Infants' sex affects neural responses to affective touch in early infancy.

Social touch is closely related to the establishment and maintenance of social bonds in humans, and the sensory brain circuit for gentle brushing is already active soon after birth. Brain development is known to be sexually dimorphic, but the potential effect of sex on brain activation to gentle touch remains unknown. Here, we examined brain activation to gentle skin stroking, a tactile stimulation that resembles affective or social touch, in term-born neonates. Eighteen infants aged 11-36 days, recruited from the FinnBrain Birth Cohort Study, were included in the study. During natural sleep, soft brush strokes were applied to the skin of the right leg during functional magnetic resonance imaging (fMRI) at 3 cm/s velocity. We examined potential differences in brain activation between males (n = 10) and females (n = 8) and found that females had larger blood oxygenation level dependent (BOLD) responses (brushing vs. rest) in bilateral orbitofrontal cortex (OFC), right ventral striatum and bilateral inferior striatum, pons, and cerebellum compared to males. Moreover, the psychophysiological interactions (PPI) analysis, setting the left and right OFC as seed regions, revealed significant differences between males and females. Females exhibited stronger PPI connectivity between the left OFC and posterior cingulate or cuneus. Our work suggests that social touch neural responses are different in male and female neonates, which may have major ramifications for later brain, cognitive, and social development. Finally, many of the sexually dimorphic brain responses were subcortical, not captured by surface-based neuroimaging, indicating that fMRI will be a relevant technique for future studies.

Structural brain correlates of non-verbal cognitive ability in 5-year-old children: Findings from the FinnBrain birth cohort study.

Non-verbal cognitive ability predicts multiple important life outcomes, for example, school and job performance. It has been associated with parieto-frontal cortical anatomy in prior studies in adult and adolescent populations, while young children have received relatively little attention. We explored the associations between cortical anatomy and non-verbal cognitive ability in 165 5-year-old participants (mean scan age 5.40 years, SD 0.13; 90 males) from the FinnBrain Birth Cohort study. T1-weighted brain magnetic resonance images were processed using FreeSurfer. Non-verbal cognitive ability was measured using the Performance Intelligence Quotient (PIQ) estimated from the Block Design and Matrix Reasoning subtests from the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III). In vertex-wise general linear models, PIQ scores associated positively with volumes in the left caudal middle frontal and right pericalcarine regions, as well as surface area in left the caudal middle frontal, left inferior temporal, and right lingual regions. There were no associations between PIQ and cortical thickness. To the best of our knowledge, this is the first study to examine structural correlates of non-verbal cognitive ability in a large sample of typically developing 5-year-olds. The findings are generally in line with prior findings from older age groups, with the important addition of the positive association between volume / surface area in the right medial occipital region and non-verbal cognitive ability. This finding adds to the literature by discovering a new brain region that should be considered in future studies exploring the role of cortical structure for cognitive development in young children.

Effect of xenon on brain injury, neurological outcome, and survival in patients after aneurysmal subarachnoid hemorrhage-study protocol for a randomized clinical trial.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a neurological emergency, affecting a younger population than individuals experiencing an ischemic stroke; aSAH is associated with a high risk of mortality and permanent disability. The noble gas xenon has been shown to possess neuroprotective properties as demonstrated in numerous preclinical animal studies. In addition, a recent study demonstrated that xenon could attenuate a white matter injury after out-of-hospital cardiac arrest. METHODS: The study is a prospective, multicenter phase II clinical drug trial. The study design is a single-blind, prospective superiority randomized two-armed parallel follow-up study. The primary objective of the study is to explore the potential neuroprotective effects of inhaled xenon, when administered within 6 h after the onset of symptoms of aSAH. The primary endpoint is the extent of the global white matter injury assessed with magnetic resonance diffusion tensor imaging of the brain. DISCUSSION: Despite improvements in medical technology and advancements in medical science, aSAH mortality and disability rates have remained nearly unchanged for the past 10 years. Therefore, new neuroprotective strategies to attenuate the early and delayed brain injuries after aSAH are needed to reduce morbidity and mortality. TRIAL REGISTRATION: ClinicalTrials.gov NCT04696523. Registered on 6 January 2021. EudraCT, EudraCT Number: 2019-001542-17. Registered on 8 July 2020.

