Quantitative Magnetic Resonance Spectroscopy Research Articles

Spatiospectral image processing workflow considerations for advanced MR spectroscopy of the brain.

Magnetic resonance spectroscopy (MRS) is one of the few non-invasive imaging modalities capable of making neurochemical and metabolic measurements in vivo. Traditionally, the clinical utility of MRS has been narrow. The most common use has been the "single-voxel spectroscopy" variant to discern the presence of a lactate peak in the spectra in one location in the brain, typically to evaluate for ischemia in neonates. Thus, the reduction of rich spectral data to a binary variable has not classically necessitated much signal processing. However, scanners have become more powerful and MRS sequences more advanced, increasing data complexity and adding 2 to 3 spatial dimensions in addition to the spectral one. The result is a spatially- and spectrally-variant MRS image ripe for image processing innovation. Despite this potential, the logistics for robustly accessing and manipulating MRS data across different scanners, data formats, and software standards remain unclear. Thus, as research into MRS advances, there is a clear need to better characterize its image processing considerations to facilitate innovation from scientists and engineers. Building on established neuroimaging standards, we describe a framework for manipulating these images that generalizes to the voxel, spectral, and metabolite level across space and multiple imaging sites while integrating with LCModel, a widely used quantitative MRS peak-fitting platform. In doing so, we provide examples to demonstrate the advantages of such a workflow in relation to recent publications and with new data. Overall, we hope our characterizations will lower the barrier of entry to MRS processing for neuroimaging researchers.

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

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

Extraction Optimization and Qualitative/Quantitative Determination of Bioactive Abietane-Type Diterpenes from Three Salvia Species (Common Sage, Greek Sage and Rosemary) by 1H-qNMR.

The objective of this study was the optimization of the extraction process and the qualitative and quantitative determination of the bioactive metabolites: 12-O-methylcarnosic acid (12MCA), carnosic acid (CA), carnosol (CS), 7-O-methyl-epi-rosmanol (7MER) and rosmanol (RO) in infusions, decoctions, turbulent flow extracts, tinctures and oleolites from three Salvia species: Salvia officinalis L. (common sage, SO), Salvia fruticosa Mill. (Greek sage, SF) and Salvia rosmarinus Spenn (syn Rosmarinus officinalis L.) (rosemary, SR), using Quantitative Proton Nuclear Magnetic Resonance Spectroscopy (1H-qNMR). Regarding the aqueous extracts, decoctions appeared to be richer sources of the studied metabolites than infusions among the three plants. For SR, the turbulent flow extraction under heating was the most efficient one. The optimum time for the preparation of decoctions was found to be 5 min for SF and SO and 15 min for SR. It is noteworthy that SR tinctures were not stable in time due to decomposition of the abietane-type diterpenes CA and CS because of the polar solvent used for their preparation. Contrary to this finding, the oleolites of SR appeared to be very stable. Olive oil as a solvent for extraction was very protective for the contained abietane-type diterpenes. A preliminary stability study on the effect of the storage time of the SF on the abietane-type diterpenes content showed that the total quantity of abietanes decreased by 16.51% and 40.79% after 12 and 36 months, respectively. The results of this investigation also demonstrated that 1H-qNMR is very useful for the analysis of sensitive metabolites, like abietane-type diterpenes, that can be influenced by solvents used in chromatographic analysis.

