Impact of Vaccination Status on Outcome of Patients With COVID-19 and Acute Ischemic Stroke Undergoing Mechanical Thrombectomy.

BACKGROUND: Data on impact of COVID-19 vaccination and outcomes of patients with COVID-19 and acute ischemic stroke undergoing mechanical thrombectomy are scarce. Addressing this subject, we report our multicenter experience. METHODS AND RESULTS: This was a retrospective analysis of patients with COVID-19 and known vaccination status treated with mechanical thrombectomy for acute ischemic stroke at 20 tertiary care centers between January 2020 and January 2023. Baseline demographics, angiographic outcome, and clinical outcome evaluated by the modified Rankin Scale score at discharge were noted. A multivariate analysis was conducted to test whether these variables were associated with an unfavorable outcome, defined as modified Rankin Scale score >3. A total of 137 patients with acute ischemic stroke (48 vaccinated and 89 unvaccinated) with acute or subsided COVID-19 infection who underwent mechanical thrombectomy attributable to vessel occlusion were included in the study. Angiographic outcomes between vaccinated and unvaccinated patients were similar (modified Thrombolysis in Cerebral Infarction ≥2b: 85.4% in vaccinated patients versus 86.5% in unvaccinated patients; P=0.859). The rate of functional independence (modified Rankin Scale score, ≤2) was 23.3% in the vaccinated group and 20.9% in the unvaccinated group (P=0.763). The mortality rate was 30% in both groups. In the multivariable analysis, vaccination status was not a significant predictor for an unfavorable outcome (P=0.957). However, acute COVID-19 infection remained significant (odds ratio, 1.197 [95% CI, 1.007-1.417]; P=0.041). CONCLUSIONS: Our study demonstrated no impact of COVID-19 vaccination on angiographic or clinical outcome of COVID-19-positive patients with acute ischemic stroke undergoing mechanical thrombectomy, whereas worsening attributable to COVID-19 was confirmed.

Could Phosphorous MR Spectroscopy Help Predict the Severity of Vasospasm? A Pilot Study.

One of the main causes of the dismal prognosis in patients who survive the initial bleeding after aneurysmal subarachnoidal hemorrhage is the delayed cerebral ischaemia caused by vasospasm. Studies suggest that cerebral magnesium and pH may potentially play a role in the pathophysiology of this adverse event. Using phosphorous magnetic resonance spectrocopy (31P-MRS), we calculated the cerebral magnesium (Mg) and pH levels in 13 patients who suffered from aSAH. The values between the group that developed clinically significant vasospasm (n = 7) and the group that did not (n = 6) were compared. The results of this study show significantly lower cerebral Mg levels (p = 0.019) and higher pH levels (p < 0.001) in the cumulative group (all brain voxels together) in patients who developed clinically significant vasospasm. Further clinical studies on a larger group of carefully selected patients are needed in order to predict clinically significant vasospasm.

Relationship between Brain Function and Microstructural Brain Maturation in Preterm Infants.

INTRODUCTION: Preterm infants are at risk for impairment in brain maturation at term equivalent age (TEA). Diffusion tensor imaging (DTI) is a powerful magnetic resonance imaging (MRI) technique, quantitatively reflecting microstructural brain development of white matter regions with parameters such as fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Amplitude-integrated electroencephalography (aEEG) assesses electrocortical activity and brain function. METHODS: Aim of this study was to investigate a possible correlation between functional and microstructural brain maturation using neonatal aEEG and DTI-MRI at TEA. The study was conducted as a retrospective single-center study in 446 infants born below 32 gestational weeks. Spearman rank's correlation coefficients were calculated between aEEG (total maturation score) and FA/ADC value. To compare aEEG and DTI-MRI to neurodevelopmental outcome at 24 months of corrected age, we performed a multivariate linear regression analysis. RESULTS: Analysis showed an all-time significant correlation between total maturation score and FA/ADC values of the corpus callosum at TEA with the strongest correlation at day 2, day 3, week 3, and week 4. After including perinatal variables in the model, this correlation remained highly significant at day 2 and 3. When comparing the association of aEEG and DTI-MRI to outcome, both the total maturation score at day 2, day 3, and FA/ADC of the splenium of the corpus callosum showed a significant correlation. CONCLUSION: This study indicates that early monitoring of functional brain maturation may predict later assessment of microstructural brain development of corpus callosum in preterm infants with a relation to neurodevelopmental outcome.

