Ratio Of Choline Research Articles

A green and recyclable ternary deep eutectic solvent for extracting flavonol glycoside from Ginkgo leaves: Mechanism insights based on molecular level

A novel ternary deep eutectic solvent (DES) was designed for the green and efficient extraction of flavonol glycosides (FG) from Ginkgo leaves. The DES consisted of a molar ratio of choline chloride/acetic acid/1,2-propylene glycol of 1:2:3. The optimal extraction conditions were determined to a solid-liquid ratio of 42 mg/mL, an extraction time of 11.8 h, and an extraction temperature of 51℃. The extraction yield of FG was 7.8 mg/g, which demonstrated a notable enhancement in comparison to conventional extraction. Kinetics and morphology analysis revealed that the extraction process involved considerable dissolution and diffusion of the solute. Additionally, a molecular investigation using density functional theory (DFT) indicated that the interaction between the DES and FG was primarily governed by hydrogen bonding and van der Waals force. Notably, the ternary DES exhibited stronger interactions with FG, which were the key factors for better extraction efficiency. Furthermore, efficient recovery of FG from the DES solution was also achieved, with a recovery rate of 94.63%. Moreover, the recovered DES could be reused directly at least five cycles.

Extraction of canola protein via natural deep eutectic solvents compared to alkaline treatments: Isolate characteristics and protein structural and functional properties

The capacity of four formulations of natural deep eutectic solvents (NDESs) for extraction of canola protein was compared to alkaline extractions at pH 12 and pH 9. NDESs were prepared with a 1:2:1 ratio of choline chloride/d-sorbitol, glycerol, d-glucose or urea/water. The urea formulation showed the lowest viscosity and density and highest polarity; and extracted a bright-yellow isolate with extraction efficiency of 52.89% and protein content of 84.03%. The rest of NDESs extracted light-green isolates with efficiencies of approximately 44%. Furthermore, All NDESs offered lower extraction efficiencies than pH 12 (68.34%, dark-green isolate) but higher than pH 9 (39.14%, yellow isolate). Molecular analysis via SE-HPLC and SDS-PAGE showed the presence of cruciferins and napins in all isolates, but higher napin contents for NDES isolates with cruciferin-to-napin ratios of around 60:40. NDESs also altered the secondary and tertiary structure of the protein to a lesser extent. The functionality analyses at pH range of 3–7 revealed better solubility for pH 9 (72.09%–39.35%) and glycerol formulation (68.61%–39.05%) isolates; and better foaming properties for all NDES isolates, possibly due to their higher napin contents. NDES isolates also showed better emulsifying properties at pH 5 and 7, while alkaline isolates produced more stable emulsions at pH 3, possibly due to the better solubility of their cruciferins at pH 3. Overall, NDES isolates offered higher extraction efficiencies and a close functionality compared to pH 9 isolate, better color and functionality than pH 12 isolate, and better preservation of native protein structure compared to both alkaline treatments.

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.

The diagnostic challenge of lack of choline level elevation on 1H-MR spectroscopy in grade II-III gliomas.

The accurate diagnosis of brain tumour is very important in modern neuro-oncology medicine. Magnetic resonance spectroscopy (MRS) is supposed to be a promising tool for detecting cancerous lesions. However, the interpretation of MRS data is complicated by the fact that not all cancerous lesions exhibit elevated choline (Cho) levels. The main goal of our study was to investigate the lack of Cho lesion /Cho ref elevation in the population of grade II-III gliomas. 89 cases of gliomas grade II and III were used for the retrospective analysis - glioma (astrocytoma or oligodendroglioma) grade II (74 out of 89 cases [83%]) and III (15 out of 89 cases [17%]) underwent conventional MRI extended by MRS before treatment. Histopathological diagnosis was obtained either by biopsy or surgical resection. Gliomas were classified to the group of no-choline elevation when the ratio of choline measured within the tumour (Cho lesion ) to choline from NABT (Cho ref ) were equal to or lower than 1. Significant differences were observed between ratios of Cho lesion /Cr lesion calculated for no-choline elevation and glial tumour groups as well as in the NAA lesion /Cr lesion ratio between the no-choline elevation group and glial tumour group. With consistent data concerning choline level elevation and slightly lower NAA value, the Cho lesion /NAA lesion ratio is significantly higher in the WHO II glial tumour group compared to the no-choline elevation cases ( p < 0.000). In the current study the results demonstrated possibility of lack of choline elevation in patients with grade II-III gliomas, so it is important to remember that the lack of elevated choline levels does not exclude neoplastic lesion.

