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Background and aims Neuropsychiatric symptoms in hepatitis C (HCV) patients resemble those of patients with autoimmune hepatitis (AIH) or primary biliary cholangitis (PBC), whilst the mechanisms behind them are unknown. Here we looked for cerebral metabolic and/or microstructural alterations in patients with HCV, AIH or PBC as possible causes behind these symptoms. Methods Patients with HCV infection (n = 17), AIH (n = 14) or PBC (n = 11) and age-adjusted healthy controls (n = 18) underwent brain magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS) and psychometric assessment of memory and attention. Brain relative proton density (PD) and T2 relaxation time (T2) were determined in 17 regions of interest (ROIs), as were the concentrations of N-acetyl-aspartate, choline, creatine, myo-inositol and glutamine + glutamate in frontal- (fWM) and parietal white matter (pWM). One-way analysis of variance and Kruskal-Wallis tests were used for group comparison. Correlations between altered neuropsychological findings and MRI/MRS observations were estimated with the Spearman ρ test. Results HCV, AIH and PBC patients revealed similar alterations in brain PD and metabolites compared to controls: significantly decreased PD in 7/17 ROIs in the HCV group, 16/17 ROIs in the PBC group and 14/17 ROIs in the AIH group, significantly increased N-acetyl-aspartate in fWM in all patients, significantly increased choline in the PBC group in both fWM and pWM, in the AIH group only in pWM and with a trend in the HCV group in pWM. Correlation analysis did not reveal significant associations between MRI/MRS alterations and neuropsychological dysfunction. Conclusion The findings suggest similar pathophysiological mechanisms behind neuropsychiatric symptoms associated with HCV infection, AIH and PBC.

Major depressive disorder (MDD) is characterized by dysregulation of stress systems and by abnormalities in cerebral energy metabolism. Stress induction has been shown to impact neurometabolism in healthy individuals. Contrarily, neurometabolic changes in response to stress are insufficiently investigated in MDD patients. Metabolic stress was induced in MDD patients (MDD, N = 24) and in healthy individuals (CTRL, N = 22) by application of an established fasting protocol in which calorie intake was omitted for 72 h. Both study groups were comparable regarding age, gender distribution, and body mass index (BMI). Fasting-induced effects on brain high-energy phosphate levels and membrane phospholipid metabolism were assessed using phosphorus-31 magnetic resonance spectroscopy (31P-MRS). Two-way repeated measures ANOVAs did not reveal significant interaction effects (group x fasting) or group differences in adenosine triphosphate (ATP), phosphocreatine (PCr), inorganic phosphate (Pi), phosphomonoesters (PME), phosphodiesters (PDE), or pH levels between MDD and CTRL. Fasting, independent of group, significantly increased ATP and decreased Pi levels and an overall increase in PME/PDE ratio as marker for membrane turnover was observed. Overall these results indicate reactive changes in cerebral energetics and in membrane phospholipid metabolism in response to fasting. The observed effects did not significantly differ between CTRL and MDD, indicating that neurometabolic adaptation to metabolic stress is preserved in MDD patients.

Objective: Parkinson’s disease (PD) is the second most common neurodegenerative disease in the elderly. In early stages of PD, patients typically display normal brain magnet resonance imaging (MRI) in routine screening. Advanced imaging approaches are necessary to discriminate early PD patients from healthy controls. In this study, microstructural changes in relevant brain regions of early PD patients were investigated by using quantitative MRI methods.Methods: Cerebral MRI at 3T was performed on 20 PD patients in early stages and 20 age and sex matched healthy controls. Brain relative proton density, T1, T2, and T2′ relaxation times were measured in 14 regions of interest (ROIs) in each hemisphere and compared between patients and controls to estimate PD related alterations.Results: In comparison to matched healthy controls, the PD patients revealed decreased relative proton density in contralateral prefrontal subcortical area, upper and lower pons, in ipsilateral globus pallidus, and bilaterally in splenium corporis callosi, caudate nucleus, putamen, thalamus, and mesencephalon. The T1 relaxation time was increased in contralateral prefrontal subcortical area and centrum semiovale, putamen, nucleus caudatus and mesencephalon, whereas T2 relaxation time was elevated in upper pons bilaterally and in centrum semiovale ipsilaterally. T2′ relaxation time did not show significant changes.Conclusion: Early Parkinson’s disease is associated with a distinct profile of brain microstructural changes which may relate to clinical symptoms. The quantitative MR method used in this study may be useful in early diagnosis of Parkinson’s disease. Limitations of this study include a small sample size and manual selection of the ROIs. Atlas-based or statistical mapping methods would be an alternative for an objective evaluation. More studies are necessary to validate the measurement methods for clinical use in diagnostics of early Parkinson’s disease.

Aging effects on striato-thalamic metabolism in healthy human brains were studied in vivo using short-TE whole brain 1H-MR spectroscopic imaging (wbMRSI) on eighty healthy subjects aged evenly between 20 to 70 years at 3T. Relative concentrations of N-acetyl-aspartate (NAA), choline, total creatine (tCr), myo-inositol (mI), glutamate, and glutamine in bilateral caudate nucleus, putamen, pallidum, and thalamus were determined using signal normalization relative to brain tissue water. Linear regression analysis was used to analyze the age-dependence of the metabolite concentrations. The metabolite concentrations revealed spatial inhomogeneity across brain regions and metabolites. With age, NAA decreased significantly in bilateral caudate nucleus and putamen, left pallidum, and left thalamus, tCr decreased in left putamen and bilateral pallidum, mI increased in bilateral caudate nucleus and right thalamus, and spectral linewidth increased in left putamen and right thalamus. In conclusion, normal aging of striato-thalamic metabolism in healthy human is associated with regional specific decreases of NAA and tCr and increases of mI, which may reflect the individual role of each brain structure within brain functionality.

