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Background Simulation using a mock scanner preparation is beneficial for pediatric patients undergoing magnetic resonance imaging (MRI) without sedation for the assessment of neurocognitive function. However, using a simulation protocol for improving the completion of pediatric MRI has not been studied extensively. Methods A simulation protocol using a mock scanner “Zero-Tesla” preparation immediately before 3T MRI was utilized based on participants’ demographics. The success rate of each protocol step was compared between children with typical development (TD) and those with neurodevelopmental disorders (NDDs). Results Two-hundred forty-one children (4-17 years; 152 males, 89 females; 42.3% TD and 57.7% NDDs) were included. Acceptable MRI qualities were obtained for 100 (98.0%) and 130 (93.5%) children in the TD and NDD groups, respectively. In the NDD group, Zero-T application rates were higher in the young childhood (TD vs NDD; 2% vs 56%, p Conclusions Use of a simulation protocol could contribute to the successful completion of advanced MRI without sedation in children with TD and NDDs.

The objective of this study was to investigate lobule-specific cerebellar structural alterations relevant to clinical behavioral characteristics of Prader-Willi syndrome (PWS). We performed a case-control study of 21 Japanese individuals with PWS (age; median 21.0, range 13–50 years, 14 males, 7 females) and 40 age- and sex-matched healthy controls with typical development. Participants underwent 3-Tesla magnetic resonance imaging. Three-dimensional T1-weighted images were assessed for cerebellar lobular volume and adjusted for total intracerebellar volume (TIV) using a spatially unbiased atlas template to give a relative volume ratio. A region of interest analysis included the deep cerebellar nuclei. A correlation analysis was performed between the volumetric data and the clinical behavioral scores derived from the standard questionnaires (hyperphagia, autism, obsession, and maladaptive index) for global intelligence assessment in paired subgroups. In individuals with PWS, TIV was significantly reduced compared with that of controls (p 3). Decreased relative lobular volume ratios were observed in posterior inferior lobules with age, sex, and TIV as covariates (Crus I, Crus II, lobules VIIb, VIIIa, VIIIb, and IX). However, increased ratios were found in the dentate nuclei bilaterally in individuals with PWS (p −3was as follows: left, 1.58 (0.26); right, 1.67 (0.30). The altered lobular volume ratios showed negative correlations with hyperphagic and autistic characteristics and positive correlations with obsessive and intellectual characteristics. This study provides the first objective evidence of topographic patterns of volume differences in cerebellar structures consistent with clinical behavioral characteristics in individuals with PWS and strongly suggests a cerebellar contribution to altered functional brain connectivity in PWS.

Background: Prader–Willi syndrome (PWS) is a genetic syndrome with clinical behavioral phenotypes, including autistic characteristics. However, brain functional connectivity (Fc) remains underrepor...

Ultra-high field magnetic resonance imaging (MRI) has been introduced for use in pediatric developmental neurology. While higher magnetic fields have certain advantages, optimized techniques with specific considerations are required to ensure rational and safe use in children and those with pediatric neurological disorders (PNDs). Here, we summarize our initial experience with clinical translational studies that utilized 7 tesla (T)-MRI in the fields of developmental neurology. T2-reversed images and three-dimensional anisotropy contrast imaging enabled the depiction of targeted pathological brain structures with better spatial resolution. Diffusion imaging and susceptibility-weighted imaging enabled visualization of intracortical, subcortical, and intratumoral microstructures in vivo within highly limited scan times appropriate for patients with PNDs. 7T-MRI appears to have significant potential to enhance the depiction of the structural and functional properties of the brain, particularly those associated with atypical brain development.

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 T2 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 T2 and proton density, T1 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 T1 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 T2, and disproportionally short T1. 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.

In this paper, rotational element electronically scanned array(REESA) is proposed. REESA is composed of helical array which is fed by waveguide and connected to a motor. The beam scanning performance is calculated and feasibility of REESA is shown.

