掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

<title>Abstract</title>An increase in number of neurons is presumed to underlie the enhancement of cognitive abilities in brain evolution. The evolution of human cognition is then expected to have accompanied a prolongation of net neural-processing time due to the accumulation of processing time of individual neurons over an expanded number of neurons. Here, we confirmed this prediction and quantified the amount of prolongation in vivo, using noninvasive measurements of brain responses to sounds in unanesthetized human and nonhuman primates. Latencies of the N1 component of auditory-evoked potentials recorded from the scalp were approximately 40, 50, 60, and 100 ms for the common marmoset, rhesus monkey, chimpanzee, and human, respectively. Importantly, the prominent increase in human N1 latency could not be explained by the physical lengthening of the auditory pathway, and therefore reflected an extended dwell time for auditory cortical processing. A longer time window for auditory cortical processing is advantageous for analyzing time-varying acoustic stimuli, such as those important for speech perception. A novel hypothesis concerning human brain evolution then emerges: the increase in cortical neuronal number widened the timescale of sensory cortical processing, the benefits of which outweighed the disadvantage of slow cognition and reaction.

DOI： 10.1038/s41598-022-05053-w

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その他リンク： https://www.nature.com/articles/s41598-022-05053-w

掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI AG  

Background: Elucidation of the mechanism of amyloid-β accumulation plays an important role in therapeutic strategies for Alzheimer’s disease (AD). The aim of this study is to elucidate the relationship between the function of the blood–cerebrospinal fluid barrier (BCSFB) and the clearance of amyloid-β (Aβ). Methods: Twenty-five normal older adult volunteers (60–81 years old) participated in this PET study for clarifying the relationship between interstitial water flow and Aβ accumulation. Water dynamics were analyzed using two indices in [15O]H2O PET, the influx ratio (IR) and drain rate (DR), and Aβ accumulation was assessed qualitatively by [18F]flutemetamol PET. Results: [15O]H2O PET examinations conducted initially and after 2 years showed no significant changes in both indices over the 2-year period (IR: 1.03 ± 0.21 and 1.02 ± 0.20, DR: 1.74 ± 0.43 and 1.67 ± 0.47, respectively). In [18F]flutemetamol PET, on the other hand, one of the 25 participants showed positive results and two showed positive changes after 2 years. In these three participants, the two indices of water dynamics showed low values at both periods (IR: 0.60 ± 0.15 and 0.60 ± 0.13, DR: 1.24 ± 0.12 and 1.11 ± 0.10). Conclusions: Our results indicated that BCSFB function disturbances could be followed by Aβ accumulation, because the reduced interstitial flow preceded amyloid accumulation in the positive-change subjects, and amyloid accumulation was not observed in the older adults with sufficiently high values for the two indices. We believe that further elucidation of interstitial water flow will be the key to developing therapeutic strategies for AD, especially with regard to prevention.

DOI： 10.3390/jcm11206118

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掲載種別：研究論文（学術雑誌）  

DOI： 10.3174/ajnr.A7666

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.ynirp.2022.100116

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Persistent postural-perceptual dizziness (PPPD) is a chronic vestibular syndrome lasting more than 3 months. The core vestibular symptoms are dizziness, unsteadiness, and non-spinning vertigo, which are exacerbated by upright posture or walking, active or passive motion, and exposure to moving or complex visual stimuli. Among these, visual exacerbation is a key feature of PPPD for which the neural mechanisms are unknown. We hypothesized that vestibular symptoms may be exacerbated by visual stimuli through gaze behavioral change after exposure to moving or complex visual stimuli. The study aimed to examine gaze stability after exposure to moving visual stimuli in patients with PPPD. METHODS: Fourteen healthy controls (HCs), 27 patients with PPPD, and 12 patients with unilateral vestibular hypofunction (UVH), showing chronic vestibular symptoms for >3 months, were enrolled in the study. The participants were instructed to fixate on the gazing point at the center of a screen for 30 s before and after 90 s of exposure to moving visual stimuli. Gaze stability, best represented by the bivariate contour ellipse area (BCEA), was compared among three groups, both before and after exposure to the moving visual stimuli. Comparisons between pre- and post-moving visual stimuli in BCEA were also conducted. Correlation between the post/pre ratio of BCEA and vestibular tests, several clinical symptom scales including the Dizziness Handicap Inventory, Niigata PPPD Questionnaire, and Hospital Anxiety and Depression Scale, and the exacerbation of dizziness by exposure to moving visual stimuli was examined in the PPPD group. RESULTS: BCEA, both before and after exposure to moving visual stimuli in the PPPD group, was not different from that in HC and UVH groups. In the PPPD group, BCEA increased significantly after exposure to moving visual stimuli. The post/pre ratio of BCEA correlated with the occurrence of exacerbation of the dizziness sensation by exposure to moving visual stimuli; however, it did not correlate with vestibular tests or clinical symptom scales. CONCLUSION: Patients with PPPD were more likely to exhibit gaze instability after exposure to moving visual stimuli, which potentially exacerbated vestibular symptoms. This phenomenon may help elucidate the neural mechanisms of visual exacerbation in patients with PPPD.

DOI： 10.3389/fnhum.2022.1056556

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Hindawi Limited  

The glycine level in the brain is known to be altered in neuropsychiatric disorders, such as schizophrenia and Alzheimer’s disease (AD). Several studies have reported the in vivo measurement of glycine concentrations in the brain using proton magnetic resonance spectroscopy (1H-MRS), but 1H-MRS is not capable of imaging the distribution of glycine concentration with high spatial resolution. Chemical exchange saturation transfer magnetic resonance imaging (CEST-MRI) is a new technology that can detect specific molecules, including amino acids, in tissues. To validate the measurements of glycine concentrations in living tissues using CEST from glycine to water (GlyCEST), we extracted the brain tissues from mice and performed biochemical tests. In wild-type C57BL/6 mice, GlyCEST effects were found to be higher in the thalamus than in the cerebral cortex (<inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M1">
<mi>P</mi>
<mo>&lt;</mo>
<mn>0.0001</mn>
</math>
</inline-formula>, paired t-test), and this result was in good agreement with the biochemical results. In 5xFAD mice, an animal model of AD, GlyCEST measurements demonstrated that glycine concentrations in the cerebral cortex (<inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M2">
<mi>P</mi>
<mo>&lt;</mo>
<mn>0.05</mn>
</math>
</inline-formula>, unpaired t-test) and thalamus (<inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M3">
<mi>P</mi>
<mo>&lt;</mo>
<mn>0.0001</mn>
</math>
</inline-formula>, unpaired t-test), but not in the hippocampus, were decreased compared to those in wild-type mice. These findings suggest that we have successfully applied the CEST-MRI technique to map the distribution of glycine concentrations in the murine brain. The present method also captured the changes in cerebral glycine concentrations in mice with AD. Imaging the distribution of glycine concentrations in the brain can be useful in investigating and elucidating the pathological mechanisms of neuropsychiatric disorders.

DOI： 10.1155/2021/8988762

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その他リンク： http://downloads.hindawi.com/journals/cmmi/2021/8988762.xml

記述言語：英語   掲載種別：研究論文（学術雑誌）  

We have previously published a study on the reliable detection of 2-hydroxyglutarate (2HG) in lower-grade gliomas by magnetic resonance spectroscopy (MRS). In this short article, we re-evaluated five glioma cases originally assessed as isocitrate dehydrogenase (IDH) wildtype, which showed a high accumulation of 2HG, and were thought to be false-positives. A new primer was used for the detection of IDH2 mutation by Sanger sequencing. Adequate tissue for DNA analysis was available in 4 out of 5 cases. We found rare IDH2 mutations in two cases, with IDH2 R172W mutation in one case and IDH2 R172K mutation in another case. Both cases had very small mutant peaks, suggesting that the tumor volume was low in the tumor samples. Thus, the specificity of MRS for detecting IDH1/2 mutations was higher (81.3%) than that originally reported (72.2%). The detection of 2HG by MRS can aid in the diagnosis of rare, non-IDH1-R132H IDH1 and IDH2 mutations in gliomas.

DOI： 10.3390/diagnostics11112129

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Cerebral small vessel disease (CSVD) causes dementia and gait disturbance due to arteriopathy. Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a hereditary form of CSVD caused by loss of high-temperature requirement A1 (HTRA1) serine protease activity. In CARASIL, arteriopathy causes intimal thickening, smooth muscle cell (SMC) degeneration, elastic lamina splitting, and vasodilation. The molecular mechanisms were proposed to involve the accumulation of matrisome proteins as substrates or abnormalities in transforming growth factor β (TGF-β) signaling. Here, we show that HTRA1-/- mice exhibited features of CARASIL-associated arteriopathy: intimal thickening, abnormal elastic lamina, and vasodilation. In addition, the mice exhibited reduced distensibility of the cerebral arteries and blood flow in the cerebral cortex. In the thickened intima, matrisome proteins, including the hub protein fibronectin (FN) and latent TGF-β binding protein 4 (LTBP-4), which are substrates of HTRA1, accumulated. Candesartan treatment alleviated matrisome protein accumulation and normalized the vascular distensibility and cerebral blood flow. Furthermore, candesartan reduced the mRNA expression of Fn1, Ltbp-4, and Adamtsl2, which are involved in forming the extracellular matrix network. Our results indicate that these accumulated matrisome proteins may be potential therapeutic targets for arteriopathy in CARASIL.

DOI： 10.1172/JCI140555

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記述言語：日本語   出版者・発行元：(一社)日本脳循環代謝学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To assess the effect of maintenance therapy on visual outcomes in preventing recurrences one year after first onset in patients with aquaporin-4 antibody (AQP4Ab)-positive optic neuritis. STUDY DESIGN: Retrospective study. METHODS: The medical charts of 56 patients with optic neuritis (22 with AQP4Ab-positive and 34 with AQP4Ab-negative) at Niigata University Medical and Dental Hospital were retrospectively analyzed. Clinical characteristics, including visual acuity and number of recurrences one year after first onset, were compared among patients who were AQP4Ab-positivie with and those without maintenance therapy such as oral prednisolone and azathioprine, as well as those who were AQP4Ab-negative. RESULTS: The mean ages were 49.3 and 45.2 years in the AQP4Ab-positive and the AQP4Ab-negative groups. The female to male ratio was 21:1 and 18:16 in the two groups, respectively. Multiple between-group comparison showed a statistically significant difference in visual acuity one year after first onset between the AQP4Ab-positive without maintenance therapy group and the AQP4Ab-negative group (0.05 (median, same applies below) vs. 1.0, p < 0.01). There was also a statistically significant difference in the number of recurrences in the year after first onset between the AQP4Ab-positive with and without maintenance therapy groups (1 vs. 0, p < 0.01). CONCLUSION: This study demonstrates that patients with AQP4Ab-positive optic neuritis without maintenance therapy had the poorest visual acuity and the most recurrences one year after first onset. These results indicate that reducing the number of recurrences with maintenance therapy could improve the visual outcomes in patients with AQP4Ab-positive optic neuritis.

DOI： 10.1007/s10384-021-00858-0

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記述言語：日本語   出版者・発行元：日本脳腫瘍病理学会  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Proton magnetic resonance spectroscopy(1H-MRS)is a non-invasive method for evaluating brain function and metabolism. 1H-MRS can quantify low-molecular-weight metabolites in a living brain; it shows their spectra without tracer administration. In this paper, we introduce 1H-MRS and MRS for imaging the distribution of metabolites. The applications of 1H-MRS imaging for several neurological disorders will be outlined.

DOI： 10.11477/mf.1436204411

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: Details of the posterior eye water dynamics are unclear. Aquaporin-4 (AQP4), a water channel, plays an important role in water dynamics in the central nervous system and is also present in the ocular tissue. The purpose of this study was to reveal the role of AQP4 in the water dynamics of the posterior eye using in vivo JJ vicinal coupling proton exchange (JJVCPE) magnetic resonance imaging (MRI) of AQP4 knockout (KO) mice and their wild-type littermates (controls). Methods: JJVCPE MRI of the eye was performed on five AQP4 KO mice and seven control mice. We assessed the normalized signal intensities of a region of interest (ROI) set in the vitreous body after H217O administration. The results of the two groups were compared using a two-tailed Mann-Whitney U test. Results: A statistical analysis revealed that the normalized ROI signal intensities at the steady state were significantly lower (P = 0.010, <0.05) in the AQP4 KO mice (mean ± SD, 84.5% ± 2.7%) than the controls (mean ± SD, 88.8% ± 1.9%). Conclusions: The present study using JJVCPE MRI of the eye demonstrated that retinal AQP4 has a potential role in the regulation of water inflow into the vitreous body. Absence of AQP4 in the KO mice probably induces lower water outflow from the vitreous body. Our results could help clarify the pathogenesis of various ocular diseases.

DOI： 10.1167/iovs.62.2.24

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Hindawi Limited  

Many of the focal neurological symptoms associated with Alzheimer’s disease (AD) are due to synaptic loss. Glutamate chemical exchange saturation transfer (GluCEST) magnetic resonance imaging (MRI) is a candidate method to assess synaptic dysfunction. We assessed chronological changes in GluCEST in a 5xFAD mouse model of AD, comparing Glucest effects and regional cerebral blood flow (CBF). GluCEST effects and CBF in 5xFAD mice aged 1–15 months and their littermates (WT) were measured. Neurite orientation dispersion and density imaging (NODDI) MRI reflecting dendritic/axonal density was also measured and compared with GluCEST in 7-month-old mice. While regional CBF’s decrease began at 7 months, GluCEST-reduction effects preceded hypoperfusion of the temporal cortex and hippocampus. While longitudinal 5xFAD mouse measurements revealed a correlation between the regional GluCEST effects and CBF, a generalized linear mixed model revealed statistically different correlations in cortical and basal brain regions. Further, NODDI-derived neurite density correlated with GluCEST effects in the parietal cortex, but not in the hippocampus, thereby revealing regional differences in pathophysiological mechanisms. Finally, GluCEST’s effects correlated with regional synaptophysin. These results demonstrate that GluCEST can reflect subtle synaptic changes and may be a potential imaging method for AD diagnosis as well as serve as a biomarker of AD progression.

