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Background: Eclampsia is a serious pregnancy complication and is associated with cerebral edema and infarctions. However, the underlying pathophysiology of eclampsia remains poorly explored., Objective: This study aimed to assess the pathophysiology of eclampsia using specialized magnetic resonance imaging to measure diffusion, perfusion, and vasospasm., Study Design: This was a cross-sectional study recruiting consecutive pregnant women between April 2018 and November 2021 at Tygerberg Hospital, Cape Town, South Africa. Women with eclampsia, preeclampsia, and normotensive pregnancies who underwent magnetic resonance imaging after birth were recruited. The main outcome measures were cerebral infarcts, edema, and perfusion using intravoxel incoherent motion imaging and vasospasm using magnetic resonance imaging angiography. The imaging protocol was established before inclusion., Results: Here, 49 women with eclampsia, 20 women with preeclampsia, and 10 normotensive women were included. Cerebral infarcts were identified in 34% of women with eclampsia and 5% of women with preeclampsia (risk difference, 0.29; 95% confidence interval, 0.06-0.52; P=.012). However, no cerebral infarct was identified in normotensive controls. Women with eclampsia were more likely to have vasogenic cerebral edema than women with preeclampsia (80% vs 20%, respectively; risk difference, 0.60; 95% confidence interval, 0.34-0.85; P<.001) and normotensive women (risk difference, 0.80; 95% confidence interval, 0.47-1.00; P<.001). Diffusion was increased in women with eclampsia in the parieto-occipital white matter (mean difference, 0.02 × 10 -3 mm 2 /s; 95% confidence interval, 0.00-0.05; P=.045) and caudate nucleus (mean difference, 0.02 × 10 -3 mm 2 /s; 95% confidence interval, 0.00-0.04; P=.033) compared with women with preeclampsia. In addition, diffusion was increased in women with eclampsia in the frontal white matter (mean difference, 0.07 × 10 -3 mm 2 /s; 95% confidence interval, 0.02-0.12; P=.012), parieto-occipital white matter (mean difference, 0.05 × 10 -3 mm 2 /s; 95% confidence interval, 0.02-0.07; P=.03), and caudate nucleus (mean difference, 0.04 × 10 -3 mm 2 /s; 95% confidence interval, 0.00-0.07; P=.028) compared with normotensive women. Perfusion was decreased in edematous regions. Hypoperfusion was present in the caudate nucleus in eclampsia (mean difference, -0.17 × 10 -3 mm 2 /s; 95% confidence interval, -0.27 to -0.06; P=.003) compared with preeclampsia. There was no sign of hyperperfusion. Vasospasm was present in 18% of women with eclampsia and 6% of women with preeclampsia. However, no vasospasm was present in the controls., Conclusion: Eclampsia was associated with cerebral infarcts, vasogenic cerebral edema, vasospasm, and decreased perfusion, which are not usually evident on standard clinical imaging. This finding may explain why some patients have cerebral symptoms and signs despite having normal conventional imaging., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Premenstrual dysphoric disorder (PMDD) is a depressive disorder triggered by fluctuations of progesterone and estradiol during the luteal phase of the menstrual cycle. Selective progesterone receptor modulation (SPRM), while exerting an antagonistic effect on progesterone and maintaining estradiol on moderate levels, has shown beneficial effects on the mental symptoms of PMDD. Progesterone is also known for its neuroprotective effects, while synthetic progestins have been suggested to promote myelination. However, the impact of SPRM treatment on white matter microstructure is unexplored., Methods: Diffusion tensor imaging was employed to collect data on white matter integrity in patients with PMDD, before and after treatment with ulipristal acetate (an SPRM) or placebo, as part of a double-blind randomized controlled-trial. Tract based spatial statistics were performed to investigate SPRM treatment vs. placebo longitudinal effects on fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD), on the whole white matter skeleton., Results: Voxel-wise analyses indicated no change over time in any white matter microstructure metrics in individuals treated with SPRM versus placebo. Improvement in PMDD symptoms did not correlate with changes in white matter microstructure. In secondary, exploratory, cross-sectional comparisons during treatment, the SPRM group displayed lower FA and higher MD, RD, and AD than the placebo group in several tracts., Conclusion: The main findings suggest that SPRM treatment did not impact white matter microstructure compared with placebo. However, secondary exploratory analyses yielded between-group differences after treatment, which call for further investigation on the tracts potentially impacted by progesterone antagonism., Clinical Trial Registration: EUDRA-CT 2016-001719-19; "Selective progesterone receptor modulators for treatment of premenstrual dysphoric disorder. A randomized, double-blind, placebo-controlled study."; https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-001719-19/SE., Competing Interests: Declaration of competing interest EC receives funds from the Swedish Research Council (2015–00495), EU FP7-People-Cofund (INCA 600398) and SciLifeLab. The study drugs were provided by Gedeon Richter, but no further financial or design- related involvement was foreseen. R. Lanzenberger received investigator-initiated research funding from Siemens Healthcare regarding clinical research using PET/MR. He is a shareholder of the start-up company BM Health GmbH since 2019. The rest of the authors report no further financial interest or conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Sediments polluted with hydrophobic organic contaminants (HOCs) and metals can pose environmental risks, yet effective remediation remains a challenge. We investigated a new composite sorbent comprising granular activated carbon (GAC) and a calcium-silicate (Polonite®, PO) for thin-layer capping of polluted sediment, with the aim to sequester both HOCs and metals. Box cores were collected in polluted Oskarshamn harbor, Sweden, and the sediments were treated with GAC and/or Polonite in a 10-week mesocosm study to measure endpoints ranging from contaminant immobilization to ecological side effects on native fauna and biogeochemical processes. The GAC particle size was 300-500 μm to reduce negative effects on benthic fauna (by being non-ingestible) and of biogenic origin (coconut) to have a small carbon footprint compared with traditional fossil ACs. The calcium-silicate was a fine-grained industrial by-product used to target metals and as a carrier for GAC to improve the cap integrity. GAC decreased the uptake of dioxins (PCDD/Fs) in the bivalve Macoma balthica by 47 % and the in vitro bioavailability of PCB by 40 %. The composite cap of GAC + Polonite decreased sediment-to-water release of Pb < Cu < Ni < Zn < Cd by 42-98 % (lowest to highest decrease) and bioaccumulation of Cd < Zn < Cu in the worm Hediste diversicolor by 50-65 %. Additionally, in vitro bioavailability of Pb < Cu < Zn, measured using digestive fluid extraction, decreased by 43-83 %. GAC showed no adverse effects on benthic fauna while Polonite caused short-term adverse effects on fauna diversity and abundance, partly due to its cohesiveness, which, in turn, can improve the cap integrity in situ. Fauna later recovered and bioturbated the cap. Both sorbents influenced biogeochemical processes; GAC sorbed ammonium, Polonite decreased respiration, and both sorbents reduced denitrification. In conclusion, the side effects were relatively mild, and the cap decreased the release and bioavailability of both HOCs and metals effectively, thus offering a promising sustainable and cost-effective solution to remediating polluted sediments., Competing Interests: Declaration of competing interest We have no conflicts of interests to disclose. The funding sources did not have any participation in the research., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Sediments contaminated with hazardous metals pose risks to humans and wildlife, yet viable management options are scarce. In a series of laboratory experiments, we characterized Polonite® - an activated calcium-silicate - as a novel sorbent for thin-layer capping of metal-contaminated sediments. We tested a fine-grained by-product from the Polonite production as a cheap and sustainable sorbent. First, Polonite was reacted with solutions of Cu, Pb, and Zn, and the surface chemistry of the Polonite was examined using, e.g., scanning electron microscopy to investigate metal sorption mechanisms. Batch experiments were conducted by adding Polonite to industrially contaminated harbor sediment to determine sorption kinetics and isotherms. Importantly, we measured if the Polonite could reduce metal bioavailability to sediment fauna by performing digestive fluid extraction (DFE). Finally, a cap placement technique was studied by applying a Polonite slurry in sedimentation columns. The results showed rapid metal sorption to Polonite via several mechanisms, including hydroxide and carbonate precipitation, and complexation with metal oxides on the Polonite surface. Isotherm data revealed that the sediment uptake capacity (K f ) for Cu, Pb, and Zn increased by a factor of 25, 21, and 14, respectively, after addition of 5% Polonite. The bioavailability of Cu, Pb, and Zn was reduced by 70%, 65%, and 54%, respectively, after a 25% Polonite addition. In conclusion, we propose that sediment treatment with low doses of the Polonite by-product can be a cheap, sustainable, and effective remediation method compared to other more intrusive methods such as dredging or conventional isolation capping., Competing Interests: Declaration of competing interest We have no conflicts of interests to disclose. The funding sources did not have any participation in the research., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Impaired cognitive ability is one of the most frequently reported neuropsychiatric symptoms in the post-COVID phase among patients. It is unclear whether this condition is related to structural or functional brain changes., Purpose: In this study, we present a multimodal magnetic resonance imaging study of 36 post-COVID patients and 36 individually matched controls who had a mild form of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infection from March 2020 to February 2022. This study aimed to investigate structural and functional brain alterations and their correlation with post-COVID symptoms and neurocognitive functions., Materials and Methods: The study protocol comprised an assessment of physical fatigue [Fatigue Severity Scale (FSS)], mental fatigue (Mental Fatigue Scale (MFS)], depression [Montgomery Asberg Depression Rating Scale (MADRS)], anxiety [Hospital Anxiety and Depression Scale (HAD)], post-COVID Symptoms Severity Score, and neurocognitive status [Repeatable Battery for the Assessment of Neuropsychological Status Update (RBANS)]. The magnetic resonance imaging protocol included morphological sequences, arterial spin labeling (ASL) and dynamic susceptibility contrast-enhanced (DSC) perfusion, diffusion tensor imaging (DTI), and resting-state functional magnetic resonance imaging (fMRI) sequences. Using these protocols, the assessments of macrostructural abnormalities, perfusion, gray matter density, white matter integrity, and brain connectivity were performed., Results: Post-COVID patients had higher levels of physical fatigue, mental fatigue, depression, and anxiety than controls and showed cognitive impairment in all the RBANS domains except in Visuospatial/Construction. The subjective mental fatigue correlated with objective impaired cognitive ability in the RBANS test, particularly in the Attention domain. There were no differences between patients and controls regarding macrostructural abnormalities, regional volumes, regional perfusion metrics, gray matter density, or DTI parameters. We observed a significant positive correlation between RBANS Total Scale Index score and gray matter volume in the right superior/middle-temporal gyrus ( p < 0.05) and a significant negative correlation between the white matter integrity and post-COVID symptoms ( p < 0.05) in the same area. The connectivity differences were observed between patients and controls in a few regions, including the right middle frontal gyrus, an important area of convergence of the dorsal and ventral attention networks. We also noted a positive correlation between post-COVID symptoms and increased connectivity in the right temporoparietal junction, which is part of the ventral attention system., Conclusion: In non-hospitalized subjects with post-COVID, we did not find any structural brain changes or changes in perfusion, compared to controls. However, we noted differences in connectivity within an important area for attention processes, which may be associated with post-COVID brain fog., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Fineschi, Fahlström, Fällmar, Haller and Wikström.)

