Exercise-induced changes in intramuscular total creatine concentration measured with 1H magnetic resonance spectroscopy: A pilot study.

Total amount of creatine (Cr) and phosphocreatine, or total creatine (tCr), may have a significant impact on the performance of skeletal muscles. In sports such as bodybuilding, it is popular to take Cr supplements to maintain tCr level. However, no study has explored the quantitative relationship between exercise intensity and the induced change in muscle's tCr. In this well-controlled study, straight-leg plantar flexion with specific load and duration was performed by 10 healthy subjects inside an MRI scanner, immediately followed by 1H MR spectroscopy (MRS) for measuring tCr concentration in gastrocnemius. For repeatability assessment, the experiment was repeated for each subject on two different days. Across all the subjects, baseline tCr was 46.6 ± 2.4 mM, ranging from 40.6 to 50.1 mM; with exercise, tCr significantly decreased by 10.9% ± 1.0% with 6-lb load and 21.0% ± 1.3% with 12-lb load (p < 0.0001). Between two different days, baseline tCr, percentage decrease induced by exercise with a 6-lb and 12-lb load differed by 2.2% ± 2.3%, 11.7% ± 6.0% and 4.9% ± 3.2%, respectively. In conclusion, the proposed protocol of controlled exercise stimulation and MRS acquisition can reproducibly monitor tCr level and its exercise-induced change in skeletal muscles. The measured tCr level is sensitive to exercise intensity, so can be used to quantitatively assess muscle performance or fatigue.

The Impact of MRI-Based Advanced Neuroimaging on Neurooncologists' Clinical Decision-Making in Patients With Posttreatment High-Grade Glioma: A Prospective Survey-Based Study.

Background: Advanced MRI-based neuroimaging techniques, such as perfusion and spectroscopy, have been increasingly incorporated into routine follow-up protocols in patients treated for high-grade glioma (HGG), to help differentiate tumor progression from treatment effect. However, these techniques' influence on clinical management remains poorly understood. Objective: To evaluate the impact of MRI-based advanced neuroimaging on clinical decision-making in patients with HGG in the posttreatment setting. Methods: This prospective study, performed at a comprehensive cancer center from March 1, 2017, to October 31, 2020, included adult patients treated by chemoradiation for WHO grade 4 diffuse glioma who underwent MRIbased advanced neuroimaging (comprising multiple perfusion imaging sequences and spectroscopy) to further evaluate findings on conventional MRI equivocal for tumor progression versus treatment effect. The ordering neuro-oncologists completed surveys before and after each advanced neuroimaging session. The percent of care episodes with a change between the intended and actual management plan on the surveys conducted before and after advanced neuroimaging, respectively, was computed and compared with a previously published percent using the Wald test for independent samples proportions. Results: The study included 63 patients (mean age, 55±13 years; 36 women, 27 men) who underwent 70 advanced neuroimaging sessions. Ordering neuro-oncologists' intended and actual management plans on the surveys completed before and after advanced neuroimaging, respectively, differed in 44% (31/70, [95% CI: 33-56%]) of episodes, which differed from the previously published frequency of 8.5% (5/59) (p<.001). These management plan changes included selection of a different plan for 6/8 episodes with an intended plan to enroll patients in a clinical trial, 12/19 episodes with an intended plan to change chemotherapeutic agents, 4/8 episodes with an intended plan of surgical intervention, and 1/2 episodes with an intended plan of re-irradiation. The ordering neuro-oncologists found advanced neuroimaging to be helpful in 93% (95% CI: 87%-99%) (65/70) of episodes. Conclusion: Neuro-oncologists' management plans changed in a substantial fraction of adult patients with HGG who underwent advanced neuroimaging to further evaluate conventional MRI findings equivocal for tumor progression versus treatment effect. Clinical Impact: The findings support incorporation of advanced neuroimaging into HGG posttreatment monitoring protocols.

Maternal prenatal immune activation associated with brain tissue microstructure and metabolite concentrations in newborn infants.

