Atherosclerosis is a major contributor to global morbidity and mortality. Although atherosclerosis is a systemic disease, its burden varies considerably across vessel beds, which may translate into ...differences in mortality risk.
From 2003 to 2006, a sample of 2408 elderly participants (mean age, 69.6±6.7 years; 52.4% female) from the population-based Rotterdam Study underwent computed tomography to quantify atherosclerotic calcification in the coronary arteries, aortic arch, extracranial, and intracranial internal carotid arteries. Mortality follow-up was complete until January 1, 2012. We investigated associations of calcification in each vessel bed with mortality using Cox regression, adjusting for age, sex, and cardiovascular risk factors. Next, all vessel beds were included into 1 model to investigate independency of associations. Finally, we investigated the predictive value of calcification beyond the predictors included in the Pooled Cohort equations. During 15 775 person-years of follow-up, 283 participants died. Larger calcification volumes in all vessels were related to higher risks of all-cause mortality, cardiovascular, and noncardiovascular mortality, independent of cardiovascular risk factors. Most prominent associations were found for aortic arch calcification and cardiovascular mortality (age- and sex-adjusted hazard ratio per 1-SD increase 2.72 95% confidence interval, 1.85-4.02), independent of calcification elsewhere (hazard ratio, 1.75 (95% confidence interval, 1.13-2.72). Calcification in any vessel improved prediction for all 3 outcomes.
Atherosclerotic load in major vessel beds is associated with an increased risk of death. In particular, aortic arch calcification volume yields unique information with regard to mortality in addition to atherosclerosis in other vessel beds.
Neuroimaging studies of typically developing children and adolescents have provided valuable information on global and regional developmental trajectories of brain development. As these studies ...become larger and population-based, they are generating an intersection between the fields of developmental neuroscience and epidemiology. However, few of these studies have adequately probed the contribution of multiple environmental and genetic factors on brain development. Studies designed to optimally evaluate the role of multiple environmental and genetic factors on brain development require both large sample sizes and the prospective collection of multiple environmental factors. The Generation R Study is a large, prospective, prenatal-cohort study of nearly 10,000 children that began in 2002 in Rotterdam, the Netherlands. In September of 2009, 6–8 year old children from the Generation R Study were invited to participate in a magnetic resonance imaging component of the study. We provide an overview of the study design and experience for the first 801 children recruited for the neuroimaging component of the study. The protocol includes a 1-h neuropsychological assessment using the NEPSY-II, a mock scanning session, and a neuroimaging session that includes high-resolution structural, diffusion tensor, and resting-state functional MRI sequences. Image quality has been good to excellent in over 80 % of the children to date. The infusion of imaging into the Generation R Study will set the stage for evaluating the role of multiple environmental and genetic factors in both typical and atypical neurodevelopment.
A pulmonary artery to aorta ratio (PA:A) >1 is a proxy of pulmonary hypertension. It is not known whether this measure carries prognostic information in the general population and in individuals with ...chronic obstructive pulmonary disease (COPD).Between 2003 and 2006, 2197 participants from the population-based Rotterdam Study (mean±sd age 69.7±6.7 years; 51.3% female), underwent cardiac computed tomography (CT) scanning with PA:A quantification, defined as the ratio between the diameters of the pulmonary artery and the aorta. COPD was diagnosed based on spirometry or clinical presentation and obstructive lung function measured by a treating physician. Cox regression was used to investigate the risk of mortality.We observed no association between 1-sd increase of PA:A and mortality in the general population. Larger PA:A was associated with an increased risk of mortality in individuals with COPD, particularly in moderate-to-severe COPD (hazard ratio 1.36, 95% CI 1.03-1.79). We demonstrated that the risk of mortality in COPD was driven by severe COPD, and that this risk increased with decreasing diffusing capacity.Larger PA:A is not associated with mortality in an older general population, but is an independent determinant of mortality in moderate-to-severe COPD. Measuring PA:A in CT scans obtained for other indications may yield important prognostic information in individuals with COPD.
Increasing evidence suggests that atherosclerotic plaque composition rather than plaque size is linked to ischemic cardiovascular events, yet largescale population-based data in asymptomatic ...individuals remain scarce.
This study sought to investigate carotid plaque composition in relation to incident stroke and coronary heart disease (CHD) in a population-based setting.
Between 2007 and 2012, 1,349 persons (mean age 72 years, 49.5% women) from the population-based Rotterdam Study who were free from a history of stroke or CHD, in whom carotid ultrasonography showed subclinical atherosclerosis, and who underwent high-resolution magnetic resonance imaging of the carotid arteries to assess plaque characteristics. These included the presence of specific plaque components (intraplaque hemorrhage IPH, lipid-rich necrotic core, and calcification), and measures of plaque size (maximum plaque thickness and presence of stenosis of more than 30%). Individuals were continuously followed for the occurrence of stroke or CHD until January 1, 2015. The authors used Cox regression models to assess the association of the plaque characteristics with the incidence of stroke and CHD, with adjustments for age, sex, and cardiovascular risk factors.