Association of cumulative prenatal adversity with infant subcortical structure volumes and child problem behavior and its moderation by a coexpression polygenic risk score of the serotonin system.

Prenatal adversity has been linked to later psychopathology. Yet, research on cumulative prenatal adversity, as well as its interaction with offspring genotype, on brain and behavioral development is scarce. With this study, we aimed to address this gap. In Finnish mother-infant dyads, we investigated the association of a cumulative prenatal adversity sum score (PRE-AS) with (a) child emotional and behavioral problems assessed with the Strengths and Difficulties Questionnaire at 4 and 5 years (N = 1568, 45.3% female), (b) infant amygdalar and hippocampal volumes (subsample N = 122), and (c) its moderation by a hippocampal-specific coexpression polygenic risk score based on the serotonin transporter (SLC6A4) gene. We found that higher PRE-AS was linked to greater child emotional and behavioral problems at both time points, with partly stronger associations in boys than in girls. Higher PRE-AS was associated with larger bilateral infant amygdalar volumes in girls compared to boys, while no associations were found for hippocampal volumes. Further, hyperactivity/inattention in 4-year-old girls was related to both genotype and PRE-AS, the latter partially mediated by right amygdalar volumes as preliminary evidence suggests. Our study is the first to demonstrate a dose-dependent sexually dimorphic relationship between cumulative prenatal adversity and infant amygdalar volumes.

Prenatal maternal depressive symptoms are associated with neonatal left amygdala microstructure in a sex-dependent way.

Exposures to prenatal maternal depressive symptoms (PMDS) may lead to neurodevelopmental changes in the offspring in a sex-dependent way. Although a connection between PMDS and infant brain development has been established by earlier studies, the relationship between PMDS exposures measured at various prenatal stages and microstructural alterations in fundamental subcortical structures such as the amygdala remains unknown. In this study, we investigated the associations between PMDS measured during gestational weeks 14, 24 and 34 and infant amygdala microstructural properties using diffusion tensor imaging. We explored amygdala mean diffusivity (MD) alterations in response to PMDS in infants aged 11 to 54 days from birth. PMDS had no significant main effect on the amygdala MD metrics. However, there was a significant interaction effect for PMDS and infant sex in the left amygdala MD. Compared with girls, boys exposed to greater PMDS during gestational week 14 showed significantly higher left amygdala MD. These results indicate that PMDS are linked to infants' amygdala microstructure in boys. These associations may be relevant to later neuropsychiatric outcomes in the offspring. Further research is required to better understand the mechanisms underlying these associations and to develop effective interventions to counteract any potential adverse consequences.

Sex differences, asymmetry, and age-related white matter development in infants and 5-year-olds as assessed with tract-based spatial statistics.

The rapid white matter (WM) maturation of first years of life is followed by slower yet long-lasting development, accompanied by learning of more elaborate skills. By the age of 5 years, behavioural and cognitive differences between females and males, and functions associated with brain lateralization such as language skills are appearing. Diffusion tensor imaging (DTI) can be used to quantify fractional anisotropy (FA) within the WM and increasing values correspond to advancing brain development. To investigate the normal features of WM development during early childhood, we gathered a DTI data set of 166 healthy infants (mean 3.8 wk, range 2-5 wk; 89 males; born on gestational week 36 or later) and 144 healthy children (mean 5.4 years, range 5.1-5.8 years; 76 males). The sex differences, lateralization patterns and age-dependent changes were examined using tract-based spatial statistics (TBSS). In 5-year-olds, females showed higher FA in wide-spread regions in the posterior and the temporal WM and more so in the right hemisphere, while sex differences were not detected in infants. Gestational age showed stronger association with FA values compared to age after birth in infants. Additionally, child age at scan associated positively with FA around the age of 5 years in the body of corpus callosum, the connections of which are important especially for sensory and motor functions. Lastly, asymmetry of WM microstructure was detected already in infants, yet significant changes in lateralization pattern seem to occur during early childhood, and in 5-year-olds the pattern already resembles adult-like WM asymmetry.