Background: Hemodynamic changes are seen in the feeding arteries of arteriovenous malformations (AVMs). Phase-contrast MRI (PC-MRI) enables the acquisition of hemodynamic information from blood vessels. There is insufficient knowledge on which flow or velocity parameter best discriminates AVMs from healthy subjects., Purpose: To evaluate PC-MRI-measured flow and velocity in feeding arteries of AVMs before and, when possible, also after treatment and to compare these measurements to corresponding measurements in healthy controls., Materials and Methods: Highest flow (HF), lowest flow (LF), mean flow (MF), peak systolic velocity (PSV), end-diastolic velocity (EDV), and mean velocity (MV) were measured in feeding arteries in patients with intracranial AVMs using 2D PC-MRI at 3 T. Measurements were compared to previously reported values in healthy individuals. Values in patients above the 95th percentile in the healthy cohort were categorized as pathological. Nidus volume was measured using 3D time-of-flight MR angiography., Results: Ten patients with diagnosed AVMs were examined with PC-MRI. Among these, three patients also underwent follow-up PC-MRI after treatment. Pathological velocities (PSV, EDV, and MV) were seen in all five subjects with a nidus larger or equal to 5.7 cm 3 , whereas pathological flow values were not seen in all, that is, pathologic HF in three, pathologic LF in two, and pathologic MF in two. After treatment, there was a decrease in flow and velocity (all measured parameters). After treatment, velocities (PSV, EDV, and MV) were no longer abnormal compared to healthy controls., Conclusion: Patients with a large AVM nidus show pathological velocities, but less consistent flow increases. Following treatment, velocities normalize., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Paired cerebral blood flow (CBF) measurement is usually acquired before and after vasoactive stimulus to estimate cerebrovascular reserve (CVR). However, CVR may be confounded because of variations in time-to-maximum CBF response (t max ) following acetazolamide injection. With a mathematical model, CVR can be calculated insensitive to variations in t max , and a model offers the possibility to calculate additional model-derived parameters. A model that describes the temporal CBF response following a vasodilating acetazolamide injection is proposed and evaluated., Methods: A bi-exponential model was adopted and fitted to four CBF measurements acquired using arterial spin labelling before and initialised at 5, 15 and 25 min after acetazolamide injection in a total of fifteen patients with Moyamoya disease. Curve fitting was performed using a non-linear least squares method with a priori constraints based on simulations., Results: Goodness of fit (mean absolute error) varied between 0.30 and 0.62 ml·100 g -1 ·min -1 . Model-derived CVR was significantly higher compared to static CVR measures. Maximum CBF increase occurred earlier in healthy- compared to diseased vascular regions., Conclusions: The proposed mathematical model offers the possibility to calculate CVR insensitive to variations in time to maximum CBF response which gives a more detailed characterisation of CVR compared to static CVR measures. Although the mathematical model adapts generally well to this dataset of patients with MMD it should be considered as experimental; hence, further studies in healthy populations and other patient cohorts are warranted., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Children born very preterm often exhibit atypical gaze behaviors, affect recognition difficulties and are at risk for cerebral white matter damage. This study explored links between these sequalae. In 24 12-year-old children born very preterm, ventricle size using Evans and posterior ventricle indices, and corpus callosum area were used to measure white matter thickness. The findings revealed a correlation between less attention towards the eyes and larger ventricle size. Ventricle and posterior corpus callosum sizes were correlated to affect-recognition proficiency. Findings suggest a link between white matter damage, gaze behavior, and affect recognition accuracy, emphasizing a relation with social perception., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Background: Fetal ultrasound has limitations, especially if the patient is obese or in cases with oligohydramnios. Magnetic resonance imaging (MRI) can then be used as a complement, but only few studies have focused on examinations in the second trimester., Purpose: To validate MRI as a complement to diagnose fetal anomalies in the second trimester., Material and Methods: This retrospective study retrieved data from January 2008 to July 2012 from the Fetal Medicine Unit and Department of Radiology at Uppsala University Hospital. Ultrasound and MRI findings were reviewed in 121 fetuses in relation to the final diagnosis, including postpartum follow-up and autopsy results., Results: Of the 121 fetuses, 51 (42%) had a CNS anomaly and 70 (58%) a non-CNS anomaly diagnosed or suspected. MRI provided additional information in 21% of all cases without changing the management and revealed information that changed the management of the pregnancy in 13%. When a CNS anomaly was detected or suspected, the MRI provided additional information in 22% and changed the management in 10%. The corresponding figures for non-CNS cases were 21% and 16%, respectively. The proportion of cases with additional information that changed the management was especially high in patients with a BMI >30 kg/m 2 (25%) and in patients with oligohydramnios (38%). In five cases in category III, false-positive ultrasound findings were identified., Conclusions: MRI in the second trimester complements ultrasound and improves diagnosis of fetal CNS- and non-CNS anomalies especially when oligohydramnios or maternal obesity is present., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Premenstrual dysphoric disorder (PMDD) is a mood disorder for which selective progesterone receptor modulator (SPRM) treatment has been demonstrated to be beneficial. The neural signatures of this treatment have been so far identified as greater fronto-cingulate reactivity during aggressive response to provocation, but no changes in terms of gray matter structure. White matter has recently been found to differ between patients with PMDD and healthy controls. The present study thus sought to investigate the relationship between white matter volume and SPRM treatment in patients with PMDD. A pharmaco-neuroimaging study was conducted on patients with PMDD participating in a randomized controlled trial. Participants underwent magnetic resonance imaging before and after treatment randomization to ulipristal acetate (an SPRM), or placebo, for three months. The interaction effect of treatment by time on white matter volume (WMV) was assessed. Voxel based morphometry analyses were performed on both a whole brain exploratory level and on regions of interest. No treatment effect was observed on WMV in any region, including the anterior thalamic radiations, cingulum, forceps minor, fornix, inferior fronto-occipital fasciculus, superior cerebellar peduncle, superior longitudinal fasciculus, and uncinate fasciculus. This is the first finding to indicate that no white matter volume alterations follow three-month progesterone antagonism, suggesting that white matter volume does not participate in symptom relief upon SPRM treatment for PMDD., Competing Interests: Declaration of Competing Interest The study drugs were provided by Gedeon Richter, but they had no further involvement in the study design, data collection, analysis, findings’ interpretation, or manuscript preparation. RL received travel grants and/or conference speaker honoraria within the last three years from Bruker BioSpin MR, Heel, and support from Siemens Healthcare regarding clinical research using PET/MR. He is a shareholder of the start-up company BM Health GmbH since 2019. ISP has served occasionally on advisory boards or acted as invited speaker at scientific meetings for Asarina Pharma, Bayer Health Care, Gedeon Richter, Peptonics, Shire/Takeda, Sandoz, and Lundbeck A/S. All other authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Radiological imaging to examine intracranial blood vessels is critical for preoperative planning and postoperative follow-up. Automated segmentation of cerebrovascular anatomy from Time-Of-Flight Magnetic Resonance Angiography (TOF-MRA) can provide radiologists with a more detailed and precise view of these vessels. This paper introduces a domain generalized artificial intelligence (AI) solution for volumetric monitoring of cerebrovascular structures from multi-center MRAs. Our approach utilizes a multi-task deep convolutional neural network (CNN) with a topology-aware loss function to learn voxel-wise segmentation of the cerebrovascular tree. We use Decorrelation Loss to achieve domain regularization for the encoder network and auxiliary tasks to provide additional regularization and enable the encoder to learn higher-level intermediate representations for improved performance. We compare our method to six state-of-the-art 3D vessel segmentation methods using retrospective TOF-MRA datasets from multiple private and public data sources scanned at six hospitals, with and without vascular pathologies. The proposed model achieved the best scores in all the qualitative performance measures. Furthermore, we have developed an AI-assisted Graphical User Interface (GUI) based on our research to assist radiologists in their daily work and establish a more efficient work process that saves time., (© 2024. The Author(s).)

