The question remains whether reduced cerebral blood flow (CBF) leads to brain atrophy or vice versa. We studied the longitudinal relation between CBF and brain volume in a community-dwelling ...population. In the Rotterdam Study, 3011 participants (mean age 59.6 years (s.d. 8.0)) underwent repeat brain magnetic resonance imaging to quantify brain volume and CBF at two time points. Adjusted linear regression models were used to investigate the bidirectional relation between CBF and brain volume. We found that smaller brain volume at baseline was associated with a steeper decrease in CBF in the whole population (standardized change per s.d. increase of total brain volume (TBV) = 0.296 (95% confidence interval (CI) 0.200; 0.393)). Only in persons aged ≥ 65 years, a lower CBF at baseline was associated with steeper decline of TBV (standardized change per s.d. increase of CBF = 0.003 (95% CI −0.004; 0.010) in the whole population and 0.020 (95% CI 0.004; 0.036) in those aged ≥65 years of age). Our results indicate that brain atrophy causes CBF to decrease over time, rather than vice versa. Only in persons aged >65 years of age did we find lower CBF to also relate to brain atrophy.
Medical imaging capable of generating imaging biomarkers, specifically radiology and nuclear medicine image acquisition and analysis processes, differs from frequently used comparators like blood or ...urine biomarkers. This difference arises from the sample acquisition methodology. While different analysis methodologies and equipment provide slightly different results in any analytical domain, unlike blood or urine analysis where the samples are obtained by simple extraction or excretion, in radiology the acquisition of the sample is heterogeneous by design, since complex equipment from different vendors is used. Therefore, with this additional degree of freedom in medical imaging, there is still risk of persistent heterogeneity of image quality through time, due to different technological implementations across vendors and protocols used in different centres. Quantitative imaging biomarkers have yet to demonstrate an impact on clinical practice due to this lack of comprehensive standardisation in terms of technical aspects of image acquisition, analysis algorithms, processes and clinical validation.
The aim is establishing a standard methodology based on metrology for the validation of image acquisition and analysis methods used in the extraction of biomarkers and radiomics data. The appropriate implementation of the guidelines herein proposed by radiology departments, research institutes and industry will allow for a significant reduction in inter-vendor & inter-centre variability in imaging biomarkers and determine the measurement error obtained, enabling them to be used in imaging-based criteria for diagnosis, prognosis or treatment response, ultimately improving clinical workflows and patient care. The validation of developed analytical methods must be based on a technical performance validation and clinical validation.
Antithrombotic treatment plays a key role in stroke prevention, but their direct effects on the composition of carotid artery atherosclerotic plaques are unknown. To investigate the association of ...antithrombotic treatment with carotid artery plaque composition, with a specific focus on an intraplaque haemorrhage (IPH).
From the population-based Rotterdam Study, 1740 participants with carotid atherosclerosis on ultrasound (mean age 72.9 years, 46.0 women) underwent magnetic resonance imaging of the carotid arteries to assess plaque composition. Information on the use of oral anticoagulants vitamin K antagonists (VKA) and antiplatelet agents (salicylates), including duration of use and dosage, was obtained from pharmacy records for all participants. We used logistic regression models to assess the association between the use of anticoagulants and antiplatelet agents, and the different plaque components adjusting for confounders. Current and past use of VKA adjusted odds ratio (OR): 1.88, 95% confidence interval (CI): 0.74-4.75 and OR 1.89, 95% CI: 0.91-3.93 and antiplatelet agents (OR: 1.22, 95% CI: 0.91-1.62), and (OR: 1.23, 95% CI: 0.86-1.75) showed positive trend with a higher presence of IPH. Also, a longer duration of use was associated with a higher frequency of IPH (OR: 3.15, 95% CI: 1.23-8.05) for the use of VKA, and longer duration of the use for antiplatelet agents showed a positive trend (OR: 1.21, 95% CI: 0.88-1.67). We also found that higher levels of international normalized ratio above 2.97 for VKA (OR: 1.48, 95% CI: 1.03-2.15) and higher daily defined dosage than 1.0 for antiplatelet agents (OR: 1.50, 95% CI: 1.21-1.87) were related to a higher frequency of IPH. We found no association with lipid core or calcification.
The use of antithrombotic treatment relates to a higher frequency of IPH in carotid atherosclerotic plaques.
