Association of Acute Infarct Topography With Development of Cerebral Palsy and Neurologic Impairment in Neonates With Stroke.

BACKGROUND AND OBJECTIVES: Research investigating neonatal arterial ischemic stroke (NAIS) outcomes have shown that combined cortical and basal ganglia infarction or involvement of the corticospinal tract predict cerebral palsy (CP). The research question was whether voxel-based lesion-symptom mapping (VLSM) on acute MRI can identify brain regions associated with CP and neurodevelopmental impairments in NAIS. METHODS: Newborns were recruited from prospective Australian and Swiss pediatric stroke registries. CP diagnosis was based on clinical examination. Language and cognitive-behavioral impairments were assessed using the Pediatric Stroke Outcome Measure, dichotomized to good (0-0.5) or poor (≥1), at ≥18 months of age. Infarcts were manually segmented using diffusion-weighted imaging, registered to a neonatal-specific brain template. VLSM was conducted using MATLAB SPM12 toolbox. A general linear model was used to correlate lesion masks with motor, language, and cognitive-behavioral outcomes. Voxel-wise t-statistics were calculated, correcting for multiple comparisons using family-wise error (FWE) rate. RESULTS: Eighty-five newborns met the inclusion criteria. Infarct lateralization was left hemisphere (62%), right (8%), and bilateral (30%). At a median age of 2.1 years (interquartile range 1.9-2.6), 33% developed CP and 42% had neurologic impairments. Fifty-four grey and white matter regions correlated with CP (t > 4.33; FWE < 0.05), including primary motor pathway regions, such as the precentral gyrus, and cerebral peduncle, and regions functionally connected to the primary motor pathway, such as the pallidum, and corpus callosum motor segment. No significant correlations were found for language or cognitive-behavioral outcomes. DISCUSSION: CP after NAIS correlates with infarct regions directly involved in motor control and in functionally connected regions. Areas associated with language or cognitive-behavioral impairment are less clear.

Associations of Sex, Age, and Cardiometabolic Risk Profiles With Brain Structure and Cognition: A UK Biobank Latent Class Analysis.

BACKGROUND AND OBJECTIVES: It is unknown whether there are sex-related profiles of cardiometabolic health that contribute differently to age-related changes in brain health during midlife. We studied how latent classes of middle-aged individuals clustering by age, sex, menopause, and cardiometabolic health were associated with brain structure and cognitive performance. METHODS: Health, brain, and abdominal MRI data from the UK Biobank cohort (men and women aged >40 years in the United Kingdom) were used. We applied latent class analysis to identify groups of individuals based on age, sex, menopausal status, and cardiometabolic health. We examined associations of class membership with brain volumes (total brain volume [TBV], gray matter volume [GMV], white matter volume [WMV], hippocampal volume, and white matter hyperintensity volume) and cognitive performance. RESULTS: Data were available for 36,420 individuals (mean age 64.9 years, 48.5% women). Eight latent classes differing in age, sex, and cardiometabolic risk were identified. Class 1 (reference class) included individuals with the lowest probability of older age and cardiometabolic risk, and the healthiest levels of brain volumes and cognition. In those aged >60 years, but not in those aged 50-60 years, the negative associations of age with TBV, GMV, and WMV were greater in the class comprising healthier older women than classes comprising older men of varying cardiometabolic and vascular health. There were no age-class interactions for cognitive test performance. DISCUSSION: Latent class analysis detected groups of middle-aged individuals clustering by cardiometabolic health. The relationship of age with brain volumes varies by sex, menopausal status, and cardiometabolic health profile.

Mild brain lesions do not affect brain volumes in moderate-late preterm infants.

PURPOSE: It is unknown whether frequently occurring mild brain lesions affect brain volumes in moderate (MP2; 32+0-33+6 weeks' gestation) and late (LP3; 34+0-35+6 weeks' gestation) preterm infants. Therefore, we aimed to investigate the effect of mild brain lesions on brain volumes in moderate-late preterm (MLPT4) infants and to compare brain volumes between MP and LP infants. METHODS: From August 2017 to November 2019, eligible MLPT infants born at Isala Women and Children's Hospital were enrolled in a prospective cohort study (Brain Imaging in Moderate-late Preterm infants 'BIMP-study'). MRI was performed around term equivalent age (TEA5). MRI scans were assessed for (mild) brain lesions. T2-weighted images were used for automatic segmentation of eight brain structures. Linear regression analysis was performed to compare absolute and relative brain volumes between infants with and without mild brain lesions and between MP and LP infants. RESULTS: 36 MP and 68 LP infants were included. In infants with mild brain lesions, intracranial volume (B = 27.4 cm3, p = 0.02), cerebrospinal fluid (B = 8.78 cm3, p = 0.01) and cerebellar volumes (B = 1.70 cm3, p = 0.03) were significantly larger compared to infants without mild brain lesions. After correction for weight and postmenstrual age at MRI, these volumes were no longer significantly different. LP infants had larger brain volumes than MP infants, but differences were not significant. Relative brain volumes showed no significant differences in both analyses. CONCLUSION: Neither having mild brain lesions, nor being born moderate prematurely affected brain volumes at TEA in MLPT infants.