Background: Phase-contrast magnetic resonance imaging (PC-MRI) quantifies blood flow and velocity noninvasively. Challenges arise in neurovascular disorders due to small vessels. We evaluated the impact of voxel size, number of signal averages (NSA), and velocity encoding (VENC) on PC-MRI measurement accuracy and precision in a small-lumen vessel phantom., Methods: We constructed an in vitro model with a constant flow rate using a 2.2-mm inner diameter plastic tube. A reservoir with a weight scale and timer was used as standard reference. Gradient-echo T1 weighted PC-MRI sequence was performed on a 3-T scanner with varying voxel size (2.5, 5.0, 7.5 mm 3 ), NSA (1, 2, 3), and VENC (200, 300, 400 cm/s). We repeated measurements nine times per setting, calculating mean flow rate, maximum velocity, and least detectable difference (LDD)., Results: PC-MRI flow measurements were higher than standard reference values (mean ranging from 7.3 to 9.5 mL/s compared with 6.6 mL/s). Decreased voxel size improved accuracy, reducing flow rate measurements from 9.5 to 7.3 mL/s. The LDD for flow rate and velocity varied between 1 and 5%. The LDD for flow rate decreased with increased voxel size and NSA (p = 0.033 and 0.042). The LDD for velocity decreased with increased voxel size (p < 10 -16 ). No change was observed when VENC varied., Conclusions: PC-MRI overestimated flow. However, it has high precision in a small-vessel phantom with constant flow rate. Improved accuracy was obtained with increasing spatial resolution (smaller voxels). Improved precision was obtained with increasing signal-to-noise ratio (larger voxels and/or higher NSA)., Relevance Statement: Phase-contrast MRI is clinically used in large vessels. To further investigate the possibility of using phase-contrast MRI for smaller intracranial vessels in neurovascular disorders, we need to understand how acquisition parameters affect phase-contrast MRI-measured flow rate and velocity in small vessels., Key Points: • PC-MRI measures flow and velocity in a small lumen phantom with high precision but overestimates flow rate. • The precision of PC-MRI measurements matches the precision of standard reference for flow rate measurements. • Optimizing PC-MRI settings can enhance accuracy and precision in flow rate and velocity measurements., (© 2024. The Author(s).)

Although most pituitary neuroendocrine tumors (PitNETs)/pituitary adenomas remain intrasellar, a significant proportion of tumors show parasellar invasive growth and 6% to 8% infiltrate the bone structures, thus affecting the prognosis. There is an unmet need to identify novel markers that can predict the parasellar growth of PitNETs. Furthermore, mechanisms that regulate bone invasiveness of PitNETs and factors related to tumor vascularization are largely unknown. We used genome-wide mRNA analysis in a cohort of 77 patients with PitNETs of different types to explore the differences in gene expression patterns between invasive and noninvasive tumors with respect to the parasellar growth and regarding the rare phenomenon of bone invasiveness. Additionally, we studied the genes correlated to the contrast enhancement quotient, a novel radiological parameter of tumor vascularization. Most of the genes differentially expressed related to the parasellar growth were genes involved in tumor invasiveness. Differentially expressed genes associated with bone invasiveness are involved in NF-κB pathway and antitumoral immune response. Lack of clear clustering regarding the parasellar and bone invasiveness may be explained by the influence of the cell lineage-related genes in this heterogeneous cohort of PitNETs. Our transcriptomics analysis revealed differences in the molecular fingerprints between invasive, including bone invasive, and noninvasive PitNETs, although without clear clustering. The contrast enhancement quotient emerged as a radiological parameter of tumor vascularization, correlating with several angiogenesis-related genes. Several of the top genes related to the PitNET invasiveness and vascularization have potential prognostic and therapeutic application requiring further research., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Purpose: Very preterm birth increases risk for neonatal white matter injury, but there is limited data on to what extent this persists into adolescence and how this relates to ophthalmological outcomes. The aim of this study was to assess brain MRI findings in 12-year-old children born very preterm compared to controls and their association with concurrent ophthalmological outcomes., Methods: We included 47 children born very preterm and 22 full-term controls (gestational age <32 and >37 weeks, respectively). Brain MRI findings were studied in association with concurrent ophthalmological outcomes at 12-year follow-up., Results: Evans index (0.27 vs 0.25, p<0.001) and a proposed "posterior ventricle index" (0.47 vs 0.45, p=0.018) were increased in children born very preterm. Higher gestational age associated with larger corpus callosum area (β=10.7, 95%CI 0.59-20.8). Focal white matter lesions were observed in 15 (32%) of very preterm children and in 1 (5%) of full-term controls. Increased posterior ventricle index increased risk for visual acuity ≤1.0 (OR=1.07×10 11 , 95%CI=7.78-1.48×10 21 ) and contrast sensitivity <0.5 (OR=2.6×10 27 , 95%CI=1.9×10 8 -3.5×10 46 ). Decreased peritrigonal white matter thickness associated with impaired visual acuity (β=0.04, 95%CI 0.002-0.07)., Conclusion: More white matter lesions and evidence of lower white matter volume were found in children born very preterm compared with full-term controls at 12-year follow-up. The association between larger posterior ventricle index and reduced visual acuity and contrast sensitivity suggests disturbances of the posterior visual pathway due to diffuse white matter lesions., (© 2023. The Author(s).)

Denitrification in sediments is a key microbial process that removes excess fixed nitrogen, while dissimilatory nitrate reduction to ammonium (DNRA) converts nitrate to ammonium. Although microorganisms are responsible for essential nitrogen (N) cycling, it is not yet fully understood how these microbially mediated processes respond to toxic hydrophobic organic compounds (HOCs) and metals. In this study, we sampled long-term polluted sediment from the outer harbor of Oskarshamn (Baltic Sea), measured denitrification and DNRA rates, and analyzed taxonomic structure and N-cycling genes of microbial communities using metagenomics. Results showed that denitrification and DNRA rates were within the range of a national reference site and other unpolluted sites in the Baltic Sea, indicating that long-term pollution did not significantly affect these processes. Furthermore, our results indicate an adaptation to metal pollution by the N-cycling microbial community. These findings suggest that denitrification and DNRA rates are affected more by eutrophication and organic enrichment than by historic pollution of metals and organic contaminants., (© 2023. The Author(s).)

