Association between serum triglycerides and stroke type, severity, and prognosis. Analysis in 6558 patients.

BACKGROUND AND OBJECTIVES: Hypertriglyceridemia (HT) may increase the risk of stroke. Limited studies have shown that stroke severity and infarction size are smaller in patients with HT. We explored the relationship between triglyceride levels and stroke risk factors, severity and outcome in a large prospective database. DESIGN: Prospective Cross-sectional study. SETTING: We retrospectively interrogated the Qatar Stroke Database in all patients admitted between 2014-2022 with acute ischemic stroke and evaluated the relationship between triglyceride, diabetes, stroke severity (measured on NIHSS), stroke type (TOAST classification) and the short- (mRS at 90 days) and long-term outcomes (MACE at 1 year) in patients with HT. PARTICIPANTS: Six thousand five hundred fifty-eight patients ≥20 years were included in this study RESULTS: Six thousand five hundred fifty-eight patients with ischemic stroke [mean age 54.6 ± 12. 9; male 82.1%) were included. Triglyceride levels upon admission were low-normal (≤1.1 mmol/L) in 2019 patients, high-normal (1.2-1.7 mmol/L) in 2142 patients, borderline-high (1.8-2.2 mmol/L) in 1072 patients and high (≥2.3 mmol/L) in 1325 patients. Higher triglyceride levels were associated with stroke and increased likelihood of having diabetes, obesity, active smoking, and small vessel/lacunar stroke type. An inverse relationship was noted whereby higher triglyceride levels were associated with lower stroke severity and reduced likelihood of poorer outcome (mRS 3-6) at discharge and 90 days. Long-term MACE events were less frequent in patients with higher triglyceride levels. After adjusting age, gender, diabetes, prior stroke, CAD, and obesity, multivariate analysis showed that hypertension and triglyceride levels were higher in mild ischemic strokes patients. CONCLUSIONS: Increasing triglycerides are associated with higher risk of small vessel disease and requires further prospective cohort studies for confirmation.

Cardiac Magnetic Resonance Imaging in Individuals With Prenatal Alcohol Exposure.

Background: Prenatal alcohol exposure (PAE) has teratogenic effects on numerous body systems including the heart. However, research magnetic resonance imaging (MRI) studies in humans with PAE have thus far been limited to the brain. This study aims to use MRI to examine heart structure and function, brain volumes, and body composition in children and adolescents with PAE. Methods: Heart, brain, and abdominal 3T MRI of 17 children, adolescents, and young adults with PAE and 53 unexposed controls was acquired to measure: (1) left ventricular ejection fraction, end-diastolic volume, end-systolic volume, stroke volume, cardiac output, longitudinal strain, circumferential strain, and heart mass; (2) total brain, cerebellum, white matter, grey matter, caudate, thalamus, putamen, and globus pallidus volumes; and (3) subcutaneous fat, visceral fat, muscle fat, and muscle (body composition). Results: Cardiac MRI revealed no abnormalities in the PAE group on evaluation by a paediatric cardiologist and by statistical comparison with a control group. Cardiac parameters in both groups were in line with previous reports, including expected sex- and age-related differences. Cerebellum, caudate, and globus pallidus volumes were all smaller. Body mass index and subcutaneous fat percent were higher in females with PAE relative to control females, but lower in males with PAE relative to control males. Conclusions: Children with PAE did not have abnormalities in MRI-derived measures of cardiac structure or function despite smaller brain volumes and sex-specific differences in body composition relative to healthy controls.

