Developmental change of brain volume in Rett syndrome in Taiwan.

OBJECTIVE: Rett syndrome (RTT) is characterized by neurological regression. This pioneering study investigated the effect of age on brain volume reduction by analyzing magnetic resonance imaging findings in participants with RTT, ranging from toddlers to adults. METHODS: Functional evaluation and neuroimaging were performed. All scans were acquired using a Siemens Tim Trio 3 T scanner with a 32-channel head coil. RESULTS: The total intracranial volume and cerebral white matter volume significantly increased with age in the control group compared with that in the RTT group (p < 0.05). Cortical gray matter volume reduction in the RTT group continued to increase in bilateral parietal lobes and left occipital lobes (p < 0.05). The differences in cortical gray matter volume between typically developing brain and RTT-affected brain may tend to continuously increase until adulthood in both temporal lobes although not significant after correction for multiple comparison. CONCLUSIONS: A significant reduction in brain volume was observed in the RTT group. Cortical gray matter volume in the RTT group continued to reduce in bilateral parietal lobes and left occipital lobes. These results provide a baseline for future studies on the effect of RTT treatment and related neuroscience research.

Adjustment of Regional Cortical Thickness Measures for Global Cortical Thickness Obscures Deficits Across the Schizophrenia Spectrum: A Cautionary Note About Normative Modeling of Brain Imaging Data.

Recent neuroimaging studies and publicly disseminated analytic tools suggest that regional morphometric analyses covary for global thickness. We empirically demonstrated that this statistical approach severely underestimates regional thickness dysmorphology in psychiatric disorders. Study 1 included 90 healthy control participants, 51 participants at clinical high risk for psychosis, and 78 participants with early-illness schizophrenia. Study 2 included 56 healthy control participants, 83 participants with nonaffective psychosis, and 30 participants with affective psychosis. We examined global and regional thickness correlations, global thickness group differences, and regional thickness group differences with and without global thickness covariation. Global and regional thickness were strongly correlated across groups. Global thickness was lower in the schizophrenia spectrum groups than the other groups. Regional thickness deficits in schizophrenia spectrum groups were attenuated or eliminated with global thickness covariation. Eliminating the variation that regional thickness shares with global thickness eliminated disease-related effects. This statistical approach results in erroneous conclusions that regional thickness is normal in disorders like schizophrenia or clinical high risk syndrome.

Genetic variants for head size share genes and pathways with cancer.

The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer.

Impact of adult-onset multiple sclerosis on MRI-based intracranial volume: A study in clinically discordant monozygotic twins.

OBJECTIVE: Intracranial volume (ICV) represents the maximal brain volume for an individual, attained prior to late adolescence and remaining constant throughout life after. Thus, ICV serves as a surrogate marker for brain growth integrity. To assess the potential impact of adult-onset multiple sclerosis (MS) and its preceding prodromal subclinical changes on ICV in a large cohort of monozygotic twins clinically discordant for MS. METHODS: FSL software was used to derive ICV estimates from 3D-T1-weighted-3 T-MRI images by using an atlas scaling factor method. ICV were compared between clinically affected and healthy co-twins. All twins were compared to a large healthy reference cohort using standardized ICV z-scores. Mixed models assessed the impact of age at MS diagnosis on ICV. RESULTS: 54 twin-pairs (108 individuals/80female/42.45 ± 11.98 years), 731 individuals (375 non-twins, 109/69 monozygotic/dizygotic twin-pairs; 398female/29.18 ± 0.13 years) and 35 healthy local individuals (20male/31.34 ± 1.53 years). In 45/54 (83 %) twin-pairs, both clinically affected and healthy co-twins showed negative ICV z-scores, i.e., ICVs lower than the average of the healthy reference cohort (M = -1.53 ± 0.11, P<10-5). Younger age at MS diagnosis was strongly associated with lower ICVs (t = 3.76, P = 0.0003). Stratification of twin-pairs by age at MS diagnosis of the affected co-twin (≤30 versus > 30 years) yielded lower ICVs in those twin pairs with younger age at diagnosis (P = 0.01). Comparison within individual twin-pairs identified lower ICVs in the MS-affected co-twins with younger age at diagnosis compared to their corresponding healthy co-twins (P = 0.003). CONCLUSION: We offer for the first-time evidence for strong associations between adult-onset MS and lower ICV, which is more pronounced with younger age at diagnosis. This suggests pre-clinical alterations in early neurodevelopment associated with susceptibility to MS both in individuals with and without clinical manifestation of the disease.

