Ratios Of N-acetylaspartate Research Articles

Metabolic Profile of Cerebellum in Posterior Fossa Tumor Survivors: Correlation With Memory Impairment

AimsThe cerebellum is a key structure in working and procedural memory. The aim of the present prospective exploratory study was to investigate, the metabolic characteristics of the cerebellum in posterior fossa tumor (PFT) survivors using 3D proton magnetic resonance spectroscopy imaging (3D MRSI), to determine whether metabolites could be useful biomarkers of memory impairment. Materials and methodsSixty participants were included in the IMPALA study, divided into three groups: 22 irradiated PFT, 17 nonirradiated PFT, and 21 healthy controls matched with irradiated PFT for age, sex, and handedness. PFT survivors were treated at least 5 years ago, either by surgery or a combination of surgery, chemotherapy, and radiotherapy. All participants underwent working and procedural memory tests and multimodal MRI including a 3D MRSI sequence. N-acetylaspartate (NAA), choline (Cho), creatine (Cr), and lactate (Lac) metabolite values were extracted from the cerebellum for comparisons between groups, correlations with neurocognitive test scores, and radiotherapy doses. ResultsMedian (range) age at neurocognitive tests was 18 (7–26) years. Median Cho, Cr, NAA, and Lac values, and the ratio of NAA to the sum of metabolites were significantly lower for PFT survivors than for healthy controls (p < 0.05). Scores on working and procedural memory tests were significantly lower for PFT survivors (p < 0.004) and correlated with median and maximum Cho and NAA values (0.28 <r < 0.49, p < 0.04). Except for creatine, the other metabolites were not significantly different between irradiated and nonirradiated survivors. MRSI values in the cerebellum were not correlated with either total dose or doses received by this structure. ConclusionResults revealed changes in cerebellar metabolic values in PFT survivors that were closely correlated with memory deficits, suggesting that some metabolites could be used as markers of cognitive decline, but this will require validation on a larger sample size.

Applications of magnetic resonance spectroscopy in diagnosis of neurodegenerative diseases: A systematic review

BackgroundMagnetic resonance spectroscopy (MRS) is an imaging technique used to measure metabolic changes in the tissue. Due to the lack of evidence, MRS is not a priority in diagnosing neurodegenerative diseases because it is a relatively specialized technique that requires specialized equipment and expertise to perform and interpret. This systematic review aimed to present a comprehensive collection of MRS results in the most common neurodegenerative diseases. MethodsA systematic search of four electronic databases (PubMed, Scopus, Web of Science, and ScienceDirect) was conducted for studies published from 2017 to 2022. Articles that provided specific biomarker levels were selected, and studies that assessed the diseases via treatment, featured MRS applying nuclei other than 1H, or compared different animal models were excluded. ResultsA total of 25 articles, plus 3 articles for extra information in the introduction, were included in this review. Six of the most common neurodegenerative diseases, i.e., Alzheimer's and Parkinson's disease, Huntington chorea, ataxia, multiple sclerosis (MS), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) were examined via MRS. The changes and ratios of N-acetylaspartate (NAA) could be seen in all of these disorders, which could lead to early diagnosis. However, there are other biomarkers, such as Cr and Chon, which can give convincing results. DiscussionThis observational study is the first synthesis of the latest evidence proving metabolic changes during neurodegenerative diseases using MRS as a diagnosis method. The findings indicate decreased N-acetylaspartate (NAA) and NAA/Cr ratios in Alzheimer's disease (AD), Parkinson's disease (PD), ataxias, and MS, reflecting neuronal loss or dysfunction. Increased choline and myo-inositol were noted in some studies, suggesting cell membrane turnover and neuroinflammation. Findings were less consistent for other metabolites like glutamate and gamma-aminobutyric acid. However, there were limitations due to the lack of studies on the same volumes of interest (VOIs) and the small number of participants.

Radiation-induced bystander effect on the brain after fractionated spinal cord irradiation of aging rats