EMERGING MR IMAGING AND SPECTROSCOPY APPLICATIONS FOR AGING RESEARCH IN MODEL ORGANISMS

Abstract Advances in quantitative magnetic resonance imaging and spectroscopy (MRI/MRS) methodology have enabled probing tissue microstructure and function with exquisite specificity and sensitivity in human and model systems. Using this technology to examine changes in tissue microstructure and function in aging or pathology has the potential to provide a window into the underlying age-related diseases’ mechanisms, and to nominate MR biomarkers for longitudinal assessment and intervention. Water molecules within biological tissues undergo interactions with their environment through nuclear relaxation, magnetization transfer, chemical exchange, and diffusion. These processes are sensitive to underlying local tissue properties such as density, microstructure, temperature, acidity, composition, and geometry. Through use of combinations of magnetic fields and radiofrequency pulse formalisms, MRI/MRS provides unique sensitivity and specificity to probe these mechanisms in all biological tissues. Advances in acquisition strategies, hardware designs, computational analyses, and signal modeling have positioned MRI/MRS as powerful emerging noninvasive modalities to studying biological tissue to differentiate normal from abnormal cell-level processes. These techniques are based on multicomponent relaxometry or diffusion, magnetization transfer, high-dimensional imaging or spectroscopy, susceptibility imaging, cerebral functioning, etc. However, their integration in clinical trials and investigations is still limited. This session will provide an overview about these emerging MRI/MRS techniques, their value and application in studying aging. The overarching goal is to generate further interest within the scientific community, disseminate and integrate these mature and unique noninvasive approaches in research settings and routine clinical protocols to advance our understanding of aging processes.

Bone Marrow Adiposity Alterations in Type 2 Diabetes Are Sex-Specific and Associated with Serum Lipid Levels.

Type 2 diabetes (T2D) has negative effects on skeletal health. A proposed mechanism of diabetic bone disease connects hyperlipidemia to increased bone marrow adiposity and decreased bone quality. Previous research on Type 1 diabetes reported positive associations between serum lipid levels and marrow adiposity, but no data exist for T2D. In addition, marrow adiposity is sex-dependent in healthy populations, but sex has not been addressed adequately in previous reports of marrow adiposity in T2D. The purpose of this study was to quantify associations of marrow adiposity and composition with T2D status, serum lipid levels, and sex. T2D patients and normoglycemic controls (n = 39/37) were included. Single-voxel magnetic resonance spectroscopy (MRS) was performed at the spine and tibia. Quantitative MRS outcomes of marrow adiposity and composition were calculated. Linear regression models were used to compare MRS outcomes among groups and to evaluate associations of MRS outcomes with serum lipid levels. All analyses were performed on sex-stratified subgroups. Total, unsaturated, and saturated fat content at the spine were lower in T2D participants compared to controls in age-adjusted models; these differences were significant in men but not in women. In our study cohort, total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were lower in T2D participants compared to controls. Adjustment for LDL, HDL, and statin use attenuated the association of T2D status with unsaturated fat but not saturated fat in men. Further analysis confirmed significant associations between serum lipid levels and MRS outcomes. Specifically, we found a positive association between LDL cholesterol and total marrow fat in the male T2D group and a negative association between HDL and total marrow fat in the female T2D group. In conclusion, our results suggest that marrow adiposity and composition are associated with lipid levels as well as T2D status, and these relationships are sex-specific. © 2023 American Society for Bone and Mineral Research (ASBMR).

Quantitative GABA magnetic resonance spectroscopy as a measure of motor learning function in the motor cortex after subarachnoid hemorrhage.

The neural mechanisms underlying gross and fine motor dysfunction after subarachnoid hemorrhage (SAH) remain unknown. The γ-aminobutyric acid (GABA) deficit hypothesis proposes that reduced neuronal GABA concentrations and the subsequent lack of GABA-mediated inhibition cause motor impairment after SAH. This study aimed to explore the correlation between GABA levels and a behavioral measure of motor performance in patients with SAH. Motor cortical GABA levels were assessed in 40 patients with SAH and 10 age-matched healthy controls using proton magnetic resonance spectroscopy. The GABA and N-acetylasparate (NAA) ratio was measured in the normal gray matter within the primary motor cortex. The relationship between GABA concentration and hand-motor performance was also evaluated. Results showed significantly lower GABA levels in patients with SAH's left motor cortex than in controls (GABA/NAA ratio: 0.282 ± 0.085 vs. 0.341 ± 0.031, respectively; p = 0.041). Reaction times (RTs), a behavioral measure of motor performance potentially dependent on GABAergic synaptic transmission, were significantly longer in patients than in controls (936.8 ± 303.8 vs. 440.2 ± 67.3 ms, respectively; p < 0.001). Moreover, motor cortical GABA levels and RTs exhibited a significant positive linear correlation among patients (r = 0.572, rs = 0.327, p = 0.0001). Therefore, a decrease in GABA levels in the primary motor cortex after SAH may lead to impaired cortical inhibition of neuronal function and indicates that GABA-mediated synaptic transmission in the motor cortex is critical for RT.

