Total Brain Research Articles

Degree of joint risk factor control and incident all cause dementia in hypertensive patients

Abstract Background Hypertension (HT) is a known modifiable risk factor for dementia. This study evaluates the impact of effectively controlling multiple modifiable risk factors in HT patients on the incidence of dementia. Methods Data from the UK Biobank (2006-2010) were used in this longitudinal study, including essential HT patients and non-HT participants, excluding those with pre-existing dementia or less than two years of follow-up. The study focused on seven risk factors: physical activity, smoking status, blood pressure, body mass index, glycosylated hemoglobin levels, lipids, and urinary Albumin-to-Creatinine Ratio. The Cox model evaluated the association between the degree of risk factor control and the incidence of dementia, while linear regression models analyzed the brain abnormalities among different risk factor control groups. Results Of 291,720 participants, 86,675 had HT. Over a median follow-up of 14.3 years, dementia developed in 2,002 HT and 1,379 non-HT participants. Compared with non-HT individuals, a gradual decrease in dementia risk in HT patients with the number of well-controlled risk factors was observed (hazard ratio: 2.01 [95% confidence interval (CI) 1.73-2.34] to 1.25 [95% CI 1.13-1.40]). While within HT patients, with the highest level of control lowering the risk to 0.63 (95% CI [0.54-0.73]). Moreover, HT patients with better well-controlled risk factors had lower geometric mean for white matter hyperintensity volume and increased total brain parenchymal volume, gradually narrowing the gap with non-HT individuals. Conclusion In HT patients, a higher degree of well-controlled risk factors seemed to be associated with progressively lower risks of dementia and brain abnormalities.HRs of all-cause dementia in patientsGMRs of different risk factors on target

Large sample size MRI measurements to assess the relation between cardiac function and structure and white matter hyperintensity volumes

Abstract Background People with established cardiovascular disease (CVD) are at risk of early cognitive decline, and neurological diseases such as dementia. CVD and neurological diseases share common risk factors, such as blood pressure, sedentary lifestyle, as well as genomic risk factors such as mutations in APOE4 [1]. It's unclear to what extent the co-occurrence of CVD and neurological diseases is explained by these risk factors, or whether there is a direct association where CVD is a first step towards poorer neurological health. White matter hyperintensities (WMH) of presumed vascular origin are damaged areas in the brain observed through magnetic resonance imaging (MRI). These lesions are associated with progressive neurological disease such as vascular dementia, as well with risk factors for CVD [2]. Purpose We set out to determine to what extent CMR measurements associated with WMH independent of known cerebrovascular risk factors. Methods Cardiac and brain MRI images were analysed for 23,963 UK biobank (UKB) participants. WMH analysis included 5 brain regions (Frontal[F], Parietal[P], Temporal[T], Occipital[O], Basal Ganglia and Thalami [BGT]) and total brain WMH volume. Cardiac traits included stroke volumes, atrial volumes, ejection fractions of right and left chambers, left ventricular (LV) strain, LV wall thickness and aortic areas. Multivariable regression analysis was carried out, where each cardiac trait was regressed on each brain region and adjusted for: age, difference between age at initial visit and imaging visit, sex, systolic and diastolic blood pressure, Hba1c, household income, educational status, Townsend score and family history of disease (Alzheimer’s, Parkinson's, high blood pressure, stroke, heart disease) . Results were evaluated against a multiple testing correct p-value threshold of 0.05, reflecting the number of principle components(n=10) necessary to explain 90% of the cardiac trait variability. Results For 5 cardiac traits (right ventricular stroke volume, left atrial stroke volume, left ventricular stroke volume, left ventricular ejection fraction and right ventricular end diastolic volume) higher values were associated with lower WMH volumes in all brain regions. Additionally, some cardiac traits such as LV cardiac output associated with specific brain regions (T, O, BGT). Additionally, APOE- ε4 stratified analyses indicated, homozygous carriers show a greater association between higher minimum LA and RA volumes and higher WMH volumes in the occipital lobe. Conclusions This study gives an insight into the WMH burden in a large population of adults. It highlights the associations of cardiac traits with white matter hyperintensity volumes in different brain regions independent of known risk factors. Using cardiac traits as surrogate markers of different cardiac disease could explain how cardiac functionality defines WMH volume distribution and subsequently the wider relationship between CVD and cerebrovascular disease.Figure 1Graphical Abstract

Sex differences in association between dietary sodium intake and white matter hyperintensity volume