We investigated the influence of the so-called bystander effect on metabolic and histopathological changes in the rat brain after fractionated spinal cord irradiation. The study was initiated with adult Wistar male rats (n = 20) at the age of 9 months. The group designated to irradiation (n = 10) and the age-matched control animals (n = 10) were subjected to an initial measurement using in vivo proton magnetic resonance spectroscopy (1H MRS) and magnetic resonance imaging (MRI). After allowing the animals to survive until 12 months, they received fractionated spinal cord irradiation with a total dose of 24 Gy administered in 3 fractions (8 Gy per fraction) once a week on the same day for 3 consecutive weeks. 1H MRS and MRI of brain metabolites were performed in the hippocampus, corpus striatum, and olfactory bulb (OB) before irradiation (9-month-old rats) and subsequently 48 h (12-month-old) and 2 months (14-month-old) after the completion of irradiation. After the animals were sacrificed at the age of 14 months, brain tissue changes were investigated in two neurogenic regions: the hippocampal dentate gyrus (DG) and the rostral migratory stream (RMS). By comparing the group of 9-month-old rats and individuals measured 48 h (at the age of 12 months) after irradiation, we found a significant decrease in the ratio of total N-acetyl aspartate to total creatine (tNAA/tCr) and gamma-aminobutyric acid to tCr (GABA/tCr) in OB and hippocampus. A significant increase in myoinositol to tCr (mIns/tCr) in the OB persisted up to 14 months of age. Proton nuclear magnetic resonance (1H NMR)-based plasma metabolomics showed a significant increase in keto acids and decreased tyrosine and tricarboxylic cycle enzymes. Morphometric analysis of neurogenic regions of 14-month-old rats showed well-preserved stem cells, neuroblasts, and increased neurodegeneration. The radiation-induced bystander effect more significantly affected metabolite concentration than the distribution of selected cell types.

Assessment of sepsis-associated encephalopathy by quantitative magnetic resonance spectroscopy in a rat model of cecal ligation and puncture

Proton magnetic resonance spectroscopy (1H-MRS) is the only non-invasive technique to quantify neurometabolic compounds in the living brain. We used 1H-MRS to evaluate the brain metabolites in a rat model of Sepsis-associated encephalopathy (SAE) established by cecal ligation and puncture (CLP). 36 male Sprague-Dawley rats were randomly divided into sham and CLP groups. Each group was further divided into three subgroups: subgroup O, subgroup M, and subgroup N. Neurological function assessments were performed on the animals in the subgroup O and subgroup N at 24 h, 48 h, and 72 h. The animals in the subgroup M were examined by magnetic resonance imaging (MRI) at 12 h after CLP. Compared with the sham group, the ratio of N-acetylaspartate (NAA) to creatine (Cr) in the hippocampus was significantly lower in the CLP group. The respective ratios of lactate (Lac), myo-inositol (mIns), glutamate and glutamine (Glx), lipid (Lip), and choline (Cho) to Cr in the CLP group were clearly higher than those in the sham group. Cytochrome c, intimately related to oxidative stress, was elevated in the CLP group. Neurofilament light (NfL) chain and glial fibrillary acidic protein (GFAP) scores in the CLP group were significantly higher than those in the sham group, while zonula occludens-1 (ZO-1) was downregulated. Compared with the sham group, the CLP group displayed higher values of oxygen extraction fraction (OEF), central venous–arterial partial pressure of carbon dioxide (P (cv-a) CO2), and central venous lactate (VLac). In contrast, jugular venous oxygen saturation (SjvO2) declined. In the present study, 1H-MRS could be used to quantitatively assess brain injury in terms of microcirculation disorder, oxidative stress, blood–brain barrier disruption, and glial cell activation through changes in metabolites within brain tissue.

Diagnostic algorithm for glioma grading using dynamic susceptibility contrast‑enhanced magnetic resonance perfusion and proton magnetic resonance spectroscopy.

The present retrospective study aimed to investigate the diagnostic capacity of and design a diagnostic algorithm for dynamic susceptibility contrast-enhanced MRI (DSCE-MRI) and proton magnetic resonance spectroscopy (1H-MRS) in grading low-grade glioma (LGG) and high-grade glioma (HGG). This retrospective study enrolled 57 patients, of which 14 had LGG and 43 had HGG, five had World Health Organization grade 1, nine had grade 2, 20 had grade 3 and 23 had grade 4 glioma. All subjects underwent a standard 3T MRI brain tumor protocol with conventional MRI (cMRI) and advanced techniques, including DSCE-MRI and 1H-MRS. The associations of grade categorization with parameters in tumor and peritumor regions in the DSCE-MRI were examined, including tumor relative cerebral blood volume (TrCBV) and peripheral relative (Pr)CBV, as well as Tr and Pr cerebral blood flow (CBF) and 1H-MRS, including the creatine (Cr) and N-acetyl aspartate (NAA) ratios of choline (Cho), i.e. the TCho/NAA, PCho/NAA, TCho/Cr and PCho/Cr metabolite ratios. The data were compared using the Mann-Whitney U-test, independent samples t-test, Chi-square test, Fisher's exact test and receiver operating characteristic curve analyses. Decision tree analysis established an algorithm based on cutoffs for specified significant parameters. The PrCBF had the highest performance in the preoperative prediction of histological glioma grading, followed by the TrCBV, PrCBF, TrCBV, PCho/NAA, PCho/Cr, TCho/NAA and TCho/Cr. An algorithm based on TrCBV, PrCBF and TCho/Cr had a diagnostic accuracy of 100% for LGG and 90.7% for HGG and a misclassification risk of 7%. The cutoffs (sensitivity and specificity) were 2.48 (86 and 100%) for TrCBV, 1.26 (83.7 and 100%) for PrCBF and 3.18 (69.8 and 78.6%) for TCho/Cr. In conclusion, the diagnostic algorithm using TrCBV, PrCBF and TCho/Cr values, which were obtained from DSCE-MRI and 1H-MRS, increased diagnostic accuracy to 100% for LGGs and 90.7% for HGGs compared to previous studies using conventional MRI. This non-invasive advanced MRI diagnostic algorithm is recommended for clinical application for constructing preoperative strategies and prognosis of patients with glioma.