DOI： 10.1155/2020/8831936

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その他リンク： http://downloads.hindawi.com/journals/cmmi/2020/8831936.xml

掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.ecns.2020.07.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

Vanishing white matter disease (VWM) is an autosomal recessive neurological disorder caused by mutation(s) in any subunit of eukaryotic translation initiation factor 2B (eIF2B), an activator of translation initiation factor eIF2. VWM occurs with mutation of the genes encoding eIF2B subunits (EIF2B1, EIF2B2, EIF2B3, EIF2B4, and EIF2B5). However, little is known regarding the underlying pathogenetic mechanisms or how to treat patients with VWM. Here we describe the identification and detailed analysis of a new spontaneous mutant mouse harboring a point mutation in the Eif2b5 gene (p.Ile98Met). Homozygous Eif2b5I98M mutant mice exhibited a small body, abnormal gait, male and female infertility, epileptic seizures, and a shortened lifespan. Biochemical analyses indicated that the mutant eIF2B protein with the Eif2b5I98M mutation decreased guanine nucleotide exchange activity on eIF2, and the level of the endoplasmic reticulum stress marker activating transcription factor 4 was elevated in the 1-month-old Eif2b5I98M brain. Histological analyses indicated up-regulated glial fibrillary acidic protein immunoreactivity in the astrocytes of the Eif2b5I98M forebrain and translocation of Bergmann glia in the Eif2b5I98M cerebellum, as well as increased mRNA expression of an endoplasmic reticulum stress marker, C/EBP homologous protein. Disruption of myelin and clustering of oligodendrocyte progenitor cells were also indicated in the white matter of the Eif2b5I98M spinal cord at 8 months old. Our data show that Eif2b5I98M mutants are a good model for understanding VWM pathogenesis and therapy development. Cover Image for this issue: doi: 10.1111/jnc.14751.

DOI： 10.1111/jnc.14887

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/jnc.14887

記述言語：日本語   出版者・発行元：(株)メジカルビュー社  

＜文献概要＞成人の代表的な脳実質内腫瘍は神経膠腫,転移性脳腫瘍,中枢神経原発性リンパ腫(PCNSL)である。それぞれ治療方針が異なるため,術前画像診断はきわめて重要である。頭部CT,MRIなどでの鑑別が難しい場合は,MRSが診断の一助となる。本稿では脳実質内腫瘍におけるプロトンMRSの特徴および診断のピットフォールについてまとめた。

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIM: Although fluid-attenuated inversion recovery vascular hyperintensities may be frequently seen in acute large-artery ischemic stroke, reports on their prognostic utility had been conflicting due to lack of quantitative evaluation of the perfusion status based on the signal intensity. We hypothesized that greater hyperintensity represents more severe hypoperfusion. METHODS: Overall, 27 patients with acute occlusion of the proximal middle cerebral artery were divided into 2 groups, based on their signal intensity in the insular segment of middle cerebral artery on the affected side, relative to that of the insular cortex: the low signal intensity group (hypo- or isointense signals, n = 12) and the high signal intensity group (hyperintense signals, n = 15). Using dynamic susceptibility contrast magnetic resonance imaging, we assessed the time of the maximum value of the residue function and mean transit time, in the entire middle cerebral artery cortical area and diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Score regions, including the corona radiata. RESULTS: The high signal intensity group had significantly longer time of the maximum value of the residue function in all the diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Score regions, except the M3 and M6 regions, and significantly longer mean transit time in the M1 and M4 regions. CONCLUSIONS: Quantitative analysis of the perfusion parameters revealed more severely compromised and widely disturbed perfusion status in the high signal intensity group than in the low signal intensity group.

DOI： 10.1016/j.jstrokecerebrovasdis.2019.104467

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記述言語：日本語   出版者・発行元：(一社)日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：(一社)日本臨床神経生理学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Pitch classes (e.g., do, re, and mi) in music evoke color sensations in pitch class-color synesthesia, which is a recently described form of synesthesia in musicians. The synesthetic color sensations were confirmed to be consistent over an extended time interval, fulfilling a widely-accepted criterion for the authenticity of synesthesia. However, it remains unclear whether the color sensations occurred automatically (i.e., without voluntary effort), which is another defining property of synesthesia. We utilized the Stroop paradigm to investigate this issue in 10 pitch class-color synesthetes. Participants were visually presented with pitch class names in font colors that were either congruent or incongruent with the participants' own color sensations. The speed for reporting the font color was slower when it was incongruent with the synesthetic sensation than when it was congruent. The finding verifies the authenticity of pitch class-color synesthesia by demonstrating that the color sensations occur automatically, even when unnecessary.

DOI： 10.1016/j.concog.2019.04.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Absolute pitch (AP) is the ability to identify the pitch names of arbitrary musical tones without being given a reference pitch. The acquisition of AP typically requires early musical training, the critical time window for which is similar to that for the acquisition of a first language. This study investigated the left-right asymmetry of the auditory cortical functions responsible for AP by focusing on the T-complex of auditory evoked potentials (AEPs), which shows morphological changes during the critical period for language acquisition. AEPs evoked by a pure-tone stimulus were recorded in high-AP musicians, low-AP musicians, and non-musicians (n = 19 each). A balanced non-cephalic electrode (BNE) reference was used to examine the left-right asymmetry of the N1a and N1c components of the T-complex. As a result, a left-dominant N1c was observed only in the high-AP musician group, indicating "AP negativity," which has previously been described as an electrophysiological marker of AP. Notably, this hemispheric asymmetry was due to a diminution of the right N1c rather than enhancement of the left N1c. A left-dominant N1a was found in both musician groups, irrespective of AP. N1c and N1a exhibited no left-right asymmetry in non-musicians. Hence, music training and the acquisition of AP are both accompanied by a left-dominant hemispheric specialization of auditory cortical functions, as indexed by N1a and N1c, respectively, but the N1c asymmetry in AP possessors was due to reduced neural activities in the right hemisphere. The use of a BNE is recommended for evaluating these radially oriented components of the T-complex.

DOI： 10.3389/fnins.2019.00809

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Matrix metalloproteinases (MMPs) damage the neurovascular unit, promote the blood-brain barrier (BBB) disruption following ischemic stroke, and play essential roles in hemorrhagic transformation (HT), which is one of the most severe side effects of thrombolytic therapy. However, no biomarkers have presently been identified that can be used to track changes in the distribution of MMPs in the brain. Here, we developed a new 19F-molecular ligand, TGF-019, for visualizing the distribution of MMPs in vivo using 19F-magnetic resonance spectroscopic imaging (19F-MRSI). We demonstrated TGF-019 has sufficient sensitivity for the specific MMPs suspected in evoking HT during ischemic stroke, i.e., MMP2, MMP9, and MMP3. We then utilized it to assess those MMPs at 22 to 24 hours after experimental focal cerebral ischemia on MMP2-null mice, as well as wild-type mice with and without the systemic administration of the recombinant tissue plasminogen activator (rt-PA). The 19F-MRSI of TGN-019-administered mice showed high signal intensity within ischemic lesions that correlated with total MMP2 and MMP9 activity, which was confirmed by zymographic analysis of ischemic tissues. Based on the results of this study, 19F-MRSI following TGN-019 administration can be used to assess potential therapeutic strategies for ischemic stroke.

DOI： 10.1155/2019/8908943

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The blood-brain barrier (BBB), which imposes significant water permeability restriction, effectively isolates the brain from the systemic circulation. Seemingly paradoxical, the abundance of aquaporin-4 (AQP-4) on the inside of the BBB strongly indicates the presence of unique water dynamics essential for brain function. On the basis of the highly specific localization of AQP-4, namely, astrocyte end feet at the glia limitans externa and pericapillary Virchow-Robin space, we hypothesized that the AQP-4 system serves as an interstitial fluid circulator, moving interstitial fluid from the glia limitans externa to pericapillary Virchow-Robin space to ensure proper glymphatic flow draining into the cerebrospinal fluid. The hypothesis was tested directly using the AQP-4 facilitator TGN-073 developed in our laboratory, and [O]H2O JJ vicinal coupling proton exchange MRI, a method capable of tracing water molecules delivered into the blood circulation. The results unambiguously showed that facilitation of AQP-4 by TGN-073 increased turnover of interstitial fluid through the system, resulting in a significant reduction in [O]H2O contents of cortex with normal flux into the cerebrospinal fluid. The study further suggested that in addition to providing the necessary water for proper glymphatic flow, the AQP-4 system produces a water gradient within the interstitial space promoting circulation of interstitial fluid within the BBB.

DOI： 10.1097/WNR.0000000000000990

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Aquaporin (AQP) water channels play a significant role in mesenchymal microvascular proliferation and infiltrative growth. AQPs are highly expressed in malignant astrocytomas, and a positive correlation is observed between their expression levels and histological tumor grade. OBJECTIVE: To examine the utility of aquaporin positron emission tomography (PET) for differentiating between astrocytoma grade III and grade IV using the AQP radioligand [11C]TGN-020. METHODS: Fifteen astrocytoma patients, grade III (n = 7) and grade IV (n = 8), and 10 healthy volunteers underwent [11C]TGN-020 aquaporin PET imaging. Surgical tissues of astrocytoma patients were examined for histopathological grading using the WHO classification standard and expression of AQP1 and AQP4 immunohistochemically. RESULTS: Mean standardized uptake values of astrocytoma grade III and IV (0.51 ± 0.11 vs 1.50 ± 0.44, respectively) were higher than normal white matter (0.17 ± 0.02, P < .001) for both tumor grades. Importantly, mean standardized uptake values of astrocytoma grade IV were significantly higher than grade III (P < .01). CONCLUSION: Our study demonstrated that [11C]TGN-020 aquaporin PET imaging differentiated between astrocytoma grades III and IV. We suggest its clinical application as a noninvasive diagnostic tool would lead to advancements in the management of these malignant brain tumors.

DOI： 10.1093/neuros/nyx314

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We have previously reported that reliable detection of 2-hydroxyglutarate (2HG) in isocitrate dehydrogenase (IDH)-mutant WHO grade 2 and 3 gliomas is possible utilizing 3.0-T single-voxel magnetic resonance spectroscopy (SVMRS). We set out to determine whether the same method could be applied to detect 2HG in IDH-mutant glioblastoma. Forty-four patients harboring glioblastoma underwent pre-operative MRS evaluation to detect 2HG and other metabolites. Presence of IDH-mutations was determined by IDH1 R132H immunohistochemical analysis and DNA sequencing of surgically obtained tissues. Six out of 44 (13.6%) glioblastomas were IDH-mutant. IDH-mutant glioblastoma exhibited significantly higher accumulation of 2HG (median 3.191 vs. 0.000 mM, p < 0.0001, Mann-Whitney test). A cutoff of 2HG = 0.897 mM achieved high sensitivity (100.0%) and specificity (92.59%) in determining IDH-mutation in glioblastoma. Glioblastoma with high 2HG accumulation did not have significantly longer overall survival than glioblastoma with low 2HG accumulation (p = 0.107, log-rank test). Non-invasive and reliable detection of 2HG in IDH-mutant glioblastoma was possible by 3.0-T SVMRS.

DOI： 10.1007/s10143-017-0908-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Society for Medical and Biological Engineering  

DOI： 10.14326/abe.7.156

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記述言語：英語  

BackgroundThe aim of the present study was to investigate maturational changes in glutamate (Glu) in the human cerebral cortex from childhood to young adulthood using 3.0-Tesla proton magnetic resonance spectroscopy (1H-MRS), which is capable of quantifying Glu in vivo.MethodsNormal volunteers comprising 11 children (aged 4-13 years) and 11 young adults (aged 18-33 years) participated in the study. Single-voxel point-resolved spectroscopy (PRESS, repetition time/echo time=2,000/80 ms) was performed on the frontal and occipital cortices, and the Glu-to-creatine ratio (Glu/Cr) and N-acetylaspartate-to-creatine ratio (NAA/Cr) were determined.ResultsIn both the frontal and occipital cortices, Glu/Cr was significantly lower during young adulthood relative to that during childhood. NAA/Cr did not differ significantly between the two age groups.ConclusionThis study has provided objective evidence that cerebral cortical Glu/Cr decreases between childhood and young adulthood. The observed decrease in Glu/Cr may reflect the simultaneous occurrence of maturational changes, such as changes in cortical microstructure and the intercellular compartmentation of Glu metabolism.

