Tractography based on diffusion tensor imaging (DTI) allows visualization of white matter tracts. In this study, protocols to reconstruct eleven major white matter tracts are described. The protocols ...were refined by several iterations of intra- and inter-rater measurements and identification of sources of variability. Reproducibility of the established protocols was then tested by raters who did not have previous experience in tractography. The protocols were applied to a DTI database of adult normal subjects to study size, fractional anisotropy (FA), and T2 of individual white matter tracts. Distinctive features in FA and T2 were found for the corticospinal tract and callosal fibers. Hemispheric asymmetry was observed for the size of white matter tracts projecting to the temporal lobe. This protocol provides guidelines for reproducible DTI-based tract-specific quantification.
The impact of genetic and environmental factors on human brain structure is of great importance for understanding normative cognitive and brain aging as well as neuropsychiatric disorders. However, ...most studies of genetic and environmental influences on human brain structure have either focused on global measures or have had samples that were too small for reliable estimates. Using the classical twin design, we assessed genetic, shared environmental, and individual-specific environmental influences on individual differences in the size of 96 brain regions of interest (ROIs). Participants were 474 middle-aged male twins (202 pairs; 70 unpaired) in the Vietnam Era Twin Study of Aging (VETSA). They were 51–59 years old, and were similar to U.S. men in their age range in terms of sociodemographic and health characteristics. We measured thickness of cortical ROIs and volume of other ROIs. On average, genetic influences accounted for approximately 70% of the variance in the volume of global, subcortical, and ventricular ROIs and approximately 45% of the variance in the thickness of cortical ROIs. There was greater variability in the heritability of cortical ROIs (0.00–0.75) as compared with subcortical and ventricular ROIs (0.48–0.85). The results did not indicate lateralized heritability differences or greater genetic influences on the size of regions underlying higher cognitive functions. The findings provide key information for imaging genetic studies and other studies of brain phenotypes and endophenotypes. Longitudinal analysis will be needed to determine whether the degree of genetic and environmental influences changes for different ROIs from midlife to later life.
Background
Women with ST‐elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention historically experience worse in‐hospital outcomes compared to men.
Hypothesis
...Implementation of a regional STEMI system will reduce care gaps in reperfusion times and in‐hospital outcomes between women and men.
Methods
1928 patients (413 women, 21.4%) presented with an acute STEMI between June 2007 and March 2016. The population was divided into an early cohort (n = 728 patients, 2007‐May 2011), and a late cohort (n = 1200 patients, June 2011–2016). The primary endpoints evaluated were reperfusion times and in‐hospital outcomes.
Results
Compared to men, women experienced significant delays in first medical contact (FMC) to arrival at the emergency room (26.0 vs. 22.0 min, p < 0.001) and FMC‐to‐device (109 vs. 101 min p = 0.001). Women had higher incidences of post‐PCI heart failure and death compared to men (p < 0.05). Following multivariable adjustment, no mortality difference was observed for women versus men (adjusted OR; 0.82; 95% confidence interval CI, 0.51–1.34; p = 0.433) or for early versus late cohorts (adjusted OR; 1.04; 95% CI, 0.68–1.60; p = 0.856).
Conclusion
Following STEMI regionalization, women continued to experience significantly longer reperfusion times, although there was no difference in adjusted mortality. These results highlight the ongoing disparity of STEMI care between women and men, and suggest that regionalization alone is insufficient to close sex‐based care gaps.
Cortical surface area measures appear to be functionally relevant and distinct in etiology, development, and behavioral correlates compared with other size characteristics, such as cortical ...thickness. Little is known about genetic and environmental influences on individual differences in regional surface area in humans. Using a large sample of adult twins, we determined relative contributions of genes and environment on variations in regional cortical surface area as measured by magnetic resonance imaging before and after adjustment for genetic and environmental influences shared with total cortical surface area. We found high heritability for total surface area and, before adjustment, moderate heritability for regional surface areas. Compared with other lobes, heritability was higher for frontal lobe and lower for medial temporal lobe. After adjustment for total surface area, regionally specific genetic influences were substantially reduced, although still significant in most regions. Unlike other lobes, left frontal heritability remained high after adjustment. Thus, global and regionally specific genetic factors both influence cortical surface areas. These findings are broadly consistent with results from animal studies regarding the evolution and development of cortical patterning and may guide future research into specific environmental and genetic determinants of variation among humans in the surface area of particular regions.