The Effect of Postnatal Cytomegalovirus Infection on (Micro)structural Cerebral Development in Very Preterm Infants at Term-Equivalent Age.

INTRODUCTION: There are some data indicating a negative impact of postnatal cytomegalovirus (CMV) infection on long-term neurodevelopmental outcome of preterm infants. So far, there is only little knowledge about a cerebral imaging correlate of these neurodevelopmental alterations induced by postnatal CMV infection in preterm infants. The aim of the current study was to investigate the effect of postnatal CMV infection on the incidence of brain injury and on microstructural brain maturation in very preterm infants at term-equivalent age. METHODS: Infants <32 gestational weeks (02/2011-11/2018) received cerebral MRI including axial diffusion-weighted images at term-equivalent age. All infants were screened for CMV infection using urine/saliva samples, and infection was regarded as acquired postnatal if a sample became positive >5 postnatal days. We compared brain injury as well as fractional anisotropy and apparent diffusion coefficient in 14 defined cerebral regions between infants with and without postnatal CMV infection. RESULTS: 401 infants were eligible, of whom 18 (4.5%) infants had a postnatal CMV infection. There were no significant differences in rates of brain injury or in microstructural brain development between both groups. This applied equally to the subgroup of infants <28 gestational weeks. CONCLUSION: Although infants with postnatal CMV infection were born more immature and more frequently suffered from complications related to immaturity, we neither observed a higher rate of preterm brain injury nor disadvantageous alterations in microstructural brain maturation at term-equivalent age.

Microstructural Brain Development and Neurodevelopmental Outcome of Very Preterm Infants of Mothers with Gestational Diabetes Mellitus.

INTRODUCTION: There are data linking gestational diabetes mellitus (GDM) with adverse neurodevelopmental outcome in the offspring. We investigated the effect of GDM on microstructural brain development and neurodevelopmental outcome of very preterm infants. MATERIALS AND METHODS: Preterm infants <32 gestational weeks of mothers with GDM obtained cerebral magnetic resonance imaging (MRI) including diffusion-tensor imaging at term-equivalent age. For every infant, two gestational age-, sex-, and MRI scanner type-matched controls were included. Brain injury was assessed and fractional anisotropy (FA) and apparent diffusion coefficient (ADC) measured in 14 defined cerebral regions. Neurodevelopmental outcome was quantified at the corrected age of 24 months using the Bayley Scales of Infant Development. RESULTS: We included 47 infants of mothers with GDM and 94 controls. There were no differences in neonatal morbidity between the groups, nor in any type of brain injury. The GDM group showed significantly higher FA values in the centrum semiovale, the posterior limb of the internal capsule and the pons bilaterally, in the corpus callosum and the right occipital white matter, as well as lower ADC values in the right centrum semiovale, the right occipital white matter and the corpus callosum. Neurodevelopmental outcome did not differ between the groups. CONCLUSION: We found no impairment of brain development in GDM-exposed infants compared to matched controls, but differences in white matter microstructure in specific regions indicating an enhanced maturation. However, neurodevelopmental outcome was equal in both groups. Further studies are needed to better understand brain maturation in preterm infants exposed to GDM.

Attachment Trauma Is Associated with White Matter Fiber Microstructural Alterations in Adolescents with Anorexia Nervosa before and after Exposure to Psychotherapeutic and Nutritional Treatment.

