Takeharu Yoshikawa

Normal aging in the central nervous system: quantitative MR diffusion-tensor analysis.

The purpose of this study is to elucidate changes in mean diffusivity (ADC) and fractional anisotropy (FA) using MR diffusion tensor imaging (DTI) in the central nervous system during normal aging. We studied 50 normal volunteers (30 men, 20 women; mean age 44.8 +/- 14.0; age range, 21-69 years) without disorders affecting the central nervous system. The frontal, parietal white matter, lentiform nucleus, posterior limb of internal capsule, thalamus, genu and splenium of the corpus callosum were selected for investigation. There was no significant difference in ADC or FA between male and female or between the right and left hemisphere. A significant ADC increase with advancing age was observed in frontal white matter (P = 0.010) and lentiform nucleus (P = 0.022). A significant FA decline was found only in the genu of the corpus callosum (P < 0.001) with advancing age. Quantitative diffusion tensor analysis correlate with normal aging and may help in assessing normal age-related changes and serve as a standard for comparison with neurodegenerative disorders.

Spectrum of Epstein-Barr virus-related diseases: a pictorial review

Epstein-Barr virus (EBV) prevails among more than 90% of the adult population worldwide. Most primary infections occur during young childhood and cause no or only nonspecific symptoms; then the virus becomes latent and resides in lymphocytes in the peripheral blood. Inactive latent EBV usually causes no serious consequences, but once it becomes active it can cause a wide spectrum of malignancies: epithelial tumors such as nasopharyngeal and gastric carcinomas; mesenchymal tumors such as follicular dendritic cell tumor/sarcoma; and lymphoid malignancies such as Burkitt lymphoma, lymphomatoid granulomatosis, pyothorax-associated lymphoma, immunodeficiency-associated lymphoproliferative disorders, extranodal natural killer (NK) cell/T-cell lymphoma, and Hodgkin’s lymphoma. The purpose of this article is to describe the spectrum of EBV-related diseases and their key imaging findings. EBV-related lymphoproliferative disorders and lymphomas are especially common in immunocompromised patients. Awareness of their clinical settings and imaging spectrum contributes to early detection and early treatment of possibly life-threatening disorders.

Pancreas divisum as a predisposing factor for chronic and recurrent idiopathic pancreatitis: initial in vivo survey

Background It is a controversial issue whether pancreas divisum (PD) induces pancreatitis. All previous studies have investigated this issue based on endoscopic procedures, which inevitably involve a selection bias. Objectives To determine the unbiased prevalence rate of PD in a community population and to investigate the effect of PD on idiopathic pancreatitis using a non-invasive magnetic resonance (MR) technique. Design Cross-sectional study. Patients The study enrolled 504 subjects from the community who participated in the medical check-up programme and 46 patients with idiopathic pancreatitis (8 acute, 23 chronic, 15 recurrent) extracted from 70 122 consecutive MR studies performed at an academic tertiary care hospital. Interventions All subjects underwent magnetic resonance (MR) scanning and medical examination. Main outcome measures Statistical comparison between subjects from the community and patients with idiopathic pancreatitis was made for the rate of PD (and its subtypes: classical PD, PD with absent ventral duct, and incomplete PD), MR findings, and clinical features. Results Multiple logistic regression analysis revealed PD as a significant factor that induces pancreatitis (OR 23.4; p<0.0001). The PD rate was significantly higher for all/chronic/recurrent idiopathic pancreatitis patients (35%/43%/33%; p<0.001 for all) than for subjects in the community group (2.6%), but was not higher for acute pancreatitis (13%; p=0.357). All PD subtypes were indicated to induce idiopathic pancreatitis but showed different associations with each onset type of pancreatitis. Conclusions This is the first study to describe the prevalence of PD and PD subtypes in a community population and their association with idiopathic pancreatitis in vivo based on the findings of non-invasive MR and with minimal selection bias. It is concluded that PD should be considered a predisposing factor for chronic and recurrent pancreatitis.

Meta-analysis of genome-wide association studies for panic disorder in the Japanese population

Panic disorder (PD) is a moderately heritable anxiety disorder whose pathogenesis is not well understood. Due to the lack of power in previous association studies, genes that are truly associated with PD might not be detected. In this study, we conducted a genome-wide association study (GWAS) in two independent data sets using the Affymetrix Mapping 500K Array or Genome-Wide Human SNP Array 6.0. We obtained imputed genotypes for each GWAS and performed a meta-analysis of two GWAS data sets (718 cases and 1717 controls). For follow-up, 12 single-nucleotide polymorphisms (SNPs) were tested in 329 cases and 861 controls. Gene ontology enrichment and candidate gene analyses were conducted using the GWAS or meta-analysis results. We also applied the polygenic score analysis to our two GWAS samples to test the hypothesis of polygenic components contributing to PD. Although genome-wide significant SNPs were not detected in either of the GWAS nor the meta-analysis, suggestive associations were observed in several loci such as BDKRB2 (P=1.3 × 10−5, odds ratio=1.31). Among previous candidate genes, supportive evidence for association of NPY5R with PD was obtained (gene-wise corrected P=6.4 × 10−4). Polygenic scores calculated from weakly associated SNPs (P<0.3 and 0.4) in the discovery sample were significantly associated with PD status in the target sample in both directions (sample I to sample II and vice versa) (P<0.05). Our findings suggest that large sets of common variants of small effects collectively account for risk of PD.