Establishment of the Flory-Fox Equation for Polymethyl Methacrylate (PMMA) Using Differential Scanning Calorimetry (DSC) and Determination of Tacticity Using Quantitative Proton Nuclear Magnetic Resonance Spectroscopy (qHNMR)

Establishment of the Flory-Fox Equation for Polymethyl Methacrylate (PMMA) Using Differential Scanning Calorimetry (DSC) and Determination of Tacticity Using Quantitative Proton Nuclear Magnetic Resonance Spectroscopy (qHNMR)

Quantitative magnetic resonance spectroscopy and imaging analysis of the lipid content in the psoas major and its association with intervertebral disc degeneration: a cross-sectional study

Aim: It is shown that the diminished function of the psoas major is mainly associated with increased lipid content; nonetheless, whether the fat content of the psoas major is associated with intervertebral disc degeneration (IVDD) is still under study. It is hypothesized that IVDD is correlated with the lipid content of the psoas major and that IVDD can be comprehensively investigated using quantitative magnetic resonance imaging (MRI). Consequently, this study aimed to analyse the association between the psoas major extramyocellular lipid (EMCL) and intramyocellular lipid (IMCL) content and disc degeneration quantified using MRI T2 mapping in patients with chronic low back pain (CLBP). Methods: In this study, 20 men and 23 women (mean age, 63.1 years ± 2.6 years) underwent magnetic resonance spectroscopy (MRS). The psoas major IMCL and EMCL content of patients was analysed. T2 values of the anterior annulus fibrosus (AF), nucleus pulposus (NP), and posterior AF were evaluated using MRI T2 mapping. Multiple linear regression analysis was used to determine the possible correlations of the psoas major EMCL and IMCL content with the T2 values of the anterior AF, NP, and posterior AF. Results: The EMCL content and T2 values of the anterior AF were significantly and negatively correlated [standardised partial regression coefficient (β) = −0.60, P &lt; 0.01]. There were no significant correlations between the EMCL content and T2 values of the NP (β = −0.16, P = 0.30) or posterior AF (β = −0.14, P = 0.49) or between the IMCL content and T2 values of the anterior AF (β = −0.04, P = 0.82), NP (β = 0.05, P = 0.73), or posterior AF (β = −0.11, P = 0.58). Conclusions: The EMCL content and T2 values of the anterior AF were correlated. Conversely, the IMCL content and T2 values were not correlated.

Quantitative magnetic resonance spectroscopy of depression: The value of short-term metabolite changes in predicting treatment response.

Although various prediction models of the antidepressant response have been established, the results have not been effectively applied to heterogeneous depression populations, which has seriously limited their clinical value. This study tried to build a more specific and stable model to predict treatment response in depression based on short-term changes in hippocampal metabolites. Seventy-four major depressive disorder (MDD) patients and 20 healthy controls in the test set were prospectively collected and retrospectively analyzed. Subjects underwent magnetic resonance spectroscopy (MRS) once a week during 6 weeks of treatment. Hippocampal regions of interest (ROIs) were extracted by using a voxel iteration scheme combined with standard brain templates. The short-term differences in hippocampal metabolites between and within groups were screened. Then, the association between hippocampal metabolite changes and clinical response was analyzed, and a prediction model based on logistic regression was constructed. In addition, a validation set (n = 60) was collected from another medical center to validate the predictive abilities. After 2-3 weeks of antidepressant treatment, the differences in indicators (tCho wee0-2, tCho wee0-3 and NAA week0-3) were successfully screened. Then, the predictive abilities of these three indicators were revealed in the logistic regression model, and the optimal prediction effect was found in d(tCho) week0-3-d(NAA) week0-3 (AUC = 0.841, 95%CI = 0.736-0.946). In addition, their predictive abilities were further confirmed with the validation set. The small sample size and the need for multiple follow-ups limited the statistical ability to detect other findings. The predictive model in this study presented accurate prediction and strong verification effects, which may provide early guidance for adjusting the treatment regimens of depression and serve as a checkpoint at which the eventual treatment outcome can be predicted.

