Total Intracranial Volume Research Articles

Sex differences in brain MRI using deep learning toward fairer healthcare outcomes

This study leverages deep learning to analyze sex differences in brain MRI data, aiming to further advance fairness in medical imaging. We employed 3D T1-weighted Magnetic Resonance images from four diverse datasets: Calgary-Campinas-359, OASIS-3, Alzheimer's Disease Neuroimaging Initiative, and Cambridge Center for Aging and Neuroscience, ensuring a balanced representation of sexes and a broad demographic scope. Our methodology focused on minimal preprocessing to preserve the integrity of brain structures, utilizing a Convolutional Neural Network model for sex classification. The model achieved an accuracy of 87% on the test set without employing total intracranial volume (TIV) adjustment techniques. We observed that while the model exhibited biases at extreme brain sizes, it performed with less bias when the TIV distributions overlapped more. Saliency maps were used to identify brain regions significant in sex differentiation, revealing that certain supratentorial and infratentorial regions were important for predictions. Furthermore, our interdisciplinary team, comprising machine learning specialists and a radiologist, ensured diverse perspectives in validating the results. The detailed investigation of sex differences in brain MRI in this study, highlighted by the sex differences map, offers valuable insights into sex-specific aspects of medical imaging and could aid in developing sex-based bias mitigation strategies, contributing to the future development of fair AI algorithms. Awareness of the brain's differences between sexes enables more equitable AI predictions, promoting fairness in healthcare outcomes. Our code and saliency maps are available at https://github.com/mahsadibaji/sex-differences-brain-dl.

Age-related volume decrease in subcortical gray matter is a part of healthy brain aging in men.

With the global population aging, the number of individuals over 60 is expected to double by 2050. Brain volume increases until age 13, stabilizes between 18 and 35, then declines by 0.2% annually. Magnetic resonance imaging (MRI) studies highlight significant gray matter atrophy, necessitating differentiation between normal aging and neurodegeneration. This study assessed the impact of aging on subcortical gray matter in healthy males to identify biomarkers of physiological aging. A retrospective study of 106 healthy males who underwent brain MRI from 2012 to 2016, divided into two age groups: younger and older than 35years. MRI scans were performed using a 3T machine, and volumetric analysis was conducted with VolBrain software. Subcortical gray matter volumes were compared between groups. The Shapiro-Wilk test evaluated normality. Student's t-test and Mann-Whitney U test were used for statistical analysis, with significance defined as p < 0.05. Total intracranial volume was comparable between age groups (p = 0.527). Significant volume reductions (p < 0.05) were observed in subcortical gray matter structures, including the nucleus accumbens, caudate nucleus, globus pallidus, putamen, thalamus, and ventral diencephalon, particularly on the right side in the elderly group. Subcortical gray matter volume in healthy males shows significant differences between older and younger individuals (p < 0.05), with asymmetrical reduction and certain structures on the right aging more rapidly. These findings are significant for distinguishing healthy aging from neurodegeneration.

Brain structural associations of syntactic complexity and diversity across schizophrenia spectrum and major depressive disorders, and healthy controls

Deviations in syntax production have been well documented in schizophrenia spectrum disorders (SSD). Recently, we have shown evidence for transdiagnostic subtypes of syntactic complexity and diversity. However, there is a lack of studies exploring brain structural correlates of syntax across diagnoses. We assessed syntactic complexity and diversity of oral language production using four Thematic Apperception Test pictures in a sample of N = 87 subjects (n = 24 major depressive disorder (MDD), n = 30 SSD patients both diagnosed according to DSM-IV-TR, and n = 33 healthy controls (HC)). General linear models were used to investigate the association of syntax with gray matter volume (GMV), fractional anisotropy (FA), axial (AD), radial (RD), and mean diffusivity (MD). Age, sex, total intracranial volume, group, interaction of group and syntax were covariates of no interest. Syntactic diversity was positively correlated with the GMV of the right medial pre- and postcentral gyri and with the FA of the left superior-longitudinal fasciculus (temporal part). Conversely, the AD of the left cingulum bundle and the forceps minor were negatively correlated with syntactic diversity. The AD of the right inferior-longitudinal fasciculus was positively correlated with syntactic complexity. Negative associations were observed between syntactic complexity and the FA of the left cingulum bundle, the right superior-longitudinal fasciculus, and the AD of the forceps minor and the left uncinate fasciculus. Our study showed brain structural correlates of syntactic complexity and diversity across diagnoses and HC. This contributes to a comprehensive understanding of the interplay between linguistic and neural substrates in syntax production in psychiatric disorders and HC.

Artificial gravity: an effective countermeasure for microgravity-induced headward fluid shift?