Magnetic Resonance Spectroscopy of Brain Metabolism in Fetuses With Congenital Heart Disease

BackgroundCongenital heart disease (CHD) remains a significant risk factor for neurologic injury because altered fetal hemodynamics may be unable to support typical brain development during critical periods of growth and maturation. ObjectivesThe primary objective was to assess differences in the cerebral biochemical profile between healthy fetuses and fetuses with complex CHD and to relate these with infant outcomes. MethodsPregnant participants underwent fetal magnetic resonance imaging with cerebral proton magnetic resonance spectroscopy acquisitions as part of a prospective observational study. Cerebral metabolites of N-acetyl aspartate, creatine, choline, myo-inositol, scyllo-inositol, lactate, and relevant ratios were quantified using LCModel. ResultsWe acquired 503 proton magnetic resonance spectroscopy images (controls = 333; CHD = 170) from 333 participants (controls = 221; CHD = 112). Mean choline levels were higher in CHD compared with controls (CHD 2.47 IU [Institutional Units] ± 0.44 and Controls 2.35 IU ± 0.45; P = 0.02), whereas N-acetyl aspartate:choline ratios were lower among CHD fetuses compared with controls (CHD 1.34 ± 0.40 IU vs controls 1.44 ± 0.48 IU; P = 0.001). Cerebral lactate was detected in all cohorts but increased in fetuses with transposition of the great arteries and single-ventricle CHD (median: 1.63 [IQR: 0.56-3.27] in transposition of the great arteries and median: 1.28 [IQR: 0-2.42] in single-ventricle CHD) compared with 2-ventricle CHD (median: 0.79 [IQR: 0-1.45]). Cerebral lactate also was associated with increased odds of death before discharge (OR: 1.75; P = 0.04). ConclusionsCHD is associated with altered cerebral metabolites in utero, particularly in the third trimester period of pregnancy, which is characterized by exponential brain growth and maturation, and is associated with survival to hospital discharge. The long-term neurodevelopmental consequences of these findings warrant further study.

Magnetic resonance spectroscopy (MRS) of multifidus muscle metabolites in chronic low back pain (CLBP).

The purpose of the study was to investigate several potential imaging biomarkers of CLBP that may be useful for diagnosis and treatment efficacy evaluation. Proton magnetic resonance spectroscopy (1H-MRS) was used to detect the content and ratio of creatine (Cr), choline (Cho), and lipid (Lip) in the multifidus muscle (Mm) in patients with CLBP and to test for relationships between these metabolites and pain severity and duration. Sixty patients with CLBP (experimental group) and sixty-nine asymptomatic volunteers (control group) underwent routine diagnostic magnetic resonance imaging of the lumbar spine. 1H-MRS was acquired with single-voxel MR spectroscopy. The MRS region of interest for measuring Cho, Cr, and Lip concentrations was determined at the L4/5 multifidus muscle (Mm), bilaterally. The contents and ratios of Cr, Cho, and Lip in bilateral and ipsilateral-to-pain (or matched control side) Mm were obtained, and the integral ratios of different metabolites obtained by using Cr as an internal reference were statistically analyzed. There were no significant within-group differences in the contents and ratios of Lip, Cr, Cho, Lip/Cr, and Cho/Cr between the left and right Mm of the healthy control group (p > 0.05) or the CLBP group (p > 0.05). The CLBP group showed a much higher Lip and Lip/Cr ratio in the bilateral Mm compared to the healthy control group (p < 0.05) but there were no between-group differences in Cr, Cho, or the Cho/Cr ratio (p > 0.05). The severity of CLBP was correlated with Lip (p < 0.05). Using 1H-MRS, we demonstrated higher Lip and Lip/Cr ratios in the Mm of patients with CLBP, compared to asymptomatic controls. Mm Lip was correlated with CLBP intensity. An increase in Lip in the Mm may be a characteristic finding in CLBP and may offer a useful prognostic marker for guiding rehabilitation strategies.