Imbalance of thalamic metabolites in an experimental model of hypertension: role of bergamot polyphenols.

Cerebral metabolites are associated with different physiological and pathological processes in brain tissue. Among them, the concentrations of N-acetylaspartate (NAA) and choline-containing compounds (Cho) in the thalamic region are recognized and analyzed as important predictive markers of brain impairment. The relationship among hypertension, modulation of brain metabolite levels and cerebral diseases is of recent investigation, leaving many unanswered questions regarding the origin and consequences of the metabolic damage caused in grey and white matter during hypertension. Here we provide evidence for the influence of hypertension on NAA and Cho ratios in hypertensive rat thalamus and how the use of natural occurring compounds ameliorates the balance of thalamic metabolites.

Early metabolic alterations in the normal‑appearing grey and white matter of patients with clinically isolated syndrome suggestive of multiple sclerosis: A proton MR spectroscopic study.

Proton magnetic resonance spectroscopy (1H-MRS) is an advanced method of examining metabolic profiles. The present study aimed to assess in vivo metabolite levels in areas of normal-appearing grey (thalamus) and white matter (centrum semiovale) using 1H-MRS in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis and compare them to healthy controls (HCs). Data from 35 patients with CIS (CIS group), of which 23 were untreated (CIS-untreated group) and 12 were treated (CIS-treated group) with disease-modifying-therapies (DMTs) at the time of 1H-MRS, and from 28 age- and sex-matched HCs were collected using a 3.0 T MRI and single-voxel 1H-MRS (point resolved spectroscopy sequence; repetition time, 2,000 msec; time to echo, 35 msec). Concentrations and ratios of total N-acetyl aspartate (tNAA), total creatine (tCr), total choline (tCho), myoinositol, glutamate (Glu), glutamine (Gln), Glu + Gln (Glx) and glutathione (Glth) were estimated in the thalamic-voxel (th) and centrum semiovale-voxel (cs). For the CIS group, the median duration from the first clinical attack to 1H-MRS was 102 days (interquartile range, 89.5.-131.5). Compared with HCs, significantly lower Glx(cs) (P=0.014) and ratios of tCho/tCr(th) (P=0.026), Glu/tCr(cs) (P=0.040), Glx/tCr(cs) (P=0.004), Glx/tNAA(th) (P=0.043) and Glx/tNAA(cs) (P=0.015) were observed in the CIS group. No differences in tNAA levels were observed between the CIS and the HC groups; however, tNAA(cs) was higher in the CIS-treated than in the CIS-untreated group (P=0.028). Compared with those in HC group, decreased Glu(cs) (P=0.019) and Glx(cs) levels (P=0.014) and lower ratios for tCho/tCr(th) (P=0.015), Gln/tCr(th) (P=0.004), Glu/tCr(cs) (P=0.021), Glx/tCr(th) (P=0.041), Glx/tCr(cs) (P=0.003), Glx/tNAA(th) (P=0.030) and Glx/tNAA(cs) (P=0.015) were found in the CIS-untreated group. The present findings showed alterations in the normal-appearing grey and white matter of patients with CIS; moreover, the present results suggested an early indirect treatment effect of DMTs on the brain metabolic profile of these patients.

Spectroscopic MRI-Guided Proton Therapy in Non-Enhancing Pediatric High-Grade Glioma.

