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Intracranial internal carotid artery (iICA) calcification is associated with stroke and is often seen as a proxy of atherosclerosis of the intima. However, it was recently shown that these calcifications are predominantly located in the tunica media and internal elastic lamina (medial calcification). Intimal and medial calcifications are thought to have a different pathogenesis and clinical consequences and can only be distinguished through ex vivo histological analysis. Therefore, our aim was to develop CT scoring method to distinguish intimal and medial iICA calcification in vivo. First, in both iICAs of 16 cerebral autopsy patients the intimal and/or medial calcification area was histologically assessed (142 slides). Brain CT images of these patients were matched to the corresponding histological slides to develop a CT score that determines intimal or medial calcification dominance. Second, performance of the CT score was assessed in these 16 patients. Third, reproducibility was tested in a separate cohort. First, CT features of the score were circularity (absent, dot(s), <90°, 90-270° or 270-360°), thickness (absent, ≥1.5mm, or <1.5mm), and morphology (indistinguishable, irregular/patchy or continuous). A high sum of features represented medial and a lower sum intimal calcifications. Second, in the 16 patients the concordance between the CT score and the dominant calcification type was reasonable. Third, the score showed good reproducibility (kappa: 0.72 proportion of agreement: 0.82) between the categories intimal, medial or absent/indistinguishable. The developed CT score shows good reproducibility and can differentiate reasonably well between intimal and medial calcification dominance in the iICA, allowing for further (epidemiological) studies on iICA calcification.

We related composition of cerebral thrombi to stroke subtype and attenuation on non-contrast CT (NCCT) to gain more insight in etiopathogenesis and to validate thrombus attenuation as a new imaging biomarker for acute stroke. We histopathologically investigated 22 thrombi retrieved after mechanical thrombectomy in acute stroke patients. First, thrombi were classified as fresh, lytic or organized. Second, percentages of red blood cells (RBCs), platelets and fibrin and number of red, white (respectively RBCs or platelets outnumbering other components with ≥ 15%) or mixed thrombi were compared between large artery atherosclerosis (LAA), cardioembolism, dissection and unknown subtype. Third, correlation between attenuation and RBCs, platelets and fibrin was calculated using Pearson's correlation coefficients (r). Thrombi were fresh in 73% (n = 16), lytic in 18% (n = 4) and organized in 9% (n = 2). The stroke cause was LAA in eight (36%), cardioembolism in six (27%), dissection in three (14%), and unknown in five (23%) patients. LAA thrombi showed the highest percentage RBCs (median 50 (range 35-90)), followed by dissection (35 (20-40), p = 0.05), cardioembolism (35 (5-45), p = 0.013) and unknown subtype (25 (2-40), p = 0.006). No differences in platelets (p = 0.16) and fibrin (p = 0.52) between subtypes were found. LAA thrombi were classified as red or mixed (both n = 4), cardioembolisms as mixed (n = 5) or white (n = 1) and dissection as mixed (n = 3). There was a moderate positive correlation between attenuation and RBCs (r = 0.401, p = 0.049), and weak negative correlations with platelets (r = -0.368, p = 0.09) and fibrin (r = -0.073, p = 0.75). The majority of cerebral thrombi is fresh. There are no differences in age of thrombi between subtypes. LAA thrombi have highest percentages RBCs, cardioembolism and unknown subtype lowest. No relationship exists between subtype and platelets or fibrin percentages. We found a correlation between the RBC-component and thrombus attenuation, which improves validation of thrombus attenuation on NCCT as an imaging biomarker for stroke management.