Mutations in the gene encoding hypoxanthine-guanine phosphoribosyltransferase (HPRT) cause Lesch-Nyhan disease (LND) and its variants (LNV). Due to the technical problems for measuring the HPRT activity in vitro, discordances between the residual HPRT activity and the clinical severity were found. 5-Phosphoribosyl 1-pyrophosphate (PRPP) is a substrate for HPRT. Since increased PRPP concentrations were observed in erythrocytes from patients with LND and LNV, we have turned our attention to erythrocyte PRPP as a biomarker for the phenotype classification. In the present work, a method for determination of PRPP concentration in erythrocyte was developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with multiple reaction monitoring (MRM). Packed erythrocyte samples were deproteinized by heating and the supernatants were injected into the LC-MS/MS system. All measurement results showed good precision with RSD6%. PRPP concentrations of nine normal male subjects, four male patents with LND and six male patients with LNV were compared. The PRPP concentrations in erythrocyte from patients with LND were markedly increased compared with those from normal subjects, and those from patients with LNV were also increased but the degree was smaller than those with LND. The increase pattern of PRPP concentration in erythrocyte from patients with HPRT deficiency was consistent with the respective phenotypes and was correlated with the disease severity. PRPP concentration was suggested to give us supportive information for the diagnosis and the phenotype classification of LND and LNV.

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 700μ, the superior microscopic resolution of MRI of 4 μ presents a strong incentive for research into ligand-based molecular MRI. METHODS 17O exhibits JJ vicinal coupling with a covalently bound proton in a hydroxyl group. This 17O 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 β-amyloid distribution in human APP overexpressed transgenic mice in vivo following injection of 17O labeled Pittsburg compound B (17O-PiB). RESULTS JJVCPE imaging successfully imaged 17O-PiB, unequivocally establishing that 17O 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.

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 area 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.

PURPOSE This study investigated the relationship between the degree of mandibular alveolar ridge resorption and the number of denture adjustments after insertion of dentures in complete denture wearers. METHODS The subjects were 77 complete denture patients (34 males, 43 females, mean age 69.1+/-8.1 years). Using bite plates of Gothic arch tracing for new denture production, the width, height, and inclination toward the tentative occlusal plane of the mandibular alveolar ridge corresponding to the canine areas (C), first premolar areas (P1), second premolar areas (P2), and first molar areas (M1) were measured bilaterally, and the relationship with the number of denture adjustment was evaluated. RESULTS The mean of number of denture adjustments was 4.4+/-1.8 times (male 3.8 times, female 5.0 times), showing a significant difference between males and females (p

Methyl 4,6-O-benzylidene-2,3-dideoxy-3-C-p-tolylsulfonyl-2-C-p-tolylthio-β-d-glucopyranoside and its 5a-carba-dl-analog exit mainly in a non-chair conformation in solutions, but the latter occupies a chair conformation in a solid state.

Purpose : This study clarified the relationship between regular denture wear and neuroticism.Materials and Methods : The subjects were 60 patients (28 males and 32 females) who underwent prosthodontic treatment using plate dentures made by the same dentist. Their mean age was 65.6±7.5 years. After adequate explanation of the purpose and importance of this study, psychological tests using the Cornell Medical Index (CMI) were performed with informed consent. The association between denture wear and neuroticism was evaluated.Results : Fifty-five patients regularly wore their new dentures. The other patients (all were females) used dentures during meals but could not regularly wear them. The classification and distribution of the CMI neurosis areas were as follows : 34 patients (56.7%) were classified as Group I (psychologically normal), 20 (33.3%) as Group II (quasi-normal), 3 (5.0%) as Group III (quasi-neurotic), and 3 (5.0%) as Group IV (neurotic). The patients who could not regularly wear their dentures showed high values among the criteria for the discrimination of neuroses, i.e., inadequacy, depression, anxiety, anger, tension, cardiovascular system, fatigability, and frequency of illness. Many of them were classified as Group III (quasi-neurotic) or IV (neurotic).Conclusion : Compared to patients who could regularly wear their dentures, those who could not regularly wear their dentures showed higher values for eight of the nine criteria for the discrimination of neuroses, which indicated marked neuroticism. These results suggested an association between patients who cannot regularly wear their dentures and neuroticism.