DOI： 10.1038/pr.2017.101

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Society for Neuroscience  

The neural processes underlying self-initiated behavior (behavior that is initiated without an external stimulus trigger) are not well understood. This event-related fMRI study investigated the neural origins of self-initiated behaviors in humans, by identifying brain regions that increased in neural activities several seconds prior to self-initiated movements. Subjects performed a hand grasping task under two conditions: a free-timing and cued timing condition. The supplementary motor area (SMA) began to activate several seconds prior to self-initiated movement (accounting for hemodynamic delay), representing a potential blood oxygenation level-dependent (BOLD) signal correlate of the readiness potential (RP) on electroencephalogram (EEG), referred to here as “readiness BOLD signals.” Significant readiness BOLD signals were also observed in the right frontoparietal areas, precuneus, and insula, all of which are known to contribute to internally-generated behaviors, but with no prior evidence for such early and slow accumulation of neural activities. Moreover, visual and auditory cortices also exhibited clear readiness BOLD signals with similar early onsets, even absent external stimulation. Slow accumulation of neural activities throughout distributed cortical areas, including sensory, association, and motor cortices, underlies the generation of self-initiated behaviors. These findings warrant reconsideration of the prevailing view that the SMA or some other specific locus in frontoparietal cortex serves as the ultimate neural origin of self-initiated movement.

DOI： 10.1523/ENEURO.0183-17.2017

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記述言語：英語  

The unique properties of brain capillary endothelium, critical in maintaining the blood-brain barrier (BBB) and restricting water permeability across the BBB, have important consequences on fluid hydrodynamics inside the BBB hereto inadequately recognized. Recent studies indicate that the mechanisms underlying brain water dynamics are distinct from systemic tissue water dynamics. Hydrostatic pressure created by the systolic force of the heart, essential for interstitial circulation and lymphatic flow in systemic circulation, is effectively impeded from propagating into the interstitial fluid inside the BBB by the tightly sealed endothelium of brain capillaries. Instead, fluid dynamics inside the BBB is realized by aquaporin-4 (AQP-4), the water channel that connects astrocyte cytoplasm and extracellular (interstitial) fluid. Brain interstitial fluid dynamics, and therefore AQP-4, are now recognized as essential for two unique functions, namely, neurovascular coupling and glymphatic flow, the brain equivalent of systemic lymphatics.

DOI： 10.3390/ijms18081798

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3390/ijms18081798

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier B.V.  

DOI： 10.1016/j.ensci.2016.10.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND PURPOSE: Presence of an intimal flap is a critical imaging finding in diagnosing intracranial artery dissection (ICAD). Recent reports showed that high-resolution magnetic resonance imaging (MRI) was better at identifying intimal flaps as compared with routine MRI techniques used in clinical settings. However, no current standardized sequence for high-resolution MRI without gadolinium enhancement produces images of satisfactory quality with clinically tolerable scanning times. This study evaluated a nonenhanced high-resolution fast spin echo (HR-FSE) MRI sequence for visualizing intimal flaps in patients with ICAD. SUBJECTS AND METHODS: Three patients with ICAD underwent plain MRI examination using a 2-dimensional T2-weighted FSE imaging sequence optimized for our 3T system (in-plane pixel size, .23 mm × .23 mm; slice thickness 3 mm with no interslice gap), as well as scanning with conventional modalities, including CT angiography, magnetic resonance angiography, and digital subtraction angiography. We assessed whether these imaging methods could visualize an intimal flap and/or double lumen sign in the participants and compared the results between HR-FSE and the other modalities. RESULTS: HR-FSE images clearly showed intimal flaps and double lumen signs in all 3 patients, whereas the conventional modalities identified a double lumen sign in only 2 of the 3 patients. CONCLUSIONS: The present method of optimized HR-FSE imaging with a 3T system improved visualization of intimal flaps and should thus be considered for assessing patients with suspected ICAD that cannot be definitively diagnosed by conventional imaging modalities.

DOI： 10.1111/jon.12380

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Molecular imaging implies the method capable of pictorially displaying distribution of target molecules and their relative concentration in space. In clinical medicine, where non-invasiveness is mandatory, diagnostic molecular imaging has been considered virtually identical to positron emission tomography (PET). However, there is another powerful, apparently underutilized molecular imaging, namely, proton magnetic resonance spectroscopic imaging (1H-MRSI). The technique can detect target molecules endogenous in brain in virtue of their own specific resonance frequencies (chemical shift) and can create quantitative images of each molecule. 1H-MRSI is conventionally utilized for imaging relatively easily detectable molecules such as N-acetyl-aspartate or lactate. More recently, however, the method is extended into imaging of more challenging molecules such as glutamate or γ-aminobutyric acid (GABA). In this small review, we summarize basic concept of 1H-MRSI and introduce an advanced technique, i.e. chemical exchange saturation transfer magnetic resonance imaging (CEST MRI), which made realistic glutamate imaging in vivo possible.

DOI： 10.1272/jnms.84.160

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記述言語：英語  

In the central nervous system, progranulin, a glycoprotein growth factor, plays a crucial role in maintaining physiological functions, and progranulin gene mutations cause TAR DNA-binding protein-43-positive frontotemporal lobar degeneration. Although several studies have reported that progranulin plays a protective role against ischaemic brain injury, little is known about temporal changes in the expression level, cellular localization, and glycosylation status of progranulin after acute focal cerebral ischaemia. In addition, the precise mechanisms by which progranulin exerts protective effects on ischaemic brain injury remains unknown. Furthermore, the therapeutic potential of progranulin against acute focal cerebral ischaemia, including combination treatment with tissue plasminogen activator, remains to be elucidated. In the present study, we aimed to determine temporal changes in the expression and localization of progranulin after ischaemia as well as the therapeutic effects of progranulin on ischaemic brain injury using in vitro and in vivo models. First, we demonstrated a dynamic change in progranulin expression in ischaemic Sprague-Dawley rats, including increased levels of progranulin expression in microglia within the ischaemic core, and increased levels of progranulin expression in viable neurons as well as induction of progranulin expression in endothelial cells within the ischaemic penumbra. We also demonstrated that the fully glycosylated mature secretory isoform of progranulin (∼88 kDa) decreased, whereas the glycosylated immature isoform of progranulin (58-68 kDa) markedly increased at 24 h and 72 h after reperfusion. In vitro experiments using primary cells from C57BL/6 mice revealed that the glycosylated immature isoform was secreted only from the microglia. Second, we demonstrated that progranulin could protect against acute focal cerebral ischaemia by a variety of mechanisms including attenuation of blood-brain barrier disruption, neuroinflammation suppression, and neuroprotection. We found that progranulin could regulate vascular permeability via vascular endothelial growth factor, suppress neuroinflammation after ischaemia via anti-inflammatory interleukin 10 in the microglia, and render neuroprotection in part by inhibition of cytoplasmic redistribution of TAR DNA-binding protein-43 as demonstrated in progranulin knockout mice (C57BL/6 background). Finally, we demonstrated the therapeutic potential of progranulin against acute focal cerebral ischaemia using a rat autologous thrombo-embolic model with delayed tissue plasminogen activator treatment. Intravenously administered recombinant progranulin reduced cerebral infarct and oedema, suppressed haemorrhagic transformation, and improved motor outcomes (P = 0.007, 0.038, 0.007 and 0.004, respectively). In conclusion, progranulin may be a novel therapeutic target that provides vascular protection, anti-neuroinflammation, and neuroprotection related in part to vascular endothelial growth factor, interleukin 10, and TAR DNA-binding protein-43, respectively.

DOI： 10.1093/brain/awv079

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: To investigate whether water influx into cerebrospinal fluid (CSF) space is reduced in Alzheimer's patients as previously shown in the transgenic mouse model for Alzheimer's disease. METHODS: Ten normal young volunteers (young control, 21-30 years old), ten normal senior volunteers (senior control, 60-78 years old, MMSE ≥ 29), and ten Alzheimer's disease (AD) patients (study group, 59-84 years old, MMSE: 13-19) participated in this study. All AD patients were diagnosed by neurologists specializing in dementia based on DSM-IV criteria. CSF dynamics were analyzed using positron emission tomography (PET) following an intravenous injection of 1,000 MBq [15O]H2O synthesized on-line. RESULTS: Water influx into CSF space in AD patients, expressed as influx ratio, (0.755 ± 0.089) was significantly reduced compared to young controls (1.357 ± 0.185; p < 0.001) and also compared to normal senior controls (0.981 ± 0.253, p < 0.05). Influx ratio in normal senior controls was significantly reduced compared to young controls (p < 0.01). CONCLUSION: Water influx into the CSF is significantly reduced in AD patients. β-amyloid clearance has been shown to be dependent on interstitial flow and CSF production. The current study indicates that reduction in water influx into the CSF may disturb the clearance rate of β-amyloid, and therefore be linked to the pathogenesis of AD. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000011939.

DOI： 10.1371/journal.pone.0123708

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Patients with myotonic dystrophy type 1 (DM1) (n = 14) were compared with healthy controls (n = 13) using 3.0 T proton magnetic resonance spectroscopy ((1)H-MRS) to investigate brain pathophysiology. (1)H-MRS imaging revealed reduced N-acetylaspartate to creatine ratio (NAA/Cr) in multiple brain regions (average 24%), suggesting diffuse brain abnormalities among patients with DM1. Single-voxel (1)H-MRS among patients with DM1 showed (1) reduced NAA in both the frontal cortex (23%) and frontal white matter (31%) and unaltered myo-inositol, suggesting neuronal abnormalities without significant gliosis; and (2) elevated glutamine in the frontal cortex (36%) and reduced glutamate in the frontal white matter (20%) among patients with DM1, suggesting abnormalities in the glutamatergic system in the brain of patients with DM1. We consider that these results reflect brain abnormalities that cannot be detected by neuropathological assessment in patients with DM1.

DOI： 10.1159/000371575

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記述言語：英語  

N-acetylaspartate (NAA) appears in a prominent peak in proton magnetic resonance spectroscopy ((1)H-MRS) of the brain. Exhibition by NAA of time-dependent attenuation that reflects energy metabolism during the acute stage of cerebral ischemia makes this metabolite a unique biomarker for assessing ischemic stroke. Although magnetic resonance (MR) imaging is a powerful technique for inspecting the pathological changes that occur during ischemic stroke, biomarkers that directly reflect the drastic metabolic changes associated with acute-stage ischemia are strongly warranted for appropriate therapeutic decision-making in daily clinical settings. In this review, we provide a brief overview of NAA metabolism and focus on the use of attenuation in NAA as a means for assessing the pathophysiological changes that occur during the acute stage of ischemic stroke.

DOI： 10.2463/mrms.2014-0039

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記述言語：英語  

Recent studies on cerebrospinal fluid (CSF) homeostasis emphasize the importance of water influx into the peri-capillary (Virchow-Robin) space through aquaporin 4 (AQP-4). This water flow is believed to have the functionality equivalent to the systemic lymphatic system and plays a critical role in beta-amyloid clearance. Using a newly developed molecular imaging technique capable of tracing water molecules, in vivo, water influx into the CSF was quantitatively analyzed in senile plaque (SP) bearing transgenic Alzheimer's disease (AD) model mice. The results unequivocally demonstrated that water influx into CSF is significantly impaired in SP-bearing transgenic mice, the degree of which being virtually identical to that previously observed in AQP-4 knockout mice. The study strongly indicates that disturbance in AQP-4-based water flow and, hence, impairment in beta-amyloid clearance play a significant role in SP formation.

DOI： 10.1179/1743132814Y.0000000434

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Previous magnetic resonance spectroscopy (MRS) and mass spectroscopy studies have shown accumulation of 2-hydroxyglutarate (2HG) in mutant isocitrate dehydrogenase (IDH) gliomas. IDH mutation is known to be a powerful positive prognostic marker in malignant gliomas. Hence, 2HG accumulation in gliomas was assumed to be a positive prognostic factor in gliomas, but this has not yet been proven. Here, we analyzed 52 patients harboring World Health Organization (WHO) grade II and III gliomas utilizing 3.0-tesla MRS. RESULTS: Mutant IDH gliomas showed significantly higher accumulation of 2HG (median 5.077 vs. 0.000, p =0.0002, Mann-Whitney test). 2HG was detectable in all mutant IDH gliomas, whereas in 10 out of 27 (37.0%) wild-type IDH gliomas, 2HG was below the detectable range (2HG =0) (p =0.0003, chi-squared test). Screening for IDH mutation by 2HG analysis was highly sensitive (cutoff 2HG =1.489 mM, sensitivity 100.0%, specificity 72.2%). Gliomas with high 2HG accumulation had better overall survival than gliomas with low 2HG accumulation (p =0.0401, Kaplan-Meier analysis). DISCUSSION: 2HG accumulation detected by 3.0-tesla MRS not only correlates well with IDH status, but also positively correlates with survival in WHO grade II and III gliomas.

DOI： 10.1186/s40478-014-0158-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

BACKGROUND
Development of molecular MR imaging (MRI) similar to PET imaging using contrast agents such as gadolinium as probe have been inherently hampered by incompatibility between potential probe (charged molecules) and membrane permeability. Nevertheless, considering the inherent spatial resolution limit for PET of 700 mu, the superior microscopic resolution of MRI of 4 mu presents a strong incentive for research into ligand-based molecular MRI.
METHODS
O-17 exhibits JJ vicinal coupling with a covalently bound proton in a hydroxyl group. This O-17 coupled proton can be ionized in water solution and interexchange with other water protons. This property can be utilized as "probe" in T2-weighted imaging and developed into ligand-based molecular MRI. We examined beta-amyloid distribution in human APP overexpressed transgenic mice in vivo following injection of O-17 labeled Pittsburg compound B (O-17-PiB).
RESULTS
JJVCPE imaging successfully imaged O-17-PiB, unequivocally establishing that O-17 JJVCPE imaging can be developed into PET-like molecular MRI in clinical medicine.
CONCLUSIONS
The study represents the first successful ligand-based molecular MRI in vivo. This is also the first in vivo amyloid imaging using MRI. High-resolution molecular MRI with high specificity under clinical settings, such as in vivo microscopic imaging of senile plaque, is a foreseeable aim.