Comparison of the prognostic value of early-phase proton magnetic resonance spectroscopy and diffusion tensor imaging with serum neuron-specific enolase at 72 h in comatose survivors of out-of-hospital cardiac arrest-a substudy of the XeHypotheca trial.

PURPOSE: We compared the predictive accuracy of early-phase brain diffusion tensor imaging (DTI), proton magnetic resonance spectroscopy (1H-MRS), and serum neuron-specific enolase (NSE) against the motor score and epileptic seizures (ES) for poor neurological outcome after out-of-hospital cardiac arrest (OHCA). METHODS: The predictive accuracy of DTI, 1H-MRS, and NSE along with motor score at 72 h and ES for the poor neurological outcome (modified Rankin Scale, mRS, 3 - 6) in 92 comatose OHCA patients at 6 months was assessed by area under the receiver operating characteristic curve (AUROC). Combined models of the variables were included as exploratory. RESULTS: The predictive accuracy of fractional anisotropy (FA) of DTI (AUROC 0.73, 95% CI 0.62-0.84), total N-acetyl aspartate/total creatine (tNAA/tCr) of 1H-MRS (0.78 (0.68 - 0.88)), or NSE at 72 h (0.85 (0.76 - 0.93)) was not significantly better than motor score at 72 h (0.88 (95% CI 0.80-0.96)). The addition of FA and tNAA/tCr to a combination of NSE, motor score, and ES provided a small but statistically significant improvement in predictive accuracy (AUROC 0.92 (0.85-0.98) vs 0.98 (0.96-1.00), p = 0.037). CONCLUSION: None of the variables (FA, tNAA/tCr, ES, NSE at 72 h, and motor score at 72 h) differed significantly in predicting poor outcomes in this patient group. Early-phase quantitative neuroimaging provided a statistically significant improvement for the predictive value when combined with ES and motor score with or without NSE. However, in clinical practice, the additional value is small, and considering the costs and challenges of imaging in this patient group, early-phase DTI/MRS cannot be recommended for routine use. TRIAL REGISTRATION: ClinicalTrials.gov NCT00879892, April 13, 2009.

Maternal psychological distress associates with alterations in resting-state low-frequency fluctuations and distal functional connectivity of the neonate medial prefrontal cortex.

Prenatal stress exposure (PSE) has been observed to exert a programming effect on the developing infant brain, possibly with long-lasting consequences on temperament, cognitive functions and the risk for developing psychiatric disorders. Several prior studies have revealed that PSE associates with alterations in neonate functional connectivity in the prefrontal regions and amygdala. In this study, we explored whether maternal psychological symptoms measured during the 24th gestational week had associations with neonate resting-state network metrics. Twenty-one neonates (nine female) underwent resting-state fMRI scanning (mean gestation-corrected age at scan 26.95 days) to assess fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo). The ReHo/fALFF maps were used in multiple regression analysis to investigate whether maternal self-reported anxiety and/or depressive symptoms associate with neonate functional brain features. Maternal psychological distress (composite score of depressive and anxiety symptoms) was positively associated with fALFF in the neonate medial prefrontal cortex (mPFC). Anxiety and depressive symptoms, assessed separately, exhibited similar but weaker associations. Post hoc seed-based connectivity analyses further showed that distal connectivity of mPFC covaried with PSE. No associations were found between neonate ReHo and PSE. These results offer preliminary evidence that PSE may affect functional features of the developing brain during gestation.

Test-retest reliability of diffusion tensor imaging scalars in 5-year-olds.

