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Delirium is associated with long-term cognitive dysfunction and with increased brain atrophy. However, it is unclear whether these problems result from or predisposes to delirium. We aimed to investigate preoperative to postoperative brain changes, as well as the role of delirium in these changes over time. We investigated the effects of surgery and postoperative delirium with brain MRIs made before and 3 months after major elective surgery in 299 elderly patients, and an MRI with a 3 months follow-up MRI in 48 non-surgical control participants. To study the effects of surgery and delirium, we compared brain volumes, white matter hyperintensities and brain infarcts between baseline and follow-up MRIs, using multiple regression analyses adjusting for possible confounders. Within the patients group, 37 persons (12%) developed postoperative delirium. Surgical patients showed a greater decrease in grey matter volume than non-surgical control participants [linear regression: B (95% confidence interval) = -0.65% of intracranial volume (-1.01 to -0.29, P < 0.005)]. Within the surgery group, delirium was associated with a greater decrease in grey matter volume [B (95% confidence interval): -0.44% of intracranial volume (-0.82 to -0.06, P = 0.02)]. Furthermore, within the patients, delirium was associated with a non-significantly increased risk of a new postoperative brain infarct [logistic regression: odds ratio (95% confidence interval): 2.8 (0.7-11.1), P = 0.14]. Our study was the first to investigate the association between delirium and preoperative to postoperative brain volume changes, suggesting that delirium is associated with increased progression of grey matter volume loss.

White matter hyperintensity (WMH) shape has been associated with the severity of the underlying brain pathology, suggesting it is a potential neuroimaging marker of WMH impact on brain function.In 563 patients with vascular disease (58 +/- 10 years), we examined the relationship between WMH volume, shape, and cognitive functioning. WMH volume and shape were automatically determined on 1.5T brain MRI data. Standardized linear regression analyses estimated the association between WMH volume and shape (concavity index, solidity, convexity, fractal dimension, and eccentricity) and memory and executive functioning, adjusted for age, sex, educational level, and reading ability.Larger WMH volumes were associated with lower executive functioning Z-scores ( b (95%-CI):-0.09 (-0.17;-0.01)). Increased shape complexity of periventricular/confluent WMH associated with lower exec-utive functioning (concavity index + 1SD:-0.13 (-0.20;-0.06); solidity-1SD:-0.09 (-0.17;-0.02)) and lower memory function (fractal dimension + 1SD:-0.10 (-0.18;-0.02)). Of note, the association between concav-ity index and executive functioning was independent of WMH volume (-0.12 (-0.19;-0.04)). Our results suggest that WMH shape contains additional information about WMH burden, not other-wise captured by WMH volume.(c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

Asymptomatic low-grade carotid artery stenosis (LGCS) is a common finding in patients with manifest arterial disease, however its relationship with brain MRI changes and cognitive decline is unclear. We included 902 patients (58 ± 10 years; 81% male) enrolled in the Second Manifestations of Arterial Disease – Magnetic Resonance (SMART-MR) study without a history of cerebrovascular disease. LGCS was defined as 1–49% stenosis on baseline carotid ultrasound, whereas no LGCS (reference category) was defined as absence of carotid plaque. Brain and white matter hyperintensity (WMH) volumes and cognitive function were measured at baseline and after 4 (n = 480) and 12 years (n = 222) of follow-up. Using linear mixed-effects models, we investigated associations of LGCS with progression of brain atrophy, WMH, and cognitive decline. LGCS was associated with greater progression of global brain atrophy (estimate −0.03; 95%CI, −0.06 to −0.01; p = 0.002), and a greater decline in executive functioning (estimate −0.02; 95%CI, −0.031 to −0.01; p

Introduction: It has been hypothesized that carotid artery stenosis (CAS) may lead to greater atrophy of subserved brain regions; however, prospective studies on the impact of CAS on progression of hemispheric brain atrophy are lacking. We examined the association between CAS and progression of hemispheric brain atrophy. Methods: We included 654 patients (57 ± 9 years) of the SMART-MR study, a prospective cohort study of patients with manifest arterial disease. Patients had baseline CAS duplex measurements and a 1.5T brain MRI at baseline and after 4 years of follow-up. Mean change in hemispheric brain volumes (% of intracranial volume [ICV]) was estimated between baseline and follow-up for left-sided and right-sided CAS across three degrees of stenosis (mild [≤29%], moderate [30–69%], and severe [≥70%]), adjusting for demographics, cerebrovascular risk factors, and brain infarcts. Results: Mean decrease in left and right hemispheric brain volumes was 1.15% ICV and 0.82% ICV, respectively, over 4 years of follow-up. Severe right-sided CAS, compared to mild CAS, was associated with a greater decrease in volume of the left hemisphere (B = −0.49% ICV, 95% CI: −0.86 to −0.13) and more profoundly of the right hemisphere (B = −0.90% ICV, 95% CI: −1.27 to −0.54). This pattern was independent of cerebrovascular risk factors, brain infarcts, and white matter hyperintensities on MRI, and was also observed when accounting for the presence of severe bilateral CAS. Increasing degrees of left-sided CAS, however, was not associated with greater volume loss of the left or right hemisphere. Conclusions: Our data indicate that severe (≥70%) CAS could represent a risk factor for greater ipsilateral brain volume loss, independent of cerebrovascular risk factors, brain infarcts, or white matter hyperintensities on MRI. Further longitudinal studies in other cohorts are warranted to confirm this novel finding.