Objective: A small posterior fossa (PF) has been hypothesized to explain the increased incidence of trigeminal neuralgia (TN) in females and could make microvascular decompression (MVD) more challenging. The aim of this study was to investigate the association between the PF volume and dimensions in relation to biological sex, type of neurovascular conflict (NVC), and outcome after MVD in classic TN., Methods: In this observational study, 84 patients with TN operated on with MVD with a preoperative head computed tomography(CT) scan were included. Eighty-two adults without TN who had undergone head CT for other reasons were included as controls. PF volume and dimensions (x-axis, y-axis, and z-axis) were evaluated on the CT scans. For the patients with TN, Barrow Neurological Institute (BNI) grade was evaluated 6 months after MVD., Results: There was no difference in PF volume or dimensions between the patients with TN and controls. Women showed a smaller volume and narrower (x-axis) PF than men, but these differences did not manifest when comparing patients with TN and controls within each sex. Patients with an NVC involving the superior cerebellar artery had a narrower (x-axis) and shorter (y-axis) PF than did patients with an NVC resulting from other arteries. PF volume or dimensions were not associated with BNI grade after MVD., Conclusions: PF anatomy was related to the NVC type but did not differ between patients with TN and controls and was not related to the surgical outcome after MVD., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Many women are pregnant during several percent of their lives. Occasionally, there is a need for neuroradiological examinations during pregnancy or lactation. In our clinical work, we regularly see that female patients are being withheld relevant diagnostic scans during pregnancy, due to insufficient knowledge or an unbalanced comparison between benefits and risks. This article describes the current knowledge regarding conditions for performing CT and MRI scans in pregnant and lactating patients, including the use of contrast media. PET scans and reactions to contrast media are briefly mentioned, but interventional radiology is not discussed.

Purpose: Moyamoya (MM) disease is characterized by progressive intracranial arterial stenosis. Patients commonly need revascularization surgery to optimize cerebral blood flow (CBF). Estimation of CBF and cerebrovascular reserve (CVR) is therefore necessary before and after surgery. However, assessment of CBF before and after indirect revascularization surgery with the multiple burr hole (MBH) technique in MM has not been studied extensively. In this study, we describe our initial experience using arterial spin labeling magnetic resonance perfusion imaging (ASL-MRI) for CBF and CVR assessment before and after indirect MBH revascularization surgery in MM patients., Methods: Eleven MM patients (initial age 6-50 years, 1 male/10 female) with 19 affected hemispheres were included. A total of 35 ASL-MRI examinations were performed using a 3D-pCASL acquisition before and after i.v. acetazolamide challenge (1000 mg in adults and 10 mg/kg in children). Twelve MBH procedures were performed in seven patients. The first follow-up ASL-MRI was performed 7-21 (mean 12) months after surgery., Results: Before surgery, CBF was 46 ± 16 (mean ± SD) ml/100 g/min and CVR after acetazolamide challenge was 38.5 ± 9.9 (mean ± SD)% in the most affected territory (middle cerebral artery). In cases in which surgery was not performed, CVR was 56 ± 12 (mean ± SD)% in affected hemispheres. After MBH surgery, there was a relative change in CVR compared to baseline (preop) of + 23.5 ± 23.3% (mean ± SD). There were no new ischemic events., Conclusion: Using ASL-MRI we followed changes in CBF and CVR in patients with MM. The technique was encouraging for assessments before and after revascularization surgery., (© 2023. The Author(s).)

Background: Cerebral hemodynamics in moyamoya disease (MMD) is complex and needs further elucidation. The primary aim of the study was to determine the association of the cerebrovascular reserve (CVR) with cerebral blood flow (CBF) disturbances, oxygen extraction fraction (OEF max ), and energy metabolism ( CMRO 2 max ) in MMD, using arterial spin label magnetic resonance imaging (ASL-MRI) before and after acetazolamide administration., Methods: Thirty-nine ASL-MRI scans with a concurrent acetazolamide challenge from 16 MMD patients at the Uppsala University Hospital, Sweden, 2016-2021, were retrospectively analyzed. CBF was assessed before and 5, 15, and 25 min after acetazolamide administration, and the maximal response CVR max was used for further analyses. Dynamic susceptibility contrast (DSC) MRI was performed 30 min after acetazolamide injection, and the data were analyzed using the Cercare Medical Neurosuite to assess capillary transit time heterogeneity (CTTH; indicating microvascular function), OEF max , and CMRO 2 max ., Results: In the ACA territory, a lower CVR max was associated with lower baseline CBF, higher CTTH, and higher OEF max but not with CMRO 2 max in generalized estimating equation models. In the MCA territory, lower CVR max was associated with lower baseline CBF and higher CMRO 2 max but not with CTTH and OEF max. ., Conclusion: Altogether, a compromised CVR in MMD patients reflected disturbances in macro-/microvascular blood flow, oxygenation, and CMRO 2 . ASL-MRI with acetazolamide challenge is a feasible and radiation-free alternative to positron emission tomography (PET) imaging in MMD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Svedung Wettervik, Fahlström, Wikström, Lewén and Enblad.)

Background: Immunoglobulin gamma (IgG) oligoclonal bands (OCB) in the cerebrospinal fluid (CSF) are absent in a small group of multiple sclerosis (MS) patients. According to previous research, OCB-negative MS patients differ genetically but not clinically from OCB-positive MS patients. However, whether OCB-negative MS is a unique immunological and clinical entity remains unclear. The absence of OCB poses a significant challenge in diagnosing MS. (1) Objective: The objective of this study was twofold: (1) to determine the prevalence of OCB-negative MS patients in the Uppsala region, and (2) to assess the frequency of misdiagnosis in this patient group. (2) Methods: We conducted a retrospective study using data from the Swedish MS registry (SMSreg) covering 83% of prevalent MS cases up to 20 June 2020 to identify all MS patients in the Uppsala region. Subsequently, we collected relevant information from the medical records of all OCB-negative MS cases, including age of onset, gender, presenting symptoms, MRI features, phenotype, Expanded Disability Status Scale (EDSS) scores, and disease-modifying therapies (DMTs). (3) Results: Out of 759 MS patients identified, 69 had an OCB-negative MS diagnosis. Upon re-evaluation, 46 patients had a typical history and MRI findings of MS, while 23 had unusual clinical and/or radiologic features. An alternative diagnosis was established for the latter group, confirming the incorrectness of the initial MS diagnosis. The average EDSS score was 2.0 points higher in the MS group than in the non-MS group ( p = 0.001). The overall misdiagnosis rate in the cohort was 33%, with 22% of misdiagnosed patients having received DMTs. (4) Conclusions: Our results confirm that the absence of OCB in the CSF should raise suspicion of possible misdiagnosis in MS patients and prompt a diagnostic reassessment.

Background: Trigeminal neuralgia (TN), a severe type of facial pain, is mainly caused by a neurovascular conflict (NVC). The severity of the NVC seems associated with the outcome following microvascular decompression (MVD) surgery. This study aimed to investigate the outcome after MVD and whether it is affected by NVC severity and sex., Methods: TN patients (n = 109) were followed for 5 to 10 years after MVD. Barrow Neurology Index (BNI), Patients Global Impression of Change (PGIC), complications, and time to relapse were evaluated. The NVC severity was retrospectively reviewed from presurgical MRI. Demographic and clinical factors and NVC severity were analyzed for potential association with outcome after MVD., Results: The success rate (BNI ≤ 2) was 80% after 5 to 10 years follow-up for TN patients with severe NVC (grade 2-3) and 56% for TN patients with mild NVC (grade 0-1, P = 0.003). No sex difference was observed in outcome for patients with both mild (P = 0.924) and severe NVC (P = 0.883) respectively. Three patients (2.8%) during the hospital stay, and two patients (1.8%) at 6 weeks, experienced a complication requiring invasive treatment. At long-term 52/109 patients (47.7%) reported some type of persistent adverse event, of which the majority were mild and required no treatment., Conclusions: MVD offers an 80% probability of long-term pain relief in TN patients with severe NVC, with low frequency of serious complications. NVC severity significantly affects outcome after MVD, while no sex differences in outcome were found. In consistency with previous work, the results stress the importance of adequate neuroradiological assessment of the NVC for preoperative patient selection., (© 2023. The Author(s).)