Contexte: L'exposition prénatale à l'alcool (EPA) engendre des effets tératogènes dans de nombreux systèmes et organes du corps humain, notamment le cœur. Cependant, la recherche à l'aide de l'imagerie par résonance magnétique (IRM) chez des humains ayant des antécédents d'EPA s'est limitée aux effets sur le cerveau jusqu'à maintenant. Cette étude vise à utiliser l'IRM pour examiner la fonction et la structure du cœur, le volume de diverses parties du cerveau ainsi que la composition corporelle chez des enfants et des adolescents ayant des antécédents d'EPA. Méthodologie: Chez 17 enfants, adolescents et jeunes adultes ayant été exposés à l'alcool au stade prénatal et chez 53 personnes n'ayant pas d'antécédents d'EPA, des images du cœur, du cerveau et de l'abdomen ont été acquises par la technique d'IRM 3T afin de mesurer : i) la fraction d'éjection du ventricule gauche, le volume télédiastolique, le volume télésystolique, le volume de sang éjecté, le débit cardiaque, la déformation longitudinale, la déformation circonférentielle et la masse cardiaque; ii) les volumes du cerveau en entier, du cervelet, de la substance blanche, de la substance grise, du noyau caudé, du thalamus, du putamen et du globus pallidus; et iii) le pourcentage de tissu adipeux contenu sous la peau, dans les viscères et dans les muscles ainsi que le pourcentage de muscles (composition corporelle). Résultats: Les images obtenues par l'IRM cardiaque n'ont pas révélé d'anomalies chez le groupe ayant des antécédents d'EPA après évaluation par un cardiologue pédiatrique et comparaison statistique avec le groupe témoin. Les paramètres cardiaques mesurés chez les deux groupes reflétaient les données ayant été précédemment rapportées, y compris les attentes liées aux différences quant au sexe et à l'âge. Les volumes du cervelet, du noyau caudé et du globus pallidus étaient diminués chez les personnes ayant des antécédents d'EPA. Alors que l'indice de masse corporelle et le pourcentage de tissu adipeux sous-cutané étaient plus élevés chez les personnes de sexe féminin ayant des antécédents d'EPA que chez les personnes de sexe féminin appartenant au groupe témoin, ces mêmes paramètres se trouvaient diminués chez les personnes de sexe masculin ayant des antécédents d'EPA comparativement aux personnes de sexe masculin appartenant au groupe témoin. Conclusions: Chez les enfants ayant des antécédents d'EPA, les mesures de la fonction et de la structure cardiaques dérivées des données de l'IRM ne présentaient pas d'anomalies, bien qu'une diminution du volume de certaines parties du cerveau et des différences dans la composition corporelle propres au sexe aient été observées dans ce groupe comparativement aux personnes en santé appartenant au groupe témoin.

A Normative Brain MRI Database of Neurotypical Participants from 5 to 90 Years of Age.

Brain magnetic resonance imaging (MRI) studies of clinical populations often require comparison to a normative 'control' cohort, usually of similar age/sex, scanned with the same protocol. The goal here was to create a normative brain MRI database of common quantitative methods to be used in comparisons with a variety of neurological disorders across the lifespan. 378 neurotypical controls (aged 5-90 years; median 31 years; 216 females, 162 males) completed brain MRI, cognitive testing, clinical assessment, and a demographics questionnaire. In addition, this large normative sample will yield novel insight into healthy brain development and aging.

Longitudinal hippocampal diffusion-weighted imaging and T2 relaxometry demonstrate regional abnormalities which are stable and predict subfield pathology in temporal lobe epilepsy.

OBJECTIVE: High-resolution (1 mm isotropic) diffusion tensor imaging (DTI) of the hippocampus in temporal lobe epilepsy (TLE) patients has shown patterns of hippocampal subfield diffusion abnormalities, which were consistent with hippocampal sclerosis (HS) subtype on surgical histology. The objectives of this longitudinal imaging study were to determine the stability of focal hippocampus diffusion changes over time in TLE patients, compare diffusion and quantitative T2 abnormalities of the sclerotic hippocampus, and correlate presurgical mean diffusivity (MD) and T2 maps with postsurgical histology. METHODS: Nineteen TLE patients and 19 controls underwent two high-resolution (1 mm isotropic) DTI and 1.1 × 1.1 × 1 mm3  T2 relaxometry scans (in a subset of 16 TLE patients and 9 controls) of the hippocampus at 3T, with a 2.6 ± 0.8 year inter-scan interval. Within-participant hippocampal volume, MD and T2 were compared between the scans. Contralateral hippocampal changes 2.3 ± 1.0 years after surgery and ipsilateral preoperative MD maps versus postoperative subfield histopathology were evaluated in eight patients who underwent surgical resection of the hippocampus. RESULTS: Reduced volume and elevated MD and T2 of sclerotic hippocampi remained unchanged between longitudinal scans. Focal regions of elevated MD and T2 in bilateral hippocampi of HS TLE were detected consistently at both scans. Regions of high MD and T2 correlated and remained consistent over time. Volume, MD, and T2 remained unchanged in postoperative contralateral hippocampus. Regional elevations of MD identified subfield neuron loss on postsurgical histology with 88% sensitivity and 88% specificity. Focal T2 elevations identified subfield neuron loss with 75% sensitivity and 88% specificity. SIGNIFICANCE: Diffusion and T2 abnormalities in ipsilateral and contralateral hippocampi remained unchanged between the scans suggesting permanent microstructural alterations. MD and T2 demonstrated good sensitivity and specificity to detect hippocampal subfield neuron loss on postsurgical histology, supporting the potential that high-resolution hippocampal DTI and T2 could be used to diagnose HS subtype before surgery.