Comparison of approaches to control for intracranial volume in research on the association of brain volumes with cognitive outcomes.

Most neuroimaging studies linking regional brain volumes with cognition correct for total intracranial volume (ICV), but methods used for this correction differ across studies. It is unknown whether different ICV correction methods yield consistent results. Using a brain-wide association approach in the MRI substudy of UK Biobank (N = 41,964; mean age = 64.5 years), we used regression models to estimate the associations of 58 regional brain volumetric measures with eight cognitive outcomes, comparing no correction and four ICV correction approaches. Approaches evaluated included: no correction; dividing regional volumes by ICV (proportional approach); including ICV as a covariate in the regression (adjustment approach); and regressing the regional volumes against ICV in different normative samples and using calculated residuals to determine associations (residual approach). We used Spearman-rank correlations and two consistency measures to quantify the extent to which associations were inconsistent across ICV correction approaches for each possible brain region and cognitive outcome pair across 2320 regression models. When the association between brain volume and cognitive performance was close to null, all approaches produced similar estimates close to the null. When associations between a regional volume and cognitive test were not null, the adjustment and residual approaches typically produced similar estimates, but these estimates were inconsistent with results from the crude and proportional approaches. For example, when using the crude approach, an increase of 0.114 (95% confidence interval [CI]: 0.103-0.125) in fluid intelligence was associated with each unit increase in hippocampal volume. However, when using the adjustment approach, the increase was 0.055 (95% CI: 0.043-0.068), while the proportional approach showed a decrease of -0.025 (95% CI: -0.035 to -0.014). Different commonly used methods to correct for ICV yielded inconsistent results. The proportional method diverges notably from other methods and results were sometimes biologically implausible. A simple regression adjustment for ICV produced biologically plausible associations.

Normative reference data for intracranial volume in children: The results of CT volumetry.

BACKGROUND: Intracranial volume (ICV) is an important indicator of the development of the brain and skull in children. At present, there is a lack of ICV growth standards based on large infant and children samples. Our aim was to assess the normal range of the ICV variation in Russian children using a modern automatic system for constructing the endocranial cavity (Endex) and to provide growth standards of the ICV for clinical practice. METHODS: High-resolution head CT scans were obtained from 673 apparently healthy children (380 boys and 293 girls) aged 0-17 years and transformed into the ICV estimates using the Endex software. The open-source software RefCurv utilizing R and the GAMLSS add-on package with the LMS method was then used for the construction of smooth centile growth references for ICV according to age and sex. RESULTS: We demonstrated that the ICVs estimates calculated using the Endex software are perfectly comparable with those obtained by a conventional technique (i.e. seed feeling). Sex-specific pediatric growth charts for ICV were constructed. CONCLUSIONS: This study makes available for use in clinical practice ICV growth charts for the age from 0 to 17 based on a sample of 673 high-resolution CT images.

Volume-based and Surface-Based Methods in Autism Compared with Healthy Controls Are Free surfer and CAT12 in Agreement?