Diffusion tensor imaging (DTI) has provided great insights into the microstructural features of the developing brain. However, DTI images are prone to several artifacts and the reliability of DTI scalars is of paramount importance for interpreting and generalizing the findings of DTI studies, especially in the younger population. In this study, we investigated the intrascan test-retest repeatability of four DTI scalars: fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in 5-year-old children (N = 67) with two different data preprocessing approaches: a volume censoring pipeline and an outlier replacement pipeline. We applied a region of interest (ROI) and a voxelwise analysis after careful quality control, tensor fitting and tract-based spatial statistics. The data had three subsets and each subset included 31, 32, or 33 directions thus a total of 96 unique uniformly distributed diffusion encoding directions per subject. The repeatability of DTI scalars was evaluated with intraclass correlation coefficient (ICC(3,1)) and the variability between test and retest subsets. The results of both pipelines yielded good to excellent (ICC(3,1) > 0.75) reliability for most of the ROIs and an overall low variability (<10%). In the voxelwise analysis, FA and RD had higher ICC(3,1) values compared to AD and MD and the variability remained low (<12%) across all scalars. Our results suggest high intrascan repeatability in pediatric DTI and lend confidence to the use of the data in future cross-sectional and longitudinal studies.

Effect of number of diffusion-encoding directions in diffusion metrics of 5-year-olds using tract-based spatial statistical analysis.

Methodological aspects and effects of different imaging parameters on DTI (diffusion tensor imaging) results and their reproducibility have been recently studied comprehensively in adult populations. Although MR imaging of children's brains has become common, less interest has been focussed on researching whether adult-based optimised parameters and pre-processing protocols can be reliably applied to paediatric populations. Furthermore, DTI scalar values of preschool aged children are rarely reported. We gathered a DTI dataset from 5-year-old children (N = 49) to study the effect of the number of diffusion-encoding directions on the reliability of resultant scalar values with TBSS (tract-based spatial statistics) method. Additionally, the potential effect of within-scan head motion on DTI scalars was evaluated. Reducing the number of diffusion-encoding directions deteriorated both the accuracy and the precision of all DTI scalar values. To obtain reliable scalar values, a minimum of 18 directions for TBSS was required. For TBSS fractional anisotropy values, the intraclass correlation coefficient with two-way random-effects model (ICC[2,1]) for the subsets of 6 to 66 directions ranged between 0.136 [95%CI 0.0767;0.227] and 0.639 [0.542;0.740], whereas the corresponding values for subsets of 18 to 66 directions were 0.868 [0.815;0.913] and 0.995 [0.993;0.997]. Following the exclusion of motion-corrupted volumes, minor residual motion did not associate with the scalar values. A minimum of 18 diffusion directions is recommended to result in reliable DTI scalar results with TBSS. We suggest gathering extra directions in paediatric DTI to enable exclusion of volumes with motion artefacts and simultaneously preserve the overall data quality.

Subcortical and hippocampal brain segmentation in 5-year-old children: Validation of FSL-FIRST and FreeSurfer against manual segmentation.

Developing accurate subcortical volumetric quantification tools is crucial for neurodevelopmental studies, as they could reduce the need for challenging and time-consuming manual segmentation. In this study, the accuracy of two automated segmentation tools, FSL-FIRST (with three different boundary correction settings) and FreeSurfer, were compared against manual segmentation of the hippocampus and subcortical nuclei, including the amygdala, thalamus, putamen, globus pallidus, caudate and nucleus accumbens, using volumetric and correlation analyses in 80 5-year-olds. Both FSL-FIRST and FreeSurfer overestimated the volume on all structures except the caudate, and the accuracy varied depending on the structure. Small structures such as the amygdala and nucleus accumbens, which are visually difficult to distinguish, produced significant overestimations and weaker correlations with all automated methods. Larger and more readily distinguishable structures such as the caudate and putamen produced notably lower overestimations and stronger correlations. Overall, the segmentations performed by FSL-FIRST's default pipeline were the most accurate, whereas FreeSurfer's results were weaker across the structures. In line with prior studies, the accuracy of automated segmentation tools was imperfect with respect to manually defined structures. However, apart from amygdala and nucleus accumbens, FSL-FIRST's agreement could be considered satisfactory (Pearson correlation > 0.74, intraclass correlation coefficient (ICC) > 0.68 and Dice score coefficient (DSC) > 0.87) with highest values for the striatal structures (putamen, globus pallidus, caudate) (Pearson correlation > 0.77, ICC > 0.87 and DSC > 0.88, respectively). Overall, automated segmentation tools do not always provide satisfactory results, and careful visual inspection of the automated segmentations is strongly advised.