Abstract 6353: Metabolic changes in the spleen and pancreas induced by PDAC xenografts with or without glutamine transporter downregulation

Abstract Introduction: Our ongoing studies are focused on characterizing metabolic changes induced in the organs of mice with cachexia-inducing Pa04C human pancreatic cancer xenografts. Because pancreatic cancer cells are glutamine dependent [1], we downregulated the glutamine transporter SLC1A5 in Pa04C cells to determine if metabolic changes induced in the spleen and pancreas by Pa04C tumors were normalized when SLC1A5 was downregulated in these tumors. Metabolic patterns were characterized using high-resolution quantitative 1H magnetic resonance spectroscopy (MRS) of spleen and pancreas tissue obtained from normal mice and mice with Pa04C tumors and mice with Pa04C tumors with SLC1A5 downregulated. Method: Patient derived cachexia-inducing Pa04C pancreatic cancer cells were lentivirally transduced to express shRNA to stably downregulate SLC1A5. Mice were euthanized once tumors were ~500 mm3, the spleen and pancreas were excised and snap frozen. Snap frozen spleen (normal n= 5, Pa04C n= 11, Pa04C_SLC1A5 n= 10) and pancreas (normal n= 4, Pa04C n= 16, Pa04C_SLC1A5 n= 10) tissue samples were pulverized for dual phase extraction. The aqueous phase was used for 1H MRS analysis. Topspin 3.5 software was used for data processing and analyses. Results and Discussion: Significant downregulation of SLC1A5 mRNA and protein was confirmed in Pa04C_SLC1A5 cells and tumors. SLC1A5 downregulation resulted in significant growth delay and attenuation of weight loss. A comparison of normal mice vs empty vector/wild type tumor (EV/WT) bearing mice identified significant changes in succinate, aspartate and fumarate in the spleen, lactate, acetate, pyruvate, methionine, asparagine, creatine, choline phosphocholine, uracil, histidine and phenylalanine in the pancreas, with leucine, isoleucine, valine, alanine, glutamate, glutamine, glutathione, glycerophosphocholine, glycine, glucose and tyrosine commonly altered in the spleen and pancreas. A comparison of normal vs Pa04C_ SLC1A5 tumor bearing mice identified similar metabolic changes in the spleen and pancreas but these were reduced. Fumarate did not change in the spleen, and of the metabolic changes common to spleen and pancreas, glutamine did not change when tumor SLC1A5 was downregulated. Metabolite changes induced only in the pancreas were also similar to normal vs EV/WT with the exception of a change in glutamine with SLC1A5 downregulation and no change in lactate. Our data highlight the profound metabolic changes in spleen and pancreas metabolism that occur with growth of a cachexia-inducing pancreatic cancer xenograft, and the impact on these metabolic patterns as a result of downregulating the glutamine transporter in these cancer cells. The metabolic patterns identified in the spleen and pancreas may provide novel targets to reduce the morbidity from cachexia. Reference: 1. Son J et al, Nature. 2013;496(7443):101-5. Citation Format: Raj Kumar Sharma, Santosh Kumar Bharti, Balaji Krishnamachary, Yelena Mironchik, Paul Winnard Jr., Marie-France Penet, Zaver M. Bhujwalla. Metabolic changes in the spleen and pancreas induced by PDAC xenografts with or without glutamine transporter downregulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6353.

Distinguishing Tumor Admixed in a Radiation Necrosis (RN) Background: 1H and 2H MR With a Novel Mouse Brain-Tumor/RN Model.

