Characteristic brain hypoperfusion by 99mTc-ECD single photon emission computed tomography (SPECT) in patients with the first-episode schizophrenia.

OBJECTIVE: In this study, we evaluated brain perfusion in patients with first-episode medicated schizophrenia using the new analytical method, statistical parametric mapping (SPM) applied to single photon emission computed tomography (SPECT). METHOD: We performed SPECT with 99-Tc-ethyl cysteinate dimer (99mTc-ECD) of the brain and magnetic resonance imaging (MRI) in patients with schizophrenia (n=30) and control subjects matched for age and gender (n=37). A voxel-by-voxel group analysis was performed using SPM2 (Z>3.0, P<0.001, uncorrected for multiple comparisons). RESULT: In comparison with control subjects, the volumes of the bilateral frontal areas were found to be decreased on MRI. Blood flow was found to be reduced in the bilateral temporal areas in the patients with schizophrenia on SPECT. CONCLUSION: In this study, patients with first-episode schizophrenia appeared to have significant bilateral temporal hypoperfusion, although temporal volumes were not significantly decreased in comparison with control subjects. Abnormality of temporal lobe blood flow in schizophrenia may show that functional changes occur earlier than structural changes, and may assist in the diagnosis of schizophrenia.

Demonstration of cerebellar atrophy in neuroacanthocytosis of 2 siblings.

SUMMARY: Neuroacanthocytosis is a rare hereditary disorder characterized by involuntary choreiform movements and erythrocytic acanthocytosis in the peripheral blood. Clinical manifestations of this disorder resemble those of Huntington disease (HD). Neuroimaging features of neuroacanthocytosis are atrophy and signal intensity change of the striata on MR imaging, as in HD. We report herein the cases of 2 siblings with neuroacanthocytosis showing cerebellar atrophy as well as atrophy and signal intensity changes of striata.

Radiation-induced xerostomia: objective evaluation of salivary gland injury using MR sialography.

BACKGROUND AND PURPOSE: Xerostomia (dry mouth) is one of the serious complications of head and neck irradiation and has a strong influence on a patient's activities of daily living. MR sialography with salivary secretion stimulation provides additional functional information (salivary secretion reserve) and may contribute to the evaluation of the severity of xerostomia and predict the risk of developing a radiation-induced xerostomia. This aim of the study was to analyze MR sialography as an objective tool to evaluate radiation-induced salivary injury. MATERIALS AND METHODS: MR sialography with salivary secretion stimulation was performed in 16 patients with head and neck malignancy before and after irradiation therapy. Multivariate (stepwise multiple regression) analysis was performed to analyze the nonstimulated and stimulated MR sialography findings and the clinical severity of xerostomia. RESULTS: Multivariate analysis of the preirradiation study revealed no significant independent variables that could predict the clinical severity of xerostomia. In the postirradiation study, following regression with 2 independent variables (secretion response of the submandibular gland [rSG] and parotid gland visualization on stimulated MR sialography [sPG]) could explain 70% of the cases: xerostomia severity grade = 0.681 + 0.871 x rSG - 0.471 x sPG. CONCLUSIONS: MR sialography is a useful method for visualization of salivary gland radiation injury and estimation of the severity of radiation-induced xerostomia. Insufficiency of secretion reserve at the irradiated submandibular gland has the strongest influence on xerostomia severity. Our investigation suggests that careful submandibular gland protection may lead to prevention and avoidance of radiation-induced xerostomia.

Usefulness of diffusion-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging in the diagnosis of prostate transition-zone cancer.

