Morphologic Features of Carotid Plaque Rupture Assessed by Optical Coherence Tomography.

BACKGROUND AND PURPOSE: Rupture of the plaque fibrous cap and subsequent thrombosis are the major causes of stroke. This study evaluated morphologic features of plaque rupture in the carotid artery by using optical coherence tomography in vivo. MATERIALS AND METHODS: Thirty-six carotid plaques with high-grade stenosis were prospectively imaged by optical coherence tomography. "Plaque rupture" was defined as a plaque containing a cavity that had overlying residual fibrous caps. The fibrous cap thickness was measured at its thinnest part for both ruptured and nonruptured plaques. The distance between the minimum fibrous cap thickness site and the bifurcation point was also measured. Optical coherence tomography identified 24 ruptured and 12 nonruptured plaques. RESULTS: Multiple ruptures were observed in 9 (38%) patients: Six patients had 2 ruptures in the same plaque, 2 patients had 3 ruptures in the same plaque, and 1 patient had 5 ruptures in the same plaque. Most (84%) of the fibrous cap disruptions were identified at the plaque shoulder and near the bifurcation point (within a 4.2-mm distance). The median thinnest cap thickness was 80 µm (interquartile range, 70-100 µm), and 95% of ruptured plaques had fibrous caps of <130 µm. Receiver operating characteristic analysis revealed that a fibrous cap thickness of <130 µm was the critical threshold value for plaque rupture in the carotid artery. CONCLUSIONS: Plaque rupture was common in high-grade stenosis and was located at the shoulder of the carotid plaque close to the bifurcation. A cap thickness of <130 µm was the threshold for plaque rupture in the carotid artery.

Glycoprotein nonmetastatic melanoma protein B (GPNMB) as a novel neuroprotective factor in cerebral ischemia-reperfusion injury.

Glycoprotein nonmetastatic melanoma protein B (GPNMB) is a type I transmembrane protein reported to have neuroprotective effects in the neurodegenerative disease amyotrophic lateral sclerosis (ALS). We investigated whether GPNMB is also neuroprotective against brain ischemia-reperfusion injury (IRI). Focal ischemia/reperfusion injury was induced via filament middle cerebral artery occlusion (MCAO) for 2h, followed by reperfusion upon withdrawal of the filament. We assessed the neuroprotective effects of GPNMB using transgenic (Tg) mice which over expressing GPNMB or recombinant GPNMB which has the sequence of human extracellular GPNMB. The results showed that GPNMB was up-regulated after IRI, and that genomic over-expression of GPNMB significantly ameliorated infarct volume. Next, we investigated the protective mechanisms of GPNMB via Western blotting and immunohistochemistry (IHC). Phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2), and protein kinase B (Akt), were increased in the GPNMB Tg group according to Western blotting data. IHC analysis showed that GPNMB was expressed not only in neurons, but also in astrocytes, produced labeling patterns similar to that in human brain ischemia. Furthermore, recombinant GPNMB also decreased infarction volume. These results indicate that GPNMB protected neurons against IRI, and phosphor-Akt and phosphor-ERK might be a part of the protective mechanisms, and that the neuroprotective effect of GPNMB was seemingly induced by the extracellular sequence of GPNMB. In conclusion, these findings indicate that GPNMB has neuroprotective effects against IRI, via phosphorylation of ERK1/2 and Akt, suggesting that GPNMB may be a therapeutic target for ischemia-reperfusion injuries.

A Rho kinase (ROCK) inhibitor, fasudil, prevents matrix metalloproteinase-9-related hemorrhagic transformation in mice treated with tissue plasminogen activator.

Thrombolysis with tissue plasminogen activator (tPA) is the only FDA-approved therapy for acute ischemic stroke. However, hemorrhagic transformation, neurotoxicity, and a short treatment time window comprise major limitations for thrombolytic therapy. The purpose of the present study was to investigate whether fasudil, a Rho kinase (ROCK) inhibitor, would prevent tPA-associated hemorrhagic transformation and extend the reperfusion window in an experimental stroke model in mice. Mice subjected to 6-h middle cerebral artery occlusion were treated with delayed tPA alone, with combined tPA plus fasudil, or with a vehicle. We used histological and neurobehavioral measures to assess the effects of the treatment at 18 h and 7 days after the reperfusion. To investigate the mechanism of fasudil's beneficial effects further, we also performed an in vitro study with tPA and fasudil in human brain microvascular endothelial cells. Combination therapy with tPA plus fasudil prevented the development of hemorrhagic transformation, but did not reduce the infarct volumes. These changes significantly reduced mortality and increased locomotor activity at 7 days after the reperfusion. Furthermore, the administration of both drugs prevented injury to the human brain endothelial cells via the reduction of matrix metalloproteinase-9 (MMP-9) activity. These findings indicate that fasudil prevents the hemorrhagic transformation induced by focal cerebral ischemia in mice treated with tPA, at least in part, by inhibiting the increased activity of MMP-9 in endothelial cells.