In the present study, we explore the role of attachment for microstructural white matter (WM) changes in adolescents with anorexia nervosa (AN) before and after exposure to short-term and nutritional treatment. The case sample consisted of 22 female adolescent inpatients with AN (mean age: 15.2 ± 1.2 years) and the control sample were 18 gender-matched healthy adolescents (mean age: 16.8 ± 0.9 years). We performed a 3T MRI in the patient group during the acute state of AN and after weight restoration (duration: 2.6 ± 1 months) and compared the data to a healthy control group. To classify attachment patterns, we used the Adult Attachment Projective Picture System. In the patient sample, over 50% were classified with an attachment trauma/unresolved attachment status. Prior to treatment exposure, fractional anisotropy (FA) reductions and concordant mean diffusivity (MD) increases were evident in the fornix, the corpus callosum and WM regions of the thalamus, which normalized in the corpus callosum and the fornix post-therapy in the total patient sample (p < 0.002). In the acute state, patients with an attachment trauma demonstrated significant FA decreases compared to healthy controls, but no MD increases, in the corpus callosum and cingulum bilaterally, which remained decreased after therapy. Attachment patterns seem to be associated with region-specific changes of WM alterations in AN.

Evaluation of visual food stimuli paradigms on healthy adolescents for future use in fMRI studies in anorexia nervosa.

BACKGROUND: Mostly, visual food stimuli paradigms for functional Magnetic Resonance Imaging are used in studies of eating disorders. However, the optimal contrasts and presentation modes are still under discussion. Therefore, we aimed to create and analyse a visual stimulation paradigm with defined contrast. METHODS: In this prospective study, a block-design fMRI paradigm with conditions of randomly altering blocks of high- and low-calorie food images and images of fixation cross was established. Food pictures were rated in advance by a group of patients diagnosed with anorexia nervosa to address the dedicated perception of patients with eating disorders. To optimize the scanning procedure and fMRI contrasts we have analysed neural activity differences between high-calorie stimuli versus baseline (H vs. X), low-calorie stimuli versus baseline (L vs. X) and high- versus low-calorie stimuli (H vs. L). RESULTS: By employing the developed paradigm, we were able to obtain results comparable to other studies and analysed them with different contrasts. Implementation of the contrast H versus X led to increased blood-oxygen-level-dependent signal (BOLD) mainly in unspecific areas, such as the visual cortex, the Broca´s area, bilaterally in the premotor cortex and the supplementary motor area, but also in thalami, insulae, the right dorsolateral prefrontal cortex, the left amygdala, the left putamen (p < .05). When applying the contrast L versus X, an enhancement of the BOLD signal was detected similarly within the visual area, the right temporal pole, the right precentral gyrus, Broca´s area, left insula, left hippocampus, the left parahippocampal gyrus, bilaterally premotor cortex and thalami (p < .05). Comparison of brain reactions regarding visual stimuli (high- versus low-calorie food), assumed to be more relevant in eating disorders, resulted in bilateral enhancement of the BOLD signal in primary, secondary and associative visual cortex (including fusiform gyri), as well as angular gyri (p < .05). CONCLUSIONS: A carefully designed paradigm, based on the subject's characteristics, can increase the reliability of the fMRI study, and may reveal specific brain activations elicited by this custom-built stimuli. However, a putative disadvantage of implementing the contrast of high- versus low-calorie stimuli might be the omission of some interesting outcomes due to lower statistical power. Trial registration NCT02980120.

Although the relationship with food is crucial for living, its underlying mechanisms (e.g., neurological, cognitive, physiological) are still not fully discovered. The development of functional magnetic resonance imaging made it possible to explore brain's responses to images of food. However, a proper methodological analysis of the research paradigm is still lacking. Here, we present the optimization of visual food stimuli paradigms achieved by comparison of neural activations of 20 female healthy adolescents after applying particular contrasts (i.e., high- versus low-calorie food images, high-calorie food images versus baseline, low-calorie food images versus baseline). Application of the contrast high- versus low-calorie food images resulted in stronger neural activation in visual cortex (including fusiform gyri) and angular gyri. This study highlights the importance of choosing a proper contrast regarding the study hypothesis, as it may induce more specific results. However, it may lead to loss of some outcomes, due to lower statistical power. Additionally, we have performed an evaluation of visual food stimuli chosen by patients diagnosed with anorexia nervosa. They have selected images of the most and the least willingly eaten meals. Although they didn't know the exact calorie content, they chose intuitively photos later classified as extremely high- or low-caloric.