Radiation therapy (RT) is a critical part of definitive therapy for pediatric high-grade glioma (pHGG). RT is designed to treat residual tumor defined on conventional MRI (cMRI), though pHGG lesions may be ill-characterized on standard imaging. Spectroscopic MRI (sMRI) measures endogenous metabolite concentrations in the brain, and Choline (Cho)/N-acetylaspartate (NAA) ratio is a highly sensitive biomarker for metabolically active tumor. We provide a preliminary report of our study introducing a novel treatment approach of whole brain sMRI-guided proton therapy for pHGG. An observational cohort (c1 = 10 patients) receives standard of care RT; a therapeutic cohort (c2 = 15 patients) receives sMRI-guided proton RT. All patients undergo cMRI and sMRI, a high-resolution 3D whole-brain echo-planar spectroscopic imaging (EPSI) sequence (interpolated resolution of 12 µL) prior to RT and at several follow-up timepoints integrated into diagnostic scans. Treatment volumes are defined by cMRI for c1 and by cMRI and Cho/NAA ≥ 2x for c2. A longitudinal imaging database is used to quantify changes in lesion and metabolite volumes. Four subjects have been enrolled (c1 = 1/c2 = 3) with sMRI imaging follow-up of 4-18 months. Preliminary data suggest sMRI improves identification of pHGG infiltration based on abnormal metabolic activity, and using proton therapy to target sMRI-defined high-risk regions is safe and feasible.

Asymmetry of Gray- and White-Matter Volume and Metabolites in the Central-Vestibular System in Healthy Individuals

This study was designed to determine whether there was an asymmetry of structure and neurochemical activity of the interhemispheric vestibular-cortical system between healthy individuals and patients with vestibular failure. Previous studies have identified differences in gray-matter-volume (GMV) and white-matter-volume (WMV) asymmetry in the central-vestibular system and in concentrations of brain metabolites in the parietal lobe 2 (PO2) between patients with vestibulopathy and healthy controls. However, a comparison of the left and right sides in the healthy controls has not been made conclusively. This study included 23 healthy right-handed volunteers, and was carried out between March 2016 and March 2020. A three-dimensional T1-weighted image was used to calculate the GMV and WMV of the central-vestibular network on both sides, and proton magnetic resonance spectroscopy (H1MRS) was employed to analyze the brain metabolites in the PO2 area. The relative ratios of N-acetylaspartate (NAA)/tCr, tNAA/tCr, glycerophosphocholine (GPC)/tCr, Glx/tCr, and myo-inositol/tCr were quantified from the proton-MRS data. GMV and WMV differed significantly between the right and left vestibular-cortical regions. The GMVs of the right PO2, caudate, insula, and precuneus were significantly higher than those of the same locations on the left side; however, in the Rolandic operculum, the GMV on the left was significantly higher than on the right. In the PO2, Rolandic operculum, thalamus, and insula, the WMV on the left side was higher than on the right side of the corresponding location. However, the right caudate and precuneus WMV were higher than the left at the same location. In the H1MRS study, the Glx/tCr and GPC/tCr ratios on the left side were significantly higher than on the right. In comparison, the NAA/tCr and tNAA/tCr ratios showed contrasting results. The NAA/tCr ratio (r = -0.478, p = 0.021), tNAA/tCr ratio (r = -0.537, p = 0.008), and Glx/tCr ratio (r = -0.514, p = 0.012) on the right side showed a significant negative correlation with the participants' age. There was no relationship between GMV and metabolites on either side. Brain structure and concentrations of brain metabolites related to the vestibular system may differ between the two hemispheres in healthy individuals. Therefore, the asymmetry of the central-vestibular system should be considered when performing imaging.

Strength gains after 12 weeks of resistance training correlate with neurochemical markers of brain health in older adults: a randomized control 1H-MRS study

Physical exercise is considered a potent countermeasure against various age-associated physiological deterioration processes. We therefore assessed the effect of 12 weeks of resistance training on brain metabolism in older adults (age range: 60–80 years). Participants either underwent two times weekly resistance training program which consisted of four lower body exercises performed for 3 sets of 6–10 repetitions at 70–85% of 1 repetition maximum (n = 20) or served as the passive control group (n = 21). The study used proton magnetic resonance spectroscopy to quantify the ratio of total N-acetyl aspartate, total choline, glutamate-glutamine complex, and myo-inositol relative to total creatine (tNAA/tCr, tCho/tCr, Glx/tCr, and mIns/tCr respectively) in the hippocampus (HPC), sensorimotor (SM1), and prefrontal (dlPFC) cortices. The peak torque (PT at 60°/s) of knee extension and flexion was assessed using an isokinetic dynamometer. We used repeated measures time × group ANOVA to assess time and group differences and correlation coefficient analyses to examine the pre-to-post change (∆) associations between PT and neurometabolite variables. The control group showed significant declines in tNAA/tCr and Glx/tCr of SM1, and tNAA/tCr of dlPFC after 12 weeks, which were not seen in the experimental group. A significant positive correlation was found between ∆PT knee extension and ∆SM1 Glx/tCr, ∆dlPFC Glx/tCr and between ∆PT knee flexion and ∆dlPFC mIns/tCr in the experimental group. Overall, findings suggest that resistance training seems to elicit alterations in various neurometabolites that correspond to exercise-induced “preservation” of brain health, while simultaneously having its beneficial effect on augmenting muscle functional characteristics in older adults.