A simple technique for repair of distal limb prolapse of a loop colostomy.

Several procedures have been proposed for the prolapse of a loop colostomy. However, most are associated with a high recurrence rate or are rather expensive. We have newly developed a simple, safe, and inexpensive method, which is a modification of Thiersch's method, for repair of distal limb prolapse of a loop colostomy.

Visualization of internal carotid artery atherosclerotic plaques in symptomatic and asymptomatic patients: a comparison of optical coherence tomography and intravascular ultrasound.

BACKGROUND AND PURPOSE: OCT has been reported as a high-resolution imaging tool for characterizing plaque in the coronary arteries. The present study aimed to evaluate the ability of OCT to visualize carotid artery plaques compared with that of IVUS in asymptomatic and symptomatic patients. MATERIALS AND METHODS: OCT was performed for 34 plaques (17 symptomatic, 17 asymptomatic) in 30 patients during CAS under a proximal cerebral protection method. OCT was performed before balloon angioplasty and after stent placement. IVUS was also performed just after OCT. RESULTS: No technical or neurologic complications were encountered by using OCT. An inner catheter was used in 12 of 34 procedures (35.3%) for advancing the OCT image wire beyond the site of stenosis. OCT clearly visualized intraluminal thrombus in 15 of 34 plaques (44.1%), whereas IVUS detected a thrombus in 1 plaque (2.9%, P < .001). Neovascularization was demonstrated in 13 of 34 plaques (38.2%) by OCT, but not by IVUS (0%, P < .001). Intraluminal thrombus was more frequently observed in symptomatic plaques (13 of 17, 76.5%) than in asymptomatic plaques (2 of 17, 11.8%; P < .001). Interobserver and intraobserver variability with OCT diagnosis was excellent for thrombus, ulceration, neovascularization, and lipid pool. CONCLUSIONS: The present findings suggest that OCT can safely and precisely visualize human carotid plaques during CAS and that intraluminal thrombus and neovascularization are more frequently detected in symptomatic plaques.

Hypoxia promotes expansion of the CD133-positive glioma stem cells through activation of HIF-1alpha.

Hypoxia contributes to the progression of a variety of cancers by activating adaptive transcriptional programs that promote cell survival, motility and tumor angiogenesis. Although the importance of hypoxia and subsequent hypoxia-inducible factor-1alpha (HIF-1alpha) activation in tumor angiogenesis is well known, their role in the regulation of glioma-derived stem cells is unclear. In this study, we show that hypoxia (1% oxygen) promotes the self-renewal capacity of CD133-positive human glioma-derived cancer stem cells (CSCs). Propagation of the glioma-derived CSCs in a hypoxic environment also led to the expansion of cells bearing CXCR4 (CD184), CD44(low) and A2B5 surface markers. The enhanced self-renewal activity of the CD133-positive CSCs in hypoxia was preceded by upregulation of HIF-1alpha. Knockdown of HIF-1alpha abrogated the hypoxia-mediated CD133-positive CSC expansion. Inhibition of the phosphatidylinositol 3-kinase(PI3K)-Akt or ERK1/2 pathway reduced the hypoxia-driven CD133 expansion, suggesting that these signaling cascades may modulate the hypoxic response. Finally, CSCs propagated at hypoxia robustly retained the undifferentiated phenotype, whereas CSCs cultured at normoxia did not. These results suggest that response to hypoxia by CSCs involves the activation of HIF-1alpha to enhance the self-renewal activity of CD133-positive cells and to inhibit the induction of CSC differentiation. This study illustrates the importance of the tumor microenvironment in determining cellular behavior.

Fluid-fluid level formation: a rare finding of extracranial head and neck schwannomas.

