Whole-Brain Magnetic Resonance Spectroscopy Reveals Distinct Alterations in Neurometabolic Profile in Progressive Supranuclear Palsy.

BACKGROUND: Progressive supranuclear palsy (PSP) is an atypical Parkinsonian syndrome characterized by supranuclear gaze palsy, early postural instability, and a frontal dysexecutive syndrome. Contrary to normal brain magnetic resonance imaging in Parkinson's disease (PD), PSP shows specific cerebral atrophy patterns and alterations, but these findings are not present in every patient, and it is still unclear if these signs are also detectable in early disease stages. OBJECTIVE: The aim of the present study was to analyze the metabolic profile of patients with clinically diagnosed PSP in comparison with matched healthy volunteers and PD patients using whole-brain magnetic resonance spectroscopic imaging (wbMRSI). METHODS: Thirty-nine healthy controls (HCs), 29 PD, and 22 PSP patients underwent wbMRSI. PSP and PD patients were matched for age and handedness with HCs. Clinical characterization was performed using the Movement Disorder Society Unified Parkinson's Disease Rating Scale, PSP rating scale, and DemTect (test for cognitive assessment). RESULTS: In PSP patients a significant reduction in N-acetyl-aspartate (NAA) was detected in all brain lobes. Fractional volume of the cerebrospinal fluid significantly increased in PSP patients compared to PD and healthy volunteers. CONCLUSIONS: In PSP much more neuronal degeneration and cerebral atrophy have been detected compared with PD. The most relevant alteration is the decrease in NAA in all lobes of the brain, which also showed a partial correlation with clinical symptoms. However, more studies are needed to confirm the additional value of wbMRSI in clinical practice. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Brain metabolic and microstructural alterations associated with hepatitis C virus infection, autoimmune hepatitis and primary biliary cholangitis.

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.

Reduced microglia activity in patients with long-term immunosuppressive therapy after liver transplantation.

PURPOSE: Calcineurin inhibitors (CNI) can cause long-term impairment of brain function. Possible pathomechanisms include alterations of the cerebral immune system. This study used positron emission tomography (PET) imaging with the translocator protein (TSPO) ligand 18F-GE-180 to evaluate microglial activation in liver-transplanted patients under different regimens of immunosuppression. METHODS: PET was performed in 22 liver-transplanted patients (3 CNI free, 9 with low-dose CNI, 10 with standard-dose CNI immunosuppression) and 9 healthy controls. The total distribution volume (VT) estimated in 12 volumes-of-interest was analyzed regarding TSPO genotype, CNI therapy, and cognitive performance. RESULTS: In controls, VT was about 80% higher in high affinity binders (n = 5) compared to mixed affinity binders (n = 3). Mean VT corrected for TSPO genotype was significantly lower in patients compared to controls, especially in patients in whom CNI dose had been reduced because of nephrotoxic side effect. CONCLUSION: Our results provide evidence of chronic suppression of microglial activity in liver-transplanted patients under CNI therapy especially in patients with high sensitivity to CNI toxicity.

Physiological neuronal decline in healthy aging human brain - An in vivo study with MRI and short echo-time whole-brain (1)H MR spectroscopic imaging.

Knowledge of physiological aging in healthy human brain is increasingly important for neuroscientific research and clinical diagnosis. To investigate neuronal decline in normal aging brain eighty-one healthy subjects aged between 20 and 70years were studied with MRI and whole-brain (1)H MR spectroscopic imaging. Concentrations of brain metabolites N-acetyl-aspartate (NAA), choline (Cho), total creatine (tCr), myo-inositol (mI), and glutamine+glutamate (Glx) in ratios to internal water, and the fractional volumes of brain tissue were estimated simultaneously in eight cerebral lobes and in cerebellum. Results demonstrated that an age-related decrease in gray matter volume was the largest contribution to changes in brain volume. Both lobar NAA and the fractional volume of gray matter (FVGM) decreased with age in all cerebral lobes, indicating that the decreased NAA was predominantly associated with decreased gray matter volume and neuronal density or metabolic activity. In cerebral white matter Cho, tCr, and mI increased with age in association with increased fractional volume, showing altered cellular membrane turn-over, energy metabolism, and glial activity in human aging white matter. In cerebellum tCr increased while brain tissue volume decreased with age, showing difference to cerebral aging. The observed age-related metabolic and microstructural variations suggest that physiological neuronal decline in aging human brain is associated with a reduction of gray matter volume and neuronal density, in combination with cellular aging in white matter indicated by microstructural alterations and altered energy metabolism in the cerebellum.

Reproducibility and reliability of short-TE whole-brain MR spectroscopic imaging of human brain at 3T.

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.

Cerebral white matter lesions in patients with cirrhosis - causative for hepatic encephalopathy or bystanders?

BACKGROUND & AIMS: Focal white matter lesions mimicking microvascular lesions were connected to the development of hepatic encephalopathy (HE) in patients with cirrhosis. This study aims to assess the relationship between cerebrovascular risk factors and the prevalence and extent of these lesions in patients with cirrhosis, as well as their impact upon cognitive function. METHODS: 55 cirrhotic patients underwent neurological examination, psychometric testing and magnetic resonance imaging. T2-weighted images were reviewed for white matter lesions by a neuroradiologist and a neurologist, independently. Patients were allocated into three groups: (i) no or <5, (ii) 6-15 and (iii) more than 15 lesions. Allocation was confirmed by a senior neuroradiologist blinded for the clinical data. The patient groups were compared concerning age, underlying liver disease, mortality, MELD Score, history of HE, treatment for HE, cerebrovascular risk factors and psychometric test results. Regression analysis was performed to identify risk factors for the presence and extent of white matter lesions. RESULTS: Patient groups 2 and 3 were older and showed worse results in the psychometric tests than group 1 (P < 0.05). Correlation analyses showed a significant relationship between the number of white matter lesions and the grade of HE (P < 0.001) and cognitive function (P < 0.05), but no interrelationship between the lesions and cerebrovascular risk factors or other factors tested. CONCLUSIONS: Focal white matter lesions in patients with cirrhosis do not represent cerebrovascular small-vessel disease but are related to the pathology of HE. Further studies are needed to clarify the mechanisms behind in detail.