High-resolution diffusion tensor imaging identifies hippocampal volume loss without diffusion changes in individuals with prenatal alcohol exposure.

BACKGROUND: Magnetic resonance imaging (MRI) studies of prenatal alcohol exposure (PAE) commonly report reduced hippocampal volumes, which animal models suggest may result from microstructural changes that include cell loss and altered myelination. Diffusion tensor imaging (DTI) is sensitive to microstructural changes but has not yet been used to study the hippocampus in PAE. METHODS: Thirty-six healthy controls (19 females; 8 to 24 years) and 19 participants with PAE (8 females; 8 to 23 years) underwent high-resolution (1 mm isotropic) DTI, anatomical T1-weighted imaging, and cognitive testing. Whole-hippocampus, head, body, and tail subregions were manually segmented to yield DTI metrics (mean, axial, and radial diffusivities-MD, AD, and RD; fractional anisotropy-FA), volumes, and qualitative assessments of hippocampal morphology and digitations. Automated segmentation of T1-weighted images was used to corroborate manual whole-hippocampus volumes. RESULTS: Gross morphology and digitation counts were similar in both groups. Whole-hippocampus volumes were 18% smaller in the PAE than the control group on manually traced diffusion images, but automated T1-weighted image segmentations were not significantly different. Subregion segmentation on DTI revealed reduced volumes of the body and tail, but not the head. There were no significant differences in diffusion metrics between groups for any hippocampal region. Correlations between age and volume were not significant in either group, whereas negative correlations between age and whole-hippocampus MD/AD/RD, and head/body (but not tail) MD/AD/RD were significant in both groups. There were no significant effects of sex, group by age, or group by sex for any hippocampal metric. In controls, seven positive linear correlations were found between hippocampal volume and cognition; five of these were left lateralized and included episodic and working memory, and two were right lateralized and included working memory and processing speed. In PAE, left tail MD positively correlated with executive functioning, and right head MD negatively correlated with episodic memory. CONCLUSIONS: Reductions of hippocampal volumes and altered relationships with memory suggest disrupted hippocampal development in PAE.

Lifespan Volume Trajectories From Non-harmonized T1-Weighted MRI Do Not Differ After Site Correction Based on Traveling Human Phantoms.

Multi-site imaging consortiums strive to increase participant numbers by pooling data across sites, but scanner related differences can bias results. This study combines data from three research MRI centers, including three different scanner models from two vendors, to examine non-harmonized T1-weighted brain imaging protocols in two cohorts. First, 23 human traveling phantoms were scanned twice each at all three sites (six scans per person; 138 scans total) to quantify within-participant variability of brain volumes (total brain, white matter, gray matter, lateral ventricles, thalamus, caudate, putamen and globus pallidus), and to calculate site-specific correction factors for each structure. Sample size calculations were used to determine the number of traveling phantoms needed to achieve effect sizes for observed differences to help guide future studies. Next, cross-sectional lifespan volume trajectories were examined in 856 healthy participants (5-91 years of age) scanned at these sites. Cross-sectional trajectories of volume versus age for each structure were then compared before and after application of traveling phantom based site-specific correction factors, as well as correction using the open-source method ComBat. Although small systematic differences between sites were observed in the traveling phantom analysis, correction for site using either method had little impact on the lifespan trajectories. Only white matter had small but significant differences in the intercept parameter after ComBat correction (but not traveling phantom based correction), while no other fits differed. This suggests that age-related changes over the lifespan outweigh systematic differences between scanners for volumetric analysis. This work will help guide pooling of multisite datasets as well as meta-analyses of data from non-harmonized protocols.

High resolution diffusion tensor imaging of the hippocampus across the healthy lifespan.