Thrust imparted from a Magneto-Plasma-Dynamic thruster is directly measured by using a pendulum type thrust target and is successfully increased twice by applying a magnetic nozzle. The presently obtained thrust performance shows a thrust of ~ 6 N and a specific impulse of ~ 9000 sec for the discharge current of 6 kA. The plasma axial flow velocity is increased up to 40 km/sec near the thruster exit when increasing the magnetic nozzle field strength. Further downstream region the plasma flow is decelerated and an increase in an ion temperature is simultaneously detected. The results suggest that the axial flow energy is converted into the thermal ion energy.

Independent component analysis (ICA) has been shown as a promising tool for the analysis of functional magnetic resonance imaging (fMRI) time series. Each of these studies, however, used a general‐purpose algorithm for performing ICA and the computational efficiency and accuracy of elicited neuronal activations have not been discussed in much detail. We have previously proposed a direct search method for improving computational efficiency. The method, which is based on independent component‐cross correlation‐sequential epoch (ICS) analysis, utilizes a form of the fixed‐point ICA algorithm and considerably reduces the time required for extracting desired components. At the same time, it is shown that the accuracy of detecting physiologically meaningful components is much improved by tailoring the contrast function used in the algorithm. In this study, further improvement was made to this direct search method by integrating an optimal contrast function. Functional resolution of activation maps could be controlled with a suitable selection of the contrast function derived from prior knowledge of the spatial patterns of physiologically desired components. A simple skewness‐weighted contrast function was verified to extract sufficiently precise activation maps from the fMRI time series acquired using a 3.0 Tesla MRI system. Hum. Brain Mapping 15:54–66, 2001. © 2001 Wiley‐Liss, Inc.

目的: 本研究は全部床義歯患者におけるタツピングポイントの安定性と新義歯の調整回数との関連について明らかにすることである.方法: 調査対象者は81名 (男性35名, 女性46名, 平均年齢69.2±8.0歳) の無歯顎患者である.新義歯製作の過程でタッピングポイントとゴシックアーチの記録を行い, タッピングポイントとゴシックアーチのアペックス間の距離, タッピングポイントの偏位方向, タッピングポイントの収束度を分析し, 義歯調整回数との関連を検討した.結果: 義歯の調整回数は平均4.4±1.8回 (男性3.8回, 女性4.9回) であった. アペックスとタッピングポイント間の距離は平均0.8±1.0mm (男性0.5mm, 女性1.0mm) であった.アペックスとタッピングポイント間の距離が0.6mm以上の37名におけるタッピングポイントの偏位方向は前方偏位が15名 (40.5%), 側方偏位が22名 (59.5%) であった. タッピングポイントは収束していたものが70名 (86.4%), 収束していなかったものが11名 (13.6%) であった. 調整回数が多い症例はアペックスとタッピングポイント間の距離が0.6mm以上の割合が増加した.結論: 全部床義歯患者における義歯調整回数とゴシックアーチのアペックスとタッピングポイント間距離との間に高い関連が認められ, アペックスとタッピングポイント間の距離が0.6mm以上の症例では義歯装着後, 調整回数が多くなることが示唆された.

A new technique for functional magnetic resonance imaging (fMRI) time series analysis is presented. The technique referred to here as independent component-cross correlation-sequential epoch (ICS) analysis is a hybrid technique of two standard methodologies of biological signal analysis, namely, data driven methods, represented by independent component analysis, and hypothesis driven methods, represented by a general linear model. The technique successfully identified four functionally discrete areas within the primary sensorimotor cortex (SMI) in normal human subjects based on blood oxygenation level dependent (BOLD) contrast functional magnetic resonance imaging (fMRI) time series performed on a high field (3.0 T) system. Each of the four areas identified corresponded to the four physiological subdivisions of SMI, recognized in primates to be essential for voluntary hand motion, namely, 4 anterior (MI-4a) and 4 posterior (MI-4p) of the primary motor cortex, and 3a and the ‘classical’ (Brodmann areas 1, 2, and 3b) primary sensory cortex, respectively. ICS analysis appears to be a highly reliable and versatile technique for fMRI time series analysis.

