Reduction Of N-acetylaspartate Research Articles

Abnormal metabolites in the dorsolateral prefrontal cortex of female epilepsy patients with migraine without aura.

Epilepsy and migraine without aura (MWoA) are often comorbid, but the exact mechanisms are unclear. Magnetic resonance spectroscopy (1H-MRS) may help to understand the neurometabolic mechanisms in patients with epilepsy comorbid with MWoA (EWM). In this prospective cross-sectional study, we recruited 64 female patients, including 24 with EWM, 20 with epilepsy, and 20 with MWoA, as well as 20 age-level-matched and educational-level-matched female healthy controls from our hospital between August 2021 and November 2022. A single-voxel point-resolved spectroscopy sequence was used to acquire spectra of the bilateral dorsolateral prefrontal cortices (DLPFCs). Metabolites were quantified by linear combination model software, and the values were corrected for the partial volume effect of cerebrospinal fluid. MRS data comparisons were performed with multivariate analyses of variance. Correlation analyses were calculated between metabolites and main clinical data. The results showed that N-acetyl aspartate (NAA) was asymmetrical between the bilateral DLPFCs. Both NAA and myoinositol were significantly reduced in EWM than in healthy controls. Choline-containing compounds (Cho) were higher in MWoA than in the other three groups. Correlation analyses revealed that NAA of the right DLPFC and Cho of the bilateral DLPFCs in EWM were negatively related to migraine frequency. In addition, glutamate and glutamine (Glu and Gln, Glx) of the right DLPFC in EWM were negatively correlated with migraine severity. Our findings suggested that comorbid epilepsy and MWoA in female patients can lead to a synergistic reduction of both NAA and myoinositol, reflecting more serious injuries of neurons and glial cells.

Neurometabolic topography and associations with cognition in Alzheimer's disease: A whole-brain high-resolution 3D MRSI study.

Altered neurometabolism, detectable via proton magnetic resonance spectroscopic imaging (1H-MRSI), is spatially heterogeneous and underpins cognitive impairments in Alzheimer's disease (AD). However, the spatial relationships between neurometabolic topography and cognitive impairment in AD remain unexplored due to technical limitations. We used a novel whole-brain high-resolution 1H-MRSI technique, with simultaneously acquired 18F-florbetapir positron emission tomography (PET) imaging, to investigate the relationship between neurometabolic topography and cognitive functions in 117 participants, including 22 prodromal AD, 51 AD dementia, and 44 controls. Prodromal AD and AD dementia patients exhibited spatially distinct reductions in N-acetylaspartate, and increases in myo-inositol. Reduced N-acetylaspartate and increased myo-inositol were associated with worse global cognitive performance, and N-acetylaspartate correlated with five specific cognitive scores. Neurometabolic topography provides biological insights into diverse cognitive dysfunctions. Whole-brain high-resolution 1H-MRSI revealed spatially distinct neurometabolic topographies associated with cognitive decline in AD, suggesting potential for noninvasive brain metabolic imaging to track AD progression. Whole-brain high-resolution 1H-MRSI unveils neurometabolic topography in AD. Spatially distinct reductions in NAA, and increases in mI, are demonstrated. NAA and mI topography correlates with global cognitive performance. NAA topography correlates with specific cognitive performance.

Reduction of N-acetyl aspartate (NAA) in association with relapse in early-stage psychosis: a 7-Tesla MRS study

Understanding the biological underpinning of relapse could improve the outcomes of patients with psychosis. Relapse is elicited by multiple reasons/triggers, but the consequence frequently accompanies deteriorations of brain function, leading to poor prognosis. Structural brain imaging studies have recently been pioneered to address this question, but a lack of molecular investigations is a knowledge gap. Following a criterion used for recent publications by others, we defined the experiences of relapse by hospitalization(s) due to psychotic exacerbation. We hypothesized that relapse-associated molecules might be underscored from the neurometabolites whose levels have been different between overall patients with early-stage psychosis and healthy subjects in our previous report. In the present study, we observed a significant decrease in the levels of N-acetyl aspartate in the anterior cingulate cortex and thalamus in patients who experienced relapse compared to patients who did not. Altogether, decreased N-acetyl aspartate levels may indicate relapse-associated deterioration of neuronal networks in patients.

