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The detection of a secondary inorganic phosphate (Pi) resonance, a possible marker of mitochondrial content in vivo, using phosphorus magnetic resonance spectroscopy (31P-MRS), poses technical challenges at 3 Tesla (T). Overcoming these challenges is imperative for the integration of this biomarker into clinical research. To evaluate the repeatability and reliability of measuring resting skeletal muscle alkaline Pi (Pialk) using with 31P-MRS at 3 T. After an initial set of experiments on five subjects to optimize the sequence, resting 31P-MRS of the quadriceps muscles were acquired on two visits (~4 days apart) using an intra-subjects design, from 13 sedentary to moderately active young male and female adults (22 ± 3 years old) within a whole-body 3 T MR system. Measurement variability attributed to changes in coil position, shimming procedure, and spectral analysis were quantified. 31P-MRS data were acquired with a 31P/-proton (1H) dual-tuned surface coil positioned on the quadriceps using a pulse-acquire sequence. Test-retest absolute and relative repeatability was analyzed using the coefficient of variation (CV) and intra-class correlation coefficients (ICC), respectively. After sequence parameter optimization, Pialk demonstrated high intra-subject repeatability (CV: 10.6 ± 5.4%, ICC: 0.80). Proximo-distal change in coil position along the length of the quadriceps introduced Pialk quantitation variability (CV: 28 ± 5%), due to magnetic field inhomogeneity with more distal coil locations. In contrast, Pialk measurement variability due to repeated shims from the same muscle volume (0.40 ± 0.09mM; CV: 6.6%), and automated spectral processing (0.37 ± 0.01mM; CV: 2.3%), was minor. The quantification of Pialk in skeletal muscle via surface coil 31P-MRS at 3 T demonstrated excellent reproducibility. However, caution is advised against placing the coil at the distal part of the quadriceps to mitigate shimming inhomogeneity.

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OBJECTIVES: Magnetic resonance imaging (MRI) is a critical noninvasive technique for evaluating liver steatosis, with efficient and precise fat quantification being essential for diagnosing liver diseases. This study leverages 5 T ultra-high-field MRI to demonstrate the clinical significance of liver fat quantification, and explores the consistency and accuracy of the Proton Density Fat Fraction (PDFF) in the liver across different magnetic field strengths and measurement methodologies. METHODS: The study involved phantoms with lipid contents ranging from 0 % to 30 % and 35 participants (21 females, 14 males; average age 30.17 ± 13.98 years, body mass index 25.84 ± 4.76, waist-hip ratio 0.84 ± 0.09). PDFF measurements were conducted using chemical shift encoded (CSE) MRI at 5 T, 3 T, and 1.5 T, alongside magnetic resonance spectroscopy (MRS) at 5 T and 1.5 T for both liver and phantoms, analyzed using jMRUI software. The MRS-derived PDFF values served as the reference standard. Repeatability of 5 T MRI measurements was assessed through correlation analysis, while accuracy was evaluated using linear regression analysis against the reference standards. RESULTS: The CSE-PDFF measurements at 5 T demonstrated strong consistency with those at 3 T and 1.5 T, showing high intraclass correlation coefficients (ICC) of 0.988 and 0.980, respectively (all p < 0.001). There was also significant consistency across ROIs within liver lobes, with ICC values ranging from 0.975 to 0.986 (all p < 0.001). MRS-PDFF measurements for both phantoms and liver at 5 T and 1.5 T exhibited substantial agreement, with ICC values of 0.996 and 0.980, respectively (all p < 0.001). Particularly, ICC values for ROIs in the liver ranged from 0.963 to 0.990 (all p < 0.001). Despite overall agreement, statistically significant differences were noted in specific ROIs within the liver lobes (p = 0.004 and 0.012). The CSE and MRS PDFF measurements at 5 T displayed strong consistency, with an ICC of 0.988 (p < 0.001), and significant agreement was also found between 5 T CSE and 1.5 T MRS PDFF measurements, with an ICC of 0.978 (p < 0.001). Agreement was significant within the ROIs of the liver lobes on the same platform at 5 T, with ICC values ranging from 0.986 to 0.991 (all p < 0.001). CONCLUSION: PDFF measurements at 5 T MR imaging exhibited both accuracy and repeatability, indicating that 5 T imaging provides reliable quantification of liver fat content and shows substantial potential for clinical diagnostic applications.