Global cerebral hypoperfusion may be involved in the aetiology of brain atrophy; however, long-term longitudinal studies on this relationship are lacking. We examined whether reduced cerebral blood flow was associated with greater progression of brain atrophy. Data of 1165 patients (61 ± 10 years) from the SMART-MR study, a prospective cohort study of patients with arterial disease, were used of whom 689 participated after 4 years and 297 again after 12 years. Attrition was substantial. Total brain volume and total cerebral blood flow were obtained from magnetic resonance imaging scans and expressed as brain parenchymal fraction (BPF) and parenchymal cerebral blood flow (pCBF). Mean decrease in BPF per year was 0.22% total intracranial volume (95% CI: –0.23 to –0.21). Mean decrease in pCBF per year was 0.24 ml/min per 100 ml brain volume (95% CI: –0.29 to –0.20). Using linear mixed models, lower pCBF at baseline was associated with a greater decrease in BPF over time ( p = 0.01). Lower baseline BPF, however, was not associated with a greater decrease in pCBF ( p = 0.43). These findings indicate that reduced cerebral blood flow is associated with greater progression of brain atrophy and provide further support for a role of cerebral blood flow in the process of neurodegeneration.

BACKGROUND AND PURPOSE: The clinical relevance of cortical microinfarcts has recently been established; however, studies on microinfarcts in the deep gray matter are lacking. We examined the risk factors and MR imaging correlates of microinfarcts in the deep gray matter on 7T MR imaging and their relation to cognitive functioning.\MATERIALS AND METHODS: Within the Second Manifestations of ARTerial disease?Magnetic Resonance (SMART-MR) study, 213 patients (mean age, 68 [SD, 8]?years) had a risk-factor assessment, 7T and 1.5T brain MR imaging, and a cognitive examination. Microinfarcts on 7T MR imaging were defined as lesions of < 5 mm. Regression models were used to examine the age-adjusted associations among risk factors, MR imaging markers, and microinfarcts. Cognitive function was summarized as composite and domain-specific z scores. RESULTS: A total of 47 microinfarcts were found in 28 patients (13%), most commonly in the thalamus. Older age, history of stroke, hypertension, and intima-media thickness were associated with microinfarcts. On 1.5T MR imaging, cerebellar infarcts (relative risk = 2.75; 95% CI, 1.4?5.33) and lacunes in the white (relative risk = 3.28; 95% CI, 3.28?6.04) and deep gray matter (relative risk?= 3.06; 95% CI, 1.75?5.35) were associated with microinfarcts, and on 7T MR imaging cortical microinfarcts (relative risk = 2.33; 95% CI, 1.32?4.13). Microinfarcts were also associated with poorer global cognitive functioning (mean difference in the global z score between patients with multiple microinfarcts versus none = ?0.97; 95% CI, ?1.66 to ?0.28, P = .006) and across all cognitive domains. CONCLUSIONS: Microinfarcts in the deep gray matter on 7T MR imaging were associated with worse cognitive functioning and risk factors and MR imaging markers of small-vessel and large-vessel disease. Our findings suggest that microinfarcts in the deep gray matter may represent a novel imaging marker of vascular brain injury.

The underlying structural correlates of predisposition to postoperative delirium remain largely unknown. A combined analysis of preoperative brain magnetic resonance imaging (MRI) markers could improve our understanding of the pathophysiology of delirium. Therefore, we aimed to identify different MRI brain phenotypes in older patients scheduled for major elective surgery, and to assess the relation between these phenotypes and postoperative delirium. Markers of neurodegenerative and neurovascular brain changes were determined from MRI brain scans in older patients (n = 161, mean age 71, standard deviation 5 years), of whom 24 (15%) developed delirium. A hierarchical cluster analysis was performed. We found six distinct groups of patients with different MRI brain phenotypes. Logistic regression analysis showed a higher odds of developing postoperative delirium in individuals with multi-burden pathology (n = 15 (9%), odds ratio (95% confidence interval): 3.8 (1.1–13.0)). In conclusion, these results indicate that different MRI brain phenotypes are related to a different risk of developing delirium after major elective surgery. MRI brain phenotypes could assist in an improved understanding of the structural correlates of predisposition to postoperative delirium.

ObjectiveTo determine whether white matter hyperintensity (WMH) markers on MRI are associated with long-term risk of mortality and ischemic stroke.MethodsWe included consecutive patients with manifest arterial disease enrolled in the Second Manifestations of Arterial Disease–Magnetic Resonance (SMART-MR) study. We obtained WMH markers (volume, type, and shape) from brain MRI scans performed at baseline using an automated algorithm. During follow-up, occurrence of death and ischemic stroke was recorded. Using Cox regression, we investigated associations of WMH markers with risk of mortality and ischemic stroke, adjusting for demographics, cardiovascular risk factors, and cerebrovascular disease.ResultsWe included 999 patients (59 ± 10 years; 79% male) with a median follow-up of 12.5 years (range 0.2–16.0 years). A greater periventricular or confluent WMH volume was independently associated with a greater risk of vascular death (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.13–1.47) for a 1-unit increase in natural log-transformed WMH volume and ischemic stroke (HR 1.53, 95% CI 1.26–1.86). A confluent WMH type was independently associated with a greater risk of vascular (HR 1.89, 95% CI 1.15-3.11) and nonvascular death (HR 1.65, 95% CI 1.01–2.73) and ischemic stroke (HR 2.83, 95% CI 1.36-5.87). A more irregular shape of periventricular or confluent WMH, as expressed by an increase in concavity index, was independently associated with a greater risk of vascular (HR 1.20, 95% CI 1.05–1.38 per SD increase) and nonvascular death (HR 1.21, 95% CI 1.03–1.42) and ischemic stroke (HR 1.28, 95% CI 1.05–1.55).ConclusionsWMH volume, type, and shape are associated with long-term risk of mortality and ischemic stroke in patients with manifest arterial disease.

