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.

Cervical artery tortuosity-a reliable semi-automated magnetic resonance-based method.

Background: Assessments of subclinical connective tissue disorders depend on complex approaches, emphasizing the need for more accessible methods applicable to clinical routine. Therefore, we aimed to establish a reliable approach assessing cervical vessel tortuosity, which is known to be associated with such disorders. Methods: Magnetic resonance angiography (MRA) images of ReSect study participants [single-center prospective cohort of spontaneous cervical artery dissection (sCeAD) patients] were used. Each patient underwent the same magnetic resonance imaging (MRI) protocol. The segmentation procedure was done using MATrix LABoratory 9.4 [up-sampling of raw MRA images, distance metric (DM) calculation], ITK-SNAP [region of interest (ROI) determination, vessel segmentation] and Vascular Modelling ToolKit (centerline determination). To assess inter-user variability and validity, we (I) had two blinded independent users segment all arteries and we (II) compared the results of our method to visual appraisal of vessel tortuosity done by two blinded expert neuro-radiologists. Results: A total of 526 extracranial cervical arteries were available for analysis. The inter-user variability of our method users was below 0.5% throughout. Overall, our method outperformed the visual tortuosity appraisal, as the visual grading underestimated the DM in 38.8% subjects when tasked to assess overall cervical artery tortuosity (both vertebral and internal carotid arteries) and in 16.6% and 33.3% respectively if tasked to grade anterior or posterior circulation separately. Conclusions: We present a reliable method to assess cervical artery tortuosity derived from MRA images applicable in clinical routine and future research investigating the potential correlation of sCeAD and connective tissue disorder.

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.

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.

Characterization and diagnostic potential of R2* in early-stage progressive supranuclear palsy variants.

INTRODUCTION: Iron accumulation in subcortical brain nuclei has been shown to be differentially increased in atypical parkinsonian disorders. It is unclear whether the patterns of iron accumulation are consistent between variants of progressive supranuclear palsy (PSP) and their diagnostic utility in early to moderately advanced stages of the diseases. METHODS: Brain iron content (R2*) was quantified using magnetic resonance imaging in patients clinically diagnosed as PSP - parkinsonism (PSP-P, n = 15), PSP - Richardson's syndrome (PSP-RS, n = 14), Parkinson's disease (PD, n = 15), or the parkinsonian variant of multiple system atrophy (MSA-P, n = 14) using established criteria, and healthy controls (HC). Disease duration was less than 5 years in all patients. The quantification of regional R2* was performed using a semi-automatized approach. RESULTS: Significant group differences in R2*, primarily within the red nucleus and the substantia nigra, were identified between PSP, PD, MSA-P, and HC, but not between PSP-P and PSP-RS. However, distinct R2* correlation patterns across brain regions were observed for the different groups. Good classification performances (sensitivity and specificity >80%) were only obtained for PSP vs. HC. For all other comparisons, sensitivity and/or specificity was below <70%. CONCLUSION: Iron accumulation in subcortical brain nuclei has distinct correlated patterns in PSP-P and PSP-RS, which could be reflecting different pathophysiological mechanisms. Increased iron content in these nuclei appears to be a predictor for atypical parkinsonian disorders such as PSP and MSA. Further studies are required to reproduce this finding and elucidate the evolution of these patterns over the course of the disease.

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.

Investigating the Migraine Cycle over 21 Consecutive Days Using Proton Magnetic Resonance Spectroscopy and Resting-State fMRI: A Pilot Study.

Recent neuroimaging studies have revealed important aspects of the underlying pathophysiological mechanisms of migraine suggesting abnormal brain energy metabolism and altered functional connectivity. Proton magnetic resonance spectroscopy (1H-MRS) studies investigated migraine patients in the interictal or ictal state. This first-of-its-kind study aimed to investigate the whole migraine cycle using 1H-MRS and resting-state functional magnetic resonance imaging (fMRI). A migraine patient underwent 1H-MRS and resting-state fMRI for 21 consecutive days, regardless of whether he was in an interictal or ictal state. Metabolite ratios were assessed and compared to the intrinsic connectivity of subcortical brain areas. Probable migraine phase-dependent changes in N-acetyl aspartate (NAA)/total creatine (tCr) and choline (Cho)/tCr levels are found in the left occipital lobe and left basal ganglia. NAA reflects neuronal integrity and Cho cellular membrane turnover. Such abnormalities may increase the susceptibility to excitatory migraine triggers. Functional connectivity between the right hippocampus and right or left pallidum was strongly correlated to the NAA/Cho ratio in the right thalamus, suggesting neurochemical modulation of these brain areas through thalamic connections. To draw statistically significant conclusions a larger cohort is needed.