The human hippocampus is difficult to image given its small size, location, shape, and complex internal architecture. Structural magnetic resonance imaging (MRI) has shown age-related hippocampal volume changes that vary along the anterior-posterior axis. Diffusion tensor imaging (DTI) provides complementary measures related to microstructure, but there are few hippocampus DTI studies investigating change with age in healthy participants, and all have been limited by low spatial resolution. The current study uses high resolution 1 mm isotropic DTI of 153 healthy volunteers aged 5-74 years to investigate diffusion and volume trajectories of the hippocampus (whole, head, body, and tail) and correlations with memory. Hippocampal volume showed age-related changes that differed between head (peaking at midlife), body (no changes), and tail (decreasing across the age span). Fractional anisotropy (FA) and mean, axial, and radial diffusivities (MD, AD, RD) yielded peaks or minima, respectively, at ~30-35 years in all three subregions of the hippocampus. Greater magnitude changes were observed during development than in aging. Age trajectories for both volume and DTI were similar between males and females. Correlations between tests of memory and FA and/or volume were significant in younger subjects (5-17 years), but not in 18-49 year olds or 50-74 year olds. MD was significantly correlated with memory performance in 18-49 year olds, but not in other age groups. Given the diffusion-weighted image contrast and resolution, head digitations could be examined revealing that the majority of subjects had 3-4 (48%) or 2 (32%) bilaterally with no effect of age. One millimeter isotropic DTI yielded high quality diffusion-weighted maps of the human hippocampus that showed regionally specific age effects and cognitive correlations along the anterior-posterior axis from 5 to 74 years.

R2* and quantitative susceptibility mapping in deep gray matter of 498 healthy controls from 5 to 90 years.

Putative MRI markers of iron in deep gray matter have demonstrated age related changes during discrete periods of healthy childhood or adulthood, but few studies have included subjects across the lifespan. This study reports both transverse relaxation rate (R2*) and quantitative susceptibility mapping (QSM) of four primary deep gray matter regions (thalamus, putamen, caudate, and globus pallidus) in 498 healthy individuals aged 5-90 years. In the caudate, putamen, and globus pallidus, increases of QSM and R2* were steepest during childhood continuing gradually throughout adulthood, except caudate susceptibility which reached a plateau in the late 30s. The thalamus had a unique profile with steeper changes of R2* (reflecting additive effects of myelin and iron) than QSM during childhood, both reaching a plateau in the mid-30s to early 40s and decreasing thereafter. There were no hemispheric or sex differences for any region. Notably, both R2* and QSM values showed more inter-subject variability with increasing age from 5 to 90 years, potentially reflecting a common starting point in iron/myelination during childhood that diverges as a result of lifestyle and genetic factors that accumulate with age.

Peri-hematoma corticospinal tract integrity in intracerebral hemorrhage patients: A diffusion-tensor imaging study.

BACKGROUND: The impact of perihematoma edema in Intracerebral Hemorrhage (ICH) on white matter integrity is uncertain. Fractional Anisotropy (FA), as measured with Diffusion Tensor Imaging (DTI), can be used to assess white matter microstructure. We tested the hypotheses that sections of the Corticospinal Tract (CST) passing through perihematoma edema would 1) have low FA relative to the contralateral CST and 2) would predict NIHSS motor score in ICH patients. METHODS: Patients were prospectively imaged with DTI at 48 h and 7 days after onset. Edema volume/extent was measured on CT at baseline and 24 h. FA, mean, axial and radial diffusivity were measured in the perihematoma edema, contralateral CST and sections of CST passing through the edema ('edematous CST'). RESULTS: Patients (n = 27, mean age 67 ± 13) were scanned with DTI at a median (IQR) of 42.3 (24.5) hours and 7.7 (1.8) days from onset. Median acute ICH volume was 8.8 (22) ml. FA in edematous CST at 72 h was decreased (0.37 ± 0.03) relative to contralateral CST (0.52 ± 0.06; p < 0.0001). Day 7 FA in edematous CST (0.35 ± 0.08) was also decreased compared to contralateral CST (0.54 ± 0.06; p < 0.0001). FA remained stable between 72 h (0.37 ± 0.03) and day 7 (0.35 ± 0.07; p = 0.350). FA at 72 h (ρ = -0.22, p = 0.420) and day 7 (ρ = -0.14, p = 0.624) was unrelated to 90-day motor score. CONCLUSIONS: FA is decreased in the CST where it passes through the edema. Decreased FA in the edematous CST remained stable over time, was unrelated to motor score, and may represent water infiltration into the tracts rather than axonal injury.