The impacts of nicotinamide and inositol on the available cells and product performance of industrial baker's yeasts

A suitable nutrient supply, especially of vitamins, is very significant for the deep display of the inherent genetic properties of microorganisms. Here, using the chemically defined minimal medium (MM) for yeast, nicotinamide and inositol were confirmed to be more beneficial for the performance of two industrial baker's yeasts, a conventional and a high-sugar-tolerant strain. Increasing nicotinamide or inositol to proper levels could enhance the both strains on cell growth and activity and product performance, including trehalose accumulation and leavening performance. The activity of key enzymes (PCK, TPS) and the content of intermediate metabolites (G6P, UDPG) in the trehalose synthesis pathway were promoted by a moderate supply of nicotinamide and inositol. That were also proved that an appropriate amount of niacinamide promoted the transcription of longevity-related genes (PNC1, SIR2), and the proper concentration of inositol altered the phospholipid composition in cells, namely, phosphatidylinositol and phosphatidyl choline. Furthermore, the cell growth and the leavening performance of the both strains were promoted after adjusting inositol to choline to the proper ratio, resulting directly in content changes of phosphatidylinositol and phosphatidyl choline in the cells. While the two strains responded to the different proper ratio of inositol to choline probably due to their specific physiological characteristics. Such beneficial effects of increased nicotinamide levels were confirmed in natural media, molasses and corn starch hydrolyzed sugar media. Meanwhile, such adjustment of inositol to choline ratio could lessen the inhibition of excess inositol on cell growth of the two tested strains in corn starch hydrolyzed sugar media. However, in molasse, such phenomenon was not observed probably since there was higher Ca2+ in it. The results indicated that the effects of nutrient factors, such as vitamins, on cell growth and other properties found out from the simple chemically defined minimal medium were an effective measure to use in improving the recipe of natural media at least for baker's yeast.

Prolonged local delivery of doxorubicin to cancer cells using lipid liquid crystalline system

Exploring efficient strategies to eradicate the tumor tissue and enhance patient outcomes still remained a serious challenge. Systemic toxicity of the current chemotherapeutics and their low concentration in the tumor site limited reaching a practical approach in their administration and combinational therapy. Besides, complicated delivery platforms could not receive the marketing approval due to difficulties in scale up procedures. To this aim, we developed a simple injectable local delivery platform which provided a sufficient dose of the chemotherapeutic in the cancerous tissue with sustained release properties. Herein, various injectable in situ forming LLC formulations loaded with doxorubicin (DOX) were developed. Although there were many previous studies on lipid liquid crystal (LLC) based formulations, their performance as an injectable intratumoral depot system for local chemotherapy has not been extensively investigated yet. In the current study we developed 18 formulations of DOX loaded LLCs using Box-Behnken method via different ratios of phosphatidyl choline: sorbitan monooleate (PC: SMO), N-Methyl-2-pyrrolidone (NMP), and tween 80. The physicochemical properties of the formulations were investigated and their in vivo tumor inhibition efficiencies in C26 tumor bearing mouse model was further studied. The results indicated that DOX loaded PC: SMO/NMP/Tween 80 (50:50/50/2 w/w%) and DOX loaded PC: SMO/NMP (50:50/50 w/w%) formulations were syringeable with pseudoplastic behavior. Also, they could release the cargo in a sustained manner for 60 days. Compared to intravascular administration of DOX, intratumoral injection of the developed formulations led to a significant decrease in tumor volume and enhancement of the survival rate in murine tumor model. Additionally, animal imaging studies proved their prolonged accumulation in the tumor site. Histopathological studies showed that treatment with the DOX-loaded LLC formulations did not cause any systemic toxicity to vital organs. Taken together, we believe that the developed simple and efficient local delivery platform can be further used in combinational therapies and treatment of various solid tumors.

