Futoshi Mihara

Perfusion Imaging of Brain Tumors Using Arterial Spin-Labeling : Correlation with Histopathologic Vascular Density

BACKGROUND AND PURPOSE: We investigated the relationship between tumor blood-flow measurement based on perfusion imaging by arterial spin-labeling (ASL-PI) and histopathologic findings in brain tumors. MATERIALS AND METHODS: We used ASL-PI to examine 35 patients with brain tumors, including 11 gliomas, 9 meningiomas, 9 schwannomas, 1 diffuse large B-cell lymphoma, 4 hemangioblastomas, and 1 metastatic brain tumor. As an index of tumor perfusion, the relative signal intensity (SI) of each tumor (%Signal intensity) was determined as a percentage of the maximal SI within the tumor per averaged SI within normal cerebral gray matter on ASL-PI. Relative vascular attenuation (%Vessel) was determined as the total microvessel area per the entire tissue area on CD-34–immunostained histopathologic specimens. MIB1 indices of gliomas were also calculated. The differences in %Signal intensity among different histopathologic types and between high- and low-grade gliomas were compared. In addition, the correlations between %Signal intensity and %Vessel or MIB1 index were evaluated in gliomas. RESULTS: Statistically significant differences in %Signal intensity were observed between hemangioblastomas versus gliomas (P < .005), meningiomas (P < .05), and schwannomas (P < .005). Among gliomas, %Signal intensity was significantly higher for high-grade than for low-grade tumors (P < .05). Correlation analyses revealed significant positive correlations between %Signal intensity and %Vessel in 35 patients, including all 6 histopathologic types (rs = 0.782, P < .00005) and in gliomas (rs = 0.773, P < .05). In addition, in gliomas, %Signal intensity and MIB1 index were significantly positively correlated (rs = 0.700, P < .05). CONCLUSION: ASL-PI may predict histopathologic vascular densities of brain tumors and may be useful in distinguishing between high- and low-grade gliomas and in differentiating hemangioblastomas from other brain tumors.

A comparative study of thallium-201 SPET, carbon-11 methionine PET and fluorine-18 fluorodeoxyglucose PET for the differentiation of astrocytic tumours

Abstract. Thallium-201, carbon-11 methionine (MET) and fluorine-18 fluorodeoxyglucose (FDG) have all been used to assess brain tumours. The aim of this study was to determine which of these tracers are of use for evaluating the histological grade and the extent of astrocytoma. 201Tl single-photon emission tomography (SPET), MET positron emission tomography (PET) and FDG PET were all performed in 23 patients (13 men, 10 women) with newly diagnosed astrocytic tumours [seven with astrocytoma (grade II), ten with anaplastic astrocytoma (grade III) and six with glioblastoma (grade IV)]. The 201Tl uptake of the tumours was evaluated by a lesion-to-normal region count ratio. Both MET and FDG uptake of the tumours was evaluated by a semiquantitative analysis using the standardized uptake value. 201Tl uptake was found to increase in rank order with histological grade and was significantly different among the three groups (grade II: 1.51±0.36; grade III: 2.58±1.50; grade IV: 7.65±3.84). MET uptake in grade II (1.49±0.44) was also significantly lower than that in both grade III (3.29±1.44) and grade IV (3.20±0.92). FDG uptake was not significantly different among the three groups (grade II: 2.90±0.45; grade III: 3.86±1.56; grade IV: 3.57±0.83). No significant correlation was observed between 201Tl uptake and either MET uptake or FDG uptake. In most patients, the extent of the increased MET uptake was the largest while that of the increased FDG uptake was the smallest. In patients with positive 201Tl uptake, the extent of the 201Tl uptake was equal to or smaller than that of gadolinium enhancement. For evaluation of histological grade of astrocytic tumours. 201Tl is therefore considered to be useful though the 201Tl uptake in some grade III astrocytomas was not different from that in grade II astrocytomas. MET was found to be highly useful for detecting astrocytomas, for differentiating between benign and malignant astrocytomas, and for evaluating the extent of astrocytomas; however, it was not sufficiently useful permit evaluation of the histological grade. FDG was not found to be useful either for evaluating the histological grade or for differentiating between benign and malignant astrocytomas.