Over-expression of N-acetylaspartate synthase exacerbates pathological energetic deficit and accelerates cognitive decline in the 5xFAD mouse.

N-acetylaspartate (NAA) is an abundant central nervous system amino acid derivative that is tightly coupled to mitochondria and energy metabolism in neurons. A reduced NAA signature is a prominent early pathological biomarker in multiple neurodegenerative diseases and becomes progressively more pronounced as disease advances. Because NAA synthesis requires aspartate drawn directly from mitochondria, we argued that this process is in direct competition with oxidative phosphorylation for substrate and that sustained high levels of NAA synthesis would be incompatible with pathological energy crisis. We show here that over-expression of the rate-limiting NAA synthetic enzyme in the hippocampus of the 5x familial Alzheimer's disease (5xFAD) mouse results in an exaggerated pathological ATP deficit and accelerated cognitive decline. Over-expression of NAA synthase did not increase amyloid burden or result in cell loss but did significantly deplete mitochondrial aspartate and impair the ability of mitochondria to oxidize glutamate for adenosine triphosphate (ATP) synthesis. These results define NAA as a sink for energetic substrate and suggest initial pathological reductions in NAA are part of a response to energetic crisis designed to preserve substrate bioavailability for mitochondrial ATP synthesis.

Metabolic heterogeneity in different subtypes of malformations of cortical development causing epilepsy: a proton magnetic resonance spectroscopy study.

The most common subtypes of malformations of cortical development (MCDs) are gray matter heterotopia (GMH), focal cortical dysplasia (FCD), and polymicrogyria (PMG). This study aimed to characterize the possible neurometabolic abnormalities and heterogeneity in different MCDs subtypes using proton magnetic resonance spectroscopy (1H-MRS). In this prospective cross-sectional study, we recruited 29 patients with MCDs and epilepsy, including ten with GMH, ten with FCD, and nine with PMG, as well as 25 age- and sex-matched healthy controls (HC) from the Epilepsy Center of West China Hospital of Sichuan University between August 2018 and November 2021. Inclusion criteria for the patients were based upon typical magnetic resonance imaging (MRI) findings of MCDs and full clinical assessment for epilepsy. Single-voxel point-resolved spectroscopy was used to acquire data from both the lesion and the normal-appearing contralateral side (NACS) in patients and from the frontal lobe in HC. Metabolite measures, including N-acetyl aspartate (NAA), myoinositol (Ins), choline (Cho), creatine (Cr), and glutamate + glutamine (Glx) concentrations, were quantitatively estimated with linear combination model (LCModel) software and corrected for the partial volume effect of cerebrospinal fluid (CSF). The NAA concentration was lower and the Ins concentration was higher in the MCDs lesions than in the NACS and in HC (P=0.002-0.007), and the Cho and Cr concentrations were higher in MCDs lesions than in HC (P=0.001-0.016). Moreover, the Cho concentration was higher in NACS than in HC (P=0.015). In the GMH lesions, the only metabolic alteration was an NAA reduction (GMH_lesion vs. HC: P=0.001). In the FCD lesions, there were more metabolite abnormalities than in the other two subtypes, particularly a lower NAA and a higher Ins than in HC and NACS (P=0.012-0.042). In the PMG lesions, Cr (lesion vs. HC or NACS: P=0.017-0.021) and Glx (lesion vs. NACS: P=0.043) were increased, while NAA was normal. Correlation analysis revealed that the Cr concentration in MCDs lesions was positively correlated with seizure frequency (r=0.411; P=0.027). Based upon 1H-MRS, our study demonstrated that different MCDs subtypes exhibited variable metabolic features, which may be associated with distinct functional and cytoarchitectural properties.