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.

Formulation and in-vitro Evaluation of Ethosomes using Anastrozole as a Modeling Drug

Anastrozole (ANZ) is a potent non-steroidal aromatase II inhibitor (AI) used to decrease or delay the progression of breast tumor growth in some women. Since ANZ could be delivered transdermally due to its physicochemical characteristics as (log p of 3.5, aqueous solubility of 0.5 mg /mL, low dosage and half-life of 46.8 hr.) so, it could be used as a modelling drug evaluation of ethosomes, the current study aimed to formulate ANZ loaded ethosomes and evaluate the formulated ethosomes for particle size and PDI, entrapment efficiency and in vitro release profile. Film hydration method was used to prepare ANZ-loaded ethosoms. using different ratios of phospholipid (Soy phosphatidyl choline) and ethanol at variables probe sonication energy and time ratios.&#x0D; polydispersity index and particle size were used to evaluate the prepared ANZ-loaded ethosoms. The optimized formula of ethosomes which contain (1% Soy phosphatidyl choline,20% ethanol subjected to 300watt sonication energy with 1/3 sonication on /off ratio) was studied for in vitro drug release. It had 127.75±0.36 nm particle diameter and 74.7136 ± 3.457 % entrapment efficiency, the release kinetics obey Korsmeyer-Peppas and non-Fickian release as R2=0.9779 and n=0.737.&#x0D; The ratios of Soy phosphatidyl choline, ethanol, sonication energy and duration had a significant impact on the particle size of ethosomes at (p0.05). The preformulating analysis of Powder X-ray diffraction (P-XRD) indicate amorphous ethosomes. Fourier transform infrared (FTIR) showed the inertness among components.

Profiling of Homocysteine Metabolic Pathway Related Metabolites in Plasma of Diabetic Mellitus Based on LC-QTOF-MS.

Background: Homocysteine (Hcy) has been found to be closely related to the occurrence of diabetes mellitus (DM) and is considered as one of the risk factors of DM. However, Hcy alone is not enough as a factor to predict DM, and our study analyzed and determined the relationship between the main metabolites involved in the Hcy metabolic pathway and DM. Methods: A total of 48 clinical samples were collected, including 18 health control samples and 30 DM samples. All standards and samples were detected by LC-QTOF-MS. Multivariate statistical analysis and k-means cluster analysis were performed to screen and confirm the metabolites significantly correlated with DM. Results: A total of 13 metabolites of the Hcy metabolic pathway were detected in the samples. The content of Hcy, cysteine, taurine, pyridoxamine, methionine, and choline were significantly increased in the DM group (p < 0.05). Hcy, choline, cystathionine, methionine, and taurine contributed significantly to the probabilistic principal component analysis (PPCA) model. The odds ratios (OR) of Hcy, cysteine, taurine, methionine, and choline were all greater than one. K-means cluster analysis showed that the Hcy, taurine, methionine, and choline were significantly correlated with the distribution of glucose values (divided into four levels: 10.5−11.7 mmol/L, 7.7−9.7 mmol/L, 6.0−6.9 mmol/L, and 5.0−5.9 mmol/L, respectively). Conclusion: Hcy, taurine, methionine, and choline can be used as risk factors for diabetes diagnosis and are expected to be used for the assessment of diabetes severity.

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.