Few human studies have assessed the association of prenatal maternal immune activation (MIA) with measures of brain development and psychiatric risk in newborn offspring. Our goal was to identify the effects of MIA during the 2nd and 3rd trimesters of pregnancy on newborn measures of brain metabolite concentrations, tissue microstructure, and motor development. This was a prospective longitudinal cohort study conducted with nulliparous pregnant women who were aged 14 to 19 years and recruited in their 2nd trimester, as well as their children who were followed through 14 months of age. MIA was indexed by maternal interleukin-6 (IL-6) and C-reactive protein (CRP) in both trimesters of pregnancy. Primary outcomes included: (1) newborn brain metabolite concentrations as ratios to creatine (N-acetylaspartate (NAA)/creatine (Cr) and choline (Cho)/Cr) measured using Magnetic Resonance Spectroscopy; (2) newborn fractional anisotropy and mean diffusivity, measured using Diffusion Tensor Imaging; and (3) indices of motor development, assessed prenatally and postnatally at ages 4- and 14-months. Maternal IL-6 and CRP levels associated significantly with both metabolites in the putamen, thalamus, insula, and the internal capsule. Maternal IL-6 associated significantly with fractional anisotropy in the putamen, caudate, thalamus, insula, and precuneus, and with mean diffusivity in the inferior parietal and middle temporal gyrus. CRP associated significantly with fractional anisotropy in the thalamus, insula, and putamen. Significant associations were found in common regions across imaging modalities, though the direction of associations differed by immune marker. In addition, both maternal IL-6 and CRP (in both trimesters) prenatally associated significantly with offspring motor development at 4- and 14-months of age. The left thalamus mediated effects of IL-6 on postnatal motor development. These findings demonstrate that levels of MIA in mid- to late pregnancy in a generally healthy sample associate with tissue characteristics in newborn brain regions that primarily support motor integration and coordination, as well as behavioral regulation. Those brain effects may contribute to differences in motor development.

Brain metabolites are associated with sleep architecture and cognitive functioning in older adults.

Sleep deficits are a possible risk factor for development of cognitive decline and dementia in older age. Research suggests that neuroinflammation may be a link between the two. This observational, cross-sectional study evaluated relationships between sleep architecture, neuroinflammation and cognitive functioning in healthy older adults. Twenty-two adults aged ≥60 years underwent whole-brain magnetic resonance spectroscopic imaging (in vivo method of visualizing increased brain temperatures as a proxy for neuroinflammation), supervised laboratory-based polysomnography, and comprehensive neurocognitive testing. Multiple regressions were used to assess relationships between magnetic resonance spectroscopic imaging-derived brain temperature and metabolites related to inflammation (choline; myo-inositol; N-acetylaspartate), sleep efficiency, time and % N3 sleep and cognitive performance. Choline, myo-inositol and N-acetylaspartate were associated with sleep efficiency and cognitive performance. Higher choline and myo-inositol in the bilateral frontal lobes were associated with slower processing speed and lower sleep efficiency. Higher choline and myo-inositol in bilateral frontoparietal regions were associated with better cognitive performance. Higher N-acetylaspartate around the temporoparietal junction and adjacent white matter was associated with better visuospatial function. Brain temperature was not related to cognitive or sleep outcomes. Our findings are consistent with the limited literature regarding neuroinflammation and its relationships with sleep and cognition in older age, which has implicated ageing microglia and astrocytes in circadian dysregulation, impaired glymphatic clearance and increased blood-brain barrier integrity, with downstream effects of neurodegeneration and cognitive decline. Inflammatory processes remain difficult to measure in the clinical setting, but magnetic resonance spectroscopic imaging may serve as a marker of the relationship between neuroinflammation, sleep and cognitive decline in older adults.

Improvements in precision and accuracy of complex- relative to real-domain linear combination model spectral fitting not necessarily recovered by zero filling.

