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Point-of-care testing (POCT) for low-concentration protein biomarkers remains challenging due to limitations in biosensor sensitivity and platform integration. This study addresses this gap by presenting a novel approach that integrates a metal-enhanced fluorescence (MEF) biosensor within a capillary flow-driven microfluidic cartridge (CFMC) for the ultrasensitive detection of the Parkinson's disease biomarker, aminoacyl-tRNA synthetase complex interacting multi-functional protein 2 (AIMP-2). Crucial point to this approach is the orientation-controlled immobilization of capture antibody on a nanodimple-structured MEF substrate within the CFMC. This strategy significantly enhances fluorescence signals without quenching, enabling accurate quantification of low-concentration AIMP-2 using a simple digital fluorescence microscope with a light-emitting diode excitation source and a digital camera. The resulting platform exhibits exceptional sensitivity, achieving a limit of detection in the pg/mL range for AIMP-2 in human serum. Additionally, the CFMC design incorporates a capillary-driven passive sample transport mechanism, eliminating the need for external pumps and further simplifying the detection process. Overall, this work demonstrates the successful integration of MEF biosensing with capillary microfluidics for point-of-care applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To investigate the association of the APOE ε4 genotype with hippocampal volume, independent of Aβ burden., Method: This cross-sectional study included 71 participants with mild cognitive impairment or mild AD. All participants were divided into carriers or non-carriers of the ε4 allele. The main outcome was hippocampal volume measured using structural magnetic resonance imaging; 18 F-florbetaben positron emission tomography was additionally performed to investigate the association of APOE ε4 genotype with hippocampal volumes, independently of Aβ burden. Analysis of covariance was conducted to compare the differences in hippocampal volumes between carriers and non-carriers of the ε4 allele after controlling for global Aβ burden or local hippocampal Aβ burden., Results: The APOE ε4 genotype was associated with a smaller right and total hippocampal volume (right: 3160.16 ± 365.71 vs. 3365.24 ± 434.88, p < 0.05; total: 6257.48 ± 790.60 vs. 6599.52 ± 840.58, p < 0.05), independent of Aβ burden., Conclusion: Our findings on the association of APOEε4 genotype with hippocampal volume independent of Aβ burden suggest that the APOEε4 genotype may contribute to hippocampal neurodegeneration through an Aβ-independent mechanism., (Copyright © 2021. Published by Elsevier B.V.)

Phosphor screens have attracted increasing global interest because they can aid the acquisition of high-quality images while simultaneously reducing exposure. However, although increasing the thickness of the phosphor screen increases exposure efficiency due to scattered light, it also leads to a broader light spread, which results in poorer resolution. Hence, in this study, we implemented a reflector using a mirror-coating technique on the surface of a phosphor screen and analyzed its characteristics in terms of luminescence intensity and resolution. We present the fabrication and measurement of the phosphor screen based on a reflector containing Gd₂O₂S:Tb. The phosphor screen containing the reflector can be fabricated via the screen-printing method and roll-to-roll sputtering method. In particular, when compared to the condition without a reflector, Al and Cu reflectors showed improvements in luminescence intensity of 15.7% and 12.2%, respectively, as well as lower full widths at half maximum of 11.45 and 9.08, respectively. This quantitatively demonstrates that Cu and Al are suitable reflector materials to improve exposure efficiency while maintaining resolution in radiography systems. Moreover, because we did not utilize an optical assembly, which improves the transmission efficiency by matching the different refractive indices of the phosphor screen and photo-detector, we believe that the quantity of photons could be further improved if the reflectors were applied to a commercial product. Thus, future studies using single-layer anti-reflector coating techniques with optical assemblies are warranted.

Milnacipran is a reuptake inhibitor of both serotonin and noradrenaline, used in the treatment of fibromyalgia with severe depression. However, few studies have been conducted on the efficacies of milnacipran drug on the functional connectivity of the neural network. The authors aimed to find the correlation between the drug efficacy and the changes in neural network in fibromyalgia patients. Resting-state-functional magnetic resonance imaging (rs-fMRI) were obtained before and after milnacipran drug administration. Graph theory indexes and small-worldness were calculated using preprocessed blood-oxygen-level-dependent signals from the rs-fMRI scans of 14 brain regions-of-interest. Statistical analyses were conducted to compare the topological network parameters. Significant changes in the neural network indexes appeared in three of the 14 brain regions-of-interest. In the pain network, the average path length on the left side of Brodmann area 32 was shortened. In the default mode network, functional connectivity changes were observed in the left lateral parietal cortex and medial prefrontal cortex. In the left lateral parietal cortex, the degree and betweenness centrality increased, whereas the clustering coefficient decreased. In the medial prefrontal cortex, local efficiency decreased. The small-worldness declined after milnacipran medication. The present results demonstrate that functional connectivity indexes in the brains of female fibromyalgia patients obtained from rs-fMRI data can be used as potential prognosis markers of milnacipran drug treatment.

Objectives: To validate a visual rating scale reflecting sub-regional patterns of putaminal hypointensity in susceptibility-weighted imaging of patients with multiple system atrophy (MSA). Methods: Using a visual rating scale (from G0 to G3), 2 examiners independently rated putaminal hypointensities of 37 MSA patients and 21 control subjects. To investigate the correlation with the scales, R2 * values and the volume of the entire putamen were measured. Results: MSA patients with parkinsonian variant had significantly higher scores than those with cerebellar variant. Visual rating scores in MSA were correlated with R2 * values [General estimating equation (GEE), Wald chi-square = 25.89, corrected p < 0.001] and volume (Wald chi-square = 75.44, corrected p < 0.001). They correlated with UPDRS motor scores. Binary logistic regression analyses revealed that the visual rating scale was a significant predictor for discriminating MSA patients from controls [multivariate model adjusted for age and sex, odds ratio 52.722 (corrected p = 0.009)]. Pairwise comparison between areas under the curve (AUCs) revealed that the visual rating scale demonstrated higher accuracy than R2 * values [difference between AUCs; univariate model = 0.247 (corrected p < 0.001); multivariate model = 0.186 (corrected p = 0.003)]. There were no significant differences in clinical characteristics between the high-iron group, defined as putamen with visual rating scale ≥ G2 and R2 * values ≥ third quartile, and the remaining patients. Conclusion: The visual rating scale, which reflects quantitative iron content and atrophy of the putamen as well as motor severities, could be useful for the discrimination and evaluation of patients with MSA., (Copyright © 2019 Lee, Kim, Kim, Kim, Mun and Lee.)

