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：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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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 BV  

DOI： 10.1016/j.ecns.2020.07.002

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担当区分：最終著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.1007/s12311-020-01163-1

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その他リンク： http://link.springer.com/article/10.1007/s12311-020-01163-1/fulltext.html

担当区分：筆頭著者   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 BV  

Aquaporin-4 (AQP4) is a water conducting membrane integral protein channel which is widely expressed in the astrocyte system of the brain. During the development of the AQP4 positron emission tomography (PET) imaging agent [11C]TGN-020 (N-(1,3,4-thiadiazol-2-yl)pyridine-3-[11C]-carboxamide), significant radioligand uptake was observed in the skull, where there was no known distribution of any aquaporin family proteins. Herein we confirmed via a newly developed method for bone-tissue immunohistology, a hitherto unrecognized distribution of AQP4, and not AQP1, in the skull. Other bony structures, by contrast, showed virtually no uptake of [11C]TGN-020, and likewise, do not express either AQP4 or AQP1. Immunohistological analysis demonstrated that the AQP4 expression in the skull is restricted to the diploë. Consequently, we suspect AQP4 plays a pivotal role in the formation and maintenance of yellow marrow and the diploë. However, elucidating the exact nature of that role will require further studies.

DOI： 10.1016/j.heliyon.2020.e03259

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担当区分：責任著者   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 BV  

Profound insight into age-related changes in γ-aminobutyric acid type A receptor (GABAA-R) distribution using iodine-123-iomazenil single photon emission computed tomography (IMZ-SPECT) can contribute to accurate in vivo evaluation. We evaluated the age-related changes in prefrontal cortex (PFC), which is the key region involved in various neurological and psychiatric diseases. In this study, IMZ-SPECT imaging data of 21 healthy males with an age range of 22-59 (mean, 38 ± 12) years were analyzed using three-dimensional stereotactic surface projection (3D-SSP). The Z-score images of the younger group (age < 40, n = 11) and the older group (age ≥ 40, n = 10) were compared. Subsequently, the mean RI-count ratios calculated for each Brodmann area (BA) by stereotactic extraction estimation method were compared between these groups. Thereafter, linear regression analysis between age and RI-count ratio was performed for all enrolled subjects. In the result, IMZ accumulation increased in bilateral BA10, 11, and the BA47 (left hemisphere) in the older group compared with the younger group. Furthermore, regression analysis demonstrated a significant positive correlation between age and RI-count ratio in these areas. Our findings indicate that GABAA-R distribution in the PFC relatively increases with age. Therefore, we concluded that the age-related changes should be considered to accurately evaluate pathophysiology of neurological and psychiatric diseases.

DOI： 10.1016/j.jocn.2019.03.044

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担当区分：責任著者   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  

We presented a case of atraumatic tetanus developed initially with severe headache. Headache may be a clue to the presence of tetanus. Clinicians who usually treat headache should consider the possibility of tetanus in patients who present with symptoms that are severe and atypical for a given patient.

DOI： 10.1002/ccr3.2024

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Informa UK Limited  

DOI： 10.1080/01616412.2018.1522413

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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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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oxford University Press (OUP)  

<title>Abstract</title>
<sec>
<title>BACKGROUND</title>
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.


</sec>
<sec>
<title>OBJECTIVE</title>
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.


</sec>
<sec>
<title>METHODS</title>
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.


</sec>
<sec>
<title>RESULTS</title>
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 &amp;lt; .001) for both tumor grades. Importantly, mean standardized uptake values of astrocytoma grade IV were significantly higher than grade III (P &amp;lt; .01).


</sec>
<sec>
<title>CONCLUSION</title>
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.


</sec>

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）   出版者・発行元：ELSEVIER SCIENCE INC  