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Gallbladder carcinoma (GBC) presents a significant clinical challenge due to its aggressive nature and often asymptomatic progression, resulting in late-stage diagnoses and a poor prognosis. Early detection and accurate staging are pivotal for improving patient outcomes, highlighting the critical role of advanced imaging techniques in oncological practice. Magnetic resonance spectroscopy (MRS) has emerged as a valuable non-invasive tool capable of assessing biochemical changes within tissues, including alterations in choline metabolism-a biomarker indicative of cell membrane turnover and proliferation. This review explores the application of MRS in evaluating choline levels in gallbladder carcinoma, synthesizing current literature to elucidate its potential in clinical settings. By analyzing studies investigating the correlation between choline levels detected via MRS and tumor characteristics, this review underscores MRS's role in enhancing diagnostic precision and guiding therapeutic decision-making. Moreover, it discusses the challenges and limitations associated with MRS in clinical practice alongside future research and technological advancement directions. Ultimately, integrating MRS into the diagnostic armamentarium for gallbladder carcinoma promises to improve early detection and treatment outcomes. This review provides insights into the evolving landscape of MRS in oncology, emphasizing its contribution to personalized medicine approaches aimed at optimizing patient care and management strategies for GBC.

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Obsessive-compulsive disorder (OCD) is linked with dysfunction in frontal-striatal, fronto-limbic, and visual brain regions. Research using proton magnetic resonance spectroscopy (1H-MRS) suggests that altered neurometabolite levels, like glutamate, may contribute to this dysfunction. However, static neurometabolite levels in OCD patients have shown inconsistent results, likely due to previous studies' limited focus on neurometabolite dynamics. We employ functional MRS (fMRS) and functional magnetic resonance imaging (fMRI) to explore these dynamics and brain activation during OCD symptom provocation. We utilized a combined 7-tesla fMRI-fMRS setup to examine task-related BOLD response and glutamate changes in the lateral occipital cortex (LOC) of 30 OCD participants and 34 matched controls during an OCD-specific symptom provocation task. The study examined main effects and between-group differences in brain activation and glutamate levels during the task. A whole sample task-effects analysis on data meeting predefined quality criteria showed significant glutamate increases (n = 41 (22 OCD, 19 controls), mean change: 3.2 %, z = 3.75, p < .001) and task activation (n = 54 (26 OCD, 28 controls), p < .001) in the LOC during OCD blocks compared to neutral blocks. However, no differences in task-induced glutamate dynamics or activation between groups were found, nor a correlation between glutamate levels and task activation. We were able to measure task-induced increases in glutamate and BOLD levels, emphasizing its feasibility for OCD research. The absence of group differences highlights the need for further exploration to discern to what extent neurometabolite dynamics differ between OCD patients and controls. Once established, future studies can use pre-post intervention fMRS-fMRI to probe the effects of therapies modulating glutamate pathways in OCD.

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OBJECTIVE: Aim: The aim of the research was to investigate associations between brain morphometric changes and short-term stroke outcome. PATIENTS AND METHODS: Materials and Methods: In this study, 294 patients with acute stroke were enrolled. All participants underwent magnetic resonance imaging (MRI) and computed tomography (CT) assessment as well as clinical-neurological and cognitive testing. RESULTS: Results: In the multivariable regression analysis, bicaudate index (OR = 1.3; 95 % CI 1.1 - 1.7, p=0.018) and ventricular index (OR = 0.7; CI 0.5 - 0.9, p=0.005) were associated with an unfavourable short-term stroke outcome. The univariable regression analysis revealed significant associations between mini-mental state examination scale score (MMSE) and width of the longitudinal cerebral fissure in the anterior part of the frontal lobes (FI) (b -0.8, 95% CI -1.6 - -0.1, p=0.037) as well as width of the cerebral fissure in the area of the skull vault (SW) (b -0.9, 95% CI -1.8 - -0.1, p=0.023). In the multivariable regression model bicaudate index was associated with MMSE score (b coefficient (b) = -1.2; 95 % CI -2.1 - -0.3, p = 0.011). CONCLUSION: Conclusions: our results show that altered brain morphometric indices are associated with unfavourable short-term stroke outcome and cognitive decline.