Whether newer risk markers for coronary heart disease (CHD) improve CHD risk prediction remains unclear.
To assess whether newer risk markers for CHD risk prediction and stratification improve ...Framingham risk score (FRS) predictions.
Prospective population-based study.
The Rotterdam Study, Rotterdam, the Netherlands.
5933 asymptomatic, community-dwelling participants (mean age, 69.1 years SD, 8.5).
Traditional CHD risk factors used in the FRS (age, sex, systolic blood pressure, treatment of hypertension, total and high-density lipoprotein cholesterol levels, smoking, and diabetes) and newer CHD risk factors (N-terminal fragment of prohormone B-type natriuretic peptide levels, von Willebrand factor antigen levels, fibrinogen levels, chronic kidney disease, leukocyte count, C-reactive protein levels, homocysteine levels, uric acid levels, coronary artery calcium CAC scores, carotid intima-media thickness, peripheral arterial disease, and pulse wave velocity).
Adding CAC scores to the FRS improved the accuracy of risk predictions (c-statistic increase, 0.05 95% CI, 0.02 to 0.06; net reclassification index, 19.3% overall 39.3% in those at intermediate risk, by FRS). Levels of N-terminal fragment of prohormone B-type natriuretic peptide also improved risk predictions but to a lesser extent (c-statistic increase, 0.02 CI, 0.01 to 0.04; net reclassification index, 7.6% overall 33.0% in those at intermediate risk, by FRS). Improvements in predictions with other newer markers were marginal.
The findings may not be generalizable to younger or nonwhite populations.
Among 12 CHD risk markers, improvements in FRS predictions were most statistically and clinically significant with the addition of CAC scores. Further investigation is needed to assess whether risk refinements using CAC scores lead to a meaningful change in clinical outcome. Whether to use CAC score screening as a more routine test for risk prediction requires full consideration of the financial and clinical costs of performing versus not performing the test for both persons and health systems.
Netherlands Organization for Health Research and Development (ZonMw).
A limited number of studies have associated adjuvant chemotherapy with structural brain changes. These studies had small sample sizes and were conducted shortly after cessation of chemotherapy. ...Results of these studies indicate local gray matter volume decrease and an increase in white matter lesions. Up till now, it is unclear if non-CNS chemotherapy is associated with long-term structural brain changes. We compared focal and total brain volume (TBV) of a large set of non-CNS directed chemotherapy-exposed breast cancer survivors, on average 21 years post-treatment, to that of a population-based sample of women without a history of cancer. Structural MRI (1.5T) was performed in 184 chemotherapy-exposed breast cancer patients, mean age 64.0 (SD = 6.5) years, who had been diagnosed with cancer on average 21.1 (SD = 4.4) years before, and 368 age-matched cancer-free reference subjects from a population-based cohort study. Outcome measures were: TBV and total gray and white matter volume, and hippocampal volume. In addition, voxel based morphometry was performed to analyze differences in focal gray matter. The chemotherapy-exposed breast cancer survivors had significantly smaller TBV (−3.5 ml,
P
= 0.019) and gray matter volume (−2.9 ml,
P
= 0.003) than the reference subjects. No significant differences were observed in white matter volume, hippocampal volume, or local gray matter volume. This study shows that adjuvant chemotherapy for breast cancer is associated with long-term reductions in TBV and overall gray matter volume in the absence of focal reductions. The observed smaller gray matter volume in chemotherapy-exposed survivors was comparable to the effect of almost 4 years of age on gray matter volume reduction. These volume differences might be associated with the slightly worse cognitive performance that we observed previously in this group of breast cancer survivors.
Objectives
Diminished function of the posterior cingulate cortex (PCC) is a typical finding in early Alzheimer’s disease (AD). It is hypothesized that in early stage AD, PCC functioning relates to or ...reflects hippocampal dysfunction or atrophy. The aim of this study was to examine the relationship between hippocampus function, volume and structural connectivity, and PCC activation during an episodic memory task-related fMRI study in mild cognitive impairment (MCI).
Method
MCI patients (n = 27) underwent episodic memory task-related fMRI, 3D-T1w MRI, 2D T2-FLAIR MRI and diffusion tensor imaging. Stepwise linear regression analysis was performed to examine the relationship between PCC activation and hippocampal activation, hippocampal volume and diffusion measures within the cingulum along the hippocampus.