(1) Purpose: Quantitative magnetic resonance imaging (qMRI) measurements can be used to sensitively estimate brain morphological alterations and may support clinical diagnosis of neurodegenerative diseases (ND). We aimed to establish a normative reference database for a clinical applicable quantitative MR morphologic measurement on neurodegenerative changes in patients, (2) Methods: Healthy subjects (HCs, n = 120) with an evenly distribution between 21 to 70 years and amyotrophic lateral sclerosis (ALS) patients (n = 11, mean age = 52.45 ± 6.80 years), as an example of ND patients, underwent magnetic resonance imaging (MRI) examinations under routine diagnostic conditions. Regional cortical thickness (rCTh) in 68 regions of interest (ROIs) and subcortical grey matter volume (SGMV) in 14 ROIs were determined from all subjects by using Computational Anatomy Toolbox. Those derived from HCs were analyzed to determine age-related differences and subsequently used as reference to estimate ALS-related alterations, (3) Results: In HCs, the rCTh (in 49/68 regions) and the SGMV (in 9/14 regions) in elderly subjects were less than those in younger subjects and exhibited negative linear correlations to age (p &lt, 0.0007 for rCTh and p &lt, 0.004 for SGMV). In comparison to age- and sex-matched HCs, the ALS patients revealed significant decreases of rCTh in eight ROIs, majorly located in frontal and temporal lobes, (4) Conclusion: The present study proves an overall grey matter decline with normal ageing as reported previously. The provided reference may be used for detection of grey matter alterations in neurodegenerative diseases that are not apparent in standard MR scans, indicating the potential of using qMRI as an add-on diagnostic tool in a clinical setting.

BACKGROUND AND PURPOSE To detect brain morphological alterations in patients with early Parkinson's disease (PD) by using magnetic resonance imaging (MRI) morphometry under radiological diagnostic conditions. METHODS T1-weighted brain images of 18 early PD patients and 18 age-sex-matched healthy controls (HCs) were analyzed with free software Computational Anatomy Toolbox (CAT12). Regional cortical thickness (rCTh) in 68 atlas-defined regions-of-interest (ROIs) and subcortical gray matter volume (SGMV) in 14 atlas-defined ROIs were determined and compared between patients and HCs by paired comparison using both ROI-wise and voxel-wise analyses. False-discovery rate (FDR) was used multiple comparison correction. Possible correlations between brain morphological changes in patients and clinical observations were also analyzed. RESULTS Comparing to the HCs, the ROI-wise analysis revealed rCTh thinning significantly in left medial orbitofrontal (P = .001), by trend (P < .05 but not significant after FDR correction) in four other ROIs located in frontal and temporal lobes, and a volume decreasing trend in left pallidum of the PD patients, while the voxel-wise analysis revealed one cluster with rCTh thinning trend located between left insula and superior temporal region of the patients. In addition, the patients showed more distinct rCTh thinning in ipsilateral hemisphere and SGMV deceasing trends in contralateral hemisphere in respect of the symptom-onset body side. CONCLUSION Brain morphological alterations in early PD patients are evident despite of their inconspicuous findings in standard MRI. Quantitative morphological measurements with CAT12 may be an applicable add-on tool for clinical diagnosis of early PD. These results have to be verified in future studies with larger patient samples.

PURPOSE: The aim of this study was to compare a recently established whole brain MR spectroscopic imaging (wbMRSI) technique using spin-echo planar spectroscopic imaging (EPSI) acquisition and the Metabolic Imaging and Data Analysis System (MIDAS) software package with single voxel spectroscopy (SVS) technique and LCModel analysis for determination of relative metabolite concentrations in aging human brain. METHODS: A total of 59 healthy subjects aged 20–70 years (n ≥ 5 per age decade for each gender) underwent a wbEPSI scan and 3 SVS scans of a 4ml voxel volume located in the right basal ganglia, occipital grey matter and parietal white matter. Concentration ratios to total creatine (tCr) for N-acetylaspartate (NAA/tCr), total choline (tCho/tCr), glutamine (Gln/tCr), glutamate (Glu/tCr) and myoinositol (mI/tCr) were obtained both from EPSI and SVS acquisitions with either LCModel or MIDAS. In addition, an aqueous phantom containing known metabolite concentrations was also measured. RESULTS: Metabolite concentrations obtained with wbMRSI and SVS were comparable and consistent with those reported previously. Decreases of NAA/tCr and increases of line width with age were found with both techniques, while the results obtained from EPSI acquisition revealed generally narrower line widths and smaller Cramer-Rao lower bounds than those from SVS data. CONCLUSION: The wbMRSI could be used to estimate metabolites in vivo and in vitro with the same reliability as using SVS, with the main advantage being the ability to determine metabolite concentrations in multiple brain structure simultaneously in vivo. It is expected to be widely used in clinical diagnostics and neuroscience.

BACKGROUND AND PURPOSE To investigate accumulative aging effects on neurometabolism in human brain and to collect a reference dataset. METHODS Fifty-four healthy volunteers aged evenly between 22 and 73 years were studied using whole-brain 1 H-MR spectroscopic imaging in combination with 31 P-MRS at 3T. Global metabolite concentrations of brain N-acetylaspartate (NAA), total choline (tCho), and total creatine (tCr), as well as phosphocreatine (PCr), adenosine-5'-triphosphate (ATP), phosphomonoesters (PME), phosphodiesters (PDE), and inorganic phosphate (Pi) were determined. Fractional volumes of brain gray matter (FVGM), white matter (FVWM), and total tissue (FVTB, GM+WM) were also estimated. RESULTS With age, NAA, ATP, and PME, as well as FVTB and FVGM decreased and tCho and FVWM increased linearly. Positive correlations were found between FVGM and global concentrations of NAA, ATP, PME, and Pi. CONCLUSION Age-related accumulative metabolic changes in aging human brain correlated with reduced neuronal metabolic activity and density, reflected by decreased NAA, reduced mitochondrial activity by decreased ATP, and reduced membrane synthesis by decreased PME. These changes are associated with age-related decrease of neuronal volume. Global NAA and ATP might be used as surrogate biomarker for monitoring aging in human brain.

Calcineurin inhibitors (CNIs) frequently induce neurological complications early after orthotopic liver transplantation (OLT). We hypothesize that longterm CNI therapy after OLT causes dose-dependent cognitive dysfunction and alteration of brain structure. In this study, 85 OLT patients (20 with CNI-free, 35 with CNI low-dose, and 30 with standard-dose CNI immunosuppression) underwent psychometric testing and cerebral magnetic resonance imaging approximately 10 years after OLT to assess brain function and structural brain alterations. A total of 33 healthy patients adjusted for age, sex, and education served as controls. Patients receiving CNI showed a significantly worse visuospatial/constructional ability compared with controls (P ≤ 0.04). Furthermore, patients on low-dose CNI therapy had an overall impaired cognitive function compared with controls (P = 0.01). The tacrolimus total dose and mean trough level were negatively correlated to cognitive function. CNI doses had been adjusted in 91% of the patients in the low-dose and CNI-free groups in the past due to CNI-induced kidney damage. Patients treated with CNI showed significantly more white matter hyperintensities (WMH) than patients on CNI-free immunosuppression and controls (P < 0.05). Both the mean cyclosporine A and tacrolimus trough levels correlated significantly with WMH. In conclusion, longterm CNI therapy carries a risk of cognitive dysfunction especially in patients who already showed nephrotoxic side effects indicating an increased susceptibility of these patients against toxic CNI effects. This subgroup of patients might benefit from a change to CNI-free immunosuppression. Liver Transplantation 24 56-66 2018 AASLD.