Altered brain white matter connectome in children and adolescents with prenatal alcohol exposure.

Diffuson tensor imaging (DTI) has demonstrated widespread alterations of brain white matter structure in children with prenatal alcohol exposure (PAE), yet it remains unclear how these alterations affect the structural brain network as a whole. The present study aimed to examine changes in the DTI-based structural connectome in children and adolescents with PAE compared to unexposed controls. Participants were 121 children and adolescents with PAE (51 females) and 119 typically-developing controls (49 females) aged 5-18 years with DTI data collected at one of four research centers across Canada. Graph-theory based analysis was performed on the connectivity matrix constructed from whole-brain white matter fibers via deterministic tractography. The PAE group had significantly decreased whole-brain global efficiency, degree centrality, and participation coefficients, as well as increased shortest path length and betweenness centrality compared to unexposed controls. Individuals with PAE had decreased connectivity between the attention, somatomotor, and default mode networks compared to controls. This study demonstrates decreased structural white matter connectivity in children and adolescents with PAE at a whole-brain level, suggesting widespread alterations in how networks are connected with each other. This decreased connectivity may underlie cognitive and behavioural difficulties in children with PAE.

Radiological Findings on Structural Magnetic Resonance Imaging in Fetal Alcohol Spectrum Disorders and Healthy Controls.

BACKGROUND: Fetal alcohol spectrum disorders (FASD) describe a range of physical, behavioral, and cognitive impairments stemming from prenatal alcohol exposure (PAE). Although case studies have demonstrated striking visible brain abnormalities in humans (enlargement of the lateral ventricles, thinning or absence of the corpus callosum, etc.), few studies have systematically determined how these radiological findings generalize to the wider population of individuals living with FASD. METHODS: This study examines rates of structural brain anomalies on magnetic resonance imaging (MRI) as determined by 2 radiologists in a retrospective blinded review of 163 controls and 164 individuals with PAE who were previously scanned as participants of past research studies. Incidental findings were categorized as normal variants, nonclinically significant incidental findings, or clinically significant incidental findings. Rates were compared between diagnostic subgroups using chi-square analysis. RESULTS: There was no significant difference in the overall rate of incidental findings between groups: 75% of controls and 73% of PAE participants had no incidental findings of any kind, and only 1% of controls and 3% of PAE participants had incidental finding of clinical significance (the remaining findings were considered nonsignificant anomalies or normal variants). When the PAE group was split by diagnosis, low-lying cerebellar tonsils, polymicrogyria, and ventricular asymmetry/enlargement were all most prevalent in subjects with fetal alcohol syndrome/partial fetal alcohol syndrome. In addition, the overall rate of incidental findings was higher (41%) in participants with FAS/pFAS, compared to 25% in controls. No participants in this relatively large sample had corpus callosum agenesis. CONCLUSIONS: Although advanced quantitative MRI research has uncovered a range of differences in brain structure associated with FASD, this qualitative radiological study suggests that routine clinical MRI does not reveal a consistent pattern of brain abnormalities that can be used diagnostically in this population.

Regional hippocampal diffusion abnormalities associated with subfield-specific pathology in temporal lobe epilepsy.

OBJECTIVE: Hippocampal sclerosis (HS) is the most common pathology and best predictor of surgical outcome for medically refractory patients with temporal lobe epilepsy (TLE). Current clinical MRI methods can detect HS, but subfield pathology is poorly characterized, limiting accurate prediction of seizure-free outcomes after surgery. Diffusion tensor imaging (DTI) can probe regional microstructural changes associated with focal hippocampal pathology, but is typically limited by low-resolution whole-brain acquisitions. METHODS: High-resolution (1 × 1 × 1 mm3) DTI, T1, and quantitative T2 of the hippocampus was acquired in 18 preoperative TLE patients and 19 healthy controls. Diffusion images were qualitatively assessed for loss of internal architecture, and whole-hippocampus diffusion, volume, and quantitative T2 were compared across groups. Regional hippocampal diffusion abnormalities were examined in all subjects and compared to histology in four subjects who underwent anterior temporal lobectomy. RESULTS: High-resolution mean diffusion-weighted images enabled visualization of internal hippocampal architecture, used to visually identify HS with 86% specificity and 93% sensitivity. Mean diffusivity (MD) elevations were regionally heterogenous within the hippocampus and varied across TLE patients. The spatial location of diffusion abnormalities corresponded with the location of focal subfield neuron loss, gliosis, and reduced myelin staining abnormalities identified with postsurgical histology in four subjects who underwent anterior temporal lobectomy. Whole-hippocampus MD and T2 relaxation times were higher, and fractional anisotropy (FA) and volumes were lower in TLE patients relative to controls. Left hippocampus MD correlated with verbal memory in the TLE group. SIGNIFICANCE: Visualization of internal architecture and focal diffusion abnormalities on high-resolution diffusion imaging suggests potential clinical utility of diffusion imaging in TLE and may have significant implications for surgical planning and prediction of seizure-free outcomes in individual patients.