Long-duration spaceflight is associated with pathophysiological changes in the intracranial compartment hypothetically linked to microgravity-induced headward fluid shift. This study aimed to determine whether daily artificial gravity (AG) sessions can mitigate these effects, supporting its application as a countermeasure to spaceflight. Twenty-four healthy adult volunteers (16 men) were exposed to 60 days of 6° head-down tilt bed rest (HDTBR) as a ground-based analog of chronic headward fluid shift. Subjects were divided equally into three groups: no AG (control), daily 30-min intermittent AG (iAG), and daily 30-min continuous (cAG). Internal carotid artery (ICA) stroke volume (ICASV), ICA resistive index (ICARI), ICA flow rate (ICAFR), aqueductal cerebral spinal fluid flow velocity (CSFV), and intracranial volumetrics were quantified at 3 T. MRI was performed at baseline, 14 and 52 days into HDTBR, and 3 days after HDTBR (recovery). A mixed model approach was used with intervention and time as the fixed effect factors and the subject as the random effect factor. Compared with baseline, HDTBR was characterized by expansion of lateral ventricular, white matter, gray matter, and brain + total intracranial cerebral spinal fluid volumes, increased CSFv, decreased ICASV, and decreased ICAFR by 52 days into HBTBR (All Ps < 0.05). ICARI was only increased 14 days into HDTBR (P < 0.05). Neither iAG nor cAG significantly affected measurements compared with HDTBR alone, indicating that 30 min of daily exposure was insufficient to mitigate the intracranial effects of headward fluid shift. Greater AG session exposure time, gravitational force, or both are suggested for future countermeasure research.NEW & NOTEWORTHY Brief exposure to continuous or intermittent artificial gravity via short-arm centrifugation was insufficient in mitigating the intracranial pathophysiological effects of the headward fluid shift simulated during head-down tilt bed rest (HDTBR). Our results suggest that greater centrifugation session duration, gravitational force, or both may be required to prevent the development of spaceflight-associated neuro-ocular syndrome and should be considered in future ground-based countermeasure studies.

Choroid Plexus Volume in Pediatric-Onset Multiple Sclerosis.

Recent studies suggest that the choroid plexus (CP) may function as a site of access of inflammatory cells into the CNS in multiple sclerosis (MS). Pediatric-onset MS (POMS) is characterized by a high inflammatory burden, as evidenced by a high relapse rate and volume of T2 lesions, making patients with POMS an informative population to evaluate choroid plexus volume (CPV). The objectives of the study were (1) to evaluate CPV at symptom onset in participants with POMS compared with healthy controls (HCs); (2) to evaluate changes in CPV in the first year of disease in participants with POMS; and (3) to evaluate associations between CPV, brain volumes, relapse activity, and disability in participants with POMS. Baseline 1.5T MRI scans were acquired from 23 participants with POMS and 23 age-matched and sex-matched HCs; 18 participants with POMS also had 12-month follow-up MRI scans. The CP of the lateral ventricles was segmented manually. CP and brain structure volumes were normalized for total intracranial volume. The number of relapses, T2 and gadolinium-enhancing T1 lesion counts, and Expanded Disability Status Scale (EDSS) scores at 12 months were also analyzed. Baseline CPVs were compared between groups using the Wilcoxon exact test, and CPV change from baseline to 12 months in participants with POMS was compared using the Wilcoxon signed-rank test. The relationship between CPV and brain volumetric measures, T2 lesion volumes, lesion count, number of relapses, and EDSS scores was assessed through Spearman correlation. The median normalized CPV was 1.51 × 10-3 (interquartile range [IQR]: 1.32-1.76) in POMS baseline scans and 1.21 × 10-3 (IQR: 1.1-1.47) in HC scans (p = 0.001). CPV did not significantly change at 12 months in the 18 participants with POMS with follow-up scans (p = 0.352). CPV in participants with POMS and HCs correlated with lateral ventricular volume (p = 0.012 for both groups) but did not correlate with brain and T2 lesion volumes or lesion count at baseline, nor with relapse activity or EDSS scores at 12 months in participants with POMS. CPV measured at baseline is greater in participants with POMS than in HCs. Baseline CPV did not predict higher disease activity or worse neurologic outcomes over 1 year. While higher CPV may be an early feature of inflammation in MS, its strong correlation with ventricular volumes could also reflect enlargement secondary to the mechanical attachment of CP to the ventricular wall.