We determined the occurrence and association of cortical cerebral microinfarcts (CMIs) at 7 T MRI with risk factors, neuroimaging markers of small and large vessel disease, and cognitive functioning. Within the Medea-7T study, a diverse cohort of older persons with normal cognition, patients with vascular disease, and memory clinic patients, we included 386 participants (68 ± 9 years) with available 7 T and 1.5 T/3T brain MRI, and risk factor and neuropsychological data. CMIs were found in 10% of participants and were associated with older age (RR = 1.79 per +10 years, 95%CI 1.28–2.50), history of stroke or TIA (RR = 4.03, 95%CI 2.18–7.43), cortical infarcts (RR = 5.28, 95%CI 2.91–9.55), lacunes (RR = 5.66, 95%CI 2.85–11.27), cerebellar infarcts (RR = 2.73, 95%CI 1.27–5.84) and decreased cerebral blood flow (RR = 1.35 per −100 ml/min, 95%CI 1.00–1.83), after adjustment for age and sex. Furthermore, participants with >2 CMIs had 0.5 SD (95%CI 0.05–0.91) lower global cognitive performance, compared to participants without CMIs. Our results indicate that CMIs on 7 T MRI are observed in vascular and memory clinic patients with similar frequency, and are associated with older age, history of stroke or TIA, other brain infarcts, and poorer global cognitive functioning.

BACKGROUND: The effectiveness of carotid endarterectomy (CEA) for stroke prevention depends on low procedural risks. The aim of this study was to assess the frequency and timing of procedural complications after CEA, which may clarify underlying mechanisms and help inform safe discharge policies.METHODS: Individual-patient data were obtained from four large carotid intervention trials (VACS, ACAS, ACST-1 and GALA; 1983-2007). Patients undergoing CEA for asymptomatic carotid artery stenosis directly after randomization were used for the present analysis. Timing of procedural death and stroke was divided into intraoperative day 0, postoperative day 0, days 1-3 and days 4-30.RESULTS: Some 3694 patients were included in the analysis. A total of 103 patients (2·l8 per cent) had serious procedural complications (18 fatal strokes, 68 non-fatal strokes, 11 fatal myocardial infarctions and 6 deaths from other causes). Of the 86 strokes, 67 (78 per cent) were ipsilateral, 17 (20 per cent) were contralateral and two (2 per cent) were vertebrobasilar. Forty-five strokes (52 per cent) were ischaemic, nine (10 per cent) haemorrhagic, and stroke subtype was not determined in 32 patients (37 per cent). Half of the strokes happened on the day of CEA. Of all serious complications recorded, 44 (42·7 per cent) occurred on day 0 (20 intraoperative, 17 postoperative, 7 with unclear timing), 23 (22·3 per cent) on days 1-3 and 36 (35·0 per cent) on days 4-30.CONCLUSION: At least half of the procedural strokes in this study were ischaemic and ipsilateral to the treated artery. Half of all procedural complications occurred on the day of surgery, but one-third after day 3 when many patients had been discharged.

The Monro-Kellie hypothesis (MKH) states that volume changes in any intracranial component (blood, brain tissue, cerebrospinal fluid) should be counterbalanced by a co-occurring opposite change to maintain intracranial pressure within the fixed volume of the cranium. In this feasibility study, we investigate the MKH application to structural magnetic resonance imaging (MRI) in observing compensating intracranial volume changes during hypercapnia, which causes an increase in cerebral blood volume. Seven healthy subjects aged from 24 to 64 years (median 32), 4 males and 3 females, underwent a 3-T three-dimensional T1-weighted MRI under normocapnia and under hypercapnia. Intracranial tissue volumes were computed. According to the MKH, the significant increase in measured brain parenchymal volume (median 6.0 mL; interquartile range 4.5, 8.5; p = 0.016) during hypercapnia co-occurred with a decrease in intracranial cerebrospinal fluid (median -10.0 mL; interquartile range -13.5, -6.5; p = 0.034). These results convey several implications: (i) blood volume changes either caused by disorders, anaesthesia, or medication can affect outcome of brain volumetric studies; (ii) besides probing tissue displacement, this approach may assess the brain cerebrovascular reactivity. Future studies should explore the use of alternative sequences, such as three-dimensional T2-weighted imaging, for improved quantification of hypercapnia-induced volume changes.

Frailty is a common syndrome in older individuals that is associated with poor cognitive outcome. The underlying brain correlates of frailty are unclear. The aim of this study was to investigate the association between frailty and MRI features of cerebral small vessel disease in a group of non-demented older individuals. We included 170 participants who were classified as frail (n = 30), pre-frail (n = 85) or non-frail (n = 55). The association of frailty and white matter hyperintensity volume and shape features, lacunar infarcts and cerebral perfusion was investigated by regression analyses adjusted for age and sex. Frail and pre-frail participants were older, more often female and showed higher white matter hyperintensity volume (0.69 [95%-CI 0.08 to 1.31], p = 0.03 respectively 0.43 [95%-CI: 0.04 to 0.82], p = 0.03) compared to non-frail participants. Frail participants showed a non-significant trend, and pre-frail participants showed a more complex shape of white matter hyperintensities (concavity index: 0.04 [95%-CI: 0.03 to 0.08], p = 0.03; fractal dimensions: 0.07 [95%-CI: 0.00 to 0.15], p = 0.05) compared to non-frail participants. No between group differences were found in gray matter perfusion or in the presence of lacunar infarcts. In conclusion, increased white matter hyperintensity volume and a more complex white matter hyperintensity shape may be structural brain correlates of the frailty phenotype.