Purpose: To perform a systematic analysis of the intrinsic contrast parameters of the FLAIR hyperintense rim (FHR), a thin layer of high intensity covering the entire surface of the cerebral cortex detected on fluid-attenuated inversion recovery (FLAIR) sequence T-2 weighted imaging performed on a 7T system, in an attempt to identify its anatomical correlate.
Methods: Fast spin echo inversion recovery (FSE-IR) and cardiac-gated fast spin echo (FSE) images were obtained with defined parameters in eight normal volunteers on a 7 T MRI system to determine T-2 and proton density, T-1 characteristics. K-means clustering analysis of parameter sets was performed using MATLAB version R2015b for the purpose of identifying the cluster reflecting FHR. The results were subsequently confirmed by independent component analysis (ICA) based on Ti behavior on FSE-IR using a MATLAB script of FastICA algorithm.
Results: The structure giving rise to FHR was found to have a unique combination of intrinsic contrast parameters of low proton density, long T-2, and disproportionally short T-5. The findings are in strong agreement with the functional and structural specifics of the glia limitans externa (GLE), a structure composed of snuggled endfeet of astrocytes containing abundant aquaporin-4 (AQP-4), the main water channel of the brain.
Conclusion: Intrinsic contrast parameters of FHR reflect structural and functional specifics of the GLE, and their values are highly dependent on the physiologic functionality of AQP-4. Microscopic imaging on a 7T system and analysis of GLE contrast parameters can be developed into a method for evaluating AQP-4 functionality.

DOI： 10.1016/j.mri.2017.08.012

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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：NATURE PUBLISHING GROUP  

BACKGROUND: The 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 (H-1-MRS), which is capable of quantifying Glu in vivo.
METHODS: Normal 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.
RESULTS: In 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.
CONCLUSION: This 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）  

DOI： 10.1523/ENEURO.0183-17

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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）   出版者・発行元：MEDICAL ASSOC NIPPON MEDICAL SCH  

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 (H-1-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. H-1-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 gamma-aminobutyric acid (GABA). In this small review, we summarize basic concept of H-1-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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担当区分：最終著者   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：WILEY  

Introduction: In this study we sought to: (1) determine the distribution of GABA(A) receptors (GABA(A)-Rs) in the brain of Duchenne muscular dystrophy (DMD) patients; and (2) ascertain if the distribution pattern correlates with cognitive dysfunction. Methods: Fourteen DMD patients [young adult (n = 7, 18-25 years old) and older adult (n = 7, 30-37 years old) groups] and 16 age-matched normal volunteers participated. GABA(A)-R distribution was assessed using I-123-IMZ-SPECT. Neuropsychological assessments were performed using 3 different test batteries, the WAIS-III, WMS-R, and Wisconsin Card Sorting Test (WCST). Results: All DMD patients showed significant decline in I-123-IMZ uptake in the prefrontal cortex (P &lt; 0.05). Although no differences were detected in the WAIS-III and WMS-R, the WCST scores of DMD patients (2.8 +/- 1.9) were significantly lower (P &lt; 0.01) than those of normal volunteers (5.4 +/- 0.7). Both abnormalities were more pronounced in older adult patients. Conclusion: The findings demonstrate that DMD is accompanied by a reduction in the prefrontal cortex distribution of GABA(A)-Rs.

DOI： 10.1002/mus.25383

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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 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 x .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）  

DOI： 10.19080/APBIJ.2018.04.555626

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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：KARGER  

Background: In patients with cerebral infarction, identifying the distribution of infarction and the relevant artery is essential for ascertaining the underlying vascular pathophysiological mechanisms and preventing subsequent stroke. However, visualization of the basal perforating arteries (BPAs) has had limited success, and simultaneous viewing of background anatomical structures has only rarely been attempted in living human brains. Our study aimed at identifying the BPAs with 7T MRI and evaluating their distribution in the subcortical structures, thereby showing the clinical significance of the technique. Methods: Twenty healthy subjects and 1 patient with cerebral infarction involving the posterior limb of the internal capsule (ICpost) and thalamus underwent 3-dimensional fast spoiled gradient-echo sequence as time-of-flight magnetic resonance angiography (MRA) at 7T with a submillimeter resolution. The MRA was modified to detect inflow signals from BPAs, while preserving the background anatomical signals. BPA stems and branches in the subcortical structures and their origins were identified on images, using partial maximum intensity projection in 3 dimensions. Results: A branch of the left posterior cerebral artery (PCA) in the patient ran through both the infarcted thalamus and ICpost and was clearly the relevant artery. In 40 intact hemispheres in healthy subjects, 571 stems and 1,421 branches of BPAs were detected in the subcortical structures. No significant differences in the numbers of stems and branches were observed between the intact hemispheres. The numbers deviated even less across subjects. The distribution analysis showed that the subcortical structures of the telencephalon, such as the caudate nucleus, anterior limb of the internal capsule, and lenticular nucleus, were predominantly supplied by BPAs from the anterior circulation. In contrast, the thalamus, belonging to the diencephalon, was mostly fed by BPAs from the posterior circulation. However, compared with other subcortical structures, the ICpost, which marks the anatomical boundary between the telencephalon and the diencephalon, was supplied by BPAs with significantly more diverse origins. These BPAs originated from the internal carotid artery (23.1%), middle cerebral artery (38.5%), PCA (17.3%), and the posterior communicating artery (21.1%). Conclusions: The modified MRI method allowed the detection of the relevant BPA within the infarcted in the stroke survivor as well as the BPAs in the subcortical structures of living human brains. Based on in vivo BPA distribution analyses, the ICpost is the transitional zone of the anterior and posterior cerebral circulations. (C) 2016 S. Karger AG, Basel

