3 +/- 2.8%, P0.05). In three patients with unfavourable outcome (severe or worse on the Glasgow Outcome Scale), end hypothermia OEF tended to be low. There was also a reduction in FDG uptake in these three patients with unfavourable outcome. The lac-JV was significantly decreased at the end ofhypothermia treatment compared with hypothermia onset (27.7 +/- 7.4 vs. 6.0 +/- 3.0 mg/dL, P0.05).The measurement of cerebral metabolism parameters, especially OEF, might be useful for estimation of hypothermia therapy in patients with unconsciousness after resuscitation after cardiac arrest.

Cerebral ischemia is believed to be an important mechanism of secondary neuronal injury in traumatic brain injury (TBI).In this study, we performed 15O2 positron emission tomography (PET) studies to measure the cerebral blood flow (CBF) and oxygen metabolism (CMRO2) in the pericontusional region in a total of 15 patients (11 males, 4 females, aged 15-81 years) who sustained TBI with contusional hematoma. PET studies were performed a mean of 13.5 +/- 9.1 days (range 2-33 days) after TBI occurred.The areas of pericontusional tissues located 10 mm away from the cerebral contusion exhibited mildly decreased CBF (89%) and severely suppressed CMRO2 (67%) when comparison was made with the remote cerebral cortex. Severely suppressed oxygen metabolism in the pericontusional tissue was observed not only in the acute stage, but also in the subacute stage after TBI, whereas blood flow was slightly recovered in the subacute stage. We also compared the PET findings obtained in the acute or subacute stage after TBI and structural abnormalities on late-stage MRI in 5 patients. The area of flow defect on the CBF-PET image developed into irreversible tissue damage (necrosis) in the chronic stage. The area of hypoperfusion surrounding the lesion partly resulted in tissue necrosis: however, a large part of the hypoperfused tissue survived in the chronic stage. Again, a significant portion of oxygen hypometabolism surrounding the lesion did not develop into tissue necrosis.We conclude that impaired cerebral blood flow and metabolism in the pericontusional region is observed even in the subacute stage after TBI and is unlikely to cause severe further neuronal damage.

Reported herein is a case of medulloblastoma with myogenic differentiation in a 3-year-old girl who died 1 year after appearance of clinical signs. Magnetic resonance imaging indicated a mass lesion in the cerebellar vermis. She underwent total resection of the tumor, followed by chemotherapy and radiotherapy in the brain and spinal cord. The resected specimen mainly consisted of densely packed cells with round-to-oval highly chromatic nuclei surrounded by scanty cytoplasm and focally of long spindle-shaped cells with elongated nuclei and eosinophilic cytoplasm showing discernible cross-striations. Immunohistochemistry indicated partial expression of synaptophysin in the former area and focal expression of desmin in the latter area. The diagnosis was medulloblastoma with myogenic differentiation, also known as medullomyoblastoma. Autopsy indicated disseminated proliferation of immature neuroglial cells with highly chromatic nuclei and scanty cytoplasm showing partial expression of synaptophysin, neurofilaments, and GFAP, and focal proliferation of round-to-oval immature cells showing immunoreactivity of myoglobin. The tumor cells had large nuclei, frequent mitoses, apoptoses, nuclear molding, and cell wrapping, indicating moderate anaplasia. Their Ki-67 labeling index was 54%. In addition, some tumor cells had double immunopositivity for synaptophysin or neurofilament and myoglobin, suggesting that the neuroectodermal cells may undergo differentiation into rhabdomyoblasts.

In this study, we examine 3CB2 expression, a marker of radial glia, after intracerebral hemorrhage (ICH). Adult male Sprague-Dawley rats received an intracaudate injection of 100 microL autologous whole blood. Animals were sacrificed, and 3CB2 expression was quantified on Western blot. Single and double labeled immunohistochemistry was used to identify which cells express 3CB2. Neurobehavioral examinations (forelimb placing test) were perfomed as an evaluation of function. By Western blot, 3CB2 was strongly expressed at day 3 and expression persisted for at least 1 month. By immunohistochemistry, 3CB2 immunoreactivity was present in large numbers of astrocytes surrounding the hematoma at day 3 after ICH. At 1 month later, 3CB2 immunoreactivity was co-localized with a neuronal marker (TUC-4). Neurobehavioral function in the 1 month after ICH group was significantly improved compared with that of 3 days after ICH. The ICH-induced 3CB2 expression in astrocytes may reflect an early response of these cells to injury, while the delayed expression in neurons might be a part of the adaptative response to injury, perhaps leading to recovery of neurobehavioral function.