Background & Objective: Although iron accumulation is thought to be associated with neurodegenerative processes, the timing of putaminal iron deposition during the disease course of multiple system atrophy (MSA) remains unclear. We sought to investigate the temporal pattern of iron deposition in the putamen of MSA patients by calculating the conditional probabilities (CPs) of multimodal MRI changes., Methods: We simultaneously measured putaminal R2*, volume and MD values of 39 probable MSA patients and 22 control subjects. The presence of significant MRI changes was defined as higher R2* and MD values, or lower volumes than cut-off values derived from mean values in control putamen. The CPs of R2* changes without MD or volume changes were then compared with those of MD or volume changes without R2* changes., Results: Regardless of the cut-off values, the CPs of R2* increments without MD or volume changes were significantly lower than those for MD or volume changes without R2* increments. The associations of R2* with volume and MD values appeared in non-linear exponential and quadratic patterns, respectively., Conclusions: Our findings suggest that putaminal iron accumulation would occur under volume atrophy or MD increments. Thus, iron deposition in the putamen of MSA patients is likely a secondary byproduct of neurodegeneration., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The thalamus plays an important role in the modulation of both focal and generalized seizures, but the mechanisms related to seizures may be different among epilepsy syndromes. The aim of this study is to investigate the thalamic atrophy in different epilepsy syndromes. We enrolled a total of 72 patients with epilepsy (22 patients with temporal lobe epilepsy with hippocampal sclerosis, 21 patients with extra-temporal lobe epilepsy, and 29 patients with juvenile myoclonic epilepsy). We analyzed structural volumes of the brain with FreeSurfer 5.1 software, and compared them among subgroups of epilepsy and normal control subjects. Moreover, we quantified correlations between the duration of epilepsy and the structural volumes with age and sex as covariates. The volumes of the ipsilateral hippocampus in temporal lobe epilepsy with hippocampal sclerosis were significantly smaller than those in extra-temporal lobe epilepsy and normal control subjects [analysis of variance (ANOVA), p < 0.001]. Although the volumes of the ipsilateral thalamus were not different from those of normal control subjects, the volumes of the ipsilateral thalamus were negatively correlated with duration of epilepsy in temporal lobe epilepsy with hippocampal sclerosis (r = -0.5, p = 0.02). However, the volumes of interest in extra-temporal lobe epilepsy and juvenile myoclonic epilepsy were not different from those in normal control subjects, and none of these structures were correlated with duration of epilepsy. These findings suggest that the role of the thalamus may be different in thalamo-limbic circuits among epilepsy syndromes., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

With increasingly strict regulations regarding patient exposure, research on digital radiography technology has recently focused on indirect methods that can produce high-quality images for a low radiation dose. In particular, medical imaging systems based on indirect methods universally use rare-earth metal phosphors, because of their high atomic number and excellent luminescence efficiency. Thus, various studies aiming to improve the luminescence efficiency of phosphors have been conducted. Despite this research, however, the current luminescence efficiencies are insufficient. Here, we report a basic study aiming to develop a phosphor screen containing a three-quarter-wave optical-thickness layer to improve the light transmission efficiency. Specifically, the fabrication and measurement of a Gd2O2S:Tb phosphor screen containing a single three-quarter-wave optical-thickness layer is presented. The screen is fabricated via a screen-printing and spin-coating method. Based on histograms of the degree of luminescence and the pixel values, we demonstrate that the light transmission efficiency is improved by the three-quarter-wave optical-thickness layer. Note that analysis of the full width at half maximum of the pixel value distribution reveals the possibility of resolution loss when obtaining medical images. Overall, the results of this study confirm that the light transmission efficiency can be improved through use of a single-layer anti-reflection coating. However, because the emission spectrum of the Gd2O2S:Tb screen is in the 480-600-nm band, it is necessary to expand the areas exhibiting the lowest reflectance to the wavelengths at the edge of this band. Thus, further study should be conducted to optimize the optical thickness.

Objective: The variability of the severity and regional distribution of pathological process in basal ganglia (BG) and brainstem-cerebellar systems results in clinical heterogeneity and represents the motor subtype of multiple system atrophy (MSA). This study aimed to quantify spatial patterns of multimodal MRI abnormalities in BG and stem-CB regions and define structural MRI findings that correlate with clinical characteristics., Methods: We simultaneously measured R2*, mean diffusivity (MD), and volume in the subcortical structures (BG, thalamus, brainstem-cerebellar regions) of 39 probable MSA and 22 control subjects. Principal component analysis (PCA) and structural equation modeling (SEM) were performed to show a model consisting of multiple inter-dependencies., Results: Structural MRI alterations were found to be significantly interrelated within BG as well as brainstem-cerebellar regions in MSA patients. PCA extracted four factors: three factors reflected alterations in R2*, MD and volume of the BG region including the caudate nucleus, putamen, and pallidum, and the remaining one factor represented degenerative changes in MD and volume of stem-CB region. In SEM, a latent variable reflecting brainstem-cerebellar degeneration did not show a significant correlation with the other latent variables associated with BG degeneration. Putaminal MD values and a PCA-driven factor reflecting MD values in the BG showed a significant correlation with UPDRS and UMSARS scores., Conclusion: Multimodal structural MRI abnormalities in MSA appear to be segregated into BG and stem-CB-related factors that can be associated with the clinical phenotype and motor severity.