The purpose of this paper is to investigate the grain orientation and properties of SrBi2Ta2O9 (SBT) ceramics with excess Bi2O3. Ordinarily fired (OF) ceramics were prepared by conventional ceramic techniques at 900–1300°C for 2 h. The grain-oriented (GO) ceramics were prepared using the hot-forging method. With addition of Bi2O3 in the amount of 0 – 1.5 wt% to the SBT of stoichiometric composition, the optimum firing temperature in OF ceramic samples gradually lowered with increasing Bi2O3 addition, and was about 1100°C in the case of 0.5 wt% of excess Bi2O3. Plastic deformation is easily accomplished using the hot forging method where Bi2O3 exists as a state of liquid phase within the sample. In fact, the GO sample with 0.5 wt% of excess Bi2O3 showed a highly structured orientation f=0.97 in the case of hot-forging at 1100°C.

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 700μ, the superior microscopic resolution of MRI of 4 μ presents a strong incentive for research into ligand-based molecular MRI. METHODS 17O exhibits JJ vicinal coupling with a covalently bound proton in a hydroxyl group. This 17O 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 β-amyloid distribution in human APP overexpressed transgenic mice in vivo following injection of 17O labeled Pittsburg compound B (17O-PiB). RESULTS JJVCPE imaging successfully imaged 17O-PiB, unequivocally establishing that 17O 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.

Complete denture wearers rarely complain about TMJ disorders. However, there aremany morphological differences of the condyle in complete denture wearers. The purpose of this study was to clarify the relationship between morphological factors of condyles and the path of protrusive mandibular movements in complete denture wearers. The subjects consisted of 107 complete denture wearers (42 males, 65females, mean age 69.7 years) without symptoms involving the TMJ. The shape, theabnormal bone changes and the size of the right and left condyles were examined by panoramic radiography. Horizontal mandibular movements were recorded for lateral deviation during protrusive movement by gothic arch tracing.The resultswere as follows:1. The shapes of the condyle were classified in four types.Type I (round) was 111 condyles (51.9%), Type II (flat anterior portion) was 34 condyles (16.2%), Type III (flat top portion) was 31 condyles (14.5%) and Type IV (flat posterior portion) was 38 condyles (17.7%).2. The abnormal bone changes of condyle were found in 56 cases (77 joints, 36.0%). The bone changes of condyle were Erosion, Osteophyte, Flattening, Concavity, Deformity, Irregular surface and Eburnation.3. A difference of the size of the right and left condyles was found in 32 cases (29.9%).4. The average lateral deviation during protrusive mandibular movement was 1.0±0.6 mm (male 0.8mm, female 1.1 mm)5. In case of less lateral deviation, the Type I tended to increase, but in case of much lateral deviation, the Type III tended to increase.6. Much lateral deviation during protrusive movement in patients appeared in a high ratio in relation to the difference of the size of condyle, abnormal bone changes of condyles and morphological changes of condyle shape.

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/mm2 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/mm2, 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.

The aim of this pilot study was to consider evaluation of the psychological effects of dental prosthetic treatments using ESAM.We examined gum chewing with and without an occlusal interference device that simulated a negative change in oral sensation in four subjects. First, we analyzed the temporal components of mandibular movement trajectories as indices for evaluating the degree to which chewing is actually impaired by occlusal interference. Subsequently, we measured brain activity before and after chewing for each of the two conditions (with or without the occlusal interference device). For brain activity, we used the four emotional indices of stress, sadness, joy and relaxation based on ESAM to estimate psychological states before and after chewing, and made a comparison between the two conditions. Statistical analyses were performed with Mann-Whitney's U-test (p0.05).The opening phase and chewing cycle were shorter when wearing the occlusal interference device in every subject. There was a significant difference for all subjects (p0.05) in the closing cycle. Therefore, because a significant difference occurred for at least one temporal component of the mandibular movement trajectory for every subject, we concluded that normal chewing in subjects was impaired by wearing the occlusal interference device. Similarly, in ESAM analyses using EEG, stress tended to increase due to occlusal interference in every subject. In addition, relaxation decreased due to occlusal interference in three subjects.The results suggested the potential for evaluating the psychological effects of dental prostheses using emotional indices based on ESAM.