Objectives: Autism Spectrum Disorder (ASD) encompasses a range of neurodevelopmental disorders, and early detection is crucial. This study aims to identify the Regions of Interest (ROIs) with significant differences between healthy controls and individuals with autism, as well as evaluate the agreement between FreeSurfer 6 (FS6) and Computational Anatomy Toolbox (CAT12) methods. Materials & Methods: Surface-based and volume-based features were extracted from FS software and CAT12 toolbox for Statistical Parametric Mapping (SPM) software to estimate ROI-wise biomarkers. These biomarkers were compared between 18 males Typically Developing Controls (TDCs) and 40 male subjects with ASD to assess group differences for each method. Finally, agreement and regression analyses were performed between the two methods for TDCs and ASD groups. Results: Both methods revealed ROIs with significant differences for each parameter. The Analysis of Covariance (ANCOVA) showed that both TDCs and ASD groups indicated a significant relationship between the two methods (p<0.001). The R2 values for TDCs and ASD groups were 0.692 and 0.680, respectively, demonstrating a moderate correlation between CAT12 and FS6. Bland-Altman graphs showed a moderate level of agreement between the two methods. Conclusion: The moderate correlation and agreement between CAT12 and FS6 suggest that while some consistency is observed in the results, CAT12 is not a superior substitute for FS6 software. Further research is needed to identify a potential replacement for this method.

Effect of cervical and lumbosacral spina bifida cystica on volumes of intracranial structures in children.

PURPOSE: Spina bifida is a major disorder that occurs when the membranes of the spinal cord and medulla fail to close during the embryonic period and affects the individual for the rest of life. Some physical, mental, and social difficulties can be observed in the lives of children with spina bifida after surgery. The aim of this study is to determine what kind of volumetric changes occur in the brain when spina bifida occurs in different regions of the cord. METHODS: The volume of intracranial structures of 14 children aged 1 to 9 years (7 cervical, 7 lumbosacral) with different levels of spina bifida compared with vol2Brain. RESULTS: Spina bifida occurring in the cervical region was found to cause a greater volumetric reduction in subcortical structures, cortex and gyrus than spina bifida occurring in the lumbosacral region. CONCLUSION: We believe that our study will help clinicians involved in the management of this disorder.

Longitudinal Associations Between Persistent Post-Concussion Symptoms and Blood Biomarkers of Inflammation and CNS-Injury After Mild Traumatic Brain Injury.

The aim of our study was to investigate the biological underpinnings of persistent post-concussion symptoms (PPCS) at 3 months following mild traumatic brain injury (mTBI). Patients (n = 192, age 16-60 years) with mTBI, defined as Glasgow Coma Scale (GCS) score between 13 and 15, loss of consciousness (LOC) <30 min, and post-traumatic amnesia (PTA) <24 h were included. Blood samples were collected at admission (within 72 h), 2 weeks, and 3 months. Concentrations of blood biomarkers associated with central nervous system (CNS) damage (glial fibrillary acidic protein [GFAP], neurofilament light [NFL], and tau) and inflammation (interferon gamma [IFNγ], interleukin [IL]-8, eotaxin, macrophage inflammatory protein-1-beta [MIP]-1ß, monocyte chemoattractant protein [MCP]-1, interferon-gamma-inducible protein [IP]-10, IL-17A, IL-9, tumor necrosis factor [TNF], basic fibroblast growth factor [FGF]-basic platelet-derived growth factor [PDGF], and IL-1 receptor antagonist [IL-1ra]) were obtained. Demographic and injury-related factors investigated were age, sex, GCS score, LOC, PTA duration, traumatic intracranial finding on magnetic resonance imaging (MRI; within 72 h), and extracranial injuries. Delta values, that is, time-point differences in biomarker concentrations between 2 weeks minus admission and 3 months minus admission, were also calculated. PPCS was assessed with the British Columbia Post-Concussion Symptom Inventory (BC-PSI). In single variable analyses, longer PTA duration and a higher proportion of intracranial findings on MRI were found in the PPCS group, but no single biomarker differentiated those with PPCS from those without. In multi-variable models, female sex, longer PTA duration, MRI findings, and lower GCS scores were associated with increased risk of PPCS. Inflammation markers, but not GFAP, NFL, or tau, were associated with PPCS. At admission, higher concentrations of IL-8 and IL-9 and lower concentrations of TNF, IL-17a, and MCP-1 were associated with greater likelihood of PPCS; at 2 weeks, higher IL-8 and lower IFNγ were associated with PPCS; at 3 months, higher PDGF was associated with PPCS. Higher delta values of PDGF, IL-17A, and FGF-basic at 2 weeks compared with admission, MCP-1 at 3 months compared with admission, and TNF at 2 weeks and 3 months compared with admission were associated with greater likelihood of PPCS. Higher IL-9 delta values at both time-point comparisons were negatively associated with PPCS. Discriminability of individual CNS-injury and inflammation biomarkers for PPCS was around chance level, whereas the optimal combination of biomarkers yielded areas under the curve (AUCs) between 0.62 and 0.73. We demonstrate a role of biological factors on PPCS, including both positive and negative effects of inflammation biomarkers that differed based on sampling time-point after mTBI. PPCS was associated more with acute inflammatory processes, rather than ongoing inflammation or CNS-injury biomarkers. However, the modest discriminative ability of the models suggests other factors are more important in the development of PPCS.