Stenting is an alternative to endarterectomy for treatment of carotid artery stenosis, but long-term efficacy is uncertain. We report long-term data from the randomised International Carotid Stenting Study comparison of these treatments. Patients with symptomatic carotid stenosis were randomly assigned 1:1 to open treatment with stenting or endarterectomy at 50 centres worldwide. Randomisation was computer generated centrally and allocated by telephone call or fax. Major outcomes were assessed by an independent endpoint committee unaware of treatment assignment. The primary endpoint was fatal or disabling stroke in any territory after randomisation to the end of follow-up. Analysis was by intention to treat ([ITT] all patients) and per protocol from 31 days after treatment (all patients in whom assigned treatment was completed). Functional ability was rated with the modified Rankin scale. This study is registered, number ISRCTN25337470. 1713 patients were assigned to stenting (n=855) or endarterectomy (n=858) and followed up for a median of 4·2 years (IQR 3·0–5·2, maximum 10·0). Three patients withdrew immediately and, therefore, the ITT population comprised 1710 patients. The number of fatal or disabling strokes (52 vs 49) and cumulative 5-year risk did not differ significantly between the stenting and endarterectomy groups (6·4% vs 6·5%; hazard ratio [HR] 1·06, 95% CI 0·72–1·57, p=0·77). Any stroke was more frequent in the stenting group than in the endarterectomy group (119 vs 72 events; ITT population, 5-year cumulative risk 15·2% vs 9·4%, HR 1·71, 95% CI 1·28–2·30, p<0·001; per-protocol population, 5-year cumulative risk 8·9% vs 5·8%, 1·53, 1·02–2·31, p=0·04), but were mainly non-disabling strokes. The distribution of modified Rankin scale scores at 1 year, 5 years, or final follow-up did not differ significantly between treatment groups. Long-term functional outcome and risk of fatal or disabling stroke are similar for stenting and endarterectomy for symptomatic carotid stenosis. Medical Research Council, Stroke Association, Sanofi-Synthélabo, European Union.

Purpose Arterial inflammation and vascular calcification are regarded as early prognostic markers of cardiovascular disease (CVD). In this study we investigated the relationship between CVD risk and arterial inflammation ( 18 F-FDG PET/CT imaging), vascular calcification metabolism (Na 18 F PET/CT imaging), and vascular calcium burden (CT imaging) of the thoracic aorta in a population at low CVD risk. Methods Study participants underwent blood pressure measurements, blood analyses, and 18 F-FDG and Na 18 F PET/CT imaging. In addition, the 10-year risk for development of CVD, based on the Framingham risk score (FRS), was estimated. CVD risk was compared across quartiles of thoracic aorta 18 F-FDG uptake, Na 18 F uptake, and calcium burden on CT. Results A total of 139 subjects (52 % men, mean age 49 years, age range 21 – 75 years, median FRS 6 %) were evaluated. CVD risk was, on average, 3.7 times higher among subjects with thoracic aorta Na 18 F uptake in the highest quartile compared with those in the lowest quartile of the distribution (15.5 % vs. 4.2 %; P  < 0.001). CVD risk was on average, 3.7 times higher among subjects with a thoracic aorta calcium burden on CT in the highest quartile compared with those in the lowest two quartiles of the distribution (18.0 % vs. 4.9 %; P  < 0.001). CVD risk was similar in subjects in all quartiles of thoracic aorta 18 F-FDG uptake. Conclusion Our findings indicate that an unfavourable CVD risk profile is associated with marked increases in vascular calcification metabolism and vascular calcium burden of the thoracic aorta, but not with arterial inflammation.

Objectives To analyse computed tomography (CT) findings of interval and post-screen carcinomas in lung cancer screening. Methods Consecutive interval and post-screen carcinomas from the Dutch–Belgium lung cancer screening trial were included. The prior screening and the diagnostic chest CT were reviewed by two experienced radiologists in consensus with knowledge of the tumour location on the diagnostic CT. Results Sixty-one participants (53 men) were diagnosed with an interval or post-screen carcinoma. Twenty-two (36 %) were in retrospect visible on the prior screening CT. Detection error occurred in 20 cancers and interpretation error in two cancers. Errors involved intrabronchial tumour ( n  = 5), bulla with wall thickening ( n  = 5), lymphadenopathy ( n  = 3), pleural effusion ( n  = 1) and intraparenchymal solid nodules ( n  = 8). These were missed because of a broad pleural attachment ( n  = 4), extensive reticulation surrounding a nodule ( n  = 1) and extensive scarring ( n  = 1). No definite explanation other than human error was found in two cases. None of the interval or post-screen carcinomas involved a subsolid nodule. Conclusions Interval or post-screen carcinomas that were visible in retrospect were mostly due to detection errors of solid nodules, bulla wall thickening or endobronchial lesions. Interval or post-screen carcinomas without explanation other than human errors are rare. Key points • 22 % of missed carcinomas originally presented as bulla wall thickening on CT. • 22 % of missed carcinomas originally presented as endobronchial lesions on CT. • All malignant endobronchial lesions presented as interval carcinomas. • In the NELSON trial subsolid nodules were not a source of missed carcinomas.