Although the information obtained from in vivo proton magnetic resonance spectroscopy (1H MRS) presents a complex-valued spectrum, spectral quantification generally employs linear combination model (LCM) fitting using the real spectrum alone. There is currently no known investigation comparing fit results obtained from LCM fitting over the full complex data versus the real data and how these results might be affected by common spectral preprocessing procedure zero filling. Here, we employ linear combination modeling of simulated and measured spectral data to examine two major ideas: first, whether use of the full complex rather than real-only data can provide improvements in quantification by linear combination modeling and, second, to what extent zero filling might influence these improvements. We examine these questions by evaluating the errors of linear combination model fits in the complex versus real domains against three classes of synthetic data: simulated Lorentzian singlets, simulated metabolite spectra excluding the baseline, and simulated metabolite spectra including measured in vivo baselines. We observed that complex fitting provides consistent improvements in fit accuracy and precision across all three data types. While zero filling obviates the accuracy and precision benefit of complex fitting for Lorentzian singlets and metabolite spectra lacking baselines, it does not necessarily do so for complex spectra including measured in vivo baselines. Overall, performing linear combination modeling in the complex domain can improve metabolite quantification accuracy relative to real fits alone. While this benefit can be similarly achieved via zero filling for some spectra with flat baselines, this is not invariably the case for all baseline types exhibited by measured in vivo data.

Multimodal investigation of neuropathology and neurometabolites in mild cognitive impairment and late-life depression with 11C-PiB beta-amyloid PET and 7T magnetic resonance spectroscopy.

Positron emission tomography (PET) and magnetic resonance spectroscopy (1H-MRS) are complementary techniques that can be applied to study how proteinopathy and neurometabolism relate to cognitive deficits in preclinical stages of Alzheimer's disease (AD)-mild cognitive impairment (MCI) and late-life depression (LLD). We acquired beta-amyloid (Aß) PET and 7 T 1H-MRS measures of GABA, glutamate, glutathione, N-acetylaspartate, N-acetylaspartylglutamate, myo-inositol, choline, and lactate in the anterior and posterior cingulate cortices (ACC, PCC) in 13 MCI and 9 LLD patients, and 13 controls. We used linear regression to examine associations between metabolites, Aß, and cognitive scores, and whether metabolites and Aß explained cognitive scores better than Aß alone. In the ACC, higher Aß was associated with lower GABA in controls but not MCI or LLD patients, but results depended upon MRS data quality control criteria. Greater variance in California Verbal Learning Test scores was better explained by a model that combined ACC glutamate and Aß deposition than by models that only included one of these variables. These findings identify preliminary associations between Aß, neurometabolites, and cognition.

Natural Products Dereplication: Databases and Analytical Methods.

The development of efficient methods for dereplication has been critical in the re-emergence of the research in natural products as a source of drug leads. Current dereplication workflows rapidly identify already known bioactive secondary metabolites in the early stages of any drug discovery screening campaign based on natural extracts or enriched fractions. Two main factors have driven the evolution of natural products dereplication over the last decades. First, the availability of both commercial and public large databases of natural products containing the key annotations against which the biological and chemical data derived from the studied sample are searched for. Second, the considerable improvement achieved in analytical technologies (including instrumentation and software tools) employed to obtain robust and precise chemical information (particularly spectroscopic signatures) on the compounds present in the bioactive natural product samples. This chapter describes the main methods of dereplication, which rely on the combined use of large natural product databases and spectral libraries, alongside the information obtained from chromatographic, UV-Vis, MS, and NMR spectroscopic analyses of the samples of interest.

A crisis awareness chain warning management model for patients with difficulties cooperating with magnetic resonance examinations.

OBJECTIVE: This case-control study tested a crisis awareness-based chain warning management model for patients with difficulties cooperating with magnetic resonance imaging (MRI) examinations. METHODS: All participants experienced difficulties cooperating with MRI examinations and underwent cranial magnetic resonance spectroscopy (MRS) and MRI at the same hospital in China. The control group (n = 1233) underwent examinations from January to June 2023 and received routine nursing care (pre-examination safety notification, instructions on cooperating during the examination, post-examination observation). A crisis awareness chain warning management model was implemented for the intervention group (n = 1352), who underwent examinations from July to December 2023. The groups were compared on average time for examination completion, quality of care and occurrence of complications. Data were collected using a self-devised data collection form. RESULTS: The average length of time to complete MRS and MRI was shorter for intervention group patients than for control group patients. The intervention group showed better pre-examination preparation, examination success rate, image quality attainment rate, and one-time examination success rate, and lower incidence of examination-related complications. CONCLUSION: This management model could increase MRI examination efficiency, improve quality of care, reduce complications and increase nurses' understanding of nursing continuity and crisis awareness.