Neonatal Brain Tissue Classification with Morphological Adaptation and Unified Segmentation.

Measuring the distribution of brain tissue types (tissue classification) in neonates is necessary for studying typical and atypical brain development, such as that associated with preterm birth, and may provide biomarkers for neurodevelopmental outcomes. Compared with magnetic resonance images of adults, neonatal images present specific challenges that require the development of specialized, population-specific methods. This paper introduces MANTiS (Morphologically Adaptive Neonatal Tissue Segmentation), which extends the unified segmentation approach to tissue classification implemented in Statistical Parametric Mapping (SPM) software to neonates. MANTiS utilizes a combination of unified segmentation, template adaptation via morphological segmentation tools and topological filtering, to segment the neonatal brain into eight tissue classes: cortical gray matter, white matter, deep nuclear gray matter, cerebellum, brainstem, cerebrospinal fluid (CSF), hippocampus and amygdala. We evaluated the performance of MANTiS using two independent datasets. The first dataset, provided by the NeoBrainS12 challenge, consisted of coronal T 2-weighted images of preterm infants (born ≤30 weeks' gestation) acquired at 30 weeks' corrected gestational age (n = 5), coronal T 2-weighted images of preterm infants acquired at 40 weeks' corrected gestational age (n = 5) and axial T 2-weighted images of preterm infants acquired at 40 weeks' corrected gestational age (n = 5). The second dataset, provided by the Washington University NeuroDevelopmental Research (WUNDeR) group, consisted of T 2-weighted images of preterm infants (born <30 weeks' gestation) acquired shortly after birth (n = 12), preterm infants acquired at term-equivalent age (n = 12), and healthy term-born infants (born ≥38 weeks' gestation) acquired within the first 9 days of life (n = 12). For the NeoBrainS12 dataset, mean Dice scores comparing MANTiS with manual segmentations were all above 0.7, except for the cortical gray matter for coronal images acquired at 30 weeks. This demonstrates that MANTiS' performance is competitive with existing techniques. For the WUNDeR dataset, mean Dice scores comparing MANTiS with manually edited segmentations demonstrated good agreement, where all scores were above 0.75, except for the hippocampus and amygdala. The results show that MANTiS is able to segment neonatal brain tissues well, even in images that have brain abnormalities common in preterm infants. MANTiS is available for download as an SPM toolbox from http://developmentalimagingmcri.github.io/mantis.

Association of Alzheimer's disease GWAS loci with MRI markers of brain aging.

Whether novel risk variants of Alzheimer's disease (AD) identified through genome-wide association studies also influence magnetic resonance imaging-based intermediate phenotypes of AD in the general population is unclear. We studied association of 24 AD risk loci with intracranial volume, total brain volume, hippocampal volume (HV), white matter hyperintensity burden, and brain infarcts in a meta-analysis of genetic association studies from large population-based samples (N = 8175-11,550). In single-SNP based tests, AD risk allele of APOE (rs2075650) was associated with smaller HV (p = 0.0054) and CD33 (rs3865444) with smaller intracranial volume (p = 0.0058). In gene-based tests, there was associations of HLA-DRB1 with total brain volume (p = 0.0006) and BIN1 with HV (p = 0.00089). A weighted AD genetic risk score was associated with smaller HV (beta ± SE = -0.047 ± 0.013, p = 0.00041), even after excluding the APOE locus (p = 0.029). However, only association of AD genetic risk score with HV, including APOE, was significant after multiple testing correction (including number of independent phenotypes tested). These results suggest that novel AD genetic risk variants may contribute to structural brain aging in nondemented older community persons.

Carotid artery anatomy and geometry as risk factors for carotid atherosclerotic disease.