Results
We found a significant relationship between PCC and hippocampus activation during successful episodic memory encoding and correct recognition in MCI patients. We found no relationship between the PCC and structural hippocampal predictors.
Conclusions
Our results indicate a relationship between PCC and hippocampus activation during episodic memory engagement in MCI. This may suggest that during episodic memory, functional network deterioration is the most important predictor of PCC functioning in MCI.
Key Points
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PCC functioning during episodic memory relates to hippocampal functioning in MCI
.
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PCC functioning during episodic memory does not relate to hippocampal structure in MCI
.
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Functional network changes are an important predictor of PCC functioning in MCI
.
Background
To investigate the location of recurrences with respect to the radiation fields in oropharynx cancer after intensity‐modulated radiotherapy and stereotactic body radiotherapy (SBRT) boost.
...Methods
Local and regional recurrences were delineated on diagnostic scans which were rigidly coregistered with treatment planning scans, then classified based on the location of the center of mass (COM) as well as volumetrically.
Results
In 195 patients, the 5‐year local and regional control were 90% and 93%, respectively. By COM, 76% of local recurrences were in‐field; 24% were out‐of‐field, significantly higher than 0%‐5% in the literature for conventional regimens (P < 0.01). Regional recurrences (19 in 12 patients) were largely within unirradiated neck levels (47%) and electively irradiated regions (42%).
Conclusions
The regimen with biological equivalent dose intensification provides excellent overall and in‐field local control. The highly conformal boost technique was, however, associated with increased out‐of‐field local failure.
Aims
Components of carotid atherosclerotic plaque such as intraplaque haemorrhage and lipid core are important determinants of plaque progression and destabilization. The association between plaque ...components and risk factors for cardiovascular disease is not well studied.
Methods and results
Participants from the population-based Rotterdam Study with carotid wall thickening on ultrasound (n = 1006) underwent high-resolution magnetic resonance imaging for carotid plaque characterization. Maximum wall thickening, the degree of stenosis, and the presence of intraplaque haemorrhage, lipid core, and calcification were assessed in both carotid arteries and their associations with cardiovascular risk factors were investigated. Intraplaque haemorrhage and lipid core were present in almost 25% of plaques, respectively, and occurred simultaneously in 9% of plaques. In men, intraplaque haemorrhage and lipid core were more prevalent compared with women (28.8 vs. 18.3 and 28.9 vs. 21.7%, respectively). Intraplaque haemorrhage occurred more frequently at older age odds ratio (OR) per 10 years 1.8, 95% confidence interval 1.6-2.1, in men (OR 2.2, 1.7-2.9), in persons with hypertension (multivariate adjusted OR 1.4, 1.1-1.8), and in current smokers (multivariate adjusted OR 1.6, 1.2-2.3). Men (OR 1.5, 1.2-1.9) and subjects with hypercholesterolaemia (multivariate adjusted OR 1.4, 1.1-1.7) more often exhibited a lipid core.
Conclusion
In subjects from the general population with carotid wall thickening, intraplaque haemorrhage and lipid core-both considered indicators of unstable plaque-are highly frequent and more prevalent in men compared with women. Furthermore, different risk factors are associated with these plaque components: hypertension and current smoking were risk factors for the presence of intraplaque haemorrhage, and hypercholesterolaemia was the only risk factor for lipid core presence.
Background and purpose
Dolichoarteriopathies of the extracranial part of the internal carotid artery (ICA) are associated with cerebrovascular events, yet information on their prevalence and risk ...factors remains limited. The aim of the present study therefore was to study the prevalence and risk factors of dolichoarteriopathies in a sample of patients with cerebrovascular symptoms from the Plaque At RISK (PARISK) study.
Methods
In a random sample of 100 patients from the PARISK study, multidetector computed tomography angiography (MDCTA) was performed as part of clinical workup. On MDCTA, we evaluated the extracranial trajectory of the ICA by measuring the length (in millimeters), the tortuosity index (TI; defined as the ICA length divided by the shortest possible distance from bifurcation to skull base), and dolichoarteriopathy type (tortuosity, coiling or kinking). Next, we investigated the association between cardiovascular risk factors and these measurements using linear and logistic regression analyses.