Peritumoral ADC Values Correlate with the MGMT Methylation Status in Patients with Glioblastoma.

Different results have been reported concerning the relationship of the apparent diffusion coefficient (ADC) values and the status of methylation as the promoter gene for the enzyme methylguanine-DNA methyltransferase (MGMT) in patients with glioblastomas (GBs). The aim of this study was to investigate if there were correlations between the ADC values of the enhancing tumor and peritumoral areas of GBs and the MGMT methylation status. In this retrospective study, we included 42 patients with newly diagnosed unilocular GB with one MRI study prior to any treatment and histopathological data. After co-registration of ADC maps with T1-weighted sequences after contrast administration and dynamic susceptibility contrast (DSC) perfusion, we manually selected one region-of-interest (ROI) in the enhancing and perfused tumor and one ROI in the peritumoral white matter. Both ROIs were mirrored in the healthy hemisphere for normalization. In the peritumoral white matter, absolute and normalized ADC values were significantly higher in patients with MGMT-unmethylated tumors, as compared to patients with MGMT-methylated tumors (absolute values p = 0.002, normalized p = 0.0007). There were no significant differences in the enhancing tumor parts. The ADC values in the peritumoral region correlated with MGMT methylation status, confirmed by normalized ADC values. In contrast to other studies, we could not find a correlation between the ADC values or the normalized ADC values and the MGMT methylation status in the enhancing tumor parts.

Slice positioning in phase-contrast MRI impacts aortic stenosis assessment.

AIMS: To determine the phase-contrast cardiovascular magnetic resonance imaging (PC-CMR) slice-position above aortic leaflet-attachment-plane (LAP) that provides flow-velocity, -volume and aortic valve area (AVA) measurements with best agreement to invasive and echocardiographic measurements in aortic stenosis (AS). METHODS AND RESULTS: Fifty-five patients with moderate/severe AS underwent cardiac catheterization, transthoracic echocardiography (TTE) and CMR. Overall, 171 image-planes parallel to LAP were measured via PC-CMR between 22 mm below and 24 mm above LAP. AVA via PC-CMR was calculated as flow-volume divided by peak-velocity during systole. Stroke volume (SV) and AVA were compared to volumetric SV and invasive AVA via the Gorlin-formula, respectively. Above LAP, SV by PC-CMR showed no significant dependence on image-plane-position and correlated strongly with volumetry (rho: 0.633, p < 0.001, marginal-mean-difference (MMD): 1 ml, 95 % confidence-interval (CI): -4 to 6). AVA assessed in image-planes 0-10 mm above LAP differed significantly from invasive measurement (MMD: -0.14 cm2, 95 %CI: 0.08-0.21). In contrast, AVA-values by PC-CMR measured 10-20 mm above LAP showed good agreement with invasive determination without significant MMD (0.003 cm2, 95 %CI: -0.09 to 0.09). Within these measurements, a plane 15 mm above LAP resulted in the lowest bias (MMD: 0.02 cm2, 95 %CI:-0.29 to 0.33). SV and AVA via TTE correlated moderately with volumetry (rho: 0.461, p < 0.001; bias: 15 ml, p < 0.001) and cardiac catheterization (rho: 0.486, p < 0.001, bias: -0.13 cm2, p < 0.001), respectively. CONCLUSION: PC-CMR measurements at 0-10 mm above LAP should be avoided due to significant AVA-overestimation compared to invasive determination. AVA-assessment by PC-CMR between 10 and 20 mm above LAP did not differ from invasive measurements, with the lowest intermethodical bias measured 15 mm above LAP.

A deep learning pipeline for the automated segmentation of posterior limb of internal capsule in preterm neonates.