BACKGROUND: Conventional T2-weighted (T2-WI) magnetic resonance imaging (MRI) has poor sensitivity for prostate transition-zone (TZ) cancer detection. PURPOSE: To retrospectively evaluate the clinical value of diffusion-weighted MRI (DW-MRI) and dynamic contrast-enhanced MRI (DCE-MRI) in combination with T2-WI for the diagnosis of TZ cancer. MATERIAL AND METHODS: Twenty-six TZ cancers in 23 patients with at least one tumor (tumor size >10 mm) located predominantly in the TZ were included in the study. Sixteen peripheral-zone (PZ) cancers in 12 patients with PZ cancer but without TZ cancer (control group) were selected by step-section pathologic maps. All patients underwent MRI and radical prostatectomy. MRI was obtained by a 1.5T superconducting system with a phased-array coil. Imaging sequences were T2-WI with fat saturation (FST2-WI), DW-MRI (single-shot echoplanar image, b=0 and 1000 s/mm(2), apparent diffusion coefficient [ADC] map findings), and DCE-MRI (3D fast spoiled gradient recalled [SPGR], contrast medium [0.2 mmol/kg], total injection time 5 s, image acquisition 30, 60, and 90 s). Sensitivity, specificity, accuracy, and positive predictive value (PPV) for the diagnosis of TZ cancer were evaluated in four protocols: A) FST2-WI alone, B) FST2-WI plus DW-MRI, C) FST2-WI plus DCE-MRI, D) FST2-WI plus DW-MRI plus DCE-MRI. RESULTS: Sensitivity, specificity, accuracy, and PPV in protocol A (FST2-WI alone) were 61.5%, 68.8%, 64.3%, and 76.2%, respectively. FST2-WI plus DW-MRI (protocol B) improved the sensitivity, specificity, accuracy, and PPV. In FST2-WI plus DW-MRI plus DCE-MRI (protocol D), the number of true-negative lesions increased and false-positive lesions decreased, and the sensitivity, specificity, accuracy, and PPV were 69.2%, 93.8%, 78.6%, and 94.7%, respectively. There was a significant difference between protocols A and D (P<0.05). CONCLUSION: Adding DW-MRI to FST2-WI in the diagnosis of prostate TZ cancer increased the diagnostic accuracy. The addition of DCE-MRI may be an option to improve the specificity and PPV of diagnosing TZ cancer with FST2-WI and DW-MRI.

Neuronal substrates for semantic memory: a positron emission tomography study in Alzheimer's disease.

We examined 57 patients with mild Alzheimer's disease by using three kinds of verbal semantic memory tests (category fluency, confrontation naming and generation of verbal definition) and correlated each score with regional cerebral glucose metabolism determined by (18)F-fluorodeoxyglucose and positron emission tomography. The scores of all three verbal semantic memory tests correlated significantly with regional cerebral glucose metabolism in the left inferior temporal gyrus, even after controlling for the effects of age, sex and educational attainment. In contrast, the scores of the word recall test did not correlate significantly with regional cerebral glucose metaboliosm in the left inferior temporal gyrus, neither before nor after controlling for these confounders. Our results suggested that the left inferior temporal lobe contributes to verbal semantic memory.

Cortical activation during retrieval of arithmetical facts and actual calculation: a functional magnetic resonance imaging study.

By using functional magnetic resonance imaging (fMRI), the neural substrates involved in mental recitation of the single-digit multiplication table and serial subtraction were studied. The former depends mostly on well-learned arithmetical facts, while the latter requires arithmetic processing. Activation during each task was compared with that in a number counting control. During the recitation of single-digit multiplication, the activated regions included the area lying along the left intraparietal sulcus, the premotor and supplementary motor areas, and the posterior portion of the left inferior frontal gyrus. The areas activated during serial subtraction included these areas as well as the bilateral prefrontal and right parietal areas. From the results obtained during retrieval of the multiplication table in this study and previous studies, it was concluded that semantic memory of the multiplication table is stored in the area lying along the intraparietal sulcus and that the frontal areas play an executive role in utilizing the semantic memory of arithmetical facts. It was assumed that the arithmetical facts requiring actual calculation are also stored in the same region. The additional activation during serial subtraction compared with the activation during retrieval of the multiplication table is probably due to the processes of actual calculation. These processes include proper alignment of digits, which may have caused the right parietal activation, and maintaining digits needed for the mental serial subtractions, which may have caused the bilateral prefrontal activation.

Impact of white matter changes on clinical manifestation of Alzheimer's disease: A quantitative study.

BACKGROUND AND PURPOSE: There have been conflicting results involving the clinical significance of white matter changes in patients with Alzheimer's disease (AD). We studied the association between the volume of white matter hyperintensities (WMHs) on T2-weighted images and cognitive, neurological, and neuropsychiatric symptoms. METHODS: The subjects were 76 AD patients who had WMHs but no obvious cerebrovascular diseases. We quantified the volume of WMHs by using fast-fluid-attenuated inversion recovery images and whole brain atrophy by using 3D spoiled gradient-echo images. Effects of WMHs and brain atrophy on dementia severity, cognitive function, neuropsychiatric disturbances, and neurological findings were examined. RESULTS: Whole brain atrophy was significantly associated with dementia severity and cognitive disturbances, as well as with grasp reflex and some kinds of neuropsychiatric disturbances. After we controlled for the effects of brain atrophy, duration of symptoms, and demographic factors, we found that WMH volume was not associated with global cognitive disturbances or dementia severity but was significantly associated with urinary incontinence, grasp reflex, and aberrant motor behaviors. Brain atrophy and WMH volume were not significantly correlated either before or after controlling for age, sex, education, and duration of symptoms. WMH volume was associated with hypertension, but brain atrophy was not positively correlated with any vascular risk factors. CONCLUSIONS: Our results support the hypothesis that WMHs in AD patients are superimposed phenomena of vascular origin. WMHs contribute to specific neurological and neuropsychiatric manifestations but not to global cognitive impairment, which is more closely associated with brain atrophy.