BACKGROUND AND PURPOSE: Intracranial atherosclerosis, a major risk factor for ischemic stroke, is thought to have different atherogenic mechanisms than extracranial atherosclerosis. Studies investigating their relationship in vivo are sparse and report inconsistent results. We studied the relationship between intracranial atherosclerosis and extracranial atherosclerosis in a cohort of patients with a history of vascular disease. MATERIALS AND METHODS: Within the Second Manifestations of ARTerial disease-Magnetic Resonance (SMART) study, cross-sectional analyses were performed in 130 patients (mean age, 68 ± 9 years) with a history of vascular disease and with assessable 7T intracranial vessel wall MR imaging data. Intracranial atherosclerosis burden was defined as the number of intracranial vessel wall lesions in the circle of Willis and its major branches. Age- and sex-adjusted unstandardized regression coefficients (b-value) were calculated with intracranial atherosclerosis burden as the dependent variable and extracranial atherosclerosis markers as independent variables. RESULTS: Ninety-six percent of patients had ≥1 vessel wall lesion, with a mean intracranial atherosclerosis burden of 8.5 ± 5.7 lesions. Significant associations were observed between higher intracranial atherosclerosis burden and carotid intima-media thickness (b = 0.53 lesions per +0.1 mm; 95% CI, 0.1-1.0 lesions), 50%-100% carotid stenosis versus no stenosis (b = 6.6 lesions; 95% CI, 2.3-10.9 lesions), ankle-brachial index ≤ 0.9 versus >0.9 (b = 4.9 lesions; 95% CI, 1.7-8.0 lesions), and estimated glomerular filtration rate (b = -0.77 lesions per +10 mL/min; 95% CI, -1.50 to -0.03 lesions). No significant differences in intracranial atherosclerosis burden were found among different categories of vascular disease. CONCLUSIONS: Intracranial atherosclerosis was associated with various extracranial markers of atherosclerosis, not supporting a different etiology.

Frailty is a common syndrome in older individuals that is associated with poor cognitive outcome. The underlying brain correlates of frailty are unclear. The aim of this study was to investigate the association between frailty and MRI features of cerebral small vessel disease in a group of non-demented older individuals. We included 170 participants who were classified as frail (n = 30), pre-frail (n = 85) or non-frail (n = 55). The association of frailty and white matter hyperintensity volume and shape features, lacunar infarcts and cerebral perfusion was investigated by regression analyses adjusted for age and sex. Frail and pre-frail participants were older, more often female and showed higher white matter hyperintensity volume (0.69 [95%-CI 0.08 to 1.31], p = 0.03 respectively 0.43 [95%-CI: 0.04 to 0.82], p = 0.03) compared to non-frail participants. Frail participants showed a non-significant trend, and pre-frail participants showed a more complex shape of white matter hyperintensities (concavity index: 0.04 [95%-CI: 0.03 to 0.08], p = 0.03; fractal dimensions: 0.07 [95%-CI: 0.00 to 0.15], p = 0.05) compared to non-frail participants. No between group differences were found in gray matter perfusion or in the presence of lacunar infarcts. In conclusion, increased white matter hyperintensity volume and a more complex white matter hyperintensity shape may be structural brain correlates of the frailty phenotype.

BackgroundCerebral microbleeds (CMB) occur in the context of cerebral small vessel disease. Other brain MRI markers of cerebral small vessel disease are associated with the occurrence of postoperative delirium (POD) and postoperative cognitive dysfunction (POCD), but for CMB this is unknown. We aimed to study the association between CMB and the occurrence of POD and POCD in older individuals.MethodsThe current study consists of 65 patients (72±5 years) from the BIOCOG study, which is a prospective, observational study of patients who underwent an elective surgery of at least 60 minutes. Patients in the current study received a preoperative cerebral MRI scan including a 3D susceptibility-weighted imaging sequence to detect CMB. The occurrence of POD was screened for twice a day until postoperative day 7 by using the DSM-5, NuDesc, CAM, and CAM-ICU. The occurrence of POCD was determined by the reliable change index model at 7 days after surgery or discharge, respectively, and 3 months after surgery. Statistical analyses consisted of logistic regression adjusted for age and gender.ResultsA total of 39 CMB were detected in 17 patients (26%) prior to surgery. POD occurred in 14 out of 65 patients (22%). POCD at 7 days after surgery occurred in 11 out of 54 patients (20%) and in 3 out of 40 patients at the 3 month follow-up (8%). Preoperative CMB were not associated with the occurrence of POD (OR (95%-CI): 0.28 (0.05, 1.57); p = 0.147) or POCD at 7 days after surgery (0.76 (0.16, 3.54); p = 0.727) or at 3 months follow-up (0.61 (0.03, 11.64); p = 0.740).ConclusionWe did not find an association between preoperative CMB and the occurrence of POD or POCD.Trial registrationclinicaltrials.gov (NCT02265263) on 23 September 2014.