Objective We investigated early postoperative hemodynamic and metabolic values using positron emission tomography (PET) scanning in subarachnoid hemorrhage (SAH) patients treated with clipping or coiling, and evaluated usefulness of PET studies in predicting late ischemic events and neurological outcome in SAH patients.

In this paper, we developed a novel catheter operating system using force sensors for medical application, which included a highly precise master-slave remote control system. We designed micro force sensors and used them in the system to ensure the operation security in intravascular neurosurgery applications. We carried out the operation simulation experiments and got the force information by force sensors when the catheter contacted the simulator of blood vessel. The experimental results indicated that the proposed force sensors-based catheter operating system works well and can be controlled remotely, and the force feedback can effectively improve operability.

Prognosis of germinoma arising in the basal ganglia or thalamus is worse compared to that in the pineal or suprasellar region. One of the reasons for poor prognosis is the difficulty in evaluating the efficacy of treatment by conventional neuroimaging tools. PET STUDIES: The usefulness of (11)C-methionine (MET) positron emission tomography (PET) in monitoring the biological nature of brain tumors has been proved in glioma patients.Herein, we describe MET-PET findings in three cases of germinomas in the basal ganglia or thalamus and discuss the use of MET-PET in the assessment of treatment response and residual tumor for the next treatment strategy. The patients showed transient increase of MET uptake in the lesions after the initial treatment. Although we did not perform histological verification, MET- PET findings suggested that active tumor cells were still alive in the lesions after the initial treatment. MET uptake gradually decreased during the course of intensive therapy in these patients. MET-PET also revealed germinoma invasion in the brain before discernible signal abnormality or mass lesion in conventional magnetic resonance images in two patients.Further studies including histological verification and long-term follow-up might validate the use of MET-PET in monitoring the treatment efficacy and evaluation of active residual tumor after the treatment.Until we understand what MET uptake truly represents, treatment strategy based on MET uptake must be carefully designed to prevent overtreatment and resultant complications.

This paper deals with a new catheter operating system for ileus treatment. We developed a highly precise remote control system by using a Master-Slave system. In order to insure the safety of the whole system, we design a simply micro force sensor. Also we expatiate on the design concept of the system and control of the system. We also carried out the operating simulation experiments ldquoin Vitrordquo. The experimental results indicated the proposed catheter operating system works properly, it can be controlled by tele-operation, and it can effectively improve the operability in to aneurysm with force feedback for intravascular neurosurgery.

The current study examined 3CB2, a marker of radial glia, expression after intracerebral hemorrhage (ICH) and intracerebral thrombin injection. Adult male Sprague-Dawley rats received an intracaudate injection of 100 microl autologous whole blood or 5 U thrombin (50 microl). Animals were sacrificed for Western blotting to quantify 3CB2 expression, and for single and double labeling immunohistochemistry to identify which cells express 3CB2. Behavioral examinations (forelimb placing test and corner turn test) were performed as an evaluation of function. By Western blot analysis, 3CB2 was strongly expressed at day 3 and the expression persisted for at least 1 month. Intracerebral injection of thrombin also upregulated 3CB2. Hirudin, a thrombin inhibitor, reduced ICH-induced 3CB2 expression. By immunohistochemistry, 3CB2 immunoreactivity was present in large numbers of glial cells surrounding the hematoma at 1 day after ICH. One month later, 3CB2 immunoreactivity was co-localized with a neuronal precursor marker, TUC-4. ICH-induced behavioral deficits were severe at 1, 3 and 7 days, with recovery at 1 month. The forelimb placing test score paralleled changes in 3CB2 expression. ICH-induced 3CB2 expression in glial cells may reflect an early response of these cells to injury, while the delayed expression in neurons might be a part of the adaptative response to injury perhaps participating in recovery of function. Thrombin has a role in 3CB2 expression in ICH.