Upregulation of vascular growth factors in multiple sclerosis: correlation with MRI findings.

Vascular permeability changes precede the development of demyelinating lesions in multiple sclerosis (MS), and vessel wall thickening and capillary proliferation are frequently seen in autopsied MS lesions. Although vascular growth factors are critical for inducing such vascular changes, their involvement in MS has not been extensively studied. Thus, we examined the involvement of various vascular growth factors in MS according to their clinical phase and subtype. We measured serum levels of vascular endothelial growth factor (VEGF), acidic and basic fibroblast growth factors (FGF) and platelet-derived growth factors (PDGFs)-AA, -AB and -BB in 50 patients with MS (27 opticospinal MS and 23 conventional MS patients) and 33 healthy controls using sandwich enzyme immunoassays. Correlations between growth factor changes and brain and spinal cord MRI findings were then analyzed. Serum VEGF concentrations were significantly higher in MS patients in relapse than in controls (p = 0.0495) and in MS patients in remission (p = 0.0003), irrespective of clinical subtype. Basic FGF was significantly increased in conventional MS patients, but not opticospinal MS patients compared with controls (p = 0.0291), irrespective of clinical phase. VEGF at relapse showed a significant positive correlation with the length of spinal cord lesions on MRI (r = 0.506, p = 0.0319). The results suggest that an increase in serum VEGF concentration might be involved in MS relapse and the formation of longitudinally extensive spinal cord lesions.

High b value diffusion-weighted imaging is more sensitive to white matter degeneration in Alzheimer's disease

It has been reported that diffusion-weighted imaging (DWI) can detect white matter degeneration in the Alzheimers disease (AD) brain. We hypothesized that imaging of the slow diffusion component using high b value DWI is more sensitive to AD-related white matter degeneration than is conventional DWI, and therefore we studied the effects of high b value on lesion-to-normal contrast and contrast-to-noise ratio (CNR). Seven AD patients and seven age-matched normal subjects were studied with full-tensor DWI at three different b values (1000, 2000, and 4000 s/mm(2)) without changing echo time or diffusion time, and the mean diffusivities in the parietal and occipital regions were measured. Statistical analyses revealed that use of higher b values significantly improves both lesion-to-normal contrast and CNR. We concluded that high b value DWI is more sensitive to AD-related white matter degeneration than is conventional DWI.

CT and MRI findings of human herpesvirus 6-associated encephalopathy: comparison with findings of herpes simplex virus encephalitis.

OBJECTIVE It is important to differentiate human herpesvirus 6 (HHV-6)-associated encephalopathy from herpes simplex encephalitis (HSE). Although these conditions are similar with regard to involvement of the mesial temporal lobe, HSE is sensitive to acyclovir but HHV-6 encephalopathy is not. We compared the imaging findings of the two conditions. MATERIALS AND METHODS We encountered eight cases of HHV-6 encephalopathy and nine cases of HSE. We divided an observation time into early, middle, and late periods defined as 0-2, 3-30, and more than 30 days from the onset of neurologic symptoms. Differences between HHV-6 encephalopathy and HSE on CT scans in the early period and in distribution and temporal changes in the affected regions on MR images in the three periods were analyzed. RESULTS At MRI in the early and middle periods, all eight patients with HHV-6 encephalopathy had exclusive involvement of the mesial temporal lobes, and all nine patients with HSE had involvement of both the mesial temporal lobes and the extratemporal regions (p < 0.01). Among patients who underwent head MRI, six of six with HHV-6 encephalopathy but none of six with HSE had resolution of high signal intensity on T2-weighted and FLAIR images (p < 0.01). Among patients who underwent head CT in the early period, none of the four with HHV-6 encephalopathy and six of the seven with HSE had abnormal findings, including parenchymal swelling, decreased attenuation of affected regions, and abnormal gyral enhancement (p < 0.05). CONCLUSION Serial MRI showed transient abnormal signal intensity in the mesial temporal lobes in patients with HHV-6 encephalopathy but persistent abnormal signal intensity in both the mesial temporal lobes and the extratemporal regions in patients with HSE. CT in the early period showed no abnormality in patients with HHV-6 encephalopathy but definite abnormal findings in patients with HSE. These differences may be useful in the differential diagnosis of the two conditions.