Abstract Background There is limited evidence on the relationship between dietary sodium intake (dNa) and brain health, and very little on sex differences in associations. Purpose To study the relationship between dNa and imaging measures of brain health in men and women from the INSIGHT 46 substudy of the MRC National Survey of Health and Development (British 1946 birth cohort). Methods Participants had measurements (dNa using 5-day food diary, anthropometrics, blood pressure (BP) body mass index (BMI)) at 60-64years. Whole-brain and hippocampal volumes, white matter hyperintensity volume (WMHV) and florbetapir amyloid-β positivity were measured using MRI-PET imaging at 69-71years. Associations (β (95% confidence intervals)) were estimated separately in men and women using generalized linear models with robust standard errors adjusted for potential confounders (age, diet quality, energy intake, socioeconomic status) or potential mediators (BMI, BP). Results Participants’ characteristics are shown in Table 1. In women but not men dNa was positively associated with higher WMHV (β[women]=32(1, 72) %/g; p=0.043; β[men]=-10(-27, 11)%/g; p=0.342); this relationship in women was independent of BMI (β = 32(1, 72)%/g; p = 0.043) or systolic BP (β = 31(1, 70)%/g; p=0.041). dNa was not associated with total brain volume, hippocampal volume or amyloid-β positivity in either sex. Conclusions Elevated sodium consumption in the diet is associated with cerebral small vessel disease in older age women but not men. This association was independent of BMI or BP.Table 1

Learning from those who thrive: protective factors and neuroimaging markers in adolescents with complex congenital heart disease and with a favorable neurodevelopmental profile

ABSTRACT Patients with complex congenital heart disease (cCHD) are at risk for neurodevelopmental impairments, yet many patients develop normally. This study investigated associations between a favorable neurodevelopmental profile and protective factors, quality of life (QoL), resilience, and brain development. Adolescents with cCHD (n = 100) were prospectively enrolled. Neurodevelopmental profiles comprised IQ, executive functions, and behavior. Standardized neuropsychological tests and questionnaires were used to assess neurodevelopmental outcomes, family factors, QoL, and resilience. Clinical data were obtained from medical charts. Cerebral MRI was acquired. Specific neurodevelopmental profiles were identified by latent profile analysis and were associated with clinical and family factors, QoL and resilience, and MRI markers. We identified two distinct groups of neurodevelopmental profiles (favorable profile: n = 57, vulnerable profile: n = 43). The favorable profile group had significantly better neurodevelopmental outcome, better family functioning, and better parental mental health compared to the vulnerable profile group. Clinical factors were not significantly associated with profile group. The favorable profile group reported significantly better QoL and resilience and had larger total brain volumes. A positive family environment may be protective for long-term neurodevelopment and may outweigh the role of clinical factors. This study underlines the importance of family-centered care to promote favorable brain development and neurodevelopmental outcome.

Sex Differences in Human Brain Structure at Birth

BackgroundSex differences in human brain anatomy have been well-documented, though remain significantly underexplored during early development. The neonatal period is a critical stage for brain development and can provide key insights into the role that prenatal and early postnatal factors play in shaping sex differences in the brain.MethodsHere, we assessed on-average sex differences in global and regional brain volumes in 514 newborns aged 0–28 days (236 birth-assigned females and 278 birth-assigned males) using data from the developing Human Connectome Project. We also assessed sex-by-age interactions to investigate sex differences in early postnatal brain development.ResultsOn average, males had significantly larger intracranial and total brain volumes, even after controlling for birth weight. After controlling for total brain volume, females showed significantly greater total cortical gray matter volumes, whilst males showed greater total white matter volumes. After controlling for total brain volume in regional comparisons, females had significantly increased white matter volumes in the corpus callosum and increased gray matter volumes in the bilateral parahippocampal gyri (posterior parts), left anterior cingulate gyrus, bilateral parietal lobes, and left caudate nucleus. Males had significantly increased gray matter volumes in the right medial and inferior temporal gyrus (posterior part) and right subthalamic nucleus. Effect sizes ranged from small for regional comparisons to large for global comparisons. Significant sex-by-age interactions were noted in the left anterior cingulate gyrus and left superior temporal gyrus (posterior parts).ConclusionsOur findings demonstrate that sex differences in brain structure are already present at birth and remain comparatively stable during early postnatal development, highlighting an important role of prenatal factors in shaping sex differences in the brain.