Bioderived deep eutectic solvent-based topical chemotherapy for squamous cell carcinoma of the skin

The properties of deep eutectic solvents (DESs) are tunable, providing a route to new functions. Choline and geranic acid (CAGE) class of DESs shows antimicrobial properties, acts as drug delivery systems, and functions as anti-obesity agents. We hypothesize that new properties are attainable by rational variation of the molar ratios of choline and geranic acid. This study assessed the anticancer properties of a series of CAGE DESs, aiming to develop novel topical chemotherapy for squamous cell carcinoma of the skin. Cell viability assay demonstrated that varying the molar ratio of choline and geranic acid provided a strategy to significantly reduce the viability of human squamous carcinoma of the skin cell line (A431) without compromising the viability of human normal skin fibroblast cell line (CRL-2091). This molar ratio did not induce CRL-2091 to release interleukin–1β (IL–1β), a biomarker of acute and chronic inflammation, suggesting that the therapeutic dose of CAGE is unlikely to trigger skin inflammation. The anticancer property of CAGE is attributable to geranic acid, which also reduced the viability of A431 and CRL-2091 cell lines. With regards to mechanism, the therapeutic dose of CAGE did not rupture the cell membrane but induced oxidative stress on the A431 cell line. Concluding, rationally varying choline and geranic acid molar ratios provides a strategy to endow new properties on CAGE as demonstrated by selective activity against squamous cell carcinoma of the skin.

Diagnostic performance of MRI perfusion and spectroscopy for brainstem glioma grading.

This study investigated the roles of dynamic susceptibility contrast (DSC) perfusion and multivoxel magnetic resonance spectroscopy (MRS) in grading brainstem glioma (BSG). Our retrospective study comprised 12 patients, including 6 with pathology verified low-grade BSGs and 6 with high-grade BSGs. We examined differences in age, relative cerebral blood volume (rCBV), regional cerebral blood flow (rCBF), and the metabolite ratios of choline (Cho)/N-acetyl aspartate (NAA) and Cho/creatine (Cr) between these two groups using the Mann-Whitney U test and Chi-square test. Receiver operating characteristic (ROC) curve analysis was used to establish cutoff values and assess their usefulness in grading BSG. The Cho/NAA metabolite ratio had the strongest preoperative predictive performance for identifying the correct histological grade among BSGs, with an area under the ROC curve (AUC) value of 0.944 (cutoff: 3.88, sensitivity [Se]: 83.3%; specificity [Sp]: 100%), followed by the Cho/Cr ratio (cutoff: 3.08; AUC: 0.917; Se: 83.3%; Sp: 100%), rCBF (cutoff: 3.56, AUC: 0.917; Se: 83.3%; Sp: 100%), rCBV (cutoff: 3.16, AUC: 0.889; Se: 100%; Sp: 66.7%), and age (cutoff: 9.5 years, AUC: 0.889; Se: 100%; Sp: 83.3%). rCBF and rCBV values comparing solid tumors with the normal brain parenchyma and the metabolite ratios for Cho/NAA and Cho/Cre may serve as useful indices for establishing BSG grading and provide important information when determining treatment planning and prognosis in patients with BSG.

JS07.4.A Correspondence of glutamine and glycine imaging based on 7T MRSI to amino acid PET