Plasma trimethylamine-n-oxide associates with reduced hippocampal volume and cognitive impairment in atrial fibrillation

Abstract Background/Introduction Atrial fibrillation (AF) is the most common cardiac arrhythmia in modern society and affected patients appear particularly vulnerable to cognitive dysfunction. Yet, the pathomechanism of this association other than thromboembolism (TE) is not fully understood. We have shown earlier an association of cognitive dysfunction with the gut microbiome derivate trimethylamine-N-oxide (TMAO), which predominantly results from the consumption of red meat. We therefore hypothesized that TMAO may affect hippocampal volume (HV) as a brain structure relevant for cognition. Purpose To demonstrate the structure-function correlation of high TMAO levels with reduced cognitive function and lower HV in a large cohort of patients with atrial fibrillation. Methods We included 1’736 patients with confirmed AF from the Swiss-AF-cohort with both, available blood samples for TMAO measurement and with brain magnetic resonance imaging (bMRI) for the determination of HV at baseline. TMAO levels were measured by liquid chromatography-mass spectrometry (LC-MS). bMRI were obtained by 1.5 or 3 Tesla scanners. HV was assessed by the FreeSurfer software (v 7.4.0) subregion segmentation module and normalized by using Sequence Adaptive Multimodal SEGmentation (SAMSEG) to determine the segmentation based intracranial volume. Patients were divided into TMAO quartiles (Q1: 0.6-3.8, Q2: 3.8-5.5, Q3: 5.5-8.5, Q4: 8.5-164.3μmol/l). Their TMAO levels were compared with their HV (unit = mm3) in linear mixed effect models adjusted for multiple covariates (model 1: age, sex, total intracranial volume (ICV), education level; model 2 = model 1 + smoking status, body mass index (BMI), alcohol consumption, physical activity; model 3 = model 2 + hypertension, coronary artery disease, previous stroke, geriatric depression scale). We assessed both unilateral HV (right = RHV, left = LHV) and bilateral HV standardized by the individual total ICV. Results Overall mean age was 72.5 years (+/-8.4 SD), 27.2% were female. Most of the patients were well educated (39.4% advanced, 48.8% middle education) and 44% never smoked. After multivariable adjustments, patients in the highest TMAO quartile showed a significant reduction of bilateral HV volume of 93.4mm3 (95% CI -179.0 to -7.8, p = 0.03). The RHV appeared more affected and was significantly reduced by 48.2mm3 (CI -93.4, -3.0, p=0.04), whereas LHV was decreased by 44.2mm3 (-89.4, 1.0, p=0.06) in the highest TMAO quartile. Conclusion(s) TMAO negatively associates with bilateral HV in patients with AF. Our results suggest a structure-function-correlation between high TMAO levels and cognitive dysfunction. The findings may be relevant for the high TMAO-exposed patients and advocates for the importance of (possible dietary) prevention in AF.

Phase-contrast MRI analysis of cerebral blood and CSF flow dynamic interactions

BackgroundFollowing the Monro-Kellie doctrine, the Cerebral Blood Volume Changes (CB_VC) should be mirrored by the Cerebrospinal Fluid Volume Changes (CSF_VC) at the spinal canal. Cervical level is often chosen to estimate CB_VC during the cardiac cycle. However, due to the heterogeneity in the anatomy of extracranial internal jugular veins and their high compliance, we hypothesize that the intracranial level could be a better choice to investigate blood and cerebrospinal fluid (CSF) interactions. This study aims to determine which level, intracranial or extracranial, is more suitable for measuring arterial and venous flows to study cerebral blood and CSF dynamics interactions.MethodsThe spinal CSF and cerebral blood flow measured at intracranial and extracranial levels were quantified using cine phase-contrast magnetic resonance imaging (PC-MRI) in 38 healthy young adults. Subsequently, CSF_VC and CB_VC were calculated, and by linear regression analysis (R2 and slope), the relationship between CB_VC at both levels and the spinal CSF_VC was compared. The differences between extracranial and intracranial measurements were assessed using either a paired Student’s t-test or Wilcoxon’s test, depending on the normality of the data distribution.ResultsThe CB_VC amplitude was significantly higher at the extracranial level (0.89 ± 0.28 ml/CC) compared to the intracranial level (0.73 ± 0.19 ml/CC; p < 0.001). CSF oscillations through the spinal canal do not completely balance blood volume changes. The R2 and the slope values obtained from the linear regression analysis between CSF and blood flows were significantly higher in magnitude for the intracranial CB_VC (R2: 0.82 ± 0.16; slope: − 0.74 ± 0.19) compared to the extracranial CB_VC (R2: 0.47 ± 0.37; slope: -0.36 ± 0.33; p < 0.001). Interestingly, extracranial CB_VC showed a greater variability compared to intracranial CB_VC.ConclusionOur results confirmed that CSF does not completely and instantaneously balance cerebral blood expansion during the cardiac cycle. Nevertheless, the resting volume is very small compared to the total intracranial volume. To our knowledge, this study is the first to demonstrate these findings using cerebral blood flow measured intracranially below the Circle of Willis. Additionally, our findings show that cerebral arterial and venous flow dynamic measurements during the cardiac cycle obtained by PC-MRI at the intracranial plane strongly correlate with CSF oscillations measured in the spinal canal. Therefore, the intracranial vascular plane is more relevant for analyzing cerebral blood and CSF interactions during the cardiac cycle compared to measurements taken at the cervical vascular level.