DOI： 10.1111/jon.12091

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記述言語：英語  

DOI： 10.1212/CPJ.0000000000000013

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記述言語：英語  

Recent studies on cerebrospinal fluid (CSF) homeostasis emphasize the importance of water flux through the pericapillary (Virchow-Robin) space for both CSF production and reabsorption (Oreskovic and Klarica hypothesis), and challenge the classic CSF circulation theory, which proposes that CSF is primarily produced by the choroid plexus and reabsorbed by the arachnoid villi. Active suppression of aquaporin-1 (AQP-1) expression within brain capillaries and preservation of AQP-1 within the choroid plexus together with pericapillary water regulation by AQP-4 provide a unique opportunity for testing this recent hypothesis. We investigated water flux into three representative regions of the brain, namely, the cortex, basal ganglia, and third ventricle using a newly developed water molecular MRI technique based on JJ vicinal coupling between O and adjacent protons and water molecule proton exchanges (JJVCPE imaging) in AQP-1 and AQP-4 knockout mice in vivo. The results clearly indicate that water influx into the CSF is regulated by AQP-4, and not by AQP-1, strongly supporting the Oreskovic and Klarica hypothesis.

DOI： 10.1097/WNR.0000000000000042

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記述言語：英語  

An angiogenesis factor, angiopoietin-1 (Ang1), is associated with the blood-brain barrier (BBB) disruption after focal cerebral ischemia. However, whether hemorrhagic transformation and cerebral edema after tissue plasminogen activator (tPA) treatment are related to the decrease in Ang1 expression in the BBB remains unknown. We hypothesized that administering Ang1 might attenuate hemorrhagic transformation and cerebral edema after tPA treatment by stabilizing blood vessels and inhibiting hyperpermeability. Sprague-Dawley rats subjected to thromboembolic focal cerebral ischemia were assigned to a permanent ischemia group (permanent middle cerebral artery occlusion; PMCAO) and groups treated with tPA at 1 h or 4 h after ischemia. Endogenous Ang1 expression was observed in pericytes, astrocytes, and neuronal cells. Western blot analyses revealed that Ang1 expression levels on the ischemic side of the cerebral cortex were decreased in the tPA-1h, tPA-4h, and PMCAO groups as compared to those in the control group (P = 0.014, 0.003, and 0.014, respectively). Ang1-positive vessel densities in the tPA-4h and PMCAO groups were less than that in the control group (p = 0.002 and <0.001, respectively) as well as that in the tPA-1h group (p = 0.047 and 0.005, respectively). These results suggest that Ang1-positive vessel density was maintained when tPA was administered within the therapeutic time window (1 h), while it was decreased when tPA treatment was given after the therapeutic time window (4 h). Administering Ang1 fused with cartilage oligomeric protein (COMP) to supplement this decrease has the potential to suppress hemorrhagic transformation as measured by hemoglobin content in a whole cerebral homogenate (p = 0.007) and cerebral edema due to BBB damage (p = 0.038), as compared to administering COMP protein alone. In conclusion, Ang1 might be a promising target molecule for developing vasoprotective therapies for controlling hemorrhagic transformation and cerebral edema after tPA treatment.

DOI： 10.1371/journal.pone.0098639

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: Intra-arterial transplantation of bone marrow mononuclear cells (BMMCs) effectively improves neuronal function and limits the infarct size. We monitored the fate of BMMCs labeled with super paramagnetic iron oxide (SPIO) until 7 days after the transplantation using high-field magnetic resonance imaging (MRI). METHODS: Male Sprague-Dawley rats were subjected to 90-minute focal ischemia using the intraluminal suture technique followed by transplantation of 1 × 10(7) BMMCs or vehicle only via the ipsilateral carotid artery immediately after reperfusion. Autologous BMMCs were labeled with SPIO by electroporation prior to ischemia. MRI studies were performed at 1 hour, 24 hours, 3 days, and 7 days after reperfusion on each rat. The total infarct volume and the volume of negative dots were measured on T2-weighted images and T2*-weighted images, respectively. RESULTS: One hour after BMMC transplantation, we confirmed wide spread distribution of BMMCs in the ischemic hemisphere as a negative dot. The volume of negative dot normalized by hemispheric volume decreased rapidly and was seldom seen at the seventh day after transplantation. The infarct volume was significantly smaller in the transplanted group than the vehicle group at 24 hours and 7 days after reperfusion. DISCUSSION: The present study established In vivo monitoring of intra-arterial transplanted SPIO-labeled BMMCs immediately after reperfusion using MRI of a rat transient focal ischemia model. The accumulation of BMMCs in ischemic lesion at the acute stage of ischemia can be part of the conditions to limit the infarct size.

DOI： 10.1179/1743132813Y.0000000171

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記述言語：英語  

The effects of the aquaporin-4 (AQP-4) inhibitor TGN-020 on regional cerebral blood flow (rCBF) was examined in wild-type (WT) and AQP-4 knockout (KO) mice in vivo. Although baseline absolute rCBF of WT and KO mice were equivalent (158.9 ± 17.7 and 155.5 ± 10.4 ml/100 g/min, respectively), TGN-020 produced a significant increase in rCBF compared with saline-treated WT mice (control), reaching a plateau 20 min after administration (118.45 ± 8.13%, P<0.01). TGN-020 showed no effect on KO mice, supporting the concept that the observed increase in rCBF in WT mice was AQP-4 dependent. Administration of acetazolamide (positive control) produced an even greater increase in rCBF in WT compared with TGN-020 and a similar response in KO mice as well, reaching a sustained plateau 5 min after administration (138.50 ± 9.75 and 138.52 ± 9.76%, respectively, P<0.01 compared with baseline or saline-treated control mice). The study demonstrated that AQP-4 plays a role in regulation of rCBF.

DOI： 10.1097/WNR.0b013e32835fc827

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1159/000353873

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記述言語：英語  

BACKGROUND: Susceptibility-weighted imaging (SWI) microscopy on a 7.0T system demonstrated the corticomedullary junction (CMJ) to be a high-susceptibility region (HSR) in young normal subjects, suggesting that functional alteration of cortical microcirculation could be assessed with this imaging method. METHODS: Focused microscopic studies were performed on the parietal association cortex in 74 normal volunteers (ages 20-79 years; 35 female, 39 male) using a SWI algorithm on a system constructed based on General Electric Signa LX (Waukesha, WI, USA), equipped with a 900-mm clear bore superconducting magnet operating at 7.0T. RESULTS: There was a clear-cut reduction in the thickness of the normal-appearing cortex (cortex, R2 = .5290, P < .001) and expansion of CMJ-HSR (R(2) = .6919, P < .001). The sum of cortex thickness and CMJ-HSR thickness was essentially constant, suggesting that the observed expansion of CMR-HSR with aging likely occurred within the cortical mantle. CONCLUSION: CMJ-HSR expands significantly as a function of aging. Since CMJ-HSR represents a functionally distinct area with relatively slow venous flow, the observed expansion is believed to reflect alteration in cerebral microcirculation with increased age, providing another clue for pathogenesis of Alzheimer's disease.

DOI： 10.1111/j.1552-6569.2011.00607.x

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：日本語  

Proton magnetic resonance spectroscopy ((1)H-MRS) non-invasively provides in vivo biochemical information on tissue metabolites. In acute stage of cerebral ischemia, N-acetyl aspartate (NAA), one of (1)H-MRS observable metabolite, declines gradually reflecting energy impairment due to oxygen depletion. In our study, decline of NAA in ischemic core linearly correlated with the time from the onset of ischemia. Therefore NAA can be utilized to time clock biomarker for the acute stage cerebral ischemia.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND PURPOSE: An important task in diagnostic imaging of acute ischemic stroke is to identify the so-called diffusion-perfusion mismatch area. We aimed to investigate the possibility of facilitating the identification process by combining independent component analysis (ICA) and diffusion-weighted MRI (DWI), with the expectation that this would eliminate the need for additional perfusion imaging to delineate perfusion lesion. METHODS: Simulations were performed to confirm the utility of an intuitively determined sequence of 14 b-factors ranging from 0 to 1,000 seconds/mm(2) for ICA separation of perfusion lesion. Corresponding DWI data from 2 stroke patients, 1 in the acute and 1 in the subacute phase, were decomposed into independent component (IC) maps, and their b-dependent amplitude decay profiles were subjected to multiexponential fitting. RESULTS: Low-perfusion areas were successfully delineated on IC maps in both patients. Comparison with the areas of diffusion lesion identifiable on relatively high b-factor images in the DWI data, for example, those at b= 1,000 seconds/mm(2) , allowed the mismatch to be identified. CONCLUSION: This study demonstrates that combining ICA and DWI enables noninvasive mapping of sluggish perfusion provided an appropriate b-sequence is applied, and that it thereby facilitates the identification of diffusion-perfusion mismatch.

DOI： 10.1111/j.1552-6569.2010.00514.x

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記述言語：英語  

BACKGROUND: The aim of this study was to find biomarkers of disease severity in multiple system atrophy of cerebellar type by imaging disease specific regions using proton magnetic resonance spectroscopy on a 3.0 T system. METHODS: We performed proton magnetic resonance spectroscopy separately in the pons and medulla on 12 multiple system atrophy of cerebellar type patients and 12 age and gender matched control subjects. The metabolite concentrations were estimated from single-voxel proton magnetic resonance spectra measured by point resolved spectroscopy, which were then correlated with clinical severity using Part I, II, and IV of the unified multiple system atrophy rating scale. RESULTS: Proton magnetic resonance spectroscopy showed that myo-inositol concentrations in both the pons and medulla were significantly higher in multiple system atrophy of cerebellar type patients compared to those of the control subjects (P < 0.05). By contrast, total N-acetylaspartate (the sum of N-acetylaspartate and N-acetylaspartylglutamate) and total choline compounds concentrations in both the pons and medulla were significantly lower in multiple system atrophy of cerebellar type patients compared to control subjects (P < 0.05). Creatine concentration in the pons was significantly higher in multiple system atrophy of cerebellar type patients compared to the control subjects (P < 0.05). Furthermore, a significant correlation was found between the myo-inositol/creatine ratio in the pons and clinical severity, defined by the sum score of unified multiple system atrophy rating scale (I+II+IV) (r = 0.76, P < 0.01). CONCLUSION: Proton magnetic resonance spectroscopy, in conjunction with a 3.0 T system, can be feasible to detect part of pathological changes in the brainstem, such as gliosis and neuronal cell loss, and the metabolites can be used as biomarkers of clinical severity in multiple system atrophy of cerebellar type patients.

DOI： 10.1002/mds.23550

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記述言語：英語  

An angiogenic factor, vascular endothelial growth factor (VEGF), might be associated with the blood-brain barrier (BBB) disruption after focal cerebral ischemia; however, it remains unknown whether hemorrhagic transformation (HT) after tissue plasminogen activator (tPA) treatment is related to the activation of VEGF signaling pathway in BBB. Here, we hypothesized that inhibition of VEGF signaling pathway can attenuate HT after tPA treatment. Rats subjected to thromboembolic focal cerebral ischemia were assigned to a permanent ischemia group and groups treated with tPA at 1 or 4 hours after ischemia. Anti-VEGF neutralizing antibody or control antibody was administered simultaneously with tPA. At 24 hours after ischemia, we evaluated the effects of the antibody on the VEGF expression, matrix metalloproteinase-9 (MMP-9) activation, degradation of BBB components, and HT. Delayed tPA treatment at 4 hours after ischemia promoted expression of VEGF in BBB, MMP-9 activation, degradation of BBB components, and HT. Compared with tPA and control antibody, combination treatment with tPA and the anti-VEGF neutralizing antibody significantly attenuated VEGF expression in BBB, MMP-9 activation, degradation of BBB components, and HT. It also improved motor outcome and mortality. Inhibition of VEGF signaling pathway may be a promising therapeutic strategy for attenuating HT after tPA treatment.

DOI： 10.1038/jcbfm.2011.9

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記述言語：英語  

Nuclear factor TAR DNA-binding protein-43 (TDP-43) is considered to play roles in pathogenesis of human neurodegenerative diseases, so-called TDP-43 proteinopathy, via its proteolytic cleavage, abnormal phosphorylation, subcellular redistribution, and insolubilization generating TDP-43-positive neuronal intracellular inclusions. The purpose of this study was to elucidate biochemical and histopathological alternations in TDP-43 specific to acute ischemic stroke. Adult male rats were subjected to a 90-min middle cerebral artery occlusion. We examined the proteolytic cleavage, phosphorylation, subcellular localization, and solubility of TDP-43 by immunoblottings and histopathological examinations using the ischemic and sham-operated cortex. The level of full-length TDP-43 (43 kDa) decreased and that of the 25-kDa C-terminal fragment increased after acute ischemic stroke, which can be explained by proteolytic cleavage of TDP-43. Cytoplasmic redistribution and altered nuclear distribution of TDP-43 was observed after acute ischemic stroke, whereas abnormal phosphorylation and insolubilization of TDP-43 as well as formation of intracellular inclusions were not observed. Ischemic neurons with the cytoplasmic redistribution of TDP-43 expressed ubiquitin and activated caspase 3 and were terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling-positive. In conclusion, biochemical and histopathological alterations in TDP-43 were identified in rats after acute ischemic stroke, although there was very less similarity between TDP-43 alterations observed in acute ischemic stroke and those observed in TDP-43 proteinopathy.