Abstract Background New approaches for 7 Tesla magnetic resonance spectroscopic imaging (MRSI) allow the simultaneous imaging of multiple neuro-oncological biomarkers with 3-4 mm resolution in clinically feasible measurement times. Specifically, the amino acids glutamine (Gln) and Glycine (Gly), were previously limited to single voxel detection at lower fields. Both could add to our capabilities to resolve heterogeneous tumour metabolism. Purpose To progress the validation of Gln and Gly as neuro-oncological markers by conducting the first comparison to amino acid PET in a cohort of glioma patients. Material and Methods In 24 glioma patients (WHO 2021 classification), we quantitatively compared 7T MRSI (3D, 3.4 mm isotropic resolution, 15 min scan time) and routine PET (FET or MET). Within manual tumour segmentations, we defined hotspot volumes of interest (VOI) for the ratios of total choline (tCho, clinical standard reference), Gln, Gly to total N-acetylaspartate (tNAA) and PET tumour-to-brain ratios (TBR), all with a cut-off threshold of 1.6. For these VOIs, we calculated VOI volumes and median ratios as well as Dice similarity coefficients (DSC) and centre of intensity distance (CoI), between MRSI and PET ratios. Results We found that Gln and Gly ratios to tNAA had a higher correspondence to PET-based amino acid metabolism than tCho. Our resulting median VOI volumes were 19.08±23.10 cm³ for tCho/tNAA, 33.68±24.60 cm³ for Gln/tNAA, and 22.38±18.49 cm³ for Gly/tNAA compared to 24.33±30.46 cm³ for PET, with correlation coefficients &amp;gt;0.5 for all MRSI hotspot values in relation to PET volumes. Median ratios were 0.52±0.13 for tCho/tNAA, 0.61±0.25 for Gln/tNAA, 0.33±0.15 for Gly/tNAA and 2.11±0.42 for PET. The median DSCs to PET amounted to 0.53±0.36 for tCho/tNAA, 0.66±0.40 for Gln/tNAA, and 0.57±0.36 for Gly/tNAA, while the median CoI distances were 0.56±0.43 cm for tCho/tNAA, 0.39±0.22 cm for Gln/tNAA, and 0.45±0.48 cm for Gly/tNAA. Conclusion With this first study that compared high-resolution 3D-MRSI at 7 Tesla to amino acid PET and a quantitative evaluation, we demonstrated that Gln and Gly corresponded better to PET than tCho, which is the main marker used in clinical MR, both within the study and compared to previous literature. Future research is needed to clearly define the benefits of 7T MRSI for neuro-oncology such as the identification of tumour microenvironments or non-invasive determination of molecular-pathologic markers. Gln could be further explored by the application of Gln-based PET tracers to MR-PET. We still see further developments of MRSI methods, such as motion correction or absolute quantification of concentrations instead of ratios, as necessary to obtain such goals.

Development, Validation, and Use of 1H-NMR Spectroscopy for Evaluating the Quality of Acerola-Based Food Supplements and Quantifying Ascorbic Acid.

Acerola (Malpighia emarginata D.C.) is an exotic fruit with high agro-industrial potential due to its high content of ascorbic acid (AA), phenolic compounds, and carotenoid pigments. Acerola fruit is processed into concentrated juice or powder to be incorporated into food supplements. The ascorbic acid content of concentrated juice or powders must be controlled and well assessed. Therefore, the development of optimal methods and procedures for the rapid and accurate determination of the ascorbic acid content in juice concentrate and juice powder remains of considerable commercial interest. NMR spectroscopy is currently a powerful spectroscopic tool for the qualitative and quantitative analysis of molecules of all types and sizes. Firstly, this article presents the NMR-based metabolomic profiling of acerola juice and concentrate powder to describe and compare their composition. Thirty-six metabolites were identified. The AA over choline ratio and the NMR metabolomic profiles could be used for authentication in the future. Secondly, a rapid (8 min), reliable, and non-destructive method for the quantification of ascorbic acid by 1D 1H-NMR spectroscopy was developed and validated. The LOD and LOQ were 0.05 and 0.15 mg/mL, respectively. These two approaches could be combined to better characterize ingredients derived from acerola and incorporated into food supplements.

Value of MRS combined with DTI in evaluating brain development of infants aged from 2 months to 2 years old.