Corrigendum: Development and validation of a deep learning-based automatic segmentation model for assessing intracranial volume: comparison with NeuroQuant, FreeSurfer, and SynthSeg.

[This corrects the article DOI: 10.3389/fneur.2023.1221892.].

Normal growth curve of choroid plexus in children: implications for assessing hydrocephalus due to choroid plexus hyperplasia.

OBJECTIVE: Pediatric hydrocephalus requires evaluation while accounting for growth of the intracranial structures, but information on choroid plexus growth in children is lacking. This study aimed to create normal growth curves for intracranial volume, choroid plexus volume, and lateral ventricles volume. Additionally, the authors aimed to objectively assess the degree of hydrocephalus caused by choroid plexus hyperplasia (CPH) and to examine the impact of surgical procedures. METHODS: This retrospective study analyzed the head CT scans of pediatric patients with minor head trauma treated at Osaka Women's and Children's Hospital between March 2006 and May 2023. The study segmented and calculated intracranial, choroid plexus, and lateral ventricles volumes. The study also calculated the correlation coefficients among these 3 parameters. Patients aged 0 to 10 years were divided into 15 age-related clusters, and mean ± SD values were calculated for each cluster. Growth curves were created by plotting mean values sequentially. Volume obtained from patients with CPH were z-normalized using mean and SD values and compared. RESULTS: A total of 229 CT scans (94 from females) were analyzed, and positive correlations were observed among intracranial volume, choroid plexus volume, and lateral ventricles volume, with the strongest correlation between the choroid plexus and lateral ventricles volumes. The growth rate of intracranial volume was rapid until approximately 20 months of age, while those of choroid plexus volume and lateral ventricles volume increased rapidly until approximately 1 year of age. Subsequently, choroid plexus volume and lateral ventricles volume plateaued at 1.5 ml and 10 ml, respectively. Three patients with CPH were enrolled and quantitatively evaluated on the basis of the z-normalized volume. Notable abnormal volumes of the choroid plexus (range z-normalized values 24.11-51.17) and lateral ventricles (46.78-122.36) were observed. In 2 patients, improvements in the z-normalized values of intracranial volume and lateral ventricles volume were observed after surgical interventions. Additionally, in 1 patient, choroid plexus volume was reduced by approximately 24% (range z-normalized values 51.17-38.93) after bilateral endoscopic plexus coagulation. CONCLUSIONS: This study provides normal growth curves for intracranial volume, choroid plexus volume, and lateral ventricles volume. Knowledge of these normal values holds the potential for objective assessment of abnormal values associated with hydrocephalus and choroid plexus diseases such as CPH.

Development and validation of a deep learning-based automatic segmentation model for assessing intracranial volume: comparison with NeuroQuant, FreeSurfer, and SynthSeg.