DOI： 10.1111/j.1471-4159.2010.06860.x

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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We investigated the in vivo effects of a novel aquaporin 4 (AQP4) inhibitor 2-(nicotinamide)-1,3,4-thiadiazole, TGN-020, in a mouse model of focal cerebral ischemia using 7.0-T magnetic resonance imaging (MRI). Pretreatment with TGN-020 significantly reduced brain edema associated with brain ischemia, as reflected by percentage of brain swelling volume (%BSV), 12.1 ± 6.3% in the treated group, compared to (20.8 ± 5.9%) in the control group (p < 0.05), and in the size of cortical infarction as reflected by the percentage of hemispheric lesion volume (%HLV), 20.0 ± 7.6% in the treated group, compared to 30.0 ± 9.1% in the control group (p < 0.05). The study indicated the potential pharmacological use of AQP4 inhibition in reducing brain edema associated with focal ischemia.

DOI： 10.1007/s10072-010-0431-1

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We herein report a rare case of cerebellopontine angle (CPA) medulloblastoma originating in the brainstem that demonstrated a very unusual clinical presentation and radiological appearances. A 25-year-old female was admitted to our hospital with a right hearing disturbance and a right facial palsy. A small non-enhanced lesion having minimal mass effect in the right CPA was identified by using a 1.5-tesla-MR system, whose size remained almost unchanged a year. The 3-tesla MR images revealed that the precise region was in the right side of the tegmentum of the lower pons to the inferior cerebellar peduncle and the flocculus. MR spectroscopic images using a 3-tesla system revealed a high ratio of choline-to-N-acetylaspartate in the region of interest in comparison to the contra-lateral side. Craniotomy and biopsy were performed. The histopathological diagnosis was medulloblastoma. The patient received craniospinal irradiation and chemotherapy, and achieved complete remission by the time of the follow-up MR images. She is now doing well with a full recovery of the right facial palsy. MR spectroscopic imaging is considered to be quite useful for the management of this rare type of brainstem tumor.

DOI： 10.1111/j.1552-6569.2008.00298.x

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: Transplantation of bone marrow cells has been reported to exert neuroprotection against cerebral ischemia. However, the effect of bone marrow mononuclear cells (BMMCs) administered immediately after reperfusion has rarely been investigated. The present study was designed to examine whether brain injury in response to transient focal ischemia can be ameliorated by BMMC administration immediately after reperfusion in rats, and to determine whether there are differences in the route of administration. MAIN METHODS: Autologous BMMCs were obtained from each rat. Rats were then subjected to transient focal ischemia followed by BMMC administration via the ipsilateral carotid artery (IA group) or the femoral vein (IV group) immediately after reperfusion. Control rats underwent the same procedure but received vehicle injection. Infarct volume was compared among the groups 24 h and 7 days after reperfusion. BMMCs were fluorescently labeled with PKH26 prior to administration to track transplanted cells. KEY FINDINGS: Total infarct volume decreased in the IA group, but not in the IV group, when compared to the vehicle group. In the ipsilateral hemisphere, PKH26 positive cell count was greater in the IA group than in the IV group. Motor function, assessed with a rotarod test, improved in the IA group compared to the vehicle group. SIGNIFICANCE: These results show significant neuroprotection after transient focal ischemia by 1 x 10(7) autologous BMMCs administered intra-arterially, but not intravenously, immediately after reperfusion in rats. The larger number of transplanted BMMCs in the brain during the early stage of reperfusion may be responsible for the protective effect.

DOI： 10.1016/j.lfs.2008.07.018

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Objective: To investigate whether the prognosis of ischemic tissues in acute cerebral ischemia can be predicted using perfusion computed tomography-derived parameters and, if so, which are the most useful.
Methods: Perfusion computed tomography was performed on 13 ischemic stroke patients within 6 hours of ischemic onset. The absolute and normalized values of regional cerebral blood flow (rCBF), regional cerebral blood volume, and regional mean transit time (rMTT) and their mirror regions were divided into those that infarcted or survived. Receiver operating characteristic analysis was subsequently conducted for these 3 parameters, and their relationship to the threshold and predictability of infarction were evaluated.
Results: Acute ischemic lesions with less than 63% of normal rCBF or more than 220% of rMTT almost invariably led to infarction; moreover, the receiver operating characteristic analysis revealed that both rMTT and rCBF, and their normalized derivatives, were equally predictive of infarction.
Conclusion: Both rCBF and rMTT can be used to predict the ultimate pathological prognosis of cerebral ischemia. Perfusion computed tomography is a very useful early-stage tool for the assessment of these patients.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Many practical therapies have been explored as clinical applications for ischemic cerebral infarction; however, most are still insufficient to treat acute stroke. We show here a potential combination therapy in a rat focal ischemic model to improve neurological symptoms as well as to reduce infarct volumes at the maximum level. We applied protein transduction technology using artificial anti-death Bcl-xl derivative with three amino acid-substitutions (Y22F, Q26N and R165K) (FNK) protein fused with a protein-transduction-domain peptide (PTD-FNK). When PTD-FNK was administrated 1 h after initiating ischemia followed by the administration of an immunosuppressant FK506 with a 30-min time lag, infarct volumes of the total brain and cortex were markedly reduced to 27% and 14%, respectively. This procedure not only reduced the infarct volume and edema, but also markedly improved neurological symptoms. The therapeutic effect continued for at least 1 week after ischemia. FK506 inhibited the transduction of PTD-FNK in vitro, which explains the requirement of a time lag for the administration of FK506. An additional in vitro experiment showed that PTD-FNK, when administered 30 min before FK506, gave the maximal protective effect by reducing the intracellular calcium concentration. We propose that this combination therapy would provide a synergistic protective effect by both drugs, reducing adverse the effects of FK506.

DOI： 10.1111/j.0022-3042.2008.05360.x

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記述言語：英語  

BACKGROUND: Microscopic application of magnetic resonance imaging (MRI) has entered the era of clinical application. One of the most important targets is the visualization of pathological findings such as senile plaques (SP), in vivo, in patients with Alzheimer's disease (AD). Such an application provides not only the most accurate diagnostic tool for clinicians but also a solid basis for scientists for developing effective treatment and preventive strategies for AD. METHODS: Focused microscopic studies were performed on parietal association cortex at the level of the centrum semiovale identified on conventional axial slices using a system constructed based on General Electric Signa LX (Waukesha, WI) equipped with a 900-mm clear bore superconducting magnet operating at 7.0 T in 10 patients (67-83-year old, five males, five females) who fulfilled the NINCD and the SADRDA criteria for probable AD, 10 age-matched controls (71-85-year old, five males, five females), and 20 young adults (22-35-year old, 10 males, 10 females) using a susceptibility weighted imaging (SWI) algorithm. RESULTS: SWI microscopy consistently provided images with SP-like pathology extending within the entire parietal cortex in all cases of AD and 2 out of 10 age-matched volunteers. CONCLUSIONS: Although the precise mechanisms leading to the higher susceptibility rendering SP-like pathology observable within the cortical mantle are not totally understood, the study unambiguously demonstrated that MR microscopy is capable of directly visualizing cortical pathology in AD patients in vivo.

DOI： 10.1111/j.1552-6569.2007.00179.x

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記述言語：英語  

To elucidate the still unclear mechanism of delayed encephalopathy after carbon monoxide (CO) poisoning, we serially performed single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) and diffusion tensor imaging (DTI) on a 3.0T system and intelligence tests in 2 patients, while they were undergoing hyperbaric oxygenation therapy. The chronological changes in (1)H-MRS- and DTI-derived parameters indicated the following: (1) White matter demyelination, aerobic metabolism inhibition, and cytotoxic edema persisted for at least 3 months even after starting the hyperbaric oxygenation therapy; (2) the axonal function and structural integrity of the white matter were initially severely impaired and then gradually and partially improved for 5 months, showing changes similar to those in the scores of the intelligence tests. The results demonstrated that brain damage after CO poisoning may persist longer than expected, and that the (1)H-MRS- and DTI-derived parameters are good indicators of the clinical progress of a patient. The combination of (1)H-MRS and DTI on a 3.0T system is useful for monitoring the changes in brain damage and the clinical symptoms of patients with delayed encephalopathy after CO poisoning.

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記述言語：日本語  

Goal of initial imaging study for acute-stage ischemic stroke are to detect focal lesion accurately and to assist the therapeutic decision. With the goal in mind, we investigated feasibilities of MRI for acute-stage ischemic stroke. Firstly, we assessed whether diffusion weighted images (DWI) raised diagnostic accuracy for acute-stage ischemic stroke. We investigated how DWI study changes the diagnosis for the patients with neurological symptom in emergency room. Out of 164 patients who visit the emergency room with neurological symptom, sensitivity, specificity and efficiency for ischemic stroke diagnosis before DWI study were 0.87, 0.85 and 0.89 respectively. DWI raised them to 0.99, 0.98 and 0.99. These result proves feasibility of DWI on diagnosis of acute-stage ischemic stoke. Secondly, we assess whether DWI and perfusion imaging (PI) can provide any information about fate of acute ischemic lesion. We compared the relationships between DWI and PI parameters (ADC, rCBF, MTT, rCBV) and tissue outcome (infracted or survived). In patients with successful recanalization, best predictor was ADC and the cut-off value was 0.90 against contra-lateral hemisphere. In patients without recanalization, rCBF at 0.66 against contra-lateral hemisphere predicted the pathological fate most accurately. This simple guidepost can be help therapeutic decision of acute-stage stroke.

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記述言語：英語  

The anti-edema effect of edaravone, a free radical scavenger, was evaluated by magnetic resonance imaging in six patients with extensive hemispheric ischemic stroke. T(2) relaxation time in the infarct core, the boundary zone of the infarct, and the noninfarcted hemisphere were calculated, and T(2) mapping was performed before and after edaravone administration. Edaravone administration significantly decreased the mean T(2) relaxation time in the boundary zone of the infarct from 121.5 +/- 9.2 (mean +/- standard deviation) to 114.5 +/- 9.9 msec (p = 0.008), but not in the core from 142.3 +/- 13.4 to 142.2 +/- 18.5 msec (p = 0.97) or the noninfarcted hemisphere from 93.0 +/- 3.7 to 93.1 +/- 3.8 msec (p = 0.91). The T(2) subtraction map clearly demonstrated shortened T(2) relaxation time in the boundary zone of the infarct. The present results indicate that edaravone can salvage the boundary zone of the infarct and is a useful cytoprotective anti-edema agent.

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記述言語：英語  

FK-506 confers a neuroprotective effect and is thought to extend the time window for thrombolytic treatment of cerebral ischemia. These effects have not been assessed in an embolic stroke model. In addition, clinical studies have raised concern that FK-506 may increase the risk of hemorrhagic transformation by damaging vascular endothelial cells. We investigated whether combined administration of recombinant tissue plasminogen activator (rt-PA) and FK-506 would extend the therapeutic time window without increasing the hemorrhagic transformation in a rat embolic stroke model. Male Sprague-Dawley rats (n=66) were subjected to embolic infarction and assigned into eight groups. Six of the groups were treated with or without FK-506 (0.3 mg/kg) administration at 60 min after embolization, together with and all six groups received systemic rt-PA administration (10 mg/kg) at 60, 90, or 120 min. Two permanent ischemia groups were administered saline either with or without FK-506. Infarct and hemorrhagic volume were assessed at 24 h after embolization. Diffusion-weighted and perfusion-weighted magnetic resonance imaging (MRI) were performed in the groups administered rt-PA at 90 min and a vehicle control group to assess whether FK-506 influenced the effectiveness of MRI in revealing ischemic lesion. FK-506 extended the therapeutic time window for systemic thrombolysis compared to rt-PA alone without increasing the risk for hemorrhage. Combined therapy with FK-506 salvaged some of the MRI, revealing ischemic lesions destined to infarction in the animals treated by rt-PA alone. Single low dose of FK-506 alone did not ameliorate the embolic infarction, but it did prove effective in extending the therapeutic time windows for thrombolysis without increasing the risk of hemorrhagic transformation.

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記述言語：英語  

OBJECT: The authors of previous studies based on diffusion tensor imaging have indicated that there are two types of peritumoral edema-namely, edema with preserved structural integrity of the glial matrix and edema with compromised glial matrix. The authors of this study hypothesized that functionality of the glutamate (Glu)-glutamine shuttle, a vital neuron-glia interaction, may be differentially affected by peritumoral edema. They tested this hypothesis using proton magnetic resonance (MR) spectroscopy on a 3.0-tesla system that is capable of quantifying Glu without need of editing. METHODS: Twenty-three patients, each with a single brain tumor mass and peritumoral edema (nine high-grade gliomas, eight metastatic brain tumors, and six meningiomas), and nine healthy individuals participated in this study. Single-voxel proton MR imaging targeting the region of peritumoral edema was performed using a 3.0-tesla system. Glutamate levels in the peritumoral edema of nonglial tumors was significantly elevated (p < 0.01) compared with edema associated with glial tumors or normal white matter. The finding confirmed that peritumoral edema in nonglial tumors is distinct from that of glial tumors, as previously indicated in diffusion tensor imaging studies. The authors hypothesized that the former condition represents a compensatory increase in activities of the Glu-glutamine shuttle brought about by simple expansion of the extracellular space due to edema. CONCLUSIONS: The assessment of Glu concentrations in peritumoral edema using 3.0-tesla proton MR spectroscopy may be developed into an objective index of the structural integrity of the glial matrix.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Progress in imaging techniques has contributed to improvements in reliable diagnosis and surgical decision making in neurosurgery. From the viewpoint of neurosurgeons, there are two major needs in the development of imaging techniques. One is greater accuracy in demonstrating the anatomy of the brain at microscopic resolutions and the other is visualization of function or metabolism that is invisible on surgical views. Use of 3.0 T magnetic resonance imaging (MRI) in clinical patients has revealed anatomy appropriate for microsurgery at high resolution, and three-dimensional reconstruction of MRI on high-specification computers helps neurosurgeons to understand the anatomy of the brain in individual patients. Functional imaging methods such as functional MRI, positron emission tomography, and magnetoencephalography have provided new insights in brain surgery, visualizing various cerebral functions on anatomic images. Recently, diffusion tensor imaging is used to visualize neural tracts passing through subcortical white matter and MR spectroscopy is used to show the metabolic status of lesions. These tools are also forms of functional imaging. New noninvasive imaging techniques are still being developed to visualize function more easily. Here, we summarize the roles of recent imaging techniques in our previous studies and discuss the future of imaging in neurosurgery.