Neurometabolic correlates of posturography in normal aging and older adults with mild cognitive impairment: Evidence from a 1H-MRS study

Proton magnetic resonance spectroscopy (1H-MRS) holds promise for revealing and understanding neurodegenerative processes associated with cognitive and functional impairments in aging. In the present study, we examined the neurometabolic correlates of balance performance in 42 cognitively intact older adults (healthy controls - HC) and 26 older individuals that were diagnosed with mild cognitive impairment (MCI). Neurometabolite ratios of total N-acetyl aspartate (tNAA), glutamate-glutamine complex (Glx), total choline (tCho) and myo-inositol (mIns) relative to total creatine (tCr) were assessed using single voxel 1H-MRS in four different brain regions. Regions of interest were the left hippocampus (HPC), dorsal posterior cingulate cortex (dPCC), left sensorimotor cortex (SM1), and right dorsolateral prefrontal cortex (dlPFC). Center-of-pressure velocity (Vcop) and dual task effect (DTE) were used as measures of balance performance. Results indicated no significant group differences in neurometabolite ratios and balance performance measures. However, our observations revealed that higher tCho/tCr and mIns/tCr in hippocampus and dPCC were generic predictors of worse balance performance, suggesting that neuroinflammatory processes in these regions might be a driving factor for impaired balance performance in aging. Further, we found that higher tNAA/tCr and mIns/tCr and lower Glx/tCr in left SM1 were predictors of better balance performance in MCI but not in HC. The latter observation hints at the possibility that individuals with MCI may upregulate balance control through recruitment of sensorimotor pathways.

Motor cortex functional connectivity is associated with underlying neurochemistry in ALS

ObjectiveTo identify structural and neurochemical properties that underlie functional connectivity impairments of the primary motor cortex (PMC) and how these relate to clinical findings in amyotrophic lateral sclerosis (ALS).Methods52 patients...

Cognitive dysfunction and neurometabolic alternations in major depressive disorder with gastrointestinal symptoms

BackgroundBrain biochemical abnormalities have been associated with major depressive disorder (MDD) and cognitive impairments. However, the cognitive performance and neurometabolic alterations of MDD patients accompanied by gastrointestinal (GI) symptoms remain to be elucidated. We aimed to reveal the features and correlation between cognitive impairments and brain biochemical abnormalities of depressed patients with GI symptoms. MethodsFifty MDD patients with GI symptoms (GI group), 46 patients without GI symptoms (NGI group) and 50 demographically matched healthy controls (HCs) underwent Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) assessments. In addition, proton magnetic resonance spectroscopy (1H-MRS) was used to obtain ratios of N-acetyl aspartate to creatine (NAA/Cr) and choline-containing compounds to creatine (Cho/Cr) in the thalamus, putamen and anterior cingulate cortex (ACC). Finally, association analysis was conducted to investigate the relationships of these measurements. ResultsCompared to HCs, participants in both the GI and NGI groups had significantly reduced performance in the six MCCB cognitive domains (all p < 0.05), except for reasoning and problem solving. Higher Cho/Cr ratios in the right thalamus (p < 0.05) and lower NAA/Cr ratios in the left putamen (p < 0.05) were found in the NGI group than in the GI group. The severity of GI symptoms was negatively correlated with Cho/Cr ratios in the right ACC (r = −0.288, p = 0.037). In addition, the T-scores of visual learning were negatively correlated with NAA/Cr ratios in the right ACC (r = −0.443, p = 0.001) and right thalamus (r = −0.335, p = 0.015). ConclusionOur findings suggest that MDD patients with GI symptoms may exhibit greater neurometabolic alternations than those without GI symptoms, while both show similar cognitive dysfunction. In addition, neurometabolic alterations in the ACC and thalamus may underlie the neural basis of GI symptoms and cognitive impairment in MDD.

Interhemispheric asymmetry of the brain in patients with type 1 diabetes mellitus and cognitive impairment.