Objective: Increasing evidence has suggested that epilepsy is a network disease. Graph theory is a mathematical tool that allows for the analysis and quantification of the brain network. We aimed to evaluate the influences of duration of epilepsy on the topological organization of brain network in focal epilepsy patients with normal MRI using the graph theoretical analysis based on diffusion tenor imaging., Methods: We prospectively enrolled 66 patients with focal epilepsy (18/66 patients were newly diagnosed) and 84 healthy subjects. All of the patients with epilepsy had normal MRI on visual inspection. All of the subjects underwent diffusion tensor imaging that was analyzed using graph theory to obtain network measures., Results: The measures of characteristic path length and small-worldness in the patients with focal epilepsy were significantly decreased, even after multiple corrections (P < .01). Moreover, the measures including mean clustering coefficient and global efficiency in the patients with epilepsy had strong tendency to decrease compared to those in healthy subjects (P = .0153 and P = .0138, respectively). When comparing the measures among the patients with newly diagnosed/chronic epilepsy and healthy subjects using ANOVA, the characteristic path length (P = .006), small-worldness (P = .032), and global efficiency (P = .004) were significantly different. In addition, the duration of epilepsy was negatively correlated with global efficiency (r = -.249, P = .0454)., Conclusions: We newly found a progressive topological disorganization of the brain network in focal epilepsy. In addition, we demonstrated disrupted topological organization in focal epilepsy, shifting toward a more random state., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Diabetes mellitus, a metabolic disorder of glucose metabolism, is mainly associated with insulin resistance to the body cells, or impaired production of insulin by the pancreatic β-cells. Insulin is mainly required to regulate glucose metabolism in type 1 diabetes mellitus patients; however, many patients with type 2 diabetes mellitus also require insulin, especially when their condition cannot be controlled solely by oral hypoglycemic agents. Hence, major research is ongoing attempting to improve the delivery of insulin in order to make it more convenient to patients who experience side effects from the conventional treatment procedure or non-adherence to insulin regimen due to multiple comorbid conditions. Conventionally, insulin is administered via subcutaneous route which is also one of the sole reasons of patient's non-compliance due to the invasiveness of this method. Several attempts have been done to improve patient compliance, reduce side effects, improve delivery adherence, and to enhance the pharmaceutical performance of the insulin therapy. Despite facing substantial challenges in developing efficient delivery systems for insulin, vast research studies have been carried out for the development of smart delivery systems to deliver insulin via ocular, buccal, pulmonary, oral, transdermal, as well as rectal routes. Therefore, the present review was aimed to overview the challenges encountered with the current insulin delivery systems and to summarize recent advancements in technology of various novel insulin delivery systems being discovered and introduced in the current market., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Objective: We hypothesized that temporal lobe epilepsy (TLE) patients with and without hippocampal sclerosis (HS) showed differences in their limbic networks. This study aimed to evaluate the role of the thalamus in TLE patients with HS., Materials and Methods: Twenty-nine TLE patients with HS and 30 controls were enrolled in this study. In addition, we included eight TLE patients without HS as a disease control group. Using whole-brain T1-weighted MRIs, we analyzed the volumes of the limbic structures, including the hippocampus, thalamus, and total cortex, with FreeSurfer 5.1. We also investigated the effective connectivity among these structures using SPSS Amos 21 based on these volumetric measures. Moreover, we quantified correlations between epilepsy duration and the volumes of these structures., Results: There was a statistically significant effective connectivity from the hippocampus to the thalamus in TLE patients with HS. Moreover, the volumes of the left and right thalamus were negatively correlated with epilepsy duration (r=-.42, P=.0315 and r=-.52, P=.0062, respectively). However, neither TLE patients without HS nor normal controls had a significant effective connectivity from the hippocampus to the thalamus., Conclusions: The limbic networks of TLE patients with and without HS could be different, and the thalamus might play a critical role in TLE patients with HS., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Although juvenile myoclonic epilepsy has been considered as a disorder of thalamo-cortical circuit, it is not determined the causality relationship between thalamus and cortex. The aim of this study was to evaluate whether juvenile myoclonic epilepsy is a disorder of thalamus or cortex. Twenty-nine patients with juvenile myoclonic epilepsy and 20 normal controls were enrolled in this study. In addition, we included 10 patients with childhood absence epilepsy as a disease control group. Using whole-brain T1-weighted MRIs, we analyzed the volumes of the structures, including hippocampus, thalamus, and total cortex, with FreeSurfer 5.1. We also investigated the effective connectivity among these structures using SPSS Amos 21 based on these volumetric measures. The structural volumes in juvenile myoclonic epilepsy were not different from those in normal controls. There was a statistically significant effective connectivity from the total cortex to the thalamus in the patients with juvenile myoclonic epilepsy. In addition, a significant effective connectivity from the hippocampus to the ipsilateral thalamus was revealed. Unlike the patients with juvenile myoclonic epilepsy, neither the patients with childhood absence epilepsy nor normal controls had a significant effective connectivity from the total cortex to the thalamus or from the thalamus to the cortex. The connectivity of brain in patients with juvenile myoclonic epilepsy could be different from that in patients with childhood absence epilepsy, and the cortex rather than the thalamus might play a critical role in the pathogenesis of juvenile myoclonic epilepsy., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Tendon and ligament (T/L) have been known to be obviously different from each other in tissue level. However, due to the overlapping gene markers, distinction in cellular level has not been clearly verified yet. Recently, the use of nuclear magnetic resonance (NMR) spectroscopy has shown the potential to detect biological markers in cellular level. Therefore, in this study we applied a non-invasive technique based on NMR spectroscopy to establish biomarkers to distinguish between T/L fibroblasts. In addition the cellular morphologies and gene expression patterns were also investigated for comparison through optical microscopy and real-time polymerase chain reaction (PCR). No difference was observed from morphology and real-time PCR results, either as expected. However, we found clear differences in their metabolomic spectra using 1H NMR spectroscopy. The calculated integral values of fatty acids (with chemical shifts at ~0.9, 1.26, 1.59, 2.05, 2.25, and 2.81 ppm), lactate (~1.33 ppm), and leucine (~2.72 ppm) were significantly different between the two types of fibroblasts. To be specific tendon group exhibited higher level of the metabolite than ligament group. In conclusion, in-cell metabolomic evaluation by NMR technique used in this study is believed to provide a promising tool in distinguishing cell types, especially T/L cells, which cannot be classified by conventional biological assays.

Purpose: This study suggests a noninvasive and repetitive measurement method using 1 H magnetic resonance spectroscopy to monitor changes in cellular metabolites within a single sample., Methods: Longitudinal acquisition of cellular metabolites from three-dimensional cultured human osteosarcoma (MG-63) cells was conducted using 3.0 Tesla 1 H MRS for 2 weeks at three time points: days 1, 7, and 14. During the MR spectroscopy (MRS) scan, cell specimen temperatures were kept constant at 37°C by a lab-developed magnetic resonance compatible thermostatic device. A DNA assay and live/dead staining of the cell specimens were carried out at each time point to verify the MRS measurements., Results: Cell viability in the proposed device did not significantly differ from that of cells in a conventional incubator (P = 0.946). Cell proliferation and choline concentration increased during the first week, but remained constant during the second week. Lactate did not change during the first week, but increased during the second week. Likewise, cell viability remained constant until day 7, then decreased., Conclusion: The proposed MRS technique results in a survivable environment for longitudinal studies of cells and provides a new way to measure metabolomic changes over time in single specimens of cells. Magn Reson Med 76:1912-1918, 2016. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

The purpose of this study was to investigate the association between brain regional gray matter volume and two subtypes of psychotic symptoms, namely paranoid and misidentification subtypes, in antipsychotic-naïve mild or moderate Alzheimer's disease (AD) patients. Forty AD patients with psychotic symptoms and 25 AD patients without psychotic symptoms were assessed for cognitive and functional impairment. Presence and subtype of psychotic symptoms were assessed by using the delusion and hallucination subscale of the Korean Neuropsychiatric Inventory (K-NPI). Structural MRI images were acquired on a 3 T scanner, and were analyzed using voxel-based morphometry (VBM) for automated analysis. The misidentification subtype is associated with more severe gray matter atrophy, and paranoid subtype is associated with less severe gray matter atrophy compared to non-psychosis group. These results suggest that the misidentification, the paranoid subtype and the non-psychosis group have a distinct neural correlation., (Copyright © 2016. Published by Elsevier Ireland Ltd.)

Objective: We evaluated the differences in brain morphology among patients with juvenile myoclonic epilepsy according to the occurrence of absence seizures., Materials and Methods: Twenty-one juvenile myoclonic epilepsy patients with (n = 6) and without (n = 15) absence seizures were enrolled. We analyzed whole-brain T1-weighted magnetic resonance imaging using FreeSurfer 5.1. Measures of cortical morphology, such as thickness, surface area, volume, and curvature, and the volumes of subcortical structures, the cerebellum, and cerebrum, were compared between the groups. Moreover, we quantified correlations between clinical variables and each measures of abnormal brain morphology., Results: Compared to normal controls, patients without absence seizures demonstrated thinning of the cortical thickness in the right hemisphere, including the post-central, lingual, orbitofrontal, and lateral occipital cortex. Compared to normal controls, patients with absence seizures had more widespread thinning of the cortical thickness, including the right post-central, lingual, orbitofrontal, and lateral occipital cortexes as well as the right inferior temporal cortex. Additionally, the volume of cerebellar white matter in patients without absence seizures was significantly smaller than that in normal controls. Patients with absence seizures had a much smaller cerebellar white matter volume than normal controls or patients without absence seizures. Moreover, there was significantly positive correlation between the age of seizure onset and the volume of cerebellar white matter in patients with juvenile myoclonic epilepsy., Conclusions: We demonstrated that there were significant brain morphology differences in patients with juvenile myoclonic epilepsy according to the presence of absence seizures. These findings support the hypothesis that juvenile myoclonic epilepsy may be a heterogeneous syndrome., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: The aim of this study is to compare gray matter (GM) volume and white matter (WM) integrity in Apolipoprotein E4 (ApoE ε4) carriers with that of ApoE ε4 noncarriers using the voxel-based morphometry and diffusion tensor imaging (DTI) to investigate the effect of the ApoE ε4 on brain structures in subjective memory impairment (SMI) without white matter hyperintensities (WMH)., Methods: Altogether, 26 participants with SMI without WMH were finally recruited from the Memory impairment clinics of Pusan National University Hospital in Korea. All participants were ApoE genotyped (ApoE ε4 carriers: n = 13, matched ApoE ε4 noncarriers: n = 13) and underwent 3-tesla magnetic resonance imaging (MRI) including 3-dimensional volumetric images for GM volume and DTI for WM integrity., Results: ApoE ε4 carriers compared with noncarriers in SMI without WMH showed the atrophy of GM in inferior temporal gyrus, inferior parietal lobule, anterior cingulum, middle frontal gyrus, and precentral gyrus and significantly lower fractional anisotropy WM values in the splenium of corpus callosum and anterior corona radiate., Conclusion: Our findings suggest that the ApoE ε4 is associated with both atrophy of GM volume and disruption of WM integrity in SMI without WMH., (Copyright © 2015 by the American Society of Neuroimaging.)