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記述言語：日本語  

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記述言語：日本語  

A thrombolytic agent, recombinant tissue plasminogen activator (rt-PA), was recently approved in Japan for use on patients within 3 hrs of the onset of cerebral infarction. In order to salvage cerebral tissue after an ischemic insult, it is crucial to detect the ischemic lesion before it becomes irreversible and to detect the core and penumbra areas of the lesion for guidance in selecting the suitable therapy. In this symposium we discuss the detection of ischemic lesions using plain CT, perfusion CT, and MRI. In the section on plain CT, we present a typical case with early CT signs. In the section on perfusion CT, we report on the feasibility and limitation of the technique for the diagnosis of acute cerebral infarction. In the section on MRI, we study the usefulness of DWI for the early and highly reliable detection of ischemic stroke.

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記述言語：英語  

BACKGROUND: The ingredients of substances implanted for breast augmentation sometimes remain unknown due to lack of information from patients. Significant clinical problems sometimes necessitate removal and reconstruction. Thus, preoperative diagnostic imaging to identify the ingredients of implants may improve the treatment decision-making process. In this report, we created a clinical imaging index. PURPOSE: Here, we summarize computed tomography (CT) and magnetic resonance imaging (MRI) imaging of implant materials to predict the ingredients of implant substances preoperatively. METHODS: A total of 104 patients with late complications after receiving breast augmentations between 1971 and 2002 were examined using CT and MRI. In addition, further examinations were conducted, including postoperative chemical analysis using Nuclear magnetic resonance (NMR) spectroscopy and MRI imaging of various implanted substances using an experimental magnetic resonance system. RESULTS: We identified the ingredients of implant materials used for breast augmentation by imaging diagnostics as follows: silicone: radiopaque-low/high (CT-MRI T1/T2); hydrogel: radiolucent-low approximately iso/high; hydrocarbon: radiolucent-high approximately iso/low approximately iso; saline: radiolucent-low/high. CONCLUSION: We have identified by imaging diagnosis the ingredients of implant materials.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objectives: To evaluate the feasibility of utilizing cerebral blood flow (CBF) index images, calculated automatically and quickly from dynamic perfusion imaging (DPI), to identify acute cerebral ischemia. We attempted to investigate (1) whether the CBF index has a threshold for assessing tissue outcome, (2) whether CBF index images can predict the resulting infracted area, and if so, (3) whether the predictive capacity of the CBF index image is comparable to the regional CBF (rCBF) image delivered from singular value decomposition (SVD) deconvolution methods, which are regarded as most accurate in predicting the final infarct area. Methods: Diffusion-weighted images (DWI) and DPI were obtained in 17 patients within 12 hours of stroke onset and follow-up magnetic resonance imaging (MRI). On 3 DPI-delivered images, namely relative regional cerebral blood volume (rrCBV), uncorrected mean transit time (MTTu) and CBF index images, univariate discriminant analysis was done to estimate cut-off values to discriminate between infarcted and noninfarcted areas. Subsequently, correlations between the initial lesion volume of 3 images together with rCBF images delivered with SVD methods and the final infarct volume on follow-up T2-weighted MRI taken at the 8th to 20th day were determined. Results: Among the 3 images, only the CBF index image was able reveal the threshold of the ischemic region. Lesion volume of CBF index images against follow-up infarct volume had the highest correlation (r = 0.995) to a linear fit and the slope was closest to 1.0 (0.91) among the 3 and had identical accuracy to the regression coefficient of rCBF images. Conclusions: CBF index images can predict final infarct volume. Evaluating CBF index images together with DWI can guide the initial assessment in the acute stage of cerebral ischemia.

DOI： 10.1097/00004728-200311000-00008

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記述言語：日本語  

Recent advances in MRI technology and the development of effective neuroprotective agents has improved the outcome of stroke. In order to salvage tissue after an ischemic insult it is important to differentiate the core and penumbra area of the ischemic lesion. The penumbra surrounds the ischemic core, damage in this area is reversible if effective neuroprotective agents are given and reperfusion occurs. In this symposium detection of penumbra in an ischemic lesion using diffusion weighted imaging (DWI) and perfusion imaging (PI), diffusion-perfusion mismatch, and indications for thrombolytic therapy are discussed. If a hypoperfusion area is revealed with PI without a corresponding lesion indicated with DWI or when the DWI lesion is less than one third of the PI lesion, combined thrombolytic and neuroprotective therapies are recommended. In contrast, when both PI and DWI show an identical lesion, only neuroprotective therapy is advised. Additionally, newly developed neuroprotective agents, especially the combined effect of rt-PA and the immunosuppressant, FK506, on an embolic infarct model are discussed.

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記述言語：英語  

OBJECTIVE: To investigate diffusion-weighted imaging (DWI) in status epilepticus, a canine model of kainic acid (KA)-induced complex partial status epilepticus (CPSE) was produced. In order to validate its usefulness, MR imaging was carried out at various times following onset of CPSE followed by histopathology. MATERIAL AND METHODS: Six normal dogs were used in this study. In each dog, a cannula was stereotactically inserted into the left amygdala. One week after surgery, all dogs were imaged at MRI. Pre-injection imaging consisted of T2 weighted (T2W) imaging, fluid attenuated inversion recovery (FLAIR), and DWI. Two weeks after surgery, five dogs received intraamygdaloid KA microinjections. One dog was used as a control. MRI was carried out at 3, 6, 12, 24 and 48 h after onset of CPSE. Animals were euthanized immediately after MRI for histopathological evaluation. The average of each apparent diffusion coefficient (ADC) in the regions of interest was calculated from each DWI. RESULTS: At 3 and 6 h, DWI hyperintensity and low ADC were found in the injected amygdala, without any T2W and FLAIR imaging changes. At 12 and 24 h, all imaging showed hyperintensity with higher ADC in the amygdala and the hippocampus. At 48 h, all imaging techniques showed continued hyperintensity, but ADC showed a trend towards normalization. This increasing hyperintensity in DWIs were in agreement with the degree of histopathology during CPSE. SUMMARY: This study suggests that DWI is a useful imaging method for finding the epileptic focus or for examining potential epileptic brain damage in status epilepticus.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

rt-PA improves neurological outcome if it is administered at early time of stroke, and intracerebral hemorrhage is the main complication of thrombolytic therapy and it proves sometimes fatal. The aims of this study are to clarify the correlation between the efficacy of rt-PA, the severity of hemorrhage and treatment delay, using the developed embolic infarction model. Fibrin-rich clots were used to occlude MCA on Sprague–Dawley rats. Alteplase of 10 mg/kg was administrated via femoral vein at 30 (n=7), 60 (n=10), 90 (n=6) and 120 (n=6) min after clot embolization and vehicle group (n=10) received saline. Twenty four hours after embolization, brains were perfused with PBS and TTC stain was utilized to measure the infarct volume. Hemorrhage volume was quantified with spectrophotometric assay of extraction from ischemic hemisphere. Infarction was significantly smaller in the groups administrated altepalse at 30, 60 and 90 min and hemorrhage was significantly less in the group of 30 min than vehicle group. However, administration of alteplase at 120 min did not ameliorate infarction and more significantly increased hemorrhage than vehicle group. In these results, we clearly showed that vascular therapeutic time window of this model can be within 120 min and treatment delay of thrombolysis enhanced the severity of hemorrhagic transformation. © 2003, Elsevier B.V. All rights reserved.

DOI： 10.1016/S0531-5131(03)00066-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The aim of this study is to assess the anticerebral edema effect of glycerol on a large cerebral infarction with magnetic resonance imaging (MRI). Glycerol, which is widely used as an osmotic agent against cerebral edema, could exacerbate brain tissue shift, since it has been suggested that glycerol might shrink a noninfarcted hemisphere and worsen the mass effect after a large hemispheric cerebral infarction. To investigate these issues, changes in a large hemispheric infarction with cerebral edema were studied using MRI before and after glycerol administration. Infarct volumes, normal brain tissue volumes and lateral ventricle volumes, in addition to signal intensities of T(2)-weighted images, were measured in six patients before and after administration of 300 ml of glycerol. Ventricle volumes were significantly increased (p=0.0015) and the T(2) signal intensity of the post-treatment ischemic region decreased after glycerol administration. In contrast, no significant differences in either cerebral volume or T(2) signal intensity were seen in the noninfarcted hemisphere before and after administration. Our data suggest that glycerol does not exacerbate the mass effect on a large hemispheric infarction.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Dynamic contrast enhanced magnetic resonance imaging (dynamic MRI) represents a MRI version of non-diffusible tracer methods, the main clinical use of which is the physiological construction of what is conventionally referred to as perfusion images. The raw data utilized for constructing MRI perfusion images are time series of pixel signal alterations associated with the passage of a gadolinium containing contrast agent. Such time series are highly compatible with independent component analysis (ICA), a novel statistical signal processing technique capable of effectively separating a single mixture of multiple signals into their original independent source signals (blind separation). Accordingly, we applied ICA to dynamic MRI time series. The technique was found to be powerful, allowing for hitherto unobtainable assessment of regional cerebral hemodynamics in vivo.

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記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）   出版者・発行元：ELSEVIER SCIENCE BV  

To clarify regional difference in H-1 magnetic resonance spectral changes in the acute stage of focal cerebral ischemia, and to assess whether any correlation exists between spectral changes in acute stage and pathological outcome in the chronic stage, we measured the non-volume selected H-1-MRSI serially in the acute stage of focal ischemia in rat brain and correlated histopathological findings. The focal ischemia was induced by intraluminal MCA thread occlusion. After induction of focal ischemia, H-1-MR Spectroscopic Images (MRSI) were taken serially up to 10 h after the occlusion. NAA in the peri-ischemic area was maintained. On the other hand, the decline of NAA in the ischemic lesion was linear and drastic during the first 10 h after MCA occlusion, and the rates of decline of NAA concentrations up to 10 h after induction of ischemia, calculated with linear regression, were 0.44 m mol/kg/h in the ischemic core and 0.29 m mol/kg/h in the ischemic rim (p &lt; 0.05). Lactate accumulated significantly in all three areas. Decreasing depth of NAA during the acute stage of cerebral ischemia identifies the formation of the ischemic core and can be used as a predictor for histological outcome. (C) 2003 Elsevier Science B.V. All rights reserved.

DOI： 10.1016/S0531-5131(03)00025-6

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記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）   出版者・発行元：SPRINGER-VERLAG WIEN  

Background and purpose. To evaluate the feasibility of utilizing cerebral blood flow (CBF) index images, we attempted to investigate 1) whether CBF index images can reveal the resulting infracted area, 2) whether the CBF index can correlate other modality (SPECT).
Methods. DWI and DPI were obtained in 17 patients within 12 hours of stroke onset and follow up MRI. On three DPI delivered images, namely relative regional cerebral blood volume (rrCBV), uncorrected mean transit time (MTTu) and CBF index images, correlations between initial lesion volume of and follow up infarction volume of three images and rCBF images delivered with singular value decomposition (SVD) methods were assessed. Then Tc-99m-ECD SPECT was taken immediately after MRI to correlate to MRI data.
Results. Among the three images, lesion volume of CBF index images against follow up infarct volume had the highest correlation (r = 0.995) to a linear fit and the slope was closest to 1.0 (0.91) and had identical accuracy to the regression coefficient of rCBF images. CBF index well correlated to SPECT delivered CBF.
Conclusion. CBF index images can accurately predict final infarct volume. Evaluating CBF index images together with DWI can guide the initial assessment in the acute stage of cerebral ischemia.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語  

The therapeutic efficacy of ozagrel sodium (ozagrel), alone and in combination with heparin, and its therapeutic time window were studied in a photochemically induced thrombotic cerebral infarction rat model. Cerebral artery thrombosis was induced by irradiating the brain with green light through intact skull using rose bengal as the photosensitizing dye. One set of animals was treated immediately after thrombosis with (1) vehicle, (2) 10 mg/kg ozagrel in saline, intravenously (i.v.), (3) 150 U/kg unfractioned heparin, subcutaneously (s.c.), or (4) ozagrel, i.v. plus heparin, s.c. Infarct volume was significantly smaller and edema was reduced in the ozagrel-treated groups compared to the vehicle-treated group; heparin did not convey additional benefit. In another set of animals, rats were given either vehicle or 10 mg/kg ozagrel in saline, i.v., 60 min or 120 min after induction of thrombosis. Ozagrel reduced infarct volume, but its effect diminished with delayed administration. The therapeutic window was determined to be less than 60 minutes after induction of thrombosis.