Lower activity of cholesteryl ester transfer protein (CETP) and the risk of dementia: a Mendelian randomization analysis

BackgroundElevated concentrations of low-density lipoprotein cholesterol (LDL-C) are linked to dementia risk, and conversely, increased plasma concentrations of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein-A1 (Apo-A1) associate with decreased dementia risk. Inhibition of cholesteryl ester transfer protein (CETP) meaningfully affects the concentrations of these blood lipids and may therefore provide an opportunity to treat dementia.MethodsDrug target Mendelian randomization (MR) was employed to anticipate the on-target effects of lower CETP concentration (μg/mL) on plasma lipids, cardiovascular disease outcomes, autopsy confirmed Lewy body dementia (LBD), as well as Parkinson’s dementia.ResultsMR analysis of lower CETP concentration recapitulated the blood lipid effects observed in clinical trials of CETP-inhibitors, as well as protective effects on coronary heart disease (odds ratio (OR) 0.92, 95% confidence interval (CI) 0.89; 0.96), heart failure, abdominal aortic aneurysm, any stroke, ischemic stroke, and small vessel stroke (0.90, 95%CI 0.85; 0.96). Consideration of dementia related traits indicated that lower CETP concentrations were associated higher total brain volume (0.04 per standard deviation, 95%CI 0.02; 0.06), lower risk of LBD (OR 0.81, 95%CI 0.74; 0.89) and Parkinson’s dementia risk (OR 0.26, 95%CI 0.14; 0.48). APOE4 stratified analyses suggested the LBD effect was most pronounced in APOE-ε4 + participants (OR 0.61 95%CI 0.51; 0.73), compared to APOE-ε4- (OR 0.89 95%CI 0.79; 1.01); interaction p-value 5.81 × 10− 4.ConclusionsThese results suggest that inhibition of CETP may be a viable strategy to treat dementia, with a more pronounced effect expected in APOE-ε4 carriers.

Uncovering mediational pathways behind racial and socioeconomic disparities in brain volumes: insights from the UK Biobank study.

Mediation pathways explaining racial/ethnic and socioeconomic (SES) disparities in structural MRI markers of brain health remain underexplored. We examined racial/ethnic and SES disparities in sMRI markers and tested total, direct, and indirect effects through lifestyle, health-related, and cognition factors using a structural equations modeling approach among 36,184 UK Biobank participants aged 40-70years at baseline assessment (47% men). Race (non-White vs. White) and lower SES-predicted poorer brain sMRI volumetric outcomes at follow-up, with racial/ethnic disparities in sMRI outcomes involving multiple pathways and SES playing a central role in those pathways. Mediational patterns differed across outcomes, with the SES-sMRI total effect being partially mediated for all outcomes. Over 20% of the total effect (TE) of race/ethnicity on WMH was explained by the indirect effect (IE), by a combination of different pathways going through SES, lifestyle, health-related, and cognition factors. This is in contrast to < 10% for total brain, gray matter (GM), white matter (WM), and frontal GM left/right. Another significant finding is that around 57% of the total effect for SES and the normalized white matter hyperintensity (WMH) was attributed to an indirect effect. This effect encompasses many pathways that involve lifestyle, health-related, and cognitive aspects. Aside from WMH, the percent of TE of SES mediated through various pathways ranged from ~ 5% for WM to > 15% up to 36% for most of the remaining sMRI outcomes, which are composed mainly of GM phenotypes. Race and SES were important determinants of brain volumetric outcomes, with partial mediation of racial/ethnic disparities through SES, lifestyle, health-related, and cognition factors.

The Relationship Between Physical Activity and Non-Modifiable Risk Factors on Alzheimer's Disease and Brain Health Markers: A UK Biobank Study.