Introduction: Single-delay Arterial Spin Labeling (ASL)-based spatial coefficient of variation (CoV CBF ) has been suggested as a measure of hemodynamic disturbance in patients with cerebrovascular diseases. However, spatial CoV CBF and other histogram-based parameters such as skewness and kurtosis and the volume of the arterial transit time artefact (ATA vol ), has not been evaluated in patients with MMD nor against cerebrovascular reserve (CVR). The aim of this study was to assess whether any associations between spatial CoV CBF , skewness, kurtosis, and ATA vol are present and to analyze any potential associations with CVR, derived from single-delay ASL in patients with MMD., Methods: Fifteen MMD patients were included before or after revascularization surgery. Cerebral blood flow (CBF) maps were acquired using pseudo-continuous ASL before, and 5, 15, and 25 min after an intravenous acetazolamide injection. CVR max was defined as the highest percentual increase in CBF at any of the three post-injection time points. A vascular territory template was spatially normalized to each patient, including the bilateral anterior, middle, and posterior cerebral arteries. All affected anterior and middle cerebral artery regions and all unaffected posterior cerebral artery regions were included, based on Suzuki grading by digital subtraction angiography., Results: Significant differences between affected and unaffected regions were found for CBF, CVR max , and ATA vol . No association was found between CVR max and any other parameter. High correlations were found between spatial CoV CBF , skewness and ATA vol ., Conclusion: Spatial CoV CBF derived from single-delay ASL does not correlate with CVR in patients with MMD. Moreover, skewness and kurtosis did not provide additional information of clinical value., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Fahlström, Svedung Wettervik, Enblad, Lewén and Wikström.)

Background: Of interest to women's mental health, a wealth of studies suggests sex differences in nicotine addiction and treatment response, but their psychoneuroendocrine underpinnings remain largely unknown. A pathway involving sex steroids could indeed be involved in the behavioural effects of nicotine, as it was found to inhibit aromatase in vitro and in vivo in rodents and non-human primates, respectively. Aromatase regulates the synthesis of oestrogens and, of relevance to addiction, is highly expressed in the limbic brain., Methods: The present study sought to investigate in vivo aromatase availability in relation to exposure to nicotine in healthy women. Structural magnetic resonance imaging and two [ 11 C]cetrozole positron emission tomography (PET) scans were performed to assess the availability of aromatase before and after administration of nicotine. Gonadal hormones and cotinine levels were measured. Given the region-specific expression of aromatase, a ROI-based approach was employed to assess changes in [ 11 C]cetrozole non-displaceable binding potential., Results: The highest availability of aromatase was found in the right and left thalamus. Upon nicotine exposure, [ 11 C]cetrozole binding in the thalamus was acutely decreased bilaterally (Cohen's d = -0.99). In line, cotinine levels were negatively associated with aromatase availability in the thalamus, although as non-significant trend., Conclusions: These findings indicate acute blocking of aromatase availability by nicotine in the thalamic area. This suggests a new putative mechanism mediating the effects of nicotine on human behaviour, particularly relevant to sex differences in nicotine addiction., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Roux-en-Y gastric bypass (RYGB) leads to beneficial effects on glucose homeostasis, and attenuated hormonal counterregulatory responses to hypoglycemia are likely to contribute. RYGB also induces alterations in neural activity of cortical and subcortical brain regions. We aimed to characterize RYGB-induced changes in resting-state connectivity of specific brain regions of interest for energy homeostasis and behavioral control during hypoglycemia., Method: Ten patients with BMI > 35 kg/m 2 were investigated with brain PET/MR imaging during a hyperinsulinemic normo- and hypoglycemic clamp, before and 4 months after RYGB. Hormonal levels were assessed throughout the clamp. Resting-state (RS) fMRI scans were acquired in the glucose-lowering phase of the clamp, and they were analyzed with a seed-to-voxel approach., Results: RS connectivity during initiation of hypoglycemia was significantly altered after RYGB between nucleus accumbens, thalamus, caudate, hypothalamus and their crosstalk with cortical and subcortical regions. Connectivity between the nucleus accumbens and the frontal pole was increased after RYGB, and this was associated with a reduction of ACTH (r = -0.639, p = 0.047) and cortisol (r = -0.635, p = 0.048) responses. Instead, connectivity between the caudate and the frontal pole after RYGB was reduced and this was associated with less attenuation of glucagon response during the hypoglycemic clamp (r = -0.728, p = 0.017), smaller reduction in fasting glucose (r = -0.798, p = 0.007) and less excess weight loss (r = 0.753, p = 0.012). No other significant associations were found between post-RYGB changes in ROI-to-voxel regional connectivity hormonal responses and metabolic or anthropometric outcomes., Conclusion: RYGB alters brain connectivity during hypoglycemia of several neural pathways involved in reward, inhibitory control, and energy homeostasis. These changes are associated with altered hormonal responses to hypoglycemia and may be involved in the glucometabolic outcome of RYGB., (© 2022. The Author(s).)

Premenstrual dysphoric disorder (PMDD) is characterized by severe cyclic mood symptoms emerging in the luteal phase of the menstrual cycle. The variation in progesterone levels and its metabolites during the luteal phase seems critical to the occurrence of PMDD symptoms. Notably, the efficacy of selective progesterone receptor modulator (SPRM) treatment on the mental symptoms of PMDD has been recently demonstrated. In the present study, structural magnetic resonance imaging was used to assess the effects of SPRM treatment, compared with placebo, on grey matter morphology in women with PMDD. In total, 35 women were scanned during the luteal phase, before and after three months of treatment with SPRM or placebo. Symptom severity was assessed using the Daily Record of Severity of Problems (DRSP), while gonadal hormone levels were measured by liquid chromatography-tandem mass spectrometry. Region-of-interest and whole-brain approaches were employed to perform voxel-based morphometry analyses, subcortical volumetric analyses, and surface-based morphometry analyses. No interaction or main effects of treatment and time were observed on grey matter volume and cortical surface measures (cortical thickness, gyrification index, sulcal depth, and fractal dimension). The relationship between change in brain morphology and symptom severity was also explored but no treatment-dependant grey matter structure change was related to symptom severity change. These findings suggest that SPRM treatment does not impart macrostructural changes onto grey matter structure, at least in the short term., Competing Interests: Conflict of Interest RL received travel grants and/or conference speaker honoraria within the last three years from Bruker BioSpin MR, Heel, and support from Siemens Healthcare regarding clinical research using PET/MR. He is a shareholder of the start-up company BM Health GmbH since 2019. ISP has served occasionally on advisory boards or acted as invited speaker at scientific meetings for Asarina Pharma, Bayer Health Care, Gedeon Richter, Peptonics, Shire/Takeda, Sandoz, and Lundbeck A/S. All other authors declare that they have no conflict of interest., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: A wide range of neuroradiological findings has been reported in patients with coronavirus disease 2019 (COVID-19), ranging from subcortical white matter changes to infarcts, haemorrhages and focal contrast media enhancement. These have been descriptively but inconsistently reported and correlations with clinical findings and biomarkers have been difficult to extract from the literature. The purpose of this study was to quantify the extents of neuroradiological findings in a cohort of patients with COVID-19 and neurological symptoms, and to investigate correlations with clinical findings, duration of intensive care and biomarkers in blood., Material and Methods: Patients with positive SARS-CoV-2 and at least one new-onset neurological symptom were included from April until July 2020. Nineteen patients were examined regarding clinical symptoms, biomarkers in blood and MRI of the brain. In order to quantify the MRI findings, a semi-quantitative neuroradiological severity scale was constructed a priori, and applied to the MR images by two specialists in neuroradiology., Results and Conclusions: The score from the severity scale correlated significantly with blood biomarkers of CNS injury (glial fibrillary acidic protein, total-tau, ubiquitin carboxyl-terminal hydrolase L1) and inflammation (C-reactive protein), Glasgow Coma Scale score, and the number of days spent in intensive care. The underlying radiological assessments had inter-rater agreements of 90.5%/86% (for assessments with 2/3 alternatives). Total intraclass correlation was 0.80. Previously reported neuroradiological findings in COVID-19 have been diverse and heterogenous. In this study, the extent of findings in MRI examination of the brain, quantified using a structured report, shows correlation with relevant biomarkers., (Copyright © 2021 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Premenstrual dysphoric disorder (PMDD) is a female-specific condition classified in the Diagnostic and Statical Manual-5th edition under depressive disorders. Alterations in grey matter volume, cortical thickness and folding metrics have been associated with a number of mood disorders, though little is known regarding brain morphological alterations in PMDD. Here, women with PMDD and healthy controls underwent magnetic resonance imaging (MRI) during the luteal phase of the menstrual cycle. Differences in grey matter structure between the groups were investigated by use of voxel- and surface-based morphometry. Machine learning and multivariate pattern analysis were performed to test whether MRI data could distinguish women with PMDD from healthy controls. Compared to controls, women with PMDD had smaller grey matter volume in ventral posterior cortices and the cerebellum (Cohen's d = 0.45-0.76). Region-of-interest analyses further indicated smaller volume in the right amygdala and putamen of women with PMDD (Cohen's d = 0.34-0.55). Likewise, thinner cortex was observed in women with PMDD compared to controls, particularly in the left hemisphere (Cohen's d = 0.20-0.74). Classification analyses showed that women with PMDD can be distinguished from controls based on grey matter morphology, with an accuracy up to 74%. In line with the hypothesis of an impaired top-down inhibitory circuit involving limbic structures in PMDD, the present findings point to PMDD-specific grey matter anatomy in regions of corticolimbic networks. Furthermore, the results include widespread cortical and cerebellar regions, suggesting the involvement of distinct networks in PMDD pathophysiology., (© 2022. The Author(s).)