Lung volumes are increased in fetuses with transposition of the great arteries on intrauterine MRI.

Fetal brain size is decreased in some children with complex CHDs, and the distribution of blood and accompanying oxygen and nutrients is regionally skewed from early fetal life dependent on the CHD. In transposition of the great arteries, deoxygenated blood preferentially runs to the brain, whereas the more oxygenated blood is directed towards the lungs and the abdomen. Knowledge of whether this impactsintrauterine organ development is limited. We investigated lung, liver, and total intracranial volume in fetuses with transposition of the great arteries using MRI.Eight fetuses with dextro-transposition and without concomitant disease or chromosomal abnormalities and 42 fetuses without CHD or other known diseases were scanned once or twice at gestational age 30 through 39 weeks. The MRI scans were conducted on a 1.5T system, using a 2D balanced steady-state free precession sequence. Slices acquired covered the entire fetus, slice thickness was 10 mm, pixel size 1.5 × 1.5 mm, and scan duration was 30 sec.The mean lung z score was significantly larger in fetuses with transposition compared with those without a CHD; mean difference is 1.24, 95% CI:(0.59;1.89), p < 0.001. The lung size, corrected for estimated fetal weight, was larger than in the fetuses without transposition; mean difference is 8.1 cm3/kg, 95% CI:(2.5;13.7 cm3/kg), p = 0.004.In summary, fetuses with dextro-transposition of the great arteries had both absolute and relatively larger lung volumes than those without CHD. No differences were seen in liver and total intracranial volume. Despite the small number of cases, the results are interesting and warrant further investigation.

Children had smaller brain volumes and cortical surface areas after prenatal opioid maintenance therapy exposure.

The studies have shown that infants with prenatal OMT exposure had smaller brain volumes than non-exposed controls, but long-term outcome data are lacking. We examined 5-13-year-old OMT-exposed children with brain MRI and tested motor and visual-motor functions and possible associations between brain morphology and outcome. To this retrospective cohort study, we recruited 55 children with prenatal OMT exposure and 59 age- and gender-matched controls. They were examined with brain MRI, Movement-ABC and Beery-VMI. MRI images were processed with the Free Surfer® software to obtain volumetrics and estimates of cortical surface area and thickness. We used a general linear regression model (GLM) to calculate group differences. The children in the OMT group had smaller mean total intracranial volume (ICV), 1407 cm3 (CI 95% 1379-1434) versus 1450 cm3 (CI 95% 1423-1476) in the control group (p = 0.026). After adjusting for ICV, significant group differences persisted for volumes of amygdala, basal ganglia and mid-posterior part of corpus callosum. Cortical surface area was smaller in the left caudal middle frontal gyrus and the right inferior parietal lobule in the OMT-group. Visual-motor function was significantly correlated with ICV. Prenatal OMT exposure may alter early brain development with possible negative long-term functional consequences.

Associations between parental rearing style and amygdala and hippocampal subfield abnormalities in drug-naive females with anorexia nervosa

BackgroundAltered volumes in the hippocampus and amygdala have been linked to anorexia nervosa (AN). This study aimed to investigate amygdala and hippocampal subfields volume abnormalities in AN patients, and their associations with parental rearing practices and clinical psychological characteristics.MethodsThis study included twenty-nine drug-naive females with AN from West China Hospital of Sichuan University, China, and fifty-nine age- and gender-matched healthy controls (HCs) recruited through advertisement. All participants underwent T1-weighted imaging. Amygdala and hippocampal subfields volume was calculated using FreeSurfer 7.0. The Core Self-Evaluation Scale (CSES) and Rosenberg Self-Esteem Scale (RSES) were used to assess the psychological characteristics of AN patients. The Egna Minnen av Barndoms Uppfostran (EMBU) was employed to evaluate parental rearing practices. Group differences in brain volumes were analyzed with covariates like age and total intracranial volume (TIV). Partial correlation analysis explored the correlations between brain region volumes and clinical psychological characteristics.ResultsAN patients exhibited lower RSES and CSES scores, and more adverse parental rearing style than healthy norms. After adjusting for covariates, AN patients showed decreased gray matter volume (GMV) in the left medial (Me) and cortical (Co) nucleus, as well as in the right hippocampal-amygdala transition area (HATA). GMV in the left Me was correlated with years of education among HCs but not among AN patients. GMV in the right HATA was positively correlated with paternal penalty and severity, as well as maternal overinterference.ConclusionThis study supports structure abnormalities in amygdala and hippocampus in AN patients and suggests that parental rearing practices may be associated with hippocampal abnormalities, potentially contributing to the pathophysiology of AN. Addressing appropriate parental rearing styles may offer a positive impact on AN.

