Aortic calcification: A postmortem CT validation study in a middle-aged population

Background: Computed tomography (CT)-detected aortic calcification is strongly associated with aortic stiffness and is an accurate predictor of cardiovascular and all-cause mortality and cognitive decline. Some previous pathologic studies have shown calcium accumulation in the medial layer of the vessel wall, while others have suggested localisation in the atherosclerotic intimal layer. Objectives: The aim of this study was to histologically validate CT findings of aortic calcification for detectability and location in the aortic wall. Methods: We acquired postmortem CT images and collected 170 aortic tissue samples from five different locations in the thoracic and abdominal aorta of 40 individuals who underwent autopsy. Microscopic slides were stained with haematoxylin and eosin and elastic van Gieson stain. Calcified lesions were characterised and calcifications were manually annotated in the intima and media. The presence and morphology of calcifications were scored on CT images. Results: The mean age of the autopsied individuals was 63 years, and 28 % died of cardiovascular disease. Calcifications were present in 74/170 (44 %) samples. Calcification was more common in the abdominal aorta than in the thoracic aorta. In all samples with calcifications, 99 % were located in the intimal layer. Only 16/170 samples had a small amount of medial arterial calcification. The histological results showed an 85 % concordance for the presence or absence of CT calcifications. There was complete inter-method agreement for annularity of calcifications in 68 % of the samples (linear weighted kappa 0.68 (95 %CI 0.60–0.77). Conclusions: Aortic calcifications visible on CT are located in the intimal layer of the abdominal aorta wall, at least in aortas that are not aneurysmatic or dissected. The presence and annularity of these calcifications can be reliably determined by CT

Plasma Level of Pyrophosphate Is Low in Pseudoxanthoma Elasticum Owing to Mutations in the ABCC6 Gene, but It Does Not Correlate with ABCC6 Genotype

BACKGROUND: Pseudoxanthoma elasticum (PXE), a monogenic disorder resulting in calcification affecting the skin, eyes and peripheral arteries, is caused by mutations in the ABCC6 gene, and is associated with low plasma inorganic pyrophosphate (PP i). It is unknown how ABCC6 genotype affects plasma PP i. METHODS: We studied the association of ABCC6 genotype (192 patients with biallelic pathogenic ABCC6 mutations) and PP i levels, and its association with the severity of arterial and ophthalmological phenotypes. ABCC6 variants were classified as truncating or non-truncating, and three groups of the 192 patients were formed: those with truncating mutations on both chromosomes ( n = 121), those with two non-truncating mutations ( n = 10), and a group who had one truncating and one non-truncating ABCC6 mutation ( n = 61). The hypothesis formulated before this study was that there was a negative association between PP i level and disease severity. RESULTS: Our findings confirm low PP i in PXE compared with healthy controls (0.53 ± 0.15 vs. 1.13 ± 0.29 µM, p < 0.01). The PP i of patients correlated with increasing age (β: 0.05 µM, 95% CI: 0.03-0.06 per 10 years) and was higher in females (0.55 ± 0.17 vs. 0.51 ± 0.13 µM in males, p = 0.03). However, no association between PP i and PXE phenotypes was found. When adjusted for age and sex, no association between PP i and ABCC6 genotype was found. CONCLUSIONS: Our data suggest that the relationship between ABCC6 mutations and reduced plasma PP i may not be as direct as previously thought. PP i levels varied widely, even in patients with the same ABCC6 mutations, further suggesting a lack of direct correlation between them, even though the ABCC6 protein-mediated pathway is responsible for ~60% of this metabolite in the circulation. We discuss potential factors that may perturb the expected associations between ABCC6 genotype and PP i and between PP i and disease severity. Our findings support the argument that predictions of pathogenicity made on the basis of mutations (or on the structure of the mutated protein) could be misleading

MRI predicts 5-year joint bleeding and development of arthropathy on radiographs in hemophilia

Magnetic resonance imaging (MRI) is considered as the reference standard to assess early joint changes in hemophilia. However, the clinical relevance of MRI findings is still unknown. The aim of this prospective study was to assess the predictive value of MRI for 5-year joint bleeding and progression of arthropathy in patients with hemophilia. Both knees and ankles of patients with hemophilia and absent or limited arthropathy on radiographs were assessed by using MRI and radiographs. MRI scans were scored according to the International Prophylaxis Study Group MRI score for hemophilic arthropathy. Patients were followed up for 5 years, including assessment of joint bleeding and repeated radiographic assessment. Associations between baseline MRI findings with 5-year bleeding and progression of arthropathy were expressed as odds ratios (OR), adjusted for severity of disease and joint bleeding history. Baseline assessment included 104 joints of 26 patients with hemophilia (median age, 21 years). Four ankles with severe joint changes were excluded. Follow-up was available for 96 (92%) of 104 joints. During 5 years of follow-up, bleeding was reported for 36% of joints. Five-year bleeding was significantly increased in joints with synovial hypertrophy at 80% vs 27% in joints without synovial hypertrophy (OR, 10.1; 95% confidence interval, 3.4-31.3). In joints with normal baseline radiographs, any osteochondral or synovial changes on MRI were associated with radiographic changes 5 years later (positive predictive value, 75%; negative predictive value, 98%). Joints with synovial hypertrophy on MRI had a significantly higher chance of 5-year bleeding. All MRI changes, except effusion, were strong predictors for development of arthropathy on radiographs