Prenatal and early-life environmental factors, family demographics and cortical brain anatomy in 5-year-olds: an MRI study from FinnBrain Birth Cohort.

The human brain develops dynamically during early childhood, when the child is sensitive to both genetic programming and extrinsic exposures. Recent studies have found links between prenatal and early life environmental factors, family demographics and the cortical brain morphology in newborns measured by surface area, volume and thickness. Here in this magnetic resonance imaging study, we evaluated whether a similar set of variables associates with cortical surface area and volumes measured in a sample of 170 healthy 5-year-olds from the FinnBrain Birth Cohort Study. We found that child sex, maternal pre-pregnancy body mass index, 5 min Apgar score, neonatal intensive care unit admission and maternal smoking during pregnancy associated with surface areas. Furthermore, child sex, maternal age and maternal level of education associated with brain volumes. Expectedly, many variables deemed important for neonatal brain anatomy (such as birth weight and gestational age at birth) in earlier studies did not associate with brain metrics in our study group of 5-year-olds, which implies that their effects on brain anatomy are age-specific. Future research may benefit from including pre- and perinatal covariates in the analyses when such data are available. Finally, we provide evidence for right lateralization for surface area and volumes, except for the temporal lobes which were left lateralized. These subtle differences between hemispheres are variable across individuals and may be interesting brain metrics in future studies.

Allometry in the corpus callosum in neonates: Sexual dimorphism.

The corpus callosum (CC) is the largest fiber tract in the human brain, allowing interhemispheric communication by connecting homologous areas of the two cerebral hemispheres. In adults, CC size shows a robust allometric relationship with brain size, with larger brains having larger callosa, but smaller brains having larger callosa relative to brain size. Such an allometric relationship has been shown in both males and females, with no significant difference between the sexes. But there is some evidence that there are alterations in these allometric relationships during development. However, it is currently not known whether there is sexual dimorphism in these allometric relationships from birth, or if it only develops later. We study this in neonate data. Our results indicate that there are already sex differences in these allometric relationships in neonates: male neonates show the adult-like allometric relationship between CC size and brain size; however female neonates show a significantly more positive allometry between CC size and brain size than either male neonates or female adults. The underlying cause of this sexual dimorphism is unclear; but the existence of this sexual dimorphism in neonates suggests that sex-differences in lateralization have prenatal origins.

Feasibility of FreeSurfer Processing for T1-Weighted Brain Images of 5-Year-Olds: Semiautomated Protocol of FinnBrain Neuroimaging Lab.

Pediatric neuroimaging is a quickly developing field that still faces important methodological challenges. Pediatric images usually have more motion artifact than adult images. The artifact can cause visible errors in brain segmentation, and one way to address it is to manually edit the segmented images. Variability in editing and quality control protocols may complicate comparisons between studies. In this article, we describe in detail the semiautomated segmentation and quality control protocol of structural brain images that was used in FinnBrain Birth Cohort Study and relies on the well-established FreeSurfer v6.0 and ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) consortium tools. The participants were typically developing 5-year-olds [n = 134, 5.34 (SD 0.06) years, 62 girls]. Following a dichotomous quality rating scale for inclusion and exclusion of images, we explored the quality on a region of interest level to exclude all regions with major segmentation errors. The effects of manual edits on cortical thickness values were relatively minor: less than 2% in all regions. Supplementary Material cover registration and additional edit options in FreeSurfer and comparison to the computational anatomy toolbox (CAT12). Overall, we conclude that despite minor imperfections FreeSurfer can be reliably used to segment cortical metrics from T1-weighted images of 5-year-old children with appropriate quality assessment in place. However, custom templates may be needed to optimize the results for the subcortical areas. Through visual assessment on a level of individual regions of interest, our semiautomated segmentation protocol is hopefully helpful for investigators working with similar data sets, and for ensuring high quality pediatric neuroimaging data.