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Antimicrobial resistance is a global threat, and pet-associated strains may pose a risk to human health. Equine veterinarians are at high risk of carrying methicillin-resistant staphylococci (MRS), but specific risk factors remain elusive, and few data are available for other personnel involved in the horse industry. The prevalence, characteristics, and risk factors for nasal carriage of MRS in horses and their caregivers were studied in northwestern Italy. Nasal swabs from 110 asymptomatic horses housed at 21 barns and 34 human caregivers were collected. Data on barns, horses, and personnel were acquired through questionnaires. The samples were incubated in selective media, and the bacterial isolates were identified by mass spectrometry. Risk factors were investigated by Poisson regression. MRS were isolated from 33 horses (30%), 11 humans (32.4%) and 3 environmental samples (14.2%). Most isolates were multidrug resistant (MDRS). The prevalence of MRS and MDRS was greater in racehorses and their personnel than in pleasurable and jumping/dressing horses. MRS carriage in caregivers was associated with an increased prevalence of MRS carriage in horses. The frequency of antimicrobial treatments administered in the barn during the last 12 months was a risk factor for MRS carriage in horses [prevalence ratio (PR) 3.97, 95% CI 1.11, 14.13] and caregivers (PR 2.00, 95% CI 1.05, 3.82), whereas a good ventilation index of the horse tabling environment was a protective factor (PR 0.43, 95% CI 0.20, 0.92). Our data reveal relevant interactions occurring between bacterial communities of horses and humans that share the same environment, suggesting that One Health surveillance programs should be implemented.

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Background: Evidence from animal and human studies suggests glutamatergic dysfunction in posttraumatic stress disorder (PTSD). The purpose of this study was to investigate glutamate abnormalities in the dorsolateral prefrontal cortex (DLFPC) of individuals with PTSD using 7T MRS, which has better spectral resolution and signal-to-noise ratio than lower field strengths, thus allowing for better spectral quality and higher sensitivity. We hypothesized that individuals with PTSD would have lower glutamate levels compared to trauma-exposed individuals without PTSD and individuals without trauma exposure. Additionally, we explored potential alterations in other neurometabolites and the relationship between glutamate and psychiatric symptoms. Methods: Individuals with PTSD (n = 27), trauma-exposed individuals without PTSD (n = 27), and individuals without trauma exposure (n = 26) underwent 7T MRS to measure glutamate and other neurometabolites in the left DLPFC. The severities of PTSD, depression, anxiety, and dissociation symptoms were assessed. Results: We found that glutamate was lower in the PTSD and trauma-exposed groups compared to the group without trauma exposure. Furthermore, N-acetylaspartate (NAA) was lower and lactate was higher in the PTSD group compared to the group without trauma exposure. Glutamate was negatively correlated with depression symptom severity in the PTSD group. Glutamate was not correlated with PTSD symptom severity. Conclusion: In this first 7T MRS study of PTSD, we observed altered concentrations of glutamate, NAA, and lactate. Our findings provide evidence for multiple possible pathological processes in individuals with PTSD. High-field MRS offers insight into the neurometabolic alterations associated with PTSD and is a powerful tool to probe trauma- and stress-related neurotransmission and metabolism in vivo.

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INTRODUCTION: Regional glucose hypometabolism resulting in glutamate loss has been shown as one of the characteristics of Alzheimer's disease (AD). Because the impact of AD varies between the sexes, we utilized glutamate-weighted chemical exchange saturation transfer (GluCEST) magnetic resonance imaging (MRI) for high-resolution spatial mapping of cerebral glutamate and investigated subregional changes in a sex-specific manner. METHODS: Eight-month-old male and female AD mice harboring mutant amyloid precursor protein (APPNL-F/NL-F: n = 36) and wild-type (WT: n = 39) mice underwent GluCEST MRI, followed by proton magnetic resonance spectroscopy (1H-MRS) in hippocampus and thalamus/hypothalamus using 9.4T preclinical MR scanner. RESULTS: GluCEST measurements revealed significant (p ≤ 0.02) glutamate loss in the entorhinal cortex (% change ± standard error: 8.73 ± 2.12%), hippocampus (11.29 ± 2.41%), and hippocampal fimbriae (19.15 ± 2.95%) of male AD mice. A similar loss of hippocampal glutamate in male AD mice (11.22 ± 2.33%; p = 0.01) was also observed in 1H-MRS. DISCUSSIONS: GluCEST MRI detected glutamate reductions in the fimbria and entorhinal cortex of male AD mice, which was not reported previously. Resilience in female AD mice against these changes indicates an intact status of cerebral energy metabolism. HIGHLIGHTS: Glutamate levels were monitored in different brain regions of early-stage Alzheimer's disease (AD) and wild-type male and female mice using glutamate-weighted chemical exchange saturation transfer (GluCEST) magnetic resonance imaging (MRI). Male AD mice exhibited significant glutamate loss in the hippocampus, entorhinal cortex, and the fimbriae of the hippocampus. Interestingly, female AD mice did not have any glutamate loss in any brain region and should be investigated further to find the probable cause. These findings demonstrate previously unreported sex-specific glutamate changes in hippocampal sub-regions using high-resolution GluCEST MRI.