Infectious Lesion Simulating Malignant Neoplasm. Clinical Case and Literature Review

The extrapulmonary manifestations of tuberculosis (TBC) that affect the Central Nervous System (CNS), by hematogenous dissemination, are an infrequent entity. Intracranial tuberculomas are the least common form of tuberculosis in CNS. Represent a granulomatous inflammatory process with cerebral involvement. The prognosis is related to the early diagnosis, the degree of surgical resection and the complemen-tary treatment with antituberculous drugs. We describe an infrequent clinical case of cerebral tuberculoma that simulated a malignant neoplasm, and also performed a literature review. A clinical case about a 31-year-old female with no relevant medical history. She described a sud-denly diplopia, without previous trauma. The patient was evaluated by Ophthalmology, which iden-tified papillary edema, with no other alterations. In this context was performed a Brain CT/MRI, which showed an intra-axial, left frontobasal lesion with perilesional edema, ring contrast enhancement and a hypodense/hypointense central area. Spectroscopy showed a reduction in n-acetylaspartate (NAA) with a peak in creatine and choline, suggestive of a malignant tumor. The patient underwent surgery, having performed a frontal left craniotomy and complete excision of a nodular, capsulated, avascular lesion with a spongy consistency. Subsequently, the histological diagnosis of tuberculoma was confirmed. We describe an infrequent clinical case of cerebral tuberculoma which, due to the characteristics presented in the preoperative studies, was suggestive of a malignant tumor that was not confirmed, which is the particularity of this case. The patient presents a good clinical and imaging evolution during the follow-up period.

Multiparametric magnetic resonance imagingfor detection of pathological changes in the central nervous system of a mouse model of multiple sclerosis in vivo.

Multiple sclerosis (MS) is an autoimmune disease involving demyelination and axonal damage in the central nervous system (CNS). In this study, we investigated pathological changes in the lumbar spinal cord of C57BL/6 mice induced with progressive experimental autoimmune encephalomyelitis (EAE) disease using 9.4-T magnetic resonance imaging (MRI). Multiparametric MRI measurements including MR spectroscopy, diffusion tensor imaging (DTI) and volumetric analyses were applied to detect metabolic changes in the CNS of EAE mice. Compared with healthy mice, EAE mice showed a significant reduction in N-acetyl aspartate and increases in choline, glycine, taurine and lactate. DTI revealed a significant reduction in fractional anisotropy and axial diffusivity and an increase in radial diffusivity in the lumbar spinal cord white matter (WM), while in the grey matter (GM), fractional anisotropy increased. High-resolution structural imaging also revealed lumbar spinal cord WM hypertrophy and GM atrophy. Importantly, these MRI changes were strongly correlated with EAE disease scoring and pathological changes in the lumbar (L2-L6), particularly WM demyelination lesions and aggregation of immune cells (microglia/macrophages and astrocytes) in this region. This study identified changes in MRI biomarker signatures that can be useful for evaluating the efficacy of novel drugs using EAE models in vivo.

Neurodegenerative Changes in the Brains of the 5xFAD Alzheimer’s Disease Model Mice Investigated by High-Field and High-Resolution Magnetic Resonance Imaging and Multi-Nuclei Magnetic Resonance Spectroscopy

This study aimed to investigate morphological and metabolic changes in the brains of 5xFAD mice. Structural magnetic resonance imaging (MRI) and 1H magnetic resonance spectroscopy (MRS) were obtained in 10- and 14-month-old 5xFAD and wild-type (WT) mice, while 31P MRS scans were acquired in 11-month-old mice. Significantly reduced gray matter (GM) was identified by voxel-based morphometry (VBM) in the thalamus, hypothalamus, and periaqueductal gray areas of 5xFAD mice compared to WT mice. Significant reductions in N-acetyl aspartate and elevation of myo-Inositol were revealed by the quantification of MRS in the hippocampus of 5xFAD mice, compared to WT. A significant reduction in NeuN-positive cells and elevation of Iba1- and GFAP-positive cells supported this observation. The reduction in phosphomonoester and elevation of phosphodiester was observed in 11-month-old 5xFAD mice, which might imply a sign of disruption in the membrane synthesis. Commonly reported 1H MRS features were replicated in the hippocampus of 14-month-old 5xFAD mice, and a sign of disruption in the membrane synthesis and elevation of breakdown were revealed in the whole brain of 5xFAD mice by 31P MRS. GM volume reduction was identified in the thalamus, hypothalamus, and periaqueductal gray areas of 5xFAD mice.