Adaptive response of human brain to stress plays a key role in maintaining health. Knowledge about how stress affects neurometabolism may help to understand adaptive stress responses, and distinguish maladaptation in neuropsychiatric disorders. In this study, neurometabolic responses to fasting stress in healthy women were investigated. Fifteen healthy females were examined for mood and cognition and using whole-brain MR spectroscopic imaging before and immediately after a 72-h fasting. Results were compared to 15 age-matched healthy females who did not taken part in fasting (non-fasting). Maps of the distributions in the brain of N-acetylaspartate (NAA), total choline (tCho), total creatine (tCr), glutamine/glutamate (Glx), and myo-Inositol (mI) were derived. Metabolite concentrations of each brain lobe and cerebellum measured before fasting were compared to those of post-fasting and non-fasting by repeated-measures ANOVA. After fasting, mood scores significantly increased. Glx decreased in all nine brain regions, tCho in eight, NAA in four and tCr in one, with Glx having the greatest change and the frontal lobes being the most affected brain region. In conclusion, fasting directly influences neurometabolism, and the adaptive brain response to maintain energy homeostasis under food deprivation in healthy women is associated with metabolite-selective and region-dependent changes of metabolite contents.

Major depressive disorder (MDD) is a severe mental disorder with a neurobiological basis that is poorly understood. Several studies demonstrated widespread, functional and neurometabolic alterations in MDD. However, little is known about whole brain neurometabolic alterations in MDD.Thirty-two patients with MDD and 32 paired on a one-to-one basis healthy controls (CTRL) underwentDecreased NAA, tCho, and tCr were found in the right frontal and right parietal lobe in MDD compared to CTRL, and to a lesser extent in the left frontal lobe. Furthermore, in MDD increased glutamine was observed in the right frontal lobe and bitemporal lobes, and increased glutamate in the cerebellum.Altered global neurometabolism examined using

Accurate estimation of the state of charge (SOC) of lithium batteries is the research hotspot. As a dynamic recurrent neural network, Elman neural network has a simple structure and can adapt to time-varying characteristics, which have led to its widespread application in the field of SOC prediction. However, the simple network structure can also cause problems such as low learning efficiency, easy to fall into local extremes, and difficulty converge to the optimal weight solution. This paper proposes to combine the whale optimization algorithm (WOA) with genetic algorithm (GA) to optimize the weights and thresholds of the Elman neural network, thus improving the learning speed and prediction accuracy. We select three parameters of current, voltage and temperature as system variables, and simulate the experimental data. The experimental results show that, compared with the traditional Elman neural network and the Elman neural network optimized only by genetic algorithm, the hybrid algorithm performs best. The number of network iterations is small, and the average error drops below 1%.

PURPOSE: To study brain metabolic changes under normal aging and to collect reference data for the study of neurodegenerative diseases. METHODS: A total of 55 healthy subjects aged 20–70 years (n ≥ 5 per age decade for each gender) underwent whole-brain magnetic resonance spectroscopic imaging at 3T after completing a DemTect test and the Beck depressions inventory II to exclude cognitive impairment and mental disorder. Regional concentrations of N–acetylaspartate (NAA), choline-containing compounds (Cho), total creatine (tCr), glutamine and glutamate (Glx), and myo-inositol (mI) were determined in 12 brain regions of interest (ROIs). The two-sided t-test was used to estimate gender differences and linear regression analysis was carried out to estimate age dependence of brain regional metabolite contents. RESULTS: Brain regional metabolite concentrations changed with age in the majority of selected brain regions. The NAA decreased in 8 ROIs with a rate varying from −4.9% to −1.9% per decade, reflecting a general reduction of brain neuronal function or volume and density in older age; Cho increased in 4 ROIs with a rate varying from 4.3% to 6.1%; tCr and mI increased in one ROI (4.2% and 8.2% per decade, respectively), whereas Glx decreased in one ROI (–5.1% per decade), indicating an inhomogeneous increase of cell membrane turnover (Cho) with altered energy metabolism (tCr) and glutamatergic neuronal activity (Glx) as well as function of glia cell (mI) in normal aging brain. CONCLUSION: Healthy aging up to the seventh decade of life is associated with regional dependent alterations of brain metabolism. These results provide a reference database for future studies of patients.

Objective: To estimate alterations in neurometabolic profile of patients with early stage Parkinson's disease (PD) by using a short echo-time whole brain magnetic resonance spectroscopic imaging (wbMRSI) as possible biomarker for early diagnosis and monitoring of PD.Methods: 20 PD patients in early stage (H&Y ≤ 2) without evidence of severe other diseases and 20 age and sex matched healthy controls underwent wbMRSI. In each subject brain regional concentrations of metabolites N-acetyl-aspartate (NAA), choline (Cho), total creatine (tCr), glutamine (Gln), glutamate (Glu), and myo-inositol (mIns) were obtained in atlas-defined lobar structures including subcortical basal ganglia structures (the left and right frontal lobes, temporal lobes, parietal lobes, occipital lobes, and the cerebellum) and compared between patients and matched healthy controls. Clinical characteristics of the PD patients were correlated with spectroscopic findings.Results: In comparison to controls the PD patients revealed altered lobar metabolite levels in all brain lobes contralateral to dominantly affected body side, i.e., decreases of temporal NAA, Cho, and tCr, parietal NAA and tCr, and frontal as well as occipital NAA. The frontal NAA correlated negatively with the MDS-UPDRS II (R = 22120.585, p = 0.008), MDS-UPDRS IV (R = −0.458, p = 0.048) and total MDS-UPDRS scores (R = −0.679, p = 0.001).Conclusion: In early PD stages metabolic alterations are evident in all contralateral brain lobes demonstrating that the neurodegenerative process affects not only local areas by dopaminergic denervation, but also the functional network within different brain regions. The wbMRSI-detectable brain metabolic alterations reveal the potential to serve as biomarkers for early PD.