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The prevalence of frailty is increasing, and it is associated with increased risk of diseases and adverse outcomes. Although substantial research has focused on post-stroke frailty, understanding of pre-stroke frailty remains limited. Our aim was to synthesize literature on pre-stroke frailty and stroke risk to explore their relationship and impact on prognosis. A systematic search of multiple databases was conducted to identify cohort studies published until October 28, 2023. Meta-analysis was conducted using a random effects model. Heterogeneity was assessed with the I² statistic, and publication bias was evaluated using Begg's test. Finally, we included 11 studies (n = 1,660,328 participants). The pooled hazard ratios (HRs) for stroke risk associated with pre-stroke frailty compared to non-frail individuals was 1.72 (95% confidence interval, CI: 1.46-2.02, p = 0.002, I2 = 69.2%, Begg's test: p = 0.536). The pooled HRs for mortality and the pooled relative risk (RRs) modified Rankin Scale (mRs) associated with pre-stroke frailty were 1.68 (95% CI: 1.10-2.56, p = 0.136, I2 = 49.9%, Begg's test: p = 0.296) and 3.11 (95% CI: 1.77-5.46, p = 0.192, I2 = 39.4%, Begg's test: p = 1.000), respectively. In conclusion, pre-stroke frailty is strongly associated with stroke risk and impacts its prognosis, irrespective of the measurement method. Future research should focus on prospective studies to assess the effects of early intervention for frailty. This has significant implications for primary healthcare services and frailty management.

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BACKGROUND AND OBJECTIVES: Conventional magnetic resonance imaging (MRI) used for detecting possible antibody-negative autoimmune encephalitis (AIE) often fails to meet the diagnostic requirements of this disease. Positron emission tomography (PET) with a translocator protein radioligand can help visualize microglia distribution density in inflammation-related diseases, thereby offering potentially incremental value to conventional MRI for the in vivo assessment of possible antibody-negative AIE. METHODS: In this prospective study, 15 participants diagnosed with possible antibody-negative AIE and 10 healthy controls were enrolled (ClinicalTrials.gov: NCT05293405, dated March 15, 2022). All participants underwent hybrid 18F-DPA714 PET/MRI and evaluation for modified Rankin scale (mRS) score, clinical assessment scale for AIE (CASE), and appropriate antibodies. A positive finding was defined as the intensity of 18F-DPA714 uptake that was above a threshold of mean standardized uptake value ratio (SUVR) + two standard deviations of SUVR within the corresponding brain regions of healthy controls. RESULTS: The positive detection rate of 18F-DPA714 PET for possible antibody-negative AIE was significantly higher than that of brain MRI (10/15 [67%] vs. 3/15 [20%]; P = 0.039). In addition, both the intensity and extent of 18F-DPA714 uptake were significantly associated with the CASE score (P = 0.002 and 0.001). Meanwhile, SUVR levels in the cerebellar region were significantly higher in patients with ataxia than in those without ataxia (P = 0.006). Furthermore, 18F-DPA714 uptake decreased in 5/10 [50%] patients who underwent follow-up PET/MRI, which mirrored their symptom relief. CONCLUSION: 18F-DPA714 PET demonstrated its potentially incremental value to conventional MRI for detecting possible antibody-negative AIE.