Saliva and plasma metabolome changes during anoestrus, the oestrous cycle and early gestation in the mare: A pilot study.

Successful reproductive management of domestic mammals depends primarily upon timely identification of oestrous cycle stages. There is a need to develop an alternative non-invasive, welfare-friendly, accurate and reliable method to identify reproductive cycle stages. This is of particular interest for horse breeders, because horses are high-value farm animals that require careful management and individual monitoring. Saliva sampling is non-invasive, painless and welfare-friendly. Thus, we performed a metabolomic analysis of equine saliva during different reproductive stages to identify changes in the salivary metabolome during anoestrus, the oestrous cycle and early gestation. We compared the saliva and plasma metabolomes to investigate the relationship between the two fluids according to the physiological stage. We collected saliva and plasma samples from six mares during seasonal anoestrus, during the follicular phase 3 days, 2 days and 1 day before ovulation and the day when ovulation was detected, during the luteal phase 6 days after ovulation, and during early gestation 18 days after ovulation and insemination. Metabolome analysis was performed by proton-nuclear magnetic resonance spectroscopy. We identified 58 and 51 metabolites in saliva and plasma, respectively. The levels of four metabolites or groups of metabolites in saliva and five metabolites or groups of metabolites in plasma showed significant modifications during the 4 days until ovulation, ie 3 days prior to and on the day of ovulation. The levels of 11 metabolites or groups of metabolites in saliva and 17 metabolites or groups of metabolites in plasma were significantly different between the seasonal anoestrus and the ovarian cyclicity period. The physiological mechanisms involved in the onset of ovarian cyclicity and in ovulation induced modifications of the metabolome both in plasma and saliva. The metabolites whose salivary levels changed during the reproductive cycle could be potential salivary biomarkers to detect the reproductive stage in a welfare friendly production system. In particular, we propose creatine and alanine as candidate salivary biomarkers of ovulation and of the onset of ovarian cyclicity, respectively. However, extensive validation of their reliability is required. Our study contributes to extend to domestic mammals the use of saliva as a non-invasive alternative diagnostic fluid for reproduction in a welfare-friendly production system.

Lower distress intolerance is associated with higher glutathione levels in adolescent cannabis users.

Cannabis (CB) use and psychological stressors increase oxidative stress in the brain. Glutathione (GSH), the most abundant antioxidant in the brain, protects against oxidative stress. Furthermore, distress intolerance, the inability to tolerate psychological or physiological stress is a risk factor for CB use. The relationship between CB use, brain GSH levels and distress intolerance remains unknown. Therefore, we examined GSH levels in the anterior cingulate cortex (ACC), as a measure of oxidative stress, and its relationship with distress intolerance in adolescent CB users and healthy controls (HC). Sixteen HC and 17 CB-using adolescents were included in the analysis. GSH levels were measured in the ACC using a metabolite-edited proton magnetic resonance spectroscopy sequence on a 3 T scanner. Distress intolerance was assessed using the Distress Intolerance Index (DII) and CB use was evaluated using a structured clinical interview. In the CB group, lower CSF-corrected GSH levels in the ACC were correlated with higher DII scores. However, no significant between group differences were observed for ACC CSF-corrected GSH levels or on DII scores. No significant correlations were observed in the HC group between GSH levels and DII. Our findings suggests that the association between lower GSH levels and greater distress intolerance in CB users might reflect alterations in the balance between protective and oxidative stress conditions linked to the ability to tolerate distress. Further examination into this relationship can provide important insights into neurobiological correlates and risk factors associated with CB use to help inform preventive and treatment targets in the future.

Diffusion magnetic resonance spectroscopy captures microglial reactivity related to gut-derived systemic lipopolysaccharide: A preliminary study.