Measurement of the heat transfer coefficient at the vessel wall was made in a jet mixing vessel with rotating nozzle around the vessel axis. The observed heat transfer coefficient was correlated with power input per unit volume, and the resultant correlation equation at low nozzle rotation speed roughly agreed with that for an agitated vessel with anchor. The heat transfer coefficient at higher nozzle rotation speed decreased with increase of the nozzle rotation speed (i.e., the innerr shaft rotation speed) and approached that for coaxial rotating cylinders. Baffle plates in the jet mixing vessel did not improve the heat transfer coefficient.

We investigated whether or not frame composition spontaneously selected by individuals exhibit a natural left shift in preference of luminosity, as previously suggested, by examining biases in luminosity imprinted in photographs taken under three different conditions: (i) daytime pictures taken outside without determination of frame composition (N=4153); (ii) daytime pictures taken outside with determination of frame composition (N=4035); and (iii) pictures taken inside with determination of frame composition (N=4045). As anticipated, there was a strong vertical gradient of luminance grayscale intensity, reflecting natural day light distribution, for pictures of categories (i) and (ii). Similarly, a minor vertical gradient was detected for pictures of category (iii), indicating common room lighting conditions. To our great interest, there was a consistent leftward tilt of ca. 2 and 9 degrees found in the vertical gradients for pictures of categories (ii) and (iii), respectively, but not for pictures of category (i). The result provides clear-cut evidence that there is indeed a natural preference for a leftward bias in luminosity for frame composition.

Hemispheric specialization is a prominent characteristic of the human brain. Should the ‘dominant’ hemisphere possess diierential neural organization for language production in the ‘higher order’ cortex, it would be rational to consider that the primary motor cortex may also show similar hemispheric specialization for speech production. In order to test this hypothesis, we investigated the spatial distribution of neural activities associated with phonation (M1p), silent tongue motion (M1t), and vocalization (M1v) within the primary motor cortex, utilizing independent component^ cross correlation^ sequential epoch analysis of high-¢eld functional magnetic resonance imaging time series. While M1t showed no signi¢cant diierences between the two hemispheres, M1p and M1v exhibited signi¢cant hemispheric diierences. The study demonstrated direct evidence that human primary motor cortex possesses clearcut hemispheric specialization similar to that observed for the higher order cortices. NeuroReport 17:1091^1095 � c 2006 Lippincott Williams & Wilkins.

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.

In order to identify the precise location of the primary motor area for the diaphragm with respect to the classical motor homunculus, functional magnetic resonance imaging (fMRI) experiments were performed utilizing independent component-cross correlation- sequential epoch (ICS) analysis on a high-field (3.0 Tesla) system. Activations which correlated with voluntary diaphragmatic motion mapped onto the area anterolateral to that for voluntary hand motion (internal control in ICS analysis). Multiple subject analysis yielded the primary motor cortex for the diaphragm to be (+/-48, -4, 47) in the Talairach and Tournoux coordinates. The results were highly consistent with the previously reported cortical area for the diaphragm determined by transcranial electrical/magnetic stimulation.

We identified a novel heterozygous single-nucleotide substitution 1400 T right curved arrow C (Leu 467 Pro) in the seventh exon of the interferon-gamma receptor 1 (IFNGR1) gene. This substitution was detected in 6 of the 89 allergic patients but not in the 72 non-allergic subjects. There was a difference in the L467P frequency between the allergic patients and the non-allergic subjects (Fisher's exact test: p=0.033). The 6 patients with L467P have allergic diseases such as bronchial asthma and/or allergic rhinitis. Furthermore, a familial analysis for L467P revealed a linkage between allergic diseases and L467P. Serum IgE levels of the patients with L467P were higher than those of the non-allergic subjects (p=0.001). Our previous studies have been shown that interferon-gamma (IFN-gamma) production by PBMCs in the allergic patients was lower than that in the non-allergic subjects. In this study, although IFN-gamma production in the allergic patients with L467P was equivalent to that in the non-allergic subjects, their serum IgE levels were high and they had allergic diseases. Our results suggest that some allergic patients have IFNGR dysfunction, and that L467P in the IFNGR1 gene is one of candidate susceptibility genes for allergic diseases.