The purpose of this prospective study was to clarify the individual and combined role of l-methyl-11C-methionine-positron emission tomography (MET-PET) and 3′-deoxy-3′-[18F]fluorothymidine (FLT)-PET in tumor detection, noninvasive grading, and assessment of the cellular proliferation rate in newly diagnosed histologically verified gliomas of different grades. Forty-one patients with newly diagnosed gliomas were investigated with MET-PET before surgery. Eighteen patients were also examined with FLT-PET. MET and FLT uptakes were assessed by standardized uptake value of the tumor showing the maximum uptake (SUVmax), and the ratio to uptake in the normal brain parenchyma (T/N ratio). All tumors were graded by the WHO grading system using surgical specimens, and the proliferation activity of the tumors were determined by measuring the Ki-67 index obtained by immunohistochemical staining. On semiquantitative analysis, MET exhibited a slightly higher sensitivity (87.8%) in tumor detection than FLT (83.3%), and both tracers were 100% sensitive for malignant gliomas. Low-grade gliomas that were false negative on MET-PET also were false negative on FLT-PET. Although the difference of MET SUVmax and T/N ratio between grades II and IV gliomas was statistically significant (P

BACKGROUND The aim of the present study was to evaluate cerebral metabolism monitoring during therapeutic hypothermia for global ischemic brain damage after cardiopulmonary resuscitation (CPR). METHODS Jugular venous sampling and positron emission tomography (PET) were used. Seven comatose patients with cardiopulmonary arrest underwent hypothermia treatment as soon as possible after CPR. The body temperature of these patients was maintained at 34 degrees C for 72 h. Rewarming was performed at a rate of 1 degrees C/day. To monitor jugular venous saturation (SjO2) and lactate (lac-JV), a fiberoptic catheter was inserted into the jugular bulb. Oxygen extraction fraction (OEF) was calculated using the difference between arterial oxygen saturation (SaO2) and SjO2. 18F-fluorodeoxyglucose (FDG) PET was performed to investigate cerebral glucose metabolism at the end of therapeutic hypothermia. FINDINGS The OEF was significantly increased at the end of hypothermia in four patients with favorable outcome on the Glasgow Outcome Scale (hypothermia onset 15.3 +/- 2.0% vs. hypothermia end 30.3 +/- 2.8%, P < 0.05). In three patients with unfavourable outcome (severe or worse on the Glasgow Outcome Scale), end hypothermia OEF tended to be low. There was also a reduction in FDG uptake in these three patients with unfavourable outcome. The lac-JV was significantly decreased at the end ofhypothermia treatment compared with hypothermia onset (27.7 +/- 7.4 vs. 6.0 +/- 3.0 mg/dL, P < 0.05). CONCLUSIONS The measurement of cerebral metabolism parameters, especially OEF, might be useful for estimation of hypothermia therapy in patients with unconsciousness after resuscitation after cardiac arrest.

BACKGROUND: Hyperbaric oxygen (HBO) therapy has been shown to improve outcome after brain injury, however its mechanisms are not understood. The purpose of the present study was to investigate the effect of hyperbaric oxygen (HBO) therapy on the cerebral circulation and metabolism of patients with disturbances in consciousness after head injury in the subacute phase. METHODS: Seven head injury patients underwent HBO treatment after leaving the intensive care unit. Oxygen (100% O2, 2.7 atm absolute) was delivered to patients in a hyperbaric chamber for 60 min every 24 h (total five treatments/patient). Cerebral circulation monitoring (mean flow velocity: mFV, and pulsatility index: PI at horizontal portion of middle cerebral artery by transcranial Doppler) and cerebral metabolism monitoring (arterio-jugular venous difference of oxygen: AJDO2 and jugular venous lactate: lac-JV) before and after the series of treatments were evaluated. FINDINGS: Both PI and lac-JV were significantly decreased after HBO theatment, while there were no significant changes in mFV and AJDO2. The decreased PI and lac-JV after HBO therapy might indicate that this treatment couples cerebral circulation and metabolism. CONCLUSIONS: The measurement of cerebral circulation and metabolism parameters, especially PI and lac-JV, is useful for estimation of effect of HBO therapy in patients with distubances in consciousness after head injury in the subacute phase.