Many neuropsychiatric diseases are related to the abnormal development of brain tissue in infants. This study aims to analyze the changes in the parameters of magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) in brain development of infants aged from 2 months to 2 years old, and to explore the value of MRS combined with DTI in evaluating brain development of infants aged from 2 months to 2 years old. A total of 116 normal infants, who received whole brain MRS and DTI examinations after delivery in Children Hospital of Shanxi Province from September 2020 to May 2021, were selected and were divided into a group A (n=7, at the age of 2-6 months), a group B (n=28, at the age of 7-12 months), a group C (n=41, at the age of 13-18 months), and a group D (n=40, at the age of 19-24 months). After collecting the MRS and DTI data, statistical analysis was performed to compare DTI parameters and MRS metabolic products ratio. There were significant differences in the DTI parameters of frontal lobe, temporal lobe, occipital lobe, hind limb of internal capsule, fore limb of internal capsule, knee of corpus callosum, splenium of corpus callosum, and optic radiation among the 4 groups (P<0.05 or P<0.01). The values of fractional anisotropy (FA) showed an upward trend from the group A to the group D, while the values of apparent diffusion coefficient (ADC), axial diffusivity (AD), and radial diffusivity (RD) showed a downward trend, and the changes of parameters tended to slow down with age. In the left or right lentiform nucleus, the ratio of choline (Cho)/creatine (Cr) was decreased from the group A to the group D, and the group D was significantly lower than the group A and B (all P<0.01). The ratio of Cho/N-acetyl aspartate (NAA) was decreased from the group A to the group D, and the group D was significantly lower than the group A, B, and C (left lentiform nucleus, P<0.05 or P<0.01) or the group A, B (right lentiform nucleus, both P<0.01). The ratio of glutamine/glutamate (Glx)/Cr was decreased from the group A to the group D, and the group D was significantly lower than the group A, B and C (P<0.05 or P<0.01). The ratio of myo-inositol (mI)/Cr was increased from the group A to the group D, and the group D was significantly higher than the group A, B, and C (P<0.05 or P<0.01). The ratio of NAA/Cr was increased from the group A to the group D, and the group B, C, and D were significantly higher than the group A (P<0.05 or P<0.01). The ratios of mI/Cr and NAA/Cr in different brain regions from the group A to the group D showed an upward trend, and the ratios of Cho/Cr, Cho/NAA, and Glx/Cr showed a downward trend. The variation of each parameter tends to decrease with age. MRS and DTI can detect the brain development of infants aged from 2 months to 2 years old, and provide a basis for predicting brain diseases.

Evaluation of Central Nervous System Tuberculomas by Using Modern Diagnostic Techniques

Aim: To assess central nervous system tuberculomas by using modern MRI techniques such as Diffusion MRI (dMRI), Nuclear magnetic resonance spectroscopy (NMR spectroscopy) and BOLD venographic imaging. Study design: A retrospective study design Study setting: From 5th Feb 2021 to 5th Feb 2022 at the department of Neurology of Ibe-e-Siena Hospital, Multan. Methods: A retrospective study was conducted in the neurology department of Ibe-e-Siena Hospital &amp; Research Institute Multan from 5th February 2021 to 5th February 2022. A total of 100 patients with suspected intracranial tuberculomas were included in the study. Advanced MRI techniques, including Diffusion MRI (dMRI), Nuclear magnetic resonance spectroscopy (NMR spectroscopy) and BOLD venographic imaging and conventional MRI, was performed on the patients. The study was approved by the ethical committee of the hospital, and all the patients provided their written consent for inclusion in the study Results: NMR spectroscopy evaluation showed that N-acetylaspartate /Creatine and N-acetylaspartate /Choline ratios of tuberculomas did not differ significantly from malignant brain lesions (p&gt;0.04). But the malignant brain lesion (2.59) were significantly higher than the Choline/Creatine ratio of tuberculomas(1.29). BOLD venographic imaging evaluation showed no hypointense peripheral ring in malignant brain lesions but showed complete and regular rings in 36 (58.1%) of tuberculomas. Conclusion: Diffusion MRI did not help distinguish tuberculomas from metastasis and gliomas. However, NMR spectroscopy did offer this advantage by evaluating their unique metabolite pattern. BOLD venographic imaging showed the presence of a complete peripheral hypointense ring helping in diagnosing tuberculomas Keywords: Intracranial tuberculomas, Nuclear magnetic resonance spectroscopy, diffusion MRI,