Objective: The purpose of this study was to determine whether gray matter volumes are associated with treatment response of psychotic symptoms in Alzheimer's disease (AD) patients., Method: Risperidone, which is commonly used as an atypical antipsychotic drug, was administered in a clinical setting for 6 weeks from April 2012 to February 2013 to 25 antipsychotic-naïve AD patients with psychosis, diagnosed according to Jeste and Finkel's proposed diagnostic criteria for psychosis of Alzheimer's disease. Psychotic symptoms were rated with the Korean version of the Neuropsychiatric Inventory (K-NPI) at baseline and at 6 weeks, and treatment response was defined as the change in K-NPI score from baseline to 6 weeks. Gray matter volumes were measured with magnetic resonance imaging and voxel-based morphometry at baseline. Age, gender, years of education, total intracranial volume, apolipoprotein E genotype, dosage of risperidone, the baseline scores on the Korean version of the Mini-Mental State Examination, and the baseline psychotic and nonpsychotic symptoms scores on the K-NPI were measured as covariates of no interest., Results: We found that treatment response of psychotic symptoms to risperidone in antipsychotic-naïve AD patients was positively associated with both left and right putamina, left parahippocampal gyrus, and left amygdala volume after controlling covariates of no interest (uncorrected P < .001, KE > 100 voxels)., Conclusions: Therefore, we conclude that gray matter volumes of putamina, left parahippocampal gyrus, and left amygdala are associated with treatment response of psychotic symptoms after 6 weeks of treatment with risperidone in antipsychotic-naïve AD patients with psychosis. These results suggest that the volumes of specific gray matter regions probably contribute to treatment response of psychotic symptoms in AD patients., Trial Registration: ClinicalTrials.gov identifier: NCT01198093., (© Copyright 2016 Physicians Postgraduate Press, Inc.)

Aims: The aim of the present study was to investigate whether the effects of vitamin B12 and homocysteine on brain volume are influenced by apolipoprotein E (APOE) genotype. We examined the effects in each subgroup (APOE ε4 carriers and non-carriers) of Alzheimer's disease (AD) patients and healthy normal controls., Methods: Forty participants with AD and 20 healthy normal controls were recruited from memory impairment clinics at Pusan National University Hospital in Korea. All participants were APOE genotyped and underwent magnetic resonance imaging, including 3-D volumetric images for grey matter (GM) volume. A multiple regression model integrated into statistical parametric mapping was used to see if there was any correlation between vitamin B12 or homocysteine and GM volume in each subgroup (APOE ε4 carriers and non-carriers) of AD patients and healthy normal controls., Results: There was a significant positive correlation between serum concentrations of vitamin B12 and regional GM volume in APOE ε4 carriers with AD but not in non-carriers. We also found that there was a significant negative correlation between serum concentrations of homocysteine and regional GM volume in APOE ε4 non-carriers with AD but not in carriers (P < 0.001, uncorrected for multiple comparisons; extent threshold = 100 voxel)., Conclusion: The present findings suggest that the effects of vitamin B12 and homocysteine on GM volume might be influenced by APOE genotype., (© 2015 The Authors. Psychogeriatrics © 2015 Japanese Psychogeriatric Society.)

Objective: We hypothesize that pre-existing susceptible structures in the brain may be associated with the development of newly diagnosed partial epilepsy of unknown etiology., Methods: Twenty-two patients with newly diagnosed partial epilepsy of unknown etiology and 36 healthy controls were enrolled in this study. In addition, we included 24 patients with chronic partial epilepsy of unknown etiology as a disease control group. We analyzed whole-brain T1-weighted MRIs using FreeSurfer 5.1. The volumes of the hippocampus, amygdala, thalamus, caudate, putamen, pallidum, brainstem, cerebellar gray and white matter, as well as cerebral gray and white matter were compared between the groups. We also analyzed the changes in brain volumes associated with the chronicity of epilepsy in the patients with chronic epilepsy compared to newly diagnosed epilepsy., Results: The volume of cerebellar white matter in patients with newly diagnosed epilepsy was significantly smaller than that which was observed in the healthy controls (p=0.0001). This finding was also observed in patients with chronic epilepsy (p<0.0001). Cerebral white matter volume was negatively correlated with the duration of epilepsy (r=-0.4, p=0.04)., Conclusion: These findings support our hypothesis that cerebellar white matter changes may constitute a pre-existing susceptible structure in the brain that is associated with the development of partial epilepsy of unknown etiology. In addition, cerebral white matter was the structure that was the most vulnerable to the progression of epilepsy., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Magnetic resonance imaging (MRI) can be useful not only for the diagnosis of multiple system atrophy (MSA) itself, but also to distinguish between different clinical subtypes. This study aimed to investigate whether there are differences in the progression of subcortical atrophy and iron deposition between two variants of MSA. Two serial MRIs at baseline and follow-up were analyzed in eight patients with the parkinsonian variant MSA (MSA-P), nine patients with cerebellar variant MSA (MSA-C), and fifteen patients with Parkinson's disease (PD). The R2* values and volumes were calculated for the selected subcortical structures (caudate nucleus, putamen, globus pallidus, and thalamus) using an automated region-based analysis. In both volume and R2*, a higher rate of progression was identified in MSA-P patients. Volumetric analysis showed significantly more rapid progression of putamen and caudate nucleus in MSA-P than in MSA-C. With regard to R2* changes, a significant increase at follow-up and a higher rate of progression were identified in the putamen of MSA-P group compared to MSA-C and PD groups. This longitudinal study revealed different progression rates of MRI markers between MSA-P and MSA-C. Iron-related degeneration in the putamen may be more specific for MSA-P.