SUMMARY: We present 3 cases of extracranial head and neck schwannomas exhibiting fluid-fluid levels. In the described cases, CT and MR imaging showed predominantly cystic components, intermixed with cellular components. Histopathologic examinations of excised specimens revealed hemosiderin deposition, reflecting intratumoral hemorrhages, which was presumably a cause of fluid-fluid levels. Although fluid-fluid levels are nonspecific findings, schwannoma should be considered when radiologic images demonstrate marked cystic formation with fluid-fluid levels in extracranial head and neck tumors.

Analysis of 11C-methionine uptake in low-grade gliomas and correlation with proliferative activity.

BACKGROUND AND PURPOSE: The relationship of (11)C-methionine (MET) uptake and tumor activity in low-grade gliomas (those meeting the criteria for World Health Organization [WHO] grade II gliomas) remains uncertain. The aim of this study was to compare MET uptake in low-grade gliomas and to analyze whether MET positron-emission tomography (PET) can estimate tumor viability and provide evidence of malignant transformation. MATERIALS AND METHODS: We studied glioma metabolic activity in 49 consecutive patients with newly diagnosed grade II gliomas by using MET PET before surgical resection. On MET PET, we measured tumor/normal brain uptake ratio (T/N ratio) in 21 diffuse astrocytomas (DAs), 12 oligodendrogliomas (ODs), and 16 oligoastrocytomas (OAs). We compared MET T/N ratio among these 3 tumors and investigated possible correlation with proliferative activity, as measured by Mib-1 labeling index (LI). RESULTS: MET T/N ratios of DA, OD, and OA were 2.11 +/- 0.87, 3.75 +/- 1.43, and 2.76 +/- 1.27, respectively. The MET T/N ratio of OD was significantly higher than that of DA (P < .005). In comparison of MET T/N ratios with the Mib-1 LI, a significant correlation was shown in DA (r = 0.63; P < .005) but not in OD and OA. CONCLUSION: MET uptake in DAs may be closely associated with tumor viability, which depends on increased amino acid transport by an activated carrier-mediated system. DAs with lower MET uptake were considered more quiescent lesions, whereas DA with higher MET uptake may act more aggressively.

Present status of Moyamoya disease in Japan.

To gain an overview of the current status of Moyamoya disease in Japan, we reviewed the 2002-2004 report of the Research Committee on Moyamoya Disease and the clinical data of Moyamoya patients treated at Gifu University Hospital during the past 2 years. According to the report, a nationwide epidemiological survey performed in 2004 revealed that approximately 7500 Japanese were treated for Moyamoya disease; their number doubled during the last 10 years. Moyamoya associated with headache was newly added as a subtype; as many as 5% of Moyamoya patients experience headache. Three-dimensional (3D) stereotactic statistical cerebral blood flow (CBF) analysis was reported as useful for the stratification of the cerebral hemodynamics in Moyamoya disease. To develop treatment guidelines for hemorrhagic Moyamoya, a prospective randomized control trial begun in 2001 is ongoing. During the past 2 years, 23 patients with Moyamoya disease were treated at our hospital. Of these, 17 presented with transient ischemic attacks/infarction, 4 with intracranial hemorrhage (ICH), and 2 with headache. One patient who presented with ICH died during the acute stage, the remaining 22 patients were successfully treated by direct bypass surgery.

Metabolic assessment of gliomas using 11C-methionine, [18F] fluorodeoxyglucose, and 11C-choline positron-emission tomography.

BACKGROUND AND PURPOSE: Positron-emission tomography (PET) is a useful tool in oncology. The aim of this study was to assess the metabolic activity of gliomas using (11)C-methionine (MET), [(18)F] fluorodeoxyglucose (FDG), and (11)C-choline (CHO) PET and to explore the correlation between the metabolic activity and histopathologic features. MATERIALS AND METHODS: PET examinations were performed for 95 primary gliomas (37 grade II, 37 grade III, and 21 grade IV). We measured the tumor/normal brain uptake ratio (T/N ratio) on each PET and investigated the correlations among the tracer uptake, tumor grade, tumor type, and tumor proliferation activity. In addition, we compared the ease of visual evaluation for tumor detection. RESULTS: All 3 of the tracers showed positive correlations with astrocytic tumor (AT) grades (II/IV and III/IV). The MET T/N ratio of oligodendroglial tumors (OTs) was significantly higher than that of ATs of the same grade. The CHO T/N ratio showed a significant positive correlation with histopathologic grade in OTs. Tumor grade and type influenced MET uptake only. MET T/N ratios of more than 2.0 were seen in 87% of all of the gliomas. All of the tracers showed significantly positive correlations with Mib-1 labeling index in ATs but not in OTs and oligoastrocytic tumors. CONCLUSION: MET PET appears to be useful in evaluating grade, type, and proliferative activity of ATs. CHO PET may be useful in evaluating the potential malignancy of OTs. In terms of visual evaluation of tumor localization, MET PET is superior to FDG and CHO PET in all of the gliomas, due to its straightforward detection of "hot lesions".