DOI： 10.1159/000443538

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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）   出版者・発行元：JPN SOC MAGNETIC RESONANCE IN MEDICINE  

N-acetylaspartate (NAA) appears in a prominent peak in proton magnetic resonance spectroscopy (H-1-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   掲載種別：研究論文（学術雑誌）   出版者・発行元：MANEY PUBLISHING  

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：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Society of Nuclear Medicine  

To investigate a potential application of ordered subsets expectation maximization (OSEM) algorithm for clinical [15O]H2O PET studies, region of interest (ROI) measurements were performed on both images with OSEM and fitered back projection (FBP). Forty OSEM images were reconstructed with variable combinations of numbers of the subset (1-40) and iteration times (2-12). PET scans were acquired using a PET/CT scanner (Discovery ST Elite, GE), and 3T-MRI images were obtained for fusion images. The mean values were measured on the frontal cortical regions in the middle cerebral artery distribution. Differences of the values between the OSEM and FBP were evaluated as %Error. Relationship between ROI mean values and the iteration times was investigated on the OSEM images. The smallest %Error 0.4% was measured in the combination of the subset number 10 and iteration times 8 [10, 8], and in that of [28, 2]. The mean values were stable with iteration number 8 or more. OSEM image with [28, 2] was reconstructed in a shorter time (2.5 min) than that with [10, 8] (6 min). OSEM image with [28, 2] was superior to that with [10, 8] in the qualitative evaluation. The mean values on OSEM images with [28, 2] were comparable with those on FBP images with little artifacts and higher spatial resolution. OSEM with optimal parameter setting seemed applicable for both quantitative and qualitative [15O]H2O PET studies.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

BACKGROUND AND PURPOSE Aquaporin 4 (AQP-4) is the most abundant aquaporin isoform in the brain. Alterations in its expression and distribution have been correlated with the progression of several clinical disorders; however, the specific roles of AQP-4 in those disorders are not well understood. Visualizing AQP-4 in vivo is expected to provide fresh insights into its roles in disease pathology, as well as aiding the clinical assessment of those disorders. METHODS We developed a 11C-labeled analogue of the AQP-4 ligand TGN-020 (2-nicotinamido-1,3,4-thiadiazole) suitable for in vivo positron emission tomography (PET) imaging. RESULTS In the present study, we report the first PET images of AQP-4 in the human brain. The results unequivocally demonstrated a specific distribution pattern for AQP-4 within the brain, namely, the subpial and perivascular endfeet of astrocytes. The choroid plexus, where both AQP-4 and AQP-1 are expressed, also showed substantial uptake of the ligand. CONCLUSIONS Based on these initial results, we believe [11C]TGN-020 PET will be valuable in determining the role of AQP-4 in disease progression, and for the clinical assessment of water homeostasis under various settings.

