Proton Magnetic Resonance Research Articles

Chronic citalopram effects on the brain neurochemical profile and perfusion in a rat model of depression detected by the NMR techniques – spectroscopy and perfusion

BackgroundMajor depressive disorder (MDD) is a mental illness with a high worldwide prevalence and suboptimal pharmacological treatment, which necessitates the development of novel, more efficacious MDD medication. Nuclear magnetic resonance (NMR) can non-invasively provide insight into the neurochemical state of the brain using proton magnetic resonance spectroscopy (1H MRS), and an assessment of regional cerebral blood flow (rCBF) by perfusion imaging. These methods may provide valuable in vivo markers of the pathological processes underlying MDD. MethodsThis study examined the effects of the chronic antidepressant medication, citalopram, in a well-validated MDD model induced by bilateral olfactory bulbectomy (OB) in rats. 1H MRS was utilized to assess key metabolite ratios in the dorsal hippocampus and sensorimotor cortex bilaterally, and arterial spin labelling was employed to estimate rCBF in several additional brain regions. ResultsThe 1H MRS data results suggest lower hippocampal Cho/tCr and lower cortical NAA/tCr levels as a characteristic of the OB phenotype. Spectroscopy revealed lower hippocampal Tau/tCr in citalopram-treated rats, indicating a potentially deleterious effect of the drug. However, the significant OB model–citalopram treatment interaction was observed using 1H MRS in hippocampal mI/tCr, Glx/tCr and Gln/tCr, indicating differential treatment effects in the OB and control groups. The perfusion data revealed higher rCBF in the whole brain, hippocampus and thalamus in the OB rats, while citalopram appeared to normalise it without affecting the control group. ConclusionCollectively, 1H MRS and rCBF approaches demonstrated their capacity to capture an OB-induced phenotype and chronic antidepressant treatment effect in multiple brain regions.

Application of proton magnetic resonance spectroscopy in metabolic alterations of prefrontal white and gray matter in depression adolescents

BACKGROUND Cases of depression among adolescents are gradually increasing. The study of the physiological basis of cognitive function from a biochemical perspective has therefore been garnering increasing attention. Depression has been hypothesized to be associated with the brain biochemical metabolism of the anterior cingulate gyrus, frontal lobe white matter, and the thalamus. AIM To explore the application of proton magnetic resonance spectroscopy (1H-MRS) in the metabolic alterations in the prefrontal white matter (PWM) and gray matter (GM) in adolescents with depression. METHODS 1H-MRS was performed for semi-quantitative analysis of the biochemical metabolites N-acetylaspartate (NAA), choline (Cho) complexes, creatine (Cr), and myo-inositol (mI) in bilateral PWM, anterior cingulate GM, and thalami of 31 adolescent patients with depression (research group) and 35 healthy adolescents (control group), and the NAA/Cr, Cho/Cr, and mI/Cr ratios were calculated. Meanwhile, Hamilton Depression Scale (HAMD) and Wechsler Memory Scale were used to assess the degree of depression and memory function in all adolescents. The correlation of brain metabolite levels with scale scores was also analyzed. RESULTS The research group had markedly higher HAMD-24 scores and lower memory quotient (MQ) compared with the control group (P < 0.05). Adolescents with depression were found to have lower bilateral PWM NAA/Cr and Cho/Cr ratios compared with healthy adolescents (P < 0.05). The mI/Cr ratios were found to be similar in both groups (P > 0.05). The bilateral anterior cingulate GM NAA/Cr, Cho/Cr, and mI/Cr also did not demonstrate marked differences (P > 0.05). No statistical inter-group difference was determined in NAA/Cr of the bilateral thalami (P > 0.05), while bilateral thalamic Cho/Cr and mI/Cr were reduced in teenagers with depression compared with healthy adolescents (P < 0.05). A significant negative correlation was observed between the HAMD-24 scores in adolescents with depression with bilateral PWM NAA/Cr and Cho/Cr and were inversely linked to bilateral thalamic Cho/Cr and mI/Cr (P < 0.05). In adolescents with depressions, MQ positively correlated with right PWH NAA/Cr, left PWH Cho/Cr, and bilateral thalamic Cho/Cr and mI/Cr. CONCLUSION PWM and thalamic metabolic abnormalities might influence teen depression, and the reduction in bilateral PWM NAA/Cr and Cho/Cr could be related to the neuropathology of adolescents with depression suffering from memory impairment. There exists a possibility of dysfunction of nerve cell membrane phospholipids in the thalami of adolescent patients with depression.