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記述言語：英語  

Monteplase, a modified recombinant tissue plasminogen activator (rt-PA), has a long half-life and reduces binding to plasminogen activator inhibitor. In this study we investigated whether its systemic administration reduces infarct volume without increasing the risk of intra-cerebral hemorrhage. The effect of the drug was tested on an embolic stroke rat model that uses white clots. Thirty minutes after clot embolization, rats were infused with 2.2 mg kg(-1) of monteplase or the same amount of saline, over 60 min. Relative regional cerebral blood flow had recovered 60 min after monteplase administration and infarct volume was significantly smaller 24 h after clot embolization in the monteplase-treated rats (47.0 mm3) than in the saline-treated rats (130.4 mm3). Also, the hemorrhagic transformation area was significantly smaller in monteplase-treated rats (0.8 mm2 vs. 18.0 mm2, respectively). These results indicate monteplase can be a promising thrombolytic agent for treatment of the acute stage of cerebral ischemia.

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記述言語：日本語   出版者・発行元：特定非営利活動法人 日本バイオレオロジー学会  

DOI： 10.11262/jpnbr1987.16.3_61

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その他リンク： https://jlc.jst.go.jp/DN/JALC/10009198035?from=CiNii

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

The purpose of this study was to determine whether regional differences in metabolites can be seen chronologically in permanent focal cerebral ischemia using H-1 magnetic resonance spectroscopic imaging (MRSI), and whether these changes reflect pathological outcome. Regional variation in metabolites after permanent focal ischemia were, investigated longitudinally in rats using H-1 MRSI for a total of 7 days and then compared to histopathological findings. Four hours after the induction of ischemia. N-acetyl-L-aspartate (NAA) levels in the lateral caudo-putamen and the somatosensory cortex, core ischemic regions, decreased 22 and 40%, respectively. This reduction in NAA was coupled with a marked rise in lactate. In the medial caudo-putamen, the ischemic rim, however, NAA was preserved in spite of a marked increase in lactate. By 24 h post ischemia, the levels of NAA in medial caudo-putamen (ischemic rim in caudate) also decreased significantly. However NAA in cingulated cortex (ischemic rim in cortex) decreased more gradually between 24 and 48 h. This regional difference can reflect the severity of metabolic derangement in the acute stage. After 96 h following ischemia, the levels of all metabolites detected by H-1 MRSI had decreased and the levels of NAA decline reflected the severity of histopathological damage. In conclusion, the regional metabolic differences could be assessed by H-1 MRSI chronologically. and the depth of NAA decline reflected histopathological changes in the chronic stage. (C) 2001 Elsevier Science B.V. All rights reserved.

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記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）  

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記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）  

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記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Medical Association of Nippon Medical School  

Gd-DTPA has a T1 shortening effect that enhances the contrast in MRI and is widely used for the clinical evaluation of CNS diseases, though it is not suitable for the detection of cerebral ischemic regions during the superacute stage. Superparamagnetic iron oxide particles have a T2 shortening effect on relaxation time, reducing signal intensity on T2- weighted MRI in normal cerebral tissue. From this perspective we tested the feasibility of detecting ischemic lesions during the superacute stage using superparamagnetic iron oxide particles-enhanced MRI. Male Sprague-Dawley rats were anesthetized using pentobarbital and the left middle cerebral artery was permanently occluded (lt.-PMCAO) using a modified version of the Koizumi method. After lt.-PMCAO, 100 μmoles Fe/kg, 1 ml/kg magnetite, superparamagnetic iron oxide particles, (magnetite-injected group, n=9) or physiological saline (vehicle-injected group, n=9) was injected into the femoral vein. T2-weighted MR images were performed at designated time points immediately after injection of magnetite or vehicle on a 6.34 T MR unit. Additionally, in separate animals coronal sections of the brain were stained with 4% 2, 3, 5 triphenyl-tetrazoline-chloride (TTC) to confirm the infarct region. In the magnetite-injected group, a high signal area at the region of lt.-MCA was visible within 20 to 30 min following lt.-PMCAO, whereas in the vehicle-injected group no high signal ischemic area could be confirmed until 3 h after lt.-PMCAO. Infarction was noticed in the TTC staining 3 h following lt.-PMCAO. In this study magnetite injection allowed the detection of ischemia in the occluded MCA area on T2-weighted MRI during the superacute stage. These results suggest that ischemia during the superacute stage can be evaluated using magnetic enhanced MRI.

DOI： 10.1272/jnms1923.65.201

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Medical Association of Nippon Medical School  

The superacute stage of focal ischemia can be visualized using T2- weighted MRI following the injection of superparamagnetic iron oxide particles (magnetite). In this study we evaluated the optimal time point, i.e. the time producing the strongest signal, for the injection of magnetite using T2-weighted MRI following left permanent middle cerebral artery occlusion (lt.-PMCAO). Male Sprague-Dawley rats were anesthetized and the left middle cerebral artery (lt.-MCA) was permanently occluded. Magnetite was then injected into the femoral vein after 20 to 30 min of lt.-PMCAO. T2- weighted MR images were taken immediately, and 15 and 30 min after magnetite injection. A high signal area at the region of the lt.-MCA was clearly seen on the T2-weighted MRI immediately after magnetite injection. However, it became less clear after 15 min, and by 30 min could not be distinguished. These results suggest that magnetite should be injected immediately prior to T2-weighted MR imaging during the superacute stage of focal ischemia.

DOI： 10.1272/jnms1923.65.135

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Lippincott Williams and Wilkins  

The authors examined two Japanese siblings with a recessive hereditary spastic paraplegia (HSP) with dementia and a thin corpus callosum. Both showed thalamic glucose hypometabolism on PET. Recessive HSP with a thin corpus callosum is a rare disorder, with less than 20 reported patients, that may be a Japanese subtype of HSP.

DOI： 10.1212/WNL.51.6.1751

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記述言語：日本語   出版者・発行元：公益社団法人 日本放射線技術学会  

DOI： 10.6009/jjrt.KJ00001351709

CiNii Article

CiNii Books

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The metabolism of [1‐13C]glucose in the rat brain during hypoxia was investigated by 13C NMR spectroscopy. Male Wistar rats, weighing 100–120 g, were anesthetized with ketamine (50 ˜ 75 mg/kg i.p.) and ventilated mechanically with a mixture of 30% oxygen, 69.5% nitrogen and 0.5% halothane. [1‐13C]glucose (250 mg/kg) was infused twice, at 10 minute intervals, through the femoral vein. For the control group (n = 4), the oxygen concentration of the inspiratory gas was maintained at 30% by vol throughout the experiments. For the hypoxia group (n = 6), the oxygen concentration in the inspiratory gas was reduced to 6–7% (93–94% nitrogen) and maintained for 30 min following [1‐13C]glucose infusion. 13C NMR spectra were measured by a gated proton‐decoupling method without a nuclear Overhauser effect. The [1‐13C]glucose infusion gave apparent signals of the C1 carbon in the α‐ and β‐anomers of [1‐13C]glucose at 92.7 and 96.7 ppm, respectively. Signals of the C2, C3 and C4 carbon atoms in glutamate and/or glutamine (glx) also appeared at 55, 27 and 34 ppm, respectively. The intensity of glx‐C2 and glx‐C3 signals increased later than that of glx‐C4. The time lag between the different glx signals may reflect the turnover rate of the TCA cycle. Under the hypoxic condition, the signal of C3 carbon in lactate appeared at 21 ppm and increased. The α‐glucose signal diminished during hypoxia, whereas the β‐glucose signal kept its intensity. The difference in changes of the signal intensity between α‐ and β‐glucose suggests that α‐glucose is consumed more than β‐glucose in the hypoxic brain. Copyright © 1989 John Wiley &amp
Sons, Ltd.

DOI： 10.1002/nbm.1940020305

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記述言語：日本語   出版者・発行元：(一社)日本認知症学会  

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記述言語：日本語   出版者・発行元：(公社)日本整形外科学会  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J01133&link_issn=&doc_id=20190731130002&doc_link_id=%2Ffj2ortho%2F2019%2F009307%2F003%2F0450-0455%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Ffj2ortho%2F2019%2F009307%2F003%2F0450-0455%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：日本基礎心理学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）  

Web of Science

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(公社)日本整形外科学会  

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記述言語：日本語   出版者・発行元：(株)臨床評価刊行会  

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記述言語：英語   出版者・発行元：OXFORD UNIV PRESS  

DOI： 10.1093/brain/awx141

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記述言語：日本語   出版者・発行元：(株)中外医学社  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：SAGE PUBLICATIONS INC  

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記述言語：日本語   出版者・発行元：日本脳神経CI学会  

2-ヒドロキシグルタル酸(2HG)は正常組織では殆ど検出されないが、IDH変異を有するグリオーマでは蓄積する。IDH変異を有するグリオーマ症例で、3T-single voxel Magnetic Resonance Spectroscopy(3T-SVMRS)を用いて、2HGを検出できることを報告した。その内容を、1)IDH変異と2HG、2)IDH変異を有するグリオーマの特異なbiology、3)3T-SVMRSの撮像条件、4)SVMRSによる2HGの検出、5)2HGの測定の臨床的意義、の5項目に分けて解説した。

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J-GLOBAL

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記述言語：英語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(株)インナービジョン  

新潟大学脳研究所は、脳神経外科と神経内科の臨床2科、神経病理部門、そして統合脳機能研究センターなどを有している。同センターの中田力名誉教授(当時・教授/センター長)の発案により実現した、3T MRIを用いた死後画像解析システムが稼働している。われわれのポリシーは、死亡時画像診断(以下、Ai)施行後直ちに病理解剖を行い、画像情報と組織所見を統合して病態理解につなげようとするものである。Aiを剖検の代替手段として行おうとするものではない。本稿では、神経疾患を対象として当研究所が取り組んでいる死後画像解析システムと病理解剖について紹介する。(著者抄録)

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記述言語：日本語   出版者・発行元：(公社)日本放射線技術学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：(株)インナービジョン  

脳腫瘍の画像診断は、(1)存在・局在診断(腫瘍性病変の検出と部位・進展範囲の把握)、(2)質的(腫瘍の組織型と悪性度)診断推定と鑑別診断、(3)術前情報取得、(4)術後評価、(5)治療効果判定のいずれにも大きく関与する。CTは、(1)(2)における腫瘍の石灰化の検出、(3)での頭蓋骨描出などにおいて有用であるが、MRI情報はすべての過程において重要である。本稿では、神経膠腫の(2)(3)における当施設でのMRI撮像について、症例を提示して示す。なお、3T MRI装置を用いたMRスペクトロスコピー(MRS)、arterial spin labeling(ASL)法による灌流MRI、拡散テンソル画像(DTI)、three dimensional anisotropy contrast(3D-AC)法による神経線維描出は、本学脳研究所統合脳機能研究センターの協力を得て行っている。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

脳組織のダイナミックな代謝動態を捉え得るというプロトン磁気共鳴スペクトロスコピー(1H-MRS)の特徴は将来、神経救急疾患のdecision makingに関して重要な武器となる可能性を秘めている。虚血性脳血管障害1H-MRSの撮像の実際と、そのスペクトルから読み取ることができる病態に関して自験例を示しつつ概説した。

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：新潟県医師会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

脳虚血による神経細胞障害における核蛋白TAR DNA結合蛋白-43(TDP-43)の関与を明らかにすることを目的として、TDP-43の細胞内局在変化、限定分解、ユビキチン化、封入体形成、不溶化、異常リン酸化の有無を、ラット中大脳動脈閉塞モデルを用いて検討した。この結果、脳虚血後、TDP-43の核から細胞質への局在変化が生じること、限定分解により25kDaC末端断片が生成されること、TDP-43が細胞質に移行した神経細胞は、高率にユビキチン陽性、TUNEL反応陽性となるものの、封入体形成や不溶化、異常リン酸化は生じないことを明らかにした。以上より、虚血性神経細胞障害に、細胞内局在変化や限定分解に伴うTDP-43の生理的機能の喪失(loss of function)が関与する可能性が示唆された。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本小児神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(株)日本臨床社  

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2010&ichushi_jid=J01205&link_issn=&doc_id=20101210240043&doc_link_id=%2Fag6niria%2F2010%2Fs06810%2F044%2F0244-0248%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fag6niria%2F2010%2Fs06810%2F044%2F0244-0248%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：新潟県医師会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：(株)メディカ出版  

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記述言語：日本語   出版者・発行元：日本脳神経外科コングレス  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：日本語   出版者・発行元：(株)医学書院  

超高磁場(7T)装置の特性として、信号・ノイズ比、磁化率効果、緩和時間、B1不均一性、比吸収率について解説し、7T装置を用いた脳神経学研究の現状について概説した。7T装置は一般臨床装置としてではなく、あくまでも特殊臨床装置として開発されている。7T装置で臨床的に有用であることが示されたものの殆どが磁化率強調画像(SWI)によるもので、アルツハイマー病における老人斑、脳腫瘍の術前診断や詳細解析などに威力を発揮している。7T装置において最も期待されている機能画像はスペクトロスコピックイメージングによる代謝画像である。

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2010&ichushi_jid=J01228&link_issn=&doc_id=20100205020002&doc_link_id=10.11477%2Fmf.1436101104&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1436101104&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

3T clinical MR system上において、日常臨床への応用が可能なComplete cross-sectional 1H-MRSIを開発し、正常成人例および脳腫瘍をはじめとした疾患例に応用した。正常成人例では脳内の各部位における1H-MRSIにて明瞭に測定されるN-アセチル・アスパルテート(NAA)、クレアチニン+リン酸クレアチニン(Cr)、コリン化合物(Cho)の分布状態の差異が描出可能であった。疾患例では多形性神経膠芽腫の腫瘍内の代謝物分布のheterogeneityを明確に描出し得た。Complete cross-sectional 1H-MRSIは臨床におけるmetabolic mapping法として有用であり、今後の臨床応用が期待される。(著者抄録)