Association of the HLA-DRB1 alleles with characteristic MRI features of Asian multiple sclerosis.

Background In Asian patients with multiple sclerosis (MS), a paucity of brain lesions and longitudinally extensive spinal cord lesions (LESCLs) extending three or more vertebral segments are characteristic findings on magnetic resonance imaging (MRI). We aimed to disclose possible factors contributing to the development of such MRI features. Method Genotyping of HLA-DRB1 and -DPB1 alleles was performed in 121 consecutive Japanese patients with clinically definite MS based on the Poser criteria and 125 healthy controls. Possible factors associated with MRI features were determined by multiple logistic analysis. Patients with MS were classified based on the presence or absence of brain lesions fulfilling the Barkhof criteria (Barkhof brain lesions) and LESCLs. Barkhof brain lesion–negative (−) patients had a markedly lower frequency of HLA-DRB1*0901 than controls (P corr < 0.05), whereas the frequency of DRB1*1501 was increased in the Barkhof brain lesion–positive (+) group, although this increase was not significant after correction. No Barkhof(−)LESCL(+) patients carried DRB1*0901 (P corr < 0.05), despite this being the most common allele in Japanese. The Barkhof(−)LESCL(−) group showed a significant increase in the frequency of DRB1*0405 compared with controls (P corr < 0.05). None of the DPB1 alleles were significantly different among the groups. Using multiple logistic analysis, the absence of oligoclonal bands was positively associated with an absence of Barkhof brain lesions, whereas a higher EDSS score was positively associated with the presence of LESCLs; however, the presence of anti-aquaporin-4 antibodies was not associated with either feature. Conclusion The characteristic MRI features in Asians are partly related to distinct HLA-DRB1 gene alleles and an absence of oligoclonal bands.

Heterogeneity and continuum of multiple sclerosis in Japanese according to magnetic resonance imaging findings

There are two distinct subtypes of multiple sclerosis (MS) in Asians: optic-spinal (OSMS) and conventional (CMS). Longitudinally extensive spinal cord lesions (LESCLs) extending over three or more vertebral segments are characteristic of patients with OSMS, yet in Asians, one-fourth of CMS patients also have LESCLs. To clarify the distinction between LESCLs in OSMS and CMS, and to characterize the relationship between the presence of LESCLs and brain magnetic resonance imaging (MRI) findings, we studied 142 patients with clinically definite MS of relapsing-remitting onset and 12 patients with primary progressive MS (PPMS) by MRI of the whole spinal cord and brain. The former was diagnosed by Poser criteria, including 57 with OSMS, 67 with CMS and 18 with brainstem-spinal form of MS, while the latter by McDonald criteria. The presence of LESCLs throughout the entire clinical course was significantly more common in OSMS patients than in CMS patients, while brain lesions fulfilling the Barkhof criteria (Barkhof brain lesions) were significantly more common in CMS patients than OSMS patients. LESCLs in OSMS patients most frequently affected the upper to middle thoracic cord, with either holocord or central gray matter involvement. By contrast, 70% of LESCLs in CMS patients predominantly affected the peripheral white matter of the mid-cervical cord. LESCLs in patients with PPMS also showed preferential involvement of the peripheral white matter of the mid-cervical cord. One-third of OSMS patients had neither LESCLs nor Barkhof brain lesions more than 10 years after disease onset, and showed significantly milder disability than OSMS patients with LESCLs. These findings suggest that LESCLs are heterogeneous between OSMS and CMS patients, and that there are distinct subtypes of MS in Japanese, according to clinical and MRI findings.