Individualised non-contrast MRI-based risk estimation and shared decision-making in men with a suspicion of prostate cancer: protocol for multicentre randomised controlled trial (multi-IMPROD V.2.0).

INTRODUCTION: European Association of Urology and UK National Institute for Health and Care Excellence guidelines recommend that all men with suspicions of prostate cancer should undergo prebiopsy contrast enhanced, that is, multiparametric prostate MRI. Subsequent prostate biopsies should also be performed if MRI is positive, that is, Prostate Imaging-Reporting and Data System (PI-RADS) scores 3-5. However, several retrospective post hoc analyses have shown that this approach still leads to many unnecessary biopsy procedures. For example, 88%-96% of men with PI-RADS, three findings are still diagnosed with clinically non-significant prostate cancer or no cancer at all. METHODS AND ANALYSIS: This is a prospective, randomised, controlled, multicentre trial, being conducted in Finland, to demonstrate non-inferiority in clinically significant cancer detection rates among men undergoing prostate biopsies post-MRI and men undergoing prostate biopsies post-MRI only after a shared decision based on individualised risk estimation. Men without previous diagnosis of prostate cancer and with abnormal digital rectal examination findings and/or prostate-specific antigen between 2.5 ug/L and 20.0 ug/L are included. We aim to recruit 830 men who are randomised at a 1:1 ratio into control (all undergo biopsies after MRI) and intervention arms (the decision to perform biopsies is based on risk estimation and shared decision-making). The primary outcome of the study is the proportion of men with clinically significant prostate cancer (Gleason 4+3 prostate cancer or higher). We will also compare the overall biopsy rate, benign biopsy rate and the detection of non-significant prostate cancer between the two study groups. ETHICS AND DISSEMINATION: The study (protocol V.2.0, 4 January 2021) was approved by the Ethics Committee of the Hospital District of Southwest Finland (IORG number: 0001744, IBR number: 00002216; trial number: 99/1801/2019). Participants are required to provide written informed consent. Full reports of this study will be submitted to peer-reviewed journals, mainly urology and radiology. TRIAL REGISTRATION NUMBER: NCT04287088; the study is registered at ClinicalTrials.gov.

Sex-specific associations between maternal pregnancy-specific anxiety and newborn amygdalar volumes - preliminary findings from the FinnBrain Birth Cohort Study.

Previous literature links maternal pregnancy-specific anxiety (PSA) with later difficulties in child emotional and social cognition as well as memory, functions closely related to the amygdala and the hippocampus. Some evidence also suggests that PSA affects child amygdalar volumes in a sex-dependent way. However, no studies investigating the associations between PSA and newborn amygdalar and hippocampal volumes have been reported. We investigated the associations between PSA and newborn amygdalar and hippocampal volumes and whether associations are sex-specific in 122 healthy newborns (68 males/54 females) scanned at 2-5 weeks postpartum. PSA was measured at gestational week 24 with the Pregnancy-Related Anxiety Questionnaire Revised 2 (PRAQ-R2). The associations were analyzed with linear regression controlling for confounding variables. PSA was associated positively with left amygdalar volume in girls, but no significant main effect was found in the whole group or in boys. No significant main or sex-specific effect was found for hippocampal volumes. Although this was an exploratory study, the findings suggest a sexually dimorphic association of mid-pregnancy PSA with newborn amygdalar volumes.

ASIC-E4: Interplay of Beta-Amyloid, Synaptic Density and Neuroinflammation in Cognitively Normal Volunteers With Three Levels of Genetic Risk for Late-Onset Alzheimer's Disease - Study Protocol and Baseline Characteristics.

