Arterial input functions in dynamic susceptibility contrast MRI (DSC-MRI) in longitudinal evaluation of brain metastases.

BACKGROUND: Dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) could be helpful to separate true disease progression from pseudo-progression in brain metastases when assessing the need for retreatment. However, the selection of arterial input functions (AIFs) is not standardized for analysis, limiting its use for this application. PURPOSE: To compare population-based AIFs, AIFs specific to each patient, and AIFs specific to every visit in the longitudinal follow-up of brain metastases. MATERIAL AND METHODS: Longitudinal data were collected from eight patients before treatment (6 of 8 patients) and after treatment (6-17 visits). Imaging was performed using a 1.5-T MRI system. Lesions were segmented by subtracting precontrast images from postcontrast images. Cerebral blood volume (rCBV) and cerebral blood flow (rCBF) were computed, and Pearson's product moment correlation coefficients were calculated to evaluate similarity of DSC parameters dependent on various AIF choices across time. AIF shape characteristics were compared. Parameter differences between white matter (WM) and gray matter (GM) were obtained to determine which AIF choice maximizes tissue differentiation. RESULTS: Although DSC parameters follow similar patterns in time, the various AIF selections cause large parameter variations with relative standard deviations of up to ±60%. AIFs sampled in one patient across sessions more similar in shape than AIFs sampled across patients. Estimates of rCBV based on scan-specific AIFs differentiated better between perfusion in WM and GM than patient-specific or population-based AIFs (P ≤ 0.02). CONCLUSION: Results indicate that scan-specific AIFs are the best choice for DSC-MRI parameter estimations in the longitudinal follow-up of brain metastases.

Preoperative quantitative dynamic contrast-enhanced MRI and diffusion-weighted imaging predict aggressive disease in endometrial cancer.

Background Quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) may yield preoperative tumor biomarkers relevant for prognosis and therapy in cancer. Purpose To explore the value of preoperative DCE-MRI and DWI for the prediction of aggressive disease in endometrial cancer patients. Material and Methods Preoperative MRI (1.5-T) from 177 patients were analyzed and imaging parameters reflecting tumor microvasculature (from DCE-MRI) and tumor microstructure (from DWI) were estimated. The derived imaging parameters were explored in relation to clinico-pathological stage, histological subtype and grade, molecular markers, and patient outcome. Results Low tumor blood flow (Fb) and low rate constant for contrast agent intravasation (kep) were associated with high-risk histological subtype ( P ≤ 0.04 for both) and tended to be associated with poor prognosis ( P ≤ 0.09). Low tumor apparent diffusion coefficient (ADC) value and large tumor volume were both significantly associated with deep myometrial invasion ( P < 0.001 for both) and were also unfavorable prognostic factors ( P = 0.05 and P < 0.001, respectively). Conclusion DCE-MRI and DWI represent valuable supplements to conventional MRI by providing preoperative imaging biomarkers that predict aggressive disease in endometrial cancer patients.

In vivo MR spectroscopy predicts high tumor grade in endometrial cancer.

Background In vivo magnetic resonance spectroscopy (MRS) enables non-invasive measurements of tumor metabolites. Choline-containing metabolites play a key role in tumor metabolism. Purpose To explore whether preoperative MRS-derived tumor choline levels are associated with clinical and histological features in endometrial carcinomas. Material and Methods Preoperative pelvic magnetic resonance imaging (MRI) (1.5T), including structural and diffusion-weighted imaging and localized multivoxel proton MR (1H-MR) spectroscopy, was performed in 77 prospectively included patients with histologically confirmed endometrial carcinomas. Relative levels of total choline-containing metabolites (tCho) in tumor and myometrium were measured using the ratios: tCho/Creatine; tCho/Water; and tCho/Noise. MRS parameters were analyzed in relation to histological subtype and grade, surgicopathological staging parameters, MRI-measured tumor volume, and tumor apparent diffusion coefficient (ADC) value and clinical outcome. Results Tumor tissue had significantly higher ratios for tCho/Creatine, tCho/Water, and tCho/Noise than normal myometrial tissue ( P < 0.001 for all). High tumor tCho/Water ratio was significantly associated with high tumor grade in endometrioid tumors ( P = 0.02). Tumor tCho/Creatine ratio was positively correlated to MRI-measured tumor volume (rs = 0.25; P = 0.03). Conclusion High choline levels in tumor are associated with high-risk features. In vivo MRS may potentially aid in the preoperative risk stratification in endometrial cancer.