Regional differences in cerebral blood flow during recitation of the multiplication table and actual calculation: a positron emission tomography study.

UNLABELLED: Regional cerebral differences in activation by two types of calculation, quantitative number processing and use of rote verbal arithmetic memory, were investigated. METHODS: The two types of processing were induced by serial number subtraction (the Subtra-task) and recitation of the multiplication table (the Multi-task), respectively. Regional cerebral blood flow (rCBF) under the two tasks was measured in ten healthy right-handed Japanese men using (15)O-labeled water and positron emission tomography (PET). Statistical parametric mapping (SPM) was used for estimating rCBF differences during these tasks. RESULTS: The activated areas during the Subtra-task were consistent with those reported to be involved in quantitative number processing. Although most of the regions activated during the Multi-task were in common with the regions activated during the Subtra-task, the spatial extent of the activation during the Multi-task was smaller. Moreover, the left lenticular nucleus was activated during the Multi-task, but not in the Subtra-task, while the prefrontal cortex was activated in the Subtra-task but not in the Multi-task. CONCLUSION: The difference in the regions activated by the two tasks, and the difference in the spatial extent of each region by the two tasks indicated that the anatomical networks of the two processes were segregated.

Corticobasal degeneration: evaluation of cortical atrophy by means of hemispheric surface display generated with MR images.

PURPOSE: To determine the characteristics of cortical atrophy in corticobasal degeneration and Alzheimer disease by using a hemispheric surface display generated with magnetic resonance (MR) images. MATERIALS AND METHODS: The magnitude and extent of cortical atrophy were evaluated with MR hemispheric surface display and volumetric measurement in three groups: 17 patients with corticobasal degeneration, 17 matched patients with Alzheimer disease, and 17 matched healthy control subjects. RESULTS: The extent and magnitude of cortical atrophy were larger in the group with corticobasal degeneration than in the group with Alzheimer disease. The parasagittal and paracentral regions were significantly more atrophic in patients with corticobasal degeneration than in patients with Alzheimer disease (P <.05). The mean hemispheric-to-total intracranial volume ratios were significantly smaller in the patients with corticobasal degeneration (61%) and those with Alzheimer disease (64%) than in control subjects (69%). Asymmetry of hemispheric volume was significantly larger in the group with corticobasal degeneration than in the control group. CONCLUSION: The extent of cortical atrophy in corticobasal degeneration is more widespread than was previously thought. Parasagittal and paracentral atrophy is a distinctive feature of corticobasal degeneration and distinguishes it from Alzheimer disease.

Autolysis of calpain large subunit inducing irreversible dissociation of stoichiometric heterodimer of calpain.

Calpain, a calcium dependent cysteine protease, consists of a catalytic large subunit and a regulatory small subunit. Two models have been proposed to explain calpain activation: an autolysis model and a dissociation model. In the autolysis model, the autolyzed form is the active species, which is sensitized to Ca2+. In the dissociation model, dissociated large subunit is the active species. We have reported that the Ca2+ concentration regulates reversible dissociation of subunits. We found further that in chicken micro/m-calpain autolysis of the large subunit induces irreversible dissociation from the small subunit as well as activation. So we could propose a new mechanism for activation of the calpain by combining our findings. Our model insists that autolyzed large subunit remains dissociated from the small subunit even after the removal of Ca2+ to keep it sensitized to Ca2+. This model could be expanded to other calpains and give a new perspective on calpain activation.

Effect of the apolipoprotein E epsilon4 allele on white matter hyperintensities in dementia.

BACKGROUND AND PURPOSE: The clinical significance of the apoE epsilon4 allele in white matter changes in patients with dementia has been a subject of debate. We studied the association between the apoE epsilon4 allele and white matter hyperintensities (WMHs) before and after control for (1) potential vascular risk factors and (2) the presence of lacunar infarcts in patients with dementia. METHODS: The subjects were 131 patients with dementia who had either Alzheimer's disease or vascular dementia, or a combination of these 2 types of dementia, with or without WMHs, lacunar infarcts, or both. The association of the epsilon4 allele with WMHs was examined before and after control for age, sex, duration of symptoms, education level, severity of dementia, presence of lacunar infarcts, and potential vascular risk factors, including hypertension, diabetes mellitus, lipid disorders, smoking habit, drinking habit, and cardiac diseases. RESULTS: WMHs were observed in 73 (55.7%) of the patients. Neither the number of apoE epsilon4 alleles nor their presence was significantly associated with WMHs before or after control for the potential confounding factors. Multiple logistic regression analyses revealed that age, the presence of hypertension, and the presence of lacunar infarcts were independently associated with WMHs. CONCLUSIONS: The apoE epsilon4 allele was not associated with WMHs in patients with dementia. The fact that WMHs were significantly associated with hypertension and lacunar infarcts may indicate an ischemic origin of WMHs.

