The developmental trajectory of 1H-MRS brain metabolites from childhood to adulthood.

Human brain development is ongoing throughout childhood, with for example, myelination of nerve fibers and refinement of synaptic connections continuing until early adulthood. 1H-Magnetic Resonance Spectroscopy (1H-MRS) can be used to quantify the concentrations of endogenous metabolites (e.g. glutamate and γ -aminobutyric acid (GABA)) in the human brain in vivo and so can provide valuable, tractable insight into the biochemical processes that support postnatal neurodevelopment. This can feasibly provide new insight into and aid the management of neurodevelopmental disorders by providing chemical markers of atypical development. This study aims to characterize the normative developmental trajectory of various brain metabolites, as measured by 1H-MRS from a midline posterior parietal voxel. We find significant non-linear trajectories for GABA+ (GABA plus macromolecules), Glx (glutamate + glutamine), total choline (tCho) and total creatine (tCr) concentrations. Glx and GABA+ concentrations steeply decrease across childhood, with more stable trajectories across early adulthood. tCr and tCho concentrations increase from childhood to early adulthood. Total N-acetyl aspartate (tNAA) and Myo-Inositol (mI) concentrations are relatively stable across development. Trajectories likely reflect fundamental neurodevelopmental processes (including local circuit refinement) which occur from childhood to early adulthood and can be associated with cognitive development; we find GABA+ concentrations significantly positively correlate with recognition memory scores.

GABA and glutamate response to social processing: a functional MRS feasibility study.

Several studies have suggested that atypical social processing in neurodevelopmental conditions (e.g. autism) is associated with differences in excitation and inhibition, through changes in the levels of glutamate and gamma-aminobutyric acid (GABA). While associations between baseline metabolite levels and behaviours can be insightful, assessing the neurometabolic response of GABA and glutamate during social processing may explain altered neurochemical function in more depth. Thus far, there have been no attempts to determine whether changes in metabolite levels are detectable using functional MRS (fMRS) during social processing in a control population. We performed Mescher-Garwood point resolved spectroscopy edited fMRS to measure the dynamic response of GABA and glutamate in the superior temporal sulcus (STS) and visual cortex (V1) while viewing social stimuli, using a design that allows for analysis in both block and event-related approaches. Sliding window analyses were used to investigate GABA and glutamate dynamics at higher temporal resolution. The changes of GABA and glutamate levels with social stimulus were largely non-significant. A small decrease in GABA levels was observed during social stimulus presentation in V1, but no change was observed in STS. Conversely, non-social stimulus elicited changes in both GABA and glutamate levels in both regions. Our findings suggest that the current experimental design primarily captures effects of visual stimulation, not social processing. Here, we discuss the feasibility of using fMRS analysis approaches to assess changes in metabolite response.

Functional MRS studies of GABA and glutamate/Glx - A systematic review and meta-analysis.

Functional magnetic resonance spectroscopy (fMRS) can be used to investigate neurometabolic responses to external stimuli in-vivo, but findings are inconsistent. We performed a systematic review and meta-analysis on fMRS studies of the primary neurotransmitters Glutamate (Glu), Glx (Glutamate + Glutamine), and GABA. Data were extracted, grouped by metabolite, stimulus domain, and brain region, and analysed by determining standardized effect sizes. The quality of individual studies was rated. When results were analysed by metabolite type small to moderate effect sizes of 0.29-0.47 (p < 0.05) were observed for changes in Glu and Glx regardless of stimulus domain and brain region, but no significant effects were observed for GABA. Further analysis suggests that Glu, Glx and GABA responses differ by stimulus domain or task and vary depending on the time course of stimulation and data acquisition. Here, we establish effect sizes and directionality of GABA, Glu and Glx response in fMRS. This work highlights the importance of standardised reporting and minimal best practice for fMRS research.

Noninvasive NMR/MRS Metabolic Parameters to Evaluate Metabolic Syndrome in Rats.