Within- and between-session reproducibility of GABA measurements with MR spectroscopy.

PURPOSE: The reproducibility of the MEGA-PRESS (MEshcher-GArwood Point RESolved Spectroscopy) MR spectroscopy sequence for the measurement of gamma- aminobutyric acid (GABA) is addressed, focusing on optimizing the number of repetitions at two voxel locations in the human brain and associated possibilities in analysis tools. MATERIALS AND METHODS: Two 20-min MEGA-PRESS acquisitions were run (echo time = 68 ms, repetition time = 1800 ms, repetitions = 328): one from a 21 mL volume in the anterior cingulate cortex (ACC) and one from a 22 mL volume in the left Broca's area in 21 healthy male volunteers (age 32 years ± 6[SD]). Subjects were scanned twice with identical protocols, 1 week apart. Data were acquired on a 3 Tesla GE Discovery 750 scanner using a 32-channel head coil. Spectroscopy data were partitioned into shorter epochs, numerically equivalent to scans of progressively increasing duration, and compared both within and between sessions. Three different analysis schemes were applied: (1) Vendor prototype preprocessor, with quantification by LCModel. (2) Pure Gannet pipeline. (3) Preprocessing with Gannet, and quantification with LCModel. The coefficient of variation (CV) were calculated as a measure of reproducibility. RESULTS: Increasing the number of repetitions showed improvements for within- and between-session reproducibility up to around 218 repetitions. (CV ranging from 4 to 14%). Gannet combined with LCModel approach proved the best method. (CV = 4-5%). Measurements from the ACC area had higher CVs than the Broca area. (CV = 6-14% versus 4-7%). CONCLUSION: Measurement in the Broca area yields better reproducibility than the ACC. With appropriate acquisition times and preprocessing tools, measurements from the ACC area are also reliable. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:421-430.

Loss of Dopamine Transporter Binding and Clinical Symptoms in Dementia With Lewy Bodies.

BACKGROUND: Little is known about the underlying mechanisms of clinical symptoms in dementia with Lewy bodies. The aim of this study was to explore the association between loss of striatal dopamine transporter binding and symptoms in dementia with Lewy bodies. METHODS: Thirty-five patients with dementia with Lewy bodies underwent single-photon emission computerized tomography brain imaging with N-ω-fluoropropyl-2ß-carbomethoxy-3ß-(4-iodophenyl)nortropane ([(123) I]FP-CIT). Associations between striatal binding ratios and motor (UPDRS), psychiatric (Neuropsychiatric Inventory; [NPI]), and cognitive (Mini-Mental State Examination [MMSE] and neuropsychological tests) symptoms were assessed by linear regression analysis. RESULTS: The explorative analysis showed that the motor UPDRS was negatively associated with putamen dopamine transporter binding, whereas no association with striatal dopamine transporter binding was found for total NPI, hallucinations, apathy, depression, anxiety, and MMSE scores. However, in post-hoc analysis, executive impairment was positively associated with dopamine transporter loss after adjustment of age and gender. CONCLUSIONS: Dopamine deficiency in patients with dementia with Lewy bodies was associated with severity of motor symptoms, but did not correlate significantly with ratings of neurobehavioral disturbances or overall cognition.

Default-mode network functional connectivity is closely related to metabolic activity.