Enlarged brain perivascular spaces correlate with blood plasma osmolality in the healthy population: A longitudinal study

Enlarged perivascular spaces (EPVS) are increasingly recognized as an MRI detectable feature of neuroinflammatory processes and age-related neurodegenerative changes. Understanding perivascular characteristics in healthy individuals is crucial for their applicability as a reference for pathological changes. Limited data exists on the EPVS load and interhemispheric asymmetry in distribution among young healthy subjects. Despite the known impact of hydration on brain morphometric studies, blood plasma osmolality's effect on EPVS remains unexplored.This study investigated the influence of age, total intracranial volume (TIV), and blood plasma osmolality on EPVS characteristics in 59 healthy adults, each undergoing MRI and osmolality assessment twice within 14.8 months (mean ± 4 months). EPVS analysis was conducted in the centrum semiovale using high-resolution automated segmentation, followed by an optimization algorithm to enhance EPVS segmentation accuracy. Linear Mixed Effects model was used for the statistical analysis, which unveiled significant inter-individual variability in EPVS load and inter-hemispheric asymmetry. EPVS volume increased with age, higher TIV and lower blood plasma osmolality levels. Our findings offer valuable insights into EPVS characteristics among the healthy population, establishing a foundation to further explore age-related and pathological changes.

Acceleration of brain aging after small-volume infarcts.

Previous studies have shown that stroke patients exhibit greater neuroimaging-derived biological "brain age" than control subjects. This difference, known as the brain age gap (BAG), is calculated by comparing the chronological age with predicted brain age and is used as an indicator of brain health and aging. However, whether stroke accelerates the process of brain aging in patients with small-volume infarcts has not been established. By utilizing longitudinal data, we aimed to investigate whether small-volume infarctions can significantly increase the BAG, indicating accelerated brain aging. A total of 123 stroke patients presenting with small-volume infarcts were included in this retrospective study. The brain age model was trained via established protocols within the field of machine learning and the structural features of the brain from our previous study. We used t-tests and regression analyses to assess longitudinal brain age changes after stroke and the associations between brain age, acute stroke severity, and poststroke outcome factors. Significant brain aging occurred between the initial and 6-month follow-ups, with a mean increase in brain age of 1.04 years (t = 3.066, p < 0.05). Patients under 50 years of age experienced less aging after stroke than those over 50 years of age (p = 0.245). Additionally, patients with a National Institute of Health Stroke Scale score >3 at admission presented more pronounced adverse effects on brain aging, even after adjusting for confounders such as chronological age, sex, and total intracranial volume (F 1,117 = 7.339, p = 0.008, η 2 = 0.059). There were significant differences in the proportional brain age difference at 6 months among the different functional outcome groups defined by the Barthel Index (F 2,118 = 4.637, p = 0.012, η 2 = 0.073). Stroke accelerates the brain aging process, even in patients with relatively small-volume infarcts. This phenomenon is particularly accentuated in elderly patients, and both stroke severity and poststroke functional outcomes are closely associated with accelerated brain aging. Further studies are needed to explore the mechanisms underlying the accelerated brain aging observed in stroke patients, with a particular focus on the structural alterations and plasticity of the brain following minor strokes.

QSM-detected iron accumulation in the cerebellar gray matter is selectively associated with executive dysfunction in non-demented ALS patients.