Neuroinflammation is a key component underlying multiple neurological disorders, yet non-invasive and cost-effective assessment of in vivo neuroinflammatory processes in the central nervous system remains challenging. Diffusion weighted magnetic resonance spectroscopy (dMRS) has shown promise in addressing these challenges by measuring diffusivity properties of different neurometabolites, which can reflect cell-specific morphologies. Prior work has demonstrated dMRS utility in capturing microglial reactivity in the context of lipopolysaccharide (LPS) challenges and serious neurological disorders, detected as changes of microglial neurometabolite diffusivity properties. However, the extent to which such dMRS metrics are capable of detecting subtler and more nuanced levels of neuroinflammation in populations without overt neuropathology is unknown. Here we examined the relationship between intrinsic, gut-derived levels of systemic LPS and dMRS-based apparent diffusion coefficients (ADC) of choline, creatine, and N-acetylaspartate (NAA) in two brain regions: the thalamus and the corona radiata. Higher plasma LPS concentrations were significantly associated with increased ADC of choline and NAA in the thalamic region, with no such relationships observed in the corona radiata for any of the metabolites examined. As such, dMRS may have the sensitivity to measure microglial reactivity across populations with highly variable levels of neuroinflammation, and holds promising potential for widespread applications in both research and clinical settings.

Emerging Role of Functional Magnetic Resonance Spectroscopy (MRS) to Monitor Response to Kinase Inhibitors in Cancer.

Inhibitors of kinases involved in signaling and other intracellular pathways, have revolutionized cancer treatment by providing highly targeted and effective therapies. However, timely monitoring treatment response remains a considerable challenge since conventional methods such as assessing changes in tumor volume do not adequately capture early responses or resistance development, due to the predominantly cytostatic rather than cytotoxic effect of kinase inhibitors. Magnetic resonance spectroscopy (MRS) is a non-invasive imaging technique that can provide insights into cellular metabolism by detecting changes in metabolite concentrations. By measuring metabolite levels, MRS offers a means to assess treatment response in real-time, providing earlier indications of efficacy or resistance compared to conventional imaging modalities. Bruton's Tyrosine Kinase (BTK) is a critical enzyme involved in B-cell receptor signaling. BTK inhibitors have been approved for the treatment of Mantle Cell Lymphoma (MCL) and other B-cell malignancies. Recent studies involving genome-scale gene expression, metabolomic, and fluxomic analyses have demonstrated that ibrutinib, an index BTK inhibitor, profoundly affects the key metabolic pathways in MCL cells., including glycolysis, glutaminolysis, pentose shunt, TCA cycle and phospholipid metabolism. Importantly, the effects of ibrutinib on MCL cells directly and proportionately correlates with their sensitivity to the drug. Consequently, changes in specific metabolite concentrations detectable non-invasively by MRS such as lactate and alanine reflecting mostly the status of cellular glycolysis and glutaminolysis, respectively, have emerged as potential biomarkers for predicting response and resistance of MCL cells to BTK inhibition, both in vitro and in vivo. Preparations to validate the utility of these biomarkers in clinical setting are under way. These studies may pave the way to monitor therapeutic response to kinase inhibitors also in other types of cancer.

Considerations for event-related gamma-aminobutyric acid functional magnetic resonance spectroscopy.

The use of sequential proton magnetic resonance spectroscopy (MRS) to follow glutamate and gamma-aminobutyric acid (GABA) changes during functional task-based paradigms, functional MRS (fMRS), has increased. This technique has been used to investigate GABA dynamics during both sensory and behavioural tasks, usually with long 'block design' paradigms. Recently, there has been an increase in interest in the use of short stimuli and 'event-related' tasks. While changes in glutamate can be readily followed by collecting multiple individual transients (or shots), measurement of GABA, especially at 3 T, is usually performed using editing techniques like Mescher-Garwood point-resolved spectroscopy (MEGA-PRESS), which by its nature is a dual shot approach. This poses problems when considering an event-related experiment, where it is unclear when GABA may change, or how this may affect the individual subspectra of the MEGA-PRESS acquisition. To address this issue, MEGA-PRESS data were simulated to reflect the effect of a transient change in GABA concentration due to a short event-related stimulus. The change in GABA was simulated for both the ON and OFF subspectra, and the effect of three different conditions (increase only during ON acquisition, increase during OFF acquisition and increase across both) on the corresponding edited GABA spectrum was modelled. Results show that a transient increase in GABA that only occurs during the ON subspectral acquisition, while not changing the results much from when GABA is changed across both conditions, will give a much larger change in the edited GABA spectrum than a transient increase that occurs only during the OFF subspectral acquisition. These results suggest that researchers should think carefully about the design of any event-related fMRS studies using MEGA-PRESS, as well as the analysis of other functional paradigms where transient changes in GABA may be expected. Experimental design considerations are therefore discussed, and suggestions are made.