(1) Background: Ectopic fat deposition and its effects, metabolic syndrome, have been significantly correlated to lifestyle and caloric consumption. There is no specific noninvasive evaluation tool being used in order to establish clinical markers for tracing the metabolic pathway implicated in obesity-related abnormalities that occur in the body as a result of a high-fat diet (HFD). The purpose of this work is to investigate in vivo ectopic fat distribution and in vitro metabolite profiles given by HFDs, as well as how they are inter-related, in order to find surrogate metabolic biomarkers in the development of metabolic syndrome utilizing noninvasive approaches. (2) Methods: Male Wistar rats were divided into a standard normal chow diet, ND group, and HFD group. After 16 weeks of different diet administration, blood samples were collected for proton nuclear magnetic resonance (1H NMR) and biochemical analysis. Magnetic resonance imaging/proton magnetic resonance spectroscopy (MRI/1H MRS) was performed on the abdomen, liver, and psoas muscle of the rats. (3) Results: Visceral fat showed the strongest relationship with blood cholesterol. Although liver fat content (LFC) was not associated with any biophysical profiles, it had the highest correlation with metabolites such as (-CH2)n very-low-density lipoprotein/low-density lipoprotein (VLDL/LDL), lactate, and N-acetyl glycoprotein of serum 1H NMR. HFD showed no obvious influence on muscle fat accumulation. Acetoacetate, N-acetyl glycoprotein, lactate, (-CH2)n VLDL/LDL, and valine were the five possible metabolic biomarkers used to differentiate HFD from ND in the present study. (4) Conclusions: Our study has validated the influence of long-term HFD-induced ectopic fat on body metabolism as well as the metabolic profile deterioration both in vivo and in vitro.

Advanced Molecular Imaging (MRI/MRS/1H NMR) for Metabolic Information in Young Adults with Health Risk Obesity.

BACKGROUND: Obesity or being overweight is a medical condition of abnormal body fat accumulation which is associated with a higher risk of developing metabolic syndrome. The distinct body fat depots on specific parts of the anatomy have unique metabolic properties and different types of regional excessive fat distribution can be a disease hazard. The aim of this study was to identify the metabolome and molecular imaging phenotypes among a young adult population. METHODS: The amount and distribution of fat and lipid metabolites profile in the abdomen, liver, and calf muscles of 46 normal weight, 17 overweight, and 13 obese participants were acquired using MRI and MR spectroscopy (MRS), respectively. The serum metabolic profile was obtained using proton NMR spectroscopy. NMR spectra were integrated into seven integration regions, which reflect relative metabolites. RESULTS: A significant metabolic disorder symptom appeared in the overweight and obese group, and increased lipid deposition occurred in the abdomen, hepatocytes, and muscles that were statistically significant. Overall, the visceral fat depots had a marked influence on dyslipidemia biomarkers, blood triglyceride (r = 0.592, p < 0.001), and high-density lipoprotein cholesterol (r = -0.484, p < 0.001). Intrahepatocellular lipid was associated with diabetes predictors for hemoglobin (HbA1c%; r = 0.379, p < 0.001) and for fasting blood sugar (r = 0.333, p < 0.05). The lipid signals in serum triglyceride and glucose signals gave similar correspondence to biochemical lipid profiles. CONCLUSIONS: This study proves the association between alteration in metabolome in young adults, which is the key population for early prevention of obesity and metabolic syndrome. This study suggests that dyslipidemia prevalence is influenced mainly by the visceral fat depot, and liver fat depot is a key determinant for glucose metabolism and hyperglycemia. Moreover, noninvasive advanced molecular imaging completely elucidated the impact of fat distribution on the anthropometric and laboratory parameters, especially indices of the metabolic syndrome biomarkers in young adults.

Waist Circumference and BMI Are Strongly Correlated with MRI-Derived Fat Compartments in Young Adults.

Young adulthood is increasingly considered as a vulnerable age group for significant weight gain, and it is apparent that there is an increasing number of new cases of metabolic syndrome developing among this population. This study included 60 young adult volunteers (18-26 years old). All participants obtained a calculated total abdominal fat percentage, subcutaneous fat percentage, and visceral fat percentage using a semiautomatic segmentation technique from T1-weighted magnetic resonance imaging (MRI) images of the abdomen. The results show strongest correlation between abdominal fat and BMI (r = 0.824) followed by subcutaneous fat (r = 0.768), and visceral fat (r = 0.633) respectively, (p < 0.001 for all, after having been adjusted for age and gender). Among anthropometric measurements, waist circumference showed strong correlation with all fat compartments (r = 0.737 for abdominal, r = 0.707 for subcutaneous fat, and r = 0.512 for visceral fat; p < 0.001 for all). The results obtained from examining the blood revealed that there was a moderate positive correlation relationship between all fat compartments with triglyceride, high-density lipoprotein, and fasting glucose levels (p < 0.05 for all). This study suggests that both BMI and waist circumference could be used to assess the fat compartments and treatment targets to reduce the risk of metabolic disorders and health risks in the young adult population.