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BACKGROUND: Despite different intracranial tumour subtypes varying largely in their prognoses and recommended treatment regimens, they can have markedly similar appearances on standard radiology, especially in paediatric patients where they tend to occur in the midline. There is a need for a non-invasive, accurate method of determining tumour diagnosis to help expedite treatment planning. Existing studies have found magnetic resonance spectroscopy (MRS) to have value in diagnosing intracranial tumours in adults. The aim of this study was to investigate whether MRS could be accurate in diagnosing and grading paediatric intracranial tumours. METHODS: The hospital database was retrospectively searched for paediatric intracranial tumour patients ≤18 years that had 1.5 T MRS data available. Medical and demographic data were collected from existing records including MRS metabolites N-acetylaspartate (NAA), creatine (Cr), and choline (Cho), and final histopathologic diagnosis. MRS metabolites were then statistically compared against final histopathologic diagnosis. RESULTS: In total, 166 patients were included. In the overall cohort, the tumour to control tissue Cr ratio was significantly higher in grade 1 than grade 4 tumours (P=0.03), and tumour Cho/Cr was significantly higher in grade 4 than grade 1 tumours (P=0.004). When analyzing tumour subtypes, control tissue Cr was significantly higher in embryonal/germ cell tumours than glial tumours (P=0.044). Binary logistic regression models including MRS metabolite ratios and age, sex, and tumour location covariates could diagnose grade 4 tumours [area under the curve (AUC) =0.857], and grade 1 tumours (AUC =0.766) with reasonable accuracy. CONCLUSIONS: This study suggests that MRS has benefits in the non-invasive diagnosis of paediatric intracranial tumours, in particular, identifying low- and high-grade tumours. Future advances in MRS technology, and larger cross-sectional studies will be necessary to improve the clinical integration of MRS for accurate non-invasive paediatric intracranial tumour diagnosis.

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This work aims to develop and implement a pulse-acquire sequence for three-dimensional (3D) single-voxel localized 13C MRS in humans at 7 T, in conjunction with bilevel broadband 1H decoupling, and to test its feasibility in vitro and in vivo in human calf muscle with emphasis on the detection of glycogen C1-C6. A localization scheme suitable for measuring fast-relaxing 13C signals in humans at 7 T was developed and implemented using the outer volume suppression (OVS) and one-dimensional image selected in vivo spectroscopy (ISIS-1D) schemes, similar to that which was previously reported in humans at 4 T. The 3D 13C localization scheme was followed by uniform 13C adiabatic excitation, all complemented with an option for bilevel broadband 1H decoupling to improve both 13C sensitivity and spectral resolution at 7 T. The performance of the pulse-acquire sequence was investigated in vitro on phantoms and in vivo in the human calf muscle of three healthy volunteers, while measuring glycogen C1-C6. In addition, T1 and T2 of glycogen C1-C6 were measured in vitro at 7 T, as well as T1 of glycogen C1 in vivo. The glycerol C2 and C1,3 lipid resonances were efficiently suppressed in vitro at 7 T using the OVS and ISIS-1D schemes, allowing distinct detection of glycogen C2-C6. While some glycerol remained in calf muscle in vivo, the intense lipid at 130 ppm was efficiently suppressed. The 13C sensitivity and spectral resolution of glycogen C1-C6 in vitro and glycogen C1 in vivo were improved at 7 T using bilevel broadband 1H decoupling. The T1 and T2 of glycogen C1-C6 in vitro at 7 T were consistent compared with those at 8.5 T, while the T1 of glycogen C1 in vivo at 7 T resulted similar to that in vitro. Localized 13C MRS is feasible in human calf muscle in vivo at 7 T, and this will allow further extension of this method for 13C MRS measurements such as in the brain.