Over the last decade, the brain's default-mode network (DMN) and its function has attracted a lot of attention in the field of neuroscience. However, the exact underlying mechanisms of DMN functional connectivity, or more specifically, the blood-oxygen level-dependent (BOLD) signal, are still incompletely understood. In the present study, we combined 2-deoxy-2-[(18) F]fluoroglucose positron emission tomography (FDG-PET), proton magnetic resonance spectroscopy ((1) H-MRS), and resting-state functional magnetic resonance imaging (rs-fMRI) to investigate more directly the association between local glucose consumption, local glutamatergic neurotransmission and DMN functional connectivity during rest. The results of the correlation analyzes using the dorsal posterior cingulate cortex (dPCC) as seed region showed spatial similarities between fluctuations in FDG-uptake and fluctuations in BOLD signal. More specifically, in both modalities the same DMN areas in the inferior parietal lobe, angular gyrus, precuneus, middle, and medial frontal gyrus were positively correlated with the dPCC. Furthermore, we could demonstrate that local glucose consumption in the medial frontal gyrus, PCC and left angular gyrus was associated with functional connectivity within the DMN. We did not, however, find a relationship between glutamatergic neurotransmission and functional connectivity. In line with very recent findings, our results lend further support for a close association between local metabolic activity and functional connectivity and provide further insights towards a better understanding of the underlying mechanism of the BOLD signal.

Effects of ECT in treatment of depression: study protocol for a prospective neuroradiological study of acute and longitudinal effects on brain structure and function.

BACKGROUND: Major depression can be a serious and debilitating condition. For some patients in a treatment resistant depressive episode, electroconvulsive treatment (ECT) is the only treatment that is effective. Although ECT has shown efficacy in randomized controlled trials, the treatment is still controversial and stigmatized. This can in part be attributed to our lack of knowledge of the mechanisms of action. Some reports also suggest potential harmful effects of ECT treatment and memory related side effects have been documented. METHODS/DESIGN: The present study will apply state of the art radiology through advanced magnetic resonance imaging (MRI) techniques to investigate structural and functional brain effects of ECT. As a multi-disciplinary collaboration, imaging findings will be correlated to psychiatric response parameters, neuropsychological functioning as well as neurochemical and genetic biomarkers that can elucidate the underlying mechanisms. The aim is to document both treatment effects and potential harmful effects of ECT. SAMPLE: n = 40 patients in a major depressive episode (bipolar and major depressive disorder). Two control groups with n = 15 in each group: age and gender matched healthy volunteers not receiving ECT and patients undergoing electrical cardioversion (ECV) for atrial fibrillation (AF). Observation time: six months. DISCUSSION: The study will contribute to our understanding of the pathophysiology of major depression as well as mechanisms of action for the most effective treatment for the disorder; ECT.

Cognitive executive impairment and dopaminergic deficits in de novo Parkinson's disease.

Cognitive impairment in Parkinson's disease (PD) is common and does directly impact patients' everyday functioning. However, the underlying mechanisms of early cognitive decline are not known. This study explored the association between striatal dopaminergic deficits and cognitive impairment within a large cohort of early, drug-naïve PD patients and tested the hypothesis that executive dysfunction in PD is associated with striatal dopaminergic depletion. A cross-sectional multicenter cohort of 339 PD patients and 158 healthy controls from the Parkinson's Progression Markers Initiative study was analyzed. Each individual underwent cerebral single-photon emission CT (SPECT) and a standardized neuropsychological assessment with tests of memory as well as visuospatial and executive function. SPECT imaging was performed with [(123) I]FP-CIT, and specific binding ratios in left and right putamen and caudate nucleus were calculated. The association between specific binding ratios, cognitive domain scores, and age was analyzed using Pearson's correlations, partial correlation, and conditional process analysis. A small, but significant, positive association between total striatal dopamine transporter binding and the attention/executive domain was found (r = 0.141; P = 0.009) in PD, but this was not significant after adjusting for age. However, in a moderated mediation model, we found that cognitive executive differences between controls and patients with PD were mediated by an age-moderated striatal dopaminergic deficit. Our findings support the hypothesis that nigrostriatal dopaminergic deficit is associated with executive impairment, but not to memory or visuospatial impairment, in early PD.

The STRAT-PARK cohort: A personalized initiative to stratify Parkinson's disease.