Purpose: A reference reagent, 3-(trimethylsilyl) propionic-2, 2, 3, 3-d4 acid sodium (TSP), has been used frequently in nuclear magnetic resonance (NMR) and magnetic resonance spectroscopy (MRS) as an internal reference to identify cell and tissue metabolites, and determine chemical and protein structures. This reference material has been exploited for the quantitative and dynamic analyses of metabolite spectra acquired from cells. The aim of this study was to evaluate the cytotoxicity of TSP on three-dimensionally, agarose gel, cultured cells., Materials and Methods: A human osteosarcoma cell line (MG-63) was selected, and cells were three dimensionally cultured for two weeks in an agarose gel. The culture system contained a mixture of conventional culture medium and various concentrations (0, 1, 3, 5, 7, 10, 20 30 mM) of TSP. A DNA quantification assay was conducted to assess cell proliferation using Quant-iT PicoGreen dsDNA reagent and kit, and cell viability was determined using a LIVE/DEAD Viability/Cytotoxicity kit. Both examinations were performed simultaneously at 1, 3, 7 and 14 days from cell seeding., Results: In this study, the cytotoxicity of TSP in the 3D culture of MG-63 cells was evaluated by quantifying DNA (cell proliferation) and cell viability. High concentrations of TSP (from 10 to 30 mM) reduced both cell proliferation and viability (to 30% of the control after one week of exposure), but no such effects were found using low concentrations of TSP (0-10 mM)., Conclusions: This study shows that low concentrations of TSP in 3D cell culture medium can be used for quantitative NMR or MRS examinations for up to two weeks post exposure.

This study aimed to investigate the clinical and radiological findings in patients with transient global amnesia and to evaluate structural abnormalities using voxel-based morphometry. The subjects were diagnosed with transient global amnesia. For the voxel-based morphometry analyses, Statistical Parametric Mapping, running on the MATLAB platform (MathWorks, Natick, MA, USA), was employed to analyze the structural differences between patients with transient global amnesia and control subjects. Eighty patients met the inclusion criteria. Twenty-three patients (29%) were men, and 57 patients (71%) were women. There were significantly more women among the transient global amnesia patients compared with the general Korean population. MRI revealed hippocampal cavities in 41 patients (51%), and the incidence of such cavities was significantly different from that of the control subjects (24%). There were no differences in the clinical factors between the patients with and without hippocampal cavities. Diffusion-weighted imaging was performed in 54 patients, and 13 patients (24%) exhibited high signal intensity in the hippocampus. There were also no differences in the clinical factors between the patients with and without high signal intensities in the hippocampus on diffusion-weighted imaging. Twenty-six patients underwent three-dimensional volumetric T1-weighted imaging that produced results suitable for voxel-based morphometry, and these patients presented with gray matter volume reductions in the hippocampus, cingulum, and cerebellum. There were significant structural differences in the limbic structures between patients with transient global amnesia and the control subjects that might have contributed to vulnerability of the memory pathways of the patients with transient global amnesia., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: This study proposes an automated diagnostic method to classify patients with Alzheimer's disease (AD) of degenerative etiology using magnetic resonance imaging (MRI) markers., Methods: Twenty-seven patients with subjective memory impairment (SMI), 18 patients with mild cognitive impairment (MCI), and 27 patients with AD participated. MRI protocols included three dimensional brain structural imaging and diffusion tensor imaging to assess the cortical thickness, subcortical volume and white matter integrity. Recursive feature elimination based on support vector machine (SVM) was conducted to determine the most relevant features for classifying abnormal regions and imaging parameters, and then a factor analysis for the top-ranked factors was performed. Subjects were classified using nonlinear SVM., Results: Medial temporal regions in AD patients were dominantly detected with cortical thinning and volume atrophy compared with SMI and MCI patients. Damage to white matter integrity was also accredited with decreased fractional anisotropy and increased mean diffusivity (MD) across the three groups. The microscopic damage in the subcortical gray matter was reflected in increased MD. Classification accuracy between pairs of groups (SMI vs. MCI, MCI vs. AD, SMI vs. AD) and among all three groups were 84.4% (±13.8), 86.9% (±10.5), 96.3% (±4.6), and 70.5% (±11.5), respectively., Conclusion: This proposed method may be a potential tool to diagnose AD pathology with the current clinical criteria.

Background: We evaluated the cortical morphology in patients with orthostatic intolerance., Methods: Thirty patients with orthostatic intolerance, as well as age- and sex-matched normal controls, were enrolled in this study. We divided the patients into orthostatic hypotension (n = 22) and postural tachycardia syndrome (n = 8) groups based on their response to a head-up tilt table test. We analyzed whole-brain T1-weighted MRI images using FreeSurfer 5.1. The measures of cortical morphology were compared between the groups., Results: The cortical thickness in the right hemisphere, including the medial orbitofrontal, peri-calcarine, post-central, inferior temporal, and lateral occipital cortex, and in the peri-calcarine cortex of the left hemisphere was thinned in patients with orthostatic hypotension compared to normal controls. The other measures of cortical morphology, including the surface area, volume, and curvatures, did not differ between patients with orthostatic hypotension and normal controls. However, none of the measures of cortical morphology differed between patients with postural tachycardia syndrome and normal controls., Conclusions: We demonstrated that the cortical morphology significantly changed in patients with orthostatic hypotension but not in patients with postural tachycardia syndrome compared to normal controls. These findings support the hypothesis that orthostatic intolerance is a heterogeneous syndrome., (© 2015 S. Karger AG, Basel.)

Purpose: To analyze the characteristics of neuropsychological profiles and gray matter volume in de novo, drug-naïve Parkinson's disease with mild cognitive impairment (PD-MCI)., Methods: Fifty-two newly diagnosed PD patients were assessed with neuropsychological testing, and PD-MCI was defined in patients with at least one or more abnormal cognitive test domains. PD with normal cognition (PD-NC) did not meet the criteria for PD-MCI or PD with dementia. Brain MRI scans was acquired from the patients and healthy controls (HC). The imaging processing and analysis of the gray matter (GM) volume were performed platform to determine the difference between PD-MCI and PD-NC., Results: There were no differences of motor subscores between PD-MCI and PD-NC. The clinical dementia rating, global deterioration scale, and verbal memory were significantly worse in PD-MCI than in PD-NC. GM volume loss was observed in the right hippocampus, right cuneus, and right precuneus in PD-NC compared to in the HC. PD-MCI had significantly decreased GM volume in the bilateral temporal and frontal areas compared with that of the HC. The GM volume was significantly decreased in the right temporal pole, left precuneus, medial frontal and posterior cingulated gyrus in PD-MCI compared with PD-NC., Conclusions: Clinical dementia ratings and global deterioration scales could differentiate PD-MCI from PD-NC. Verbal memory impairment is characterized as a cognitive deficit of de novo PD-MCI and is associated with the posterior cortical area., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Aims: An association between white matter hyperintensities (WMH) and cognitive dysfunction has long been recognized. However, subjects with identically appearing WMH on magnetic resonance imaging present with a wide variance in cognitive function ranging from normal cognition to dementia. The aim of this study was to compare cortical atrophy and integrity of white matter of patients with subcortical vascular dementia of Binswanger type (SVaD-BT) with those of the normal cognition group with WMH (ncWMH)., Methods: Eleven patients with SVaD-BT and 11 age-, sex-, education- and grade of WMH-matched ncWMH underwent magnetic resonance imaging, including 3-D volumetric images for cortical atrophy and diffusion tensor imaging for integrity of white matter., Results: Compared to ncWMH, SVaD-BT patients showed cortical atrophies in frontal (i.e. frontal pole, precentral gyrus and frontal medial cortex) and occipital areas (i.e. lingual gyrus) followed by atrophies in temporal (i.e. fusiform cortex and middle temporal gyrus) areas. Along with cortical atrophies, reduced integrity with low fractional anisotropy and high mean diffusivity values in genu and splenium of the corpus callosum were detected in SVaD-BT patients., Conclusions: Our findings suggest that cognitive decline from ncWMH to SVaD-BT may be associated with cortical atrophy and reduced integrity of white matter., (© 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.)