BACKGROUND: Detailed characterization of early pathophysiological changes in preclinical Alzheimer's disease (AD) is necessary to enable development of correctly targeted and timed disease-modifying treatments. ASIC-E4 study ("Beta-Amyloid, Synaptic loss, Inflammation and Cognition in healthy APOE ε4 carriers") combines state-of-the-art neuroimaging and fluid-based biomarker measurements to study the early interplay of three key pathological features of AD, i.e., beta-amyloid (Aß) deposition, neuroinflammation and synaptic dysfunction and loss in cognitively normal volunteers with three different levels of genetic (APOE-related) risk for late-onset AD. OBJECTIVE: Here, our objective is to describe the study design, used protocols and baseline demographics of the ASIC-E4 study. METHODS/DESIGN: ASIC-E4 is a prospective observational multimodal imaging study performed in Turku PET Centre in collaboration with University of Gothenburg. Cognitively normal 60-75-year-old-individuals with known APOE ε4/ε4 genotype were recruited via local Auria Biobank (Turku, Finland). Recruitment of the project has been completed in July 2020 and 63 individuals were enrolled to three study groups (Group 1: APOE ε4/ε4, N = 19; Group 2: APOE ε4/ε3, N = 22; Group 3: APOE ε3/ε3, N = 22). At baseline, all participants will undergo positron emission tomography imaging with tracers targeted against Aß deposition (11C-PIB), activated glia (11C-PK11195) and synaptic vesicle glycoprotein 2A (11C-UCB-J), two brain magnetic resonance imaging scans, and extensive cognitive testing. In addition, blood samples are collected for various laboratory measurements and blood biomarker analysis and cerebrospinal fluid samples are collected from a subset of participants based on additional voluntary informed consent. To evaluate the predictive value of the early neuroimaging findings, neuropsychological evaluation and blood biomarker measurements will be repeated after a 4-year follow-up period. DISCUSSION: Results of the ASIC-E4 project will bridge the gap related to limited knowledge of the synaptic and inflammatory changes and their association with each other and Aß in "at-risk" individuals. Thorough in vivo characterization of the biomarker profiles in this population will produce valuable information for diagnostic purposes and future drug development, where the field has already started to look beyond Aß.

Magnetic resonance imaging-guided transurethral ultrasound ablation for benign prostatic hyperplasia: 12-month clinical outcomes of a phase I study.

OBJECTIVES: To investigate the safety and feasibility of magnetic resonance imaging (MRI)-guided transurethral ultrasound ablation (TULSA) for the treatment of benign prostatic obstruction (BPO). PATIENTS AND METHODS: An investigator-initiated, prospective, registered (NCT03350529), phase I study enrolled men with lower urinary tract symptoms due to benign prostatic hyperplasia in need of surgical intervention. Patients were followed for 12 months after TULSA. Uroflowmetry, prostate-specific antigen (PSA) level, and a comprehensive set of functional questionnaires including the Expanded Prostate cancer Index Composite-26, International Prostate Symptom Score (IPSS) and five-item version of the International Index of Erectile Function were obtained at baseline and every 3 months afterwards. MRI was obtained at baseline, and at 3 and 12 months after TULSA. Medication use before and after TULSA were recorded. Adverse events (AEs) were reported using the Clavien-Dindo classification. RESULTS: A total of 10 men underwent TULSA with no severe AEs encountered. The baseline median (interquartile range [IQR]) age and prostate volume were 68 (63-72) years and 53 (45-66) mL, respectively. At baseline, six patients were moderately symptomatic and four patients severely symptomatic. Nine patients at baseline were on BPO medication. The median (IQR) improvement in the IPSS was 82%, from 17.5 (15.3-23.0) at baseline to 4.0 (2.3-6.3) at 12 months. Similarly, the median maximum urinary flow rate improved by 101%, from a median (IQR) of 12.4 (8.8-17.6) mL/s at baseline to 21.8 (17.6-26.5) mL/s at 12 months. Improvements were already seen at 3 months. The median prostate volume and PSA reduction at 12 months were 33% and 48%, respectively. There were no changes in continence, sexual, erectile or bowel functions. At 12 months, five out of six men with normal ejaculatory function before TULSA reported normal antegrade ejaculations. All patients taking BPO medication before TULSA discontinued medication after TULSA. CONCLUSION: TULSA appears to be a safe and effective treatment for BPO, with promising 12-month follow-up outcomes. Further studies with larger cohorts are needed to confirm the observed results.

