Hidemasa Takao

Free-breathing diffusion-weighted imaging for the assessment of inflammatory activity in Crohn's disease.

To investigate the application of free‐breathing diffusion‐weighted MR imaging (DWI) to the assessment of disease activity in Crohns disease.

Effects of Age and Gender on White Matter Integrity

BACKGROUND AND PURPOSE: DTI provides a sensitive measure of change in the microstructure of white matter integrity. The purpose of our study was to investigate age-related changes, sex differences, and age-by-sex interactions in white matter integrity (FA, AD, and RD) across the whole brain with a large sample. MATERIALS AND METHODS: A total of 857 healthy subjects (mean age = 56.1 ± 9.9 years; age range = 24.9–84.8 years) were included in this study. All subjects were scanned at 3T. With use of TBSS, we examined the effects of age and sex on FA, AD, and RD in the white matter. RESULTS: Global FA was negatively correlated with age (R2 = 0.18, P < .0001), and global AD and RD were positively correlated with age (AD: R2 = 0.02, P < .0001; RD: R2 = 0.19, P < .0001). The correlation between age and global AD, however, was weak. Voxelwise analysis revealed a number of regions where FA was negatively correlated with age, with most of these regions showing a significant positive correlation between RD and age. There was a significant age-related FA increase in several white matter regions. Voxelwise analysis also revealed many regions where FA, AD, or RD differed between men and women; however, no region showed a significant interaction between age and sex. CONCLUSIONS: Our results suggest that age-related changes in white matter integrity are more strongly associated with myelin sheath degeneration than with axonal degeneration, and that, in some specific regions, the number of remyelinated axons might increase with age. Our results also suggest that there are no sex differences in the aging process of the white matter.

Mitigation of Sociocommunicational Deficits of Autism Through Oxytocin-Induced Recovery of Medial Prefrontal Activity: A Randomized Trial

IMPORTANCE Sociocommunicational deficits make it difficult for individuals with autism spectrum disorders (ASD) to understand communication content with conflicting verbal and nonverbal information. Despite growing prospects for oxytocin as a therapeutic agent for ASD, no direct neurobiological evidence exists for oxytocins beneficial effects on this core symptom of ASD. This is slowing clinical application of the neuropeptide. OBJECTIVE To directly examine whether oxytocin has beneficial effects on the sociocommunicational deficits of ASD using both behavioral and neural measures. DESIGN, SETTING, AND PARTICIPANTS At the University of Tokyo Hospital, we conducted a randomized, double-blind, placebo-controlled, within-subject-crossover, single-site experimental trial in which intranasal oxytocin and placebo were administered. A total of 40 highly functioning men with ASD participated and were randomized in the trial. INTERVENTIONS Single-dose intranasal administration of oxytocin (24 IU) and placebo. MAIN OUTCOMES AND MEASURES Using functional magnetic resonance imaging, we examined effects of oxytocin on behavioral neural responses of the participants to a social psychological task. In our previous case-control study using the same psychological task, when making decisions about social information with conflicting verbal and nonverbal contents, participants with ASD made judgments based on nonverbal contents less frequently with longer time and could not induce enough activation in the medial prefrontal cortex. Therefore, our main outcomes and measures were the frequency of the nonverbal information-based judgments (NVJs), the response time for NVJs, and brain activity of the medial prefrontal cortex during NVJs. RESULTS Intranasal oxytocin enabled the participants to make NVJs more frequently (P = .03) with shorter response time (P = .02). During the mitigated behavior, oxytocin increased the originally diminished brain activity in the medial prefrontal cortex (P < .001). Moreover, oxytocin enhanced functional coordination in the area (P < .001), and the magnitude of these neural effects was predictive of the behavioral effects (P ≤ .01). CONCLUSIONS AND RELEVANCE These findings provide the first neurobiological evidence for oxytocins beneficial effects on sociocommunicational deficits of ASD and give us the initial account for neurobiological mechanisms underlying any beneficial effects of the neuropeptide. TRIAL REGISTRATION umin.ac.jp/ctr Identifier: UMIN000002241 and UMIN000004393.

Clinical and neural effects of six-week administration of oxytocin on core symptoms of autism.