Background: Neuroimaging studies in patients with idiopathic rapid eye movement sleep behavior disorder (iRBD) show similar structural and functional changes to alpha-synucleinopathies, including PD. Until now, there have been few attempts to characterize brain iron deposition in iRBD. The aim of this study was to investigate brain iron content in patients with iRBD using quantitative magnetic resonance imaging (MRI)., Methods: 3-T MRI was performed in 15 patients with iRBD and 20 age-matched healthy control subjects. In order to evaluate the iron-related neurodegenerative changes, we assessed volume and transverse relaxation rate (R2*) simultaneously. We used both region-based and voxel-based analysis., Results: No significant differences in R2* values were found between iRBD groups and healthy control subjects. There were no areas of significantly reduced or increased gray matter and white matter volume in the iRBD group. Instead, lateral ventricle volumes measured automatically by FreeSurfer were significantly larger in patients with iRBD than in healthy controls (P < 0.05)., Conclusion: The present study suggests that iron-related R2* values may not be an imaging biomarker for neurodegeneration in iRBD., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: The purpose of this study was to evaluate the metabolomic changes in 3D-cultured human mesenchymal stem cells (hMSCs) in alginate beads, so as to identify biomarkers during chondrogenesis using (1)H nuclear magnetic resonance (NMR) spectroscopy., Materials and Methods: hMSCs (2×10(6) cells/mL) were seeded into alginate beads, and chondrogenesis was allowed to progress for 15 days. NMR spectra of the chondrogenic hMSCs were obtained at 4, 7, 11, and 15 days using a 14.1-T (600-MHz) NMR with the water suppression sequence, zgpr. Real-Time polymerase chain reaction (PCR) was performed to confirm that that the hMSCs differentiated into chondrocytes and to analyze the metabolomic changes indicated by the NMR spectra., Results: During chondrogenesis, changes were detected in several metabolomes as hMSC chondrogenesis biomarkers, e.g., fatty acids, alanine, glutamate, and phosphocholine. The metabolomic changes were compared with the Real-Time PCR results, and significant differences were determined using statistical analysis. We found that changes in metabolomes were closely related to biological reactions that occurred during the chondrogenesis of hMSCs., Conclusions: In this study, we confirm that metabolomic changes detected by (1)H-NMR spectroscopy during chondrogenic differentiation of 3D-cultured hMSCs in alginate beads can be considered as biomarkers of stem cell differentiation.

Purpose: To assess the efficacy of pregabalin by showing differences in the neuronal activities of fibromyalgia (FM) patients before and after longitudinal treatment using functional magnetic resonance imaging (fMRI)., Materials and Methods: In total, 21 female patients with FM and 11 age- and gender-matched healthy controls participated. FM patients underwent fMRI at baseline and following pharmacological therapy with pregabalin to diminish their pain. Pressure-pain stimuli were delivered on the subject's thumbnail bed during fMRI scans. Brain activation regions in fMRI were evaluated for longitudinal changes using a paired t-test. Changes in clinical features were also assessed with the Fibromyalgia Impact Questionnaire (FIQ), Brief Fatigue Inventory (BFI), Beck Depression Inventory (BDI), Widespread Pain Index (WPI), Symptom Severity Scale Score (SSS), and State-Trait Anxiety Inventory (STAI)., Results: Clinical scores were reduced significantly following therapy with five of the six clinical tests (FIQ, BFI, BDI, WPI, SSS; p < 0.05). Brain activation post-treatment was significantly lower than that pre-treatment in 13 regions of the brain (p < 0.001)., Conclusions: Our findings confirm that pregabalin influences aspects of the whole pain matrix, using fMRI, inducing longitudinal changes in neuronal activity during the pain state, and that it reduces pain and other core symptoms of FM. This method could be applied to other longitudinal clinical trials of pharmacological treatments for FM.

It is a matter of debate whether increased brain iron levels are the cause or only the consequence of neurodegenerative process in degenerative parkinsonism. The aim of this study is to characterize disease-related changes in volumes and iron-related R2 values of basal ganglia and thalamus. 13 patients with progressive supranuclear palsy (PSP), 15 with a parkinsonian variant of multiple system atrophy (MSA-p), 29 with Parkinson's disease (PD), and 21 age-matched controls underwent 3-Tesla MRI. The R2 values and volumes were calculated for the selected subcortical structures (caudate nucleus, putamen, globus pallidus, and thalamus) using an automated region-based analysis. Voxel-based analysis was also performed to visualize a topographical correlation of R2 value and volume. The PSP group had significantly higher R2 values in globus pallidus and caudate nucleus (p < 0.05), whereas the MSA-p group had higher R2 values in putamen (p < 0.001) than PD and controls. The globus pallidus in PSP and the putamen in MSA-p were the most significant areas of atrophy to differentiate PSP, MSA-p and PD (AUC = 0.856, 0.832, respectively, p < 0.001). The R2 values in both structures increased in parallel with the extent of atrophy. They were negatively correlated with volumes in putamen (r = -0.777, p < 0.001) and globus pallidus (r = -0.409, p = 0.025) of MSA-p, and globus pallidus (r = -0.4, p = 0.043) of PSP. Voxel-based analysis identified higher R2 values in more severely atrophic sub-regions in these structures. We observed topographical differences of iron deposition as well as atrophy between MSA-p and PSP. Increased iron levels were related to the structural atrophy in basal ganglia. Our results imply that iron accumulation is likely an epiphenomenon of the degenerative process.