The STRAT-PARK initiative aims to provide a platform for stratifying Parkinson's disease (PD) into biological subtypes, using a bottom-up, multidisciplinary biomarker-based and data-driven approach. PD is a heterogeneous entity, exhibiting high interindividual clinicopathological variability. This diversity suggests that PD may encompass multiple distinct biological entities, each driven by different molecular mechanisms. Molecular stratification and identification of disease subtypes is therefore a key priority for understanding and treating PD. STRAT-PARK is a multi-center longitudinal cohort aiming to recruit a total of 2000 individuals with PD and neurologically healthy controls from Norway and Canada, for the purpose of identifying molecular disease subtypes. Clinical assessment is performed annually, whereas biosampling, imaging, and digital and neurophysiological phenotyping occur every second year. The unique feature of STRAT-PARK is the diversity of collected biological material, including muscle biopsies and platelets, tissues particularly useful for mitochondrial biomarker research. Recruitment rate is ∼150 participants per year. By March 2023, 252 participants were included, comprising 204 cases and 48 controls. STRAT-PARK is a powerful stratification initiative anticipated to become a global research resource, contributing to personalized care in PD.

Dynamic contrast-enhanced MRI in endometrial carcinoma identifies patients at increased risk of recurrence.

OBJECTIVES: To study the feasibility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for assessment of tumour microvasculature in endometrial carcinoma patients, and to explore correlations with histological subtype, clinical course and microstructural characteristics based on apparent diffusion coefficient (ADC) values. METHODS: Diffusion-weighted imaging (DWI) and three-dimensional DCE-MRI (1.5 T) with high temporal resolution (2.49 s) were acquired preoperatively in 55 patients. Quantitative modelling allowed the calculation of four independent parameters describing microvasculature: blood flow (Fb), extraction fraction (E), capillary transit time (Tc) and transfer constant from the extravascular extracellular space [EES] to blood (Kep); and four derived parameters: blood volume (Vb), volume of EES (Ve), capillary permeability surface area product (PS) and transfer from blood to EES (Ktrans). RESULTS: Endometrial carcinoma tissue exhibited reduced Fb, E, Vb, Ve, PS and Ktrans compared with normal myometrium. Non-endometrioid carcinomas (n = 12) had lower Fb, and E than endometrioid carcinomas (n = 43; P < 0.05). Tumour Ve positively correlated with tumour ADC value (r = 0.29, P = 0.03). Reduced survival was observed in patients with low tumour Fb and high tumour Tc (P < 0.05). CONCLUSIONS: We demonstrate the feasibility of DCE-MRI in reflecting histological subtype and clinical course in primary endometrial carcinomas. DCE-MRI may potentially provide future biomarkers for preoperative risk stratification in endometrial carcinomas. KEY POINTS: • Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) offers new information about endometrial carcinoma. • Pelvic DCE-MRI with subsequent quantitative modelling seems feasible in endometrial carcinoma patients. • Low tumour perfusion is a feature of a more aggressive tumour subtype. • DCE-MRI provides potential biomarkers for preoperative risk stratification in endometrial carcinoma patients.

Alcohol-induced changes in cerebral blood flow and cerebral blood volume in social drinkers.

AIMS: Although it is known that alcohol has vasoactive properties, previous studies have not investigated the relationship between cerebral blood flow (CBF) and cerebral blood volume (CBV) after alcohol consumption. The aim of this study was to investigate effects of alcohol on CBF and CBV, both globally and regionally, in social drinkers. METHODS: The method of choice was dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI). Eight males were scanned twice on two separate days; once after consumption of alcohol (blood-alcohol concentration (BAC) of 0.08%) and once sober. RESULTS: The results showed an average increase of CBF after alcohol consumption, both in grey matter (GM) and in white matter (WM), with a CBF(BAC of 0.08%)/CBF(baseline) ratio of 1.2. Regional increases in CBF were seen in areas close to where the large brain-feeding blood vessels enter the brain, in the thalamus region and in the frontal brain regions. The lowest CBF changes were seen in the occipital brain regions. There was also an increase in CBV after alcohol consumption, in particular across WM regions. CONCLUSION: In conclusion, a BAC of 0.08% causes both an average increase in global and regional CBF. There was stronger correlation between alcohol-induced changes in CBF and CBV in WM than in GM, suggesting the vasculature in the WM to be relatively more affected than the GM. Simultaneous measurements of CBF and CBV after acute alcohol intoxication in social drinkers are important in basic human neuroscience research to elucidate and understand brain physiology in the presence of exogenous neuro-pharmaceutical manipulations.