Autism spectrum disorder is a prevalent neurodevelopmental disorder with no established pharmacological treatment for its core symptoms. Although previous literature has shown that single-dose administration of oxytocin temporally mitigates autistic social behaviours in experimental settings, it remains in dispute whether such potentially beneficial responses in laboratories can result in clinically positive effects in daily life situations, which are measurable only in long-term observations of individuals with the developmental disorder undergoing continual oxytocin administration. Here, to address this issue, we performed an exploratory, randomized, double-blind, placebo-controlled, crossover trial including 20 high-functional adult males with autism spectrum disorder. Data obtained from 18 participants who completed the trial showed that 6-week intranasal administration of oxytocin significantly reduced autism core symptoms specific to social reciprocity, which was clinically evaluated by Autism Diagnostic Observation Scale (P = 0.034, PFDR < 0.05, Cohens d = 0.78). Critically, the improvement of this clinical score was accompanied by oxytocin-induced enhancement of task-independent resting-state functional connectivity between anterior cingulate cortex and dorso-medial prefrontal cortex (rho = -0.60, P = 0.011), which was measured by functional magnetic resonance imaging. Moreover, using the same social-judgement task as used in our previous single-dose oxytocin trial, we confirmed that the current continual administration also significantly mitigated behavioural and neural responses during the task, both of which were originally impaired in autistic individuals (judgement tendency: P = 0.019, d = 0.62; eye-gaze effect: P = 0.03, d = 0.56; anterior cingulate activity: P = 0.00069, d = 0.97; dorso-medial prefrontal activity: P = 0.0014, d = 0.92; all, PFDR < 0.05). Furthermore, despite its longer administration, these effect sizes of the 6-week intervention were not larger than those seen in our previous single-dose intervention. These findings not only provide the evidence for clinically beneficial effects of continual oxytocin administration on the core social symptoms of autism spectrum disorder with suggesting its underlying biological mechanisms, but also highlight the necessity to seek optimal regimens of continual oxytocin treatment in future studies.

Gray and white matter asymmetries in healthy individuals aged 21-29 years: a voxel-based morphometry and diffusion tensor imaging study.

The hemispheres of the human brain are functionally and structurally asymmetric. The study of structural asymmetries provides important clues to the neuroanatomical basis of lateralized brain functions. Previous studies have demonstrated age‐related changes in morphology and diffusion properties of brain tissue. In this study, we simultaneously explored gray and white matter asymmetry using voxel‐based morphometry (VBM) and diffusion tensor imaging (DTI) in 109 young healthy individuals (58 females and 51 males). To eliminate the potential confounding effects of aging and handedness, we restricted the study to right‐handed subjects aged 21–29 years. VBM and voxel‐based analysis of fractional anisotropy (FA) maps derived from DTI revealed a number of gray matter volume asymmetries (including the right frontal and left occipital petalias and leftward asymmetry of the planum temporale) and white matter FA asymmetries (including leftward asymmetry of the arcuate fasciculus, cingulum, and corticospinal tract). There was no significant effect of sex on gray and white matter asymmetry. Leftward volume asymmetry of the planum temporale and leftward FA asymmetry of the arcuate fasciculus were simultaneously demonstrated. Post hoc analysis showed that the gray matter volume of the planum temporale and FA of the arcuate fasciculus were positively related (Pearson correlation coefficient, 0.43; P < 0.0001). The results of our study demonstrate gray and white matter asymmetry in right‐handed healthy young adults and suggest that leftward volume asymmetry of the planum temporale and leftward FA asymmetry of the arcuate fasciculus may be related. Hum Brain Mapp, 2010.

Detection of hepatocellular carcinoma by Gd-EOB-DTPA-enhanced liver MRI: comparison with triple phase 64 detector row helical CT.