Objective: There have been various studies showing increased iron levels in parkinsonian disorders. The purpose of this study was to demonstrate topographical differences of brain iron deposition between progressive supranuclear palsy (PSP) and the parkinsonian variant of multiple system atrophy (MSA-p) with SWI images., Methods: A total of 11 patients with PSP, 12 with MSA-p, 15 with Parkinson's disease (PD), and 20 age-matched healthy controls underwent SWI of the brain. Mean phase shift values of the red nucleus (RN), substantia nigra (SN), head of the caudate nucleus (CN), globus pallidus (GP), putamen (PUT), and thalamus (TH) were calculated and compared between groups. A voxel-based analysis of the processed SWI was performed to determine topographical differences of iron-related hypointense signals in PUT, GP, and TH., Results: Patients with PSP and MSA-p had significantly higher levels of iron deposition than control and PD groups. Comparing patients with PSP and MSA-p, differences were found in iron concentrations of the RN, SN, GP, and TH, which were higher in the PSP group. However, iron levels in the PUT were higher in the MSA group (p<0.05). The area under curve (AUC) indicated that the PUT was the most valuable nucleus in differentiating MSA-p from PSP and PD according to phase shift values (AUC=0.836). Meanwhile the GP (AUC=0.869) and TH (AUC=0.884) were the two most valuable nuclei in differentiating PSP from MSA-p and PD. Voxel-based analysis showed subregional differences in iron-related hypointense signals in the PUT, GP, and TH between MSA-p and PSP groups. Patients with MSA-p had significant increases of iron-related hypointense signals in the posterolateral PUT and adjacent lateral aspect of the GP, whereas the PSP group had increased hypodense signals in the anterior and medial aspects of the GP and TH., Conclusion: Our data demonstrate that pathological iron accumulations are more prevalent and severe in PSP compared to MSA-p. The distribution of high-iron-content regions in this study reflects pathoanatomically relevant sites. This finding allows for the use of MRI-based brain iron mapping as a technique to indirectly identify pathological changes., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: To observe brain activation induced by functional electrical stimulation, voluntary contraction, and the combination of both using functional magnetic resonance imaging (fMRI)., Methods: Nineteen healthy young men were enrolled in the study. We employed a typical block design that consisted of three sessions: voluntary contraction only, functional electrical stimulation (FES)-induced wrist extension, and finally simultaneous voluntary and FES-induced movement. MRI acquisition was performed on a 3.0 T MR system. To investigate activation in each session, one-sample t-tests were performed after correcting for false discovery rate (FDR; p < 0.05). To compare FES-induced movement and combined contraction, a two-sample t-test was performed using a contrast map (p < 0.01)., Results: In the voluntary contraction alone condition, brain activation was observed in the contralateral primary motor cortex (MI), thalamus, bilateral supplementary motor area (SMA), primary sensory cortex (SI), secondary somatosensory motor cortex (SII), caudate, and cerebellum (mainly ipsilateral). During FES-induced wrist movement, brain activation was observed in the contralateral MI, SI, SMA, thalamus, ipsilateral SII, and cerebellum. During FES-induced movement combined with voluntary contraction, brain activation was found in the contralateral MI, anterior cingulate cortex (ACC), SMA, ipsilateral cerebellum, bilateral SII, and SI.The activated brain regions (number of voxels) of the MI, SI, cerebellum, and SMA were largest during voluntary contraction alone and smallest during FES alone. SII-activated brain regions were largest during voluntary contraction combined with FES and smallest during FES contraction alone. The brain activation extent (maximum t score) of the MI, SI, and SII was largest during voluntary contraction alone and smallest during FES alone. The brain activation extent of the cerebellum and SMA during voluntary contraction alone was similar during FES combined with voluntary contraction; however, cerebellum and SMA activation during FES movement alone was smaller than that of voluntary contraction alone or voluntary contraction combined with FES. Between FES movement alone and combined contraction, activated regions and extent due to combined contraction was significantly higher than that of FES movement alone in the ipsilateral cerebellum and the contralateral MI and SI., Conclusions: Voluntary contraction combined with FES may be more effective for brain activation than FES-only movements for rehabilitation therapy. In addition, voluntary effort is the most important factor in the therapeutic process.

Background: Helicobacter pylori can cause hypochlorhydria in some hosts and predispose to diarrheal infections., Aims: We tested the hypothesis that chronic H. pylori infection increases the risk of diarrheal illness due to an acid-sensitive organism: enteropathogenic Escherichia coli (EPEC)., Methods: After testing healthy adult volunteers for H. pylori, 19 infected and 26 uninfected subjects had gastric pH probes placed and were given 5-10 × 10(9) EPEC organisms; six had previously received a proton pump inhibitor. We measured diarrhea and created a composite gastroenteritis severity score based on symptoms in the 48 h following exposure. Outcomes were compared using logistic regression and analysis of covariance., Results: More H. pylori-infected (36.8%) than H. pylori-uninfected subjects (7.7%) were hypochlorhydric (P = 0.02). Six (31.6%) H. pylori-infected and five H. pylori-uninfected subjects (19.2%) developed diarrhea (P = 0.34). Hypochlorhydria was a strong risk factor for diarrhea [odds ratio (OR) 6.25, confidence interval (CI): 1.29-30.35]. After adjusting for hypochlorhydria and EPEC dose, H. pylori was not associated with diarrhea (OR 0.89, CI: 0.17-4.58). Among those with symptoms, H. pylori-infected subjects had lower gastroenteritis severity score than did H. pylori-uninfected subjects (2.6, CI: 1.9-3.4 versus 1.5, CI: 1.1-1.9, P = 0.01), particularly if they were also hypochlorhydric (3.8, CI: 2.3-5.3 versus 1.9, CI: 1.3-2.5, P = 0.02)., Conclusions: In adults, H. pylori infection was associated with hypochlorhydria but had no detectable effect on occurrence of diarrhea. Among symptomatic subjects, H. pylori infection decreased severity of gastroenteritis.

We investigated the biocompatibility of semi-microporous segmented polyetherurethane (SPEU) that was coated with human microvascular endothelial cells. Three types of prosthesis were examined: (1) non-porous (control), (2) SPEU without a collagen coating (PNC) and (3) collagen-coated SPEU (PC). The attachment and proliferation of endothelial cells on SPEU (PNC and PC prostheses) was twice as great as in the control prostheses and endothelial cell adhesion in the PC prostheses was 1.4-times greater than in the PNC prostheses. The degree of endothelial cell coverage in the control prostheses was significantly lower than in the PNC and PC prostheses (P < 0.05), and there was no significant difference between the PNC and PC prostheses in the degree of endothelial cell coverage. As regards the retention of endothelial cells under simulated blood-flow conditions, the PNC prostheses exhibited a greater decrease in endothelial cell coverage, as compared to the PC prostheses (P < 0.05). Similarly, the PNC prostheses exhibited less platelet adhesion than the PC prostheses (P < 0.05). In summary, the semi-microporous SPEU offered better surfaces to anchor and culture for endothelial cells, and had superior anti-coagulant properties, as compared to nonporous SPEU. The coating of SPEU with collagen influenced both the attachment of endothelial cells and blood coagulation on the SPEU.

The present study was performed to determine the characteristics of the biochemical metabolites related to gastric cancer using ex vivo (1)H magnetic resonance spectroscopy (MRS), and to assess the clinical usefulness. A total of 35 gastric specimens resected during surgery for gastric cancer were used to compare MR spectra. A 1.5-T (64-MHz) clinical MR imager equipped with facilities for spectroscopy was used to obtain MR spectra from 33 gastric specimens. High-resolution (1)H nuclear magnetic resonance (NMR) spectra of the remains of two specimens were also examined with a 9.4-T (400-MHz) NMR spectrometer. Localized spectroscopic measurements were performed in two layers of gastric tissue, the proper muscle layer and the composite mucosa/submucosa layer. T(2) FSE and 3D SPGR images were used to determine the voxel size and the location for MRS data collection. MR spectra were obtained using the single-voxel PRESS technique with parameters of TR/TE = 2000/30 ms, NA = 256, and voxel size = 3 x 3 x 3 mm(3) (27 microL). Cancerous and noncancerous gastric tissues in the voxel were determined by histopathological analysis. On 9.4-T ex vivo NMR spectroscopy, the following metabolite peaks were found: lipids at 0.9 ppm (CH(3)) and 1.3 ppm (CH(2)); alanine (beta-CH(3)) at 1.58 ppm; N-Acetyl neuraminic acid (NANA: sialic acid) at 2.03 ppm; and glutathione at 2.25 ppm in normal gastric tissue layers. In the 1.5-T MR system, broad and featureless spectral peaks of the various metabolites in normal human gastric tissue were observed at 0.9 ppm, 1.3 ppm, 2.0 ppm, and 2.2 ppm regardless of gastric tissue layer. In specimens (Borrmann type III) with tubular adenocarcinoma, resonance peaks were observed at 1.26 ppm, 1.36 ppm (doublet of lactate), and 3.22 ppm (choline). Cancer lesions showed decreased levels of lipid peaks, showing the significant lactate doublet peaks, and increased intensity of the choline peak as compared with noncancerous gastric tissue. We found that decreased levels of lipids and increases in lactate and choline peaks in gastric tissue were markers for malignancy in gastric lesions. Information provided by ex vivo (1)H MRS, together with the development of in vivo (1)H MRS with high field strength and high resolution, may be very useful for the diagnosis of gastric cancer in clinical situation.