Identification of neurotransmitter imbalances in the cingulate cortex of NMOSD patients using magnetic resonance spectroscopy.

Cognitive impairment affects 29-67% of patients with neuromyelitis optica spectrum disorder. Previous studies have reported glutamate homeostasis disruptions in astrocytes, leading to imbalances in gamma-aminobutyric acid levels. However, the association between these neurotransmitter changes and cognitive deficits remains inadequately elucidated. Point RESolved Spectroscopy and Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy techniques were utilized to evaluate gamma-aminobutyric acid, glutamate, glutathione levels, and excitation/inhibition balance in the anterior cingulate cortex, posterior cingulate cortex, and occipital cortex of 39 neuromyelitis optica spectrum disorder patients and 41 healthy controls. Cognitive function was assessed using neurocognitive scales. Results showed decreased gamma-aminobutyric acid levels alongside increased glutamate, glutathione, and excitation/inhibition ratio in the anterior cingulate cortex and posterior cingulate cortex of neuromyelitis optica spectrum disorder patients. Specifically, within the posterior cingulate cortex of neuromyelitis optica spectrum disorder patients, decreased gamma-aminobutyric acid levels and increased excitation/inhibition ratio correlated significantly with anxiety scores, whereas glutathione levels predicted diminished executive function. The results suggest that neuromyelitis optica spectrum disorder patients exhibit dysregulation in the GABAergic and glutamatergic systems in their brains, where the excitation/inhibition imbalance potentially acts as a neuronal metabolic factor contributing to emotional disorders. Additionally, glutathione levels in the posterior cingulate cortex region may serve as predictors of cognitive decline, highlighting the potential benefits of reducing oxidative stress to safeguard cognitive function in neuromyelitis optica spectrum disorder patients.

Time Course of High-Energy Phosphate Depletion During Cold Storage of Human Heart Grafts Using the Celsior Solution.

The aim of this study was to provide insight into high-energy phosphate compound concentration dynamics under realistic clinical cold-storage conditions using the Celsior solution in seven heart grafts discarded from transplantation. The hearts of seven local donors (three males, four females, age 37 ± 17 years, height 175 ± 5 cm, weight 75 ± 9 kg) initially considered for transplantation and eventually discarded were submitted to a Magnetic Resonance Spectroscopy observation in a clinical Magnetic Resonance Imaging scanner over at least 9 h. The grafts remained in their sterile container at 4°C during the entire examination. Hence, Phosphocreatine (PCr), adenosine triphosphate (ATP), inorganic phosphate (Pi) and intracellular pH were recorded non-destructively at a 30-minute interval. With the ischemic time Ti, the concentration ratios decreased at PCr/ATP = 1.68-0.0028·Tis, Pi/ATP = 1.38 + 0.0029·Tis, and intracellular pH at 7.43-0.0012·Tis. ATP concentration remained stable for at least 9 h and did not decrease as long as phosphocreatine was detectable. Acidosis remained moderate. In addition to the standard parameters assessed at the time of retrieval, Magnetic Resonance Spectroscopy can provide an assesment of the metabolic status of heart grafts before transplantation. These results show how HEPC metabolites deplete during cold storage. Although many parameters determine graft quality during cold storage, the dynamics of HEPC and intracellular pH may be helpful in the development of strategies aiming at extending the ischemic time.

Chloride Voltage-Gated Channel 2 (CLCN2)-Related Leukoencephalopathy Exhibiting Reduced Choline Levels on Magnetic Resonance Spectroscopy.

In this article, we report the third case of chloride voltage-gated channel 2 (CLCN2)-related leukoencephalopathy (CC2L) in Japan. The patient presented with headache, vertigo, and mild visual impairment. The CLCN2 variant of the patient, NM_004366.6:c.61dup, p.(Leu21Profs*27), was also found in two other Japanese patients as this variant is relatively common in the Japanese population. Magnetic resonance imaging (MRI) revealed T2 prolongation with reduced diffusion in the bilateral posterior limbs of the internal capsule, cerebral peduncles, and superior and middle cerebellar peduncles. Magnetic resonance spectroscopy (MRS) of normal-appearing white matter revealed decreased choline content. This represents the first evidence of decreased choline levels in CC2L, highlighting the superior sensitivity of MRS over MRI.