Segmentation of specific brain tissue from MRI volumes is of great significance for brain disease diagnosis, progression assessment, and monitoring of neurological conditions. Manual segmentation is time-consuming, laborious, and subjective, which significantly amplifies the need for automated processes. Over the last decades, the active development in the field of deep learning, especially convolutional neural networks (CNNs), and the associated performance improvements have increased the demand for the application of CNN-based methods to provide consistent measurements and quantitative analyses. In this paper, we present an efficient deep learning approach for the segmentation of brain tissue. More specifically, we address the problem of segmentation of the posterior limb of the internal capsule (PLIC) in preterm neonates. To this end, we propose a CNN-based pipeline comprised of slice-selection modules and a multi-view segmentation model, which exploits the 3D information contained in the MRI volumes to improve segmentation performance. One special feature of the proposed method is its ability to identify one desired slice out of the whole image volume, which is relevant for pediatricians in terms of prognosis. To increase computational efficiency, we apply a strategy that automatically reduces the information contained in the MRI volumes to its relevant parts. Finally, we conduct an expert rating alongside standard evaluation metrics, such as dice score, to evaluate the performance of the proposed framework. We demonstrate the benefit of the multi-view technique by comparing it with its single-view counterparts, which reveals that the proposed method strikes a good balance between exploiting the available image information and reducing the required computing power compared to 3D segmentation networks. Standard evaluation metrics as, well as expert-based assessment, confirm the good performance of the proposed framework, with the latter being more relevant in terms of clinical applicability. We demonstrate that the proposed deep learning pipeline can compete with the experts in terms of accuracy. To prove the generalisability of the proposed method, we additionally assess our deep learning pipeline to data from the Developing Human Connectome Project (dHCP).

Limbic Responses to Aversive Visual Stimuli during the Acute and Recovery Phase of Takotsubo Syndrome.

The role of the limbic system in the acute phase and during the recovery of takotsubo syndrome needs further clarification. In this longitudinal study, anatomical and task-based functional magnetic resonance imaging of the brain was performed during an emotional picture paradigm in 19 postmenopausal female takotsubo syndrome patients in the acute and recovery phases in comparison to sex- and aged-matched 15 healthy controls and 15 patients presenting with myocardial infarction. Statistical analyses were performed based on the general linear model where aversive and positive picture conditions were included in order to reveal group differences during encoding of aversive versus positive pictures and longitudinal changes. In the acute phase, takotsubo syndrome patients showed a lower response in regions involved in affective and cognitive emotional processes (e.g., insula, thalamus, frontal cortex, inferior frontal gyrus) while viewing aversive versus positive pictures compared to healthy controls and patients presenting with myocardial infarction. In the recovery phase, the response in these brain regions normalized in takotsubo syndrome patients to the level of healthy controls, whereas patients 8-12 weeks after myocardial infarction showed lower responses in the limbic regions (mainly in the insula, frontal regions, thalamus, and inferior frontal gyrus) compared to healthy controls and takotsubo syndrome patients. In conclusion, compared to healthy controls and patients suffering from acute myocardial infarction, limbic responses to aversive visual stimuli are attenuated during the acute phase of takotsubo syndrome, recovering within three months. Reduced functional brain responses in the recovery phase after a myocardial infarction need further investigation.

Magnetic Resonance Spectroscopy in Diagnosis and Follow-Up of Gliomas: State-of-the-Art.

Preoperative grade prediction is important in diagnostics of glioma. Even more important can be follow-up after chemotherapy and radiotherapy of high grade gliomas. In this review we provide an overview of MR-spectroscopy (MRS), technical aspects, and different clinical scenarios in the diagnostics and follow-up of gliomas in pediatric and adult populations. Furthermore, we provide a recap of the current research utility and possible future strategies regarding proton- and phosphorous-MRS in glioma research.

Cerebral Energy Status and Altered Metabolism in Early Brain Injury After Aneurysmal Subarachnoid Hemorrhage: A Prospective 31P-MRS Pilot Study.