We identified a novel heterozygous single-nucleotide substitution 1400 T right curved arrow C (Leu 467 Pro) in the seventh exon of the interferon-gamma receptor 1 (IFNGR1) gene. This substitution was detected in 6 of the 89 allergic patients but not in the 72 non-allergic subjects. There was a difference in the L467P frequency between the allergic patients and the non-allergic subjects (Fisher's exact test: p=0.033). The 6 patients with L467P have allergic diseases such as bronchial asthma and/or allergic rhinitis. Furthermore, a familial analysis for L467P revealed a linkage between allergic diseases and L467P. Serum IgE levels of the patients with L467P were higher than those of the non-allergic subjects (p=0.001). Our previous studies have been shown that interferon-gamma (IFN-gamma) production by PBMCs in the allergic patients was lower than that in the non-allergic subjects. In this study, although IFN-gamma production in the allergic patients with L467P was equivalent to that in the non-allergic subjects, their serum IgE levels were high and they had allergic diseases. Our results suggest that some allergic patients have IFNGR dysfunction, and that L467P in the IFNGR1 gene is one of candidate susceptibility genes for allergic diseases.

We conducted a longitudinal investigation with the QOL questionnaire (revised version 2001) before and after the 4-week-administration of a leukotriene receptor antagonist pranlukast. A significant improvement in the4 yrs group was observed at week 1, and that inor = 4 yrs group at week 2. Under these conditions, the overall QOL score, physical domains and mental domains, significantly improved in both the4 yrs group and theor = 4 yrs group. Overall, a slight correlation was observed between ratio changes in QOL scores and differences in symptom scores. However, no correlation was found in part of patients, suggesting that the QOL questionnaire allows measurement of mental changes in the patients themselves and their parents or caregivers for therapeutic effects which cannot be determined with ordinary physical findings only. In "event present" group, a significant difference in physical and mental domains was revealed by the comparison of QOL scores before and after administration. And furthermore in "event absence" group, the p-value for physical domain and mental domain was 0.0505 and 0.0912 in the4 yrs group, respectively, 0.0101 and 0.0446 in theor = 4 yrs group, respectively. The above results led us to consider the QOL questionnaire (revised version 2001) useful for routine medical care. Furthermore, pranlukast was considered useful for improvement not only of physical symptoms of bronchial asthma but also of the patient's QOL, although the placebo effects in this open trial must be considered.

Functional asymmetry of the parietal lobes during piano performance was assessed utilizing independent component-cross correlation-sequential epoch analysis of functional magnetic resonance imaging time series. Eight right handed musically trained subjects played the piano with their right hand, left hand, or both hands as cued by visually presented musical scores. The areas activated included the posterior parietal cortex (PPC) and the primary sensorimotor areas (SM1). While unilateral SM1 activation was correlated to motion of the corresponding contralateral hand, PPC activation was correlated to piano performance irrespective of hand modality. Furthermore, PPC activation exhibited significant asymmetry, with left hemisphere dominance. The results indicate that the left parietal lobe plays a significant role in the cortical processes of piano performance.