Features of regional cerebral glucose metabolism abnormality in corticobasal degeneration.

We studied regional cerebral glucose metabolism in 15 patients with a clinical diagnosis of corticobasal degeneration (CBD), 15 patients with probable Alzheimer's disease (AD), and 15 healthy controls for 19 brain regions. Asymmetry in regional glucose metabolism was found in the central and frontal cortices in patients with CBD as compared with either the normal controls or the patients with AD. Regional glucose metabolism in CBD patients was significantly lower in the paracentral and superior parietal areas and thalamus than in patients with AD. Relative glucose metabolism in patients with CBD was significantly higher in the posterior cingulate, medial temporal and basal frontal areas, and significantly lower in the paracentral and superior parietal areas than in those with AD. These features of regional glucose metabolic abnormality in CBD may correspond to neurological and cognitive disturbances peculiar to CBD.

Evaluation of standardized uptake value to assess cerebral glucose metabolism.

PURPOSE: When the cerebral metabolic rate of glucose (CMRglc) is to be measured, arterial blood sampling is usually required for fluorine-18 fluorodeoxyglucose (FDG) and positron emission tomography (PET) studies. However, blood sampling is inconvenient because it requires several staff members and is invasive for patients. METHODS: To assess cerebral glucose metabolism by a noninvasive and simplified method, the authors used the standardized uptake value (SUV), which requires no input function or blood sampling. The study participants included 18 healthy volunteers (4 men and 14 women; mean +/- SD age, 68.2+/-6.3 years), 18 patients with mild Alzheimer's disease (AD) (4 men and 14 women; mean +/- SD age, 68.8+/-7.3 years), and 18 patients with moderate AD (5 men and 13 women, mean +/- SD age, 69.5+/-8.5 years). Regional CMRglc and regional cerebral SUV were measured in the three groups using FDG PET, and the correlation between global CMRglc and global SUV was estimated. RESULTS: The correlation coefficients of global CMRglc and global SUV in the healthy volunteers, mild AD patients, and moderate AD patients were 0.82, 0.67, and 0.62, respectively. Compared with the healthy persons, the patients with mild AD showed significantly decreased CMRglc in the temporal, frontal, and parietal cortices, but they did not show significantly decreased SUV in any region. Patients with moderate AD had significantly decreased CMRglc in the temporal, frontal, occipital, parietal, and sensorimotor cortices and significantly decreased SUV in the temporal, frontal, occipital, and parietal cortices. CONCLUSION: The SUV would be useful as a semiquantitative index of cerebral glucose metabolism only in healthy persons or those with mild AD.

A diagnostic method for suspected Alzheimer's disease using H(2)15O positron emission tomography perfusion Z score.

We developed cerebral perfusion Z score map (Z map) images using H(2)15O and positron emission tomography (PET), and examined their use in diagnosing Alzheimer's disease (AD). Cerebral blood flow (CBF) images were obtained using the PET and H(2)15O autoradiographic method. The best region for normalising the CBF value to remove individual variantion was determined. Then CBF images were transformed to Talairach's standard space, and each pixel value of an individual's image set was normalized to the mean value of the sensorimotor area. Based on the CBF images of 20 normal volunteers, normative mean and standard deviation (SD) CBF images were constructed. Then, each pixel value of the axial CBF images in 28 patients with probable AD and 10 further normal volunteers was converted to a Z score (Z = [normal mean--individual value]/normal SD). A Z map, showing pixels exceeding a threshold of Z score > 2 on MRI of standardised anatomical space was demonstrated. These 38 Z maps were interpreted by four radiologists. When regions in the temporoparietal area were found with Z scores > 2, the subject was diagnosed as having AD. A receiver operating characteristic (ROC) analysis was performed to compare the conventional CBF images and Z maps. The diagnostic performance of the Z map was superior to that of visual inspection of conventional CBF images (mean areas under the ROC curve of the four radiologists were 0.946 and 0.584, respectively). These results indicate that a Z map obtained in this way is superior to conventional PET for diagnosing AD.