INTRODUCTION: Von Willebrand Factor (VWF), ADAMTS13, fibrinogen and fibrinogen γ' are associated with an increased risk of ischemic stroke. Carotid atherosclerosis is an important risk factor for ischemic stroke. Characteristics of the vulnerable plaque; intraplaque hemorrhage (IPH), plaque ulceration and lipid-rich necrotic core (LRNC) can be visualized with imaging techniques. Since atherosclerosis might attribute to the association between coagulation factors and ischemic stroke risk, the aim of this study is to investigate the association between coagulation factors and atherosclerotic plaque characteristics in more detail. MATERIALS AND METHODS: In 182 patients of the Plaque-At-RISK study (prospective multicenter cohort study) with a recent transient ischemic attack (TIA) or ischemic stroke and a symptomatic mild-to-moderate carotid artery stenosis, we measured VWF antigen (VWF:Ag), ADAMTS13 activity, fibrinogen (Clauss), and fibrinogen γ'. Presence of plaque ulceration, IPH volume and LRNC volume were determined by Multidetector-Row Computed Tomography (MDCTA, n = 160) and Magnetic Resonance Imaging (MRI, n = 172). Linear regression analysis was used to assess the association between imaging biomarkers and coagulation factors. RESULTS: VWF:Ag or ADAMTS13 levels were not significantly associated with plaque ulceration, IPH and LRNC. We found an inverse association between fibrinogen and fibrinogen γ' and IPH volume (B = -23.40 mm3/g/L, p = 0.01 and B = -161.73 mm3/g/L, p = 0.01) and between fibrinogen and fibrinogen γ' and LRNC volume (B = -38.89 mm3 g/L, p

Introduction Blood pressure (BP) regulation is important in patients with carotid artery atherosclerotic disease. Concomitant subclavian artery stenosis (SAS) might lead to an underestimation of the true systemic BP in the monitoring of these patients. This study aimed to assess the prevalence of the inter-arm BP difference in patients undergoing carotid intervention and its association with ipsilateral significant subclavian stenosis and clinical outcome. Methods Bilateral BP measurements and vascular imaging (CTA and MRA) of both subclavian arteries and the innominate artery were assessed in 182 symptomatic patients with carotid artery stenosis undergoing revascularisation in the International Carotid Stenting Study (ICSS). Data were separately analysed according to previously described cutoff values for systolic BP (SBP) differences of ≥10 and 50% diameter reduction. Results Of the 182 patients, 39 (21%) showed an inter-arm difference in SBP >15 mmHg. The mean inter-arm SBP difference associated with ipsilateral SAS was 14 mmHg. SAS was present in 21/182 (12%) patients. Only two patients (1%) had bilateral stenotic disease. An inter-arm SBP difference of ≥20 mmHg was associated with unilateral SAS (RR 11.8; 95% CI 3.2–43.1) with a sensitivity of 23% and a specificity of 98%. Patients were followed up for a median of 4.0 years (IQR 3.0–6.0; maximum 7.5). Risk of stroke or death during follow-up was 20.0% (95% CI 11.1–28.9) in patients with, and 15.1% (95% CI 12.3–17.9) in patients without SAS (p = .561). The hospital stay was longer in patients with significant SAS (5.0 days, SD 4.9 vs. 2.7 days, SD 4.3, p = .035). Conclusion The present study is the first to affirm the clinical need for the measurement of inter-arm BP differences in patients undergoing carotid revascularisation, especially in the post-operative phase in the prevention of cerebral hyperperfusion.

Arterial spin labeling (ASL) has undergone significant development since its inception; yet, standardized images processing procedures remain elusive. We present ExploreASL, a robust open source ASL image processing pipeline for clinical studies. Initiated through the European COST action ASL network, this joint effort provides integration and analysis of both single- and multi-center datasets across different operating systems. ExploreASL is optimized for both native- and standard-space analyses, and provides visual and automatic quality control on all intermediate and final images, allowing exploration of ASL datasets from multiple perspectives.

Arterial spin labeling (ASL) has undergone significant development since its inception, with a focus on improving standardization and reproducibility of its acquisition and quantification. In a community-wide effort towards robust and reproducible clinical ASL image processing, we developed the software package ExploreASL, allowing standardized analyses across centers and scanners. The procedures used in ExploreASL capitalize on published image processing advancements and address the challenges of multi-center datasets with scanner-specific processing and artifact reduction to limit patient exclusion. ExploreASL is self-contained, written in MATLAB and based on Statistical Parameter Mapping (SPM) and runs on multiple operating systems. The toolbox adheres to previously defined international standards for data structure, provenance, and best analysis practice. ExploreASL was iteratively refined and tested in the analysis of >10,000 ASL scans using different pulse-sequences in a variety of clinical populations, resulting in four processing modules: Import, Structural, ASL, and Population that perform tasks, respectively, for data curation, structural and ASL image processing and quality control, and finally preparing the results for statistical analyses on both single-subject and group level. We illustrate ExploreASL processing results from three cohorts: perinatally HIV-infected children, healthy adults, and elderly at risk for neurodegenerative disease. We show the reproducibility for each cohort when processed at different centers with different operating systems and MATLAB versions, and its effects on the quantification of gray matter cerebral blood flow. ExploreASL facilitates the standardization of image processing and quality control, allowing the pooling of cohorts to increase statistical power and discover between-group perfusion differences. Ultimately, this workflow may advance ASL for wider adoption in clinical studies, trials, and practice.

Neurodegenerative and neurovascular diseases lead to heterogeneous brain abnormalities. A combined analysis of these abnormalities by phenotypes of the brain might give a more accurate representation of the underlying aetiology. We aimed to identify different MRI phenotypes of the brain and assessed the risk of future stroke and mortality within these subgroups. In 1003 patients (59 ± 10 years) from the Second Manifestations of ARTerial disease-Magnetic Resonance (SMART-MR) study, different quantitative 1.5T brain MRI markers were used in a hierarchical clustering analysis to identify 11 distinct subgroups with a different distribution in brain MRI markers and cardiovascular risk factors, and a different risk of stroke (Cox regression: from no increased risk compared to the reference group with relatively few brain abnormalities to HR = 10.34; 95% CI 3.80↔28.12 for the multi-burden subgroup) and mortality (from no increased risk compared to the reference group to HR = 4.00; 95% CI 2.50↔6.40 for the multi-burden subgroup). In conclusion, within a group of patients with manifest arterial disease, we showed that different MRI phenotypes of the brain can be identified and that these were associated with different risks of future stroke and mortality. These MRI phenotypes can possibly classify individual patients and assess their risk of future stroke and mortality.