EVALUATION OF ANTIOXIDANT ACTIVITY OF NOVEL ORGANOTIN COMPLEXES DERIVED FROM A NEWLY SYNTHESIZED LIGAND AND THEIR STRUCTURAL CHARACTERIZATION

In this work, of New Ligand [(E)-5-hydroxy-4-(3-(4-methoxy phenyl) acryl amido) naphthalene -1- sulfonic acid] (ANS) was prepared by reflexing reaction of 4-amino-5-hydroxy naphthalene sulfonic acid with para methoxy cinnamic acid, this produced and described chemical was employed as ligand to prepare tri and di-organotin complexes by condensation reaction with the salts of organotin chloride (phenyl, butyl, and methyl tin chloride). Specialized methods, including elemental analysis, (tin and proton) magnetic resonance, and infrared spectra, were used to identify the complexes. DPPH (2,2-diphenyl-1-picrylhydrazyl) and CUPRAC (Cupric Reducing Antioxidant Capacity) are both commonly used methods for measuring antioxidant capacity in various samples. Due to the tin moiety, the produced tri and di-tin complexes gave higher percentage inhibition than the ligand in both techniques; also, the triphenyltin complex performed the best when compared to the others. The results of this study are expected to contribute to the understanding of the structure-activity relationship of organotin complexes and their potential as antioxidants, which may have implications for developing novel therapeutic agents with antioxidant properties.

Multimodal MRI and 1H-MRS for Preoperative Stratification of High-Risk Molecular Subtype in Adult-Type Diffuse Gliomas

Isocitrate dehydrogenase (IDH) and O6-methylguanine-DNA methyltransferase (MGMT) genes are critical molecular markers in determining treatment options and predicting the prognosis of adult-type diffuse gliomas. Objectives: this study aimed to investigate whether multimodal MRI enables the differentiation of genotypes in adult-type diffuse gliomas. Methods: a total of 116 adult-type diffuse glioma patients (61 males, 51.5 (37, 62) years old) who underwent multimodal MRI before surgery were retrospectively analysed. Multimodal MRI included conventional MRI, proton magnetic resonance spectroscopy (1H-MRS), and diffusion tensor imaging (DTI). Conventional visual features, N-acetyl-aspartate (NAA)/Creatine (Cr), Choline (Cho)/Cr, Cho/NAA, fractional anisotropy (FA), mean diffusivity (MD), and diffusion histogram parameters were extracted on the whole tumour. Multimodal MRI parameters of IDH-mutant and IDH-wildtype gliomas were compared using the Mann–Whitney U test, Student’s t-test, or Pearson chi-square tests. Logistic regression was used to select the MRI parameters to predict IDH-mutant gliomas. Furthermore, multimodal MRI parameters were selected to establish models for predicting MGMT methylation in the IDH-wildtype gliomas. The performance of models was evaluated by the receiver operating characteristics curve. Results: a total of 56 patients with IDH-mutant gliomas and 60 patients with IDH-wildtype glioblastomas (GBM) (37 with methylated MGMT and 17 with unmethylated MGMT) were diagnosed by 2021 WHO classification criteria. The enhancement degree (OR = 4.298, p < 0.001), necrosis/cyst (OR = 5.381, p = 0.011), NAA/Cr (OR = 0.497, p = 0.037), FA-Skewness (OR = 0.497, p = 0.033), MD-Skewness (OR = 1.849, p = 0.035), FAmean (OR = 1.924, p = 0.049) were independent factors for the multimodal combined prediction model in predicting IDH-mutant gliomas. The combined modal based on conventional MRI, 1H-MRS, DTI parameters, and histogram performed best in predicting IDH-wildtype status (AUC = 0.890). However, only NAA/Cr (OR = 0.17, p = 0.043) and FA (OR = 0.38, p = 0.015) were associated with MGMT methylated in IDH-wildtype GBM. The combination of NAA/Cr and FA-Median is more accurate for predicting MGMT methylation levels than using these elements alone (AUC, 0.847 vs. 0.695/0.684). Conclusions: multimodal MRI based on conventional MRI, 1H-MRS, and DTI can provide compound imaging markers for stratified individual diagnosis of IDH mutant and MGMT promoter methylation in adult-type diffuse gliomas.