Background and purpose: To develop and validate a deep learning-based automatic segmentation model for assessing intracranial volume (ICV) and to compare the accuracy determined by NeuroQuant (NQ), FreeSurfer (FS), and SynthSeg. Materials and methods: This retrospective study included 60 subjects [30 Alzheimer's disease (AD), 21 mild cognitive impairment (MCI), 9 cognitively normal (CN)] from a single tertiary hospital for the training and validation group (50:10). The test group included 40 subjects (20 AD, 10 MCI, 10 CN) from the ADNI dataset. We propose a robust ICV segmentation model based on the foundational 2D UNet architecture trained with four types of input images (both single and multimodality using scaled or unscaled T1-weighted and T2-FLAIR MR images). To compare with our model, NQ, FS, and SynthSeg were also utilized in the test group. We evaluated the model performance by measuring the Dice similarity coefficient (DSC) and average volume difference. Results: The single-modality model trained with scaled T1-weighted images showed excellent performance with a DSC of 0.989 ± 0.002 and an average volume difference of 0.46% ± 0.38%. Our multimodality model trained with both unscaled T1-weighted and T2-FLAIR images showed similar performance with a DSC of 0.988 ± 0.002 and an average volume difference of 0.47% ± 0.35%. The overall average volume difference with our model showed relatively higher accuracy than NQ (2.15% ± 1.72%), FS (3.69% ± 2.93%), and SynthSeg (1.88% ± 1.18%). Furthermore, our model outperformed the three others in each subgroup of patients with AD, MCI, and CN subjects. Conclusion: Our deep learning-based automatic ICV segmentation model showed excellent performance for the automatic evaluation of ICV.

The association between duration of breastfeeding and the trajectory of brain development from childhood to young adulthood: an 8-year longitudinal study.

Breastfeeding has been associated with several short- and long-term health benefits, including positive cognitive and behavioral outcomes. However, the impact of breastfeeding on structural brain development over time remains unclear. We aimed to assess the association between breastfeeding duration in childhood and the developmental trajectory of overall cortical thickness, cortical area, and total intracranial volume during the transition from childhood to early adulthood. Participants included 670 children and adolescents with 1326 MRI scans acquired over 8 years from the Brazilian High-Risk Cohort for Mental Conditions (BHRCS). Breastfeeding was assessed using a questionnaire answered by the parents. Brain measures were estimated using MRI T1-weighted images at three time points, with 3-year intervals. Data were evaluated using generalized additive models adjusted for multiple confounders. We found that a longer breastfeeding duration was directly associated with higher global cortical thickness in the left (edf = 1.0, F = 6.07, p = 0.01) and right (edf = 1.0, F = 4.70, p = 0.03) hemispheres. For the total intracranial volume, we found an interaction between duration of breastfeeding and developmental stage (edf = 1.0, F = 6.81, p = 0.009). No association was found between breastfeeding duration and brain area. Our study suggests that the duration of breastfeeding impacts overall cortical thickness and the development of total brain volume, but not area. This study adds to the evidence on the potential impact of breastfeeding on brain development and provides relevant insights into the mechanisms by which breastfeeding might confer cognitive and mental health benefits.

Accuracy of skull stripping in a single-contrast convolutional neural network model using eight-contrast magnetic resonance images.