Identification of Metabolic Phenotypes in Young Adults with Obesity by 1H NMR Metabolomics of Blood Serum.

(1) Since the obesity prevalence rate has been consistently increasing, it is necessary to find an effective way to prevent and treat it. Although progress is being made to reduce obesity in the young adult population, a better understanding of obesity-related metabolomics and related biochemical mechanisms is urgently needed for developing appropriate screening strategies. Therefore, the aim of this study is to identify the serum metabolic profile associated with young adult obesity and its metabolic phenotypes. (2) Methods: The serum metabolic profile of 30 obese and 30 normal-weight young adults was obtained using proton nuclear magnetic resonance spectroscopy (1H NMR). 1H NMR spectra were integrated into 24 integration regions, which reflect relative metabolites, and were used as statistical variables. (3) Results: The obese group showed increased levels of lipids, glucose, glutamate, N-acetyl glycoprotein, alanine, lactate, 3 hydroxybutyrate and branch chain amino acid (BCAA), and decreased levels of choline as compared with the normal-weight group. Non-hyperlipidemia obese adults showed lower levels of lipids and lactate, glutamate, acetoacetate, N-acetyl glycoprotein, isoleucine, and higher levels of choline and glutamine, as compared with hyperlipidemic obese adults. (4) Conclusions: This study reveals valuable findings in the field of metabolomics and young adult obesity. We propose several serum biomarkers that distinguish between normal weight and obese adults, i.e., glutamine (higher in the normal group, p < 0.05), and lactate, BCAAs, acetoacetate and 3-hydroxybutyrate (higher in the obese group, p < 0.05). In addition, visceral fat and serum TG, glutamate, acetoacetate, N-acetyl glycoprotein, unsaturated lipid, isoleucine, and VLDL/LDL are higher (p < 0.05) in the obese with hyperlipidemia. Therefore, they can be used as biomarkers to identify these two types of obesity.

Magnetic Resonance Spectroscopy of Hepatic Fat from Fundamental to Clinical Applications.

The number of individuals suffering from fatty liver is increasing worldwide, leading to interest in the noninvasive study of liver fat. Magnetic resonance spectroscopy (MRS) is a powerful tool that allows direct quantification of metabolites in tissue or areas of interest. MRS has been applied in both research and clinical studies to assess liver fat noninvasively in vivo. MRS has also demonstrated excellent performance in liver fat assessment with high sensitivity and specificity compared to biopsy and other imaging modalities. Because of these qualities, MRS has been generally accepted as the reference standard for the noninvasive measurement of liver steatosis. MRS is an evolving technique with high potential as a diagnostic tool in the clinical setting. This review aims to provide a brief overview of the MRS principle for liver fat assessment and its application, and to summarize the current state of MRS study in comparison to other techniques.

Effects of obesity on the lipid and metabolite profiles of young adults by serum 1H-NMR spectroscopy.

BACKGROUND: Overweight (OW) is considered a risk for various metabolic diseases. However, its effects as a mechanism that alters the metabolite profiles remain unclear. The purpose of this study is to investigate the effects that OW has on the lipid and metabolite profiles in young adults. METHODS: The serum metabolite profiles of 46 young adults of normal weight and those considered OW were studied by Proton nuclear magnetic resonance spectroscopy (1H NMR) technique. RESULTS: 1H NMR metabolite analysis shows the alteration of metabolic levels and increased levels of CH2 lipids and CH3 lipids, which are used as unique biomarkers to identify OW subjects from the normal weight groups. CONCLUSION: This present study reveals that OW contributes to the systemic metabolism and the metabolite alteration among young adults. The alteration in serum lipids level could shed the light on metabolic syndrome pathogenesis in young adults and needs further elucidation.

Effects of muscle fiber orientation to main magnetic field on muscle metabolite profiles for magnetic resonance spectroscopy acquisition.