Rapid reperfusion of the infarct-related artery is the cornerstone of therapy for the management of acute ST-elevation myocardial infarction (STEMI). Canada’s geography presents unique challenges for ...timely delivery of reperfusion therapy for STEMI patients. The Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology STEMI guideline was developed to provide advice regarding the optimal acute management of STEMI patients irrespective of where they are initially identified: in the field, at a non-percutaneous coronary intervention-capable centre or at a percutaneous coronary intervention-capable centre. We had also planned to evaluate and incorporate sex and gender considerations in the development of our recommendations. Unfortunately, inadequate enrollment of women in randomized trials, lack of publication of main outcomes stratified according to sex, and lack of inclusion of gender as a study variable in the available literature limited the feasibility of such an approach. The Grading Recommendations, Assessment, Development, and Evaluation system was used to develop specific evidence-based recommendations for the early identification of STEMI patients, practical aspects of patient transport, regional reperfusion decision-making, adjunctive prehospital interventions (oxygen, opioids, antiplatelet therapy), and procedural aspects of mechanical reperfusion (access site, thrombectomy, antithrombotic therapy, extent of revascularization). Emphasis is placed on integrating these recommendations as part of an organized regional network of STEMI care and the development of appropriate reperfusion and transportation pathways for any given region. It is anticipated that these guidelines will serve as a practical template to develop systems of care capable of providing optimal treatment for a wide range of STEMI patients.
La reperfusion rapide de l’artère responsable de l’infarctus est la pierre angulaire thérapeutique de la prise en charge de l’infarctus aigu du myocarde avec élévation du segment ST (STEMI). Les caractéristiques géographiques du Canada posent des défis particuliers pour prodiguer aux patients victimes d’un STEMI une reperfusion dans les délais requis. Les lignes directrices sur l’STEMI de la Société canadienne de cardiologie et de l’Association canadienne de cardiologie d’intervention ont été élaborées pour formuler des recommandations sur la prise en charge aiguë optimale des patients victimes d’un STEMI sans égard à l’endroit où l’infarctus a été initialement constaté, que ce soit à l’extérieur ou dans un établissement en mesure ou incapable de pratiquer une intervention coronarienne percutanée. Nous avions prévu d’évaluer également et d’intégrer la prise en compte du sexe et du genre dans l’élaboration de nos recommandations. Malheureusement, le nombre insuffisant de femmes recrutées dans les essais avec répartition aléatoire, le manque de publications sur les critères d’évaluation principaux stratifiés en fonction du sexe et l’omission fréquente du sexe à titre de variable de l’étude dans la littérature limitaient la faisabilité d’une telle approche. Le système GRADE (« Grading Recommendations, Assessment, Development, and Evaluation ») a été utilisé pour formuler des recommandations précises, fondées sur des données probantes, pour le repérage précoce des patients victimes d’un STEMI, les aspects pratiques concernant le transport des patients, la prise de décision au sujet de la reperfusion au niveau régional, les interventions d’appoint préhospitalières (oxygène, opioïdes, traitement antiplaquettaire), ainsi que les aspects procéduraux de la reperfusion mécanique (voie d’accès, thrombectomie, traitement antithrombotique, étendue de la revascularisation). Une importance particulière est accordée à l’intégration de ces recommandations à un réseau régional structuré de prise en charge du STEMI et à l’élaboration de parcours appropriés de reperfusion et de transport dans chaque région. On s’attend à ce que ces lignes directrices servent de modèle pratique pour l’élaboration de systèmes de soins permettant d’offrir un traitement optimal à un large éventail de patients victimes d’un STEMI.
Background Although global brain structure is highly heritable, there is still variability in the magnitude of genetic influences on the size of specific regions. Yet, little is known about the ...patterning of those genetic influences, i.e., whether the same genes influence structure throughout the brain or whether there are regionally specific sets of genes. Methods We mapped the heritability of cortical thickness throughout the brain using three-dimensional structural magnetic resonance imaging in 404 middle-aged male twins. To assess the amount of genetic overlap between regions, we then mapped genetic correlations between three selected seed points and all other points comprising the continuous cortical surface. Results There was considerable regional variability in the magnitude of genetic influences on cortical thickness. The primary visual (V1) seed point had strong genetic correlations with posterior sensory and motor areas. The anterior temporal seed point had strong genetic correlations with anterior frontal regions but not with V1. The middle frontal seed point had strong genetic correlations with inferior parietal regions. Conclusions These results provide strong evidence of regionally specific patterns rather than a single, global genetic factor. The patterns are largely consistent with a division between primary and association cortex, as well as broadly defined patterns of brain gene expression, neuroanatomical connectivity, and brain maturation trajectories, but no single explanation appears to be sufficient. The patterns do not conform to traditionally defined brain structure boundaries. This approach can serve as a step toward identifying novel phenotypes for genetic association studies of psychiatric disorders and normal and pathological cognitive aging.