Alterations in brain glucose metabolism and in peripheral glucose metabolism have frequently been observed in major depressive disorder (MDD). The insulin independent glucose transporter 1 (GLUT1) plays a key role in brain metabolism while the insulin-dependent GLUT4 is the major glucose transporter for skeletal and cardiac muscle. We therefore examined methylation of GLUT1 and GLUT4 in fifty-two depressed inpatients and compared data to eighteen healthy comparison subjects. DNA methylation of the core promoter regions of GLUT1 and GLUT4 was assessed by bisulfite sequencing. Further factors determined were fasting glucose, cortisol, insulin, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). We found significantly increased methylation of the GLUT1 in depressed inpatients compared to healthy comparison subjects (CG). Further findings comprise increased concentrations of fasting cortisol, glucose, insulin, and increased IL-6 and TNF-α. After six weeks of inpatient treatment, significantly lower GLUT1 methylation was observed in remitted patients compared to non-remitters. GLUT4 methylation was not different between depressed patients and CG, and did not differ between remitted and non-remitted patients. Although preliminary we conclude from our results that the acute phase of major depressive disorder is associated with increased GLUT1 methylation and mild insulin resistance. The successful treatment of depression is associated with normalization of GLUT1 methylation in remitters, indicating that this condition may be reversible. Failure of normalization of GLUT1 methylation in non-remitters may point to a possible role of impeded brain glucose metabolism in the maintenance of MDD.

Introduction Major depressive disorder (MDD) is a severe mental disorder with a neurobiological basis that is poorly understood. Several studies demonstrated widespread, functional and neurometabolic alterations in MDD. However, little is known about whole brain neurometabolic alterations in MDD. Method Thirty-two patients with MDD and 32 paired on a one-to-one basis healthy controls (CTRL) underwent 1H-whole brain spectroscopic (1H-WBS) imaging. Lobar and cerebellar metabolite concentrations of brain N-acetylaspartate (NAA), total choline (tCho), total creatine (tCr), glutamine (Gln), glutamate (Glu), and myo-Inositol (mI) were assessed in patients and controls. Results Decreased NAA, tCho, and tCr were found in the right frontal and right parietal lobe in MDD compared to CTRL, and to a lesser extent in the left frontal lobe. Furthermore, in MDD increased glutamine was observed in the right frontal lobe and bitemporal lobes, and increased glutamate in the cerebellum. Conclusion Altered global neurometabolism examined using 1H-WBS imaging in MDD may be interpreted as signs of neuronal dysfunction, altered energy metabolism, and oligodendrocyte dysfunction. In particular, the parallel decrease in NAA, tCr and tCho in the same brain regions may be indicative of neuronal dysfunction that may be counterbalanced by an increase of the neuroprotective metabolite glutamine. Future prospective investigations are warranted to study the functional importance of these findings.

PurposeTo investigate cerebral microstructural alterations in patients treated with calcineurin inhibitors (CNI) after orthotopic liver transplantation (OLT) using quantitative magnetic resonance imaging (qMRI) and a cross-sectional study design.MethodsCerebral qMRI was performed in 85 patients in a median 10 years after OLT compared to 31 healthy controls. Patients were treated with different dosages of CNI or with a CNI-free immunosuppression (CNI-free: n = 19; CNI-low: n = 36; CNI-standard: n = 30). T2-, T2*- and T2'- relaxation times, as well as apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured in brain gray and white matter by using the regions of interest method.ResultsIn comparison to controls, patients revealed significantly increased T2, T2*, T2', ADC and reduced FA, predominantly in the frontal white matter, indicating microstructural brain alterations represented by increased free water (increased T2), reduced neuronal metabolism (increased T2') and a lower degree of spatial organization of the nervous fibers (reduced FA). CNI-low and CNI-free patients showed more alterations than CNI-standard patients. Analysis of their history revealed impairment of kidney function while under standard CNI dose suggesting that these patients may be more vulnerable to toxic CNI side-effects.ConclusionOur findings suggest that the individual sensitivity to toxic side effects should be considered when choosing an appropriate immunosuppressive regimen in patients after liver transplantation.

While acute neurotoxic side effects of calcineurin inhibitors (CNI) are well-known, data upon long-term effects on brain structure and function are sparse. We hypothesize that long-term CNI therapy affects the neuroimmune system, thereby, increasing the risk of neurodegeneration. Here, we measured the impact of CNI therapy on plasma levels of brain- and T cell-derived cytokines in a cohort of patients after liver transplantation (LT).Levels of T cell-mediated cytokines (e.g. Interferon-γ (IFN-γ)) and brain-derived cytokines (e.g. brain derived neurotrophic factor (BDNF), platelet derived growth factor (PDGF)) were measured by multiplex assays in plasma of 82 patients about 10 years after LT (17 with CNI free, 35 with CNI low dose, 30 with standard dose CNI immunosuppression) and 33 healthy controls. Data were related to psychometric test results and parameters of cerebral magnetic resonance imaging.IFN-γ levels were significantly higher in the CNI free LT patient group (p=0.027) compared to healthy controls. BDNF levels were significantly lower in LT patients treated with CNI (CNI low: p0.001; CNI standard: p=0.016) compared to controls. PDGF levels were significantly lower in the CNI low dose group (p=0.004) and for PDGF-AB/BB also in the CNI standard dose group (p=0.029) compared to controls. BDNF and PDGF negatively correlated with cognitive function and brain volume (p0.05) in the CNI low dose group.Our results imply that long-term treatment with CNI suppresses BDNF and PDGF expression, both crucial for neuronal signaling, cell survival and synaptic plasticity and thereby may lead to cognitive dysfunction and neurodegeneration.