PurposeDistinguishing radiation necrosis (RN) from recurrent tumor remains a vexing clinical problem with important health-care consequences for neuro-oncology patients. Here, mouse models of pure tumor, pure RN, and admixed RN/tumor are employed to evaluate hydrogen (1H) and deuterium (2H) magnetic resonance methods for distinguishing RN vs. tumor. Furthermore, proof-of-principle, range-finding deuterium (2H) metabolic magnetic resonance is employed to assess glycolytic signatures distinguishing RN vs. tumor.Materials and MethodsA pipeline of common quantitative 1H MRI contrasts, including an improved magnetization transfer ratio (MTR) sequence, and 2H magnetic resonance spectroscopy (MRS) following administration of 2H-labeled glucose, was applied to C57BL/6 mouse models of the following: (i) late time-to-onset RN, occurring 4–5 weeks post focal 50-Gy (50% isodose) Gamma Knife irradiation to the left cerebral hemisphere, (ii) glioblastoma, growing ~18–24 days post implantation of 50,000 mouse GL261 tumor cells into the left cerebral hemisphere, and (iii) mixed model, with GL261 tumor growing within a region of radiation necrosis (1H MRI only). Control C57BL/6 mice were also examined by 2H metabolic magnetic resonance.ResultsDifferences in quantitative 1H MRI parametric values of R1, R2, ADC, and MTR comparing pure tumor vs. pure RN were all highly statistically significant. Differences in these parameter values and DCEAUC for tumor vs. RN in the mixed model (tumor growing in an RN background) are also all significant, demonstrating that these contrasts—in particular, MTR—can effectively distinguish tumor vs. RN. Additionally, quantitative 2H MRS showed a highly statistically significant dominance of aerobic glycolysis (glucose ➔ lactate; fermentation, Warburg effect) in the tumor vs. oxidative respiration (glucose ➔ TCA cycle) in the RN and control brain.ConclusionsThese findings, employing a pipeline of quantitative 1H MRI contrasts and 2H MRS following administration of 2H-labeled glucose, suggest a pathway for substantially improving the discrimination of tumor vs. RN in the clinic.

Utility of magnetic resonance spectroscopy and diffusion-weighted imaging for detecting changes in the femoral head in divers with hip pain at risk for dysbaric osteonecrosis.

Ischemia before the development of dysbaric osteonecrosis (DON) in femoral heads has never been investigated. We assessed whether quantitative magnetic resonance spectroscopy (MRS) and diffusion weighted imaging (DWI) could detect dysbaric changes in divers with hip pain. This IRB-approved exploratory study recruited 17 divers [9 with hip pain (Group 1); 8 asymptomatic (Group 2)] with normal findings on radiographs and conventional magnetic resonance imaging scans were age-, gender- and body-mass-index matched to 17 non-divers as controls (Group 1C, 2C). Apparent diffusion coefficients (ADCs) and MRS spectra were obtained from regions/voxels of interest on the femoral heads of all subjects. LCModel was used to determine water content, lipid composition, and the unsaturation index in bone marrow. Mann-Whitney non-parametric test was used to compare results of quantitative MRS and ADCs of ipsilateral femoral heads between divers and controls. MRS of the ipsilateral femoral heads revealed higher water (peak: 4.7 ppm) content, lower total lipid fraction (TLF), and higher unsaturation index (UI) of lipids in Group 1 than in Group 2 (water: P=0.040; UI: P=0.022) and Group 1C (water: P=0.027; TLF: P=0.039; UI: P=0.009). In contrast, femoral head ADCs were comparable between divers and controls. Five out of nine symptomatic divers were contacted for follow-up MRS and DWI studies, and the mean difference in water content in the femoral heads of patients with osteonecrosis was also higher than that in patients with symptom relief (osteonecrosis: 0.077±0.130 vs. symptom relief: 0.003±0.010). Dysbaric change in the femoral heads of divers with hip pain can be detected using quantitative MRS, which reveals increases in water content and UI of lipids, and a decrease in TLF.

Compositional Analysis of Mixtures of Oleate Esters of Short Chain Alcohols (C1-C4) by Quantitative Proton Nuclear Magnetic Resonance Spectroscopy (qPNMR)

Compositional Analysis of Mixtures of Oleate Esters of Short Chain Alcohols (C1-C4) by Quantitative Proton Nuclear Magnetic Resonance Spectroscopy (qPNMR)

PSV-B-19 Dietary choline supplementation increases transmethylation through the one-carbon cycle in overweight cats