Taurine and N-acetylcysteine treatments prevent memory impairment and metabolite profile alterations in the hippocampus of high-fat diet-fed female mice

ABSTRACT Background: Obesity constitutes a risk factor for cognitive impairment. In rodent models, long-term exposure to obesogenic diets leads to hippocampal taurine accumulation. Since taurine has putative cyto-protective effects, hippocampal taurine accumulation in obese and diabetic models might constitute a counteracting response to metabolic stress. Objective: We tested the hypothesis that treatment with taurine or with N-acetylcysteine (NAC), which provides cysteine for the synthesis of taurine and glutathione, prevent high-fat diet (HFD)-associated hippocampal alterations and memory impairment. Methods: Female mice were fed either a regular diet or HFD. Some mice had access to 3%(w/v) taurine or 3%(w/v) NAC in the drinking water. After 2 months, magnetic resonance spectroscopy (MRS) was used to measure metabolite profiles. Memory was assessed in novel object and novel location recognition tests. Results: HFD feeding caused memory impairment in both tests, and reduced concentration of lactate, phosphocreatine-to-creatine ratio, and the neuronal marker N-acetylaspartate in the hippocampus. Taurine and NAC prevented HFD-induced memory impairment and N-acetylaspartate reduction. NAC, but not taurine, prevented the reduction of lactate and phosphocreatine-to-creatine ratio. MRS revealed NAC/taurine-induced increase of hippocampal glutamate and GABA levels. Conclusion: NAC and taurine can prevent memory impairment, while only NAC prevents alterations of metabolite concentrations in HFD-exposed female mice.

Subcortical volume reduction and cortical thinning 3 months after switching to clozapine in treatment resistant schizophrenia

The neurobiological effects of clozapine are under characterised. We examined the effects clozapine treatment on subcortical volume and cortical thickness and investigated whether macrostructural changes were linked to alterations in glutamate or N-acetylaspartate (NAA). Data were acquired in 24 patients with treatment-resistant schizophrenia before and 12 weeks after switching to clozapine. During clozapine treatment we observed reductions in caudate and putamen volume, lateral ventricle enlargement (P < 0.001), and reductions in thickness of the left inferior temporal cortex, left caudal middle frontal cortex, and the right temporal pole. Reductions in right caudate volume were associated with local reductions in NAA (P = 0.002). None of the morphometric changes were associated with changes in glutamate levels. These results indicate that clozapine treatment is associated with subcortical volume loss and cortical thinning and that at least some of these effects are linked to changes in neuronal or metabolic integrity.

P04.23 Multinodular and vacuolating neuronal tumor - advanced MRI features

Abstract BACKGROUND A rare pathology, multinodular and vacuolating neuronal tumors (MVNT) have been first described in 2013 and included in the 2016 World Health Organization Classification of Tumors of the Central Nervous System as having a distinctive radiological and cytoarchitectural appearance. This study aims to evaluate the imaging features of MVNT, it’s differential diagnosis, and possible involvement in adult-onset epilepsy. MATERIAL AND METHODS We present the case of a 29-year-old male, smoker, and drug abuser, who developed a seizure after 25 hours’ sleep deprivation, alcohol, energy drinks, cigarettes, and cocaine consumption. Cerebral CT, MRI, electroencephalogram, MR spectroscopy, and tractography was performed. RESULTS The MRI performed revealed a right, cortico-subcortical pseudo-nodular temporal lesion, non-enhancing, with a slight thickening of the adjacent cortex and right hippocampal involvement. The neurological examination was normal, but the electroencephalogram showed a right temporal irritative pattern. MR- Spectroscopy described a slight increase of choline (Cho), reduction of N-acetylaspartate (NAA), and also increased myo-inositol peak, ruling out a high-grade tumoral substrate. A tractography was also performed, excluding the other alternative diagnosis of focal cortical dysplasia, thus leaving MVNT to be the most probable explanation for the lesion. CONCLUSION Advanced MRI features were useful to increase the diagnosis accuracy. The future management consisted of image surveillance, anticonvulsant treatment, and lifestyle improvement. Adult-onset seizures are among the most frequent discovery possibilities for MVNT. In our case, it is to be seen whether the lifestyle changes and medication will prevent future seizures.