This study aimed to assess whether quantitative susceptibility imaging (QSM)-based measures of iron accumulation in the cerebellum predict cognitive and behavioral features in non-demented amyotrophic lateral sclerosis (ALS) patients. A total of ALS patients underwent 3-T MRI and a clinical assessment using the ALS Functional Rating Scale-Revised (ALSFRS-R) and the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). Regression models were applied to each subscale of the cognitive section of the ECAS and the ECAS-Carer Interview to examine the effect of QSM-based measures in white and gray matter (WM; GM) of the cerebellum, separately for right, left, and bilateral cerebellar regions of interest (ROIs). These effects were compared to those of cerebellar volumetrics in WM/GM, right and left hemispheres while controlling for demographics, disease status, and total intracranial volume. Higher QSM measures of the cerebellar GM on the left, right, and bilateral sides significantly predicted (ps ≤ 0.003) a greater number of errors on the executive functioning (EF) subscale of the ECAS (ECAS-EF). Moreover, higher GM-related, QSM measures of the cerebellum were associated with an increased probability of a below-cut-off performance on the ECAS-EF (ps ≤ 0.024). No significant effects were observed for QSM measures of the cerebellar WM or for volumetric measures on the ECAS-EF. Other ECAS measures showed no significant effects. Bilateral QSM measures of the cerebellar GM also selectively predicted performance on backward digit span and social cognition tasks. Iron accumulation within the cerebellar GM, particularly in the cerebellar cortices, may be associated with executive functioning deficits in non-demented ALS patients. Therefore, QSM-based measures could be useful for identifying the neural correlates of extra-motor cognitive deficits in ALS patients.

Deep learning assessment of disproportionately enlarged subarachnoid-space hydrocephalus in Hakim’s disease or idiopathic normal pressure hydrocephalus

Abstract Background Disproportionately enlarged subarachnoid-space hydrocephalus (DESH) is a key feature of Hakim’s disease (synonymous with idiopathic normal pressure hydrocephalus; iNPH). However, it previously had been only subjectively evaluated. Purpose This study aims to evaluate the usefulness of MRI indices, derived from deep learning segmentation of cerebrospinal fluid (CSF) spaces, for DESH detection and to establish their optimal thresholds. Materials and Methods This study retrospectively enrolled a total of 1009 participants, including 77 patients diagnosed with Hakim’s disease, 380 healthy volunteers, 163 with mild cognitive impairment, 256 with Alzheimer’s disease, and 217 with other types of neurodegenerative diseases. DESH, ventriculomegaly, tightened sulci in the high convexities, and Sylvian fissure dilatation were evaluated on three-dimensional T1-weighted MRI by radiologists. The total ventricles, high-convexity part of the subarachnoid space, and Sylvian fissure and basal cistern were automatically segmented using the CSF Space Analysis application (FUJIFILM Corporation). Moreover, DESH, Venthi, and Sylhi indices were calculated based on these 3 regions. The area under the receiver-operating characteristic curves of these indices and region volumes (volume ratios) for DESH detection were calculated. Results Of the 1009 participants, 101 (10%) presented with DESH. The DESH, Venthi, and Sylhi indices performed well with 95.0%-96.0% sensitivity and 91.5%-96.8% specificity at optimal thresholds. All patients with Hakim’s disease were diagnosed with DESH, despite variations in severity. In patients with Hakim’s disease, with or without Alzheimer’s disease, the DESH index and total ventricular volume were significantly higher compared to patients with Alzheimer’s disease, although the total intracranial cerebrospinal fluid volume was significantly lower. Conclusion DESH, Venthi, and Sylhi indices, and the volumes and volume ratios of the ventricle and high-convexity part of the subarachnoid space computed using deep learning were useful for the DESH detection that may help to improve the diagnosis of Hakim’s disease (ie, iNPH).

Abstract 56: High Blood Pressure Is Associated with Lower Brain Volume and Cortical Thickness in Healthy Young Adults

Background: High blood pressure (BP) in middle-aged and older adults is associated with lower brain volume and cortical thickness assessed with structural MRI. However, little evidence is available in young adults. Objective: We investigated the associations of high BP with brain volumes and cortical thickness in healthy young adults. We hypothesized that high BP is associated with lower brain volume and cortical thickness in young adults. Methods: This cross-sectional study included 1095 young adults (54% women, 22-37 years) from the Human Connectome Project (HCP) who self-reported not having a history of hypertension or taking antihypertensive medications. Brachial systolic (SBP) and diastolic BP (DBP) were measured with semi-automatic or manual sphygmomanometer during study visits. Structural MRI was used to measure gray matter (GM) and white matter (WM) volume and mean cortical thickness. Associations of BP and hypertension stage with total and regional brain volumes and cortical thickness were analyzed using linear regression and analysis of covariance (ANCOVA) after adjusting for age, sex, education years, body mass index (BMI), smoking, alcohol consumption history, zygosity, and total intracranial volume. Results: SBP and DBP were (mean ± SD) 123.6 ± 14.2 and 76.5 ± 10.6 mmHg, respectively (n = 1095). High DBP was associated with lower total GM ( p = 0.012), cortical GM ( p = 0.004), subcortical GM ( p = 0.012), and total WM volumes ( p = 0.031). There were no associations of SBP and hypertension stage with total brain volume and cortical thickness. High SBP and DBP were associated with lower regional cortical thickness in the parietal lobe and lingual gyrus, and lower regional cortical volume in the postcentral gyrus, inferior parietal lobe, lateral occipital gyrus, and middle temporal gyrus. Conclusion: Associations of high BP, particularly DBP, with lower total and regional brain volume and cortical thickness were observed in healthy young adults. These findings suggest the importance of prevention or control of high BP early in life for brain health.