In automated analyses of brain morphometry, skull stripping or brain extraction is a critical first step because it provides accurate spatial registration and signal-intensity normalization. Therefore, it is imperative to develop an ideal skull-stripping method in the field of brain image analysis. Previous reports have shown that convolutional neural network (CNN) method is better at skull stripping than non-CNN methods. We aimed to evaluate the accuracy of skull stripping in a single-contrast CNN model using eight-contrast magnetic resonance (MR) images. A total of 12 healthy participants and 12 patients with a clinical diagnosis of unilateral Sturge-Weber syndrome were included in our study. A 3-T MR imaging system and QRAPMASTER were used for data acquisition. We obtained eight-contrast images produced by post-processing T1, T2, and proton density (PD) maps. To evaluate the accuracy of skull stripping in our CNN method, gold-standard intracranial volume (ICVG) masks were used to train the CNN model. The ICVG masks were defined by experts using manual tracing. The accuracy of the intracranial volume obtained from the single-contrast CNN model (ICVE) was evaluated using the Dice similarity coefficient [= 2(ICVE ⋂ ICVG)/(ICVE + ICVG)]. Our study showed significantly higher accuracy in the PD-weighted image (WI), phase-sensitive inversion recovery (PSIR), and PD-short tau inversion recovery (STIR) compared to the other three contrast images (T1-WI, T2-fluid-attenuated inversion recovery [FLAIR], and T1-FLAIR). In conclusion, PD-WI, PSIR, and PD-STIR should be used instead of T1-WI for skull stripping in the CNN models.

Chronic Cough-Related Differences in Brain Morphometry in Adults: A Population-Based Study.

BACKGROUND: Individuals with cough hypersensitivity have increased central neural responses to tussive stimuli, which may result in maladaptive morphometric changes in the central cough processing systems. RESEARCH QUESTION: Are the volumes of the brain regions implicated in cough hypersensitivity different in adults with chronic cough compared with adults without chronic cough? STUDY DESIGN AND METHODS: Between 2009 and 2014, participants in the Rotterdam Study, a population-based cohort, underwent brain MRI and were interviewed for chronic cough, which was defined as daily coughing for at least 3 months. Regional brain volumes were quantified with the use of parcellation software. Based on literature review, we identified and studied seven brain regions that previously had been associated with altered functional brain activity in chronic cough. The relationship between chronic cough and regional brain volumes was investigated with the use of multivariable regression models. RESULTS: Chronic cough was prevalent in 9.6% (No. = 349) of the 3,620 study participants (mean age, 68.5 ± 9.0 years; 54.6% female). Participants with chronic cough had significantly smaller anterior cingulate cortex volume than participants without chronic cough (mean difference, -126.16 mm3; 95% CI, -245.67 to -6.66; P = .039). Except for anterior cingulate cortex, there were no significant difference in the volume of other brain regions based on chronic cough status. The volume difference in the anterior cingulate cortex was more pronounced in the left hemisphere (mean difference, -88.11 mm3; 95% CI, -165.16 to -11.06; P = .025) and in male participants (mean difference, -242.58 mm3; 95% CI, -428.60 to -56.55; P = .011). INTERPRETATION: Individuals with chronic cough have a smaller volume of the anterior cingulate cortex, which is a brain region involved in cough suppression. CLINICAL TRIAL REGISTRATION: The Netherlands National Trial Registry (NTR; www.trialregister.nl) and the World Health Organization's International Clinical Trials Registry Platform (ICTRP; www.who.int/ictrp/network/primary/en/) under the joint catalogue number NTR6831.

Three-dimensional ultrasound virtual organ computer-aided analysis to monitor fetal intracranial volume development characteristics: A multi-center study in a Chinese population.

OBJECTIVES: This study aimed to evaluate the feasibility of monitoring fetal intracranial volume using three-dimensional ultrasound virtual organ computer-aided analysis (VOCAL) technology and to analyze normal fetal brain growth. METHODS: This multi-center prospective cross-sectional study included 821 pregnant women (18-40 gestational weeks) divided into 23 groups according to gestational week. We used transabdominal three-dimensional ultrasound VOCAL to monitor fetal intracranial volume; explore the correlation between intracranial volume and gestational age, biparietal diameter (BPD), and head circumference (HC); and analyze the proportion of brain weight to body weight. RESULTS: The intracranial volume of normal fetuses conformed to the normal distribution, gradually increased with gestational age, and was highly correlated with gestational age (r = 0.977), BPD (r = 0.975), and HC (r = 0.953; p < 0.001). The median percentage of brain weight (BW) to estimated fetal weight (EFW) was between 13% and 21%, and the BW/EFW ratio showed a significant downward trend in the third trimester. The VOCAL technology monitored the fetal intracranial volume with good repeatability. CONCLUSIONS: VOCAL technology is feasible for monitoring the fetal intracranial volume, and the intracranial volume increases more than 10-times in the second and third trimesters.