With an ageing of population and a splurging epidemic of diabetes mellitus (DM), the prevalence of complications associated with pathology of the central nervous system are expected to increase, which in the future may have serious consequences for public health. It is known that one of the main manifestations of brain damage in type 1 diabetes is cognitive impairment, which is possibly associated with the peculiarities of vascularization and interhemispheric asymmetry, which requires in-depth analysis using modern neuroimaging methods. The aim of the study is to assess the symmetry of structural, metabolic and neurovascularization changes in the brain in patients with type 1 diabetes and cognitive impairment. The study included 120 patients with type 1 diabetes aged 18 to 45 years suffering from cognitive impairment, and 30 people without cognitive decline and the control group (n=30) healthy people without diabetes. Neuropsychological testing included the Montreal Cognitive Dysfunction Assessment Scale (MoCA test). For neuroimaging methods, standard magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), contrast and non-contrast-enhanced perfusion were used. Statistical processing was carried out using the SPSS Statistic 2020 software. In patients with type 1 diabetes with cognitive impairment, as manifested by impaired memory and/or attention, perfusion imaging revealed the presence of brain asymmetry zones. Standard MRI allowed to demonstrate changes in the white, gray matter and hippocampus in the right hemisphere. The results obtained were refined taking into account the topical localization, so during the perfusion study, regions with asymmetric blood flow were identified - namely, the white matter of the frontal lobe and the gray matter in the occipital lobe. Spectroscopy of the brain revealed that it was in these areas of the brain that the most significant metabolic disorders were noted – in the form of significantly altered ratio of N-acetylaspartate (NAA)/choline (Cho) on the left, along with the asymmetry in phosphocreatine level (Cr 2) on the right. In conclusion, early preclinical predictive diagnostics with the use of modern neuroimaging methods allows for timely detection of impaired vascularization and brain metabolism in this group of patients, However, decreased perfusion in the region within the region of frontal lobe white matter and temporal lobe grey matter, and hippocampal cell metabolism by spectra should be highlighted among the parameters Cr right and NAA/Cho left.

Radiological Prediction of Isocitrate Dehydrogenase (IDH) Mutational Status and Pathological Verification for Lower-Grade Astrocytomas

Background and objectiveThe isocitrate dehydrogenase (IDH) status of patients with World Health Organization (WHO) grade II or III astrocytoma is essential for understanding its biological features and determining therapeutic strategies. This study aimed to use radiological analysis to predict the IDH status of patients with lower-grade astrocytomas and to verify the pathological implications.MethodsIn this study, 47 patients with grade II (17 cases) or III astrocytomas (30 cases), based on 2016 WHO Classification, underwent methionine (MET) positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) on the same day between January 2013 and June 2020. The patients were retrospectively assessed. Immunohistochemistry showed 23 cases of IDH-mutant and 24 of IDH-wildtype. Based on fluid-attenuated recovery inversion (FLAIR)/T2 imaging, three doctors blinded to clinical data independently allocated 18 patients to the clear boundary group between the tumor and the normal brain and 29 to the unclear boundary group. The peak ratios of N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/Cr, and Cho/NAA and the tumor-to-normal region (T/N) ratio for maximum accumulation in MET-PET were calculated. For statistical analysis, Fisher’s exact test was used to assess associations between two variables, and the Mann-Whitney U test to compare the values between the IDH-wildtype and IDH-mutant groups. The optimal cut-off values of MET T/N ratio and MRS parameters for discriminating IDH-wildtype from IDH-mutant were obtained using receiver operating characteristics curves.ResultsThe unclear boundary group had significantly more IDH-wildtype cases than the clear boundary group (P<0.001). The IDH-wildtype group had significantly lower Cho/Cr (<1.84) and Cho/NAA (<1.62) ratios (P=0.02 and P=0.047, respectively) and a higher MET T/N ratio (>1.44, P=0.02) than the IDH-mutant group. The odds for the IDH-wildtype were 0.22 for patients who fulfilled none of the four criteria, including boundary status and three ratios, and 0.9 for all four criteria.ConclusionsThese results suggest that the combination of MRI, MRS, and MET-PET examination could be helpful for the prediction of IDH status in WHO grade II/III gliomas.

Similarities and differences in working memory and neurometabolism of obsessive-compulsive disorder and major depressive disorder