Abstract The objective of this study was to determine the dose-response relationship between dietary choline intake and one-carbon cycle activity in overweight cats at maintenance energy requirements. This study was approved by the University of Guelph Animal Care Committee (AUP#4118). Overweight (body condition score:≥6/9) adult male neutered cats (n = 14) received each of five choline chloride doses individually for three weeks in a 5x5 latin square design. Doses were based on body weight (BW) and the daily recommended allowance (RA) for choline for adult cats (63 mg/kg BW0.67). Doses were: 2xRA (126 mg/kg BW0.67), 4xRA (252 mg/kg BW0.67), 6xRA (378 mg/kg BW0.67), 8xRA (504 mg/kg BW0.67), and control (no additional choline). Choline was administered onto the commercial extruded cat food (3620 mg choline/kg diet), given once a day at maintenance energy requirements (130 kcal/kg BW0.4). Fasted serum samples were analyzed for metabolomics through quantitative nuclear magnetic resonance (NMR) spectroscopy and direct infusion mass spectrometry (DI-MS) at the end of each period. Data was analyzed using proc GLIMMIX in SAS, with group and period as the random effects, and dose as the fixed effect. Statistical significance was considered at P &amp;lt; 0.05. Tukey’s post-hoc test was performed to assess multiple comparisons. Choline at 6x and 8x RA appears to increase transmethylation through the one-carbon cycle, as suggested by increased serum betaine, dimethylglycine (DMG) and methionine (P &amp;lt; 0.05). Carnitine, methylated by s-adenosylmethionine (SAM), increased (P &amp;lt; 0.05). Serine and threonine, precursors for the biosynthesis of homocysteine, appear to have been spared (P &amp;lt; 0.05). Supplemental dietary choline (6x and 8xRA) may be beneficial for overweight cats, as it may increase activity of the one-carbon cycle and methyl status; which are necessary for hepatic function. To better understand the impact of choline on methylation reactions, the quantification of specific proteins, gene expression and/or conversion rates is required.

Investigation of patients with temporal lobe epilepsy using quantitative electroencephalography and magnetic resonance spectroscopy

Investigation of patients with temporal lobe epilepsy using quantitative electroencephalography and magnetic resonance spectroscopy

Identifying Biological Signatures of N-Acetylcysteine for Non-Suicidal Self-Injury in Adolescents and Young Adults.

The prevalence of non-suicidal self-injury (NSSI) is high in adolescents and young adults. However, there is a paucity of evidence-based treatments to address this clinical problem. An open-label, pilot study in the target population showed that treatment with oral N-acetylcysteine (NAC), a widely available dietary supplement, was associated with reduction in NSSI frequency. In preparation for a biologically informed design of an efficacy trial, a critical preliminary step is to clarify NAC’s biological signatures, or measures of the mechanisms underlying its clinical effects. Toward that end, we propose a 2-stage project to investigate NAC’s biological signatures (changes in glutathione (GSH) and/or glutamate (Glu)) in women with NSSI. The first stage; a double-blind randomized placebo-controlled study will focus on identifying the optimal dose to achieve meaningful change in GSH and Glu during short-term (4 weeks) NAC treatment in 36 women aged 16–24 years with NSSI. Go/No-go criteria to determine if the study will progress to the second stage include pre-specified changes in brain and blood measures of GSH. Changes in the brain GSH are measured through magnetic resonance spectroscopy (MRS). The dose for the stage 2 will be selected based on the biological changes and the tolerability observed in the stage 1. The stage 2 will seek to replicate the biological signature findings in an 8-week trial in a new patient cohort, and examine the relationships among biological signatures, NAC pharmacokinetics and clinical response. This 2-stage project is unique as it unifies clinical psychiatric measurements, quantitative MRS and pharmacological approaches in the first placebo-controlled clinical trial of NAC in young women with NSSI.Trial registration:The stage 1 trial protocol has been registered on https://clinicaltrials.gov/ with ClinicalTrials.gov ID “NCT04005053” (Registered on 02 July 2019. Available from: https://clinicaltrials.gov/ct2/show/NCT04005053).