Background: Acute changes of cerebral energy metabolism in early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (aSAH) may play a crucial role for overall neurological outcome. However, direct detection of these alterations is limited. Phosphorous magnetic resonance spectroscopy (31P-MRS) is a molecular-based advanced neuroimaging technique allowing measurements of pathophysiological processes and tissue metabolism based on various phosphorous compound metabolites. This method may provide objective assessment of both primary and secondary changes. Objective: The aim of this pilot study was to evaluate the feasibility and the diagnostic potential of early 31P-MRS in aSAH. Methods: Patients with aSAH treated for ruptured aneurysms between July 2016 and October 2017 were prospectively included in the study. 3-Tesla-MRI including 31P-MRS was performed within the first 72 h after hemorrhage. Data of the vascular territories of the anterior, middle, and posterior cerebral arteries (ACA, MCA, PCA) and the basal ganglia were separately analyzed and compared with data of a healthy age- and sex-matched control group. Phosphorous compound metabolites were quantified, and ratios of these metabolites were further evaluated. Influence of treatment modality, clinical conditions, and analgosedation were analyzed. Results: Data of 13 patients were analyzed. 31P-MRS showed significant changes in cerebral energy metabolism after aSAH in all cerebrovascular territories. Both PCr/ATP and PCr/Pi ratio were notably increased (P < 0.001). Also, Pi/ATP was significantly decreased in all cerebrovascular territories (P = 0.014). PME/PDE ratio was overall significant decreased (P < 0.001). Conclusion: 31P-MRS is a promising non-invasive imaging tool for the assessment of changes in energy metabolism after aSAH. It allows a detailed insight into EBI and seems to harbor a high potential for clinical practice.

Prophylactic Low-Dose Paracetamol Administration for Ductal Closure and Microstructural Brain Development in Preterm Infants.

INTRODUCTION: Prophylactic low-dose paracetamol administration is used to induce closure of the ductus arteriosus. Effects on the neurological outcome in preterm infants remain unknown. We compared microstructural brain development in very preterm infants with and without exposure to prophylactic paracetamol by using MR-based diffusion tensor imaging. MATERIALS AND METHODS: Infants aged <32 gestational weeks born between October 2014 and December 2018 received prophylactic paracetamol (10 mg/kg intravenously every 8 h until echocardiography after at least 72 h) and form the paracetamol group; infants born between February 2011 and September 2014 form the control group. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) at term-equivalent age were measured in 14 defined cerebral regions and compared between the groups. RESULTS: Included in the study were 340 infants, of whom 217 received prophylactic paracetamol, and 123 formed the control group. The paracetamol group showed significantly higher FA values and lower ADC values in the splenium of the corpus callosum, as well as higher FA values in the pons bilaterally, the left middle cerebellar peduncle, the right occipital white matter, and the right posterior limb of the internal capsule (p ≤ 0.02). CONCLUSION: The perceived safety of prenatal paracetamol exposure has been questioned in recent years. We found no impairment on microstructural maturation processes in the brain of preterm infants at term-equivalent age following early paracetamol administration. The clinical relevance of these imaging findings has to be determined in long-term follow-up studies on neurodevelopmental outcome.

Attachment status is associated with grey matter recovery in adolescent anorexia nervosa: Findings from a longitudinal study.

The aim of the present study was to investigate whether grey matter (GM) reductions in acute anorexia nervosa (AN) are (i) valid for adolescents (age 14-18 years), (ii) reversible following short-term psychotherapeutic and nutritional therapy and (iii) depend on psychological components like attachment trauma. 3T MRI including a high-resolution T1 MPRAGE was performed in 22 female adolescents in the acute state of AN (age: 15.2 ± 1.2 years) and after weight restoration (duration: 2.6 ± 1 months, n = 18) and compared with 18 gender-matched healthy controls. The Adult Attachment Projective Picture System was used to classify resolved and unresolved attachment patterns. GM decreases were localized in extensive cortical areas including the insula, prefrontal and cingulate cortices as well as subcortical regions during acute AN, which partially increased after therapy with a relative sparing of the hippocampus and parahippocampal gyrus. The resolved group showed more GM recovery in regions of the left hippocampus and parahippocampal gyrus, bilateral cerebellar regions, right precuneus and adjacent cingulate cortices relative to the unresolved pattern. Structural anomalies in adolescent AN that recovered after treatment may be primarily the consequence of malnutrition, whereas several regions did not display significant recovery. Attachment status seems to influence region-specific GM recovery.