Modifiable (physical activity) and non-modifiable (sex and genotype) risk factors interact to affect Alzheimer's disease (AD) risk. Further investigation is necessary to understand if these factors influence brain volume and cognition. The study aimed to assess the effect of physical activity, APOE genotype, and sex on AD risk, brain volume, and cognition. UK Biobank data from 2006 to 2023 was accessed. Physical activity was measured by accelerometers, and International Physical Activity Questionnaire. Outcomes were AD incidence; brain volume (ventricular cerebrospinal fluid and total brain); and cognition (executive function, memory, visuospatial ability, processing speed, and reaction time). Logistic and linear regression models were conducted. 69,060 participants met inclusion criteria (mean age: 62.28 years, SD: 7.84; 54.64% female). Higher self-reported (OR = 0.63, 95% CI [0.40, 1.00], p = 0.047) and accelerometer-assessed (OR = 0.96 [0.93, 0.98], p = 0.002) physical activity was associated with lower disease incidence. Smaller ventricular cerebrospinal fluid volume (β= - 65.43 [- 109.68, - 17.40], p = 0.007), and larger total brain volume (β= 4398.46 [165.11, 8631.82], p < 0.001) was associated with increased accelerometer-assessed and self-reported physical activity respectively. Both brain volume analyses were moderated by sex. Increased accelerometer-assessed physical activity levels were associated with faster reaction time (β= - 0.43 [- 0.68, - 0.18], p = 0.001); though poorer visuospatial ability (β= - 0.06 [- 0.09, - 0.03], p < 0.001), and executive function (β= 0.49 [0.31, 0.66], p < 0.001; β= 0.27 [0.10, 0.45], p = 0.002) was related to self-reported physical activity levels. Higher levels of physical activity reduce AD risk independently of non-modifiable risk factors. Moderation of sex on brain volume highlighted the importance of incorporating non-modifiable risk factors in analysis.

18F]FDG Brain Imaging Assessment in Preclinical Acute and Chronic Stress Models Using Statistical Parametric Mapping

Previous studies have used [18F]FDG as a biomarker for depression, anxiety, or chronic stress in cancer patients1,2. However, they lack specific brain patterns and assessment in preclinical models, limiting their translational potential. Hence, we set out to establish preclinical [18F]FDG brain PET as a method to evaluate stress in vivo. Lean C57BL/6J mice were exposed to acute and chronic cooling, restraint, and surgical stress. Obese mice were on a high-fat diet for eight weeks and exposed to cooling and restraint stress. [18F]FDG was injected into fasted animals under brief isoflurane anesthesia via the tail vein. Following a 60-minute distribution phase during acute stress or one day after stress exposure (chronic), animals underwent static μPET/CT scans (Siemens® Inveon). Brain images were spatially normalized, and intensity normalization was performed using proportional and histogram-based scaling3 with PMOD (V. 3.8). Normalized images were analyzed using a brain atlas (M. Mirrione) to extract regional SUV and statistical parametric mapping (SPM12) for voxel-wise comparison. Overall, in lean mice, total brain [18F]FDG-uptake was significantly reduced across all stress models except for acute restraint, whereas total uptake was unaffected in obese mice. Subsequent brain atlas analysis of lean mice revealed changes in regional uptake for all stressors except for chronic cooling, while obese mice were affected by only acute and chronic restraint. Using SPM, we validated stress-specific hypo- and hypermetabolic areas in the brains of lean mice upon acute cooling, acute and chronic restraint, and surgery and in obese mice after chronic restraint (see Figure). We also identified overlapping areas in the brain stem and hypothalamus region following acute cooling and surgery, possibly due to post-surgical hypothermia. Our findings show that static [18F]FDG-imaging is a valuable tool for noninvasively assessing brain activity in a multitude of stress models and a suitable translational tool for stress research in mice. Please click on the 'PDF' for the full abstract!

Individual cognitive traits can be predicted from task-based dynamic functional connectivity with a deep convolutional-recurrent model.

There has been increased interest in understanding the neural substrates of intelligence and several human traits from neuroimaging data. Deep learning can be used to predict different cognitive measures, such as general and fluid intelligence, from different functional magnetic resonance imaging experiments providing information about the main brain areas involved in these predictions. Using neuroimaging and behavioral data from 874 subjects provided by the Human Connectome Project, we predicted various cognitive scores using dynamic functional connectivity derived from language and working memory functional magnetic resonance imaging task states, using a 360-region multimodal atlas. The deep model joins multiscale convolutional and long short-term memory layers and was trained under a 10-fold stratified cross-validation. We removed the confounding effects of gender, age, total brain volume, motion and the multiband reconstruction algorithm using multiple linear regression. We can explain 17.1% and 16% of general intelligence variance for working memory and language tasks, respectively. We showed that task-based dynamic functional connectivity has more predictive power than resting-state dynamic functional connectivity when compared to the literature and that removing confounders significantly reduces the prediction performance. No specific cortical network showed significant relevance in the prediction of general and fluid intelligence, suggesting a spatial homogeneous distribution of the intelligence construct in the brain.