Full Activation Profiles and Integrity of Corticospinal Pathways in Adults With Bilateral Spastic Cerebral Palsy.

BACKGROUND: Dysfunction of corticospinal pathways has been implicated in motor impairments in people with bilateral spastic cerebral palsy (CP). While structural damage to corticospinal pathways in people with CP is known, its impact on the activation of these pathways is not. OBJECTIVE: To provide the first, complete activation profile of corticospinal pathways in adults with CP using a full range of transcranial magnetic stimulation (TMS) intensities and voluntary contractions. METHODS: TMS targeted the soleus muscle of 16 adults with bilateral spastic CP and 15 neurologically intact (NI) control participants. Activation profiles were generated using motor-evoked potentials (MEPs) produced by varying both stimulation intensity and degree of voluntary muscle activity. Anatomical integrity of corticospinal pathways was also measured with diffusion tractography. RESULTS: Participants with CP had smaller MEPs produced by TMS at 1.2× active motor threshold during submaximal (20%) muscle activity and smaller maximal MEPs produced under any combination of stimulation intensity and voluntary muscle activity. At a fixed stimulation intensity, increasing voluntary muscle activity facilitated MEP amplitudes to a lesser degree in the participants with CP. Consistent differences in diffusion tractography suggested structural abnormalities in the corticospinal pathways of participants with CP that correlated with maximal MEPs. CONCLUSION: People with bilateral spastic CP have impaired activation of low and high-threshold corticospinal pathways to soleus motoneurons by TMS and reduced facilitation by voluntary activity that may be associated with structural damage to these pathways. These impairments likely contribute to impaired voluntary movement.

A review of diffusion MRI of typical white matter development from early childhood to young adulthood.

Understanding typical, healthy brain development provides a baseline from which to detect and characterize brain anomalies associated with various neurological or psychiatric disorders and diseases. Diffusion MRI is well suited to study white matter development, as it can virtually extract individual tracts and yield parameters that may reflect alterations in the underlying neural micro-structure (e.g. myelination, axon density, fiber coherence), though it is limited by its lack of specificity and other methodological concerns. This review summarizes the last decade of diffusion imaging studies of healthy white matter development spanning childhood to early adulthood (4-35 years). Conclusions about anatomical location, rates, and timing of white matter development with age are discussed, as well as the influence of image acquisition, analysis, age range/sample size, and statistical model. Despite methodological variability between studies, some consistent findings have emerged from the literature. Specifically, diffusion studies of neurodevelopment overwhelmingly demonstrate regionally varying increases of fractional anisotropy and decreases of mean diffusivity during childhood and adolescence, some of which continue into adulthood. While most studies use linear fits to model age-related changes, studies with sufficient sample sizes and age range provide clear evidence that white matter development (as indicated by diffusion) is non-linear. Several studies further suggest that maturation in association tracts with frontal-temporal connections continues later than commissural and projection tracts. The emerging contributions of more advanced diffusion methods are also discussed, as they may reveal new aspects of white matter development. Although non-specific, diffusion changes may reflect increases of myelination, axonal packing, and/or coherence with age that may be associated with changes in cognition.

High resolution in-vivo diffusion imaging of the human hippocampus.