Gamma-aminobutyric acid (GABA) changes in the hippocampus and anterior cingulate cortex in patients with temporal lobe epilepsy

PurposeTo explore the changes of gamma-aminobutyric acid (GABA) levels in the bilateral hippocampus and anterior cingulate cortex (ACC) of healthy control subjects and patients with temporal lobe epilepsy (TLE) and the correlation of GABA levels with the clinical symptoms by quantitative magnetic resonance spectroscopy (MRS). MethodsN-acetylaspartate (NAA), creatine (Cr) as well as choline (Cho) and GABA levels in the bilateral hippocampus and ACC were measured in 40 patients with TLE and 26 healthy control (NC) subjects with quantitative Meshcher-Garwood point resolved spectroscopy (MEGA-PRESS). The NAA/(Cho + Cr) and GABA/Cr ratios were compared between the NC and TLE groups. Comparisons were also made between the subgroups with lateralization (left TLE, right TLE and uncertain), short (<10 years) and longer (≥10 years) clinical seizure history (CSH), low (<1/month) and higher (≥1/month) seizure frequency (SF), with and without cognitive impairment (CI) in the patients with TLE, and by antiepileptic medications. Further analyses of the clinical information and metabolite ratios between the patients with TLE with and without CI were preformed. ResultsThe GABA/Cr ratio was significantly decreased in the bilateral hippocampus (left: P = 0.028, right: P = 0.035), while the NAA/(Cho + Cr) ratio was decreased only in the right hippocampus (RH) (P = 0.004) in patients with TLE compared with that of the NCs. Whereas the NAA/(Cho + Cr) ratio showed a consistent decreasing trend in bilateral hippocampus during the CSH, it only showed a significant difference in the RH. The GABA changes in the hippocampal and ACC regions were not consistent during different stages of the disease. In the bilateral hippocampus, the GABA/Cr ratio was decreased in the short seizure history (<10 years) patients with TLE compared with NCs (left: P = 0.018, right: P = 0.012), whereas the long seizure history (≥10 years) patients with TLE showed no difference with the NCs. However, in the ACC, the GABA/Cr ratio of the CI group was significantly decreased compared with that of NCs (P = 0.015). Further analysis showed that the patients with TLE with CI had obvious atrophy of the gray matter volume (GMV) and total parenchymal brain volume (PBV); GABA/Cr ratio was decreased in ACC, but increased in bilateral hippocampus compared with that of the no cognitive impairment (NOCI) group. ConclusionThe GABA/Cr ratio was more valuable than the NAA/(Cho + Cr) ratio in evaluating the dynamic metabolite changes in patients with TLE. Importantly, the GABA changes in the hippocampal and ACC regions were not consistent during different stages of the disease. In the bilateral hippocampus, the GABA/Cr ratio was decreased at the early stage, but recovered to normal levels later. The decreased GABA/Cr ratio in the ACC might indicate more cerebral cortex was involved, resulting in more CI in patients with TLE.

Application of Quantitative Proton Nuclear Magnetic Resonance Spectroscopy for the Compositional Analysis of Short-Chain Fatty Acid Ethyl Ester Mixtures

Application of Quantitative Proton Nuclear Magnetic Resonance Spectroscopy for the Compositional Analysis of Short-Chain Fatty Acid Ethyl Ester Mixtures

Application of Quantitative Proton Nuclear Magnetic Resonance Spectroscopy for the Compositional Analysis of Short-Chain Fatty Acid Ethyl Ester Mixtures

Application of Quantitative Proton Nuclear Magnetic Resonance Spectroscopy for the Compositional Analysis of Short-Chain Fatty Acid Ethyl Ester Mixtures

LATE BREAKING NEWS E-POSTER PRESENTATION: LBP 13 rAAVrh.74.MHCK7.micro-dystrophin gene therapy in children with Duchenne muscular dystrophy: A quantitative MR biomarker study

A recent study of rAAVrh.74.MHCK7.micro-dystrophin gene therapy was well tolerated and showed substantial micro-dystrophin expression and improvements in functional outcomes post-gene transfer. Quantitative magnetic resonance imaging and spectroscopy (qMRI/MRS) data were collected in three participants from that study (aged 5-7) and were compared with natural history qMRI/MRS data from a large ongoing study (n=180; n=54 age- and corticosteroid-status matched to gene therapy treated boys and 23 age-matched unaffected controls).