BACKGROUND Cerebral ischemia is believed to be an important mechanism of secondary neuronal injury in traumatic brain injury (TBI). METHODS In this study, we performed 15O2 positron emission tomography (PET) studies to measure the cerebral blood flow (CBF) and oxygen metabolism (CMRO2) in the pericontusional region in a total of 15 patients (11 males, 4 females, aged 15-81 years) who sustained TBI with contusional hematoma. PET studies were performed a mean of 13.5 +/- 9.1 days (range 2-33 days) after TBI occurred. FINDINGS The areas of pericontusional tissues located 10 mm away from the cerebral contusion exhibited mildly decreased CBF (89%) and severely suppressed CMRO2 (67%) when comparison was made with the remote cerebral cortex. Severely suppressed oxygen metabolism in the pericontusional tissue was observed not only in the acute stage, but also in the subacute stage after TBI, whereas blood flow was slightly recovered in the subacute stage. We also compared the PET findings obtained in the acute or subacute stage after TBI and structural abnormalities on late-stage MRI in 5 patients. The area of flow defect on the CBF-PET image developed into irreversible tissue damage (necrosis) in the chronic stage. The area of hypoperfusion surrounding the lesion partly resulted in tissue necrosis: however, a large part of the hypoperfused tissue survived in the chronic stage. Again, a significant portion of oxygen hypometabolism surrounding the lesion did not develop into tissue necrosis. CONCLUSIONS We conclude that impaired cerebral blood flow and metabolism in the pericontusional region is observed even in the subacute stage after TBI and is unlikely to cause severe further neuronal damage.

The authors present a case of central neurocytoma in a 34-year-old female who had experienced intermittent headaches over a 10-year period. On computed tomographic (CT) scans and magnetic resonance images, the tumor appeared as a large, calcified mass occupying both lateral ventricles. A right parieto-occipital craniotomy was performed and the tumor was totally removed. While the light microscopic findings suggested a diagnosis of oligodendroglioma, electron microscopic examination demonstrated clear vesicles, microtubules, and synaptic structures within the abundant cytoplasmic processes of the tumor cells. Immunohistochemical examination showed the tumor cells to be strongly positive for neuron-specific enolase, sparsely positive for S-100 protein, and negative for glial fibrillary acidic protein. The final histological diagnosis was central neurocytoma. The postoperative course was uneventful and no further treatment was administered. She has no neurological deficits and CT has shown no evidence of recurrence during the 2 years since her surgery. Central neurocytoma is a rare tumor arising in the lateral ventricle, and the diagnosis is mainly based on electron microscopic findings. Since central neurocytoma appears to have a good prognosis following total removal alone, it is very important to distinguish between this and other ventricular tumors.

In this paper, we developed a force sensors-based catheter operating system. Firstly, we developed a highly precise remote control system by using a master-slave system. And in order to insure the safety of the whole system, we designed a micro force sensor as the base part in our research. Then we expatiate on the design concept of the system and control of the system. Also we carried out the operating simulation experiments "in vitro" and dealt with the operating errors. The experimental results indicated the proposed force sensors-based catheter operating system works properly, it can be controlled by tele-operation, and it can effectively improve the operability in to aneurysm with force feedback for intravascular neurosurgery.

This paper deals with a new catheter operating system for medical applications. We developed a highly precise remote control system by using a master-slave system. In order to insure the safety of the whole system, we design a simply micro force sensor. Also we expatiate on the design concept of the system and control of the system. We also carried out the operating simulation experiments "in vitro". The experimental results indicated the proposed catheter operating system works properly, it can be controlled by tele-operation, and it can effectively improve the operability in to aneurysm with force feedback for intravascular neurosurgery.

A 44-year-old man with a history of sudden onset short-term disorientation was admitted to our hospital. T2-weighted fast spin-echo MR images of the head showed increased signal intensity in the bilateral frontal and parietal white matter. Gadolinium-enhanced T1-weighted spin-echo images showed multiple areas with punctate and linear enhancement scattered in the bilateral frontal and parietal white matter. Although 18F-fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) did not display a significant increase in FDG accumulation in the bilateral frontal and parietal white matter, kinetic analysis of this scan showed increased hexokinase activity in the lesions compared to the unaffected occipital white matter. Diagnosis was made by open biopsy of the right frontal lobe and pathologic specimen was positive for lymphomatoid granulomatosis (LYG). The patient received high-dose methotrexate with CHOP (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisolone) chemotherapy and follow-up MRI showed improvement of the lesions. [18F]FDG-PET study with kinetic analysis may be useful to diagnose LYG in the central nervous system.