Evaluation of Neonatal Acute Metabolic Crisis in Maple Syrup Urine Disease with MR Diffusion and MR Spectroscopy: Case Series and Review of the Literature

AbstractMagnetic resonance imaging (MRI) findings of acute metabolic crisis in maple syrup urine disease (MSUD) in neonates were reviewed. This case cohort study included six MSUD neonates imaged during acute metabolic decompensation. Specific diffusion imaging and proton spectroscopic findings were reviewed. All patients revealed extensive intramyelinic cytotoxic edema typically involving myelinated white matter structures. Brainstem, cerebellar white matter and peduncles, midbrain, posterior limbs of internal capsules, central portions of periventricular, and perirolandic white matter regions showed typical MSUD edema. Gray matter structures such as dentate nucleus and thalamus were involved in all patients. Involvement of other deep nuclei was also noted in a few patients. None of the patients showed involvement of the superficial cortex. Reduction in N-acetyl aspartate, a prominent lactate peak, and a peak representing methyl groups of amino acids were characteristic findings seen on intermediate short echo time MR spectroscopy. Our case series outlines the importance of diffusion and spectroscopy MR techniques in the diagnosis of acute neonatal MSUD metabolic crisis.

Magnetic Resonance Spectroscopy in Evaluation of Focal Brain Lesions- A Cross-sectional Prospective Study

Introduction: The characterisation of intracranial mass lesions only with the help of conventional magnetic resonance imaging alone may be inconclusive. Magnetic Resonance Spectroscopy (MRS) is a non invasive technique which is superior to Magnetic Resonance Imaging (MRI) in the characterisation of brain lesions. Magnetic resonance spectroscopy is comparatively fast, non-invasive method that gives biochemical analysis of the normal brain parenchyma and of the pathological processes. Magnetic resonance spectroscopy has the advantage of providing characterisation of tissues based on their molecular composition. It gives information about neuronal vitality, cell proliferation, degradation and energy metabolism. Aim: To describe the spectrum of magnetic resonance spectroscopy in focal brain lesions and to detect the metabolic and biochemical changes in various focal brain lesions. Also, to distinguish neoplastic from non-neoplastic lesions. Materials and Methods: This prospective study was carried out at Department of Radiodiagnosis, Sri Manakula Vinaynagar Medical College and Hospital, Puducherry, India for a period of 18 months from November 2017 to April 2019. A total of 40 MRI brain with clinically suspected brain lesions were included in the study. Magnetic resonance spectroscopy studies were performed in all patients with focal brain lesions. On the basis of spectral and distribution patterns of the pathologic spectra seen in MR spectroscopy, a qualitative analysis was done. The metabolic area ratios Choline/Creatinine (Cho/Cr)/Cr, NAA/Cho and NAA/Cr were evaluated (NAA- N-acetyl, Cho- choline, Cr- creatine). Data was collected using prescribed proforma and analysed using Statistical Package for the Social Sciences (SPSS) 22 version software. Results: Out of the 40 patients evaluated 11 cases were high grade gliomas, seven cases were Neurocysticercosis, five low grade glioma, five meningioma, four metastasis, four tubercular abscesses, two tuberculoma and two lymphoma. Increased Cho/ Cr ratio was noted in neoplastic lesions when compared to non neoplastic lesions. Conclusion: The MRS in addition to appropriate conventional MRI sequences provides useful supplementary information and has a potential to validate treatment strategies. Neoplastic lesions show elevated choline and Cho Cr ratio with reduction in N-acetyl aspartate (NAA), whereas non neoplastic lesions show decreased Cho/Cr ratio. Hence, MRS could be a problem solving tool in differentiating neoplastic from non neoplastic lesions.