TMET-38. BIOCHEMICAL CHARACTERIZATION OF PSAMMOMATOUS MENINGIOMA USING MAGNETIC RESONANCE SPECTROSCOPY

Abstract Psammomatous meningioma is a histologic subtype of meningioma and is presented as a highly calcified intracranial or spinal lesion. Although computed tomography (CT) and short/zero echo-time MRI techniques can detect calcification in tumors, a complete biochemical profile of psammomatous meningiomas is not known. Here, we compare the metabolomic profiles of common meningiomas (WHO grade-I and grade-II) and a psammomatous meningioma using ex vivo proton magnetic resonance spectroscopy (1H MRS). The tumor specimens were collected from meningioma patients undergoing surgery for the resection of the tumor mass. Tumor samples were extracted in 5% perchloric acid, centrifuged, supernatants were vacuum dried and reconstituted in D2O containing 1.0 mM sodium 2,2-dimethyl- 2-silapentane-5-sulfonate-d₆ (DSS-d6, internal standard). Previously, we have identified the following metabolites in grade-I and grade-II meningioma tumors: leucine, isoleucine, valine, lactate, alanine, acetate, glutamate, succinate, glutamine, aspartate, creatine, phosphocreatine, phosphocholine, glycerophosphocholine, myo-inositol, scyllo-inositol, taurine, hypotaurine, glycine, phosphoethanolamine, and glucose. In the current study, psammomatous meningioma also showed the presence of all the above metabolites; however, the levels of these metabolites were lower concentrations compared to the grade-I and grade-II meningiomas, except for lactate. In addition to the above-mentioned metabolites, psammomatous meningioma showed the presence of citrate which was not detected in other meningioma subtypes. Citrate is a major component of bone and the presence of citrate (~614 µM/g, tissue) in psammomatous meningioma could be due to the calcification occurring in these tumors. Surgical pathology report of resected tissue specimen showed clusters and small whorls of meningothelial cells with scattered calcifications, consistent with psammomatous meningioma (WHO grade-I; Ki-67 = 3%). In conclusion, detection of citrate by 1H MRS in meningiomas can be helpful in the differential diagnosis of psammomatous meningiomas.

Preparation of Lipid–Polymer Conjugates by Photoiniferter Polymerization and Application to Cell Surface Modification

ABSTRACTThe growing demand for lipid–polymer conjugates (LPCs) in biomedicine highlights the need for efficient synthesis methods. This study presents a novel Y‐type photoiniferter reagent (Lipid‐PIT) with a diethyldithiocarbamate group and a diacylglycerol group. Lipid‐PIT efficiently initiated the polymerization of vinyl monomers such as oligo(ethylene glycol) methacrylate (OEGMA), N,N‐dimethylacrylamide (DMA), tert‐butyl acrylate (tBA), and n‐butyl acrylate (nBA) under UV irradiation at room temperature, yielding LPCs. Proton NMR confirmed the presence of diethyldithiocarbamate and diacylglycerol moieties at the chain ends. The polymerization kinetics of DMA showed a linear increase in molecular weight (Mn) with time, with a polydispersity (Đ) below 1.50, demonstrating high controllability. Moreover, Lipid‐PIT allows for the creation of block copolymers via secondary chain extension. In vitro assays revealed that LPCs synthesized from OEGMA monomers successfully modified L929 and HeLa cell surfaces and exhibited good biocompatibility. This study offers a rapid, efficient method for LPC synthesis with promising biomedical applications.

Simultaneous assessment of cerebral glucose and oxygen metabolism and perfusion in rats using interleaved deuterium (2H) and oxygen-17 (17O) MRS.