The human hippocampus is a key target of many imaging studies given its capacity for neurogenesis, role in long term potentiation and memory, and nearly ubiquitous involvement in neurological and psychiatric conditions. Diffusion tensor imaging (DTI) has detected microstructural abnormalities of the human hippocampus associated with various disorders, but acquisitions have typically been limited to low spatial resolution protocols designed for whole brain (e.g. > 2 mm isotropic, >8 mm3 voxels), limiting regional specificity and worsening partial volume effects. The purpose here was to develop a simple DTI protocol using readily available standard single-shot EPI at 3T, capable of yielding much higher spatial resolution images (1 x 1 x 1 mm3) of the human hippocampus in a 'clinically feasible' scan time of ~6 min. A thin slab of twenty 1 mm slices oriented along the long axis of the hippocampus enabled efficient coverage and a shorter repetition time, allowing more diffusion weighted images (DWIs) per slice per unit time. In combination with this strategy, a low b value of 500 s/mm2 was chosen to help overcome the very low SNR of a 1 x 1 x 1 mm3 EPI acquisition. 1 mm isotropic mean DWIs (averaged over 120-128 DWIs) showed excellent detail of the hippocampal architecture (e.g. morphology and digitations, sub-regions, stratum lacunosum moleculare - SLM) that was not readily visible on 2 mm isotropic diffusion images. Diffusion parameters within the hippocampus were consistent across subjects and fairly homogenous across sub-regions of the hippocampus (with the exception of the SLM and tail). However, it is expected that DTI parameters will be sensitive to microstructural changes associated with a number of clinical disorders (e.g. epilepsy, dementia) and that this practical, translatable approach for high resolution acquisition will facilitate localized detection of hippocampal pathology.

Sexual dimorphism of volume reduction but not cognitive deficit in fetal alcohol spectrum disorders: A combined diffusion tensor imaging, cortical thickness and brain volume study.

Quantitative magnetic resonance imaging (MRI) has revealed abnormalities in brain volumes, cortical thickness and white matter microstructure in fetal alcohol spectrum disorders (FASD); however, no study has reported all three measures within the same cohort to assess the relative magnitude of deficits, and few studies have examined sex differences. Participants with FASD (n = 70; 30 females; 5-32 years) and healthy controls (n = 74; 35 females; 5-32 years) underwent cognitive testing and MRI to assess cortical thickness, regional brain volumes and fractional anisotropy (FA)/mean diffusivity (MD) of white matter tracts. A significant effect of group, age-by-group, or sex-by-group was found for 9/9 volumes, 7/39 cortical thickness regions, 3/9 white matter tracts, and 9/10 cognitive tests, indicating group differences that in some cases differ by age or sex. Volume reductions for several structures were larger in males than females, despite similar deficits of cognition in both sexes. Correlations between brain structure and cognitive scores were found in females of both groups, but were notably absent in males. Correlations within a given MRI modality (e.g. total brain volume and caudate volume) were prevalent in both the control and FASD groups, and were more numerous than correlations between measurement types (e.g. volumes and diffusion tensor imaging) in either cohort. This multi-modal MRI study finds widespread differences of brain structure in participants with prenatal alcohol exposure, and to a greater extent in males than females which may suggest attenuation of the expected process of sexual dimorphism of brain structure during typical development.

Evolution of deep gray matter volume across the human lifespan.

Magnetic resonance imaging of subcortical gray matter structures, which mediate behavior, cognition and the pathophysiology of several diseases, is crucial for establishing typical maturation patterns across the human lifespan. This single site study examines T1-weighted MPRAGE images of 3 healthy cohorts: (i) a cross-sectional cohort of 406 subjects aged 5-83 years; (ii) a longitudinal neurodevelopment cohort of 84 subjects scanned twice approximately 4 years apart, aged 5-27 years at first scan; and (iii) a longitudinal aging cohort of 55 subjects scanned twice approximately 3 years apart, aged 46-83 years at first scan. First scans from longitudinal subjects were included in the cross-sectional analysis. Age-dependent changes in thalamus, caudate, putamen, globus pallidus, nucleus accumbens, hippocampus, and amygdala volumes were tested with Poisson, quadratic, and linear models in the cross-sectional cohort, and quadratic and linear models in the longitudinal cohorts. Most deep gray matter structures best fit to Poisson regressions in the cross-sectional cohort and quadratic curves in the young longitudinal cohort, whereas the volume of all structures except the caudate and globus pallidus decreased linearly in the longitudinal aging cohort. Males had larger volumes than females for all subcortical structures, but sex differences in trajectories of change with age were not significant. Within subject analysis showed that 65%-80% of 13-17 year olds underwent a longitudinal decrease in volume between scans (∼4 years apart) for the putamen, globus pallidus, and hippocampus, suggesting unique developmental processes during adolescence. This lifespan study of healthy participants will form a basis for comparison to neurological and psychiatric disorders. Hum Brain Mapp 38:3771-3790, 2017. © 2017 Wiley Periodicals, Inc.