Quantitative MRI shows cerebral microstructural damage in hemolytic-uremic syndrome patients with severe neurological symptoms but no changes in conventional MRI.

INTRODUCTION: 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. METHODS: 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. RESULTS: Significant T2 prolongation (p < 0.01) was found in the basal ganglia of all patients compared to controls. PD and ADC were not significantly altered. A significant reduction of FA in patients was seen at caput nuclei caudati (p < 0.01). CONCLUSION: Prolonged T2 relaxation time indicates cerebral microstructural damages in these patients despite their inconspicuous MRI findings. T2 relaxometry could be used as a complementary tool for the assessment of metabolic-toxic brain syndromes.

A novel positron emission tomography imaging protocol identifies seizure-induced regional overactivity of P-glycoprotein at the blood-brain barrier.

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.

Imaging evidence of early brain tissue degeneration in patients with vanishing white matter disease: a multimodal MR study.

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.

Impact of fasting on stress systems and depressive symptoms in patients with major depressive disorder: a cross-sectional study.

Major depressive disorder (MDD) is frequently associated with poor response to treatment. Common antidepressants target neurotransmission and neuronal plasticity, which require adequate energy supply. As imaging studies indicate disturbances in central energy metabolism, and caloric restriction improves neuroplasticity and impacts mood and cognition, correction of energy status might increase the effectiveness of antidepressant treatments and reduce the psychopathological symptoms of depression. Metabolic parameters, stress hormones, and brain-derived neurotrophic factor (BDNF) levels were assessed in serum of depressed inpatients (MDD, N = 21) and healthy volunteers (Ctrl, N = 28) before and after a 72 h fasting period during which only water was consumed. Depression severity was assessed by Beck's Depression Inventory (BDI)-2 sum-score and cognitive-affective and somatic sub-scores. Fasting similarly impacted metabolic parameters and stress systems in both groups. Fasting elevated BDI-2 sum-scores and somatic sub-scores in Ctrl. In MDD, fasting increased somatic-, but decreased cognitive-affective symptoms. Sub-group analyses based on BDI-2 sum-scores pre-fasting showed that cognitive-affective symptoms decreased in patients with moderate/severe but not in those with mild symptoms. This was associated with differential changes in BDNF levels. In conclusion, fasting improved cognitive-affective sub-scores in MDD patients with moderate/severe symptoms that had not responded to prior therapy. Interventions that modulate energy metabolism might directly improve cognitive-affective symptoms and/or augment therapeutic efficacy in moderate-to-severely depressed patients.

Value of quantitative analysis of routine clinical MRI sequences in ALS.

Simple morphological assessment of conventional MRI used in routine neurological diagnostic work-up lacks sensitivity and specificity for amyotrophic lateral sclerosis (ALS). Quantitative analysis of routine MRI sequences might, however, be more suitable to reveal ALS-related pathological cerebral alterations. We investigated 10 ALS patients and 10 age- and sex-matched healthy controls by MRI. Brain maps of T2 relaxation time (T2), relative proton density (PD), and apparent diffusion coefficient (ADC) were obtained. Values of these parameters were measured in 22 selected brain regions, and compared among the patients and the controls by using paired t-test with Bonferroni corrected alpha level (= 0.002). In ALS patients, increased PD was found in the pyramidal tract, corpus callosum, and white and grey matter. T2 elongation was found at the genu of corpus callosum, and at the posterior limb of the internal capsule (ICP). ADC values showed a tendency towards an increase in patients, which was only significant at the ICP. PD therefore appeared to be the most sensitive parameter for the detection of degenerative changes not only in the motor system but also in extramotor brain regions.

Macromolecule content influences proton diffusibility in gliomas.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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 < 0.01). CONCLUSION: Our results suggest that macromolecules binding protons in their vicinity are a major determinant of proton diffusivity in brain tumours in addition to other factors such as mechanical barriers like membranes or the size of the extra-cellular space.

Cerebral Microstructural Alterations in Patients With Early Parkinson's Disease Detected With Quantitative Magnetic Resonance Measurements.

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.

Clinically Applicable Quantitative Magnetic Resonance Morphologic Measurements of Grey Matter Changes in the Human Brain.

(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 < 0.0007 for rCTh and p < 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.

Alterations of Striato-Thalamic Metabolism in Normal Aging Human Brain-An MR Metabolic Imaging Study.

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.

HAX1 mutations causing severe congenital neuropenia and neurological disease lead to cerebral microstructural abnormalities documented by quantitative MRI.

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.

Age-related Brain Metabolic Changes up to Seventh Decade in Healthy Humans : Whole-brain Magnetic Resonance Spectroscopic Imaging Study.

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 t­test 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.

Altered neurometabolism in major depressive disorder: A whole brain 1H-magnetic resonance spectroscopic imaging study at 3T.

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.

Brain Morphological Alterations Are Detected in Early-Stage Parkinson's Disease with MRI Morphometry.

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.

Microstructural callosal abnormalities in normal-appearing brain of children with developmental delay detected with diffusion tensor imaging.

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.