Cerebral glucose and oxygen metabolism and blood perfusion play key roles in neuroenergetics and oxidative phosphorylation to produce adenosine triphosphate (ATP) energy molecules in supporting cellular activity and brain function. Their impairments have been linked to numerous brain disorders. This study aimed to develop an in vivo magnetic resonance spectroscopy (MRS) method capable of simultaneously assessing and quantifying the major cerebral metabolic rates of glucose (CMRGlc) and oxygen (CMRO2) consumption, lactate formation (CMRLac), and tricarboxylic acid (TCA) cycle (VTCA); cerebral blood flow (CBF); and oxygen extraction fraction (OEF) via a single dynamic MRS measurement using an interleaved deuterium (2H) and oxygen-17 (17O) MRS approach. We introduced a single-loop multifrequency radio-frequency (RF) surface coil that can be used to acquire proton (1H) magnetic resonance imaging (MRI) or interleaved low-γ X-nuclei 2H and 17O MRS. By combining this RF coil with a modified MRS pulse sequence, 17O-isotope-labeled oxygen gas inhalation, and intravenous 2H-isotope-labeled glucose administration, we demonstrate for the first time the feasibility of simultaneously and quantitatively measuring six important physiological parameters, CMRGlc, CMRO2, CMRLac, VTCA, CBF, and OEF, in rat brains at 16.4T. The interleaved 2H-17O MRS technique should be readily adapted to image and study cerebral energy metabolism and perfusion in healthy and diseased brains.

Free radical copolymerization kinetics of bio-based dibutyl itaconate and n-butyl acrylate

The free radical copolymerization of dibutyl itaconate (DBI), a monomer derived from renewable resources, and n-butyl acrylate (BA) is investigated to explore the potential of incorporating itaconate monomers into commercial acrylic resins to enhance the sustainability of coating materials. Batch experiments were conducted at 50 °C and 80 °C, varying initial monomer and initiator concentrations as well as monomer compositions, with proton NMR and size exclusion chromatography used to analyze monomer conversion profiles and polymer molar mass distributions (MMDs). The data were analyzed using a kinetic model developed to guide the experimental studies and estimate key kinetic parameters controlling copolymer composition, polymerization rate and polymer MMDs. The use of the more reactive BA as comonomer significantly increases the conversion and molar mass of the resulting copolymer. Furthermore, semi-batch operating conditions similar to current industrial practice can incorporate a substantial fraction of DBI into acrylic copolymer resins, thus enhancing their sustainability profile.

Synthesis and characterization of new organometallic lanthanides metal complexes for photodynamic therapy

New Schiff base ligand: 4-methoxy salicaldhyde-2-2-phenyl-hydrazono acetaldehíyde prepared by facile method. The molecular structures characterized by elemental analysis and proton magnetic resonance spectra (1H-NMR spectra). This spectra at the chemical shifts (3.5–10.39 ppm) confirmed the types and the numbers of protons. The sharp melting point at the range 110–112 °C confirmed purity. New optically active metal (samarium, terbium and gadolinium) complexes of the Schiff base synthesized in a one pot reaction. Vibrational IR spectra confirmed functional groups. Scanning electron microscopy micrographs confirmed that the modified microstructure of the metal complexes differed in morphology than the ligand. Powder X-ray diffraction patterns confirmed good crystalline structure. The optically activity of the solid metal complexes confirmed from electronic absorption spectra. The UV absorbance band at the wavelength range 280–390 nm and the intense phosphorescence bands up to 830 nm enabled application in photo dynamic therapy for apoptosis cancer cells by conversion triplet oxygen in the tissues into reactive singlet oxygen. Low charge transfer energy: 2.59–2.61 eV, high molar extinction coefficients (ε) at the order of magnitude \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:{10}^{6}$$\\end{document} M− 1 cm− 1 and the intense phosphorescence bands reflected good photodynamic activity. The metal complexes are thermally stable.

Fenofibrate modulates cardiac energy metabolism in moderate-severe aortic stenosis: a mechanistic double-blinded randomised controlled MR trial