Detection of Prostate Cancer Using Biparametric Prostate MRI, Radiomics, and Kallikreins: A Retrospective Multicenter Study of Men With a Clinical Suspicion of Prostate Cancer.

BACKGROUND: Accurate detection of clinically significant prostate cancer (csPCa), Gleason Grade Group ≥ 2, remains a challenge. Prostate MRI radiomics and blood kallikreins have been proposed as tools to improve the performance of biparametric MRI (bpMRI). PURPOSE: To develop and validate radiomics and kallikrein models for the detection of csPCa. STUDY TYPE: Retrospective. POPULATION: A total of 543 men with a clinical suspicion of csPCa, 411 (76%, 411/543) had kallikreins available and 360 (88%, 360/411) did not take 5-alpha-reductase inhibitors. Two data splits into training, validation (split 1: single center, n = 72; split 2: random 50% of pooled datasets from all four centers), and testing (split 1: 4 centers, n = 288; split 2: remaining 50%) were evaluated. FIELD STRENGTH/SEQUENCE: A 3 T/1.5 T, TSE T2-weighted imaging, 3x SE DWI. ASSESSMENT: In total, 20,363 radiomic features calculated from manually delineated whole gland (WG) and bpMRI suspicion lesion masks were evaluated in addition to clinical parameters, prostate-specific antigen, four kallikreins, MRI-based qualitative (PI-RADSv2.1/IMPROD bpMRI Likert) scores. STATISTICAL TESTS: For the detection of csPCa, area under receiver operating curve (AUC) was calculated using the DeLong's method. A multivariate analysis was conducted to determine the predictive power of combining variables. The values of P-value < 0.05 were considered significant. RESULTS: The highest prediction performance was achieved by IMPROD bpMRI Likert and PI-RADSv2.1 score with AUC = 0.85 and 0.85 in split 1, 0.85 and 0.83 in split 2, respectively. bpMRI WG and/or kallikreins demonstrated AUCs ranging from 0.62 to 0.73 in split 1 and from 0.68 to 0.76 in split 2. AUC of bpMRI lesion-derived radiomics model was not statistically different to IMPROD bpMRI Likert score (split 1: AUC = 0.83, P-value = 0.306; split 2: AUC = 0.83, P-value = 0.488). DATA CONCLUSION: The use of radiomics and kallikreins failed to outperform PI-RADSv2.1/IMPROD bpMRI Likert and their combination did not lead to further performance gains. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

Differences in brain changes between adults with childhood-onset epilepsy and controls: A prospective population-based study.

PURPOSE: To determine the impact of childhood-onset uncomplicated epilepsy (COE) on brain aging over 50-year prospective follow-up. METHODS: A population-based cohort of 41 aging subjects with COE and their 46 matched controls participated in a detailed in-person prospective assessment in 2012 and 2017 to characterize ongoing changes in the aging brain. RESULTS: The mean age of the COE participants was 63.2 years (SD 4.14, median 63.2, range 55.8-70.6) and 63.0 years (mean, SD 4.13, median 63.3, range 56.0-69.9) years for controls. Neurologic signs were significantly more common in COE participants not in remission (p = .015), and the most frequent abnormalities were cerebellar signs (p < .001). Neurologic signs in general (p = .008) and cerebellar signs in particular (p = .018) were significantly more common in focal than in generalized epilepsies. MRI white matter abnormalities were significantly associated with absence of vocational education (p = .011), and MRI hippocampal atrophy in COE subjects was associated with arterial hypertension versus normal blood pressure (p = .017). In the combined study cohort of COE subjects and controls, presenting neurologic signs increased both in the subjects and in the controls from the 2012 to 2017 study. CONCLUSIONS: At ultra-long-term follow-up, clinical and neuroimaging findings show tendencies to brain aging that is more accelerated in COE participants with active adult childhood-onset epilepsy, and particularly in focal epilepsy.