The Changes in 1H-MRS Metabolites in Cuprizone-Induced Model of Multiple Sclerosis: Effects of Prior Psychological Stress

Stress is considered as an important risk factor in the progression and the onset of many disorders such as multiple sclerosis. However, metabolite changes as a result of demyelination under the detrimental effects of stress are not well understood. Thus, 36 female Wistar rats (i.e., groups (1) no-cuprizone (Cont), (2) no-stress + cuprizone-treated (Cup), (3) physical stress + cuprizone-treated (P-Cup), (4) psychological stress + cuprizone-treated (Psy-Cup), (5) physical stress + no-cuprizone-treated (P), (6) psychological stress + no-cuprizone-treated (Psy)) were used in this study. Following induction of repetitive stress, cuprizone treatment was carried out for 6 weeks to instigate demyelination in all groups except the control animal. Relative metabolite concentrations of the brain were investigated by single-voxel proton magnetic resonance spectroscopy (reporting N-acetyl-aspartate (NAA), glycerophosphocholine with phosphocholine (tCho) relative to total creatine (tCr)). According to 1H-MRS, rats in the Cup group indicated a reduction in NAA/ tCr (p < 0.001) as well as tCho/ tCr (p < 0.05) compared with that in the Cont group. In contrast, in both stress + cuprizone-treated groups, NAA/tCr and tCho/tCr ratios remarkably increased versus the Cup group (p < 0.001) and the Cont group (p < 0.001 for the Psy-Cup group and p < 0.05 for the P-Cup group). Both P and Psy groups revealed normal metabolite concentrations similar to the Cont group 6 weeks post stress. Seemingly, in the case of cuprizone alone, decreased level of metabolites is mainly relevant to neuronal cell impairments. Meanwhile, as a result of oxidative stress enhancement due to stress exposure, oligodendrocyte becomes the main victim indicating the increased level of metabolite ratios.

Value of Magnetic Resonance Spectroscopy MRS in Prolonged Febrile Convulsion in Children

Abstract Background: Febrile Convulsion (FC) or Febrile Seizure (FS) is the most common type of seizures that occur in children between the ages of 6 months to 5 years with body temperature over 38oC and without any infection such as meningitis and encephalitis in the central nervous system. The incidence of FC is 5 cases per 1000 children annually. Aim of Study: To determine metabolic changes that occur in temporal lobe and hippocampus after prolonged febrile seizures, by using Magnetic Resonance Spectroscopy (MRS). Patients and Methods: Thirty patients with prolonged febrile seizures more than 15 minutes were included. Control group including thirty child age and gender healthy matched. EEG was done within 72 hour of febrile seizure to all case and control group in the study using Pediatric Neurology Department EEG machine. Also, MRS (Magnetic Resonance Spectroscopy) was done within 48h of febrile seizure to the cases and was done to the control group, by using achieva 1.5t Philips. The spectra were all acquired in conjunction with an MRS study of the brain that included coronal T2, axial & coronal FLAIR images through the temporal lobes, and axial T1 and T2 SE images through the entire brain. To obtain MRS technique, scout imaging of the brain in coronal and sagittal orientations was performed with T1 WI. The MRS was per-formed using multi-voxel technique (PRESS-CSI sequence with TE/TR=135ms/1690ms, 12 averages, FOV 120 X 120mm2). The region of interest was placed through whole temporal lobi with the voxel layer position adjusted based on the localization of hippocampi in order to examine the whole hippocampi at long distance (voxel size set to 10 X 10 X 15mm3). The resonances of major metabolites detected were as follows: The N Acetyl Aspartate (NAA) peak at 2.02ppm, the creatine (Cr) and phosphocreatine peak at 3.02ppm, and the choline (Cho) peak at 3.20ppm. Results: We found that there was high significant difference between case and control groups regarding MRS. As in the case group there was reduction of NAA and slightly increase in Cho & Cr, which lead to changes in metabolic ratios (NAA/Cr, Cho/NAA & Cho/Cr). While in the control group was normal.The optimal cut off value of NAA/Cr was less than 2.61, The sensitivity and specificity of NAA/Cr was 96.7% and 93.3% respectively and accuracy was 95%. While, the optimal cut off value of Cho/NAA more than 0.785, the sensitivity and specificity of Cho/NAA was 96.7% and 80% respectively and accuracy was 88.3%. While, the optimal cut off value of Cho/Cr less than 2.115, The sensitivity and specificity of Cho/Cr was 93.3% and 93.3% respectively and accuracy was 93.3%. Conclusion: MR spectroscopy is a very sensitive guiding tool in predicting Temporal Lobe Epilepsy (TLE) and the side of involvement in patients with TLE even in patients with MR negative studies. Also, it helps in detecting abnormal spectra of various brain metabolites at temporal lobe and hippocampus. Further more, it can detect hippocampal injury earlier and with more accurate results than EEG.

