Akira Kunimatsu

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.

Three-dimensional white matter tractography by diffusion tensor imaging in ischaemic stroke involving the corticospinal tract

Diffusion tensor MR imaging (DTI) provides information on diffusion anisotropy, which can be expressed with three-dimensional (3D) white matter tractography. We used 3D white matter tractography to show the corticospinal tract in eight patients with acute or early subacute ischaemic stroke involving the posterior limb of the internal capsule or corona radiata and to assess involvement of the tract. Infarcts and the tract were shown simultaneously, providing information on their spatial relationships. In five of the eight patients, 3D fibre tract maps showed the corticospinal tract in close proximity to the infarct but not to pass through it. All these patients recovered well, with maximum improvement from the lowest score on manual muscle testing (MMT) up to the full score through rehabilitation. In the other three patients the corticospinal tract was shown running through the infarct; reduction in MMT did not necessarily improve favourably or last longer, other than in one patient. As 3D white matter tractography can show spatial relationships between the corticospinal tract and an infarct, it might be helpful in prognosis of gross motor function.

Model-based iterative reconstruction technique for ultralow-dose chest CT: comparison of pulmonary nodule detectability with the adaptive statistical iterative reconstruction technique.

PurposeThe purpose of this study was to evaluate whether model-based iterative reconstruction (MBIR) enables dose reduction over adaptive iterative reconstruction (ASIR) while maintaining diagnostic performance. MethodsIn this institutional review board–approved and Health Insurance Portability and Accountability Act–compliant study, 59 patients (mean [SD] age, 64.7 [13.4] years) gave informed consent to undergo reference-, low-, and ultralow-dose chest computed tomography (CT) with 64-row multidetector CT. The reference- and low-dose CT involved the use of automatic tube current modulation with fixed noise indices (31.5 and 70.44 at 0.625 mm, respectively) and were reconstructed with 50% ASIR-filtered back projection blending. The ultralow-dose CT was acquired with a fixed tube current-time product of 5 mA s and reconstructed with MBIR. Two radiologists evaluated 2.5- and 0.625-mm-slice–thick axial images from low-dose ASIR and ultralow-dose MBIR, recorded the pattern of each nodule candidate, and assigned each a confidence score. A reference standard was established by a consensus panel of 2 different radiologists, who identified 84 noncalcified nodules with diameters of 4 mm or greater on reference-dose ASIR (ground-glass opacity, n = 18; partly solid, n = 11; solid, n = 55). Sensitivity in nodule detection was assessed using the McNemar test. Jackknife alternative free-response receiver operating characteristic (JAFROC) analysis was applied to assess the results including confidence scores. ResultsCompared with the low-dose CT, a 78.1% decrease in dose-length product was seen with the ultralow-dose CT. No significant differences were observed between the low-dose ASIR and the ultralow-dose MBIR for overall nodule detection in sensitivity (P = 0.48–0.69) or the JAFROC analysis (P = 0.57). Likewise, no significant differences were seen for ground-glass opacity, partly solid, or solid nodule detection in sensitivity (P = 0.08–0.65) or the JAFROC analysis (P = 0.21–0.90). ConclusionsModel-based iterative reconstruction enables nearly an 80% reduction in radiation dose for chest CT from a low-dose level to an ultralow-dose level, without affecting nodule detectability.

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.

Diminished Medial Prefrontal Activity behind Autistic Social Judgments of Incongruent Information

Individuals with autism spectrum disorders (ASD) tend to make inadequate social judgments, particularly when the nonverbal and verbal emotional expressions of other people are incongruent. Although previous behavioral studies have suggested that ASD individuals have difficulty in using nonverbal cues when presented with incongruent verbal-nonverbal information, the neural mechanisms underlying this symptom of ASD remain unclear. In the present functional magnetic resonance imaging study, we compared brain activity in 15 non-medicated adult males with high-functioning ASD to that of 17 age-, parental-background-, socioeconomic-, and intelligence-quotient-matched typically-developed (TD) male participants. Brain activity was measured while each participant made friend or foe judgments of realistic movies in which professional actors spoke with conflicting nonverbal facial expressions and voice prosody. We found that the ASD group made significantly less judgments primarily based on the nonverbal information than the TD group, and they exhibited significantly less brain activity in the right inferior frontal gyrus, bilateral anterior insula, anterior cingulate cortex/ventral medial prefrontal cortex (ACC/vmPFC), and dorsal medial prefrontal cortex (dmPFC) than the TD group. Among these five regions, the ACC/vmPFC and dmPFC were most involved in nonverbal-information-biased judgments in the TD group. Furthermore, the degree of decrease of the brain activity in these two brain regions predicted the severity of autistic communication deficits. The findings indicate that diminished activity in the ACC/vmPFC and dmPFC underlies the impaired abilities of individuals with ASD to use nonverbal content when making judgments regarding other people based on incongruent social information.