ADC textural features in patients with single brain metastases improve clinical risk models.

AIMS: In this retrospective study we performed a quantitative textural analysis of apparant diffusion coefficient (ADC) images derived from diffusion weighted MRI (DW-MRI) of single brain metastases (BM) patients from different primary tumors and tested whether these imaging parameters may improve established clinical risk models. METHODS: We identified 87 patients with single BM who had a DW-MRI at initial diagnosis. Applying image segmentation, volumes of contrast-enhanced lesions in T1 sequences, hyperintense T2 lesions (peritumoral border zone (T2PZ)) and tumor-free gray and white matter compartment (GMWMC) were generated and registered to corresponding ADC maps. ADC textural parameters were generated and a linear backward regression model was applied selecting imaging features in association with survival. A cox proportional hazard model with backward regression was fitted for the clinical prognostic models (diagnosis-specific graded prognostic assessment score (DS-GPA) and the recursive partitioning analysis (RPA)) including these imaging features. RESULTS: Thirty ADC textural parameters were generated and linear backward regression identified eight independent imaging parameters which in combination predicted survival. Five ADC texture features derived from T2PZ, the volume of the T2PZ, the normalized mean ADC of the GMWMC as well as the mean ADC slope of T2PZ. A cox backward regression including the DS-GPA, RPA and these eight parameters identified two MRI features which improved the two risk scores (HR = 1.14 [1.05;1.24] for normalized mean ADC GMWMC and HR = 0.87 [0.77;0.97]) for ADC 3D kurtosis of the T2PZ.) CONCLUSIONS: Textural analysis of ADC maps in patients with single brain metastases improved established clinical risk models. These findings may aid to better understand the pathogenesis of BM and may allow selection of patients for new treatment options.

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.

Qualitative and Quantitative Comparison of Hippocampal Volumetric Software Applications: Do All Roads Lead to Rome?

Brain volumetric software is increasingly suggested for clinical routine. The present study quantifies the agreement across different software applications. Ten cases with and ten gender- and age-adjusted healthy controls without hippocampal atrophy (median age: 70; 25-75% range: 64-77 years and 74; 66-78 years) were retrospectively selected from a previously published cohort of Alzheimer's dementia patients and normal ageing controls. Hippocampal volumes were computed based on 3 Tesla T1-MPRAGE-sequences with FreeSurfer (FS), Statistical-Parametric-Mapping (SPM; Neuromorphometrics and Hammers atlases), Geodesic-Information-Flows (GIF), Similarity-and-Truth-Estimation-for-Propagated-Segmentations (STEPS), and Quantib™. MTA (medial temporal lobe atrophy) scores were manually rated. Volumetric measures of each individual were compared against the mean of all applications with intraclass correlation coefficients (ICC) and Bland-Altman plots. Comparing against the mean of all methods, moderate to low agreement was present considering categorization of hippocampal volumes into quartiles. ICCs ranged noticeably between applications (left hippocampus (LH): from 0.42 (STEPS) to 0.88 (FS); right hippocampus (RH): from 0.36 (Quantib™) to 0.86 (FS). Mean differences between individual methods and the mean of all methods [mm3] were considerable (LH: FS -209, SPM-Neuromorphometrics -820; SPM-Hammers -1474; Quantib™ -680; GIF 891; STEPS 2218; RH: FS -232, SPM-Neuromorphometrics -745; SPM-Hammers -1547; Quantib™ -723; GIF 982; STEPS 2188). In this clinically relevant sample size with large spread in data ranging from normal aging to severe atrophy, hippocampal volumes derived by well-accepted applications were quantitatively different. Thus, interchangeable use is not recommended.