Lacunes and white matter hyperintensities (WMHs) are features of cerebral small vessel disease (CSVD) that are associated with poor functional outcomes. However, how the two are related remains unclear. In this study, we examined the association between lacunes and several WMH features in patients with a history of vascular disease. A total of 999 patients (mean age 59 ± 10 years) with a 1.5 T brain magnetic resonance imaging (MRI) scan were included from the SMART-MR study. Lacunes were scored visually and WMH features (volume, subtype and shape) were automatically determined. Analyses consisted of linear and Poisson regression adjusted for age, sex, and total intracranial volume (ICV). Patients with lacunes (n = 188; 19%) had greater total (B = 1.03, 95% CI: 0.86 to 1.21), periventricular/confluent (B = 1.08, 95% CI: 0.89 to 1.27), and deep (B = 0.71, 95% CI: 0.44 to 0.97) natural log-transformed WMH volumes than patients without lacunes. Patients with lacunes had an increased risk of confluent type WMHs (RR = 2.41, 95% CI: 1.98 to 2.92) and deep WMHs (RR = 1.41, 95% CI: 1.22 to 1.62) and had a more irregular shape of confluent WMHs than patients without lacunes, independent of total WMH volume. In conclusion, we found that lacunes on MRI were associated with WMH features that correspond to more severe small vessel changes, mortality, and poor functional outcomes.

Background and Purpose— Cerebral small-vessel disease and cerebral blood flow (CBF) are interrelated. However, the direction of the relationship is unknown, and longitudinal studies are scarce. We investigated the longitudinal relationship between CBF and white matter hyperintensities (WMHs) and lacunes, as representatives of cerebral small-vessel disease, in patients with manifest arterial disease. Methods— Within the Second Manifestations of Arterial Disease-Magnetic Resonance (SMART-MR) study, 1.5T brain magnetic resonance imaging, including an MR angiography, was obtained at baseline and after on ≈3.9 years of follow-up in 575 patients with manifest arterial disease (mean age, 57±10 years). Longitudinal associations of WMHs and lacunes with parenchymal CBF (pCBF; per 100-mL brain volume) were estimated using regression analyses, adjusted for age, sex, follow-up time, and baseline brain measures. Results— Baseline pCBF was not associated with progression of WMHs and lacunes over time. However, periventricular and deep WMHs at baseline were associated with decline in pCBF; mean (95% confidence interval) decline in pCBF per % intracranial volume increase in periventricular and deep WMH volume was −0.70 (−1.40 to −0.00) and −1.01 (−1.64 to −0.38) mL/min per 100-mL brain volume, respectively. These associations were partly explained by cardiovascular risk factors but remained significant for deep WMHs (mean decline [95% confidence interval] in pCBF per % intracranial volume increase in deep WMH volume was −0.92 [−1.56 to −0.28] mL/min per 100-mL brain volume). Lacunes were not associated with change in pCBF. Conclusions— In patients with manifest arterial disease, baseline periventricular and deep WMH volumes were associated with decline in pCBF over time, but baseline pCBF was not associated with progression of WMHs and lacunes over time.

Postoperative cognitive impairment is among the most common medical complications associated with surgical interventions – particularly in elderly patients. In our aging society, it is an urgent medical need to determine preoperative individual risk prediction to allow more accurate cost–benefit decisions prior to elective surgeries. So far, risk prediction is mainly based on clinical parameters. However, these parameters only give a rough estimate of the individual risk. At present, there are no molecular or neuroimaging biomarkers available to improve risk prediction and little is known about the etiology and pathophysiology of this clinical condition. In this short review, we summarize the current state of knowledge and briefly present the recently started BioCog project (Biomarker Development for Postoperative Cognitive Impairment in the Elderly), which is funded by the European Union. It is the goal of this research and development (R&D) project, which involves academic and industry partners throughout Europe, to deliver a multivariate algorithm based on clinical assessments as well as molecular and neuroimaging biomarkers to overcome the currently unsatisfying situation.

Background and Purpose—Patients undergoing carotid endarterectomy (CEA) for symptomatic stenosis of the internal carotid artery benefit from early intervention. Heterogeneous data are available on the influence of timing of carotid artery stenting (CAS) on procedural risk. Methods—We investigated the association between timing of treatment (0–7 days and >7 days after the qualifying neurological event) and the 30-day risk of stroke or death after CAS or CEA in a pooled analysis of individual patient data from 4 randomized trials by the Carotid Stenosis Trialists’ Collaboration. Analyses were done per protocol. To obtain combined estimates, logistic mixed models were applied. Results—Among a total of 4138 patients, a minority received their allocated treatment within 7 days after symptom onset (14% CAS versus 11% CEA). Among patients treated within 1 week of symptoms, those treated by CAS had a higher risk of stroke or death compared with those treated with CEA: 8.3% versus 1.3%, risk ratio, 6.7; 95% confidence interval, 2.1 to 21.9 (adjusted for age at treatment, sex, and type of qualifying event). For interventions after 1 week, CAS was also more hazardous than CEA: 7.1% versus 3.6%, adjusted risk ratio, 2.0; 95% confidence interval, 1.5 to 2.7 (P value for interaction with time interval 0.06). Conclusions—In randomized trials comparing stenting with CEA for symptomatic carotid artery stenosis, CAS was associated with a substantially higher periprocedural risk during the first 7 days after the onset of symptoms. Early surgery is safer than stenting for preventing future stroke.