BACKGROUND: Proton magnetic resonance spectroscopy (1H MRS) is a technique widely used for investigating metabolites in humans. Lipids are stored outside the muscle cell are called extramyocellular lipids (EMCL), and lipids stored on the inside of muscle cells are called intramyocellular lipids (IMCL). The relationship between metabolic syndrome and IMCL has been extensively studied. AIM: To determine the effects of muscle fiber orientations on muscle metabolites using 1H MRS. METHODS: Chicken muscles were used as the subject in this study. MRS spectra were performed on a 1.5T Magnetic resonance imaging machine (1.5 Tesla Philips Achieva). A single voxel (8 mm × 8 mm × 20 mm) was placed on the chicken extensor iliotibialis lateralis muscle with the muscle fiber oriented at 0°, 30°, 60°, and 90° to the main magnetic field. 1H MRS spectra were acquired using a point-resolved spectroscopy, TR = 2000 ms, TE = 30 ms, and NSA = 256. Metabolites of interest from each orientation to the main magnetic field were compared using Wilcoxon signed-rank test. Differences less than 0.05 were considered to be statistically significant with 95%CI. RESULTS: The metabolite profiles were different for each orientation of muscle fibers to the main magnetic field. The orientation at 90° was the most different compared to other orientations. The quantity of IMCL and EMCL exhibited statistically significantly changes with impacts at 30°, 60°, and 90° when compared with muscles aligned at 0° to the main magnetic field. Statistical analysis showed statistically significant IMCL (CH3), EMCL (CH3), and IMCL (CH2) at 30°, 60°, and 90° (P = 0.017, 0.018, and 0.018, respectively) and EMCL (CH2) at 30° and 60° (P = 0.017 and 0.042, respectively). EMCL (CH2) at 90° was unable to be measured in this study. The muscle lipids quantified at 30°, 60°, and 90° tended to be lower when compared to 0°. CONCLUSION: Careful positioning is one of the most important factors to consider when studying 1H MRS metabolites in muscles to ensure reproducibility and uniformity of muscle metabolite spectra.

Body mass index and its effects on liver fat content in overweight and obese young adults by proton magnetic resonance spectroscopy technique.

AIM: To assess the association between liver fat content (LFC) and weight status in young adults using proton magnetic resonance spectroscopy (1H MRS) technique. METHODS: Seventy-eight healthy young adults, between 19-30 years of age participated in this study. This group was then separated into a control of 39 subjects and an overweight/obese group (OW/OB group) consisting of 39 subjects. Blood biochemical quantity and 1H MRS was performed for LFC assessment. RESULTS: LFC was found to be almost three times higher in OW/OB group when compared to the control group. A 48.7% incidence of non-alcoholic fatty liver disease in the OW/OB group was found. Blood biochemical measurements showed statistically higher low-density lipoproteins and triglyceride, lower high-density lipoproteins, and increased glycosylated hemoglobin and fasting glucose in the OW/OB group. Body mass index was a significant independent predictor for LFC after adjusting for age and sex (multiple linear regression; ß = 0.459, P < 0.001). CONCLUSION: Due to the prevalence of high LFC in the OW/OB group, it can be proposed that weight gain and obesity are sensitive indicators of high hepatic fat content.

The influence of leg positioning on the appearance and quantification of 1H magnetic resonance muscle spectra obtained from calf muscle.

PURPOSE: To study proton magnetic resonance spectra (1H-MRS) of the muscle metabolite of a leg muscle in neutral (NEU), internal rotation (INT), and external rotation (EXT) leg positioning. MATERIAL AND METHODS: The volunteers were selected for this study. The tibialis anterior (TA), soleus (SOL), and gastrocnemius (GAS) muscles of a non-dominate leg were determined by using single-voxel spectroscopy 8 × 8 × 20 mm3 in size. 1H-MRS measurements were performed on a 1.5-Tesla magnetic resonance imaging (MRI) scanner. RESULTS: The results showed that metabolite spectrum of muscle in each NEU, INT, and EXT of leg positioning were not similar. Additionally, the quantification of IMCL (CH3) and EMCL (CH3) is significantly different in SOL. CONCLUSIONS: Our study showed that leg positioning influences the appearance and quantification of 1H-MRS in the calf muscle. Hence, it is necessary to pay close attention to positioning because it interferes with spectral fitting and quantification.