Two-dimensional thick-slice MR digital subtraction angiography for assessment of cerebrovascular occlusive diseases.

Abstract. Although spatial resolution of current MR angiography is excellent, temporal resolution has remained unsatisfactory. We evaluated clinical applicability of 2D thick-slice, contrast-enhanced subtraction MR angiography (2D-MR digital subtraction angiography) with sub-second temporal resolution in cerebrovascular occlusive diseases. Twenty-five patients with cerebrovascular occlusive diseases (8 moyamoya diseases, 10 proximal internal carotid occlusions, and 2 sinus thromboses ) were studied with a 1.5-T MR unit. The MR digital subtraction angiography (MRDSA) was performed per 0.97 s continuously just after a bolus injection of 15 ml of gadolinium chelates up to 40 s in sagittal (covering hemisphere) or coronal planes. Subtraction images were generated at a workstation. We evaluated imaging quality and hemodynamic information of MRDSA in comparison with those of routine MR imaging, non-contrast MR angiography, and X-ray intra-arterial DSA. Major cerebral arteries, all of the venous sinuses, and most tributaries were clearly visualized with 2D MRDSA. Also, pure arterial phases were obtained in all cases. The MRDSA technique demonstrated prolonged circulation in sinus thromboses, distal patent lumen of proximal occlusion, and some collateral circulation. Such hemodynamic information was comparable to that of intra-arterial DSA. Two-dimensional thick-slice MRDSA with high temporal resolution has a unique ability to demonstrate cerebral hemodynamics equivalent to that of intra-arterial DSA and may play an important role for evaluation of cerebrovascular occlusive diseases.

Time-resolved two-dimensional thick-slice magnetic resonance digital subtraction angiography in assessing brain tumors

Abstract. The aim of this study was to evaluate clinical applicability of two-dimensional (2D) thick-slice, contrast-enhanced magnetic resonance digital subtraction angiography (MRDSA) with high temporal resolution in diagnosis of brain tumors. Forty-four patients with brain tumors including, 15 meningiomas, 8 gliomas, 6 metastatic tumors, 4 neuromas, and 2 hemangioblastomas, were studied with 2D MRDSA with frame rate approximately 1 s. Images were continuously obtained following the initiation of bolus injection of gadolinium chelates for 40 s and subtraction images were generated in a workstation. We evaluated visualization of normal cranial vessels on MRDSA and compared MRDSA and intra-arterial digital subtraction angiography (IADSA) with regard to hemodynamic information. Large cerebral arteries, all venous sinuses, and most tributaries were clearly visualized. A stain was present in hypervascular tumors including all 15 meningiomas and 2 hemangioblastomas on MRDSA. Presence of a stain demonstrated on MRDSA and that on IADSA coincided in 16 of 20 cases (Spearman rank correlation value was 0.85). The location, shape, and phase of the stain on MRDSA were similar to those on IADSA. Two-dimensional MRDSA with high temporal resolution has a unique ability to demonstrate cerebral hemodynamics, such as IADSA, and can play an important role in assessing brain tumors.

Preoperative assessment of hilar cholangiocarcinoma using multidetector-row CT: correlation with histopathological findings.

PurposeOur aim was to investigate the diagnostic reliability of multidetector-row computed tomography (MDCT) for preoperative assessment of local tumoral spread in hilar cholangiocarcinoma.Mateirals and methodsThirteen of 30 consecutive patients with hilar cholangiocarcinoma who underwent surgery, excluding 17 patients who underwent biliary drainage or preoperative portal embolization, were retrospectively evaluated. Using MDCT systems of 4 detector rows or 16 detector rows, plain and dynamic contrast-enhanced images of three phases were obtained. Extent of tumor spread and lymph node metastasis were assessed with MDCT and compared with histopathological findings.ResultsThe Bismuth-Corlette classification of hilar cholangiocarcinoma with MDCT were type I, 1 patient; type IIIa, 3 patients; type IIIb, 4 patients; and type IV, 5 patients; those with histopathological findings were type I, 1 patient; type IIIa, 2 patients; type IIIb, 4 patients; and type IV, 6 patients. One patient diagnosed as type IIIa with MDCT was pathologically diagnosed as type IV. Accuracy of MDCT in tumoral spread was 92.3%, although that of lymph node metastasis was 54%.ConclusionMDCT is likely to play an important role in evaluation of focal lesion spread especially in intrapancreatic tumor invasion, although a greater number of cohort cases are necessary to clearly define its role.