Bilateral fronto-orbital advancement combined with cranial vault release using a free-floating bone flap technique for nonsyndromic unilateral coronal synostosis.

Background: The goals of operative treatment for unilateral coronal synostosis (UCS) are to improve appearance and allow unrestricted brain growth. However, for severe unilateral premature closure of the coronal suture, existing methods do not address the compression of the brain or expand the volume of the skull cavity. We report our retrospective experience with bilateral fronto-orbital advancement combined with cranial vault release using a free-floating bone flap (CVR + FFBF) technique and the resulting changes in the anterior cranial vault asymmetry index (ACVAI) and intracranial volume. Methods: Twenty patients with UCS who underwent bilateral fronto-orbital advancement combined with CVR + FFBF technique from April 2014 to May 2019 were included. Surgical efficacy was evaluated by the ACVAI and intracranial volume before the operation, 1 week after the operation, and at the last follow-up (average 19.8 months; range, 12 to 40 months). The measurement data are presented as the mean ± standard deviation and were statistically analyzed by t-test. Results: The ACVAI was 9.07%±3.55% before the operation, 3.56%±3.42% 1 week after the operation, and 3.13%±2.41% at the last follow-up. The ACVAI 1 week after the operation was significantly lower than that before the operation (t=4.827, P<0.001). There was no significant difference between the ACVAI 1 week after the operation and at the last follow-up (t=0.660, P=0.517). The intracranial volume was 1,027.85±112.25 mL in patients before the operation and 1,131.92±161.71 mL in the normal control group, which was a statistically significant difference (t=2.364, P=0.023). The intracranial volume significantly increased 1 week after surgery: 1,081.62±111.10 mL (t=8.703, P<0.001), and this trend continued at the last follow-up (1,386.90±119.30 mL) similarly to the normal control group (1,438.22±89.28 mL). At the last follow-up, there was no significant difference between the two groups (t=1.540, P=0.132). Conclusions: For the treatment of UCS, bilateral fronto-orbital advancement combined with CVR + FFBF technique offers functional and cosmetic outcomes in terms of intracranial volume expansion and fronto-orbital symmetry.

Thirty novel sequence variants impacting human intracranial volume.

Intracranial volume, measured through magnetic resonance imaging and/or estimated from head circumference, is heritable and correlates with cognitive traits and several neurological disorders. We performed a genome-wide association study meta-analysis of intracranial volume (n = 79 174) and found 64 associating sequence variants explaining 5.0% of its variance. We used coding variation, transcript and protein levels, to uncover 12 genes likely mediating the effect of these variants, including GLI3 and CDK6 that affect cranial synostosis and microcephaly, respectively. Intracranial volume correlates genetically with volumes of cortical and sub-cortical regions, cognition, learning, neonatal and neurological traits. Parkinson's disease cases have greater and attention deficit hyperactivity disorder cases smaller intracranial volume than controls. Our Mendelian randomization studies indicate that intracranial volume associated variants either increase the risk of Parkinson's disease and decrease the risk of attention deficit hyperactivity disorder and neuroticism or correlate closely with a confounder.

Association of Inner Retinal Thickness with Prevalent Dementia and Brain Atrophy in a General Older Population: The Hisayama Study.