Objective: Proton magnetic resonance spectroscopy (1H-MRS) has been used to assess the metabolic changes in the brain in patients with liver cirrhosis. Decreased myo-inositol and increased glutamine levels were noted to be the most sensitive spectroscopic markers for cirrhotic patients with hepatic encephalopathy (HE). The purpose of this study was to assess how the abnormalities seen on the 1H-MRS of the brain in patients with liver cirrhosis are related to clinical and laboratory parameters., Methods: In a prospective study, localized 1H-MRS was performed in the basal ganglia and parietal white matter regions in liver cirrhosis patients with (n = 48) and without (n = 52) HE and chronic hepatitis (CH) (n = 15), and in normal controls (n = 20)., Results: Among cirrhotic patients, the myo-inositol levels were significantly lower (p < 0.01) and the glutamine levels were higher (p < 0.05) for patients with HE than for those without HE. The myo-inositol and glutamine levels, respectively, were inversely (r = -0.50; p < 0.001) and linearly (r = 0.50; p < 0.001) related to the Child-Pugh score. However, by subgroup analysis of Child-Pugh class C patients, there were no significant differences in the myo-inositol and glutamine levels between cirrhotic patients with (n = 40) and without HE (n = 24). A follow-up study of eight cirrhotic patients with HE showed no significant differences in the myo-inositol and glutamine levels after clinical improvement of HE., Conclusions: The abnormalities seen on the 1H-MRS of the brain of patients with liver cirrhosis are not likely to reflect the severity of HE or acute alteration in the level of consciousness. Rather, we believe they represent the chronic metabolic derangement of the brain associated with hepatic functional reserve.

To assess the clinical utility of the breath-hold turbo spin-echo T2-weighted MRI in patients with acute myocardial infarction, the results of MRI were compared with those of electrocardiography, coronary angiography, and thallium-201 single photon emission tomography (SPECT) in 23 patients and 5 healthy volunteers. To compare MRI and thallium-SPECT, the left ventricle was divided into five segments, and the presence of myocardial infarction was determined in each segment. MRI demonstrated an abnormally bright signal in 49 of 140 segments (five segments each from 23 patients and 5 volunteers); thallium-SPECT showed a fixed perfusion defect in 52 segments, for an 85% diagnostic concordance rate. The size of the myocardial infarction measured on MRI corresponded well to that measured on thallium-SPECT (r = .70, P < .01). Breath-hold turbo spin-echo T2 MRI can be used for detection of acute myocardial infarction in conjunction with thallium-SPECT, especially when accurate localization of lesion, increased spatial resolution, and anatomic landmarks are needed.

Purpose: To study the effects of formalin fixation, signal intensity characteristics of the stomach-wall layers, and findings suggestive of cancerous invasion to the stomach wall in vitro with magnetic resonance (MR) imaging in humans., Materials and Methods: MR images of nine specimens of stomach cancer and 29 normal specimens were obtained at 4.7 T; 26 of the normal specimens were fixed in 10% formalin for 2 hours to 187 days before imaging. The field gradient was 10 G/cm; the spatial resolution, 0.1 mm., Results: The mucosal, submucosal, and proper-muscle layers were clearly identifiable. The submucosa of the fresh specimens had the lowest signal intensity of all specimens on both T1- and T2-weighted images (P < .01). No statistical correlation existed between signal intensity and duration of fixation. Tumor invasion was detected in seven of eight specimens with mucosal invasion, all eight specimens with submucosal invasion, and three of six specimens with muscle invasion., Conclusion: In vitro MR imaging enabled differentiation of all three layers of the stomach wall, detection of the cancer, and measurement of the depth of invasion.

Purpose: To assess the capability of gadolinium polylysine-enhanced cardiac magnetic resonance (MR) imaging in depicting normal and ischemic myocardium during occlusion and reperfusion of the left anterior descending artery., Materials and Methods: Contrast-enhanced MR images were obtained in 18 cats during 90 minutes each of occlusion and reperfusion. The change in signal intensity (SI) was compared among normal myocardium and central and peripheral ischemic zones. Results were compared with those of 2,3,5-triphenyltetrazolium chloride staining., Results: During occlusion, the ischemic zone lacked enhancement while normal myocardium had gradual enhancement. During reperfusion, the ischemic zone had strong enhancement. In cats with large infarction, the central and peripheral ischemic zones had intermediate and high SI, respectively; in cats with focal or no infarction, the entire ischemic zone had high SI., Conclusion: Occlusive and reperfused myocardial infarction can be detected at gadolinium polylysine-enhanced MR imaging by means of differential SI changes in normal myocardium and central and peripheral ischemic zones.

On the basis of the principles of the time-of-flight method and the 3-D angiogram obtained by the 2-D planar image scanning technique using 90 degrees RF pulses with short repetition time, we have obtained a coronary angiogram around the heart including the coronary arteries and veins. The cine NMR imaging technique is also incorporated in synchronizing ECG R waves to reduce the motion artifact and at the same time to induce the saturation effect on the static samples. Images of the large bulk blood flow corresponding to the heart chamber and descending aorta are further removed by postprocessing. The final 3-D angiogram is then formed by stacking the 2-D images and contrast is further enhanced by the maximum ray tracing algorithm.

A technique of extracting cardiac and respiratory motion cycles by use of projection data is proposed and studied. These extracted cardiac and respiratory motion cycles are applied to the cine imaging of heart and motion artifact reduction in abdominal imaging instead of the conventional ECG gating devices. The basic concepts and their applications are discussed. Experimental results on human volunteers obtained with the KAIS 2.0-T whole-body NMR imaging system together with the pulse sequences used for the experiments are presented.

A simple and new flow velocity measurement technique using conventional spin-echo sequence is proposed and its applications to a preclinical result are presented. This technique utilizes the phase velocity encoding effect due to 180 degrees rf and its corresponding selection gradient. This phase encoding and its phase velocity relations have been obtained by numerical solution of the Bloch equation. A flow velocity measurement obtained with a volunteer using this proposed technique indicates close agreement with other previously measured values.

A new echo-time-encoded chemical-shift imaging technique applicable to dual-peak spectroscopic imaging with large magnetic field inhomogeneity is proposed and studied. The basic concept and its applications to modest field homogeneity (approximately 3.0 ppm) as well as to relatively large field inhomogeneity (approximately 10.5 ppm) are discussed. Actual pulse sequences are given and some experimental results on human volunteers obtained with a 2.0-T KAIS NMR system are also presented.