To determine whether the obesity paradox exists in patients who undergo carotid artery stenting (CAS) or carotid endarterectomy (CEA) for symptomatic carotid artery stenosis. We combined individual patient data from 2 randomized trials (Endarterectomy vs Angioplasty in Patients with Symptomatic Severe Carotid Stenosis and Stent-Protected Angioplasty vs Carotid Endarterectomy) and 3 centers in a third trial (International Carotid Stenting Study). Baseline body mass index (BMI) was available for 1,969 patients and classified into 4 groups: 120 days after randomization). This outcome was compared between different BMI strata in CAS and CEA patients separately, and in the total group. We performed intention-to-treat multivariable Cox regression analyses. Median follow-up was 2.0 years. Stroke or death occurred in 159 patients in the periprocedural (cumulative risk 8.1%) and in 270 patients in the postprocedural period (rate 4.8/100 person-years). BMI did not affect periprocedural risk of stroke or death for patients assigned to CAS (ptrend = 0.39) or CEA (ptrend = 0.77) or for the total group (ptrend = 0.48). Within the total group, patients with BMI 25

PURPOSE: To provide insight into the effect of water T1 relaxation (T1wat ) on amide proton transfer (APT) contrast in tumors. Three different metrics of APT contrast-magnetization transfer ratio (MTRRex ), relaxation-compensated MTRRex (AREX), and traditional asymmetry (MTRasym )-were compared in normal and tumor tissues in a variety of intracranial tumors at 7 Tesla (T). METHODS: Six consented intracranial tumor patients were scanned using a low-power, three-dimensional (3D) APT imaging sequence. MTRRex and MTRasym were calculated in the region of 3 to 4 ppm. AREX was calculated by T1wat correction of MTRRex . Tumor tissue masks, which classify different tumor tissues, were drawn by an experienced neuroradiologist. ROI-averaged tumor tissue analysis was done for MTRRex , AREX, and MTRasym . RESULTS: MTRRex and MTRasym were slightly elevated in tumor-associated structures. Both metrics were positively correlated to T1wat . The correlation coefficient (R) was determined to be 0.88 (P < 0.05) and 0.92 (P < 0.05) for MTRRex and MTRasym , respectively. After T1wat correction (R = -0.21, P = 0.69), no difference between normal and tumor tissues was found for AREX. CONCLUSIONS: The strong correlation of MTRRex and MTRasym with T1wat and the absence thereof in AREX suggests that much of APT contrast in tumors for the low-power, 3D-acquisition scheme at 7 T originates from the inherent tissue water T1 -relaxation properties.

Purpose / Introduction As society ages and medical technology advances, more and more elderly undergo elective surgery. However, older patients have an increased risk of postoperative cognitive dysfunction, leading to impaired quality of life and an increased chance of becoming dependent 1. The pathophysiology of these long‐term side effects is poorly understood. New imaging biomarkers may be used to study the postoperative changes and evaluate the efficacy between different surgical or anesthetic strategies 1. In this study we explore the cerebral blood flow ﴾CBF﴿ changes following elective surgery using arterial spin labeling ﴾ASL﴿ perfusion MRI. Subjects and Methods Data were drawn from the Biomarker Development for Postoperative Cognitive Impairment in the Elderly ﴾BioCog﴿ study. Sixty‐five elderly ﴾71.7 ± 5.2 yrs, 73.9% M﴿ were scanned before and approximately 3 months after various types of elective surgery, excluding brain surgery and history of dementia. A background suppressed 2D EPI pseudo‐continuous ASL scan was performed, with labeling duration 1650 ms and post‐labeling delay slice‐range 1525‐2225 ms. CBF maps were processed2 and transformed into standard space3 using ExploreASL4. We investigated global CBF changes, cognitive decline regions and the spatial coefficient of variation ﴾CoV﴿5. Results CBF decreased with 11.4% in the white matter ﴾WM, p=0.004﴿ and with 7.6% in the gray matter ﴾GM, p=0.017﴿ ﴾Table 1﴿. We did not identify regional CBF changes ﴾data not shown﴿, suggesting that CBF decreased to a similar degree across the brain. The 8.8% WB CBF decrease was correlated with baseline WB CBF ﴾r=0.63, p

Segmentation of tissue components of atherosclerotic plaques in MRI is promising for improving future treatment strategies of cardiovascular diseases. Several methods have been proposed before with varying results. This study aimed to perform a structured comparison of various classifiers, training set sizes, and MR image sequences to determine the most promising strategy for methodology development. Five different classifiers (linear discriminant classifier (LDC), quadratic discriminant classifier (QDC), random forest (RF), and support vector classifiers with both a linear (SVM\(_{lin}\)) and radial basis function kernel (SVM\(_{rbf}\))) were evaluated. We used carotid MRI data from 124 symptomatic patients, scanned in 4 centres with 2 different MRI protocols (45 and 79 patients). Firstly, learning curves of accuracy as a function of increasing training data size showed stabilisation of performance after using \(\sim \)10–15 patients for training. Best results were found for LDC, QDC and RF. Intraplaque haemorrhage was most accurately classified in both protocols, and lowest accuracy was found for the lipid-rich necrotic core. Secondly, for LDC and RF it was shown that leaving out different MRI sequences usually negatively affects results for one or more classes. However, leaving out T2-weighted scans did not have a big impact. In conclusion, several classifiers obtain generally good results for classification of plaque components in MRI. Identification of intraplaque haemorrhage is the most promising, and lipid-rich necrotic core remains the most difficult.