Ovarian hormones fluctuations across the menstrual cycle are experienced by about 58% of women in their fertile age. Maladaptive brain sensitivity to these changes likely leads to the severe psychological, cognitive, and physical symptoms repeatedly experienced by women with Premenstrual Dysphoric Disorder (PMDD) during the late luteal phase of the menstrual cycle. However, the neuroanatomical correlates of these symptoms are unknown. The relationship between grey matter structure and PMDD symptom severity was delineated using structural magnetic resonance imaging during the late luteal phase of fifty-one women diagnosed with PMDD, combined with Voxel- and Surface-Based Morphometry, as well as subcortical volumetric analyses. A negative correlation was found between depression-related symptoms and grey matter volume of the bilateral amygdala. Moreover, the severity of affective and somatic PMDD symptoms correlated with cortical thickness, gyrification, sulcal depth, and complexity metrics, particularly in the prefrontal, cingulate, and parahippocampal gyri. The present findings provide the first evidence of grey matter morphological characteristics associated with PMDD symptomatology in brain regions expressing ovarian hormone receptors and of relevance to cognitive-affective functions, thus potentially having important implications for understanding how structural brain characteristics relate to PMDD symptomatology., (© 2022. The Author(s).)

Aim: The criteria for diagnosing abusive head trauma (AHT) are not well defined and this condition might be diagnosed on failing premises. Our aim was to review criminal AHT cases in Norwegian courts by scrutinising the underlying medical documentation., Methods: Cases were identified in the data registry for Norwegian courts from 2004 to 2015. Documentation was obtained from relevant health institutions. The medical co-authors first made independent evaluations of the documentation for each child, followed by a consensus evaluation., Results: A total of 17 children (11 boys) were identified, all diagnosed as AHT by court appointed experts, 15 were infants (mean age 2.6 months). A high proportion (41.2%) was born to immigrant parents and 31.3% were premature. The medical findings could be explained by alternative diagnoses in 16 of the 17 children; 8 boys (7 infants - mean age 2.9 months) had clinical and radiological characteristics compatible with external hydrocephalus complicated by chronic subdural haematoma. Six children (five infants with mean age 2.1 months) had a female preponderance and findings compatible with hypoxic ischaemic insults., Conclusion: The medical condition in most children had not necessarily been caused by shaking or direct impact, as was originally concluded by the court experts., (©2021 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: Premenstrual dysphoric disorder (PMDD) is a mood disorder characterized by psychological and physical symptoms. Differences in white matter have been associated with affective and anxiety disorders, which share some symptoms with PMDD. However, whether white matter structure differs between the brains of individuals with PMDD and healthy controls is not known, nor is its relation to symptom severity., Methods: We performed tract-based spatial statistics and voxel-based morphometry analyses of diffusion tensor imaging metrics and white matter volume, using 2 neuroimaging data sets ( n = 67 and n = 131) and a combined whole-brain and region-of-interest approach. We performed correlation analyses to investigate the relationship between regions with different white matter microstructure and volume and PMDD symptom severity., Results: We found greater fractional anisotropy in the left uncinate fasciculus ( d = 0.69) in individuals with PMDD compared to controls. Moreover, the volume of the right uncinate fasciculus was higher in individuals with PMDD compared to controls ( d = 0.40). As well, the severity of premenstrual depression was positively correlated with fractional anisotropy in the right superior longitudinal fasciculus ( r = 0.35)., Limitations: It is challenging to interpret group differences in diffusion tensor imaging metrics in terms of their underlying biophysical properties. The small size of the control group in the diffusion tensor imaging study may have prevented effects of interest from being detected., Conclusion: The findings of the present study provide evidence of differential cerebral white matter structure associated with PMDD and its symptoms., Competing Interests: Competing interests: R. Lanzenberger received support from Siemens Healthcare for clinical research using PET/MR, conference speaker honoraria and travel grants within the last 3 years from Bruker BioSpin MR and Heel, and he has been a shareholder of the start-up company BM Health GmbH since 2019. C.N. Epperson has received research grant support from Sage Therapeutics; he has served on an advisory board for Sage Therapeutics and has received honoraria and travel funding from Sage Therapeutics. I. Sundström-Poromaa was supported by a grant from the Swedish Research Council (2020-01801) and the Brain Foundation (F2020-0255), has served occasionally on advisory boards for Gedeon Richter and received honoraria as an invited speaker for Bayer Health Care, Gedeon Richter, Peptonics, Shire/Takeda, and Sandoz. E. Comasco receives funds from SciLifeLab. No other competing interests declared., (© 2022 CMA Impact Inc. or its licensors.)

Background: Acute subdural hematoma (ASDH) and chronic subdural hematoma (CSDH) in infants have been regarded as highly specific for abuse. Other causes of CSDH have not been investigated in a large population., Purpose: The purpose of this study was to investigate to what extent external hydrocephalus is present in infants with ASDH and CSDH undergoing evaluation for abuse., Material and Methods: Eighty-five infants suspected of being abused, with ASDH (n = 16) or CSDH (n = 69), were reviewed regarding age, risk factor profiles, craniocortical width (CCW), sinocortical width (SCW), frontal interhemispheric width (IHW), subarachnoid space width (SSW), and head circumference (HC). In infants with unilateral subdural hematoma (SDH), correlations between contralateral SSW and ipsilateral CCW and SDH width were investigated., Results: Infants with CSDH had significantly lower mortality, were more often premature and male, and had significantly higher CCW, SCW, IHW, and SSW than infants with ASDH (P < 0.05). Ipsilateral CCW (R = 0.92, P < 0.001) and SDH width (R = 0.81, P < 0.01) correlated with contralateral SSW. Increased HC was more prevalent in infants with CSDH (71%) than in infants with ASDH (14%) (P < 0.01). Forty-two infants, all with CSDH, had at least one of CCW, SCW, or IHW ≥95 th percentile. Twenty infants, all with CSDH, had CCW, SCW, and IHW >5 mm, in addition to increased HC., Conclusion: A substantial proportion of infants with CSDH who had been suspected of being abused had findings suggesting external hydrocephalus., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Pre-eclampsia, a multisystem disorder in pregnancy, is one of the most common causes of maternal morbidity and mortality worldwide. However, we lack methods for objective assessment of organ function in pre-eclampsia and predictors of organ impairment during and after pre-eclampsia. The women's and their partners' experiences of pre-eclampsia have not been studied in detail. To phenotype different subtypes of the disorder is of importance for prediction, prevention, surveillance, treatment and follow-up of pre-eclampsia.The aim of this study is to set up a multicentre database and biobank for pre-eclampsia in order to contribute to a safer and more individualised treatment and care., Methods and Analysis: This is a multicentre cohort study. Prospectively recruited pregnant women ≥18 years, diagnosed with pre-eclampsia presenting at Sahlgrenska University Hospital, Uppsala University Hospital and at Södra Älvsborgs Hospital, Sweden, as well as normotensive controls are eligible for participation. At inclusion and at 1-year follow-up, the participants donate biosamples that are stored in a biobank and they are also asked to participate in various organ-specific evaluations. In addition, questionnaires and interviews regarding the women's and partner's experiences are distributed at follow-up., Ethics and Dissemination: By creating a database and biobank, we will provide the means to explore the disorder in a broader sense and allow clinical and laboratory discoveries that can be translated to clinical trials aiming at improved care of women with pre-eclampsia. Further, to evaluate experiences and the psychological impact of being affected by pre-eclampsia can improve the care of pregnant women and their partners. In case of incidental pathological findings during examinations performed, they will be handled in accordance with clinical routine. Data are stored in a secure online database. Biobank samples are identified through the women's personal identification number and pseudonymised after identification in the biobank before analysis.This study was approved by the regional ethical review board in Gothenburg on 28 December 2018 (approval number 955-18) and by the Swedish Ethical Review Authority on 27 February 2019 (approval number 2019-00309).Results from the study will be published in international peer-reviewed journals., Trial Registration Number: ISRCTN13060768., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Pituitary neuroendocrine tumors (PitNETs) are common, generally benign tumors with complex clinical characteristics related to hormone hypersecretion and/or growing sellar tumor mass. PitNETs can be classified based on the expression pattern of anterior pituitary hormones and three main transcriptions factors (TF), SF1, PIT1 and TPIT that regulate differentiation of adenohypophysial cells. Here, we have extended this classification based on the global transcriptomics landscape using tumor tissue from a well-defined cohort comprising 51 PitNETs of different clinical and histological types. The molecular profiles were compared with current classification schemes based on immunohistochemistry. Our results identified three main clusters of PitNETs that were aligned with the main pituitary TFs expression patterns. Our analyses enabled further identification of specific genes and expression patterns, including both known and unknown genes, that could distinguish the three different classes of PitNETs. We conclude that the current classification of PitNETs based on the expression of SF1, PIT1 and TPIT reflects three distinct subtypes of PitNETs with different underlying biology and partly independent from the expression of corresponding hormones. The transcriptomic analysis reveals several potentially targetable tumor-driving genes with previously unknown role in pituitary tumorigenesis., (© 2021. The Author(s).)