PURPOSE To compare the diagnostic performance of Gd-EOB-DTPA-enhanced MRI with that of triple phase 64-MDCT in the detection of hepatocellular carcinoma (HCC). PATIENTS AND METHODS Thirty-four patients with 52 surgically proven lesions underwent Gd-EOB-DTPA-enhanced MRI and triple phase 64-MDCT. Two observers independently evaluated MR and CT imaging on a lesion-by-lesion basis. Sensitivity, positive and negative predictive values and reproducibility were evaluated. The diagnostic accuracy of each modality was assessed with alternative-free response receiver operating characteristic (ROC) analysis. RESULTS Both observers showed higher sensitivity in detecting lesions with MRI compared to CT, however, only the difference between the two imaging techniques for observer 2 was significant (P=0.034). For lesions 1cm or smaller, MRI and CT showed equal sensitivity (both 62.5%) with one observer, and MRI proved superior to CT with the other observer (MRI 75% vs. CT 56.3%), but the latter difference was not significant (P=0.083). The difference in positive and negative predictive value between the two imaging techniques for each observer was not significant (P>0.05). The areas under the ROC curve for each observer were 0.843 and 0.861 for MRI vs. 0.800 and 0.833 for CT and the differences were not significant. Reproducibility was higher using MRI for both observers, but the result was not significant (MRI 32/33 vs. CT 29/33, P=0.083). CONCLUSION Gd-EOB-DTPA-enhanced MRI tended to show higher diagnostic accuracy, sensitivity and reproducibility compared to triple phase 64-MDCT in the detection of hepatocellular carcinoma, however statistical significance was not achieved.

Relationship between liver function and liver signal intensity in hepatobiliary phase of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging.

Objective: To evaluate the effect of liver function on liver signal intensity in gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging in humans and to examine the biochemical factors related to signal intensity in the hepatobiliary phase. Methods: This study included 48 patients with suspected hepatocellular carcinoma or metachronous liver metastases from colorectal cancer. The patients were divided into 2 groups: the chronic liver dysfunction and the normal liver function. All the individuals of both groups had magnetic resonance imaging before injection and at 5, 10, 15, 20, 25, and 30 minutes after bolus administration of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid. The time point when the mean liver signal-to-noise ratio (SNR) reached a peak was determined for each group, and the mean liver SNR at the peak point was compared between the groups. In all the patients, stepwise multivariate analysis was used to evaluate the relationship between the liver SNR at the peak time point and the laboratory data, using the following biochemical factors: prothrombin time, total bilirubin level, cholinesterase level, albumin level, creatinine level, indocyanine green retention rate at 15 minutes, and Child-Pugh score. Results: The mean values of liver SNR increased gradually. The mean liver SNR reached peak at 30 minutes after contrast injection in both groups and was significantly lower in the chronic liver dysfunction group than in the normal liver function group. Indocyanine green retention rate at 15 minutes was the only significant contributor to the liver signal intensity at the peak time point (30 minutes). Conclusions: The degree of liver enhancement in the hepatobiliary phase may reflect liver cell function. The measurement of liver signal intensity in the hepatobiliary phase may be useful in predicting whole and regional hepatic functional reserves.

MR imaging of the biliary tract with Gd-EOB-DTPA: effect of liver function on signal intensity.

OBJECTIVE To quantitatively evaluate the signal intensity of the biliary tract in gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance (MR) imaging and to investigate the effect of liver function on the signal intensity of the biliary tract. MATERIALS AND METHODS A total of 32 patients with and without chronic liver disease (normal liver group, n = 15; chronic liver disease group, n = 17) were included in this study. All patients were prospectively enrolled for evaluation of known or suspected focal liver lesions. In the chronic liver disease group, the etiologies were chronic hepatitis C virus infection (n = 12) and chronic hepatitis B virus infection (n = 5). The median Child-Pugh score was 5 (range, 5-7). Each patient received the standard dose of Gd-EOB-DTPA (0.025 mmol/kg of body weight). Post-contrast T1-weighted MR images were obtained at 5, 10, 15, 20, 25, and 30 min after administration of Gd-EOB-DTPA. Maximum signal intensities (SIs) of the right and left hepatic ducts, common hepatic duct, and common bile duct were measured. Relative signal intensity was calculated as follows: relative SI = maximum SI(bileduct)/mean SI(muscle). Serum albumin level, serum total bilirubin level, prothrombin time, indocyanine green retention rate at 15 min (ICG-R15), and estimated glomerular filtration rate were entered into regression analysis. RESULTS The signal intensity of the bile duct reached a peak 30 min after administration of Gd-EOB-DTPA. The mean relative signal intensity of the right and left hepatic ducts at the peak time point was not significantly different between the two groups, while increase in signal intensity was delayed in the chronic liver disease group. The mean relative signal intensity of the common hepatic duct and that of the common bile duct at the peak time point were significantly different between the two groups (Wilcoxon rank-sum test, P = 0.03, respectively). Stepwise regression analysis revealed that ICG-R15 was a significant predictor of the signal intensity of the bile duct (right and left hepatic ducts, P = 0.04; common hepatic duct, P = 0.008; common bile duct, P = 0.003). CONCLUSIONS The results of our study demonstrate that the presence of chronic liver disease significantly affects the signal intensity of the bile duct in Gd-EOB-DTPA-enhanced MR imaging. ICG-R15 was only a significant predictor of the signal intensity of the bile duct. The signal intensity of the bile duct may reflect underlying liver function.