Cerebral metabolism after one hyperbaric oxygenation session: 1H and 31P magnetic resonance spectroscopy study

The aim of this study is to elucidate the effect of one HBO session on the concentrations of metabolites detectible by 1H and 31P magnetic resonance spectroscopy. An activation of energy metabolism that manifested in the decrease of creatinephosphate (PCr), pHint and increase α-ATP signal after a HBO session is revealed. Other ATP resonances remain unchanged. Also the reduction of N-acetyl aspartate by 3% in mediolateral prefrontal cortex (MPFC) with p<0.05 and in posterior cingulate cortex (p<0.1) was found. Glutamate levels remained unchanged after HBO session. The demonstrated metabolic changes may signify the activation of power supply processes in order to compensate the energy expenses caused by the excess of O2.

Multinodular and Vacuolating Neuronal Tumor in the Brain Depth - Atypical Presentation of a New Tumor: A Case Report

Introduction: Multinodular and Vacuolating Neuronal Tumors (MVNTs) are clinically benign lesions and was recently included in the last World Health Organization Classification of Tumors of the Central Nervous System (WHO – 2016). Recent studies have discovered specific immunomarkers that classifies the MVNTs as a new neoplasm group placed within the section covering "Neuronal and mixed neuronal-glial tumors” as a WHO grade I lesion. Case report: We present a case of a probable MVNT in a 55-year old woman, who presented with chronic pattern seizures. Conventional MRI revealed an infiltrative and multinodular pattern lesion localized in the deep left cerebral hemisphere compromising the ventral posteromedial and pulvinar surfaces of thalamus, lateral geniculate body, choroidal fissure, mammillothalamic tract, fornix and septum pellucidum, anterior commissure, extending to contralateral globus pallidus and internal capsule. Dynamic susceptibility contrast-enhanced MR perfusion and Arterial Spin Labeling (ASL) technique didn’t show any abnormalities. MR spectroscopy demonstrated a mild increase in Choline (Cho) and mild reduction in N-acetyl aspartate (NAA). No substantial difference both clinically and radiologically was observed on five years follow up. Conclusion: The diagnosis of MVNT was made considering the extremally benign biological behavior of this tumor and the typical imaging features, despite of deep localization of the lesion, and once this kind of lesion was previously described as a “don’t touch lesion” the histological, biopsy was not performed.

Serial Metabolic Evaluation of Perihematomal Tissues in the Intracerebral Hemorrhage Pig Model.

PurposePerihematomal edema (PHE) occurs in patients with intracerebral hemorrhage (ICH) and is often used as surrogate of secondary brain injury. PHE resolves over time, but little is known about the functional integrity of the tissues that recover from edema. In a pig ICH model, we aimed to assess metabolic integrity of perihematoma tissues by using non-invasive magnetic resonance spectroscopy (MRS).Materials and MethodsFourteen male Yorkshire pigs with an average age of 8 weeks were intracerebrally injected with autologous blood to produce ICH. Proton MRS data were obtained at 1, 7, and 14 days after ICH using a whole-body 3.0T MRI system. Point-resolved spectroscopy (PRESS)-localized 2D chemical shift imaging (CSI) was acquired. The concentration of N-Acetylaspartate (NAA), Choline (Cho), and Creatine (Cr) were measured within the area of PHE, tissues adjacent to the injury with no or negligible edema (ATNE), and contralesional brain tissue. A linear mixed model was used to analyze the evolution of metabolites in perihematomal tissues, with p-value < 0.05 indicating statistical significance.ResultsThe perihematoma volume gradually decreased from 2.38 ± 1.23 ml to 0.41 ± 0.780 ml (p < 0.001) over 2 weeks. Significant (p < 0.001) reductions in NAA, Cr, and Cho concentrations were found in the PHE and ATNE regions compared to the contralesional hemisphere at day 1 and 7 after ICH. All three metabolites were significantly (p < 0.001) restored in the PHE tissue on day 14, but remained persistently low in the ATNE area, and unaltered in the contralesional voxel.ConclusionThis study highlights the potential of MRS to probe salvageable tissues within the perihematoma in the sub-acute phase of ICH. Altered metabolites within the PHE and ATNE regions in addition to edema and hematoma volumes were explored as possible markers for tissue recovery. Perihematomal tissue with PHE demonstrated a more reversible injury compared to the tissue adjacent to the injury without edema, suggesting a potentially beneficial role of edema.