Clinical outcomes and relevance of composite V12 Gy in patients with four or more brain metastases treated with single fraction stereotactic radiosurgery

ObjectiveTissue V12Gy (total brain volume receiving 12Gy including target) can predict for late toxicity in single target benign disease treated with stereotactic radiosurgery(SRS). The value of this metric remains uncertain for multiple brain metastases. This retrospective cohort study reports the outcomes and to evaluate predictors of toxicity in patients with four or more brain metastases treated with single fraction SRS. Methods226 patients with 2160 metastases treated from 2014-21 were retrospectively studied. Symptomatic late toxicity (new/progressive neurological symptoms ≥ 3 months post SRS) with MRI changes suggestive of treatment-effect were analysed. Kaplan-Meier and competing risk analysis was used to assess survival and toxicity respectively. ResultsMedian number of metastases/patient was 6 (range 4-41) and median composite tissue V12Gy (inclusive of PTV) was 11.3cc (IQR 6.1cc - 17.1cc). 16/226 patients developed symptomatic late R-AE and cumulative incidence was 4.9% at 1 year and 6.9% at 2 years. Total target volume was significantly predictive of the risk of late R-AE. Volume of the largest lesion, V12Gy and V15Gy did not predict for late R-AE, but plotted graphs showed suggestions of linear relationships between dosimetric parameters and late R-AE. ConclusionWithin the limitations of this study, the cumulative incidence of symptomatic toxicity remains acceptable despite routinely accepting a composite tissue V12Gy in excess of 10cc to treat multiple brain metastases. Advances in KnowledgeV12Gy has limitations as a plan-quality metric in multiple brain metastases treated with SRS. There is insufficient evidence to have a defined target limit as <10cc.

Segmental MRI Pituitary and Hypothalamus Volumes post Fontan: An analysis of the Australian and New Zealand Fontan Registry.

ObjectiveShort stature, central hypothyroidism and infertility are common in those with a Fontan circulation. Given that the Fontan circulation often results in hepatic portal venous congestion, we hypothesize that the hypothalamic-pituitary portal circulation is also affected, contributing to subsequent hypothalamic-pituitary axis dysfunction. MethodsMRI data from the Australian and New Zealand Fontan Registry (86 cases) was compared to 86 age- and sex- matched normal published controls. Total pituitary volumes (both anterior and posterior glands) were measured using a manual tracing segmentation method, and hypothalamic (and subunit) volumes using an automated segmentation tool. Measured gland volume was normalized to total brain volumes. A generalized linear model was used for statistical analysis. ResultsNormalized total pituitary volumes (nTPV) were increased in Fontan patients compared to controls (p <0.0001), due to an increase in anterior pituitary volumes (nAPV) (p <0.0001), with no difference in normalized posterior pituitary volumes (p = 0.7). Furthermore, normalized anterior and tubular hypothalamic subunit groups) were increased in Fontan patients compared to the controls (p <0.01 and p <0.0001, respectively).The time between Fontan and MRI was positively related to nTPV, nAPV and bilateral hypothalamic volumes. nTPV increased with age, and the increase in nAPV was greater in Fontan patients. ConclusionsSegmental MRI Pituitary and Hypothalamus volumes post Fontan are increased and are related to the time since Fontan procedure. These findings are consistent with venous congestion of the anterior hypothalamic-pituitary portal venous system and may explain the high frequency of endocrine dysfunction in this patient group.

Cardiovascular Ultrasound Predictors for Brain Alterations in Fetuses With Heart Disease: An Exploratory Review of the Literature.

To identify cardiovascular ultrasound predictors for brain anomalies in fetuses with heart disease. A literature search was performed in the following databases: MEDLINE through OVID, EMBASE, Cochrane Registry Center for Controlled Trials (CENTRAL), and LILACS, from their inception until May 2023. Clinical studies, cross-sectional studies, case-control studies, cohorts, and systematic reviews were included. Data extraction was performed, and the risk of bias was assessed using the QUADAS-2 tool. Among 2705 studies evaluated, after filtering information, 10 articles were selected that met the inclusion criteria. These studies noted the following outcomes: a decrease in fetal head circumference, changes in brain maturation measured in days, decreased depth of brain fissures, and a decrease in total brain volume. The studies show a statistically significant correlation with the presence of the following cardiovascular predictors: low or mixed oxygen content in the ascending aorta (p < 0.001), retrograde flow in the aortic arch (p < 0.001), lower z values of the MCA-PI (p < 0.05), higher UA-PI z values (p < 0.01), and lower CPR (p < 0.05). In addition, lower values of left ventricular flow (p < 0.01), ductus arteriosus (p < 0.0001), and combined cardiac output index (p < 0.01) were reported. This review describes the most relevant evidence correlating the effects of hemodynamic changes that lead to states of chronic hypoxia related to the aforementioned changes in the central nervous system.