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OBJECTIVE: Meningiomas are predominantly benign, but some cases exhibit recurrent growth after surgery and undergo malignant transformation to WHO grade 2 or grade 3. Despite progress in genetic analyses, advancements in metabolomic analysis remain less established. Herein, the authors investigated metabolic activity differences between WHO grade 1 meningiomas and WHO grade 2 or 3 meningiomas by noninvasively using proton magnetic resonance spectroscopy (1H-MRS), aiming to preoperatively estimate malignancy. They also reviewed the literature to elucidate this aspect of meningioma research. METHODS: At Ryukyu University Hospital, the authors focused on 93 patients diagnosed with meningioma between 2011 and 2021. The inclusion criteria encompassed prior surgery, pathological diagnoses of meningioma, and preoperative 1H-MRS. Group I included 71 patients with WHO grade 1 meningioma and group II included 22 patients, comprising 19 and 3 with WHO grade 2 and 3 meningioma, respectively. The authors retrospectively conducted a comparative analysis of patient backgrounds and tumor metabolites. RESULTS: Group I and II did not differ significantly in terms of patient demographic characteristics (age and sex). Group II demonstrated a significantly lower extent of tumor resection (p < 0.01), higher MIB-1 labeling index (LI) (p < 0.05), higher incidence of prior irradiation (p < 0.001), and increased rate of tumor recurrence (p = 0.005) compared to group I. According to 1H-MRS, all metabolites, except lactate, displayed significantly higher median creatine (Cr) ratios in group II than group I: glutamine/Cr was 8.46, glutamate/Cr was 9.49, lipid/Cr was 11.36, and choline/Cr was 2.77. According to the receiver operating characteristic (ROC) analysis, glutamine had the largest area under the curve of 0.765 among 10 metabolites, and the cutoff value for distinguishing between group I and II was 5.76. CONCLUSIONS: In cases pathologically graded as WHO grade 2 or 3 meningiomas, metabolic products such as glutamine, glutamate, lipids, and choline increased significantly. These changes were correlated with elevation of the MIB-1 LI. In group II, the mean MIB-1 LI was 8.58, significantly higher than in group I, suggesting a strong association with pathological malignancy. Therefore, 1H-MRS may help to noninvasively predict tumor metabolic activity and tumor recurrence. Furthermore, the authors concluded from the ROC analysis that glutamine may be a potential indicator of future growth of meningioma and benefits of early surgery.

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INTRODUCTION: Acute ischemic stroke causes irreversible damage to the brain parenchyma surrounded by salvageable tissue known as the ischemic penumbra. Magnetic resonance imaging (MRI), particularly the mismatch between abnormal diffusion-weighted imaging (DWI) signals and normal fluid-attenuated inversion recovery (FLAIR) signals, plays a critical role in detecting ischemic penumbra. It also allows for the identification of patients who may benefit from reperfusion therapy. Hence, this prospective cohort study aimed to explore the correlation between DWI-FLAIR mismatch and clinical outcomes in acute ischemic stroke patients, specifically those with delayed or uncertain symptom onset, offering potential insights into reperfusion therapy. METHODOLOGY: A total of 38 thrombotic stroke patients aged above 18 were included in this prospective cohort study. Baseline data, including demographics, lifestyle factors, and medical history, were recorded. DWI-FLAIR mismatch was evaluated through brain MRI within 4.5 hours to 12 hours of symptom onset. RESULTS:  Of the cohort, 63.2% were males, predominantly in the 61-70 age group. Smoking and alcohol consumption were reported by 15.79% each. DWI-FLAIR mismatch was present in 20 out of 38 subjects. No statistically significant differences were noted in the mean National Institutes of Health Stroke Scale (NIHSS) and Modified Rankin Scale (MRS) scores between subjects with and without DWI-FLAIR mismatch. Thrombolysis in wake-up stroke subjects demonstrated a substantial reduction in mean MRS at discharge (1.29±0.95) and at six to eight weeks (1.71±1.11), suggesting potential benefits on functional outcomes. CONCLUSION:  The prevalence of DWI-FLAIR mismatch was seen in the majority of patients beyond their window period and also showed beneficiary outcomes with a mean reduction in NHISS and MRS scores following thrombolysis.