A 57-year-old female presented with a left petroclival meningioma fed by the meningohypophyseal trunk of the internal carotid artery (ICA). The enlarged tentorial marginal artery and inferior hypophyseal artery were successfully embolized with the TruFill DCS Detachable Coil System through a 0.019-inch inner diameter microcatheter. Superselective catheterization into the dorsal meningeal artery could not be achieved with the same microcatheter, because the catheter tip was too large to pass into the vessel. Subsequently the feeding artery was successfully embolized with a Guglielmi detachable coil (GDC) through a 0.016-inch inner diameter microcatheter. The patient underwent surgery without blood loss on the day after embolization. Our subjective impression was that the TruFill DCS was softer and had less resistance during insertion, whereas the GDC could be delivered through a smaller caliber system for smaller vessels. Appropriate use of the TruFill DCS and GDCs can allow efficient embolization of the feeding branches of the ICA.

OBJECTIVE: Use of the positron imaging agents, such as 11C-Methionine (MET) and 18F-Fluoromisonidazole (FMISO), is expected to lead the way for novel applications aimed at achieving efficient malignancy grading and treatment of gliomas. The aim of this study was to assess MET and FMISO PET studies to evaluate the biological effects induced by bevacizumab therapy in patients treated for high grade gliomas. METHODS: Twenty-two patients with high grade gliomas were treated biweekly with bevacizumab from July 2013 to May 2015. MR images, as well as MET and FMISO PET scans were obtained at baseline and at follow-up (4 weeks after treatment onset). MRI treatment response was evaluated by T1/T2 volumetry according to the response assessment in neuro-oncology (RANO) criteria. Based on the RANO criteria, we divided the patients into three groups (PR, SD, and PD), and compared changes of MET T/N ratio or FMISO T/B ratio between baseline and follow-up. These PET response assessments were compared in relation to PFS and OS. RESULTS: At the follow-up, MRI showed PR in 6 of 22 patients, SD in 11 of 22 patients, and PD in 5 of 22 patients. The median PFS were 13.1 months, 13.5 months and 2.4 months for PR, SD and PD, respectively. The median OS were 14.6 months, 14.5 months and 5.7 months for each group. MET and FMISO images in the PD group had a tendency to show the increase of changes. FMISO images in the SD group revealed 3 of 11 increased changes (15.1% up) and 8 of 11 decreased changes (11% down). The median PFS were 2.4 months and 16.3 months for each change, and the median OS were 9.8 months and 16.8 months. CONCLUSION: Decreased changes in FMISO-PET after bevacizumab therapy may be a useful biomarker for predicting PFS and OS in high-grade gliomas.

Background Approximately 5% to 10% of intracranial germinomas arise from the basal ganglia or thalamus. Diagnosis is usually made by stereotactic biopsy, and precise location of the biopsy target is crucial because germinoma in these sites is potentially curable. We herein describe a case with germinoma in the basal ganglia that showed nonspecific clinical and radiological findings. The usefulness of MET-PET in locating an optimal biopsy target and monitoring treatment efficacy in this case is presented. Case Description A 9-year-old boy presented with a 4-month history of dystonia in his left upper extremity. Magnetic resonance imaging of the brain showed abnormal signal intensity in the right basal ganglia, internal capsule, and corona radiata without mass formation and enhancement effect. He had been treated as having multiple sclerosis without improvements on clinical and radiological findings. The MET-PET study showed increased tracer uptake in the areas of abnormal signal intensity on the MR images, and the MRI-PET co-registered images exhibited the highest tracer uptake in the anterior limb of the internal capsule. A stereotactic biopsy targeting the highest tracer uptake lesion was performed with histologic verification of germinoma. He was intensively treated with combined chemotherapy and radiotherapy according to the MR images and MET-PET findings. After the treatment, the area of abnormal signal intensity significantly reduced in size on the follow-up MRI and lesional tracer uptake was also decreased on MET-PET images. Conclusion The MET-PET study is very useful for locating a precise biopsy target and provides useful information in monitoring treatment efficacy in the basal ganglia germinoma that showed nonspecific radiological findings.