Objective To determine whether semiautomatic volumetric software can differentiate part-solid from nonsolid pulmonary nodules and aid quantification of the solid component. Methods As per reference standard, 115 nodules were differentiated into nonsolid and part-solid by two radiologists; disagreements were adjudicated by a third radiologist. The diameters of solid components were measured manually. Semiautomatic volumetric measurements were used to identify and quantify a possible solid component, using different Hounsfield unit (HU) thresholds. The measurements were compared with the reference standard and manual measurements. Results The reference standard detected a solid component in 86 nodules. Diagnosis of a solid component by semiautomatic software depended on the threshold chosen. A threshold of −300 HU resulted in the detection of a solid component in 75 nodules with good sensitivity (90 %) and specificity (88 %). At a threshold of −130 HU, semiautomatic measurements of the diameter of the solid component (mean 2.4 mm, SD 2.7 mm) were comparable to manual measurements at the mediastinal window setting (mean 2.3 mm, SD 2.5 mm [ p  = 0.63]). Conclusion Semiautomatic segmentation of subsolid nodules could diagnose part-solid nodules and quantify the solid component similar to human observers. Performance depends on the attenuation segmentation thresholds. This method may prove useful in managing subsolid nodules. Key Points • Semiautomatic segmentation can accurately differentiate nonsolid from part-solid pulmonary nodules • Semiautomatic segmentation can quantify the solid component similar to manual measurements • Semiautomatic segmentation may aid management of subsolid nodules following Fleischner Society recommendations • Performance for the segmentation of subsolid nodules depends on the chosen attenuation thresholds

Purpose This meta-analysis was designed to evaluate the utility of preoperative axillary ultrasound combined with US-guided lymph node biopsy if indicated (AUS ± biopsy), in terms of staging the axilla and preventing two-step axillary surgery in the form of sentinel node biopsy (SNB) followed by completion axillary lymph node (ALN) dissection. Methods We systematically searched electronic databases for studies that addressed preoperative assessment of ALN status by AUS ± biopsy. A pooled estimate was calculated for the false-negative rate (FNR) of AUS ± biopsy (defined as the proportion of women with a negative AUS ± biopsy result subsequently proven to have a positive axilla) and sensitivity (defined as the proportion of women with a positive AUS ± biopsy result among all women with a tumor positive axilla). Results The pooled FNR was 25 % (95 % confidence interval [CI] = 24–27) and the pooled sensitivity was 50 % (95 % CI = 43–57). There was substantial heterogeneity across studies for both FNR ( I 2  = 69.42) and sensitivity ( I 2  = 93.25), which was not explained by between-study differences in biopsy technique, mean/median tumor size, biopsy indication, or study design. Sensitivity was increased in studies with a high prevalence of ALN metastases. Conclusions Preoperative axillary ultrasound-guided biopsy is a useful step in the process of axillary staging. Approximately 50 % of women with axillary involvement can be identified preoperatively. Still, one in four women with an ultrasound-guided biopsy-“proven” negative axilla has a positive SNB.