BACKGROUND AND PURPOSE: Traditional vascular risk factors do not completely explain the asymmetry, racial, and sex differences in carotid artery disease. Carotid anatomy and geometry may play a role in the pathogenesis of internal carotid artery (ICA) stenosis, but their effects are unknown. We hypothesized that carotid artery anatomy and geometry would be independently associated with ICA stenosis. METHOD: This is a retrospective study of patients with CT angiography at Monash Medical Centre, 2006 to 2007. Carotid arteries were segmented using semiautomated methods to estimate measures of carotid anatomy and geometry. Measurements of carotid artery geometry were performed according to the recent article by Thomas and colleagues. ICA stenosis was dichotomized as <30% or ≥ 30% stenosis. Cluster logistic regression was used to examine the associations of anatomy and geometry with stenosis accounting for the paired arteries within subjects, adjusting for age, sex, and vascular risk factors. RESULTS: Mean age of the sample (n=178) was 68.4 years (SD, 14 years). The following were independently associated with ICA stenosis: ICA radius at the bifurcation (OR, 0.20; 95% CI, 0.14-0.29), ICA angle (OR, 1.05 per degree increment; 95% CI, 1.04-1.07), age (OR, 1.05 per year increment; 95% CI, 1.03-1.07), male sex (OR, 1.72; 95% CI, 1.08-2.8), and ever-smoker (OR, 1.85; 95% CI, 1.15-2.96). CONCLUSIONS: Carotid anatomy and geometry may enhance the risk of stenosis independent of traditional vascular risk factors and may be of help in very early identification of patients at high risk of developing carotid artery atherosclerosis for aggressive intervention.

Does the principle of minimum work apply at the carotid bifurcation: a retrospective cohort study.

BACKGROUND: There is recent interest in the role of carotid bifurcation anatomy, geometry and hemodynamic factors in the pathogenesis of carotid artery atherosclerosis. Certain anatomical and geometric configurations at the carotid bifurcation have been linked to disturbed flow. It has been proposed that vascular dimensions are selected to minimize energy required to maintain blood flow, and that this occurs when an exponent of 3 relates the radii of parent and daughter arteries. We evaluate whether the dimensions of bifurcation of the extracranial carotid artery follow this principle of minimum work. METHODS: This study involved subjects who had computed tomographic angiography (CTA) at our institution between 2006 and 2007. Radii of the common, internal and external carotid arteries were determined. The exponent was determined for individual bifurcations using numerical methods and for the sample using nonlinear regression. RESULTS: Mean age for 45 participants was 56.9 ± 16.5 years with 26 males. Prevalence of vascular risk factors was: hypertension--48%, smoking--23%, diabetes--16.7%, hyperlipidemia--51%, ischemic heart disease--18.7%.The value of the exponent ranged from 1.3 to 1.6, depending on estimation methodology. CONCLUSIONS: The principle of minimum work (defined by an exponent of 3) may not apply at the carotid bifurcation. Additional factors may play a role in the relationship between the radii of the parent and daughter vessels.

Structural and functional correlates of unilateral mesial temporal lobe spatial memory impairment.

The aim of this study was to explore the effects of preoperative and postoperative lateralized mesial temporal damage on three measures of spatial learning: navigation, object location and plan drawing, and to determine the relationship between volumetry of the hippocampus and memory performance. Fifteen patients with well-characterized unilateral hippocampal sclerosis, 15 patients who had undergone unilateral anterior temporal lobectomy (ATL), and a comparison group consisting of 15 patients with idiopathic generalized epilepsy and 25 neurologically healthy participants explored a novel virtual environment. Volumetric analyses of both hippocampi were conducted on unilateral hippocampal sclerosis and idiopathic generalized epilepsy patients' T(1)-weighted magnetic resonance imaging scans. Performance of temporal lobe epilepsy (TLE) patients (either unilateral hippocampal sclerosis or anterior temporal lobectomy) on the different spatial memory variables, namely navigation, object location and plan drawing, was significantly worse relative to the comparison groups (either idiopathic generalized epilepsy or controls). Patients with right TLE did not differ from patients with left TLE on any of the spatial memory measures. An index of absolute hippocampal asymmetry did not correlate with any of the spatial memory measures. Together, our lesion and volumetry findings suggest that the domain of spatial memory is systematically related to the integrity of both right and left mesial temporal lobe, and is unlikely to be a strongly lateralized function. From the standpoint of cerebral organization (lateralization), the notion of material-specificity, which postulates that all components of verbal and spatial memory are lateralized in their entirety to the left and right hemispheres, respectively, requires modification. Instead it would appear that the notion of task-specificity is a more accurate description of patterns of lateralization of spatial memory.