Automated Method for Identification of Patients With Alzheimer's Disease Based on Three-dimensional MR Images

RATIONALE AND OBJECTIVES An automated method for identification of patients with cerebral atrophy due to Alzheimers disease (AD) was developed based on three-dimensional (3D) T1-weighted magnetic resonance (MR) images. MATERIALS AND METHODS Our proposed method consisted of determination of atrophic image features and identification of AD patients. The atrophic image features included white matter and gray matter volumes, cerebrospinal fluid (CSF) volume, and cerebral cortical thickness determined based on a level set method. The cortical thickness was measured with normal vectors on a voxel-by-voxel basis, which were determined by differentiating a level set function. The CSF spaces within cerebral sulci and lateral ventricles (LVs) were extracted by wrapping the brain tightly in a propagating surface determined with a level set method. Identification of AD cases was performed using a support vector machine (SVM) classifier, which was trained by the atrophic image features of AD and non-AD cases, and then an unknown case was classified into either AD or non-AD group based on an SVM model. We applied our proposed method to MR images of the whole brains obtained from 54 cases, including 29 clinically diagnosed AD cases (age range, 52-82 years; mean age, 70 years) and 25 non-AD cases (age range, 49-78 years; mean age, 62 years). RESULTS As a result, the area under a receiver operating characteristic (ROC) curve (Az value) obtained by our computerized method was 0.909 based on a leave-one-out test in identification of AD cases among 54 cases. CONCLUSION This preliminary result showed that our method may be promising for detecting AD patients.

An intraorbital wooden foreign body: description of a case and a variety of CT appearances

We present a case report in which a 4-year-old girl was involved in a fall that resulted in an injury of the right orbita. The girl kept a chopstick in her right hand that got into the right orbita due to this accident. Only a fraction remained in the orbita; the residual chopstick got lost. Hence, the substance of the chopstick was unknown. Computed tomography (CT) revealed a foreign body in the right orbita, but ophthalmologists had initially no indication of intervention. Further course according to the follow-up CT showed an increase of Hounsfield units (HU). These findings led to the assumption that the foreign body was made of wood. Through this, the ophthalmologists performed an evacuation. Motivated by these clinical results, we created an experimental setup that could demonstrate changes of HU in different coated chopsticks. It is concluded that wooden foreign bodies can display a variety of CT appearances depending on materials, types, coating, and time-course.

Unilaterally symptomatic moyamoya disease in children: long-term follow-up of 20 patients.

OBJECTIVE:In unilaterally symptomatic moyamoya disease in children, it remains controversial whether bypass surgery should be performed on the asymptomatic side along with on the symptomatic side. We aimed to verify the validity of our strategy of only performing bypass surgery on the symptomatic side. METHODS:Among 91 pediatric patients with moyamoya disease who underwent bypass surgery in our department between 1980 and 2004, 20 with unilateral ischemic symptoms who were followed for more than 60 months were analyzed in the present study. Initially, we only performed bypass surgery on the symptomatic side for all 20 patients. Among these 20 patients, five developed frequent transient ischemic attacks in the initially asymptomatic side and underwent a second bypass surgery on that side (Group A), eight developed sporadic transient ischemic attacks and were followed up without surgery (Group B), and seven did not experience any ischemic symptoms on the asymptomatic side (Group C). RESULTS:In total, 18 patients progressed well without cerebral infarctions after their last surgery, although some showed deterioration of angiographic stenosis and a transient decrease in the regional cerebral blood flow or cerebral perfusion reserve. One patient in Group A had an intraventricular hemorrhage 5 years after the second operation, and one in Group B had a minor stroke on the initially asymptomatic side. CONCLUSION:In unilaterally symptomatic moyamoya disease, bypass surgery for the asymptomatic side can be delayed until the development of ischemic symptoms, such as frequent transient ischemic attacks.