Prevention of in vitro and in vivo acute ischemic neuronal damage by (2S)-1-(4-amino-2,3,5-trimethylphenoxy)-3-{4-[4-(4-fluorobenzyl) phenyl]-1-piperazinyl}-2-propanol dimethanesulfonate (SUN N8075), a novel neuroprotective agent with antioxidant properties.

(2S)-1-(4-Amino-2,3,5-trimethylphenoxy)-3-{4-[4-(4-fluorobenzyl) phenyl]-1-piperazinyl}-2-propanol dimethanesulfonate (SUN N8075) is a novel antioxidant with neuroprotective properties. We examined whether SUN N8075 inhibited the neuronal damage resulting from permanent focal cerebral ischemia, and examined its neuroprotective properties in vivo and in vitro mechanism. Focal cerebral ischemia was induced by permanent middle cerebral artery occlusion in mice, and the resulting infarction, brain swelling, and neurological deficits were evaluated after 24 h or 72 h. Brain damage was assessed histochemically using terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining and antibody recognizing 4-hydroxynonenal histidine adduct (4-HNE). In the in vitro study, we examined the effects of SUN N8075 on 1) lipid peroxidation in mouse brain homogenates and 2) cell viability and caspase-3 protease activity under a hypoxic insult or FeSO(4) in rat cultured cerebrocortical neurons. SUN N8075 administered either 10 min before or at 1 h after the occlusion reduced both infarction size and neurological deficits. SUN N8075 reduced brain swelling when administered 10 min before, 1 h, or 3 h after occlusion. Furthermore, only pretreatment (administered 10 min before) decreased infarct volume and brain swelling at 72 h after middle cerebral artery occlusion. SUN N8075 reduced the number of TUNEL-positive cells and decreased the level of oxidative damage, as assessed by immunopositive staining to 4-HNE. SUN N8075 inhibited lipid peroxidation, leakage of lactate dehydrogenase, caspase-3 activation induced by in vitro hypoxia, and the neuronal damage induced by in vitro FeSO(4) exposure. These findings indicate that SUN N8075 has neuroprotective effects against acute ischemic neuronal damage in mice and may prove promising as a therapeutic drug for stroke.

Relatively decreased 11C-methionine uptake within the anaplastic component of a mixed-grade oligodendroglioma.

A 56-year-old woman presented with a mixed-grade oligodendroglioma. On 11C-methionine [MET]-positron-emission tomography images, heterogeneous uptake of MET was demonstrated in the mass lesion. The part of the lesion with higher MET uptake was identified as an ordinary oligodendroglioma, whereas the part of the lesion with lower MET uptake was an anaplastic component of oligodendroglioma. With oligodendrogliomas, we should be aware of the possibility that MET uptake decreases paradoxically with an increased anaplastic component of oligodendroglioma cells.

Focal brain glucose hypometabolism in patients with neuropsychologic deficits after diffuse axonal injury.

BACKGROUND AND PURPOSE: Neuropsychologic deficits are well-known sequelae of traumatic brain injury. However, the cerebral correlates of these deficits are still unclear. The aim of the present study was to elucidate the regions of cerebral dysfunction correlated with such neuropsychologic deficits after traumatic brain injury. METHODS: Sets of fluorine-18 fluorodeoxyglucose-positron-emission tomography (FDG-PET) images in the resting state were obtained from 12 patients with neuropsychologic deficits after diffuse axonal injury and from 32 healthy volunteers. The cortical metabolic activity of each subject's PET image sets was extracted using 3D stereotactic surface projection (3D-SSP). A "normal" data base was created using the extracted datasets of the healthy subjects. The patients' datasets were compared with the normal data base by calculating a statistical Z-score on a pixel-by-pixel basis in searches for focal metabolic abnormalities. RESULTS: Group comparisons revealed hypometabolism in the cingulate gyrus with additional involvement of the lingual gyrus and cuneus. Individual case-by-case analyses disclosed differences in the site and extent of the hypometabolism in the cingulate gyrus of each case. Predominant hypometabolism was found in the anterior cingulate gyrus of 6 patients, the middle cingulate gyrus of 2 patients, and the posterior cingulate gyrus of 4 patients. CONCLUSION: Interpretation of FDG-PET using 3D-SSP facilitates the identification of regional hypometabolism in the cerebral cortex of patients after diffuse axonal injury. Dysfunction of the cingulate gyrus, lingual gyrus, and cuneus may play a crucial role in neuropsychologic deficits after traumatic brain injury.