Comparison of skull circumference and linear measurements with csf volume mr measurements in hydrocephalus

In children with hydrocephalus, accurate and reproducible estimation of the presence, severity, and course of the condition is of paramount importance for both clinical and scientific purposes. Inthis study, 30 hydrocephalic patients were assessed with a number of commonly used methods, such as occipitofrontal skull circumference (SC) measurements, Evans ratio (ER), and bicaudate index (BCI), as well as, for comparison, another ratio of linear measurements [ventricle-skull ratio (VSR)]and MR measurements of total intracranial CSF volume. In repeated CSF volume measurements in healthy volunteers, the MR method appeared to be accurate and reproducible. This technique was simpler and easier in application, requiring less interaction than comparable MR techniques described by others. The variation coefficients were within the same range. In increased CSF volumes, our technique can be recommended; in very small CSF volumes, another technique is more adequate. Direct assessment of CSF volume as a measure of hydrocephalus was preferable over derived estimations for scientific purposes and may function as a gold standard against which to evaluate other techniques that are easier to apply clinically. In comparison, SC measurements were poor; CSF volume changes were not reflected in SC changes. VSR was preferable over ER and BCI, because it correlated more closely with CSF volume

Computed Tomography Perfusion Derived Blood-Brain Barrier Permeability Does Not Yet Improve Prediction of Hemorrhagic Transformation

Introduction: Hemorrhagic transformation (HT) in acute ischemic stroke can occur as a result of reperfusion treatment. While withholding treatment may be warranted in patients with increased risk of HT, prediction of HT remains difficult. Nonlinear regression analysis can be used to estimate blood-brain barrier permeability (BBBP). The aim of this study was to identify a combination of clinical and imaging variables, including BBBP estimations, that can predict HT. Materials and Methods: From the Dutch acute stroke study, 545 patients treated with intravenous recombinant tissue plasminogen activator and/or intra-arterial treatment were selected, with available admission extended computed tomography (CT) perfusion and follow-up imaging. Patient admission treatment characteristics and CT imaging parameters regarding occlusion site, stroke severity, and BBBP were recorded. HT was assessed on day 3 follow-up imaging. The association between potential predictors and HT was analyzed using univariate and multivariate logistic regression. To compare the added value of BBBP, areas under the curve (AUCs) were created from 2 models, with and without BBBP. Results: HT occurred in 57 patients (10%). In univariate analysis, older age (OR 1.03, 95% CI 1.006–1.05), higher admission National Institutes of Health Stroke Scale (NIHSS; OR 1.13, 95% CI 1.08–1.18), higher clot burden (OR 1.28, 95% CI 1.16–1.41), poor collateral score (OR 3.49, 95% CI 1.85–6.58), larger Alberta Stroke Program Early CT Score cerebral blood volume deficit size (OR 1.26, 95% CI 1.14–1.38), and increased BBBP (OR 2.22, 95% CI 1.46–3.37) were associated with HT. In multivariate analysis with age and admission NIHSS, the addition of BBBP did not improve the AUC compared to both independent predictors alone (AUC 0.77, 95% CI 0.71–0.83). Conclusion: BBBP predicts HT but does not improve prediction with age and admission NIHSS

Do Lacunar Infarcts Have Different Aetiologies Risk Factor Profiles of Lacunar Infarcts in Deep White Matter and Basal Ganglia : The Second Manifestations of ARTerial Disease-Magnetic Resonance Study

Background: Evidence suggests that lacunar infarcts have different etiologies, possibly related to their anatomical location and vascular territory. We investigated the risk factor profiles of patients with new lacunar infarcts in the basal ganglia and deep white matter. Methods: Within the Second Manifestations of ARTerial disease-Magnetic Resonance study, a prospective cohort on brain changes on MRI in patients with symptomatic atherosclerotic disease, 679 patients (57 ± 9 years) had vascular screening and MRI at baseline and after a mean follow-up of 3.9 years. We investigated the association between vascular risk factors at baseline and appearance of new lacunar infarcts in the basal ganglia and deep white matter at follow-up. Results: New lacunar infarcts appeared in 44 patients in the basal ganglia and in 37 patients in the deep white matter. In multivariable analysis, older age, history of cerebrovascular disease, and baseline white matter hyperintensity (WMH) volume were associated with increased risk of new lacunar infarcts in both locations. Hyperhomocysteinemia was associated with increased risk of lacunar infarcts in the basal ganglia (relative risk [RR] 2.0; 95% CI 1.0-4.2), whereas carotid stenosis >70% (RR 2.5; 95% CI 1.2-5.0), smoking (per 10 pack-year: RR 1.1; 95% CI 1.0-1.3), hypertension (RR 3.4; 95% CI 1.2-9.7), and progression of WMH volume (RR 2.4; 95% CI 1.1-5.2) were associated with increased risk of lacunar infarcts in the deep white matter. Conclusions: The different risk factor profiles for new lacunar infarcts in basal ganglia and deep white matter indicate different etiologies. The independent association between progression of WMH and new deep white matter lacunar infarcts suggest a common etiology for these radiological abnormalities