Objective. The goal of this study was to elucidate the effect of neurospheres (NS) on dementia in the mouse model of nucleus basalis of Meynert (NBM) lesion. Methods. Mouse embryonic stem cell (ES) derived neurospheres were transplanted into the frontal association cortex and barrel field of S1 cortex of C57BL/6 mice 4 weeks after including a lesion of NBM by ibotenic acid, while other healthy mice that received ES cells served as control. Behavioral tests by 8-arm radial maze were conducted 8 weeks after transplantation, and double staining of choline acetyltransferase (ChAT), serotonin, amyloid-protein (AP) and green fluorescent protein (GFP) 12 weeks aftertransplantation.Wefoundthattheneurospherestransplanted into the mouse cortex survived and produced many ChAT-positive neurons and a few serotonin- positive neurons in and around the grafts. The working memory error decreased significantly in the mice grafted with neurospheres. In contrast, the ES cells developed into teratomas in all of the controlmiceandexpressednoneurons,andtheworkingmemorydeterioratedremarkably. Conclusions. Transplantation of neurospheres, but not ES cells, into the prefrontal and parietal cortices, dramatically alleviated the cholinergic deficits and recent memory disruption in the NBM lesioned mice. J. Med. Invest. 53 : 61-69, February, 2006

A 55-year-old woman presented with consciousness disorders. Computed tomography revealed hemorrhage in the left temporoparietal region. The angiographic diagnosis was progressive sinus thrombosis from the superior sagittal sinus to the bilateral transverse sinuses. Her condition deteriorated despite heparin administration. Therefore, mechanical thrombolysis was performed for sinus thrombosis using a balloon catheter, in addition to supportive thrombolytic therapy with urokinase, resulting in sinus patency. Mechanical thrombolysis is an effective therapeutic modality for sinus thrombosis refractory to heparin administration.

A 29-year-old female presented with Basedow's disease manifesting as sudden vomiting, diarrhea, fever over 38 degrees C, transient aphasia, and numbness in her extremities. These symptoms were considered due to cerebral ischemia at a local clinic. Magnetic resonance angiography indicated stenosis of the bilateral distal internal carotid arteries and the bilateral proximal anterior cerebral and middle cerebral arteries. Thyroid swelling and exophthalmos were observed. She was transferred to our hospital. Endocrine function tests showed hyperthyroidism. The diagnosis was Basedow's disease. Her symptoms disappeared after receiving intravenous drip infusion of fluid replacement, and antithyroid and antiplatelet medication. After she became euthyroid, cerebral angiography and magnetic resonance angiography revealed improvement of the stenosis of the cerebral arteries. Stenosis of the terminal portion of the internal carotid artery associated with Basedow's disease is extremely rare. Conservative treatment mainly including antithyroid medications for Basedow's disease, and antiplatelet drugs and intravenous replacement fluid for the ischemic manifestations should be the first choice of treatment unless immediate vascular reconstruction is necessary.

Object : Matrix metalloproteinase (MMP) 2 and 9 are important for tissue breakdown in the process of tumor invasion. The aim of this study is to evaluate the relationship between the expression of MMP-2, MMP-9, MIB-1 LI and cavernous sinus invasion in pituitary adenomas. Methods : Tissue samples from 54 patients with pituitary adenomas were studied. Expression of MMP-2, MMP-9, and MIB-1 labeling index (LI) were evaluated by immunohistochemical method. In sixteen cases, the expression of MMP-2 and MMP-9 mRNA was also examined by RT-PCR assay. Results : Thirty-four patients were women and 20 were men, with a mean age of 49.9 years old (range 18-76 years). There were 12 cases with cavernous sinus invasion, and 42 were noninvasive cases. MMP-2 and MMP-9 score of invasive case (3.9±0.5, 4.1±0.4) were significantly higher than those (2.3±0.2 ; p

A 65-year-old male with an old cerebral contusion in the frontal lobes had suffered from status complex partial seizures. Ictal positron emission tomography with an F-18 fluorodeoxyglucose ([18F]FDG-PET) scan revealed hypermetabolism in the frontal, temporal and parietal lobes and the contralateral cerebellar hemisphere. The patient underwent a next-day PET scan with the 15O-labeled gas inhalation technique, which showed mild hyperperfusion and oxygen hypermetabolism in these areas. An interictal [18F]FDG-PET scan 17 days after the initial epilepsy demonstrated glucose hypometabolism of the frontal, temporal and parietal lobes and the contralateral cerebellar hemisphere. Increased glucose metabolism on the interictal PET scan and decreased glucose metabolism on an interictal PET scan in the epileptogenic supratentorial zones and the contralateral cerebellar hemisphere are interesting observations for understanding the pathophysiology in long-standing partial seizures.