Correlation between semiautomated magnetic resonance imaging volumetry of the cingulate gyrus and interictal epileptiform discharge lateralization in dogs with idiopathic epilepsy.

Brain imaging suggests the involvement of the limbic system, particularly the cingulate gyrus (GC), in dogs with idiopathic epilepsy (IE). A correlation exists between the side of interictal epileptiform discharges (IEDs) and the volume of the ipsilateral GC (GCe) in dogs with IE. Dogs admitted to the neurological consultation (32 with epileptic seizures and 13 control) were included. This retrospective, blinded study followed the International Veterinary Epilepsy Task Force recommendations for diagnosing IE at the Tier III confidence level. The IE group included 18 and 14 dogs with IEDs in the left and right hemispheres, respectively (median age: 36 months, median weight: 19.5 kg), whereas the control group included 13 dogs (median age: 32 months, median weight: 20 kg). Whole-brain and GC-volumetric assessments were performed by a semiautomated method. In the control group, the volume of the GC was: left, from 743.63 to 1001.61 mm3, right, from 789.35 to 1015.86 mm3. In the study group, the volume of the GC was: left, from 720.88 to 1054.9 mm3 and right, from 566.29 to 987.77 mm3. In dogs with IE, GCe volume was significantly lower than the mean volume of the GC in the control group relative to total intracranial volume (TIV; P = .00044). Alterations in the volume of the GC provide insights into structural changes during IE. The use of semiautomatic volumetry provides an advantage by reducing the potential for human error.

Examining The Relationship Between Lateral Ventricle Volumetric Index and Linear Indexes in Childhood and Adolescence: A Retrospective MRI Study

Objective: Indexes obtained from two-dimensional and three-dimensional measurements are used to evaluate the brain's lateral ventricle (LV) structure. However, there were limited studies on how well the Evans index (EI) and the Bicaudate index (BI), which estimate LV volume, represent the LV volumetric index (LVVI) in the childhood and adolescence period. This study investigated the relationship between LVVI and linear indexes (EI and BI) in the pediatric period regarding age and sex factors. Method: This study was performed retrospectively in 588 individuals (267 [45.4%] females) aged 1-18 years with normal brain magnetic resonance images (MRI) between 2012 and 2021. LVVI was obtained by segmenting three-dimensional T1-weighted MRIs with volBrain1.0. LVVI was obtained by dividing the LV absolute volume by the total intracranial volume. We made linear measurements for EI and BI with the 3D Slicer. In this study, we compared the data obtained from individuals in 16 different age ranges between 1-18 years old with SPSS (ver.28). Results: In our study, we found the mean value of LVVI to be 0.656±0.372%. The mean values of EI and BI were 0.242±0.025 and 0.070±0.022, respectively. In the pediatric population, we found that mean values of EI and BI were significantly higher in males than in females (p

Concurrent and longitudinal neurostructural correlates of irritability in children

Irritability, or an increased proneness to frustration and anger, is common in youth; however, few studies have examined neurostructural correlates of irritability in children. The purpose of the current study was to examine concurrent and longitudinal associations between brain structure and irritability in a large sample of 9–10-year-old children. Participants included 10,647 children from the Adolescent Brain Cognitive Developmentsm Study (ABCD Study®). We related a latent irritability factor to gray matter volume, cortical thickness, and surface area in 68 cortical regions and to gray matter volume in 19 subcortical regions using structural equation modeling. Multiple comparisons were adjusted for using the false discovery rate (FDR). After controlling for age, sex, race/ethnicity, scanner model, parent’s highest level of education, medication use, and total intracranial volume, irritability was associated with smaller volumes in primarily temporal and parietal regions at baseline. Longitudinal analyses showed that baseline gray matter volume did not predict irritability symptoms at the 3rd-year follow-up. No significant associations were found for cortical thickness or surface area. The current study demonstrates inverse associations between irritability and volume in regions implicated in emotional processing/social cognition, attention allocation, and movement/perception. We advance prior research by demonstrating that neurostructural differences associated with irritability are already apparent by age 9–10 years, extending this work to children and supporting theories positing socioemotional deficits as a key feature of irritability.