During a median of 5.1 years’ follow-up for stroke and 4.8 years for CHD, 51 individuals had a stroke and 83 developed CHD. Independent of maximum plaque thickness and cardiovascular risk factors, the presence of IPH was associated with incident stroke and CHD (fully adjusted hazard ratio: 2.42 95% confidence interval: 1.30 to 4.50, and 1.95 95% confidence interval: 1.20 to 3.14). Presence of a lipid-rich necrotic core and calcification were not associated with stroke or CHD.
The presence of IPH in the carotid atherosclerotic plaque is an independent risk factor for stroke and CHD. These findings indicate the promise of IPH as a marker of plaque vulnerability in healthy persons with subclinical atherosclerosis.
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To investigate the association between fasting serum insulin and glucose levels with atherosclerotic plaque composition in the carotid artery. Impaired insulin and glucose levels are implicated in ...the etiology of cardiovascular disease; however, their influence on the formation and composition of atherosclerotic plaque remains unclear.
In 1740 participants (mean age 72.9 years, 46% women, 14.4% diabetes mellitus) from the population-based Rotterdam Study, we performed carotid MRI to evaluate the presence of calcification, lipid core, and intraplaque hemorrhage in carotid atherosclerosis. All participants also underwent blood sampling to obtain information on serum insulin and glucose levels. Using logistic regression models, we assessed the association of serum insulin and glucose levels (per s.d. and in tertiles) with the different plaque components, while adjusting for sex, age, intima-media thickness, and cardiovascular risk factors.
Serum insulin levels were associated with the presence of intraplaque hemorrhage (adjusted odds ratio (OR): 1.42 (95% CI: 1.12-1.7)) We found no association with the presence of calcification or lipid core. Sensitivity analyses restricted to individuals without diabetes mellitus yielded similar results. No associations were found between serum glucose levels and any of the plaque components.
Serum insulin levels are associated with the presence of vulnerable components of carotid plaque, specifically with intraplaque hemorrhage. These findings suggest a complex role for serum insulin in the pathophysiology of carotid atherosclerosis and in plaque vulnerability.
Accurate prediction of clinical outcome is of utmost importance for choices regarding the endovascular treatment (EVT) of acute stroke. Recent studies on the prediction modeling for stroke focused ...mostly on clinical characteristics and radiological scores available at baseline. Radiological images are composed of millions of voxels, and a lot of information can be lost when representing this information by a single value. Therefore, in this study we aimed at developing prediction models that take into account the whole imaging data combined with clinical data available at baseline.
We included 3,279 patients from the MR CLEAN Registry; a prospective, observational, multicenter registry of patients with ischemic stroke treated with EVT. We developed two approaches to combine the imaging data with the clinical data. The first approach was based on radiomics features, extracted from 70 atlas regions combined with the clinical data to train machine learning models. For the second approach, we trained 3D deep learning models using the whole images and the clinical data. Models trained with the clinical data only were compared with models trained with the combination of clinical and image data. Finally, we explored feature importance plots for the best models and identified many known variables and image features/brain regions that were relevant in the model decision process.
From 3,279 patients included, 1,241 (37%) patients had a good functional outcome modified Rankin Scale (mRS) ≤ 2 and 1,954 (60%) patients had good reperfusion modified Thrombolysis in Cerebral Infarction (eTICI) ≥ 2b. There was no significant improvement by combining the image data to the clinical data for mRS prediction mean area under the receiver operating characteristic (ROC) curve (AUC) of 0.81 vs. 0.80 above using the clinical data only, regardless of the approach used. Regarding predicting reperfusion, there was a significant improvement when image and clinical features were combined (mean AUC of 0.54 vs. 0.61), with the highest AUC obtained by the deep learning approach.
The combination of radiomics and deep learning image features with clinical data significantly improved the prediction of good reperfusion. The visualization of prediction feature importance showed both known and novel clinical and imaging features with predictive values.
Background
Anatomic and hemodynamic similarities between renal and cerebral vessels suggest a tight link between kidney disease and brain disease. Although several distinct markers are used to ...identify subclinical kidney and brain disease, a comprehensive assessment of how these markers link damage at both end organs is lacking.
Aim
To investigate whether measures of kidney function were associated with cerebral small vessel disease on MRI.
Methods
In 2526 participants of the population-based Rotterdam Study, we measured urinary albumin-to-creatinine ratio, and estimated glomerular filtration rate based on serum creatinine and cystatin C. All participants underwent brain magnetic resonance imaging. We assessed presence of cerebral small vessel disease by calculating white matter lesion volumes and rating the presence of lacunes and cerebral microbleeds. We used multivariable linear and logistic regression to investigate the association between kidney function and cerebral small vessel disease.