BackgroundObsessive-compulsive disorder (OCD) and major depressive disorder (MDD) both showed cognitive impairment, and the altered neurometabolic may associate with cognitive impairment. However, there are limited comparative working memory (WM) and neuroimaging studies on these two disorders. Therefore, we investigated the characteristics of WM and neurometabolic changes in patients with OCD and MDD. MethodsA total of 64 unmedicated patients (32 OCD and 32 MDD), and 33 healthy controls (HC) were included to conduct WM assessment comprising Digit Span Test (DST), 2-back task and Stroop Color and Word Test (SCWT). Additionally, all subjects underwent protons magnetic resonance spectroscopy (1H-MRS) to collect neurometabolic ratios of N-acetyl aspartate (NAA) and choline-containing compounds (Cho) to creatine (Cr) in the prefrontal cortex (PFC) and lentiform nucleus (LN). Finally, differential and correlation analysis were conducted to investigate their characteristics and relationships. ResultsCompared with HC, both OCD and MDD patients exhibited a lower accuracy rate in the 2-back task, and only MDD patients performed worse in DST scores and longer reaction times in SCWT (all p < 0.05). Both OCD and MDD patients had lower NAA/Cr ratios in bilateral PFC (all p < 0.05). And the decreased NAA/Cr ratios in right PFC were positively correlated to DST scores in MDD group (r = 0.518, p = 0.003). ConclusionsBoth OCD and MDD showed WM impairment and neurometabolic alterations in PFC. Besides, MDD performed more severe and broader WM impairment compared to OCD. Moreover, the dysfunction of PFC may underlie the neural basis of WM impairment in MDD.

Taurine supplementation improves hippocampal metabolism in immature rats with intrauterine growth restriction (IUGR) through protecting neurons and reducing gliosis.

Taurine as an essential amino acid in the brain could play an important role in protecting the fetal brain of intrauterine growth restriction (IUGR). The hippocampus with IUGR showed neural metabolic disorder and structure changed that affected memory and learning ability. This study was aimed to identify the effect of taurine supplementation on the metabolism alterations and cellular composition changes of the hippocampus in IUGR immature rats. Metabolite concentrations were determined by magnetic resonance spectroscopy (MRS) in the hippocampus of juvenile rats with IUGR following taurine supplementation with antenatal or postnatal supply. The composition of neural cells in the hippocampus was observed by immunohistochemical staining (IHC) and western blotting (WB). Antenatal taurine supplementation increased the ratios of N-acetylaspartate (NAA) /creatine (Cr) and glutamate (Glu) /Cr of the hippocampus in the IUGR immature rats, but reduced the ratios of choline (Cho) /Cr and myoinositol (mI) /Cr. At the same time, the protein expression of NeuN in the IUGR rats was increased through intrauterine taurine supplementation, and the GFAP expression was reduced. Especially the effect of antenatal taurine was better than postpartum. Furthermore, there existed a positive correlation between the NAA/Cr ratio and the NeuN protein expression (R = 0.496 p < 0.001 IHC; R = 0.568 p < 0.001 WB), the same results existed in the relationship between the mI/Cr ratio and the GFAP protein expression (R = 0.338 p = 0.019 IHC; R = 0.440 p = 0.002 WB). Prenatal taurine supplementation can better improve hippocampal neuronal metabolism by increasing NAA / Cr ratio related to the number of neurons and reducing Cho / Cr ratio related to the number of glial cells.

Extensive Brain Pathologic Alterations Detected with 7.0-T MR Spectroscopic Imaging Associated with Disability in Multiple Sclerosis.

Background MR spectroscopic imaging (MRSI) allows in vivo assessment of brain metabolism and is of special interest in multiple sclerosis (MS), where morphologic MRI cannot depict major parts of disease activity. Purpose To evaluate the ability of 7.0-T MRSI to depict and visualize pathologic alterations in the normal-appearing white matter (NAWM) and cortical gray matter (CGM) in participants with MS and to investigate their relation to disability. Materials and Methods Free-induction decay MRSI was performed at 7.0 T. Participants with MS and age- and sex-matched healthy controls were recruited prospectively between January 2016 and December 2017. Metabolic ratios were obtained in white matter lesions, NAWM, and CGM regions. Subgroup analysis for MS-related disability based on Expanded Disability Status Scale (EDSS) scores was performed using analysis of covariance. Partial correlations were applied to explore associations between metabolic ratios and disability. Results Sixty-five participants with MS (mean age ± standard deviation, 34 years ± 9; 34 women) and 20 age- and sex-matched healthy controls (mean age, 32 years ± 7; 11 women) were evaluated. Higher signal intensity of myo-inositol (mI) with and without reduced signal intensity of N-acetylaspartate (NAA) was visible on metabolic images in the NAWM of participants with MS. A higher ratio of mI to total creatine (tCr) was observed in the NAWM of the centrum semiovale of all MS subgroups, including participants without disability (marginal mean ± standard error, healthy controls: 0.78 ± 0.04; EDSS 0-1: 0.86 ± 0.03 [P = .02]; EDSS 1.5-3: 0.95 ± 0.04 [P < .001]; EDSS ≥3.5: 0.94 ± 0.04 [P = .001]). A lower ratio of NAA to tCr was found in MS subgroups with disabilities, both in their NAWM (marginal mean ± standard error, healthy controls: 1.46 ± 0.04; EDSS 1.5-3: 1.33 ± 0.03 [P = .03]; EDSS ≥3.5: 1.30 ± 0.04 [P = .01]) and CGM (marginal mean ± standard error, healthy controls: 1.42 ± 0.05; EDSS ≥3.5: 1.23 ± 0.05 [P = .006]). mI/NAA correlated with EDSS (NAWM of centrum semiovale: r = 0.47, P < .001; parietal NAWM: r = 0.43, P = .002; frontal NAWM: r = 0.34, P = .01; frontal CGM: r = 0.37, P = .004). Conclusion MR spectroscopic imaging at 7.0 T allowed in vivo visualization of multiple sclerosis pathologic findings not visible at T1- or T2-weighted MRI. Metabolic abnormalities in the normal-appearing white matter and cortical gray matter were associated with disability. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Barker in this issue.