Abstract Background Aortic stenosis (AS) is associated with impaired cardiac metabolism and high-energy phosphate production which can further exacerbate the progression to HF. Myocardial lipid accumulation and reduced production of high-energy phosphates have important implications for both systolic and diastolic heart function in AS. Peroxisome proliferator-activated receptor alpha (PPAR-alpha agonist, has the potential to optimise cardiac substrate metabolism, thereby, may be effective in improving cardiac dysfunction and functional capacity in AS. Methods In this prospective, randomized, double-blind, placebo-controlled study, patients with moderate-to-severe asymptomatic AS (n=72) were randomly assigned to Fenofibrate 200 mg daily or matching placebo for 6 months in 4:1 fashion. Of the total 72 participants, 59 received Fenofibrate and 13 received placebo. All subjects underwent cardiac magnetic resonance (CMR) and exercise testing at 0 and 6 months, with follow-up data available in 47 patients. The primary end point was change in myocardial triglyceride content (MTG) determined by proton magnetic resonance spectroscopy (1H-MRS). Secondary outcome measures included change in cardiac energetics (PCr/ATP) determined by phosphorus magnetic resonance spectroscopy (31P-MRS), left ventricular strain determined by myocardial tagging and exercise capacity i.e. peak VO2 assessment via cardiopulmonary exercise testing. Results Cardiac energetics (PCr/ATP) showed statistically significant improvement in the Fenofibrate group (0.14 ± 0.48; CI: - 0.03, 0.30; p=0.05) vs placebo group (0.11 ± 0.75; CI -0.42, 0.65; p=0.64). There was also significant reduction in MTG in the Fenofibrate group (mean change -0.40 ± 0.97; 95% CI -0.74, -0.06; p=0.02). MTG content also reduced in the placebo group (mean change -0.41 ± 0.26, 95% CI -1.10, 0.18, p 0.13), but the reduction was not statistically significant. Though no significant changes were seen in the systolic function parameters, there was a significant improvement in diastolic function in the fenofibrate group only (peak diastolic longitudinal strain rate 9.6, 95% CI: 1.13, 18.1; p = 0.02). Peak VO2 did not show any significant improvement in either group. Conclusions Fenofibrate works as a metabolic modulator upregulating fatty acid metabolism in pressure overload AS hearts. Such modulation is associated with an improvement in cardiac energetics and diastolic function in moderate-severe AS.Main results from baseline to 6 monthsBaseline demographic and CMR parameters

Synthesis, characterization, and antioxidant activity of novel diorganotin(IV) complexes derived from Ibuprofen-5-aminosalicylic acid ligand

This study focuses on the preparations of a new ligand prepared by the condensation reaction between two substances ibuprofen and 5-aminosalicylic acid, and complexes of di organotin(IV) salts were prepared using this produced ligand to yield the appropriate complexes. The generated compounds were identified using FTIR and elemental analysis, in addition (tin, proton and carbon) magnetic resonance (119Sn, 1H, and 13C, NMR). Octahedral geometry was suggested for the synthesized complexes based on the observations of the spectra. Two techniques were used to examine the antioxidant activity of the compounds: DPPH and CUPRAC. Because the tin element was present, the resultant complexes exhibited a higher rate of inhibition than the ligand. Di-methyltin-di-IAS also showed a greater effect as antioxidants than the other compounds. KEY WORDS: Diorganotin(IV), Antioxidant activity, Ligand (IAS), DPPH method, CUPRAC method Bull. Chem. Soc. Ethiop. 2025, 39(1), 101-110. DOI: https://dx.doi.org/10.4314/bcse.v39i1.8

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) elicited dose-dependent shifts in the murine urinary metabolome associated with hepatic AHR-mediated differential gene expression.

Epidemiological evidence suggests an association between dioxin and dioxin-like compound (DLC) exposure and human liver disease. The prototypical DLC, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), has been shown to induce the progression of reversible hepatic steatosis to steatohepatitis with periportal fibrosis and biliary hyperplasia in mice. Although the effects of TCDD toxicity are mediated by aryl hydrocarbon receptor (AHR) activation, the underlying mechanisms of TCDD-induced hepatotoxicity are unresolved. In the present study, male C57BL/6NCrl mice were gavaged every 4 days for 28 days with 0.03 - 30 μg/kg TCDD and evaluated for liver histopathology and gene expression as well as complementary 1-dimensional proton magnetic resonance (1D- 1H NMR) urinary metabolic profiling. Urinary trimethylamine (TMA), trimethylamine N-oxide (TMAO), and 1-methylnicotinamide (1MN) levels were altered by TCDD at doses ≤ 3 μg/kg; other urinary metabolites, like glycolate, urocanate, and 3-hydroxyisovalerate, were only altered at doses that induced moderate to severe steatohepatitis. Bulk liver RNA-seq data suggested altered urinary metabolites correlated with hepatic differential gene expression corresponding to specific metabolic pathways. In addition to evaluating whether altered urinary metabolites were liver-dependent, published single-nuclear RNA-seq (snRNA-seq), AHR ChIP-seq, and AHR knockout gene expression datasets provide further support for hepatic cell-type and AHR-regulated dependency, respectively. Overall, TCDD-induced liver effects were preceded by and occurred with changes in urinary metabolite levels due to AHR-mediated changes in hepatic gene expression.