Background: Treatment of intracranial arteriovenous malformations (AVMs) includes surgery, radiation therapy, endovascular occlusion, or a combination. Proton radiation therapy enables very focused radiation, minimizing dose to the surrounding brain., Purpose: To evaluate the presence of radiation-induced changes on post-treatment MRI in patients with AVMs treated with proton radiation and to compare these with development of symptoms and nidus obliteration., Material and Methods: Retrospective review of pre- and post-treatment digital subtraction angiography and MRI and medical records in 30 patients with AVMs treated with proton radiation. Patients were treated with two or five fractions; total radiation dose was 20-35 physical Gy. Vasogenic edema (minimal, perinidal, or severe), contrast enhancement (minimal or annular), cavitation and nidus obliteration (total, partial, or none) were assessed., Results: 26 of 30 patients (87%) developed MRI changes. Vasogenic edema was seen in 25 of 30 (83%), abnormal contrast enhancement in 18 of 26 (69%) and cavitation in 5 of 30 (17%). Time from treatment to appearance of MRI changes varied between 5 and 25 months (median 7, mean 10). Seven patients developed new or deteriorating symptoms that required treatment with corticosteroids; all these patients had extensive MRI changes (severe vasogenic edema and annular contrast enhancement). Not all patients with extensive MRI changes developed symptoms. We found no relation between MRI changes and nidus obliteration., Conclusion: Radiation-induced MRI changes are seen in a majority of patients after proton radiation treatment of AVMs. Extensive MRI changes are associated with new or deteriorating symptoms., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

This study tested two sediment amendments with active sorbents: injection of aluminum (Al) into sediments and thin-layer capping with Polonite (calcium-silicate), with and without the addition of activated carbon (AC), for their simultaneous sequestration of sediment phosphorus (P), hydrophobic organic contaminants (HOCs), and metals. Sediment cores were collected from a eutrophic and polluted brackish water bay in Sweden and incubated in the laboratory to measure sediment-to-water contaminant release and effects on biogeochemical processes. We used diffusive gradients in thin-film passive samplers for metals and semi-permeable membrane devices for the HOC polychlorinated biphenyls and polycyclic aromatic hydrocarbons. Al injection into anoxic sediments completely stopped the release of P and reduced the release of cadmium (Cd, -97%) and zinc (Zn, -95%) but increased the sediment fluxes of PAH (+49%), compared to the untreated sediment. Polonite mixed with AC reduced the release of P (-70%), Cd (-67%), and Zn (-89%) but increased methane (CH 4 ) release. Adding AC to the Al or Polonite reduced the release of HOCs by 40% in both treatments. These results not only demonstrate the potential of innovative remediation techniques using composite sorbent amendments but also highlight the need to assess possible ecological side effects on, for example, sedimentary microbial processes.

Premenstrual dysphoric disorder (PMDD) is a psychiatric condition characterized by late luteal phase affective, cognitive, and physical impairment. The disorder causes significant suffering in about 5% of women in their reproductive age. Altered sensitivity of cognitive-affective brain circuits to progesterone and its downstream metabolite allopregnanolone is suggested to underlie PMDD symptomatology. Core mood symptoms include irritability and anger, with aggression being the behavioral outcome of these symptoms. The present study sought to investigate the neural correlates of reactive aggression during the premenstrual phase in women with PMDD, randomized to a selective progesterone receptor modulator (SPRM) or placebo. Self-reports on the Daily Record of Severity of Problems were used to assess PMDD symptoms and gonadal hormone levels were measured by liquid chromatography tandem mass spectrometry. Functional magnetic resonance imaging was performed in 30 women with PMDD, while performing the point subtraction aggression paradigm. Overall, a high SPRM treatment response rate was attained (93%), in comparison with placebo (53.3%). Women with PMDD randomized to SPRM treatment had enhanced brain reactivity in the dorsal anterior cingulate cortex and dorsomedial prefrontal cortex during the aggressive response condition. The fronto-cingulate reactivity during aggressive responses depended on treatment, with a negative relationship between brain reactivity and task-related aggressiveness found in the placebo but not the SPRM group. The findings contribute to define the role of progesterone in PMDD symptomatology, suggesting a beneficial effect of progesterone receptor antagonism, and consequent anovulation, on top-down emotion regulation, i.e., greater fronto-cingulate activity in response to provocation stimuli.

Cerebrovascular reserve capacity (CVR), an important predictor of ischaemic events and a prognostic factor for patients with moyamoya disease (MMD), can be assessed by measuring cerebral blood flow (CBF) before and after administration of acetazolamide (ACZ). Often, a single CBF measurement is performed between 5 and 20 min after ACZ injection. Assessment of the temporal response of the vasodilation secondary to ACZ administration using several repeated CBF measurements has not been studied extensively. Furthermore, the high standard deviations of the group-averaged CVRs reported in the current literature indicate a patient-specific dispersion of CVR values over a wide range. This study aimed to assess the temporal response of the CBF and derived CVR during ACZ challenge using arterial spin labeling in patients with MMD. Eleven patients with MMD were included before or after revascularisation surgery. CBF maps were acquired using pseudo-continuous arterial spin labeling before and 5, 15, and 25 min after an intravenous ACZ injection. A vascular territory template was spatially normalized to patient-specific space, including the bilateral anterior, middle, and posterior cerebral arteries. CBF increased significantly post-ACZ injection in all vascular territories and at all time points. Group-averaged CBF and CVR values remained constant throughout the ACZ challenge in most patients. The maximum increase in CBF occurred most frequently at 5 min post-ACZ injection. However, peaks at 15 or 25 min were also present in some patients. In 68% of the affected vascular territories, the maximum increase in CBF did not occur at 15 min. In individual cases, the difference in CVR between different time points was between 1 and 30% points (mean difference 8% points). In conclusion, there is a substantial variation in CVR between different time points after the ACZ challenge in patients with MMD. Thus, there is a risk that the use of a single post-ACZ measurement time point overestimates disease progression, which could have wide implications for decision-making regarding revascularisation surgery and the interpretation of the outcome thereof. Further studies with larger sample sizes using multiple CBF measurements post-ACZ injection in patients with MMD are encouraged., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fahlström, Wikström, Borota, Enblad and Lewén.)