Applying chemical shift images (in-phase/opposed phased) for differentiating low-grade from high-grade glioma and comparison with magnetic resonance spectroscopy.

BACKGROUND: Grading gliomas is essential for treatment decisions and patient prognosis. In this study we evaluated the in-phase and out-of-phase sequences for distinguishing high-grade (HGG) from low-grade glioma (LGG) and the correlation with magnetic resonance spectroscopy (MRS) results. METHODS: This observational study comprised patients with brain tumors referred to our center for brain MRS. The gold standard for diagnosis was based on the World Health Organization (WHO) glioma classification. A standard tumor protocol was accomplished using a 1.5­T MRS scanner. Before contrast medium administration, extra in- and out-phase sequences were acquired. Three 20-30-mm2 oval regions of interest (ROIs) were placed in the solid component and the signal loss ratio (SLR) was calculated with the following formula: SLR tumor = (SI In phase - SI Opposed phase) / SI In phase Correlations and comparisons between groups were made using the Pearson, chi-square and, independent samples t tests. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic performance. Statistical significance was set at p < 0.05. RESULTS: In total, 20 patients were included in the LGG and 13 were included in the HGG group. The mean SLR in the HGG and LGG groups was 3.66 ± 2.12 and 1.63 ± 1.86, respectively (p = 0.01). There was a statistically significant correlation between lipid lactate (0.48, p = 0.004) and free lipid (0.44, p = 0.009) concentrations on MRS with SLR. CONCLUSIONS: The SLR is a simple, rapid, and noninvasive marker for differentiating between LGG and HGG. There is a significant correlation with both the concentration and presence of free lipid and lipid-lactate peaks in MRS.

Correlation between cerebral neurotransmitters levels by proton magnetic resonance spectroscopy and HbA1c in patients with type 2 diabetes.

BACKGROUND: Cognitive dysfunction is the main manifestation of central neuropathy. Although cognitive impairments tend to be overlooked in patients with diabetes mellitus (DM), there is a growing body of evidence linking DM to cognitive dysfunction. Hyperglycemia is closely related to neurological abnormalities, while often disregarded in clinical practice. Changes in cerebral neurotransmitter levels are associated with a variety of neurological abnormalities and may be closely related to blood glucose control in patients with type 2 DM (T2DM). AIM: To evaluate the concentrations of cerebral neurotransmitters in T2DM patients exhibiting different hemoglobin A1c (HbA1c) levels. METHODS: A total of 130 T2DM patients were enrolled at the Department of Endocrinology of Shanghai East Hospital. The participants were divided into four groups according to their HbA1c levels using the interquartile method, namely Q1 (< 7.875%), Q2 (7.875%-9.050%), Q3 (9.050%-11.200%) and Q4 (≥ 11.200%). Clinical data were collected and measured, including age, height, weight, neck/waist/hip circumferences, blood pressure, comorbidities, duration of DM, and biochemical indicators. Meanwhile, neurotransmitters in the left hippocampus and left brainstem area were detected by proton magnetic resonance spectroscopy. RESULTS: The HbA1c level was significantly associated with urinary microalbumin (mALB), triglyceride, low-density lipoprotein cholesterol (LDL-C), homeostasis model assessment of insulin resistance (HOMA-IR), and beta cell function (HOMA-ß), N-acetylaspartate/creatine (NAA/Cr), and NAA/choline (NAA/Cho). Spearman correlation analysis showed that mALB, LDL-C, HOMA-IR and NAA/Cr in the left brainstem area were positively correlated with the level of HbA1c (P < 0.05), whereas HOMA-ß was negatively correlated with the HbA1c level (P < 0.05). Ordered multiple logistic regression analysis showed that NAA/Cho [Odds ratio (OR): 1.608, 95% confidence interval (95%CI): 1.004-2.578, P < 0.05], LDL-C (OR: 1.627, 95%CI: 1.119-2.370, P < 0.05), and HOMA-IR (OR: 1.107, 95%CI: 1.031-1.188, P < 0.01) were independent predictors of poor glycemic control. CONCLUSION: The cerebral neurotransmitter concentrations in the left brainstem area in patients with T2DM are closely related to glycemic control, which may be the basis for the changes in cognitive function in diabetic patients.