Role of functional brain imaging in the evaluation of vascular dementia.

There are various types of underlying damage to tissue and vessels in vascular dementia, including (1) single or multiple infarcts that involve association and limbic cortices, (2) small subcortical infarcts disrupting cortico-subcortical circuits, and (3) white matter lesions. The clinical picture of vascular dementia varies, and the role of functional brain imaging of cerebral blood flow and metabolism would be expected to be different among subtypes of vascular dementia. The role and value of functional brain imaging is limited for cortical infarcts; it is very valuable in assessing the impact on cortical function for small subcortical infarcts; and it is probably useful for evaluating white matter lesions, but this needs to be determined in further studies. At least in research of vascular dementia, functional brain imaging criteria should be included for proper patient selection. Careful studies using functional imaging tools in a well-characterized patient population will be needed.

Regional cerebral glucose metabolism and blood flow in a patient with Marchiafava-Bignami disease.

We report functional neuroimaging studies of a 54-year-old man with Marchiafava-Bignami disease (MBD). Glucose metabolic images obtained by [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography showed diffusely reduced whole brain metabolism and strongly decreased metabolism in the frontal and parietal lobes, orbital gyrus, and thalamus. Cerebral perfusion images showed a similarly decreased radioactivity pattern as the metabolic images. Functional neuroimages would be useful for understanding the pathophysiologic processes of MBD.

Tc-99m ethyl cysteinate dimer SPECT and 2-[F-18]fluoro-2-deoxy-D-glucose PET in Alzheimer's disease. Comparison of perfusion and metabolic patterns.

PURPOSE: This study compared Tc-99m ethyl cysteinate dimer (ECD) SPECT images with 2-[F-18]fluoro-2-deoxy-D-glucose (FDG) PET images in the same patients with Alzheimer's disease and determined whether ECD SPECT is as useful as FDG PET clinically. METHODS: Ten patients with probable Alzheimer's disease (mean +/- SD: age, 71 +/- 5.2 years; 6 women and 4 men; Mini-Mental State Examination score, 19.2 +/- 5.3) were evaluated in this study. Both ECD SPECT and FDG PET were performed within 1.5 months in each patient. RESULTS: ECD SPECT showed a reduction in parieto-temporal perfusion in 8 of the 10 patients, whereas FDG PET showed a reduction in temporoparietal metabolism in 9. The ECD images showed greater radiotracer uptake in the cerebellum and occipital lobe than did FDG images. The contrast between the radiotracer uptake in the sensorimotor area and that in the parietotemporal region was not as great in the ECD images as it was in the FDG images. CONCLUSION: Although ECD SPECT may not be superior to FDG PET, it is useful for the clinical evaluation of patients with Alzheimer's disease.

Regional cerebral blood flow difference between dementia with Lewy bodies and AD.

The authors studied 14 patients with dementia with Lewy bodies (DLB), 14 patients with AD, and 14 healthy control subjects with N-isopropyl-p-[123I]iodoamphetamine SPECT. Comparison with the statistical parametric mappings revealed that relative cerebral blood flow was lower in the occipital lobes and higher in the right medial temporal lobe in the DLB group than in the AD group. Decreased occipital perfusion and relatively well preserved medial temporal perfusion are features that distinguish DLB from AD.

Distinct in vivo and in vitro cytokine profiles of draining lymph node cells in acute and chronic phases of contact hypersensitivity: importance of a type 2 cytokine-rich cutaneous milieu for the development of an early-type response in the chronic phase.

Although regional lymph nodes (LN) have been extensively studied as rich sources of effector T cells in contact hypersensitivity (CH), it remains unknown whether T cell responses in the LN reflect those in effector skin sites. We previously showed that repeated elicitation of CH results in a shift in the time course of Ag-specific CH from a delayed-type hypersensitivity response to an early-type response, a reflection of a shift in cutaneous cytokine expression from a type 1 to a type 2 profile. To investigate whether repeated elicitation of CH could also drive T cell development to the type 2 phenotype in the regional draining LN, sequential cytokine gene expression after hapten application was assessed during both the acute and the chronic phase of CH. In the draining LN the shift to type 2 cytokine production was also observed, but more mixed patterns of responses were induced than in the corresponding skin sites. The chronic LN cells (LNC), when stimulated in vitro, produced markedly lower levels of type 1 cytokines and higher levels of type 2 cytokines than the acute LNC. A successful passive transfer of an early-type response by the LNC was only induced in the recipient mice when the skin sites chronically treated with hapten were elicited. These results indicate that an early-type response by regional LNC would take place only in a milieu with sufficient levels of type 2 cytokines.