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記述言語：日本語   出版者・発行元：日本脳低温療法・体温管理学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳神経外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳神経外科学会  

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記述言語：日本語   出版者・発行元：(株)先端医学社  

血栓溶解療法の治療法選択および病巣予後予測に関して、拡散強調画像(DWI)および脳灌流画像(PI)がどのように寄与するかを、自験例を中心に総説した。虚血性脳血管障害急性期にDWI、PIは個々の症例の予後を予測する「万能ツール」ではないが、他の所見をあわせることにより病巣の広がりの予測、出血性梗塞の予測に強力な武器となる可能性を秘めている。(著者抄録)

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記述言語：日本語   出版者・発行元：日本脳腫瘍病理学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳神経外科学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：(一社)日本小児神経外科学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

[目的]高磁場MRIにおいて脳虚血急性期に於ける各MRI parameterの変動を検討する。[方法]ラットに120分の一過性局所脳虚血を負荷し、負荷前から再灌流後6時間までMRI連続測定を行った。MRI撮影によりT1,T2,T2*,ADC,CBFの各parameteric mapを作成し、各parameterの経時的変化を観察した。[結果および考察]T1は虚血中急峻な上昇を呈したが、最終的にADCが正常に復した領域は低下した領域に比較して軽微な上昇を示したのみであった。この減少はCBFの変化と併せ考察した時に、inflow effectのみでは解釈できないと考えられた。T2は虚血中に一旦低下したが、これはsusceptibility effectを反映したものと考えられた。T2*は虚血中および再灌流3時間後に二相性の一過性低下を呈し、O2 supplyとconsumptionのbalanceの変化によるものと考えられた。(著者抄録)

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記述言語：日本語   出版者・発行元：日本脳腫瘍病理学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Web of Science

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記述言語：日本語   出版者・発行元：(株)医学書院  

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2007&ichushi_jid=J01228&link_issn=&doc_id=20070226100008&doc_link_id=1573387450881688704&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1573387450881688704&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

今後臨床応用が可能と考えられるMRを用いた代謝動態解析を自験例を中心に提示する。1.multi parametric MRIを用いた抗脳浮腫効果のモニタリング 抗脳浮腫効果投与前後における虚血性脳浮腫の組成、脳血流の変化を生体においてmultiparametric MRIを用いて薬剤投与前後に測定し、抗脳浮腫効果のメカニズムを虚血モデルラットにて検討し、臨床例に応用した結果を提示する。2.虚血性脳血管障害急性期における1H-MRSI 脳虚血時にNAAは経過時間に相関して減少することが動物実験で確認されているが、発症6時間以内の中大脳動脈閉塞症例に1H-MRSIを施行すると、臨床例においてもNAAが発症後の時間に相関して減少すること、虚血周辺部では中心部に比し低下速度が低いことが確認され、将来MRSIによる虚血組織の可逆性の有無を判定できる可能性を示した。(著者抄録)

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：(株)日本臨床社  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：(株)先端医学社  

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記述言語：日本語   出版者・発行元：(株)先端医学社  

現時点において臨床・実験レベルで試みられている血栓溶解療法と他剤との併用療法のストラテジーとしては,大きく脳保護療法との併用により神経兆候の改善を目的としたもの,血管内皮保護療法との併用によりrt-PA投与の重大な副作用の一つである出血性梗塞,頭蓋内出血の抑制を目的としたもの,さらに他の抗凝固薬,抗血小板薬との併用により,rt-PAの効果増強,容量の低下を目的としたものがあげられる.本稿ではストラテジーのapplicationと現状を述べる(著者抄録)

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記述言語：英語   掲載種別：速報，短報，研究ノート等（学術雑誌）  

DOI： 10.1111/j.1468-1331.2006.01206.x

Scopus

PubMed

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：(株)メジカルビュー社  

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記述言語：日本語   出版者・発行元：(株)メジカルビュー社  

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記述言語：日本語   出版者・発行元：(一社)日本集中治療医学会  

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記述言語：日本語   出版者・発行元：(株)メジカルビュー社  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(株)北隆館  

本稿では広義の分子イメージングとして脳梗塞急性期の病態診断,治療法決定に用いられ始めた拡散強調画像(DWI)および脳灌流画像(PI)の解釈について概説する.DWI,PIは脳梗塞急性期の個々の症例の予後を完全に予測する"万能ツール"ではない.しかし,その所見の意味するところをしっかり解釈し,他の所見と併せることにより急性期における治療法選択の強い武器となる可能性を秘めている.今後,日本においてもrt-PAが認可され,超急性期の血行再建が普及した場合,この適応選択に大きな力となると考えられる(著者抄録)

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：医学書房(田辺三菱製薬(株))  

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記述言語：日本語   出版者・発行元：(株)先端医学社  

生体を無侵襲にくり返し測定できるという磁気共鳴スペクトロスコピー(MRS)の特徴を活かすことにより,種々の代謝動態の解析が可能である.本稿ではMRSの基礎およびMRSを用いた代謝動態解析例の提示をおこなう(著者抄録)

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：英語   出版者・発行元：日本脳循環代謝学会  

発症から24時間以内の脳梗塞患者16例を対象に,脳梗塞急性期に施行したdynamic perfusion MRI(DPI)のデータを用い,singular value decomposition(SVD)法とnon-deconvolution法という二種類の計算方法により導き出された脳血流量を,SPECTから求めたregional cerebral blood flow(rCBF)と比較した.その結果, 1)SVD法のrCBFとCBF indexはそれぞれSPECTのrCBFと有意に相関した(r=0.919,0.817,slope=1.007,0.757). 2)SVD法のrCBFとCBF indexの相関には有意差を認めなかった(p=0.784).以上,これらのことからも,CBF index mapは習熟者による処理が不要であり短時間で計算できるため,時間の限られた脳梗塞急性期における初回の脳血流評価に使用可能であると示唆された

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記述言語：日本語   出版者・発行元：(株)メディカ出版  

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記述言語：日本語   出版者・発行元：医学書房(田辺三菱製薬(株))  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：医学書房(田辺三菱製薬(株))  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(株)医学書院  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：医学書房(田辺三菱製薬(株))  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：(株)メディカ出版  

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記述言語：日本語   出版者・発行元：医学書房(田辺三菱製薬(株))  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Web of Science

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：(一社)日本神経治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本老年医学会  

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記述言語：日本語   出版者・発行元：(一社)日本老年医学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経治療学会  

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記述言語：日本語   出版者・発行元：脳浮腫・頭蓋内圧フォーラム  

ラット局所脳梗塞モデルを用いて,glycerol投与前後における脳浮腫の組成,水の状態の変化を各種MRパラメータmapより検討した.その結果,T1に反映される脳全体の含水量はglycerol投与後,全脳で有意に短縮し,結合水の割合を反映するMTRも全脳で増加を認めた.一方,自由水の割合を反映するT2は,glycerol投与後,梗塞部位でのみ有意な短縮を示した.以上より,glycerolは正常脳および梗塞領域にわたり脳含水量を低下させる効果がみられるが,その効果は自由水を血管外に引くことによるものであると考えられた.また,虚血性脳浮腫の領域では自由水が増加しているために,その効果が著明になることが示唆された

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：英語   出版者・発行元：日本脳循環代謝学会  

急性期脳梗塞66例(アテローム血栓性脳梗塞25例,心原性脳塞栓症21例,ラクナ梗塞20例)におけるPerfusion CTの有用性と問題点を検討した.その結果,1)Perfusion CTにより虚血性病変は66例中41例で検出された.2)この66例中20例は発症6時間以内の単純CTで明らかな低吸収域がみられなかったが,Perfusion CTによってこの20例中19例で虚血性病変が検出された.3)Perfusion CTは直径10mm未満の虚血性病変の検出は不可能であったが,アテローム血栓性脳梗塞と心原性脳塞栓症において,単純CTで明らかな低吸収域が出現する前に高率に虚血性病変を検出できた.以上,これらのことからもPerfusion CTは虚血性病変の早期検出が可能であり,特に血栓溶解術の適応を決める上で有用である

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：(株)先端医学社  

脳塞栓モデルは自家自栓ないしは他の個体より作成したフィブリン血栓を血管内に注入することにより臨床における脳塞栓を模した脳虚血を作成するものであり,血栓溶解療法の基礎的な検討には欠かせないモデルと考えられている.本稿では脳塞栓モデルの歴史的な背景,実際的な作成方法とモデルの特徴,モデルのアプリケーションを述べる(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：老年期認知症研究会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：ライフサイエンス出版(株)  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭痛学会  

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記述言語：英語   出版者・発行元：日本神経化学会  

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記述言語：日本語   出版者・発行元：(株)メジカルビュー社  

近年,実用化されたMRI高速撮影法により,脳血管障害,特に虚血性脳血管障害の急性期においては多くの有益な情報が得られるようになった.そこで,虚血性脳血管障害における脳機能イメージングの基礎を概説し,MRによる脳機能イメージング法として普及しはじめた拡散強調画像(DWI),脳灌流画像(PI)の原理を概説した

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記述言語：日本語   出版者・発行元：(株)にゅーろん社  

超急性期に得られたDPIデータより種々のマップを作成し,follow up MRIとの比較を行うことにより,急性期の治療法決定に最も適したマップを決定した.DPIより計算される各種灌流mapにおいてはCBFを反映したmapがdeconvolutionの有無に関わらず,視覚上最も最終梗塞を予測するのに優れていた.non-deconvolution法によるCBF index mapは,定量性ではSVD法によるrCBF mapに及ばないものの,計算が簡単で自動処理が可能であり,かつ最終梗塞に類似した灌流異常所見を示すことより急性期の治療法決定には有用であると考えられた.rCBFの定量においてはSVD法によるrCBF mapが優れるが,脳梗塞急性期のat risk領域の評価には計算の簡単なnon-deconvolution法によるCBF index mapでも十分可能であり,急性期において可及的に治療法決定を要する場合には短時間で複雑な操作が必要ないnon-deconvolution法をmap作成,評価に用いることが可能であると考えられた

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記述言語：日本語   出版者・発行元：(一社)日本老年医学会  

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記述言語：日本語   出版者・発行元：脳浮腫・頭蓋内圧フォーラム  

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記述言語：日本語   出版者・発行元：(一社)日本神経治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経治療学会  

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記述言語：日本語   出版者・発行元：(株)先端医学社  

磁気共鳴(MR)は基本的に特定の周波数で共鳴する原子のスピンの動向を観測する測定法であり,流れの状態や,測定される原子の統合している分子の状態の変化を観測することが可能である.本稿ではその例として血流の測定法(perfusion imaging),水以外の分子に結合する水素原子のmapping(MRSI),脳組織酸素抽出量のmappingについて測定原理と虚血性脳血管障害への応用を述べる(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：(株)先端医学社  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：(株)医学書院  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：(NPO)日本バイオレオロジー学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭痛学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：脳浮腫・頭蓋内圧フォーラム  

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記述言語：日本語   出版者・発行元：(株)先端医学社  

脳血栓モデルとして開発されたphotochemichal thrombosis modelについての概説を記した.このモデルは光増感剤を全身静脈投与し,特定の血管に光を照射することにより,局所的な血管を閉塞するものであり,侵襲が少なく,皮質を中心として均一な梗塞を短時間に作成できることが特徴である.また,光源,薬剤投与量を調節することにより中大脳動脈などの大血管を閉塞することも可能である(著者抄録)

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本老年医学会  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：(一社)日本老年医学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：ライフサイエンス出版(株)  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経治療学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭痛学会  

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記述言語：日本語   出版者・発行元：(株)にゅーろん社  

脳梗塞急性期のDWI,perfusion MRI(DPI)所見から最終的に梗塞に陥る領域の血流閾値を決定できるか,もしできるならどの計算画像が評価に最も適するか検討した.脳梗塞急性期発症12時間以内にDWI,DPIを施行し,ADC imageを算出,亜急性期のT2強調画像と比較した.DWI,DPIを併用することにより脳梗塞急性期において梗塞進展の予測が可能であり,その場合DPI計算画像中ではCBF index画像が最も優れていた.又,このことよりD-P mismatchを論じる場合にはCBFを反映したPI計算画像を用いるべきであり,その場合,日常臨床においては計算が簡便なCBF indexがその評価に有用であると考えられた

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記述言語：日本語   出版者・発行元：(株)新興医学出版社  

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記述言語：日本語   出版者・発行元：(株)中山書店  

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記述言語：日本語   出版者・発行元：(一社)日本老年医学会  

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記述言語：日本語   出版者・発行元：(株)文光堂  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：脳浮腫・頭蓋内圧フォーラム  

臨床例における大梗塞病変での,glycerolによるmass effect悪化の可能性を検討した.また,その実際の抗浮腫作用を,MRIを用いる事により評価する事が出来るかを検討した.MRIを用いた多数例の検討では,glycerolにより健常側半球の体積や緩和時間に有意の変化は見られず,mass effectの悪化は見られなかった.glycerol投与により,脳室の拡大などのmass effectの軽減を示す所見及び梗塞側半球の緩和時間の短縮が見られた.これは,glycerolの抗浮腫効果を反映する物と考えられ,MRIを用いる事により,実際の脳梗塞急性期の臨床例に対する抗浮腫効果を非侵襲的に評価する事が出来た

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：千代田開発(株)  

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