DOI： 10.1111/j.1552-6569.2012.00704.x

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

The evaluation of human brain maturation in vivo is a significant problem for pediatric neurologists. MRI, especially Diffusion Tensor Imaging (DTI) and 1H-MR Spectroscopy (MRS), can be a powerful method to solve this problem. A decrease in three eigenvalues (Δλ1 &lt
Δλ2 ≓ Δλ3) and an increase in Fractional Anisotropy, as a function of brain maturation, was identified in the frontal and parietal white matter using DTI, which is a non-invasive imaging technique capable of providing a quantitative view of neural fibers and micro-environmental alterations during the myelination period. MRS, a powerful technique capable non-invasively quantifying N-acetyl-aspartate (NAA), a marker for neurons, glutamate (Glu), an excitatory neurotransmitter, and creatine (Cr), revealed a decrease in the Glu/Cr ratio, but found no changes to the NAA/Cr ratio with maturational changes in brain networks, such as a decrease in cortical synaptic density (refinement). Therefore, we suggest these two MRI techniques, DTI and MRS, can be used to provide direct, non-invasive information on brain maturation in vivo, which we believe will help elucidate the pathophysiology behind neurodevelopmental disorders that disrupt normal brain maturation.

DOI： 10.5692/clinicalneurol.53.1100

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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：AMER ASSOC NEUROLOGICAL SURGEONS  

Object. The authors assessed the role of 3D anisotropy contrast (3DAC) in evaluating specific ascending tract degeneration in patients with cervical spondylotic myelopathy (CSM).
Methods. The authors studied 10 patients (2 women, 8 men; mean age 59.8 +/- 14.6 years) with CSM and spinal cord compression below the C2-3 disc level, as well as 10 healthy control individuals (3 women, 7 men; mean age 42.0 +/- 24.1 years). Images of the cervical cord at the C2-3 level were obtained using a 3.0-T MR imaging system.
Results. Three-dimensional anisotropy contrast imaging clearly made possible tract-by-tract analysis of the fasciculus cuneatus, fasciculus gracilis, and spinocerebellar tract. Tract degeneration identified using 3DAC showed good correlation with a decline in fractional anisotropy. Degeneration of the fasciculus gracilis detected by "vector contrast" demonstrated a good correlation with Nurick grades.
Conclusions. The study unambiguously demonstrated that 3DAC imaging is capable of assessing ascending tract degeneration in patients with CSM. Degeneration of an individual tract can be easily identified as a vector contrast change on the 3DAC image, a reflection of quantitative changes in anisotropism, similar to fractional anisotropy. Excellent correlation between Nurick grades and fasciculus gracilis degeneration suggests potential application of 3DAC imaging for tract-by-tract clinical correlation. (DOI: 10.3171/2011.7.SPINE10843)

DOI： 10.3171/2011.7.SPINE10843

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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：AMER CHEMICAL SOC  

Aquaporin 4 (AQP4), the most abundant isozyme of the water specific membrane transporter aquaporin family, has now been implicated to play a significant role in the pathogenesis of various disease processes of the nervous system from epilepsy to Alzheimer&apos;s disease. Considering its clinical relevance, it is highly desirable to develop a noninvasive method for the quantitative analysis of AQP distribution in humans under clinical settings. Currently, the method of choice for such diagnostic examinations continues to be positron emission tomography (PET). Here, we report the successful development of a PET ligand for AQP4 imaging based on TGN-020, a potent AQP4 inhibitor developed previously in our laboratory. Utilizing [C-11]TGN-020, PET images were successfully generated in wild type and AQP4 null mice, providing a basis for future evaluation regarding its suitability for clinical studies.

DOI： 10.1021/cn2000525

Web of Science

PubMed

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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：DR DIETRICH STEINKOPFF VERLAG  

Diffusion characteristics of the pyramidal tract were assessed in nine patients who had clinical evidence of pyramidal tract dysfunction, utilizing lambda chart analysis (LCA). The underlying pathologic process of tract dysfunction was varied and included Pelizaeus-Merzbacher disease (PMD), Alexander disease, adrenoleukodystrophy (adreno-myeloneuropathy (AMD) type and cerebral type), amyotrophic lateral sclerosis (ALS), and Wallerian degeneration (WD). While pyramidal tract diffusion characteristics in WD indicated a pathological process characterized by replacement of normal fibers by smaller cellular component such as degenerated small fibers and/or gliosis, pyramidal tract diffusion characteristics in patients with PMD, Alexander disease, and adreno leukodystrophy of the cerebral type indicated a pathological process characterized by replacement of normal fibers by larger cellular components such as spheroids or edematous space. Pyramidal tract diffusion characteristics of patients with ALS or adrenoleukodystrophy of AMD type were relatively intact suggesting a pathological process characterized by relatively preserved structural architecture. These findings are highly consistent with known pathophysiological indices and indicate the feasibility of the clinical utility of LCA for assessing pyramidal tract physiology.