BACKGROUND Calcineurin inhibitor (CNI) neurotoxicity after liver transplantation might be due to impairment of the cerebral metabolism. AIMS To investigate CNI-related alterations of brain metabolite distributions and associations between cognitive function and brain metabolism in patients with long-term CNI treatment after liver transplantation. METHODS Eighty-two patients (19 CNI free, 34 CNI low-dose and 29 standard-dose CNI immunosuppression) 10 years after liver transplantation and 32 adjusted healthy controls underwent nonlocalised brain phosphorus magnetic resonance spectroscopy (MRS) and single voxel proton MRS in the parietal white matter to estimate brain metabolite contents. The MRS results were correlated with psychometric data assessing cognitive function. RESULTS Phosphorus metabolite concentrations with the exception of phosphocreatine (PCr) were reduced in patients compared to controls. Particularly, patients with low-dose CNI therapy showed a significant decrease in adenosine triphosphate (0.209 ± 0.012 vs 0.222 ± 0.010; P

Chronic fatigue, mood alterations and cognitive impairment are frequent accessory symptoms of HCV infection. Fatigue and mood alterations have also been observed in autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC), but not in hepatitis B virus (HBV)-infection, thus indicating an autoimmune response as possible cause of HCV infection-associated encephalopathy. Data, however, are sparse. This study aimed to prove that HCV patients feature similar to those with autoimmune liver disease but contrary to HBV patients regarding neuropsychiatric symptoms. A total of 132 noncirrhotic patients (HCV: 46, HBV: 22, AIH: 27, PBC: 29, AIH/PBC: 8) completed questionnaires addressing the domains mentioned above. Eighty-eight underwent a comprehensive neuropsychological assessment. Patient groups were compared among each other and to 33 healthy controls. Fatigue, anxiety and depression scores were significantly increased, and the SF-36 mental score significantly decreased in all patient groups compared to controls. Fatigue was significantly more pronounced in HCV than in HBV patients. HCV patients scored significantly worse than HBV patients but not AIH and PBC patients in the SF-36. HCV, AIH and PBC but not HBV patients did significantly worse than controls in word learning. Recognition of words was impaired in HCV, AIH and PBC patients and recognition of figures in HCV patients, exclusively (P ≤ 0.002). HCV patients did also worse than controls and HBV patients concerning alertness and working memory (P ≤ 0.001). The neuropsychiatric profiles of HCV patients are similar to those of AIH and PBC patients but differ from those of HBV patients, suggesting an autoimmune response as a possible cause for these differences.

BACKGROUND AND PURPOSE: Knowledge of age-related physiological changes in the human brain is a prerequisite to identify neurodegenerative diseases. Therefore, in this study whole-brain 1 H-MRS was used in combination with quantitative MR imaging to study the effects of normal aging on healthy human brain metabolites and microstructure. MATERIALS AND METHODS: Sixty healthy volunteers, 21–70 years of age, were studied. Brain maps of the metabolites NAA, creatine and phosphocreatine, and Cho and the tissue irreversible and reversible transverse relaxation times T2 and T2′ were derived from the datasets. The relative metabolite concentrations and the values of relaxation times were measured with ROIs placed within the frontal and parietal WM, centrum semiovale, splenium of the corpus callosum, hand motor area, occipital GM, putamen, thalamus, pons ventral/dorsal, and cerebellar white matter and posterior lobe. Linear regression analysis and Pearson correlation tests were used to analyze the data. RESULTS: Aging resulted in decreased NAA concentrations in the occipital GM, putamen, splenium of the corpus callosum, and pons ventral and decreased creatine and phosphocreatine concentrations in the pons dorsal and putamen. Cho concentrations did not change significantly in selected brain regions. T2 increased in the cerebellar white matter and decreased in the splenium of the corpus callosum with aging, while the T2′ decreased in the occipital GM, hand motor area, and putamen, and increased in the splenium of the corpus callosum. Correlations were found between NAA concentrations and T2′ in the occipital GM and putamen and between creatine and phosphocreatine concentrations and T2′ in the putamen. CONCLUSIONS: The effects of normal aging on brain metabolites and microstructure are region-dependent. Correlations between both processes are evident in the gray matter. The obtained data could be used as references for future studies on patients.

Accompanying the advance of neuroscientific research and modern therapeutic methods, efforts have been made to develop more practical and effective advanced magnetic resonance (MR) spectroscopic techniques. We present a brief overview on 1H-MRS techniques in neuroradiological diagnosis and several application examples of recently reported whole brain MR spectroscopic imaging technique (wbMRSI). Despite the benefits of using established 1H-MRS techniques both single voxel MR spectroscopy (SVS) and chemical shift imaging (CSI) techniques suffer from limited spatial coverage. It is always necessary to define prior to the MRS examination which brain structure is physiologically or pathologically involved and thus should be targeted with 1H-MRS. In contrast, the advanced wbMRSI allows estimating metabolite changes within a much larger brain region and at multiple brain structures simultaneously. As a developing technique for advanced analysis of cerebral metabolism a wide application of the wbMRSI in both clinical diagnostics and neuroscience could be expected.

To investigate accumulative aging effects on neurometabolism in human brain and to collect a reference dataset.Fifty-four healthy volunteers aged evenly between 22 and 73 years were studied using whole-brainWith age, NAA, ATP, and PME, as well as FVTB and FVGM decreased and tCho and FVWM increased linearly. Positive correlations were found between FVGM and global concentrations of NAA, ATP, PME, and Pi.Age-related accumulative metabolic changes in aging human brain correlated with reduced neuronal metabolic activity and density, reflected by decreased NAA, reduced mitochondrial activity by decreased ATP, and reduced membrane synthesis by decreased PME. These changes are associated with age-related decrease of neuronal volume. Global NAA and ATP might be used as surrogate biomarker for monitoring aging in human brain.

Purpose A feasibility study of an echo-planar spectroscopic imaging (EPSI) using a short echo time (TE) that trades off sensitivity, compared with other short-TE methods, to achieve whole brain coverage using inversion recovery and spatial oversampling to control lipid bleeding. Methods Twenty subjects were scanned to examine intersubject variance. One subject was scanned five times to examine intrasubject reproducibility. Data were analyzed to determine coefficients of variance (COV) and intraclass correlation coefficient (ICC) for N–acetylaspartate (NAA), total creatine (tCr), total choline (tCho), glutamine/glutamate (Glx), and myo-inositol (mI). Regional metabolite concentrations were derived by using multi-voxel analysis based on lobar-level anatomic regions. Results For whole-brain mean values, the intrasubject COVs were 14%, 15%, and 20% for NAA, tCr, and tCho, respectively, and 31% for Glx and mI. The intersubject COVs were up to 6% higher. For regional distributions, the intrasubject COVs were ≤ 5% for NAA, tCr, and tCho; ≤ 9% for Glx; and ≤15% for mI, with about 6% higher intersubject COVs. The ICCs of 5 metabolites were ≥ 0.7, indicating the reliability of the measurements. Conclusion The present EPSI method enables estimation of the whole-brain metabolite distributions, including Glx and mI with small voxel size, and a reasonable scan time and reproducibility. Magn Reson Med 73:921–928, 2015. © 2014 Wiley Periodicals, Inc.