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Background: Hereditary Spastic Paraplegias (HSP) are genetic neurodegenerative disorders affecting the corticospinal tract. No established neuroimaging biomarker is associated with this condition. Methods: A total of 46 patients affected by HSP, genetically and clinically evaluated and tested with SPRS scores, and 46 healthy controls (HC) matched by age and gender underwent a single-voxel Magnetic Resonance Spectroscopy sampling (MRS) of bilateral pre-central and pre-frontal regions. MRS data were analyzed cross-sectionally (at T0 and T1) and longitudinally (T0 vs. T1). Results: Statistically significant data showed that T0 mI/Cr in the pre-central areas of HSP patients was higher than in HC. In the left (L) pre-central area, NAA/Cr was significantly lower in HSP than in HC. In the right (R) pre-frontal area, NAA/Cr was significantly lower in HSP patients than in HC. HSP SPG4 subjects had significantly lower Cho/Cr concentrations in the L pre-central area compared to HC. Among the HSP subjects, non-SPG4 patients had significantly higher mI/Cr in the L pre-central area compared to SPG4 patients. In the R pre-frontal area, NAA/Cr was reduced, and ml/Cr was higher in non-SPG4 patients compared to SPG4 patients. Comparing "pure" and "complex" forms, NAA/Cr was higher in pHSP than in cHSP in the R pre-central and R pre-frontal areas. The longitudinal analysis, which involved fewer patients (n = 30), showed an increase in mI/Cr concentration in the L pre-frontal area among HSP subjects with respect to baseline. The patients had significantly higher SPRS scores at follow-up, with a significant positive correlation between SPRS scores and mI/Cr in the L pre-central area, while in bilateral pre-frontal areas, lower SPRS scores corresponded to higher NAA/Cr concentrations. To explore the discriminating power of MRS in correctly identifying HSP and controls, an inference tree methodology classified HSP subjects and controls with an overall accuracy of 73.9%, a sensitivity of 87.0%, and a specificity of 60.9%. Conclusion: This pilot study indicates that brain MRS is a valuable approach that could potentially serve as an objective biomarker in HSP.

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Breast Cancer Associated Susceptibility Proteins Type 1/2 (BRCA1/2) promote cellular functioning by modulating NRF2-mediated antioxidant signaling. Redox failure in women with BRCA1/2 insufficiency increases the risk for breast/ovarian/uterine cancers. Risk-reducing salpingo-oophorectomy (RRSO) is a prophylactic surgery of the reproductive organs, which is frequently conducted by the age of 40 to lower the occurrence of cancer in women with BRCA1/2 mutations. However, abrupt estrogen decline following RRSO causes ovarian failure, which implicates various cellular physiological processes, resulting in the increased release of free radicals and subsequent severe onset of menopausal symptoms. Comfort measures (e.g., hormonal replacement therapy (HRT) and mindfulness-based stress reduction (MBSR)) may improve chronological menopause-related quality of life, but their specific effects are not clear in women with gene mutations. Aiming to fill the gap, this study used path analysis to examine the effects of HRT and MBSR on menopausal symptoms among RRSO patients (N = 199, mean age = 50.5 ± 6.7 years). HRT directly alleviated the levels of urogenital symptoms (ß = -0.195, p = 0.005), which mediated its indirect significant effects on the somatic-vegetative and psychological symptoms of menopause (ß = -0.046, -0.067; both p values = 0.004, respectively), especially in BRCA2 carriers and in women who were currently physically active, premenopausal at the time of RRSO, had a high BMI, and had no history of breast cancer. It increased the severity of urogenital symptoms in women with a history of cancer. MBSR, on the other hand, was associated with indirect increases in the intensity of the somatic-vegetative and psychological symptoms of menopause (ß = 0.108, 0.029; p = 0.003, 0.033, respectively). It exerted positive direct effects on different menopausal symptoms in multigroup analysis. The results suggest that young women undergoing recent RRSO may benefit from HRT at an individual level, while their need for extensive measures to optimize their psychological wellbeing is ongoing. The adverse effects of MBSR, which are captured in the present study, imply that MBSR may interfere with redox sensitivity associated with estradiol fluctuations in BRCA1/2 carriers. Investigations are needed to test this hypothesis and elaborate on the underlying mechanisms in these women.

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PURPOSE: Recurrence for high-grade gliomas is inevitable despite maximal safe resection and adjuvant chemoradiation, and current imaging techniques fall short in predicting future progression. However, we introduce a novel whole-brain magnetic resonance spectroscopy (WB-MRS) protocol that delves into the intricacies of tumor microenvironments, offering a comprehensive understanding of glioma progression to inform expectant surgical and adjuvant intervention. METHODS: We investigated five locoregional tumor metabolites in a post-treatment population and applied machine learning (ML) techniques to analyze key relationships within seven regions of interest: contralateral normal-appearing white matter (NAWM), fluid-attenuated inversion recovery (FLAIR), contrast-enhancing tumor at time of WB-MRS (Tumor), areas of future recurrence (AFR), whole-brain healthy (WBH), non-progressive FLAIR (NPF), and progressive FLAIR (PF). Five supervised ML classification models and a neural network were developed, optimized, trained, tested, and validated. Lastly, a web application was developed to host our novel calculator, the Miami Glioma Prediction Map (MGPM), for open-source interaction. RESULTS: Sixteen patients with histopathological confirmation of high-grade glioma prior to WB-MRS were included in this study, totaling 118,922 whole-brain voxels. ML models successfully differentiated normal-appearing white matter from tumor and future progression. Notably, the highest performing ML model predicted glioma progression within fluid-attenuated inversion recovery (FLAIR) signal in the post-treatment setting (mean AUC = 0.86), with Cho/Cr as the most important feature. CONCLUSIONS: This study marks a significant milestone as the first of its kind to unveil radiographic occult glioma progression in post-treatment gliomas within 8 months of discovery. These findings underscore the utility of ML-based WB-MRS growth predictions, presenting a promising avenue for the guidance of early treatment decision-making. This research represents a crucial advancement in predicting the timing and location of glioblastoma recurrence, which can inform treatment decisions to improve patient outcomes.