Energy metabolism measured by 31P magnetic resonance spectroscopy in the healthy human brain.

BACKGROUND AND PURPOSE: Phosphorous magnetic resonance spectroscopy (31P-MRS) allows a non-invasive analysis of phosphorus-containing compounds in vivo. The present study investigated the influence of brain region, hemisphere, age, sex and brain volume on 31P-MRS metabolites in healthy adults. MATERIALS AND METHODS: Supratentorial brain 31P-MRS spectra of 125 prospectively recruited healthy volunteers (64 female, 61 male) aged 20 to 85 years (mean: 49.4 ± 16.9 years) were examined with a 3D-31P-MRS sequence at 3T, and the compounds phosphocreatine (PCr), inorganic phosphate (Pi) and adenosine triphosphate (ATP) were measured. From this data, the metabolite ratios PCr/ATP, Pi/ATP and PCr/Pi were calculated for different brain regions. In addition, volumes of gray matter, white matter and cerebrospinal fluid were determined. RESULTS: For all metabolite ratios significant regional differences and in several regions sex differences were found. In some brain regions and for some metabolites hemispheric differences were detected. In addition, changes with aging were found, which differed between women and men. CONCLUSIONS: The present results indicate that 31P-MRS metabolism varies throughout the brain, with age and between sexes, and therefore have important practical implications for the design and the interpretation of future 31P-MRS studies under physiological conditions and in patients with various cerebral diseases.

Changes in Brain Energy and Membrane Metabolism in Glioblastoma following Chemoradiation.

Brain parenchyma infiltration with glioblastoma (GB) cannot be entirely visualized by conventional magnetic resonance imaging (MRI). The aim of this study was to investigate changes in the energy and membrane metabolism measured with phosphorous MR spectroscopy (31P-MRS) in the presumably "normal-appearing" brain following chemoradiation therapy (CRT) in GB patients in comparison to healthy controls. Twenty (seven female, thirteen male) GB patients underwent a 31P-MRS scan prior to surgery (baseline) and after three months of standard CRT (follow-up examination. The regions of interest "contrast-enhancing (CE) tumor" (if present), "adjacent to the (former) tumor", "ipsilateral distant" hemisphere, and "contralateral" hemisphere were compared, differentiating between patients with stable (SD) and progressive disease (PD). Metabolite ratios PCr/ATP, Pi/ATP, PCr/Pi, PME/PDE, PME/PCr, and PDE/ATP were investigated. In PD, energy and membrane metabolism in CE tumor areas have a tendency to "normalize" under therapy. In different "normal-appearing" brain areas of GB patients, the energy and membrane metabolism either "normalized" or were "disturbed", in comparison to baseline or controls. Differences were also detected between patients with SD and PD. 31P-MRS might contribute as an additional imaging biomarker for outcome measurement, which remains to be investigated in a larger cohort.

Brain Energy Metabolism in Two States of Mind Measured by Phosphorous Magnetic Resonance Spectroscopy.