Biomarkers of Choline Metabolism in Women of Reproductive Age in Southern India

ObjectivesInadequate maternal choline intake during pregnancy has been associated with adverse pregnancy and child health outcomes – and has been identified as a potential risk factor for neural tube defects. However, there is limited data on biomarkers of choline metabolism in women of reproductive age (WRA), and few representative population-level data from India. The objective of this analysis was to examine biomarkers of choline metabolism and their correlates in WRA, as part of a population-based biomarker survey in Southern India.MethodsParticipants were WRA (15–40y; n = 980) who were not pregnant or lactating. Free choline, betaine, dimethylglycine, methionine, and trimethylamine N-oxide concentrations were evaluated via liquid chromatography tandem mass spectrometry. Linear regression models were used to examine sociodemographic (e.g., age, parity), dietary (e.g., frequency of animal source food intake), and anthropometric (e.g., body mass index [BMI], waist circumference, waist-hip ratio) correlates of biomarkers of choline metabolism, including betaine concentrations and betaine to choline ratio (B:C).ResultsBetaine concentrations (GM: 44.2 μmol/L [95% CI: 43.4, 45.0]) were 4-fold higher compared to free choline (11.1μmol/L [10.9, 11.2]) levels, with an average B:C of 4.0 [3.9, 4.1]. Increased age (β: −0.01 [SE: 0.002], P < 0.0001), multiparity (multiparous/primiparous vs. nulliparous, P < 0.0001), and increased frequency of animal source food intake (poultry, p = 0.004; red meat, p = 0.01), were associated with lower B:C. Higher BMI (betaine: β: −0.004 [SE: 0.002], p = 0.02; B:C: β: −0.02 [SE: 0.002], P < 0.0001), waist circumference (betaine: −0.002 [0.001], p = 0.02; B:C: −0.01 [0.001], P < 0.0001), and waist-hip ratio (betaine: −0.31 [0.15], p = 0.04; B:C: −1.02 [0.16], P < 0.0001), were also associated with lower betaine concentrations and B:C.ConclusionsIn this population, higher BMI and central adiposity were associated with lower betaine concentrations and B:C. Findings from this biomarker survey will inform prospective research on the role of choline biomarkers in the health and nutritional requirements of WRA.Funding SourcesCenters for Disease Control and Prevention (5U01DD001007), University of South Carolina Disability Research and Dissemination Center; Cornell DNS; NIH T32DK007158 (HMG); NIH 5T32HD087137 (AF).

Temporal profile of serum metabolites and inflammation following closed head injury in rats is associated with HPA axis hyperactivity.

Closed head injury (CHI) causes neurological disability along with systemic alterations that can activate neuro-endocrine response through hypothalamic-pituitary-adrenal (HPA) axis activation. A dysregulated HPA axis function can lead to relocation of energy substrates and alteration in metabolic pathways and inflammation at the systemic level. Assessment of time-dependent changes in serum metabolites and inflammation after both mild and moderate CHI. Along with this, serum corticosterone levels and hypothalamic microglial response were observed. Rats underwent mild and moderate weight-drop injury and their serum and hypothalamus were assessed at acute, sub-acute and chronic timepoints. Changes in serum metabolomics were determined using high resolution NMR spectroscopy. Serum inflammatory cytokine, corticosterone levels and hypothalamic microglia were assessed at all timepoints. Metabolites including lactate, choline and branched chain amino acids were found as the classifiers that helped distinguish between control and injured rats during acute, sub-acute and chronic timepoints. While, increased αglucose: βglucose and TMAO: choline ratios after acute and sub-acute timepoints of mild injury differentiated from moderate injured rats. The injured rats also showed distinct inflammatory profile where IL-1β and TNF-α levels were upregulated in moderate injured rats while IL-10 levels were downregulated in mild injured rats. Furthermore, injury specific alterations in serum metabolic and immunologic profile were found to be associated with hyperactive HPA axis, with consistent increase in serum corticosterone concentration post injury. The hypothalamic microglia showed a characteristic activated de-ramified cellular morphology in both mild and moderate injured rats. The study suggests that HPA axis hyperactivity along with hypothalamic microglial activation led to temporal changes in the systemic metabolism and inflammation. These time dependent changes in the metabolite profile of rats can further strengthen the knowledge of diagnostic markers and help distinguish injury related outcomes after TBI.