Diffusion tensor imaging of white matter and correlates to eye movement control and psychometric testing in children with prenatal alcohol exposure.

Prenatal alcohol exposure (PAE) can cause central nervous system dysfunction and widespread structural anomalies as detected by magnetic resonance imaging (MRI). This study focused on diffusion tensor imaging (DTI) of white matter in a large sample of PAE participants that allowed us to examine correlations with behavioral outcomes. Participants were confirmed PAE (n = 69, mean age = 12.5 ± 3.2 years) or typically developing control children (n = 67, mean age = 12.1 ± 3.2 years) who underwent brain MRI, eye movement tasks, and psychometric tests. A semi-automated tractography method extracted fractional anisotropy (FA) and mean diffusivity (MD) values from 15 white matter tracts. The PAE group displayed decreased FA compared with controls in multiple tracts including 3 corpus callosum regions, right corticospinal tract, and 3 left hemisphere tracts connecting to the frontal lobe (cingulum, uncinate fasciculus, and superior longitudinal fasciculus). Significant group by sex interactions were found for the genu, left superior longitudinal fasciculus, and the left uncinate, with females in the PAE group exhibiting lower FA compared with control females. Correlations were found between DTI and eye movement measures in the control group, but these same relationships were absent in the PAE group. In contrast, no correlations were found between DTI and any of the psychometric tests used in this study. These findings support the hypothesis that measures of eye movement control may be valuable functional biomarkers of the brain injury induced by PAE as these tasks reveal group differences that appear to be linked to deficits in white matter integrity in the brain. Hum Brain Mapp 38:444-456, 2017. © 2016 Wiley Periodicals, Inc.

Relationships between Head Circumference, Brain Volume and Cognition in Children with Prenatal Alcohol Exposure.

Head circumference is used together with other measures as a proxy for central nervous system damage in the diagnosis of fetal alcohol spectrum disorders, yet the relationship between head circumference and brain volume has not been investigated in this population. The objective of this study is to characterize the relationship between head circumference, brain volume and cognitive performance in a large sample of children with prenatal alcohol exposure (n = 144) and healthy controls (n = 145), aged 5-19 years. All participants underwent magnetic resonance imaging to yield brain volumes and head circumference, normalized to control for age and sex. Mean head circumference, brain volume, and cognitive scores were significantly reduced in the prenatal alcohol exposure group relative to controls, albeit with considerable overlap between groups. Males with prenatal alcohol exposure had reductions in all three measures, whereas females with prenatal alcohol exposure had reduced brain volumes and cognitive scores, but no difference in head circumference relative to controls. Microcephaly (defined here as head circumference ≤ 3rd percentile) occurred more often in prenatal alcohol exposed participants than controls, but 90% of the exposed sample had head circumferences above this clinical cutoff indicating that head circumference is not a sensitive marker of prenatal alcohol exposure. Normalized head circumference and brain volume were positively correlated in both groups, and subjects with very low head circumference typically had below-average brain volumes. Conversely, over half of the subjects with very low brain volumes had normal head circumferences, which may stem from differential effects of alcohol on the skeletal and nervous systems. There were no significant correlations between head circumference and any cognitive score. These findings confirm group-level reductions in head circumference and increased rates of microcephaly in children with prenatal alcohol exposure, but raise concerns about the predictive value of this metric at an individual-subject level.

Accelerated longitudinal cortical thinning in adolescence.

It remains unclear if changes of the cerebral cortex occur gradually from childhood to adulthood, or if adolescence marks a differential period of cortical development. In the current study of 90 healthy volunteers aged 5-32years (48 females, 85 right handed) with 180 scans (2 scans for each participant with ~4year gaps), thinning of overall mean thickness and across the four major cortical lobes bilaterally was observed across this full age span. However, the thinning rate, calculated as Δcortical thickness/Δage (mm/year) between scans of each participant, revealed an accelerated cortical thinning during adolescence, which was preceded by less thinning in childhood and followed by decelerated thinning in young adulthood. Males and females showed similarly faster thinning rates during adolescence relative to young adults. The underlying basis and role of accelerated cortical thinning during adolescence for cognition, behaviour and disorders that appear at such a stage of development remains to be determined in future work.