The cerebral hemodynamics and oxygen metabolism before and after the recanalization of the occluded sinus were evaluated using O-15 positron emission tomography (PET) scanning in a 21-year-old woman with superior sagittal sinus thrombosis. During the initial presentation, there was increased regional cerebral blood volume (rCBV) in the left frontal and parietal lobes with moderately increased rCBV in the right parietal lobe. Recanalization of the occluded sinus resulted in a normalization of elevated rCBV in the frontal and parietal lobes and improvements of rCBF and regional cerebral metabolic rate for oxygen in the occipital lobe. Clinical improvement after recombinant tissue plasminogen activator therapy was accompanied by restoration of cerebral hemodynamics and oxygen metabolism, although magnetic resonance venography showed only partial recanalization of the occluded sinus. PET evaluation of the cerebral hemodynamics and oxygen metabolism may be of value in gaining further insight into pathophysiological characteristics of human cerebral venous sinus thrombosis.

For understanding of the resistance to topoisomerase II inhibitors, 50 sublines were isolated as single clones from parental glioma cell lines by exposure to VP-16 or m-AMSA. The quantitative aspects of topoisomerase II alpha,multi drug resistant gene (MDR)-1, breast cancer resistance protein (BCRP), and multidrug resistant associated protein (MRP) 1-5 were studied by Northern blotting in 50 resistant cell lines. By understanding the function of MRP2, we picked up three drug resistant sublines (T98G-ml, T98G-m2, and gli36-VP1) that overexpressed MRP2, but did not overexpress MDR-1 or MRP1-5 except 2. Moreover, in the results of northern blot analysis of mRNA for topoisomerase II alpha identical results are observed in parental cell lines and their resistant cell lines, suggesting that alterations in topoisomerase II do not account for the resistance in these cells. To determine whether the cellular sensitivity to anticancer agents was closely associated with the cellular levels of MRP2, we established cell lines with the same levels of MRP2 as their parental cells by introducing the MRP2 antisense expression plasmid into resistant cells. Etoposide (VP-16) accumulation and efflux studies were carried out in the parental cell lines and their drug resistant cell lines. Decreases in the HS-VP-16 accumulation and increases in the efflux were observed in these drug resistant cell lines. In the cytotoxicity assay, these drug resistant cell lines were resistant to multiple topoisomerase II inhibitors with little cross resistance to vincristine, and display efflux of VP-16. We found that the resistant cells transfected with MRP2 antisense cDNA displayed increased cellular levels of VP-16 and enhanced sensitivities to topoisomerase II inhibitors. In this study on the T98G-ml, T98G-m2, and gli36-VP1 cell lines, we showed a high correlation between MRP2 mRNA and VP-16 efflux, suggesting that MRP2 could be a new transporter for topoisomerase II inhibitors.

A 2-month-old female infant had had a parietal mass since birth. Neuroimaging revealed a lipoma under the splenium of the corpus callosum that was connected to the subcutaneous lipoma via a bone defect in the cranium bifidum of the parietal region. At the age of 5 months, partial resection of only the extracranial mass was carried out. The histological diagnosis was lipoma. She grew up normally without neurological disorders during follow up for 12 years after the surgery. In the present case, the intracranial lipoma was associated with the cranium bifidum, and dysraphism was possibly involved in the pathogenesis. Resection of only the extracranial subcutaneous tumor can be performed for cosmetic reasons.

We examined the radiological and histological features of, and the influences of the expression of VEGF and its two major receptors, Flt-1 and Flk-1, on the development of peritumoral brain edema (PTBE) in patients with intracranial meningiomas. The expressions of VEGF and VEGF receptors in the immunohistochemical study were analyzed in relation to several factors, including tumor size, location, vascularity, and blood supply, as seen on digital subtraction angiographic studies. The edema volume (P = 0.0003) and edema index (P < 0.0001) had a significantly positive relation to VEGF expression. The positivity of Flt-1 and Flk-1 was mainly observed in tumor vessels; 44 cases (37.2%) were positive for the Flt-1 antibody and 37 cases (31.4%) for the Flk-1 antibody. The mean value of the edema index of the positive-Flt-1 group (5.220 ± 11.586) was significantly higher than that of the negative-Flt-1 group (1.782 ± 2.559) (P < 0.0001). The mean value of the edema index of the positive-Flk-1 group (3.925 ± 5.870) was slightly higher than that of the negative-Flk-1 group (2.671 ± 8.136) (P < 0.0001). Our data suggest that the expressions of VEGF and VEGF receptors positively relate to each other and to the formation of PTBE in patients with meningiomas.