Assessment of Conjugation Pathways in N-Methylporphyrins that Are Fused to Acenaphthylene, Phenanthrene, or Pyrene: Evidence for the Presence of Alternative Aromatic Circuits.

Acenaphtho-, phenanthro-, and pyrenopyrrole esters, readily available from Barton-Zard reactions of ethyl isocyanoacetate with nitroarenes, were reacted with methyl iodide and KOH in DMSO to give N-methylpyrroles and subsequent cleavage of the ester moieties was accomplished with KOH in ethylene glycol at 200 °C. Condensation with two equiv of an acetoxymethylpyrrole in refluxing acetic acid-2-propanol afforded a series of annulated tripyrranes. Cleavage of the terminal tert-butyl ester groups with trifluoroacetic acid, followed by condensation with a diformylpyrrole and oxidation with FeCl3, gave N-methyl acenaphtho-, phenanthro-, and pyrenoporphyrins. The N-methyl substituent effectively freezes the tautomeric equilibria to maximize interactions between the porphyrin nucleus and the fused aromatic substructures. Analysis of the proton NMR spectra provides evidence of the presence of extended aromatic circuits within these structures. Anisotropy of induced ring current (AICD) plots clearly shows the presence of 30π electron pathways in phenanthro- and pyrenoporphyrins that run around the exterior of the benzenoid fragments. These results demonstrate that N-alkylation can be used to relocate aromatic pathways in porphyrinoid systems.

Synthesis and characterization of 7-diethylamino-4-Chloromethyl coumarin: Spectroscopic analysis, molecular docking, and anticancer activity on large intestine carcinoma cells

Cancer, characterized by uncontrolled cell growth and metastasis, poses a significant global health burden, ranking as a leading cause of mortality worldwide. Colorectal cancer (CRC) specifically accounts for a substantial portion of cancer cases, with increasing incidence projected over the coming decades. While conventional treatments exist, they often entail adverse effects and limited efficacy, driving interest in natural remedies like coumarin derivatives due to their diverse biological activities and perceived safety profile. This study focuses on the synthesis and characterization of a novel compound, 7-diethylamino-4-chloromethyl coumarin (referred to as 7D4C), derived from coumarin. Structural elucidation employed Fourier transform infrared spectroscopy (FT-IR), proton and carbon-13 nuclear magnetic resonance spectroscopy (1H and 13C NMR), and mass spectrometry (MALDI-TOF-MS). Molecular docking studies were conducted to explore potential biological interactions. Furthermore, the anti-cancer potential of 7D4C was assessed using human epithelial adenocarcinom (LoVo) and healthy fibroblast (CCD-18Co) cell lines. Viability analysis, comet assay for DNA damage, and evaluation of cancer biomarkers including apoptosis, intracellular reactive oxygen species (iROS) levels, mitochondrial membrane potential (MMP), intracellular glutathione (GSH) concentration, and intracellular calcium (iCa2+) levels were performed. The synthesis of 7D4C was successfully completed, and its structure was confirmed. Molecular docking results indicate that 7D4C exhibits strong binding affinity to the p53 protein, highlighting its potential as a novel modulator of p53 activity. Subsequent investigations revealed that the synthesized compound induced apoptosis in cancer cells by reducing MMP and triggering DNA damage through the production of iROS. The promising anti-cancer activity of 7D4C in the LoVo cell line highlights its importance in coumarin-based therapies. Introducing 7D4C could significantly enhance future research in this area, leveraging insights from in vitro coumarin studies.

Neural net analysis of NMR spectra from strongly-coupled spin systems

Extracting parameters such as chemical shifts and coupling constants from proton NMR spectra is often a first step in using spectra for compound identification and structure determination. This can become challenging when scalar couplings between protons are comparable in size to chemical shift differences (strongly coupled), as is often the case with low-field (bench top) spectrometers. Here we explore the potential utility of AI methods, in particular neural networks, for extracting parameters from low-field spectra. Rather than seeking large experimental sets of spectra for training a network, we chose quantum mechanical simulation of sets, something that is possible with modern software packages and computer resources. We show that application of a network trained on 2-D J-resolved spectra and applied to a spectrum of iduronic acid, shows some promise, but also meets with some obstacles. We suggest that these may be overcome with improved pulse sequences and more extensive simulations.

