Kenichi Shimada

Cerebral perfusion pattern of idiopathic normal pressure hydrocephalus studied by SPECT and statistical brain mapping.

Objectives: To investigate the specific pattern of cerebral blood flow (CBF) in subjects with idiopathic normal pressure hydrocephalus (iNPH) using voxel-based analysis.Methods:N-isopropyl-p-[123I]iodoamphetamine (IMP) single photon emission computed tomography (SPECT) images were performed in 30 iNPH patients, who met probable iNPH criteria, 30 Alzheimer disease (AD) patients and 15 normal control (NC) subjects. Inter-group comparisons between iNPH patients and NC subjects and between AD patients and NC subjects were performed using three-dimensional stereotactic surface projection (3D-SSP) analysis. Individual 3D-SSP images of the iNPH patients were assessed by visual inspection.Results: On the Z-score maps, areas of relative hypoperfusion were recognized around the corpus callosum in all 30 iNPH patients, as well as in the Sylvian fissure regions in 19 of 30 iNPH patients which included artifacts by dilated ventricles and the Sylvian fissures. Ten frontal dominant, eight parietotemporal dominant, and 12 diffuse hypoperfusion types were demonstrated. Inter-group comparison between iNPH and NC subjects showed relative hypoperfusion in the frontal and parietotemporal areas and severe hypoperfusion around the corpus callosum and Sylvian fissure regions, while parietotemporal and posterior cingulate CBF reduction was demonstrated between the AD and NC groups.Conclusion: Voxelbased analysis showed a characteristic pattern of regional CBF reduction with frontal dominant or diffuse cerebral hypoperfusion accompanying severe hypoperfusion around the corpus callosum and Sylvian fissures with artifacts.

Voxel-Based Analysis of Gray Matter and CSF Space in Idiopathic Normal Pressure Hydrocephalus

Aims: To investigate regional morphologic changes in idiopathic normal pressure hydrocephalus (INPH) based on diagnosis with INPH Guidelines using voxel-based morphometry. Method: Three-dimensional magnetic resonance imaging was performed in 34 INPH patients, who met probable INPH criteria, probable 34 Alzheimer disease patients, and 34 normal control subjects. Results: Statistical parametric mapping was used to conduct voxel-based morphometry analysis of the morphologic data and revealed enlarged ventricles and sylvian fissures and stenotic sulci of high convexity, especially in the precuneus in the INPH group, with decreased gray matter density in the insula, caudate and thalamus. Conclusion: In INPH, morphologic change occurs in the frontoparietal high convexity with ventricular dilatations, dilated sylvian fissures and tight sulci in the medial parietal lobes.

Computer-assisted diagnostic system for neurodegenerative dementia using brain SPECT and 3D-SSP

PurposeTo develop a computer-assisted automated diagnostic system to distinguish among Alzheimer disease (AD), dementia with Lewy bodies (DLB), and other degenerative disorders in patients with mild dementia.MethodsSingle photon emission computed tomography (SPECT) images with injection of N-Isopropyl-p-[123I]iodoamphetamine (IMP) were obtained from patients with mild degenerative dementia. First, datasets from 20 patients mild AD, 15 patients with dementia with DLB, and 17 healthy controls were used to develop an automated diagnosing system based on three-dimensional stereotactic surface projections (3D-SSP). AD- and DLB-specific regional templates were created using 3D-SSP, and critical Z scores in the templates were established. Datasets from 50 AD patients, 8 DLB patients, and 10 patients with non-AD/DLB type degenerative dementia (5 with frontotemporal dementia and 5 with progressive supranuclear palsy) were then used to test the diagnostic accuracy of the optimized automated system in comparison to the diagnostic interpretation of conventional IMP-SPECT images. These comparisons were performed to differentiate AD and DLB from non-AD/DLB and to distinguish AD from DLB. A receiver operating characteristic (ROC) analysis was performed.ResultsThe area under the ROC curve (Az) and the accuracy of the automated diagnosis system were 0.89 and 82%, respectively, for AD/DLB vs. non-AD/DLB patients, and 0.70 and 65%, respectively, for AD vs. DLB patients. The mean Az and the accuracy of the visual inspection were 0.84 and 77%, respectively, for AD/DLB vs. non-AD/DLB patients, and 0.70 and 65%, respectively, for AD vs. DLB patients. The mean Az and the accuracy of the combination of visual inspection and this system were 0.96 and 91%, respectively, for AD/DLB vs. non-AD/DLB patients, and 0.70 and 66%, respectively, for AD vs. DLB patients.ConclusionThe system developed in the present study achieved as good discrimination of AD, DLB, and other degenerative disorders in patients with mild dementia as the commonly performed visual inspection of conventional SPECT images. A combination of visual inspection and this system is helpful in the differential diagnosis of patients with mild dementia.

Myocardial scintigraphy may predict the conversion to probable dementia with Lewy bodies.