Updates in Microglial Research with Respect to Brain Cancer

Microglia resides in the microenvironment of the central nervous system (CNS) and is thought to play a key role in the development and progression of brain cancer. This is because it was shown that microglia comprised a large portion of the total brain tumour mass. Besides, the origin of microglia cells in brain tumours is worth understanding as it is important to distinguish the resident macrophages from the circulating macrophages when discussing the pathology of brain tumours. Activated microgliosis has been linked to increased inflammatory mediators like cytokines, growth factors, matrix metalloproteinases (MMPs) and many more, which would facilitate tumourigenesis. Brain tumour cells also proliferate under the influence of signalling pathways, such as the toll-like receptor 2 signals. Vascular endothelial growth factor (VEGF) which is an angiogenic factor aids in the growth of tumour cells. Brain cancer cells rely on suppressing the effector arm of immune system to evade attacks by downregulating major histocompatibility complexes (MHC) class II molecules and inducing the conversion of microglia to an immunosuppressive phenotype. Glioblastoma stem cells (GSCs) that give rise to brain cancers communicate with microglia cells, which determines their growth and invasion potential. Understanding the molecular interactions of brain cancer and microglia cells would help unlock novel treatments via means of immunotherapy, immunosuppressants and utilising microglia cells to deliver nanoparticle drugs to effectively target and treat brain cancer.

The Ratio of Baseline Ventricle Volume to Total Brain Volume Predicts Postoperative Ventriculo-Peritoneal Shunt Dependency after Sporadic Vestibular Schwannoma Surgery.

Background/Objectives: Obstructive hydrocephalus associated with vestibular schwannoma (VS) is the most common in giant VS. Despite tumor removal, some patients may require ongoing ventriculo-peritoneal (VP) surgery. This investigation explores the factors contributing to the requirement for VP surgery following VS surgery in instances of persistent hydrocephalus (HCP). Methods: Volumetric MRI analyses of pre- and postoperative tumor volumes, cerebellum, cerebrum, ventricle system, fourth ventricle, brainstem, and peritumoral edema were conducted using Brainlab Smartbrush and 3D Slicer. The total brain volume was defined as the sum of the cerebrum, cerebellum, and brainstem. ROC analyses were performed to identify the optimum cut-off values of the volumetric data. Results: Permanent cerebrospinal fluid (CSF) diversion after surgery was indicated in 12 patients (12/71; 16.9%). The ratio of baseline volume fraction of brain ventricles to total brain ventricle volume (VTB ratio) was found to predict postoperative VP shunt dependency. The AUC was 0.71 (95% CI: 0.51-0.91), and the optimum threshold value (</≥0.449) yielded a sensitivity and specificity of 67% and 81%, respectively. Multivariable logistic regression analyses of imaging data (pre- and postoperative VS volume, VTB ratio, and extent of resection (%) (EoR)) and patient-specific factors revealed that an increased VTB ratio (≥0.049, OR: 6.2, 95% CI: 1.0-38.0, p = 0.047) and an EoR < 96.4% (OR: 9.1, 95% CI: 1.2-69.3, p = 0.032) were independently associated with postoperative VP shunt dependency. Conclusions: Primary tumor removal remains the best treatment to reduce the risk of postoperative persistent hydrocephalus. However, patients with an increased preoperative VTB ratio are prone to needing postoperative VP shunt surgery and may benefit from perioperative EVD placement.

MGA-Net: A novel mask-guided attention neural network for precision neonatal brain imaging