Local intra-arterial fibrinolysis in acute basilar artery occlusion.

SUMMARY: Acute basilar artery (BA) occlusion is typically associated with poor outcome; however newer diagnostic and treatment modalities have the potential to improve prognosis. In this study, six patients with acute BA occlusion were followed and the effectiveness of local intra-arterial fibrinolysis (LIF) and subsequent percutaneous transluminal angioplasty (PTA) with a balloon catheter were assessed. Of the six patients with BA occlusion observed in this study, two had extended brain stem infarction on diffusion weighted image (DWI) and were treated conservatively. The other four patients received LIF at an average of 5.2 hours from occlusion onset. Three of these four patients received additional PTA with compliant balloon catheters. All four of the patients who received LIF achieved recanalization of the BA trunk and showed a favorable clinical outcome. These findings suggest that LIF is beneficial for selected patients with BA occlusion and that successful recanalization is indicative of a good prognosis. Because of the poor prognosis associated with conservative therapy, we conclude that LIF should be attempted even for comatose patients or in cases of prolonged occlusion time.

Carotid-compression technique for the insertion of guiding catheters.

Inserting a guiding catheter into a tortuous artery for neurointerventional procedures can be difficult. In our technique, the carotid artery is manually compressed to stabilize and/or straighten the inserted wire before advancing the guiding catheter. Although this technique is not risk-free and care must be taken to avoid vascular injury by excessive compression, it is useful for the insertion of a guiding catheter into the carotid artery.

Evidence for white matter disruption in traumatic brain injury without macroscopic lesions.

BACKGROUND: Non-missile traumatic brain injury (nmTBI) without macroscopically detectable lesions often results in cognitive impairments that negatively affect daily life. AIM: To identify abnormal white matter projections in patients with nmTBI with cognitive impairments using diffusion tensor magnetic resonance imaging (DTI). METHODS: DTI scans of healthy controls were compared with those of 23 patients with nmTBI who manifested cognitive impairments but no obvious neuroradiological lesions. DTI was comprised of fractional anisotropy analysis, which included voxel-based analysis and confirmatory study using regions of interest (ROI) techniques, and magnetic resonance tractography of the corpus callosum and fornix. RESULTS: A decline in fractional anisotropy around the genu, stem and splenium of the corpus callosum was shown by voxel-based analysis. Fractional anisotropy values of the genu (0.47), stem (0.48), and splenium of the corpus callosum (0.52), and the column of the fornix (0.51) were lower in patients with nmTBI than in healthy controls (0.58, 0.61, 0.62 and 0.61, respectively) according to the confirmatory study of ROIs. The white matter architecture in the corpus callosum and fornix of patients with nmTBI were seen to be coarser than in the controls in the individual magnetic resonance tractography. CONCLUSIONS: Disruption of the corpus callosum and fornix in patients with nmTBI without macroscopically detectable lesions is shown. DTI is sensitive enough to detect abnormal neural fibres related to cognitive dysfunction after nmTBI.

Relationship between regional cerebral metabolism and consciousness disturbance in traumatic diffuse brain injury without large focal lesions: an FDG-PET study with statistical parametric mapping analysis.

BACKGROUND: The cerebral metabolism of patients in the chronic stage of traumatic diffuse brain injury (TDBI) has not been fully investigated. AIM: To study the relationship between regional cerebral metabolism (rCM) and consciousness disturbance in patients with TDBI. METHODS: 52 patients with TDBI in the chronic stage without large focal lesions were enrolled, and rCM was evaluated by fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) with statistical parametric mapping (SPM). All the patients were found to have disturbed consciousness or cognitive function and were divided into the following three groups: group A (n = 22), patients in a state with higher brain dysfunction; group B (n = 13), patients in a minimally conscious state; and group C (n = 17), patients in a vegetative state. rCM patterns on FDG-PET among these groups were evaluated and compared with those of normal control subjects on statistical parametric maps. RESULTS: Hypometabolism was consistently indicated bilaterally in the medial prefrontal regions, the medial frontobasal regions, the cingulate gyrus and the thalamus. Hypometabolism in these regions was the most widespread and prominent in group C, and that in group B was more widespread and prominent than that in group A. CONCLUSIONS: Bilateral hypometabolism in the medial prefrontal regions, the medial frontobasal regions, the cingulate gyrus and the thalamus may reflect the clinical deterioration of TDBI, which is due to functional and structural disconnections of neural networks rather than due to direct cerebral focal contusion.