Results
Worse kidney function was consistently associated with a larger white matter lesion volume (mean difference per standard deviation increase in albumin-to-creatinine ratio: 0·09, 95% confidence interval 0·05; 0·12; per standard deviation decrease in creatinine-based estimated glomerular filtration rate: −0·04, 95% confidence interval −0·08;−0·01, and per standard deviation decrease in cystatin C-based estimated glomerular filtration rate: −0·09, 95% confidence interval −0·13;−0·05). Persons with higher albumin-to-creatinine ratio or lower cystatin C-based estimated glomerular filtration rate levels had a higher prevalence of lacunes (odds ratio per standard deviation increase in albumin-to-creatinine ratio: 1·24, 95% confidence interval 1·07; 1·43). Only participants in the highest quartile of albumin-to-creatinine ratio had a higher frequency of microbleeds compared to the lowest quartile.
Conclusions
Worse kidney function is associated with cerebral small vessel disease. Of all measures of kidney function, in particular albumin-to-creatinine ratio is related to cerebral small vessel disease.
Frontotemporal lobar degeneration (FTLD) is a clinically, genetically and pathologically heterogeneous disorder. Within FTLD with ubiquitin-positive inclusions (FTLD-U), a new pathological subtype ...named FTLD-FUS was recently found with fused in sarcoma (FUS) positive, TDP-43-negative inclusions, and striking atrophy of the caudate nucleus. The aim of this study was to determine the frequency of FTLD-FUS in our pathological FTLD series, and to describe the clinical, neuroimaging and neuropathological features of FTLD-FUS, especially caudate atrophy. Demographic and clinical data collected prospectively from 387 patients with frontotemporal dementia (FTD) yielded 74 brain specimens. Immunostaining was carried out using a panel of antibodies, including AT-8, ubiquitin, p62, FUS, and TDP-43. Cortical and caudate atrophy on MRI (
n
= 136) was rated as normal, mild-moderate or severe. Of the 37 FTLD-U cases, 33 were reclassified as FTLD-TDP and four (0.11, 95%: 0.00–0.21) as FTLD-FUS, with ubiquitin and FUS-positive, p62 and TDP-43-negative neuronal intranuclear inclusions (NII). All four FTLD-FUS cases had a negative family history, behavioural variant FTD (bvFTD), and three had an age at onset ≤40 years. MRI revealed mild-moderate or severe caudate atrophy in all, with a mean duration from onset till MRI of 63 months (range 16–119 months). In our total clinical FTD cohort, we found 11 patients (0.03; 95% CI: 0.01–0.05) with bvFTD, negative family history, and age at onset ≤40 years. Caudate atrophy was present in 10 out of 136 MRIs, and included all four FUS-cases. The newly identified FTLD-FUS has a frequency of 11% in FTLD-U, and an estimated frequency of three percent in our clinical FTD cohort. The existence of this pathological subtype can be predicted with reasonable certainty by age at onset ≤40 years, negative family history, bvFTD and caudate atrophy on MRI.
Purpose:
In current clinical practice, head and neck (H&N) hyperthermia treatment planning (HTP) is solely based on computed tomography (CT) images. Magnetic resonance imaging (MRI) provides superior ...soft‐tissue contrast over CT. The purpose of the authors’ study is to investigate the relevance of using MRI in addition to CT for patient modeling in H&N HTP.
Methods:
CT and MRI scans were acquired for 11 patients in an immobilization mask. Three observers manually segmented on CT, MRI T1 weighted (MRI‐T1w), and MRI T2 weighted (MRI‐T2w) images the following thermo‐sensitive tissues: cerebrum, cerebellum, brainstem, myelum, sclera, lens, vitreous humor, and the optical nerve. For these tissues that are used for patient modeling in H&N HTP, the interobserver variation of manual tissue segmentation in CT and MRI was quantified with the mean surface distance (MSD). Next, the authors compared the impact of CT and CT and MRI based patient models on the predicted temperatures. For each tissue, the modality was selected that led to the lowest observer variation and inserted this in the combined CT and MRI based patient model (CT and MRI), after a deformable image registration. In addition, a patient model with a detailed segmentation of brain tissues (including white matter, gray matter, and cerebrospinal fluid) was created (CT and MRIdb). To quantify the relevance of MRI based segmentation for H&N HTP, the authors compared the predicted maximum temperatures in the segmented tissues (Tmax) and the corresponding specific absorption rate (SAR) of the patient models based on (1) CT, (2) CT and MRI, and (3) CT and MRIdb.
Results:
In MRI, a similar or reduced interobserver variation was found compared to CT (maximum of median MSD in CT: 0.93 mm, MRI‐T1w: 0.72 mm, MRI‐T2w: 0.66 mm). Only for the optical nerve the interobserver variation is significantly lower in CT compared to MRI (median MSD in CT: 0.58 mm, MRI‐T1w: 1.27 mm, MRI‐T2w: 1.40 mm). Patient models based on CT (Tmax: 38.0 °C) and CT and MRI (Tmax: 38.1 °C) result in similar simulated temperatures, while CT and MRIdb (Tmax: 38.5 °C) resulted in significantly higher temperatures. The SAR corresponding to these temperatures did not differ significantly.
Conclusions:
Although MR imaging reduces the interobserver variation in most tissues, it does not affect simulated local tissue temperatures. However, the improved soft‐tissue contrast provided by MRI allows generating a detailed brain segmentation, which has a strong impact on the predicted local temperatures and hence may improve simulation guided hyperthermia.
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