In this study, we introduce MGA-Net, a novel mask-guided attention neural network, which extends the U-net model for precision neonatal brain imaging. MGA-Net is designed to extract the brain from other structures and reconstruct high-quality brain images. The network employs a common encoder and two decoders: one for brain mask extraction and the other for brain region reconstruction. A key feature of MGA-Net is its high-level mask-guided attention module, which leverages features from the brain mask decoder to enhance image reconstruction. To enable the same encoder and decoder to process both MRI and ultrasound (US) images, MGA-Net integrates sinusoidal positional encoding. This encoding assigns distinct positional values to MRI and US images, allowing the model to effectively learn from both modalities. Consequently, features learned from a single modality can aid in learning a modality with less available data, such as US. We extensively validated the proposed MGA-Net on diverse and independent datasets from varied clinical settings and neonatal age groups. The metrics used for assessment included the DICE similarity coefficient, recall, and accuracy for image segmentation; structural similarity for image reconstruction; and root mean squared error for total brain volume estimation from 3D ultrasound images. Our results demonstrate that MGA-Net significantly outperforms traditional methods, offering superior performance in brain extraction and segmentation while achieving high precision in image reconstruction and volumetric analysis. Thus, MGA-Net represents a robust and effective preprocessing tool for MRI and 3D ultrasound images, marking a significant advance in neuroimaging that enhances both research and clinical diagnostics in the neonatal period and beyond.

Magnitude and kinetics of a set of neuroanatomic volume and thickness together with white matter hyperintensity is definitive of cognitive status and brain age

Even among the subjects classified as cognitively normal, there exists a subset of individuals at a given chronological age (CA) who harbor white matter hyperintensity (WMH) while another subset presents with low or undetectable WMH. Here, we conducted a comprehensive MRI segmentation of neuroanatomic structures along with WMH quantification in groups of cognitively normal (CN), cognitively impaired (CI) individuals, and individuals with an etiological diagnosis of cognitive impairment owing to Alzheimer’s Disease (CI-AD) across the early (50–64 years), intermediate (65–79 years), and late (≥80 years) age groups from the NACC cohort. Neuroanatomic volumetry quantification revealed that thinning of the parahippocampal gyrus in the early (p = 0.016) and intermediate age groups (p = 0.0001) along with an increase in CSF (p = 0.0009) delineates between CI and CI-AD subjects. Although, a significant loss of ~5–10% in volume of gray matter (p(CN vs CI) < 0.0001, p(CN vs CI-AD) < 0.0001), white matter (p(CN vs CI) = 0.002, p(CN vs CI-AD) = 0.0003) and hippocampus (p(CN vs CI) = 0.007, p(CN vs CI-AD) < 0.0001) was evident at the early age groups in the CI and CI-AD compared to CN but it was not distinct between CI and CI-AD. Using the neuroanatomic and WMH volume, and the supervised decision tree-based ML modeling, we have established that a minimum set of Three brain quantities; Total brain (GM + WM), CSF, and WMH volume, provide the Optimal quantitative features discriminative of cognitive status as CN, CI, and CI-AD. Furthermore, using the volume/thickness of 178 neuroanatomic structures, periventricular and deep WMH volume quantification for the 819 CN subjects, we have developed a quantitative index as ‘Brain Age’ (BA) depictive of neuroanatomic health at a given CA. Subjects with elevated WMH load (5–10 ml) had increased BA ( + 0.6 to +4 years) than the CA. Increased BA in the subjects with elevated WMH is suggestive of WMH-induced vascular insult leading to accelerated and early structural loss than expected for a given CA. Henceforth, this study establishes that quantification of WMH together with an optimal number of neuroanatomic features is mandatory to delve into the biological underpinning of aging and aging-associated cognitive disorders.

Ratio of pulmonary artery diameter to ascending aortic diameter and its association with right ventricular failure after left ventricular assist device implantation

BackgroundSeveral invasive hemodynamic parameters help predict right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation. However, prediction using non-invasive parameters alone has not been established. The ratio of the diameters of the pulmonary artery (PAD) to those of the ascending aorta (AoD) may indicate past hemodynamic load and cardiac dysfunction. We aimed to investigate a predictive model for RVF after LVAD implantation using non-invasive parameters including PAD/AoD ratio. MethodsWe studied 141 patients who underwent primary LVAD implantation and 117 healthy individuals with computed tomography (CT) data. RVF was defined as the need for a subsequent right ventricular assist device or intravenous inotrope administration for more than 30 days after LVAD implantation. The PAD/AoD ratio was measured at the level of the pulmonary artery bifurcation on the CT transaxial slices. ResultsRVF was observed in 29 patients. The correlation between PAD and AoD differed among healthy individuals, patients with and without RVF. Patients with RVF had higher total bilirubin and log brain natriuretic peptide (BNP) levels, a lower left ventricular end-diastolic diameter (LVDd) index, and a higher PAD/AoD ratio than those without RVF. Decision tree analysis indicated that the subgroup with a high PAD/AoD ratio (≥1.09) and a small LVDd index (<35.4 mm/m2) showed the highest probability of RVF (100 %), while the subgroup with a low PAD/AoD ratio (<1.09) and low log BNP (<2.79) showed the lowest probability of RVF (1 %). ConclusionCombining non-invasive parameters with the PAD/AoD ratio can predict RVF with high accuracy.