Purpose: To assess the association of inner retinal thickness with prevalent dementia and regional brain atrophy in a general older population of Japanese. Design: Population-based, cross-sectional study. Participants: A total of 1078 residents aged 65 years or older who participated in an eye examination, a comprehensive survey of dementia, and brain magnetic resonance imaging scanning in 2017. Methods: The thicknesses of the inner retinal layers, namely, the ganglion cell-inner plexiform layer (GC-IPL) and retinal nerve fiber layer (RNFL)-were measured by swept-source OCT (SS-OCT). The association of these retinal thicknesses with the risk of the presence of dementia was estimated using restricted cubic splines and logistic regression models. Regional brain volumes were estimated separately by applying 2 different methods: voxel-based morphometry (VBM) and analysis by FreeSurfer software. The associations of GC-IPL and RNFL thickness with each brain regional volume were analyzed using multiple regression analysis. Main Outcome Measure: Prevalent dementia and regional brain atrophy. Results: Among the study participants, 61 participants (5.7%) were diagnosed with dementia. The likelihood of the presence of dementia significantly increased with lower GC-IPL thickness after adjusting for potential confounders (odds ratio, 1.62 [95% confidence interval, 1.30-2.01] per 1 standard deviation decrement in the GC-IPL thickness), but no significant association was observed with RNFL thickness. In the VBM analyses with the multivariable adjustment, lower GC-IPL thickness was significantly associated with lower volume of known brain regions related to cognitive functions (i.e., the hippocampus, amygdala, entorhinal area, and parahippocampal gyrus) and visual functions (i.e., the cuneus, lingual gyrus, and thalamus). Meanwhile, the volume of the thalamus significantly decreased with lower RNFL thickness, but none of the brain regions related to cognitive function exhibited a volume change in association with RNFL thickness. The sensitivity analysis using FreeSurfer analysis also showed that lower GC-IPL thickness was significantly associated with lower regional brain volume/intracranial volume of the hippocampus, amygdala, cuneus, lingual gyrus, and thalamus. Conclusions: Our findings suggest that the measurement of GC-IPL thickness by SS-OCT, which is a noninvasive, convenient, and reproducible method, might be useful for identifying high-risk individuals with dementia.

Practical methods for segmentation and calculation of brain volume and intracranial volume: a guide and comparison.

Background: Accurate segmentation and calculation of total brain volume (BV) and intracranial volume (ICV) (further-volumetry) may serve various clinical tasks and research studies in neuroscience. Manual segmentation is extremely time consuming. There is a relative lack of published broad recommendations and comparisons of tools for automated volumetry, especially for users without expertise in computer science, for settings with limited resources, and when neuroimaging quality is suboptimal due to clinical circumstances. Our objective is to decrease the barrier to entry for research and clinical groups to perform volumetric cranial imaging analysis using free and reliable software tools. Methods: Automated volumetry from computed tomography (CT)/magnetic resonance imaging (MRI) scans was accomplished using 3D Slicer (v. 4.11.0), FreeSurfer (v. 7.1.1), and volBrain (v. 1.0) in a cohort of 39 patients with ischemic middle cerebral artery territory brain infarcts in the acute stage. Visual inspection for accuracy was also performed. Statistical analysis included coefficient of determination (R2) and Bland-Altman (B-A) plots. A multifaceted comparison between 3D Slicer, FreeSurfer, and volBrain from practical user perspective was performed to compile a list of distinguishing features. Results: BV: FreeSurfer, 3D Slicer, and volBrain provide similar estimations when high quality T1-MRI scans with 1 mm slices (3D scans) are available, whereas 3 mm and thicker slices (2D scans) introduce a dispersion in results. ICV: the most accurate volumetry is provided by 3D Slicer using CT scans. volBrain uses T1-MRIs and also provides good results which agree with 3D Slicer. Both of these methods may be more trustworthy than T1 MRI-derived FreeSurfer calculations. Conclusions: All three studied tools of automated intracranial and brain volumetry-3D Slicer, FreeSurfer, and volBrain-are free, reliable, require no complex programming, but still have certain limitations and significant differences. Based on our investigation findings, the readers should be able to select the right volumetry tool and neuroimaging study, and then follow provided step-by-step instructions to accomplish specific volumetry tasks.