Reduced Frontal Glutamate + Glutamine and N-Acetylaspartate Levels in Patients With Chronic Schizophrenia but not in Those at Clinical High Risk for Psychosis or With First-Episode Schizophrenia

Changes in brain pathology as schizophrenia progresses have been repeatedly suggested by previous studies. Meta-analyses of previous proton magnetic resonance spectroscopy ((1)H MRS) studies at each clinical stage of schizophrenia indicate that the abnormalities of N-acetylaspartate (NAA) and glutamatergic metabolites change progressively. However, to our knowledge, no single study has addressed the possible differences in (1)H MRS abnormalities in subjects at 3 different stages of disease, including those at ultrahigh risk for psychosis (UHR), with first-episode schizophrenia (FES), and with chronic schizophrenia (ChSz). In the current study, 24 patients with UHR, 19 FES, 25 ChSz, and their demographically matched 3 independent control groups (n = 26/19/28 for the UHR, FES, and ChSz control groups, respectively) underwent (1)H MRS in a 3-Tesla scanner to examine metabolites in medial prefrontal cortex. The analysis revealed significant decreases in the medial prefrontal NAA and glutamate + glutamine (Glx) levels, specifically in the ChSz group as indexed by a significant interaction between stage (UHR/FES/ChSz) and clinical status (patients/controls) (P = .008). Furthermore, the specificity of NAA and Glx reductions compared with the other metabolites in the patients with ChSz was also supported by a significant interaction between the clinical status and types of metabolites that only occurred at the ChSz stage (P = .001 for NAA, P = .004 for Glx). The present study demonstrates significant differences in (1)H MRS abnormalities at different stages of schizophrenia, which potentially correspond to changes in glutamatergic neurotransmission, plasticity, and/or excitotoxicity and regional neuronal integrity with relevance for the progression of schizophrenia.

Voxel-based analysis of the diffusion tensor

IntroductionDiffusion tensor imaging (DTI) has provided important insights into the neurobiological basis for normal development and aging and various disease processes in the central nervous system. The aim of this article is to review the current protocols for DTI acquisition and preprocessing and statistical testing for a voxelwise analysis of DTI, focused on statistical parametric mapping (SPM) and tract-based spatial statistics (TBSS).MethodsWe tested the effects of distortion correction induced by gradient nonlinearity on fractional anisotropy (FA) maps or FA skeletons processed via two SPM-based methods (coregistration and FA template methods), or TBSS-based method, respectively.ResultsWith two SPM-based methods, we found similar results in some points (e.g., significant FA elevation for uncorrected images in anterior-dominant white matter and for corrected images in bilateral middle cerebellar peduncles) and different results in other points (e.g., significantly larger FA for corrected images with coregistration method, but significantly smaller with FA template method in bilateral internal capsules, extending to corona radiata, and semioval centers). In contrast, there was no area with significant difference between uncorrected and corrected FA skeletons with TBSS-based method.ConclusionThe discrepancy among these results was not explained in full, but possible explanations were misregistration and smoothing for the SPM-based methods and insensitivity to FA changes outside the local centers of white matter bundles for TBSS-based method.