Tract-specific analysis of white matter integrity disruption in schizophrenia

Several studies have suggested that white matter integrity is disrupted in some brain regions in patients with schizophrenia. The purpose of this study was to assess the white matter integrity of the cingulum, uncinate fasciculus, fornix, and corpus callosum using diffusion tensor imaging (DTI). Participants comprised 39 patients with schizophrenia (19 males and 20 females) and 40 age-matched normal controls (20 males and 20 females). We quantitatively assessed the fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of the anterior cingulum, body of the cingulum, uncinate fasciculus, fornix, and corpus callosum on a tract-specific basis using diffusion tensor tractography (DTT). Group differences in FA and ADC between the patients and normal controls were sought. Additional exploratory analyses of the relationship between the FA or ADC and four clinical parameters (i.e., illness duration, positive symptom scores, negative symptom scores, and medication dosage) were performed. Results were analyzed in gender-combined and gender-separated group comparisons. FA was significantly lower on both sides of the anterior cingulum, uncinate fasciculus, and fornix in the schizophrenia patients irrespective of gender group separation. In the gender-combined analyses, significantly higher ADC values were demonstrated in the schizophrenia patients in both sides of the anterior cingulum, body of the cingulum and uncinate fasciculus, the left fornix, and the corpus callosum, compared with those of the normal controls. In the gender-separated analyses, the male patients showed higher ADC in the left anterior cingulum, the bilateral cingulum bodies, and the bilateral uncinate fasciculi. The female patients showed higher ADC in the right anterior cingulum, the left fornix, and the bilateral uncinate fasciculus. In correlation analyses, a significant negative correlation was found between illness duration and ADC in the right anterior cingulum in the gender-combined analyses. The gender-separated analyses found that the male patients had a significant negative correlation between negative symptom scores and FA in the right fornix, a positive correlation between illness duration and FA in the right anterior cingulum, and a negative correlation between illness duration and FA in the left uncinate fasciculus. Our DTI study showed that the integrity of white matter is disrupted in patients with schizophrenia. The results of our sub-analyses suggest that changes in FA and ADC may be related to negative symptom scores or illness duration.

Efficiency of Go/No-Go Task Performance Implemented in the Left Hemisphere

It is well known that the efficiency of response inhibition differs from person to person, but the neural mechanism that implements the efficiency is less understood. In the present fMRI study, we devised an index to evaluate the efficiency of response inhibition in the go/no-go task, and investigated the neural correlates of the efficiency of response inhibition. The human subjects who perform the go/no-go task with a shorter reaction time in go trials (Go-RT) and with a higher percentage of correct no-go trials (Nogo-PC) are thought to have the ability to conduct response inhibition more efficiently. To quantify the efficiency, we defined an efficiency index as the difference in the Nogo-PC between each subject and an ordinarily efficient subject, under the same Go-RT. An across-subject correlation analysis revealed that the brain activity in multiple regions in the left frontal and parietal cortex positively correlated with the efficiency index. Moreover, a test of hemispheric asymmetry with regard to the across-subject correlation revealed left-hemispheric dominance. The significant correlation in the left frontal and parietal regions complements the results of previous studies that used the stop-signal reaction time (SSRT), a well known index to evaluate the efficiency of response inhibition used in the stop-signal task. Our results also indicate that, although it is well known that the neural substrates for response inhibition common in a subject group exist dominantly in the right hemisphere, the neural substrates for efficiency exist dominantly in the left hemisphere.