While Roux-en-Y gastric bypass (RYGB) surgery in obese individuals typically improves glycemic control and prevents diabetes, it also frequently causes asymptomatic hypoglycemia. Previous work showed attenuated counterregulatory responses following RYGB. The underlying mechanisms as well as the clinical consequences are unclear. In this study, 11 subjects without diabetes with severe obesity were investigated pre- and post-RYGB during hyperinsulinemic normo-hypoglycemic clamps. Assessments were made of hormones, cognitive function, cerebral blood flow by arterial spin labeling, brain glucose metabolism by 18 F-fluorodeoxyglucose (FDG) positron emission tomography, and activation of brain networks by functional MRI. Post- versus presurgery, we found a general increase of cerebral blood flow but a decrease of total brain FDG uptake during normoglycemia. During hypoglycemia, there was a marked increase in total brain FDG uptake, and this was similar for post- and presurgery, whereas hypothalamic FDG uptake was reduced during hypoglycemia. During hypoglycemia, attenuated responses of counterregulatory hormones and improvements in cognitive function were seen postsurgery. In early hypoglycemia, there was increased activation post- versus presurgery of neural networks in brain regions implicated in glucose regulation, such as the thalamus and hypothalamus. The results suggest adaptive responses of the brain that contribute to lowering of glycemia following RYGB, and the underlying mechanisms should be further elucidated., (© 2021 by the American Diabetes Association.)

Cerebral blood flow (CBF) measurements are of high clinical value and can be acquired non-invasively with no radiation exposure using pseudo-continuous arterial spin labeling (ASL). The aim of this study was to evaluate accordance in resting state CBF between ASL (CBF ASL ) and 15 O-water positron emission tomography (PET) (CBF PET ) acquired simultaneously on an integrated 3T PET/MR system. The data comprised ASL and dynamic 15 O-water PET data with arterial blood sampling of eighteen subjects (eight patients with focal epilepsy and ten healthy controls, age 21 to 61 years). 15 O-water PET parametric CBF images were generated using a basis function implementation of the single tissue compartment model. Cortical and subcortical regions were automatically segmented using Freesurfer. Average CBF ASL and CBF PET in grey matter were 60 ± 20 and 75 ± 22 mL/100 g/min respectively, with a relatively high correlation ( r = 0.78, p < 0.001). Bland-Altman analysis revealed poor agreement (bias = -15 mL/100 g/min, lower and upper limits of agreements = -16 and 45 mL/100 g/min, respectively) with a negative relationship. Accounting for the negative relationship, the width of the limits of agreement could be narrowed from 61 mL/100 g/min to 35 mL/100 g/min using regression-based limits of agreements. Although a high correlation between CBF ASL and CBF PET was found, the agreement in absolute CBF values was not sufficient for ASL to be used interchangeably with 15 O-water PET.

Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality. The burden of disease lies mainly in low-middle income countries. The aim of this project is to establish a pre-eclampsia biobank in South Africa to facilitate research in the field of pre-eclampsia with a focus on phenotyping severe disease.The approach of our biobank is to collect biological specimens, detailed clinical data, tests, and biophysical examinations, including magnetic resonance imaging (MRI) of the brain, MRI of the heart, transcranial Doppler, echocardiography, and cognitive function tests.Women diagnosed with pre-eclampsia and normotensive controls are enrolled in the biobank at admission to Tygerberg University Hospital (Cape Town, South Africa). Biological samples and clinical data are collected at inclusion/delivery and during the hospital stay. Special investigations as per above are performed in a subset of women. After two months, women are followed up by telephonic interviews. This project aims to establish a biobank and database for severe organ complications of pre-eclampsia in a low-middle income country where the incidence of pre-eclampsia with organ complications is high. The study integrates different methods to investigate pre-eclampsia, focusing on improved understanding of pathophysiology, prediction of organ complications, and potentially future drug evaluation and discovery.

IgG4-related hypophysitis (IgG4-RH) is increasingly being reported as an isolated entity or, less frequently, as a manifestation of a multiorgan IgG4-related disease (IgG4-RD), in which typical histopathology is a cornerstone for the diagnosis. We aimed to describe the histopathological changes in the surgical specimens from patients with clinical signs of pituitary disease that fulfilled the current diagnostic criteria for IgG4-RH. Histopathological features were correlated with clinical and radiological findings. Of 19 patients with pituitary dysfunction and inflammatory changes in the surgical pituitary specimen operated on during 2011-2019, we identified five patients with typical IgG4-related pathology (lymphoplasmacytic infiltration with more than 10 IgG4-positive plasma cells per one high power microscopic field, representing at least 40% of all plasma cells and at least focal storiform fibrosis). One patient with diabetes insipidus and pachymeningitis with IgG4-related changes in a biopsy from the dura was also included. Additional histopathological changes that typically are not part of the IgG4-RH were observed: Rathke's cleft cyst in four and granulomatous changes in two patients. One patient had an elevated serum IgG4 level and systemic manifestations that could be associated with the systemic IgG4-RD. Our findings indicate that pure IgG4-RH is uncommon. All patients with pituitary dysfunction, beyond typical IgG4-related pathology, had other pathological findings that could trigger the secondary IgG4-response. Both primary pathology and secondary IgG4-related features should be reported in patients with pituitary dysfunction because their co-occurrence may cause atypical clinical and imaging features, and unexpected response to surgical and pharmacological treatment. The current criteria for the diagnosis of IgG4-RH can lead to overdiagnosis of IgG4-RH if additional pathological changes are not taken into consideration. The classification criteria of IgG4-RD proposed by the American College of Rheumatology/European League Against Rheumatism could help classify patients more properly as IgG4-RH if applied to the pituitary gland., (© 2021 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.)

Background: Cerebral complications in preeclampsia are leading causes of maternal mortality worldwide but pathophysiology is largely unknown and a challenge to study. Using an in vitro model of the human blood-brain barrier (BBB), we explored the role of vascular endothelial growth factor receptor 2 (VEGFR2) in preeclampsia., Methods: The human brain endothelial cell line (hCMEC/D3) cultured on Tranwells insert was exposed (12 hours) to plasma from women with preeclampsia (n = 28), normal pregnancy (n = 28), and nonpregnant (n = 16) controls. Transendothelial electrical resistance (TEER) and permeability to 70 kDa fluorescein isothiocyanate (FITC)-dextran were measured for the assessment of BBB integrity. We explored possible underlying mechanisms, with a focus on the expression of tight junction proteins and phosphorylation of 2 tyrosine residues of VEGFR2, associated with vascular permeability and migration (pY951) and cell proliferation (pY1175). Plasma concentrations of soluble FMS-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) were also measured., Results: hCMEC/D3 exposed to plasma from women with preeclampsia exhibited reduced TEER and increased permeability to 70 kDa FITC-dextran. These cells upregulated the messenger ribonucleic acid (mRNA) levels of VEGFR2, and pY951-VEGFR2, but reduced pY1175-VEGFR2 (P < 0.05 in all cases). No difference in mRNA expression of tight junction protein was observed between groups. There was no correlation between angiogenic biomarkers and BBB permeability., Conclusions: We present a promising in vitro model of the BBB in preeclampsia. Selective tyrosine phosphorylation of VEGFR2 may participate in the increased BBB permeability in preeclampsia irrespective of plasma concentrations of angiogenic biomarkers., (© American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Aromatase, the enzyme that in the brain converts testosterone and androstenedione to estradiol and estrone, respectively, is a putative key factor in psychoneuroendocrinology. In vivo assessment of aromatase was performed to evaluate tracer kinetic models and optimal scan duration, for quantitative analysis of the aromatase positron emission tomography (PET) ligand [ 11 C]cetrozole. Anatomical magnetic resonance and 90-min dynamic [ 11 C]cetrozole PET-CT scans were performed on healthy women. Volume of interest (VOI)-based analyses with a plasma-input function were performed using the single-tissue and two-tissue (2TCM) reversible compartment models and plasma-input Logan analysis. Additionally, the simplified reference tissue model (SRTM), Logan reference tissue model (LRTM), and standardized uptake volume ratio model, with cerebellum as reference region, were evaluated. Parametric images were generated and regionally averaged voxel values were compared with VOI-based analyses of the reference tissue models. The optimal reference model was used for evaluation of a decreased scan duration. Differences between the plasma-input- and reference tissue-based methods and comparisons between scan durations were assessed by linear regression. The [ 11 C]cetrozole time-activity curves were best described by the 2TCM. SRTM nondisplaceable binding potential (BP ND ), with cerebellum as reference region, can be used to estimate [ 11 C]cetrozole binding and generated robust and quantitatively accurate results for a reduced scan duration of 60 min. Receptor parametric mapping, a basis function implementation of SRTM, as well as LRTM, produced quantitatively accurate parametric images, showing BP ND at the voxel level. As PET tracer, [ 11 C]cetrozole can be employed for relatively short brain scans to measure aromatase binding using a reference tissue-based approach., (© 2020 The Authors. Journal of Neuroscience Research published by Wiley Periodicals LLC.)