Severe neurological symptoms in Shiga toxin-producing Escherichia coli infection associated hemolytic–uremic syndrome (STEC–HUS) are often accompanied by none or only mild alterations of cerebral magnetic resonance imaging (MRI). This study aims to analyze if quantitative MRI is able to reveal cerebral pathological alterations invisible for conventional MRI. In nine patients with STEC–HUS associated severe neurological symptoms but inconspicuous cerebral MRI findings maps of the parameters T2 relaxation time, relative proton density (PD), apparent diffusion coefficient (ADC), and fractional anisotropy (FA) were generated. Quantitative values of these parameters were measured at the basal ganglia, thalamus, and white matter of the frontal and parietal lobe and compared to those of nine age- and sex-matched controls. Significant T2 prolongation (p

The two most prevalent forms of neuronal ceroid lipofuscinosis (NCL) are the juvenile form (Batten disease, CLN3) and late infantile form (Jansky-Bielschowsky disease, CLN2). The aim of this study was to compare quantitative T2-values of brain tissue in CLN2 and CLN3 patients with reference values from age-matched normal subjects.Twenty-three CLN2 (n = 6) and CLN3 (n = 17) patients (m:f = 11:12) underwent MRI examination including a multiecho T2 sequence. Quantitative T2-values were measured in six defined regions of interest (ROIs) in the calculated quantitative T2 maps within the white matter (WM) and gray matter (GM). The extracted quantitative T2-values were compared with reference values from healthy children and young adults. Informed consent was obtained from the patients or their parents for all patients.Statistical analysis revealed elevated quantitative T2-values in nearly all ROIs placed in the WM of the CLN2 patients. In contrast to this finding, no significant differences were found for the quantitative T2-values of the CLN3 patients compared to the age-matched healthy controls in any of the defined WM ROIs. Both groups exhibited no significant alterations of the quantitative T2-values in the GM ROIs compared to the healthy subjects.Alterations of quantitative T2-values in the cerebral WM may not be a reliable sign to confirm the diagnosis in CLN3 patients but could prove valuable for diagnosis confirmation, follow-up examinations, and longitudinal monitoring of the disease progression in CLN2 patients.

To find imaging signs of active degenerative processes in vanishing white matter disease (VWM), six VWM patients and six matched controls underwent MR examinations. The data were analyzed with modified Scheltens scales for morphological findings and determined quantitatively for apparent diffusion coefficient (ADC). Single-voxel MR spectra were acquired at the parietal white matter and analyzed with LCModel. Typical VWM brain lesions were found in all patients accompanied by proton diffusion abnormalities: Increased ADC appeared in brain regions with severe myelin destruction in all patients, and reduced ADC in two of six younger patients in remaining white matter adjacent to the lesions or at the borders around the lesions, who had a short history of the disease (≤ 1 year). The MR spectroscopy revealed reductions of NAA, Cho, and Cr, which correlate to the grade of white matter abnormalities. An increase of myo-inositol as marker of reactive gliosis was missing. Thus, restricted proton diffusion was evident in younger VWM patients with short history of disease, which in combination with lack of reactive gliosis may reflect early white matter degeneration in VWM. The multimodal MR methods are useful for characterizing such tissue degeneration in brain in vivo.

Diffusion-weighted imaging (DWI) in children with diarrhoea associated haemolytic uraemic syndrome (D+HUS) and cerebral involvement was evaluated retrospectively.DWI within 24 h of onset of neurological symptoms. The apparent diffusion coefficient (ADC) was measured in grey/white matter and correlated with clinical and laboratory findings.DWI was abnormal in all. Abnormal ADC was detected in the supratentorial white matter (6/12) and cortex (1/12), the basal ganglia (5/12), the thalami (4/12), and the cerebellum (1/12). ADC was reduced in 5/12, increased in 4/12, and both in 3/12. Mean serum sodium was lower in patients with DWI abnormalities affecting the white matter (6/12), than in those with basal ganglia/thalamic involvement (6/12). Neurological outcome was normal in 4/11 and abnormal in 7/11, and 1 patient died, outcome did not correlate to either localisation or type of DWI abnormality.In D+HUS with neurological symptoms, early DWI may reveal abnormal ADC not only in the basal ganglia/thalami, but also in the white matter/cortex. Besides thrombotic microangiopathy, toxic effects of shiga toxin, azotaemia and hyponatraemia / hypoosmolality may be involved in cerebral involvement in children with D+HUS. Findings on early MRI seem not to predict clinical course or outcome.• DWI MR imaging may detect early CNS involvement in haemolytic uraemic syndrome • Different pathogenetical mechanisms may contribute to the CNS disease in HUS • Early MRI findings do not seem to allow prediction of clinical outcome.

Different compositions of the extra cellular matrix with changing concentrations of more or less hydrophilic components like proteins may have a major influence on the diffusion phenomena found in gliomas. 24 patients (14 male / 10 female) with histologically confirmed non necrotic glioma underwent preoperative MRI, including magnetisation transfer (MTR), triple echo T2 weighted (T2W) and diffusion weighted (DWI) sequences. Apparent diffusion coefficient (ADC), quantitative T2 and MTR maps were calculated and regions of interest (ROIs) were placed in the tumour centre (TU) and in the contralateral hemisphere (NWM). Informed consent was obtained. The study was approved by the local ethic comity. Mean values evaluated in the NWM / TU were (± standard deviation); ADC: 0.78 (±0.08) × 10-3 mm2/s / 1.32 (±0.27) × 10-3 mm2/s, T2: 101.66 (±12.00) ms / 252.11 (±104.53) ms, MTR: 0.52 (±0.01) / 0.40 (±0.04). The mean value of each parameter correlated highly significant with the others (p

Approximately one-third of epilepsy patients are pharmacoresistant. Overexpression of P-glycoprotein and other multidrug transporters at the blood–brain barrier is thought to play an important role in drug-refractory epilepsy. Thus, quantification of regionally different P-glycoprotein activity in the brain in vivo is essential to identify P-glycoprotein overactivity as the relevant mechanism for drug resistance in an individual patient. Using the radiolabeled P-glycoprotein substrate ( R )-[ 11 C]verapamil and different doses of coadministered tariquidar, which is an inhibitor of P-glycoprotein, we evaluated whether small-animal positron emission tomography can quantify regional changes in transporter function in the rat brain at baseline and 48 h after a pilocarpine-induced status epilepticus. P-glycoprotein expression was additionally quantified by immunohistochemistry. To reveal putative seizure-induced changes in blood–brain barrier integrity, we performed gadolinium-enhanced magnetic resonance scans on a 7.0 tesla small-animal scanner. Before P-glycoprotein modulation, brain uptake of ( R )-[ 11 C]verapamil was low in all regions investigated in control and post-status epilepticus rats. After administration of 3 mg/kg tariquidar, which inhibits P-glycoprotein only partially, we observed increased regional differentiation in brain activity uptake in post-status epilepticus versus control rats, which diminished after maximal P-glycoprotein inhibition. Regional increases in the efflux rate constant k 2 , but not in distribution volume V T or influx rate constant K 1 , correlated significantly with increases in P-glycoprotein expression measured by immunohistochemistry. This imaging protocol proves to be suitable to detect seizure-induced regional changes in P-glycoprotein activity and is readily applicable to humans, with the aim to detect relevant mechanisms of pharmacoresistance in epilepsy in vivo .