Cerebral Hemodynamic Impairment: Assessment with Resting-State Functional MR Imaging

PURPOSE To test the feasibility of noninvasive global assessment of cerebral hemodynamic impairment with use of resting-state blood oxygenation level-dependent functional magnetic resonance (MR) imaging. MATERIALS AND METHODS In this institutional review board-approved study, five patients with chronic hypoperfusion without neurologic impairment and six patients with acute stroke underwent 10-minute resting-state functional MR imaging and dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging, which was considered the standard of reference. All patients gave informed consent. The temporal shift of low-frequency signal fluctuations in each voxel compared with the averaged whole brain or global mean signal at resting-state functional MR imaging and the delay in time to peak at dynamic susceptibility-weighted contrast-enhanced perfusion imaging were computed with voxel-wise analysis. The similarity of the temporal delay maps obtained with resting-state functional MR imaging and perfusion data, as well as the stability of the resting-state functional MR imaging measurement, were evaluated with the Dice similarity coefficient (DSC) and the two-tailed t test (random-effect analysis). RESULTS The brain tissue with normal perfusion at dynamic susceptibility-weighted contrast-enhanced imaging showed no delay to global mean signal at resting-state functional MR imaging, whereas areas of abnormal perfusion with delayed time to peak (3.4 seconds ± 2.1) showed a delay at resting-state functional MR imaging that was similar to the time to peak at dynamic susceptibility-weighted contrast-enhanced perfusion imaging, both in spatial coverage (mean DSC, 0.57 ± 0.16) and tendency (t = 5.1, P < .001). Resting-state functional MR imaging measurements were highly stable (mean DSC, 0.83 ± 0.12). CONCLUSION Resting-state functional MR imaging temporal-shift analysis can noninvasively demonstrate the extent and degree of perfusion delay in patients with hypoperfusion both with and without neurologic deficit.

Comparison of pure and hybrid iterative reconstruction techniques with conventional filtered back projection: image quality assessment in the cervicothoracic region.

OBJECTIVES To evaluate the impact on image quality of three different image reconstruction techniques in the cervicothoracic region: model-based iterative reconstruction (MBIR), adaptive statistical iterative reconstruction (ASIR), and filtered back projection (FBP). METHODS Forty-four patients underwent unenhanced standard-of-care clinical computed tomography (CT) examinations which included the cervicothoracic region with a 64-row multidetector CT scanner. Images were reconstructed with FBP, 50% ASIR-FBP blending (ASIR50), and MBIR. Two radiologists assessed the cervicothoracic region in a blinded manner for streak artifacts, pixilated blotchy appearances, critical reproduction of visually sharp anatomical structures (thyroid gland, common carotid artery, and esophagus), and overall diagnostic acceptability. Objective image noise was measured in the internal jugular vein. Data were analyzed using the sign test and pair-wise Students t-test. RESULTS MBIR images had significant lower quantitative image noise (8.88 ± 1.32) compared to ASIR images (18.63 ± 4.19, P<0.01) and FBP images (26.52 ± 5.8, P<0.01). Significant improvements in streak artifacts of the cervicothoracic region were observed with the use of MBIR (P<0.001 each for MBIR vs. the other two image data sets for both readers), while no significant difference was observed between ASIR and FBP (P>0.9 for ASIR vs. FBP for both readers). MBIR images were all diagnostically acceptable. Unique features of MBIR images included pixilated blotchy appearances, which did not adversely affect diagnostic acceptability. CONCLUSIONS MBIR significantly improves image noise and streak artifacts of the cervicothoracic region over ASIR and FBP. MBIR is expected to enhance the value of CT examinations for areas where image noise and streak artifacts are problematic.

Radiofrequency Ablation of the Liver: Determination of Ablative Margin at MR Imaging with Impaired Clearance of Ferucarbotran—Feasibility Study

Institutional review board approval and informed consent were obtained. The feasibility of magnetic resonance (MR) imaging with impaired clearance of ferucarbotran to visualize ablated liver parenchyma surrounding a tumor (ablative margin [AM]) was evaluated after radiofrequency (RF) ablation of the liver. Twenty-one patients with hepatocellular carcinomas underwent RF ablation 2-7 hours after ferucarbotran-enhanced MR imaging. On unenhanced T2*-weighted images acquired after 3-5 days, AMs appeared as hypointense rims. The AM status was related to incidence of residual or recurrent tumors. This technique is feasible for visualization of AM and prediction of residual or recurrent tumors after RF ablation of the liver.