Development of automatic visceral fat volume calculation software for CT volume data.

Objective. To develop automatic visceral fat volume calculation software for computed tomography (CT) volume data and to evaluate its feasibility. Methods. A total of 24 sets of whole-body CT volume data and anthropometric measurements were obtained, with three sets for each of four BMI categories (under 20, 20 to 25, 25 to 30, and over 30) in both sexes. True visceral fat volumes were defined on the basis of manual segmentation of the whole-body CT volume data by an experienced radiologist. Software to automatically calculate visceral fat volumes was developed using a region segmentation technique based on morphological analysis with CT value threshold. Automatically calculated visceral fat volumes were evaluated in terms of the correlation coefficient with the true volumes and the error relative to the true volume. Results. Automatic visceral fat volume calculation results of all 24 data sets were obtained successfully and the average calculation time was 252.7 seconds/case. The correlation coefficients between the true visceral fat volume and the automatically calculated visceral fat volume were over 0.999. Conclusions. The newly developed software is feasible for calculating visceral fat volumes in a reasonable time and was proved to have high accuracy.

A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder

Genome-wide association studies (GWASs) have identified several susceptibility loci for bipolar disorder (BD) and shown that the genetic architecture of BD can be explained by polygenicity, with numerous variants contributing to BD. In the present GWAS (Phase I/II), which included 2964 BD and 61 887 control subjects from the Japanese population, we detected a novel susceptibility locus at 11q12.2 (rs28456, P=6.4 × 10−9), a region known to contain regulatory genes for plasma lipid levels (FADS1/2/3). A subsequent meta-analysis of Phase I/II and the Psychiatric GWAS Consortium for BD (PGC-BD) identified another novel BD gene, NFIX (Pbest=5.8 × 10−10), and supported three regions previously implicated in BD susceptibility: MAD1L1 (Pbest=1.9 × 10−9), TRANK1 (Pbest=2.1 × 10−9) and ODZ4 (Pbest=3.3 × 10−9). Polygenicity of BD within Japanese and trans-European-Japanese populations was assessed with risk profile score analysis. We detected higher scores in BD cases both within (Phase I/II) and across populations (Phase I/II and PGC-BD). These were defined by (1) Phase II as discovery and Phase I as target, or vice versa (for ‘within Japanese comparisons’, Pbest~10−29, R2~2%), and (2) European PGC-BD as discovery and Japanese BD (Phase I/II) as target (for ‘trans-European-Japanese comparison,’ Pbest~10−13, R2~0.27%). This ‘trans population’ effect was supported by estimation of the genetic correlation using the effect size based on each population (liability estimates~0.7). These results indicate that (1) two novel and three previously implicated loci are significantly associated with BD and that (2) BD ‘risk’ effect are shared between Japanese and European populations.

Entorhinal cortex volume measured with 3T MRI is positively correlated with the Wechsler Memory Scale-Revised logical/verbal memory score for healthy subjects

IntroductionPrevious studies revealed a correlation between local brain volume and cognitive function. The aim of the present study was to investigate the correlation between local gray matter volume and the Wechsler Memory Scale-Revised (WMS-R) logical/verbal memory (WMS-R-verbal) score in healthy adults using a 3 Tesla magnetic resonance scanner and voxel-based morphometry (VBM).MethodsT1-weighted magnetic resonance images were obtained in 1,169 healthy adults. The T1-weighted images in native space were bias-corrected, spatially normalized, and segmented into gray matter, white matter, and cerebrospinal fluid images with Statistical Parametric Mapping 5. To investigate regionally the specific effects of the WMS-R-verbal score on the gray matter images, simple regression analysis was performed by VBM treating age, total intracranial volume, and gender as confounding covariates. A P value of less than 0.05 corrected with false discovery rate in voxel difference was considered to be statistically significant.ResultsOur study showed a significant positive correlation between the WMS-R-verbal score and the bilateral entorhinal cortex volume. In the right entorhinal, T value is 4.75, and the size of the clusters is 155 voxels. In the left entorhinal, T value is 4.08, and the size of the clusters is 23 voxels. A significant negative correlation was not found.ConclusionTo our knowledge, this is the first VBM study showing that entorhinal cortex volume is positively correlated with the WMS-R-verbal score for healthy subjects. Therefore, in our structural neuroimaging study, we add evidence to the hypothesis that the entorhinal cortex is involved in verbal memory processing.