Results
The mean (standard deviation) length of the ICA was 93 (± 14) mm, with a median (interquartile range) TI of 1.2 (1.1–1.3). The overall prevalence of dolichoarteriopathies was 69%, with tortuosity being the most common (72%), followed by coiling (20%), and kinking (8%). We found that age and obesity were associated with a higher TI: difference per 10‐year increase in age: 0.05 (95% confidence interval CI 0.02–0.08) and 0.16 (95% CI 0.07–0.25) for obesity. Obesity and hypercholesterolemia were associated with a more severe type of dolichoarteriopathy (odds ratio OR 2.07 95% CI 1.04–4.12 and OR 2.17 95% CI 1.02–4.63, respectively).
Conclusion
Dolichoarteriopathies in the extracranial ICA are common in patients with cerebrovascular symptoms, and age, obesity and hypercholesterolemia may play an important role in the pathophysiology of these abnormalities.
We investigated the prevalence of internal carotid artery dolichoarteriopathies using quantitative measurements and traditional visual rating in a random sample of patients with cerebrovascular symptoms who underwent multidetector computed tomography angiography. Tortuosity was the most common type of dolichoarteriopathy (72%), followed by coiling (20%), and kinking (8%). Age, obesity, and hypercholesterolemia were significantly associated with a more severe type of dolichoarteriopathy and/or tortuosity index. Therefore, these cardiovascular risk factors may play an important role in the pathophysiology of these abnormalities.
Summary Background Whether infarct size modifies intra-arterial treatment effect is not certain, particularly in patients with large infarcts. We examined the effect of the baseline Alberta Stroke ...Program Early CT Score (ASPECTS) on the safety and efficacy of intra-arterial treatment in a subgroup analysis of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN). Methods MR CLEAN was a randomised, controlled, open-label, phase 3 trial of intra-arterial treatment in patients (aged ≥18 years from the Netherlands) with proximal arterial occlusion of the anterior circulation, given intra-arterial treatment within 6 h of stroke onset. The primary outcome was 90 day modified Rankin Scale (mRS) score. We estimated the intra-arterial treatment effect for all patients in MR CLEAN who had ASPECTS graded by using multivariable ordinal logistic regression analysis (a proportional odds model) to calculate the adjusted common odds ratio for a shift towards a better functional outcome according to the mRS for intra-arterial treatment and usual care than for usual care alone. We entered an interaction term into the model to test for interaction with prespecified ASPECTS subgroups: 0–4 (large infarct) versus 5–7 (moderate infarct) versus 8–10 (small infarct). MR CLEAN is registered with the Netherlands Trial Registry, number NTR1804, and the ISRCTN Registry, number ISRCTN10888758. Findings 496 patients—232 (47%) in the intra-arterial treatment and usual care group and 264 (53%) in the usual care alone group—were included in the analysis. We noted no significant difference in intra-arterial treatment effect between the ASPECTS subgroups according to 90 day ordinal mRS (adjusted common odds ratio interaction term relative to ASPECTS 8–10: ASPECTS 0–4: 0·79 95% CI 0·20–3·19, p=0·740; and ASPECTS 5–7: 1·02 0·44–2·35, p=0·966). Intra-arterial treatment did not cause a significant increase in the proportion of patients with at least one serious adverse event in any of the ASPECTS subgroups (ASPECTS 0–4: eight 73% of 11 patients in treatment and usual care group vs 11 58% of 19 in usual care alone group, p=0·42; ASPECTS 5–7: 32 59% of 54 vs 19 49% of 39, p=0·31; ASPECTS 8–10: 70 42% of 167 vs 82 40% of 206; p=0·68). For death within 7 days or within 30 days and hemicraniectomy, the differences between the intra-arterial treatment and usual care versus usual care alone groups were not significant by ASPECTS subgroups. A significantly higher proportion of patients had recurrent ischaemic stroke in the intra-arterial treatment plus usual care group than in the usual care alone group in the ASPECTS 8–10 subgroup (eight 5% vs one <1%; p=0·007). Interpretation Contrary to findings from previous studies suggesting that only patients with non-contrast CT ASPECTS of more than 7 benefit from intra-arterial treatment, data from this study suggest that patients with ASPECTS 5–7 should be treated. Further evidence is needed for patients with ASPECTS 0–4, for whom treatment might yield only marginal absolute benefit. Funding Dutch Heart Foundation, AngioCare, Medtronic/Covidien/EV3, Medac/Lamepro, Penumbra, Stryker, and Top Medical.
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