Biallelic mutations in the gene encoding HCLS-associated protein X-1 (HAX1) cause autosomal recessive severe congenital neutropenia (SCN). Some of these patients have neurological abnormalities including developmental delay, cognitive impairment, and/or epilepsy. Recent genotype-phenotype studies have shown that mutations in HAX1 affecting transcripts A (NM_006118.3) and B (NM_001018837.1) cause the phenotype of SCN with neurological impairment, while mutations affecting isoform A but not B lead to SCN without neurological aberrations. In this study, we identified a consanguineous family with two patients suffering from SCN and neurological disease caused by a novel, homozygous genomic deletion including exons 4-7 of the HAX1 gene. Quantitative MRI analyses showed generalized alterations in cerebral proton density in both of the patients, as well as in an additional unrelated patient with another HAX1 mutation (Arg86X) known to be associated with neurological manifestations. This study provides first in vivo evidence of aberrant neuroimaging findings associated with HAX1 deficiency in SCN patients.

BACKGROUND AND PURPOSE Cerebral small vessel disease is a topic of growing interest for both the scientific community and the aging society. We report the magnetic resonance imaging (MRI) characteristics of a recently found autosomal dominantly inherited microangiopathy. METHODS Eighteen members (35 to 77 years) of a large German family underwent MR scanning with a standardized MRI protocol for cerebrovascular diseases. Images were evaluated independently by two neuroradiologists. RESULTS Six family members revealed an unequivocally pathological phenotype on MRI with lacunar infarcts of the pons (6/6) and lesions of the subcortical and periventricular white matter (5/6). Lesions in the temporal lobes (1/6) and cerebral microbleeds (1/6) were uncommon. None of the patients revealed atherosclerotic changes in MR angiography. Retrospective analysis of 5 brain autopsies from previously reported patients of the same family confirmed the regular involvement of the pons. CONCLUSION This cerebral autosomal dominant arteriopathy with pontine infarcts and leukoencephalopathy is characterized by a special lesion pattern strikingly different from CADASIL. The distinct MRI characteristics with pontine lesions and rare occurrence of temporal lesions argue for a new nosological entity and may be helpful for the differential diagnosis.

Overactivity of the multidrug efflux transporter P-glycoprotein (P-gp) at the blood-brain barrier (BBB) is believed to play an important role in resistance to central nervous system drug treatment. (R)-[(11)C]verapamil (VPM) PET can be used to measure the function of P-gp at the BBB, but low brain uptake of VPM hampers the mapping of regional differences in cerebral P-gp function and expression. The aim of this study was to evaluate the dose-response relationship of two potent P-gp inhibitors and to investigate if increased brain uptake of VPM mediated by P-gp inhibition can be used to assess regional differences in P-gp activity.Two groups of Sprague-Dawley rats (n = 12) underwent single VPM PET scans at 120 min after administration of different doses of the P-gp inhibitors tariquidar and elacridar. In an additional six rats, paired VPM PET scans were performed before and after administration of 3 mg/kg tariquidar.Inhibitor administration resulted in an up to 11-fold increase in VPM brain distribution volumes (DV) with half-maximum effective dose (ED(50)) values of 3.0 +/- 0.2 and 1.2 +/- 0.1 mg/kg for tariquidar and elacridar, respectively. In paired PET scans, 3 mg/kg tariquidar resulted in regionally different enhancement of brain activity distribution, with lowest DV in cerebellum and highest DV in thalamus.Our data show that tariquidar and elacridar are able to increase VPM brain distribution in rat brain up to 11-fold over baseline at maximum effective doses, with elacridar being about three times more potent than tariquidar. Regional differences in tariquidar-induced modulation of VPM brain uptake point to regional differences in cerebral P-gp function and expression in rat brain.

Callosal fibres play an important role in psychomotor and cognitive functions. The purpose of this study was to investigate possible microstructural abnormalities of the corpus callosum in children with developmental delay, who have normal conventional brain MR imaging results. Seventeen pediatric patients (aged 1-9 years) with developmental delay were studied. Quantitative T2 and fractional anisotropy (FA) values were measured at the genu and splenium of the corpus callosum (CC). Fibre tracking, volumetric determination, as well as fibre density calculations of the CC were also carried out. The results were compared with those of the age-matched healthy subjects. A general elevation of T2 relaxation times (105 ms in patients vs. 95 ms in controls) and reduction of the FA values (0.66 in patients vs. 0.74 in controls) at the genu of the CC were found in patients. Reductions of the fibre numbers (5,464 in patients vs. 8,886 in controls) and volumes (3,415 ml in patients vs. 5,235 ml in controls) of the CC were found only in patients older than 5 years. The study indicates that despite their inconspicuous findings in conventional MRI microstructural brain abnormalities are evident in these pediatric patients suffering from developmental delay.