Dissociation of focal and large-scale inhibitory functions in the older adults: A multimodal MRI study.

BACKGROUND: The decline of inhibitory in cognitive aging is linked to reduced cognitive and mental capacities in older adults. However, this decline often shows inconsistent clinical presentations, suggesting varied impacts on different inhibition-related tasks. Inhibitory control, a multifaceted construct, involves various types of inhibition. Understanding these components is crucial for comprehending how aging affects inhibitory functions. Our research investigates the influences of aging on large-scale and focal-scale inhibitory and examines the relationship with brain markers. METHODS: We examined the impact of aging on inhibitory in 18 younger (20-35 years) and 17 older adults (65-85 years) using focal and large-scale inhibition tasks. The Gabor task assessed focal-scale inhibition, while the Stop Signal Task (SST) evaluated large-scale inhibition. Participants underwent neuropsychological assessments and MRI scans, including magnetic resonance spectroscopy (MRS) and structural and resting fMRI. RESULTS: Older adults exhibited a marked decline in inhibitory function, with slower SST responses indicating compromised large-scale inhibition. Conversely, the Gabor task showed no significant age-related changes. MRS findings revealed decreased levels of GABA, glutamate, glutamine, and NAA in the pre-SMA, correlating with observed large-scale inhibition in older adults. Additionally, pre-SMA seed-based functional connectivity analysis showed reduced brain network connections in older adults, potentially contributing to inhibitory control deficits. CONCLUSIONS: Our study elucidates the differential effects of aging on inhibitory functions. While large-scale inhibition is more vulnerable to aging, focal-scale inhibition is relatively preserved. These findings highlight the importance of targeted cognitive interventions and underscore the necessity of a multifaceted approach in aging research.

Whole-body hypothermia in mild neonatal encephalopathy: protocol for a multicentre phase III randomised controlled trial.

BACKGROUND: Mild hypoxic ischemic encephalopathy is associated with sub optimal cognition and learning difficulties at school age. Although whole-body hypothermia reduces death and disability after moderate or severe encephalopathy in high-income countries, the safety and efficacy of hypothermia in mild encephalopathy is not known. The cooling in mild encephalopathy (COMET) trial will examine if whole-body hypothermia improves cognitive development of neonates with mild encephalopathy. METHODS: The COMET trial is a phase III multicentre open label two-arm randomised controlled trial with masked outcome assessments. A total of 426 neonates with mild encephalopathy will be recruited from 50 to 60 NHS hospitals over 2 ½ years following parental consent. The neonates will be randomised to 72 h of whole-body hypothermia (33.5 ± 0.5 C) or normothermia (37.0 ± 0.5 C) within six hours or age. Prior to the recruitment front line clinical staff will be trained and certified on expanded modified Sarnat staging for encephalopathy. The neurological assessment of all screened and recruited cases will be video recorded and centrally assessed for quality assurance. If recruitment occurs at a non-cooling centre, neonates in both arms will be transferred to a cooling centre for continued care, after randomisation. All neonates will have continuous amplitude integrated electroencephalography (aEEG) at least for the first 48 h to monitor for seizures. Predefined safety outcomes will be documented, and data collected to assess resource utilization of health care. A central team masked to trial group allocation will assess neurodevelopmental outcomes at 2 years of age. The primary outcome is mean difference in composite cognitive scores on Bayley scales of Infant and Toddler development 4th Edition. DISCUSSION: The COMET trial will establish the safety and efficacy of whole-body hypothermia for mild hypoxic ischaemic encephalopathy and inform national and international guidelines in high income countries. It will also provide an economic assessment of whole-body hypothermia therapy for mild encephalopathy in the NHS on cost-effectiveness grounds. TRIAL REGISTRATION NUMBER: NCT05889507 June 5, 2023.