In seven patients with mucopolysaccharidoses (1 Hurler, 1 Hurler-Scheie, 4 Hunter, 1 Sly), cranial (1)H-magnetic resonance spectroscopy was performed to evaluate the accumulation of mucopolysaccharides and biochemical changes in the CNS in vivo before and after bone marrow transplantation (BMT). In two of seven patients, (1)H-magnetic resonance spectroscopy was performed before and after BMT. Nuclear magnetic resonance spectra of dermatan sulfate and chondroitin sulfate-C and magnetic resonance spectroscopy of chondroitin sulfate-C and urine from patients with mucopolysaccharidoses showed resonance higher than the chemical shift of myoinositol in the brain (3.7 ppm). The resonance was considered to contain signals from mucopolysaccharide molecules. The resonance was measured as presumptive mucopolysaccharides (pMPS). In white matter lesions detected by magnetic resonance imaging, pMPS/creatine ratios and choline/creatine ratios were consistently higher than control ratios. In white matter without lesions, choline/creatine ratios were higher than control ratios. Patients with higher developmental quotient or intelligence quotient tended to show higher N:-acetylaspartate/creatine ratios and lower pMPS/creatine ratios in basal ganglia. After BMT, the pMPS/creatine ratio in white matter lesions of patient 3, with Hunter syndrome, was slightly decreased, but in none of the patients was the ratio ever below the control ratios, even 7 y after BMT. In white matter without lesions, the pMPS/creatine ratio in patient 3 was decreased to the control ratios after BMT, but although the choline/creatine ratios were gradually decreased, they remained higher than the control ratio, 2 y after BMT. These results suggest that evaluation of pMPS, choline, and N:-acetylaspartate by (1)H-magnetic resonance spectroscopy is an important technique that may provide useful biochemical information in vivo on the neurologic process and the efficacy of BMT in patients with mucopolysaccharidoses.

The widely accepted method of blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI) is a subtractive approach of state related analysis based on pictorial statistics, analogous to its predecessor, H2O(15) positron emission tomography (H2O(15)-PET). Although BOLD-fMRI has been shown to have several definite advantages over H2O(15)-PET, it has also been found to be much more artifact prone. This is primarily due to pixel misalignment of raw image data. Furthermore, similar to H2O(15)-PET, conventional means for pictorial analysis in BOLD-fMRI tends to be limited by the relatively low specificity of the observed activation. To overcome this limitation, we investigated a technique for BOLD-fMRI, sequential epoch analysis (SEA), on a high-field (3.0 T) system. The method allows for experimental designs comparable to neurophysiological techniques in primates and enables determination of activation of a selected cerebral cortical region of interest corresponding to a specific task. Utilizing SEA, we successfully identified a specific area within the premotor cortex which is activated complementary to the contralateral hand motion. The findings have strong implications regarding the neurological substrate responsible for the well described clinical phenomenon of physiological mirror movements in infants. The current study validated SEA BOLD-fMRI on a high-field system as a complementary method in the pictorial analysis of conventional fMRI, effectively offsetting the inherent problems of the conventional method, principally pixel misalignment and the relatively low specificity of the observed activation.

THE cortical areas subserving music literacy were investigated using high-field (3 Tesla) functional magnetic resonance imaging (fMRI). The activation pattern associated specifically with music score reading was compared with that associated with reading text in a subject's primary and secondary language. While the areas of activation were predominantly identical for all three reading modalities, there were areas within the occipital cortex activated exclusively by music score reading. Grand analysis of the activation patterns of eight pianists unequivocally identified that the principal cortical area needed for music literacy is the cortex flanking the right transverse occipital sulcus (musical brain).

Cow's milk is one of the most common food allergens in the first year of life, with approximately 2.5% of infants experiencing an allergic reaction to it. Beta-lactoglobulin (BLG) is one of the major allergens in cow's milk. Previously, we reported that four of six T-cell clones (TCC) which were established from cow's milk allergy patients recognized BLGp97-117 as the core sequence and also recognized BLG in association with the human leucocyte antigen (HLA)-DRB1*0405 allele. Using two of these four TCCs, we evaluated the T-cell response to BLG peptides with single amino acid substitution or deletion and identified BLGp102-112 as the minimum essential region in BLGp97-117. In the alanine-scan assay, the proliferative responses of TCCs to pE108A disappeared, and the proliferative responses of TCCs to pC106A decreased. In the analog peptide proliferation assay, pY102S had retained some T-cell response to the two TCCs. Collecting these results, we propose a motif for the interaction between the HLA-DRB1*0405 allele and antigen peptide, and suggest that BLGp105-108 are important residues to retain the TCR/BLG-peptide/HLA complex. pY102A and pY102S are partial agonists for the T-cell receptor. These peptides might be considered as candidate peptides for the modification of the T-cell response to BLG in cow's milk allergy.