Hyperbaric Oxygenation Effects on Human Brain In Vivo: 1H MRS and Resting-State fMRI Study

Previously using 31P magnetic resonance spectroscopy (MRS) we have demonstrated that one hyperbaric oxygenation (HBO) session (with O2 pressure 1.2 atm) directly activates cerebral energetics: the decrease in creatine phosphate (PCr) and, possibly, the increase in nicotinamide adenine dinucleotide. The aim of this study is to elucidate the effect of one HBO session on the concentrations of metabolites detectible by 1H MRS, and on the connectivity in Default Mode Network. Absolute concentrations of the metabolites were calculated. The reduction of N-acetyl aspartate by 3% was found in mediolateral prefrontal cortex (MPFC) with p < 0.05 and in posterior cingulate cortex (p < 0.1). The resting-state functional connectivity between these zones was elevated by ~ 40%, p < 0.05 after HBO session. Glutamate levels remained unchanged after HBO. There is an indication in support of lactate growth in MPFC after HBO session. The demonstrated metabolic changes, as well as the decrease in PCr shown in previous study, may signify the activation of power supply processes to compensate the energy expenses connected with the enhancement of cerebral functional connectivity even after one HBO session.

Magnetic resonance imaging of noradrenergic neurons

Noradrenaline is a neurotransmitter involved in general arousal, selective attention, memory, inflammation, and neurodegeneration. The purpose of this work was to delineate noradrenergic neurons in vivo by T1-weighted MRI with magnetization transfer (MT). In the brainstem of human and mice, MRI identified the locus coeruleus, dorsal motor vagus nucleus, and nucleus tractus solitarius. Given (1) the long T1 and low magnetization transfer ratio for the noradrenergic cell groups compared to other gray matter, (2) significant correlation between MT MRI signal intensity and proton density, and (3) no correlation between magnetization transfer ratio (or R1) and iron, copper, or manganese in human brain, the high MRI signal of the noradrenergic neurons must be attributed to abundant water protons interacting with any T1-shortening paramagnetic ions in active cells rather than to specific T1-shortening molecules. The absence of a high MRI signal from the locus coeruleus of Ear2(−/−) mice lacking noradrenergic neurons confirms that cell bodies of noradrenergic neurons are the source of the bright MRI appearance. The observation of this high signal in DBH(−/−) mice, in 3-week-old mice, and in mice under hyperoxia/hypercapnia/hypoxia together with the general absence of neuromelanin (NM) in noradrenergic neurons of young rodents further excludes that it is due to NM, dopamine β-hydroxylase, their binding to paramagnetic ions, blood inflow, or hemoglobin. Instead, these findings indicate a high density of water protons whose T1 is shortened by paramagnetic ions as the relevant source of the high MRI signal. In the brain of APP/PS1/Ear2(−/−) mice, a transgenic model of Alzheimer’s disease, MRI detected noradrenergic neuron loss in the locus coeruleus. Proton magnetic resonance spectroscopy revealed that a 60–75% reduction of noradrenaline is responsible for a reduction of N-acetylaspartate and glutamate in the hippocampus as well as for a shortening of the water proton T2 in the frontal cortex. These results suggest that a concurrent shortage of noradrenaline in Alzheimer’s disease accelerates pathologic processes such as inflammation and neuron loss.