Lacunar lesions (LLs) and white matter lesions (WMLs) affect cognition. We assessed whether lesions located in specific white matter tracts were associated with cognitive performance taking into account total lesion burden. Within the Second Manifestations of ARTerial disease Magnetic Resonance (SMART-MR) study, cross-sectional analyses were performed on 516 patients with manifest arterial disease. We applied an assumption-free voxel-based lesion-symptom mapping approach to investigate the relation between LL and WML locations on 1.5 Tesla brain MRI and compound scores of executive functioning, memory and processing speed. Secondly, a multivariable linear regression model was used to relate the regional volume of LLs and WMLs within specific white matter tracts to cognitive functioning. Voxel-based lesion-symptom mapping identified several clusters of voxels with a significant correlation between WMLs and executive functioning, mostly located within the superior longitudinal fasciculus and anterior thalamic radiation. In the multivariable linear regression model, a statistically significant association was found between regional LL volume within the superior longitudinal fasciculus and anterior thalamic radiation and executive functioning after adjustment for total LL and WML burden. These findings identify the superior longitudinal fasciculus and anterior thalamic radiation as key anatomical structures in executive functioning and emphasize the role of strategically located vascular lesions in vascular cognitive impairment.

Objectives Multimodal non-invasive imaging plays a key role in establishing a diagnosis of PHV endocarditis. The objective of this study was to provide a systematic review of the literature and meta-analysis of the diagnostic accuracy of TTE, TEE, and MDCT in patients with (suspected) PHV endocarditis. Methods Studies published between 1985 and 2013 were identified via search and cross-reference of PubMed/Embase databases. Studies were included if (1) they reported on the non-invasive index tests TTE, TEE, or MDCT; (2) data was provided on PHV endocarditis as the condition of interest; and (3) imaging results were verified against either surgical inspection/autopsy or clinical follow-up reference standards, thereby enabling the extraction of 2-by-2 tables. Results Twenty articles (including 496 patients) met the inclusion criteria for PHV endocarditis. TTE, TEE, and MDCT + TEE had a pooled sensitivity/specificity for vegetations of 29/100 %; 82/95 %, and 88/94 %, respectively. The pooled sensitivity/specificity of TTE, TEE, and MDCT + TEE for periannular complications was 36/93 %, 86/98 %, and 100/94 %, respectively. Conclusions TEE showed good sensitivity and specificity for establishing a diagnosis of PHV endocarditis. Although MDCT data are limited, this review showed that MDCT in addition to TEE may improve sensitivity in detecting life-threatening periannular complications. Key Points • Multimodal imaging is an important ingredient of diagnostic workup for PHV endocarditis . • Transthoracic and transesophageal echography may miss life-threatening periannular complications . • MDCT can improve sensitivity for the detection of life-threatening periannular complications .

BackgroundThis study aimed to evaluate whether incidental CT findings of emphysema, airway thickening and bronchiectasis, as seen on CT scans performed for other non-pulmonary clinical indications, are associated with future acute exacerbations of COPD resulting in hospitalisation or death.MethodsThis multicentre prospective case–cohort study comprised 6406 subjects who underwent routine diagnostic chest CT for non-pulmonary indications. Using a case–cohort approach, we visually graded CT scans from cases and a random sample of ∼10% of the baseline cohort (n=704) for emphysema severity (range 0–20), airway thickening (range 0–5) and bronchiectasis (range 0–5). We used weighted Cox proportional hazards analysis to assess the independent association between CT findings and hospitalisation or death due to COPD exacerbation.ResultsDuring a median follow-up of 4.4 years (maximum 5.2 years), 338 COPD events were identified. The risk of experiencing a future acute exacerbation of COPD resulting in hospitalisation or death was significantly increased in subjects with severe emphysema (score ≥7) and severe airway thickening (score ≥3). The respective HRs were 4.6 (95% CI 3.0 to 7.1) and 5.9 (95% CI 3.4 to 10.5). Severe bronchiectasis (score ≥3) was not significantly associated with increased risk of adverse events (HR 1.5; 95% CI 0.9 to 2.5).ConclusionsMorphological correlates of COPD such as emphysema and airway thickening detected on CT scans obtained for other non-pulmonary indications are strong independent predictors of subsequent development of acute exacerbations of COPD resulting in hospitalisation or death.