Attentional set-shifting ability, commonly assessed with the Trail Making Test (TMT), decreases with increasing age in adults. Since set-shifting performance relies on activity in widespread brain ...regions, deterioration of the white matter tracts that connect these regions may underlie the age-related decrease in performance. We used an automated fiber tracking method to investigate the relationship between white matter integrity in several cortical association tracts and TMT performance in a sample of 24 healthy adults, 21–80 years. Diffusion tensor images were used to compute average fractional anisotropy (FA) for five cortical association tracts, the corpus callosum (CC), and the corticospinal tract (CST), which served as a control. Results showed that advancing age was associated with declines in set-shifting performance and with decreased FA in the CC and in association tracts that connect frontal cortex to more posterior brain regions, including the inferior fronto-occipital fasciculus (IFOF), uncinate fasciculus (UF), and superior longitudinal fasciculus (SLF). Declines in average FA in these tracts, and in average FA of the right inferior longitudinal fasciculus (ILF), were associated with increased time to completion on the set-shifting subtask of the TMT but not with the simple sequencing subtask. FA values in these tracts were strong mediators of the effect of age on set-shifting performance. Automated tractography methods can enhance our understanding of the fiber systems involved in performance of specific cognitive tasks and of the functional consequences of age-related changes in those systems.
Abstract Background We describe the evolution of a regional system designed to provide primary percutaneous coronary intervention (pPCI) as the preferred method of revascularization for ST-elevation ...myocardial infarction (STEMI) and its impact on first medical contact (FMC)-to-device times and in-hospital outcomes. Methods Patients with STEMI presenting to the Vancouver Coastal Health Authority between June 2007 and January 2015 (N = 2503) were categorized according to 3 sequential phases: phase 1 = standardization of reperfusion algorithms; phase 2 = use of prehospital electrocardiograms; phase 3 = expedited interfacility transfer for pPCI. In-hospital outcomes by phase and hospital type were analyzed using multivariable logistic regression techniques. Results Regional pPCI use increased across phases (55.0% vs 72.5% vs 86.7%; P < 0.001) and median FMC-to-device times shortened between phase 1 and later phases at both PCI-capable (117 minutes vs 92 minutes vs 97 minutes, respectively; P < 0.001) and non-PCI–capable hospitals (174 minutes vs 146 minutes vs 123 minutes, respectively; P < 0.001). Overall in-hospital mortality (9.4% vs 8.9% vs 10.3%, respectively; P = 0.54) and congestive heart failure (CHF) (15.8% vs 19.7% vs 22.0%, respectively; P = 0.056) were unchanged across phases. A trend toward increased mortality (9.0% vs 9.3% vs 12.9%, respectively; P = 0.079) and higher rates of CHF (15.7% vs 21.5% vs 25.9%, respectively; P = 0.014) were seen in PCI-capable hospitals. Conclusions Our regional STEMI model increased access to pPCI and reduced median reperfusion times. However, FMC-to-device times remained prolonged in many patients and overall clinical outcomes were not improved—in particular at PCI-capable hospitals. A strategy of pPCI as the preferred method of reperfusion may not benefit all patients in a regional model of STEMI care.
Background Guidelines recommend mineralocorticoid receptor antagonist (MRA) use in patients with left ventricular ejection fraction ≤40% following a myocardial infarction plus heart failure or ...diabetes mellitus, based on mortality benefit in the EPHESUS (Eplerenone Post‐Acute Myocardial Infarction Heart Failure Efficacy and Survival Study) trial. The objective of this study was to evaluate the real‐world utilization of MRAs for patients with ST‐segment–elevation myocardial infarction (STEMI) with left ventricular dysfunction. Methods and Results The prospective, population‐based, Vancouver Coastal Health Authority STEMI database was linked with local outpatient cardiology records from 2007 to 2018. EPHESUS criteria were used to define post‐STEMI MRA eligibility (left ventricular ejection fraction ≤40% plus clinical heart failure or diabetes mellitus, and no dialysis‐dependent renal dysfunction). The primary outcome was MRA prescription among eligible patients at discharge and the secondary outcome was MRA prescription within 3 months postdischarge. Of 2691 patients with STEMI, 317 (12%) were MRA eligible, and 70 (22%) eligible patients were prescribed an MRA at discharge. Among eligible patients with no MRA at discharge, 12/126 (9.5%) with documented postdischarge follow‐up were prescribed an MRA within 3 months. In multivariable analysis, left ventricular ejection fraction (odds ratio OR, 1.55 per 5% left ventricular ejection fraction decrease; 95% CI, 1.26–1.90) and calendar year (OR, 1.23 per year, 95% CI, 1.11–1.37) were associated with MRA prescription at discharge. Other prespecified variables were not associated with MRA prescription. Conclusions In this contemporary STEMI cohort, only 1 in 4 MRA‐eligible patients were prescribed an MRA within 3 months following hospitalization despite high‐quality evidence for use. Novel decision‐support tools are required to optimize pharmacotherapy decisions during hospitalization and follow‐up to target this gap in post‐STEMI care.
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