Effects of strategic white matter hyperintensities of cholinergic pathways on basal forebrain volume in patients with amyloid-negative neurocognitive disorders

BackgroundThe cholinergic neurotransmitter system is crucial to cognitive function, with the basal forebrain (BF) being particularly susceptible to Alzheimer’s disease (AD) pathology. However, the interaction of white matter hyperintensities (WMH) in cholinergic pathways and BF atrophy without amyloid pathology remains poorly understood.MethodsWe enrolled patients who underwent neuropsychological tests, magnetic resonance imaging, and 18F-florbetaben positron emission tomography due to cognitive impairment at the teaching university hospital from 2015 to 2022. Among these, we selected patients with negative amyloid scans and additionally excluded those with Parkinson’s dementia that may be accompanied by BF atrophy. The WMH burden of cholinergic pathways was quantified by the Cholinergic Pathways Hyperintensities Scale (CHIPS) score, and categorized into tertile groups because the CHIPS score did not meet normal distribution. Segmentation of the BF on volumetric T1-weighted MRI was performed using FreeSurfer, then was normalized for total intracranial volume. Multivariable regression analysis was performed to investigate the association between BF volumes and CHIPS scores.ResultsA total of 187 patients were enrolled. The median CHIPS score was 12 [IQR 5.0; 24.0]. The BF volume of the highest CHIPS tertile group (mean ± SD, 3.51 ± 0.49, CHIPSt3) was significantly decreased than those of the lower CHIPS tertile groups (3.75 ± 0.53, CHIPSt2; 3.83 ± 0.53, CHIPSt1; P = 0.02). In the univariable regression analysis, factors showing significant associations with the BF volume were the CHIPSt3 group, age, female, education, diabetes mellitus, smoking, previous stroke history, periventricular WMH, and cerebral microbleeds. In multivariable regression analysis, the CHIPSt3 group (standardized beta [βstd] = -0.25, P = 0.01), female (βstd = 0.20, P = 0.04), and diabetes mellitus (βstd = -0.22, P < 0.01) showed a significant association with the BF volume. Sensitivity analyses showed a negative correlation between CHIPS score and normalized BF volume, regardless of WMH severity.ConclusionsWe identified a significant correlation between strategic WMH burden in the cholinergic pathway and BF atrophy independently of amyloid positivity and WMH severity. These results suggest a mechanism of cholinergic neuronal loss through the dying-back phenomenon and provide a rationale that strategic WMH assessment may help identify target groups that may benefit from acetylcholinesterase inhibitor treatment.

Associations of Amyloid Burden, White Matter Hyperintensities, and Hippocampal Volume With Cognitive Trajectories in the 90+ Study.

Amyloid pathology, vascular disease pathology, and pathologies affecting the medial temporal lobe are associated with cognitive trajectories in older adults. However, only limited evidence exists on how these pathologies influence cognition in the oldest old. We evaluated whether amyloid burden, white matter hyperintensity (WMH) volume, and hippocampal volume (HV) are associated with cognitive level and decline in the oldest old. This was a longitudinal, observational community-based cohort study. We included participants with 18F-florbetapir PET and MRI data from the 90+ Study. Amyloid load was measured using the standardized uptake value ratio in the precuneus/posterior cingulate with eroded white matter mask as reference. WMH volume was log-transformed. All imaging measures were standardized using sample means and SDs. HV and log-WMH volume were normalized by total intracranial volume using the residual approach. Global cognitive performance was measured by the Mini-Mental State Examination (MMSE) and modified MMSE (3MS) tests, repeated every 6 months. We used linear mixed-effects models with random intercepts; random slopes; and interaction between time, time squared, and imaging variables to estimate the associations of imaging variables with cognitive level and cognitive decline. Models were adjusted for demographics, APOE genotype, and health behaviors. The sample included 192 participants. The mean age was 92.9 years, 125 (65.1%) were female, 71 (37.0%) achieved a degree beyond college, and the median follow-up time was 3.0 years. A higher amyloid load was associated with a lower cognitive level (βMMSE = -0.82, 95% CI -1.17 to -0.46; β3MS = -2.77, 95% CI -3.69 to -1.84). A 1-SD decrease in HV was associated with a 0.70-point decrease in the MMSE score (95% CI -1.14 to -0.27) and a 2.27-point decrease in the 3MS score (95% CI -3.40 to -1.14). Clear nonlinear cognitive trajectories were detected. A higher amyloid burden and smaller HV were associated with faster cognitive decline. WMH volume was not significantly associated with cognitive level or decline. Amyloid burden and hippocampal atrophy are associated with both cognitive level and cognitive decline in the oldest old. Our findings shed light on how different pathologies contributed to driving cognitive function in the oldest old.