Blood pressure variability and neuroplasticity in patients with type 2 diabetes mellitus

Analysis of the role of blood pressure (BP) variability in the formation of neuroplasticity in patients with type 2 diabetes mellitus (DM). 100 patients with type 2 DM were examined, which were divided into groups depending on the presence of cognitive impairment (CI), the control group consisted of 25 people. All examined patients underwent a clinical examination, a standard set of biochemical blood tests, plasma osteopontin levels, 24-hour blood pressure monitoring (ABPM) for 24-26 h MRI of the brain (dynamic contrast and arterial spin marks, proton spectroscopy, tractography). Patients with type 2 diabetes and CI had higher body mass index, blood levels of glycated hemoglobin, glucose, alanine aminotransferase, low-density lipoprotein, triglycerides, total cholesterol, osteopontin, and lower levels of high-density lipoprotein (p≤0.05). The level of osteopontin was higher in patients with overweight, hyperglycemia, dyslipidemia, and in patients with CI in patients with BP variability. When assessing 24-hour blood pressure monitoring (ABPM), a significant difference was found in all standard indicators, while patients with type 2 diabetes were referred to as «non-dipper», in the presence of CI they noted significantly higher values of the index of time and area of stay in the suprathreshold state. BP and variability in SBP and DBP at night, as well as the risk of occult hypertension. A decrease in cerebral blood flow was revealed according to the data of contrast and non-contrast assessment of perfusion in cortical (especially in the frontal lobe) and subcortical (mainly in the putamen) structures, associated with changes in ABPM parameters. Mean SBP and DBP day and night, as well as the index of BP variability, also affect the integrity of the corticospinal, uncinate, lower longitudinal tracts, and arcuate fasciculus. The same parameters change the metabolism of the hippocampus in terms of choline (Cho), creatine (Cr), creatine phosphate (Cr2), as well as the ratio of N-acetylaspartate (NAA)/Cho, NAA/Cr, Cho/Cr. In patients with type 2 diabetes, BP variability contributes to the formation of CI through a pro-inflammatory mechanism (osteopontin), leading to impaired brain vascularization in general, white matter structure, and hippocampal metabolism.

Childhood trauma history is linked to abnormal brain metabolism of non-medicated adult patients with major depressive disorder

ObjectivesChildhood trauma is a risk factor that may lead to persistent brain metabolic abnormalities, predisposing individuals to major depressive disorder (MDD). To better elucidate the pathogenesis of MDD, we investigated the neurometabolic changes in unmedicated MDD patients who had experienced childhood trauma (CT). MethodsIn this study, 37 unmedicated MDD patients with CT, 35 unmedicated MDD patients without CT, and 30 healthy control participants underwent high-resolution proton magnetic resonance spectroscopy (1H-MRS) examination. Bilateral metabolic ratios of N-acetylaspartate (NAA)/creatine (Cr) and choline (Cho)/Cr in the prefrontal white matter (PWM), anterior cingulate cortex (ACC), putamen, and cerebellum were obtained. ResultsMDD patients showed neurometabolic changes in the cortico-striato-cerebellar (CSC) circuit. Furthermore, MDD patients showed significantly lower NAA/Cr and higher Cho/Cr ratio in the bilateral ACC and putamen, and higher NAA/Cr and lower Cho/Cr ratio in the cerebellum. Childhood trauma reduced the Cho/Cr ratio in the left ACC, which played an important role in longer and more episodes of depression. ConclusionEarly childhood trauma has a long-lasting impact on the metabolism of adult MDD patients, leading to abnormal choline metabolism of the left ACC. Abnormal biochemical metabolism in the CSC circuit may be an underlying pathophysiology of MDD. LimitationAs this is a small cross-sectional study, the impact of childhood trauma on the different stages of depression has not been observed.