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.

Neurometabolite correlates with personality and stress in healthy emerging adults: A focus on sex differences.

Personality traits have been linked with both brain structure and function. However, the exact relationship between personality traits and other behavioural measures with neurometabolites, measured with proton magnetic resonance spectroscopy, is not clear. Here we investigated the association between behavioural measures (i.e., personality traits, resilience, perceived stress, self-esteem, hopelessness, psychological distress) and metabolite ratios (i.e., of choline-containing compounds [Cho], creatine and phosphocreatine [Cr], and N-acetyl-aspartate [NAA]) in the posterior cingulate cortex (pCC) and the dorsal anterior cingulate cortex (dACC) and surrounding white matter (WM) regions in healthy emerging adults (N = 57, 26 women, mean age=23.40 years, SD=2.50). The pCC and the dACC were selected for their known involvement as important brain network hubs and their association to five factor personality dimensions and other psychological measures. Spectral analysis as well as statistics for demographic, clinical, and imaging data were performed. Correlation and multiple regression analyses were used to test the relationship between metabolite ratios and behavioural scores in the entire sample as well as in female and male participants separately. The entire sample showed significant (p<0.05) negative correlates of stress with the NAA/Cr ratio in the pCC, and of extraversion with WM metabolite ratios. In regards of sex differences, a significantly higher NAA/Cho ratio in the pCC (p<0.05), the dACC (p<0.01), and in the left and right posterior WM matter (p<0.05), and a lower Cho/Cr ratio in the dACC (p<0.01) was detected in women. Moreover, the two sexes differed in regards of metabolite correlates of openness, conscientiousness, extraversion, agreeableness, neuroticism, stress, hopelessness, and self-esteem, and in multiple regression model predictions. Our results point to a role of the ACC in conscientiousness through its involvement in higher-order cognitive control as part of the salience network and internally directed thoughts as part of the default mode network (DMN). Furthermore, the two sexes differ in terms of metabolite correlates of openness and conscientiousness in the pCC, suggesting mental process involvement through the DMN, and of agreeableness in the dACC, possibly through involvement in social cognitive processes, particularly in women. Additionally, our results suggest that the ACC is linked to the so-called Alpha-factor of personality. Our findings on stress correlates contribute to the existing literature of the involvement of the ACC as part of the limbic system. In addition, our results suggest a possible role of the pCC in stress-regulatory processes through a possible co-involvement of stress, hopelessness, and self-esteem in the pCC in men, where higher self-esteem may help to cope with stress.

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.

Repeated 31P-Magnetic Resonance Spectroscopy in Severe Traumatic Brain Injury: Insights into Cerebral Energy Status and Altered Metabolism.

Phosphorous magnetic resonance spectroscopy (31P-MRS) is suited to noninvasively investigate energy metabolism and to detect molecules containing phosphorus in the human brain. The aim of this longitudinal study was to perform 31P-MRS at two different time points (within 72 h and between day 10-14) after severe traumatic brain injury (sTBI) to reveal alterations in cerebral energy metabolism. Twenty-six ventilated patients with sTBI, aged between 20 and 75 years, with a median initial Glasgow Coma Scale score of 5 were analyzed prospectively. The 31P-MRS data of the structurally more affected side were compared with data from contralateral normal appearing areas and with data of age- and gender-matched healthy controls. There were no significant intraindividual differences between the lesioned and the less affected side at either of the time points. In the acute phase, phosphocreatine/adenosine triphosphate (PCr/ATP) and phosphocreatine/inorganic phosphate (PCr/Pi) were significantly elevated whereas phosphomonoesters/phosphodiesters (PME/PDE) and Pi/ATP were significantly decreased in contrast to healthy controls. In the subacute phase, these differences gradually dissipated, remaining lower Pi/ATP ratio, and only partly altered levels of PCr/Pi and PME/PDE. Our data affirm that cerebral metabolism is globally altered after sTBI, demonstrating the diffuse impairment of brain bioenergetics at multiple levels, with resultant developments in terms of time.

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.