Baseline and Longitudinal MRI Markers Associated With 16-Year Mortality in Patients With Cerebral Small Vessel Disease.

Information on whether small vessel disease (SVD) reduces life expectancy is limited. Moreover, the excess mortality risk attributed specifically to SVD compared with controls from the general population has not been evaluated. This study aimed to investigate the baseline and progression of MRI markers of SVD associated with mortality in a 16-year follow-up cohort study and to determine the excess long-term mortality risk of patients with SVD. Participants with SVD from the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort (RUN DMC) study (with MRI assessments in 2006, 2011, 2015, and 2020) were followed until their death or December 1, 2021. Adjusted Cox regression analyses and linear mixed-effect regression models were used to investigate the association between MRI markers of SVD and mortality. The excess mortality risk of SVD was calculated by comparing mortality data of the RUN DMC study with the general population matched by sex, age, and calendar year. 200 of 503 (39.9%) participants died during a follow-up period of 15.9 years. Cause of death was available for 182 (91%) participants. Baseline white matter hyperintensity volume (HR 1.3 per 1-SD increase [95% CI 1.1-1.5], p = 0.010), presence of lacunes (1.5 [95% CI 1.1-2.0], p = 0.008), mean diffusivity (HR 1.1 per 1-SD increase [95% CI 1.1-1.2], p = 0.001), and total brain volume (HR 1.5 per 1-SD decrease [95% CI 1.3-1.9], p < 0.001) were associated with all-cause mortality after adjusting for age, sex, and vascular risk factors. Total brain volume decrease over time was associated with all-cause mortality after adjusting for age, sex, and vascular risk factors (HR 1.3 per 1-SD decrease [95% CI 1.1-1.7], p = 0.035), and gray matter volume decrease remained significant after additionally adjusting for its baseline volume (1.3 per 1-SD decrease [1.1-1.6], p = 0.019). Participants with a Fazekas score of 3, presence of lacunes, or lower microstructural integrity had an excess long-term mortality risk (21.8, 15.7, 10.1 per 1,000 person-years, respectively) compared with the general population. Excess long-term mortality risk only exists in patients with severe SVD (Fazekas score of 3, presence of lacunes, or lower microstructural integrity). This could help in assisting clinicians to predict the clinical outcomes of patients with SVD by severity.

Interactions between muscle volume and body mass index on brain structure in the UK Biobank.

Low skeletal muscle volume may increase dementia risk through mechanisms affecting brain structure. However, it is unclear whether this relationship exists outside of sarcopenia and/or varies by other factors. We aimed to study the interplay between skeletal muscle volume and factors, such as age, sex, and body mass index (BMI), in explaining brain structure at midlife in a cohort without sarcopenia. We used abdominal and brain magnetic resonance imaging (MRI) data from a population-based cohort enrolled in the UK Biobank. The following measures were derived: thigh fat-free muscle volume (FFMV), total brain volume (TBV), gray matter volume (GMV), white matter volume (WMV), total hippocampal volume (THV), and white matter hyperintensity volume (WMHV). Participants below sex-based grip strength thresholds suggesting probable sarcopenia were excluded. Linear regression analysis was used to study the interaction or mediation effects of age, sex, and BMI on the associations between FFMV and brain volumes. Data were available for 20,353 participants (median age 64 years, 53% female). We found interactions between thigh FFMV, BMI, and age (all p < 0.05). Greater thigh FFMV was associated with better brain volumes in those aged <64 years with normal (TBV: β = 2.0 ml/L, p = 0.004; GMV: β = 0.8 ml/L, p = 0.04; WMV: β = 1.1 ml/L, p = 0.006; WMHV: β = -0.2 ml/L, p = 3.7 × 10-5) or low BMI (TBV: β = 21.2 ml/L, p = 0.003; WMV: β = 13.3 ml/L, p = 0.002, WMHV: β = -1.1 ml/L, p = 0.04). Greater thigh muscle volume correlates with better brain volumes at midlife in people without sarcopenia, but this relationship weakens with greater age and BMI. Further study is required to investigate the underlying mechanisms to understand which components of body composition are potentially modifiable risk factors for dementia.