Diffuse white matter pathology in multiple sclerosis during treatment with dimethyl fumarate-An observational study of changes in normal-appearing white matter using proton magnetic resonance spectroscopy.

Multiple sclerosis (MS) is an inflammatory demyelinating disease with neurodegenerative features causing risk for neurologic irreversible disability over time. Examination of normal-appearing white matter (NAWM) changes in MS by proton magnetic resonance spectroscopy (1H-MRS), may detect diffuse white matter pathology that is associated with neurodegeneration. In this observational study of in total twenty-six patients with MS, starting treatment with dimethyl fumarate (DMF), we measured the absolute concentration of metabolites in periventricular NAWM using 1H-MRS at baseline and after one and three years of treatment. Metabolite concentrations were analyzed both cross-sectionally, in relation to 10 controls and longitudinally in relation to disease activity. Patients with MS had higher concentrations of myo-inositol (mIns) in NAWM at baseline compared with controls (mean 5.98 ± 1.37 (SD) and 4.32 ± 1.16 (SD), p<0.01, independent samples t-test). The disease duration was inversely correlated with concentrations of total N-acetylaspartate and N-acetylaspartylglutamate (tNA) (r = -0.62, p<0.01) in NAWM as well as positively to the ratio of mIns and tNA (r = 0.51, p = 0.03). Metabolite concentrations during one-year (n = 19) and three-years (n = 11) follow-up were generally stable. The dropouts were caused by treatment switch after one year, mainly due to new MRI activity. Cross-sectional analyses showed that there was an inverse correlation between concentrations of tNA and mIns at both baseline and at 1 and 3-years follow-up (r = -0.44 to -0.65, p = 0.04 to 0.004). Metabolite concentrations were stable during 1-year follow-up independently of disease activity. Higher concentrations of the astrogliosis marker mIns in MS compared to controls, the inverse relation between MS disease duration and the neuroaxonal integrity marker tNA, as well as the consistent inverse relation between these two metabolites during follow-up, showed that non-lesional white matter pathology is present in this cohort of MS patients in early disease stages. However, metabolite concentrations during follow-up were generally stable and did not reflect differences in disease activity among patients.

Serum metabolite and metal ions profiles for breast cancer screening

Enhancing early-stage breast cancer detection requires integrating additional screening methods with current diagnostic imaging. Omics screening, using easily collectible serum samples, could serve as an initial step. Alongside biomarker identification capabilities, omics analysis allows for a comprehensive analysis of prevalent histological types—DCIS and IDC. Employing metabolomics, metallomics, and machine learning, could yield accurate screening models with valuable insights into organism responses. Serum samples of confirmed breast cancer patients were utilized to analyze metabolite and metal ion profiles, using two distinct analysis methods, proton NMR for metabolomics and ICP-OES for metallomics. The resulting responses were then subjected to discriminant analysis, progression biomarker exploration, examination of correlations between patients’ metabolites and metal ions, and the impact of age and menopause status. Measured NMR spectra and metabolite relative integrals were used to achieve statistically significant discrimination through MVA between breast cancer and control groups. The analysis identified 24 metabolites and 4 metal ions crucial for discrimination. Furthermore, four metabolites were associated with disease progression. Additionally, there were important correlations and relationships between metabolite relative integrals, metal ion concentrations, and age/menopausal status subgroups. Quantified relative integrals allowed for discrimination between studied subgroups, validated with a holdout set. Feature importance and statistical analysis for metabolomics and metallomics extracted a set of common entities which in combination provides valuable insights into ongoing molecular disturbances and disease progression.

Regional variations in cingulate cortex glutamate levels: A magnetic resonance spectroscopy study at 3T.