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OBJECTIVES: This study aimed to determine the risk factors and stroke subtypes for young ischemic stroke patients and their outcomes at the time of discharge. METHODS: This is a retrospective cross-sectional study of ischemic stroke patients (n = 264) between the age groups of 18 and 45. The study population was divided into two broad age groups: 18 to 35 years and 36 to 45 years; and compared based on demographics, risk factors, the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, and outcomes. The outcomes were compared based on the National Institutes of Health Stroke Scale (NIHSS) and Modified Rankin Scale (MRS) systems at the time of admission and discharge. RESULTS: The mean age of patients was 37.84±6.19 years. The male-to-female ratio was 2.5:1. The most common vascular risk factors identified were diabetes (29.16%), hypertension (49.62%), dyslipidaemia (DLP, 44.4%), and smoking (10.9%). The most common TOAST subtype was large vessel disease (38.63%), followed by the undetermined category (35.6%). The elderly group showed a high proportion of strokes secondary to small vessel disease (14.13%; p = 0.03), while cardioembolic strokes were common in the female subgroup (p = 0.05). The majority of strokes were in the anterior circulation (66.6%) as compared to the posterior (25.75%), and nearly 50% of the patients had intracranial disease. Overall, there was a favourable MRS outcome at discharge. CONCLUSION: Conventional vascular risk factors are equally prevalent, even among young stroke patients. The benchmark for young stroke age is showing a downward shift as more stroke patients above the age of 35 are showing similar risk factor trends as those of their older counterparts. The majority of stroke burden still falls under the undermined category, which requires aggressive risk factor identification and management.

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Gamma-aminobutyric acid (GABA), the most important inhibitory neurotransmitter in the human brain, has long been considered essential in human behavior in general and learning in particular. GABA concentration can be quantified using magnetic resonance spectroscopy (MRS). Using this technique, numerous studies have reported associations between baseline GABA levels and various human behaviors. However, regional GABA concentration is not fixed and may exhibit rapid modulation as a function of environmental factors. Hence, quantification of GABA levels at several time points during the performance of tasks can provide insights into the dynamics of GABA levels in distinct brain regions. This review reports on findings from studies using repeated measures (n = 41) examining the dynamic modulation of GABA levels in humans in response to various interventions in the perceptual, motor, and cognitive domains to explore associations between GABA modulation and human behavior. GABA levels in a specific brain area may increase or decrease during task performance or as a function of learning, depending on its precise involvement in the process under investigation. Here, we summarize the available evidence and derive two overarching hypotheses regarding the role of GABA modulation in performance and learning. Firstly, training-induced increases in GABA levels appear to be associated with an improved ability to differentiate minor perceptual differences during perceptual learning. This observation gives rise to the 'GABA increase for better neural distinctiveness hypothesis'. Secondly, converging evidence suggests that reducing GABA levels may play a beneficial role in effectively filtering perceptual noise, enhancing motor learning, and improving performance in visuomotor tasks. Additionally, some studies suggest that the reduction of GABA levels is related to better working memory and successful reinforcement learning. These observations inspire the 'GABA decrease to boost learning hypothesis', which states that decreasing neural inhibition through a reduction of GABA in dedicated brain areas facilitates human learning. Additionally, modulation of GABA levels is also observed after short-term physical exercise. Future work should elucidate which specific circumstances induce robust GABA modulation to enhance neuroplasticity and boost performance.

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