Optic neuritis (ON) and any other early manifestation of multiple sclerosis (MS) are referred to as clinically isolated syndrome (CIS) as long as MS is suspected. In this prospective study we aimed to determine whether diffusion tensor imaging (DTI) could quantify structural changes in patients with early MS. A total of 24 patients and 15 control subjects were prospectively followed by clinical examinations and MRI. the main inclusion criterion was presentation with ON. Patients underwent serial MRI scans: MRI1 (baseline, n=24), MRI2 (mean 6.6 months, n=24), MRI3 (mean 13.0 months, n=14), MRI4 (mean 39.4 months, n=5). Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps were derived from DTI. Four regions of interest (ROIs) were defined in normal-appearing white matter (NAWM). In the temporal course FA decreased in the genu of the callosal body (GCC) from MRI1 to MRI4 (P=0.005) and in the splenium of the callosal body (SCC) (P=0.006). Patients already had lower FA values in the SCC (P

BACKGROUND AND PURPOSE: Development of callosal fibers is important for psychomotor and cognitive functions. We hypothesized that brain maturation changes are detectable beyond 2 years of age by using diffusion tensor imaging (DTI) of the corpus callosum (CC). MATERIALS AND METHODS: T2 and fractional anisotropy (FA) maps of the brain of 55 healthy subjects between 0.2 and 39 years of age were obtained. Quantitative T2 and FA values were measured at the genu and splenium of the CC (gCC and sCC). Fiber tracking, volumetric determination, and the fiber density calculations of the CC were related to age. A paired t test was used for significant differences between the values at the gCC and sCC. RESULTS: T2 relaxation times at gCC and sCC decrease fast in the first months of life and very little after 2 years of age. The FAgCC increases until 5 years of age and remains nearly constant thereafter; it showed a significant increase from 0 to 2 years versus 2–5 years, whereas there was no difference in the other age groups. FAsCC values showed no significant changes after 2 years of age. The fiber density of the CC shows a tendency of inverse age dependence from childhood to adulthood. CONCLUSION: Rapid ongoing changes in brain maturation (increase in FAgCC) are detectable until 5 years of age. DTI reveals more information about brain maturation than T2 relaxometry.

Quantification of apparent diffusion coefficient (ADC), fractional anisotropy (FA), and T2 relaxation time are increasingly important for neuroradiologic applications. A transfer of the values established for 1.5-T to 3-T MRI must be supported by a dedicated comparison with special emphasis on possible differences in the spatial distribution. In the present study, brain scans were carried out in 16 healthy volunteers at both 1.5-T and 3-T systems of the same design and gradient system. The protocol consisted of a fast spin echo (TSE) sequence, two singleshot spin echo echoplanar imaging (EPI) sequences for diffusion-weighted imaging and diffusion tensor imaging. Data from the two field strengths were compared for ADC, FA, and T2 relaxation times. The signal-to-noise ratio (SNR) was also compared for all sequences and echo times. While there were no differences in ADC and FA, the T2 relaxation time was reduced by 15% at 3 T. A higher SNR at 3 T was found for both TSE and EPI sequences as expected (p < 0.05). Special benefits of the T2 measurement at higher field strengths are possible on certain clinical conditions due to reduced T2 relaxation time. Furthermore the results of the ADC and FA obtained from patients at different field strengths could be directly compared with each other – useful in the clinical follow-up.

A 29-year-old female patient with juvenile metachromatic leukodystrophy diagnosed at age 14 years received a bone marrow transplant at age 16 years. A report was published 6 years after bone marrow transplantation concluding that the disease had slowly progressed in the 2 years following bone marrow transplantation. We now report on a further 7-year follow-up, typified by a steady state of spastic paraplegia and mild dementia. Neurophysiological, neuroradiological, and psychological status also remained stable. In the patient's leukocytes, the activity of arylsulfatase A, the enzyme deficient in untreated metachromatic leukodystrophy, was within the normal range whereas urinary sulfatides remained elevated. Data on the natural course of juvenile metachromatic leukodystrophy are rare, so in the present case it is difficult to establish whether the rather favorable course can be attributed with certainty to bone marrow transplantation. The long-term stabilization in this patient, however, suggested that bone marrow transplantation may halt the progression of juvenile metachromatic leukodystrophy.

In this pediatric case of vanishing white matter disease with early onset, rapidly progressive course, and fatal outcome, the white matter vanishing process in patient was for the first time documented morphologically in detail: An initial magnetic resonance imaging documented a normal appearing brain maturation. Rapid progressive brain lesions initiated morphologically DE NOVO in the former well myelinated deep white matter were observed six months later after disease onset, including concentric ongoing signs of restricted proton diffusion cytotoxic edema on diffusion weighted imaging. Cyst-like defects at the lesion center of the deep white matter were detected more clearly on MRI ten months later. A pathomechanism like tumor necrosis factor induced oligodendrocyte apoptosis and primary demyelination was postulated. The case demonstrates that in the presence of clinically progressive symptoms, the development of VWM is possible even if first MRI findings are negative.

To prospectively evaluate whether diffusion-tensor magnetic resonance (MR) imaging depicts differences in World Health Organization (WHO) grade II and III glial brain tumors on the basis of tumor architecture and peritumoral tract invasion.The study protocol was approved by the local ethics committee, and written informed consent was obtained. Diffusion-tensor MR imaging was performed in 23 patients (15 men, eight women; mean age, 47 years) with histologically confirmed brain gliomas. Eleven of the 23 tumors were low-grade gliomas (WHO grade II) and 12 were anaplastic gliomas (WHO grade III). Regions of interest were placed in the tumor center, tumor border, normal-appearing white matter (NAWM) adjacent to the tumor, and NAWM of the contralateral hemisphere. fractional anisotropy (FA) ratios were calculated for regions of interest in relation to the NAWM of the contralateral hemisphere. Pairwise comparisons were performed by using the Mann-Whitney U test.Median FA ratios for grade II versus grade III gliomas were 0.406 versus 0.405, respectively, for tumor center, 0.733 versus 0.449, respectively, for tumor border, and 0.962 versus 0.943, respectively, for NAWM adjacent to the tumor. Differences in FA ratio between low-grade and high-grade tumors were significant in the tumor border only (P = .01). Differences in FA ratio were not significant between low-grade and high-grade gliomas in the tumor center or in the NAWM adjacent to the tumor.The periphery of low-grade gliomas contains a considerable amount of preserved fiber tracts. In high-grade gliomas, however, most of these tracts are disarranged. Low FA ratios in the tumor center are consistent with a high degree of disorganization of myelinated fiber tracts in the center of both low-grade and high-grade gliomas.

A 23-month-old girl of consanguineous parents suffering from infantile neuronal ceroid lipofuscinosis (INCL) was studied with magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). A progressive reduction of brain volume was documented in two MRI studies within 2 months. Quantitative measurements of the T2 relaxation times showed a shorter T2 value of the thalamus bilaterally. A reduced concentration of N-acetylaspartate (NAA), and an elevated level of myo-inositol (mI) and lactate (Lac) in white matter were detected by MRS. Differential diagnosis of INCL, rather than Rett syndrome, a disease that evokes a similar clinical syndrome as INCL does, was made mainly based on the MRS data. Absence of the enzyme palmitoyl-protein-thioesterase 1 and a corresponding gene mutation in biochemical studies confirmed INCL.