Introduction: Various functional neuroimaging studies help to better understand the changes in brain activity during meditation. The purpose of this study was to investigate how brain energy metabolism changes during focused attention meditation (FAM) state, measured by phosphorous magnetic resonance spectroscopy (31P-MRS). Methods: 31P-MRS imaging was carried out in 27 participants after 7 weeks of FAM training. Metabolite ratios and the absolute values of metabolites were assessed after meditation training in two MRI measurements, by comparing effects in a FAM state with those in a distinct focused attention awake state during a backwards counting task. Results: The results showed decreased phosphocreatine/ATP (PCr/ATP), PCr/ inorganic phosphate (Pi), and intracellular pH values in the entire brain, but especially in basal ganglia, frontal lobes, and occipital lobes, and increased Pi/ATP ratio, cerebral Mg, and Pi absolute values were found in the same areas during FAM compared to the control focused attention awake state. Conclusions: Changes in the temporal areas and basal ganglia may be interpreted as a higher energetic state induced by meditation, whereas the frontal and occipital areas showed changes that may be related to a down-regulation in ATP turnover, energy state, and oxidative capacity.

Phosphorous Magnetic Resonance Spectroscopy and Molecular Markers in IDH1 Wild Type Glioblastoma.

The World Health Organisation's (WHO) classification of brain tumors requires consideration of both histological appearance and molecular characteristics. Possible differences in brain energy metabolism could be important in designing future therapeutic strategies. Forty-three patients with primary, isocitrate dehydrogenase 1 (IDH1) wild type glioblastomas (GBMs) were included in this study. Pre-operative standard MRI was obtained with additional phosphorous magnetic resonance spectroscopy (31-P-MRS) imaging. Following microsurgical resection of the tumors, biopsy specimens underwent neuropathological diagnostics including standard molecular diagnosis. The spectroscopy results were correlated with epidermal growth factor (EGFR) and O6-Methylguanine-DNA methyltransferase (MGMT) status. EGFR amplified tumors had significantly lower phosphocreatine (PCr) to adenosine triphosphate (ATP)-PCr/ATP and PCr to inorganic phosphate (Pi)-PCr/Pi ratios, and higher Pi/ATP and phosphomonoesters (PME) to phosphodiesters (PDE)-PME/PDE ratio than those without the amplification. Patients with MGMT-methylated tumors had significantly higher cerebral magnesium (Mg) values and PME/PDE ratio, while their PCr/ATP and PCr/Pi ratios were lower than in patients without the methylation. In survival analysis, not-EGFR-amplified, MGMT-methylated GBMs showed the longest survival. This group had lower PCr/Pi ratio when compared to MGMT-methylated, EGFR-amplified group. PCr/Pi ratio was lower also when compared to the MGMT-unmethylated, EGFR not-amplified group, while PCr/ATP ratio was lower than all other examined groups. Differences in energy metabolism in various molecular subtypes of wild-type-GBMs could be important information in future precision medicine approach.

Phosphorous Magnetic Resonance Spectroscopy to Detect Regional Differences of Energy and Membrane Metabolism in Naïve Glioblastoma Multiforme.

Background: Glioblastoma multiforme (GBM) is a highly malignant primary brain tumor with infiltration of, on conventional imaging, normal-appearing brain parenchyma. Phosphorus magnetic resonance spectroscopy (31P-MRS) enables the investigation of different energy and membrane metabolites. The aim of this study is to investigate regional differences of 31P-metabolites in GBM brains. Methods: In this study, we investigated 32 patients (13 female and 19 male; mean age 63 years) with naïve GBM using 31P-MRS and conventional MRI. Contrast-enhancing (CE), T2-hyperintense, adjacent and distant ipsilateral areas of the contralateral brain and the brains of age- and gender-matched healthy volunteers were assessed. Moreover, the 31P-MRS results were correlated with quantitative diffusion parameters. Results: Several metabolite ratios between the energy-dependent metabolites and/or the membrane metabolites differed significantly between the CE areas, the T2-hyperintense areas, the more distant areas, and even the brains of healthy volunteers. pH values and Mg2+ concentrations were highest in visible tumor areas and decreased with distance from them. These results are in accordance with the literature and correlated with quantitative diffusion parameters. Conclusions: This pilot study shows that 31P-MRS is feasible to show regional differences of energy and membrane metabolism in brains with naïve GBM, particularly between the different "normal-appearing" regions and between the contralateral hemisphere and healthy controls. Differences between various genetic mutations or clinical applicability for follow-up monitoring have to be assessed in a larger cohort.