DOI： 10.1007/s00415-003-0175-4

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PubMed

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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：JOHN WILEY & SONS LTD  

The absolute eigenvalues of the diffusion tensor of white matter in sixteen normal subjects in two groups representing the early developmental stage (ages 1-10 years, n = 8) and young adult stage (ages 18-34 years, n = 8) were assessed using a high-field (3.0 T) magnetic resonance (MR) system. All three eigenvalues, including the largest eigenvalue, decreased significantly with brain maturation. The rate of the decline in the two small eigenvalues was, however, much higher than that of the largest eigenvalue, resulting in an actual increase in fractional anisotropy, a commonly measured relative index. The data demonstrate that an increase in anisotropy associated with brain maturation represents a significant decline in the small eigenvalue components, rather than an increase in the largest eigenvalue. The observed pattern of eigenvalue changes is best explained by the simultaneous occurrence of two of several independent phenomena within the axonal microenvironment during the myelination process, namely, (1) decline in unrestricted water content in extra-axonal space, and (2) increase in apparent diffusivity within the axon. Copyright (C) 2003 John Wiley Sons, Ltd.

DOI： 10.1002/nbm.848

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PubMed

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記述言語：英語   掲載種別：論文集(書籍)内論文  

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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 SCIENCE INC  

Two patients are described in a family with a mitochondrial DNA T8993C point mutation. Patient 1, the proband, was a 4-year-old male, and his clinical features were consistent with those of Leigh syndrome, including lactic acidosis, motor development delay, and symmetric basal ganglia lesions on magnetic resonance imaging (MRI). His mental development was delayed mildly, but he has not demonstrated neurologic deterioration. Patient 2 was his maternal aunt. She developed her first neurologic sign at 18 months of age, thereafter her development ceased and regressed. She had lost her head control and become bedridden by 4 years of age and died at 20 years of age, demonstrating a more severe clinical course than that of Patient 1, Analysis of mitochondrial DNA from peripheral leukocytes of Patient 1 revealed a T8993C mutation of 99%. Patient 2 was demonstrated to have the same mutation at high abundance (99%) in the frozen myocardium and in the formaldehyde preserved spinal cord, with only 18% mutant mitochondrial DNA present in the formaldehyde preserved sciatic nerve. The mother of Patient 1, who was phenotypically normal (sister of Patient 2), had 35% mutant mitochondrial DNA in peripheral leukocytes, The authors' findings suggest that T8993C phenotypes are highly variable and that the proportion of the mutant mitochondrial DNA may vary among tissues and not correlate well with clinical severity. (C) 1998 by Elsevier Science Inc. All rights reserved.

DOI： 10.1016/S0887-8994(98)00070-8

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PubMed

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記述言語：日本語  

CiNii Article

CiNii Books

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記述言語：英語  

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担当区分：筆頭著者,　責任著者   記述言語：英語  

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記述言語：英語   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.jns.2017.08.2694

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担当区分：筆頭著者,　責任著者  

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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：日本語   出版者・発行元：(一社)日本高次脳機能障害学会  

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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：英語  

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担当区分：責任著者  

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記述言語：英語  

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記述言語：英語  

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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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担当区分：筆頭著者,　責任著者  

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記述言語：英語  

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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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担当区分：責任著者  

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担当区分：責任著者  

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記述言語：英語  

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担当区分：責任著者  

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担当区分：筆頭著者,　責任著者  

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担当区分：筆頭著者  

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担当区分：筆頭著者   掲載種別：記事・総説・解説・論説等（学術雑誌）  

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担当区分：筆頭著者,　責任著者  

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担当区分：最終著者  

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担当区分：筆頭著者,　責任著者   記述言語：日本語  

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担当区分：筆頭著者   記述言語：英語  

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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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担当区分：筆頭著者  

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開催年月日： 2014年1月

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開催年月日： 2013年5月 - 2013年6月

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開催年月日： 2012年5月

会議種別：口頭発表（招待・特別）  

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開催年月日： 2011年3月

会議種別：シンポジウム・ワークショップ パネル（指名）  

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開催年月日： 2009年12月

会議種別：口頭発表（招待・特別）  

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開催年月日： 2004年8月

会議種別：シンポジウム・ワークショップ パネル（指名）  

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