Objective: To compare the usefulness of brain perfusion SPECT and 123I-metaiodobenzylguanidine (123I-MIBG) in predicting the conversion of possible dementia with Lewy bodies (DLB) to probable DLB. Methods: We examined 94 patients with possible DLB based on the Consensus Criteria for the Clinical Diagnosis of DLB by N-Isopropyl-p-123I-iodoamphetamine (123I-IMP) brain perfusion SPECT and 123I-MIBG myocardial scintigraphy. After 1 year of follow-up, 33 of 94 patients met the criteria for probable DLB. 123I-IMP brain perfusion SPECT and 123I-MIBG myocardial scintigraphy were tested as predictors of the conversion from possible DLB to probable DLB. A receiver operating characteristic (ROC) analysis was performed. Results: The areas under the ROC curves for SPECT for predicting the conversion to probable DLB from possible DLB based on the occipital/cerebellum and occipital/striatum cortex ratios of blood flow counts were 0.591 and 0.585, respectively. The areas under the ROC curves for 123I-MIBG based on the early heart to mediastinum (H/M) ratio, delayed H/M ratio, and washout rate were 0.935, 0.936, and 0.884, respectively. Conclusion: 123I-MIBG myocardial scintigraphy is a good predictor of the future conversion of possible DLB to probable DLB.

Cloning of the cDNA encoding rat Presenilin-1

We isolated rat presenilin-1 (PS-1; also called S182 previously) cDNA from total brain RNA by using a reverse transcription-polymerase chain reaction (RT-PCR) technique with primers homologous to the conserved sequences of human and mouse PS-1. Rat PS-1 cDNA encoded 468 amino acids (aa) and the deduced aa sequence was highly homologous to those of the human (88.4%) and mouse (92.7%). Northern blot analysis of the rat PS-1 cDNA revealed two mRNA species in rat neurotypic pheochromocytoma and glioma cell lines (PC-12 and C6, respectively) that migrated at rates corresponding to approximately 3.0 and 7.5 kb.

Hypoperfusion of the motor cortex associated with parkinsonism in dementia with Lewy bodies

OBJECTIVE This study aimed to investigate the impact of parkinsonism on regional cerebral blood flow (rCBF) in dementia with Lewy bodies (DLB). METHOD Forty-four probable DLB patients, comprising 13 patients without parkinsonism and 31 patients with parkinsonism, and 16 normal controls were selected for this study. We evaluated the rCBF in each group by means of N-isopropyl-p-[(123)I] iodoamphetamine (IMP) and single photon emission computed tomography (SPECT). The rCBF in the different groups was compared using voxel-by-voxel Statistical Parametrical Mapping (SPM). RESULT Patients with DLB showed low rCBF in the frontal, temporal, and occipital cortex with relative sparing of the paracentral region. DLB patients with parkinsonism (DLB-P) had lower rCBF in the primary motor cortex (M1) and left supplementary motor area (SMA) than DLB patients without parkinsonism (DLB-nonP). DLB-nonP patients showed decreased rCBF in the left temporo-occipital region. CONCLUSION This study suggests that two distinct clinical entities are involved in DLB. In addition, CBF changes in the M1 and SMA are seen in the early stages of Parkinsons disease. This result would help in diagnosing DLB in the context of Lewy body (LB) disease.

Automatic Volumetry of the Cerebrospinal Fluid Space in Idiopathic Normal Pressure Hydrocephalus

Objectives: To measure the cerebrospinal fluid (CSF) space volume in idiopathic normal pressure hydrocephalus (INPH), we developed a software that allows us to automatically measure the regional CSF space and compared the volumes of the ventricle systems (VS), Sylvian fissures (SF) and sulci at high convexity and midline (SHM) among INPH patients, Alzheimers disease (AD) patients and healthy volunteers (HVs). Methods: Fifteen INPH patients, 15 AD patients and 15 HVs were retrospectively selected for this study. 3D-T1 MR images were obtained. We improved upon an automatic gray matter volume system to measure CSF spaces, adopting new regions for the template of INPH-characteristic CSF spaces and measured them. The VS, SF and SHM volumes were calculated relative to the intracranial volume. Results: The relative SHM volume of the INPH group (0.0237 ± 0.0064) was the smallest among the 3 groups (AD: 0.0477 ± 0.0109, HV: 0.0542 ± 0.0045). The VS (0.0499 ± 0.0135) and SF (0.0187 ± 0.0037) volumes of the INPH group were significantly larger than those of the AD (VS: 0.0311 ± 0.0075, SF: 0.0146 ± 0.0026) and HV groups (VS: 0.0167 ± 0.0065, SF: 0.0111 ± 0.017). Conclusion: Automatic volume measurement can be used to delineate the characteristic changes in CSF space in patients with INPH and is useful in the diagnosis of INPH.