Similarities and differences between intermittent and continuous resting-state fMRI.

Introduction: Functional Magnetic Resonance Imaging (fMRI) block-design experiments typically include active ON-blocks with presentation of cognitive tasks which are contrasted with OFF- blocks with no tasks presented. OFF-blocks in between ON-blocks can however, also be seen as a proxy for intermittent periods of resting, inducing temporary resting-states. We still do not know if brain activity during such intermittent periods reflects the same kind of resting-state activity as that obtained during a continuous period, as is typically the case in studies of the classic Default Mode Network (DMN). The purpose of the current study was therefore to investigate both similarities and differences in brain activity between intermittent and continuous resting conditions. Methods: There were 47 healthy participants in the 3T fMRI experiment. Data for the intermittent resting-state condition were acquired from resting-periods in between active task-processing periods in a standard ON-OFF block design, with three different cognitive tasks presented during ON-blocks. Data for the continuous resting-state condition were acquired during a 5 min resting period after the task-design had been presented. Results and discussion: The results showed that activity was overall similar in the two conditions, but with some differences. These differences were within the DMN network, and for the interaction of DMN with other brain networks. DMN maps showed weak overlap between conditions in the medial prefrontal cortex (MPFC), and in particular for the intermittent compared to the continuous resting-state condition. Moreover, DMN showed strong connectivity with the salience network (SN) in the intermittent resting-state condition, particularly in the anterior insula and the supramarginal gyrus. The observed differences may reflect a "carry-over" effect from task-processing to the next resting-state period, not present in the continuous resting-state condition, causing interference from the ON-blocks. Further research is needed to fully understand the extent of differences between intermittent and continuous resting-state conditions.

Brief international cognitive assessment for MS (BICAMS) and global brain volumes in early stages of MS - A longitudinal correlation study.

BACKGROUND: Cognitive impairment is common in patients with multiple sclerosis, even in the early stages of the disease. The Brief International Cognitive Assessment for multiple sclerosis (BICAMS) is a short screening tool developed to assess cognitive function in everyday clinical practice. OBJECTIVE: To investigate associations between volumetric brain measures derived from a magnetic resonance imaging (MRI) examination and performance on BICAMS subtests in early stages of multiple sclerosis (MS). METHODS: BICAMS was used to assess cognitive function in 49 MS patients at baseline and after one and two years. The patients were separated into two groups (with or without cognitive impairment) based on their performances on BICAMSs subtests. MRI data were analysed by a software tool (MSMetrix), yielding normalized measures of global brain volumes and lesion volumes. Associations between cognitive tests and brain MRI measures were analysed by running correlation analyses, and differences between subgroups and changes over time with independent and paired samples tests, respectively. RESULTS: The strongest baseline correlations were found between the BICAMS subtests and normalized whole brain volume (NBV) and grey matter volume (NGV); processing speed r = 0.54/r = 0.48, verbal memory r = 0.49/ r = 0.42, visual memory r = 0.48 /r = 0.39. Only the verbal memory test had significant correlations with T2 and T1 lesion volumes (LV) at both time points; T2LV r = 0.39, T1LV r = 0.38. There were significant loss of grey matter and white matter volume overall (NGV p<0.001, NWV p = 0.003), as well as an increase in T1LV (p = 0.013). The longitudinally defined confirmed cognitively impaired (CCI) and preserved (CCP) patients showed significant group differences on all MRI volume measures at both time points, except for NWV. Only the CCI subgroup showed significant white matter atrophy (p = 0.006) and increase in T2LV (p = 0.029). CONCLUSIONS: The present study found strong correlations between whole brain and grey matter volumes and performance on the BICAMS subtests as well as significant changes in global volumes from baseline to follow-up with clear differences between patients defined as cognitively impaired and preserved at both baseline and follow-up.

Microstructural changes precede depression in patients with relapsing-remitting Multiple Sclerosis.