Segmental high intensity on T1-weighted hepatic MR images.

BACKGROUND: We investigated the diagnostic importance of segmental high-intensity (SHI) areas not corresponding to mass lesions on T1-weighted magnetic resonance (MR) images. METHODS: We conducted a retrospective investigation of hepatic MR images obtained from 634 patients during a 4-year period at our institution. Images were compared with findings reported in the patients' medical records. There were 16 patients (2.5%) with SHI areas not corresponding to a mass lesion. We compared MR images with plain computed tomographic (CT) scans (n = 16), angiograms (n = 12), and histologic findings (n = 10). RESULTS: The segments with intrahepatic bile duct dilatation showed hyperintensity on T1-weighted images. In six of 16 patients, the biliary duct was more dilated in the area of hyperintensity than in areas without hyperintensity. The SHI areas appeared as areas of low attenuation (n = 13), high attenuation (n = 1), or isoattenuation (n = 2) on plain CT scans. Histologically, these areas showed ductular proliferation and deposition of bile pigment within the hepatocytes. CONCLUSION: Segmental areas of increased signal intensity on T1-weighted images were probably due to intrahepatic cholestasis.

Computer-Aided Diagnosis Scheme for Detection of Unruptured Intracranial Aneurysms in MR Angiography.

The detection of unruptured intracranial aneurysms is a major subject in magnetic resonance angiography (MRA) images. However,it is difficult for radiologists to detect small aneurysms on the maximum intensity projection (MIP) images, because adjacent vessels overlap with the aneurysm. The purpose of this study was to develop an automated computerized detection of aneurysms in order to assist radiologists' interpretation as a "second opinion." The vessels were first segmented from background by use of gray-level thresholding and region growing technique. The gradient concentrate (GC) filter was then applied to the segmented vessels for enhancement of aneurysm. The initial aneurysm candidate was identified in the GC image with a gray level threthold. For removal of false positives (FPs), we determined three features, i.e.,size,sphericity, and mean value of GC image in each of the candidate regions. Finally, the rule-based schemes with these features and quadratic discriminant analysis were applied for distinction between aneurysms and FPs. The sensitivity of our method for detection of aneurysms was 100% (7/7) with 1.85 FPs per patient. With our computerized scheme, all aneurysms were detected correctly with low FP rates, and would be useful in assisting radiologists for identifying correct aneurysms and for reducing the interpretation time.

Discrepancy between lesion distributions on methionine PET and MR images in patients with glioblastoma multiforme: insight from a PET and MR fusion image study.

OBJECTIVE: To examine (11)C-methyl methionine (MET) accumulation on positron emission tomographic (PET) imaging of glioblastoma multiforme to determine the distribution of metabolic abnormality compared with magnetic resonance imaging (MRI). METHODS: Contemporaneous MRI was superimposed on corresponding MET-PET images in 10 patients with newly diagnosed glioblastoma multiforme before treatment. Differences between the extended area of MET accumulation on PET imaging (MET area), the gadolinium (Gd) enhanced area on T1 weighted images (Gd area), and the abnormal high signal intensity area on T2 weighted images (T2-high area) were assessed. RESULTS: The MET area was larger than the Gd area and included the entire Gd area. The discrepancy in volume between the MET and Gd areas became greater with increasing tumour diameter. On average, 58.6% of the MET area was located within the Gd area, 90.1% within 10 mm outside the Gd area, 98.1% within 20 mm, and 99.8% within 30 mm. A newly developed Gd area had emerged in five of the 10 cases up to the time of study. In three of the five cases this was in the MET area even after complete surgical resection of the Gd area on the initial MRI; in the remaining two it originated in the residual Gd area after surgery. In all cases, the T2-high area was larger than the MET area. The MET area extended partly beyond the T2-high area in nine cases, and was completely within it in one. CONCLUSIONS: Glioblastoma multiforme cells may extend over the Gd area and more widely with increasing tumour size on Gd-MRI. The T2-high area includes the greater part of the tumour but not its entire area. The methods reported may be useful in planning surgical resection, biopsy, or radiosurgery.