Regional variations in glutamate levels across the cingulate cortex, decreasing rostral-to-caudal, have been observed previously in healthy volunteers using proton magnetic resonance spectroscopy (1H-MRS) at 7T. This study sought to explore cingulate cortex glutamate trends further by investigating whether a similar gradient could be detected at 3T, the effect of sex, as well as whether individual variations gave rise to more than one regional glutamate pattern. 1H-MRS at 3T (Phillips Elition, semi-Localization by Adiabatic Selective Refocusing, TE/TR = 32/5000) was acquired in four cingulate regions: the anterior, mid-anterior, mid-posterior, and posterior cortices, in 50 healthy participants (26F) scanned at a fixed time of day and with controlled food intake. K-means clustering was used to characterize the presence of distinct regional patterns, which were then compared between sex and clusters. In addition, cortical thickness was compared between clusters, and in relation to glutamate. Aligned with 7T findings, we demonstrated that average glutamate levels decreased rostral-to-caudal in the healthy cingulate cortex. No effect of sex was found, suggesting similar resting glutamate levels in both sexes. Interestingly, the majority of participants were characterized by glutamate levels that did not significantly change across the cingulate (65%). Different regional patterns in cortical thickness between clusters offer further evidence into these distinct glutamate variations and suggest both a neuroanatomical and functional role may lead to these findings. This study provides a much needed foundation for further research to determine the implications of neurotransmission patterns in health and disease.

THE UTILITY OF MULTIPARAMETRIC MRI IN REDUCING DIAGNOSTIC UNCERTAINTY FOR PRIMARY CNS LYMPHOMA

Abstract AIMS A key limitation in the early treatment initiation in primary central nervous system lymphoma (PCNSL) is the diagnostic delay caused by lack of recognition of a lesion as a possible lymphoma, steroid initiation, and lesion involution, often resulting in inconclusive biopsy. We highlight the importance of multiparametric MRI (MPMRI), which incorporates diffusion weighted imaging (DWI), dynamic susceptibility contrast-enhanced perfusion weighted imaging (DSC-PWI) and proton magnetic resonance spectroscopy (1H-MRS) in addition to standard MRI sequences in resolving diagnostic uncertainty for PCNSL. METHOD We present a consecutive series of 10 patients at our centre with histology-proven PCNSL (specifically, diffuse large B-cell lymphoma of the CNS) who underwent multiparametric MRI. We retrospectively analyse the qualitative and semi-quantitative parameters and assess their radiological concordance for this diagnosis. RESULTS We note overall low apparent diffusion coefficient on DWI (mean ADCmin of 0.74), high percentage signal recovery on perfusion weighted imaging (mean 170%), a high choline-creatine ratio and a high-grade lipid peak on MRS giving a “twin-tower” appearance. Nine of ten patients had MRMRI findings concordant for PCNSL, defined as at least 3 of 4 parameters being consistent for PCNSL. CONCLUSION We propose that concordance between these imaging multiparametric modalities could be used as a radiological predictor of PCNSL, reducing diagnostic delays, providing a more accurate biopsy target, and resulting in quicker treatment initiation.

Reduced GABA Levels in the ACC of Actively Drinking High Risk Individuals Compared to Recently Detoxified Alcohol-Dependent Patients.

Acute gamma-aminobutyric acid (GABAergic) effects of alcohol consumption are well-known, whereas prior research has yielded inconsistent findings regarding on adaptations of the GABAergic neurotransmitter system to chronic alcohol use. Previous studies indicate either elevated or reduced GABA levels in cortical regions such as the anterior cingulate cortex (ACC) in persons with alcohol use disorder (AUD). We tested the hypothesis that active alcohol consumption compared to abstinence contributes to GABA levels as observed in prior research on chronic alcohol use. We investigated GABA levels in the ACC of 31 healthy controls (low risk, LR), 38 high risk individuals providing an active drinking pattern (high risk, HR) and 27 recently detoxified alcohol-dependent (AD) subjects via proton magnetic resonance spectroscopy (1H-MRS). GABA levels in the ACC were significantly lower in HR compared with AD, but did neither differ between LR and AD nor between LR and HR. Also, we observed a quadratic effect indicating a distribution of GABA levels in the ACC as follows: LR > HR < AD. GABA levels were not associated with abstinence duration in AD. This study suggests that the GABAergic neurotransmitter system is blunted in AUD. More precisely GABA levels in the ACC seem to be higher in recently detoxified AD patients than in individuals at high risk which might suggest that GABA levels may increase after abstinence. No correlation was found between GABA levels and abstinence duration. Longitudinal studies are required to investigate alterations in the GABAergic system throughout the development and maintenance of AUD. No: NCT02094196. Registered 20 March 2014, https://clinicaltrials.gov/study/NCT02094196.