BACKGROUND: Multiple Sclerosis lesions in the brain and spinal cord can lead to different symptoms, including cognitive and mood changes. In this study we explore the temporal relationship between early microstructural changes in subcortical volumes and cognitive and emotional function in a longitudinal cohort study of patients with relapsing-remitting Multiple Sclerosis. METHODS: In vivo imaging in forty-six patients with relapsing-remitting Multiple Sclerosis was performed annually over 3 years magnetic resonance imaging. Microstructural changes were estimated in subcortical structures using the free water fraction, a diffusion-based MRI metric. In parallel, patients were assessed with the Hospital Anxiety and Depression Scale amongst other tests. Predictive structural equation modeling was set up to further explore the relationship between imaging and the assessment scores. In a general linear model analysis, the cohort was split into patients with higher and lower depression scores. RESULTS: Nearly all subcortical diffusion microstructure estimates at the baseline visit correlate with the depression score at the 2 years follow-up. The predictive nature of baseline free water estimates and depression subscores after 2 years are confirmed in the predictive structural equation modeling analysis with the thalamus showing the greatest effect size. The general linear model analysis shows patterns of MRI free water differences in the thalamus and amygdala/hippocampus area between participants with high and low depression score. CONCLUSIONS: Our data suggests a relationship between higher levels of free-water in the subcortical structures in an early stage of Multiple Sclerosis and depression symptoms at a later stage of the disease.

Signals between the brain and spinal cord are disrupted in people with Multiple Sclerosis. For those with relapsing-remitting Multiple Sclerosis (RRMS), symptoms get periodically better and worse over time. We looked at whether changes in the brain of people with RRMS were associated with changes in their mood over time. People who had more changes in certain areas of the brain at the start of the study were more likely to have symptoms of depression later. This work suggests that early changes in the brain may be linked to increased symptoms of depression over time in people with RRMS. We believe this could be an opportunity to provide care to those suffering from RRMS to lessen the impact of severe depression symptoms before they arise.

Dynamic susceptibility contrast MRI may contribute in prediction of stereotactic radiosurgery outcome in brain metastases.

Background: Following stereotactic radiosurgery (SRS), predicting treatment response is not possible at an early stage using structural imaging alone. Hence, the current study aims at investigating whether dynamic susceptibility contrast (DSC)-MRI estimated prior to SRS can provide predictive biomarkers in response to SRS treatment and characterize vascular characteristics of pseudo-progression. Methods: In this retrospective study, perfusion-weighted DSC-MRI image data acquired with a temporal resolution of 1.45 seconds were collected from 41 patients suffering from brain metastases. Outcome was defined based on lesion volume changes in time (determined on structural images) or death. Motion correction and manual lesion delineation were performed prior to semi-automated, voxel-wise perfusion analysis. Statistical testing was performed using linear regression and a significance threshold at P = .05. Age, sex, primary cancers (pulmonary cancer and melanoma), lesion volume, and dichotomized survival time were added as covariates in the linear regression models (ANOVA). Results: Relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) were found to be significantly lower prior to SRS treatment in patients with increasing lesion volume or early death post-SRS (P ≤ .01). Conclusion: Unfavorable treatment outcome may be linked to low perfusion prior to SRS. Pseudo-progression may be preceded by a transient rCBF increase post-SRS. However, results should be verified in different or larger patient material.

Negative valence of hallucinatory voices as predictor of cortical glutamatergic metabolite levels in schizophrenia patients.

OBJECTIVES: Negative emotional valence of auditory verbal hallucinations (AVHs) in schizophrenia can be a source of distress and is considered a strong predictor of illness severity. Previous studies have found glutamate to mediate AVH severity in frontal and temporal brain regions, however, they do not specifically address emotional valence of AVH. The role of glutamate for the experience of negative- versus positive emotional valence of AVH is therefore unknown and was investigated in the current study. METHODS: Using magnetic resonance spectroscopy (MRS), 37 schizophrenia patients had Glx (glutamate+glutamine) measured in the left superior temporal gyrus (STG), and additionally in the anterior cingulate cortex (ACC) and the right STG, or in the left inferior frontal gyrus (IFG). Self-reported emotional valence in AVH was measured with the Beliefs About Voices Questionnaire (BAVQ-R). RESULTS: Results from linear mixed models showed that negative emotional valence was associated with reduced Glx levels across all four measured brain regions in the frontal and temporal lobe. More specifically, voices that were experienced to be omnipotent (p = 0.04) and that the patients attempted to resist (p = 0.04) were related to lower Glx levels. Follow-up analysis of the latter showed that voices that evoked emotional resistance (i.e., fear, sadness, anger), rather than behavioral resistance, was a significant predictor of reduced glutamate (p = 0.02). CONCLUSION: The findings could indicate aberrant glutamatergic signaling, or increased NMDA-receptor hypoactivity in patients who experience their voices to be more emotionally negative. Overall, the study provides support for the glutamate hypothesis of schizophrenia.

The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson's disease.

We conducted a double-blinded phase I clinical trial to establish whether nicotinamide adenine dinucleotide (NAD) replenishment therapy, via oral intake of nicotinamide riboside (NR), is safe, augments cerebral NAD levels, and impacts cerebral metabolism in Parkinson's disease (PD). Thirty newly diagnosed, treatment-naive patients received 1,000 mg NR or placebo for 30 days. NR treatment was well tolerated and led to a significant, but variable, increase in cerebral NAD levels-measured by 31phosphorous magnetic resonance spectroscopy-and related metabolites in the cerebrospinal fluid. NR recipients showing increased brain NAD levels exhibited altered cerebral metabolism, measured by 18fluoro-deoxyglucose positron emission tomography, and this was associated with mild clinical improvement. NR augmented the NAD metabolome and induced transcriptional upregulation of processes related to mitochondrial, lysosomal, and proteasomal function in blood cells and/or skeletal muscle. Furthermore, NR decreased the levels of inflammatory cytokines in serum and cerebrospinal fluid. Our findings nominate NR as a potential neuroprotective therapy for PD, warranting further investigation in larger trials.

A critical re-examination of sexual dimorphism in the corpus callosum microstructure.

Recent diffusion-tensor imaging (DTI) studies suggest sexual dimorphism in the micro-structural architecture of the corpus callosum. However, the corpus callosum is also found to be larger in males than in females, a fact that might introduce a systematic bias to the analysis of DTI parameters. Diffusion parameters obtained in the larger male corpus callosum could be less affected by partial-volume averaging with surrounding non-callosal tissue than respective parameters obtained in the smaller female corpus callosum, i.e. the sex of the subject and partial-volume effects would be confounded. The objective of the present DTI study was to re-examine microstructural sex differences in the corpus callosum, while controlling for corpus callosum size differences between sexes. We compared 41 female and 34 male participants using regional tract-based spatial statistics (TBSS) analysis. Clusters of significantly higher fractional anisotropy (FA) and lower diffusion strength in males compared to females were detected in the genu and truncus of the corpus callosum. However, only the sex difference located in the anterior genu subregions could be unequivocally interpreted. This was the only cluster where the diffusion parameters did not correlate with regional callosal size. The present results indicate a stronger inter-hemispheric connectivity between the frontal lobes in males than females, which might be related to sex differences in hemispheric asymmetry and brain size.

Effects of Multi-Shell Free Water Correction on Glioma Characterization.

Diffusion MRI is a useful tool to investigate the microstructure of brain tumors. However, the presence of fast diffusing isotropic signals originating from non-restricted edematous fluids, within and surrounding tumors, may obscure estimation of the underlying tissue characteristics, complicating the radiological interpretation and quantitative evaluation of diffusion MRI. A multi-shell regularized free water (FW) elimination model was therefore applied to separate free water from tissue-related diffusion components from the diffusion MRI of 26 treatment-naïve glioma patients. We then investigated the diagnostic value of the derived measures of FW maps as well as FW-corrected tensor-derived maps of fractional anisotropy (FA). Presumed necrotic tumor regions display greater mean and variance of FW content than other parts of the tumor. On average, the area under the receiver operating characteristic (ROC) for the classification of necrotic and enhancing tumor volumes increased by 5% in corrected data compared to non-corrected data. FW elimination shifts the FA distribution in non-enhancing tumor parts toward higher values and significantly increases its entropy (p ≤ 0.003), whereas skewness is decreased (p ≤ 0.004). Kurtosis is significantly decreased (p < 0.001) in high-grade tumors. In conclusion, eliminating FW contributions improved quantitative estimations of FA, which helps to disentangle the cancer heterogeneity.