Item does not contain fulltext Cerebral microbleeds are increasingly recognised as biomarkers of small vessel disease. Several preclinical and clinical studies have suggested that chronic disruption of the blood-brain barrier is one of the mechanisms for the development of cerebral microbleeds.A 51-year-old man experienced two left parieto-occipital lobar intracerebral haemorrhages (ICHs) in the timespan of 2 years. Multiple microbleeds surrounding the two haemorrhages were found on MRI, but not at location distant from the haemorrhages. Ten months after the last haemorrhage, an MRI demonstrated a right occipital focus of contrast enhancement. Twenty months after the last ICH, a new cerebral microbleed had developed exactly at the location of the earlier contrast enhancement.This case demonstrates that blood-brain barrier disruption may be an important factor preceding the development of cerebral microbleeds.

Arterial spin labeling (ASL) perfusion MRI1 is rapidly maturing as a research tool, potential future biomarker2 and pharmacological monitoring agent3 for many diseases including neurodegeneration. There is thus a growing need for standardization of ASL image processing and quality control (QC) for voxel-based (VBA) and region-of-interest (ROI)-based analyses. Here, we present ExploreASL, a non-commercial software package that aims to harmonize image processing for ASL perfusion images for single- and multi-center studies4, 5. In addition, ExploreASL combines key structural image processing tools from recent literature to differentiate perfusion from structural effects. Initiated through the EU-funded COST-action "ASL In Dementia", ExploreASL is a collaborative framework of researchers and clinical investigators. It was already used to process ~4000 ASL images from all major MRI vendors and ASL sequences, and a large variety of patient populations. The ultimate goal is to combine data from a large number of studies and identify common and different perfusion patterns to enhance knowledge of ASL image analysis and of the role of perfusion and structural changes in neurodegenerative pathophysiology.

PURPOSE: Vessel-encoded (VE) pseudo-continuous arterial spin labeling (p-CASL) is a territorial ASL (T-ASL) technique to identify the perfusion territories of cerebral arteries. The aim of this study was to validate the output of three Vessel-encoded p-CASL image processing methods, k-means clustering with and without subsequent linear analysis and a Bayesian framework, by comparison with the perfusion maps acquired with super-selective p-CASL. METHODS: The comparison was done quantitatively using the Hausdorff distance and Dice similarity coefficient in the territories of the right and left internal carotid arteries, the basilar artery, and the right and left vertebral arteries. A qualitative comparison was done in the areas of the anterior and posterior circulation, and the deep gray matter. RESULTS: The overall agreement between the Vessel-encoded p-CASL image processing methods and super-selective p-CASL was good; with the difference that the linear analysis and the Bayesian framework were able to detect mixed perfusion. CONCLUSION: Planning-free Vessel-encoded p-CASL with k-means clustering appears suitable as a general purpose T-ASL strategy, but to determine mixed perfusion a combination with linear analysis, or the Bayesian framework is preferable, which are superior in this regard. To accurately determine the perfusion territory of a single vessel, super-selective p-CASL is still recommended.

Item does not contain fulltext INTRODUCTION: Differentiating multifocal motor neuropathy (MMN) from amyotrophic lateral sclerosis (ALS) is important, as MMN is a difficult, but treatable disorder. METHODS: We studied peripheral nerve imaging techniques in differentiating MMN from ALS by measuring the cross-sectional area (CSA) of the median and ulnar nerves in the forearms using high resolution ultrasound (HRUS) and MRI. RESULTS: HRUS CSA values of the median nerve in the forearm (P = 0.002) and the ulnar nerve distal to the sulcus (P = 0.009) were significantly enlarged in patients with MMN. There was a positive correlation between CSA as measured with HRUS and MRI (Spearman rho 0.60; P < 0.001). CONCLUSIONS: Peripheral nerve imaging is a potentially powerful technique to distinguish MMN from ALS. Muscle Nerve, 2016 Muscle Nerve 54: 1133-1135, 2016.

Normocapnic hyperoxic and hypercapnic hyperoxic gas challenges are increasingly being used in cerebrovascular reactivity (CVR) and calibrated functional MRI experiments. The longitudinal arterial blood water relaxation time (T-1a) change with hyperoxia will influence signal quantification through mechanisms relating to elevated partial pressure of plasma-dissolved O-2 (pO(2)) and increased oxygen bound to hemoglobin in arteries (Y-a) and veins (Y-v). The dependence of T-1a on Y-a and Y-v has been elegantly characterized ex vivo; however, the combined influence of pO(2), Y-a and Y-v on T(1a)in vivo under normal ventilation has not been reported. Here, T-1a is calculated during hyperoxia in vivo by a heuristic approach that evaluates T-1-dependent arterial spin labeling (ASL) signal changes to varying gas stimuli. Healthy volunteers (n=14; age, 31.5 +/- 7.2years) were scanned using pseudo-continuous ASL in combination with room air (RA; 21% O-2/79% N-2), hypercapnic normoxic (HN; 5% CO2/21% O-2/74% N-2) and hypercapnic hyperoxic (HH; 5% CO2/95% O-2) gas administration. HH T-1a was calculated by requiring that the HN and HH cerebral blood flow (CBF) change be identical. The HH protocol was then repeated in patients (n=10; age, 61.4 +/- 13.3years) with intracranial stenosis to assess whether an HH T-1a decrease prohibited ASL from being performed in subjects with known delayed blood arrival times. Arterial blood T-1a decreased from 1.65s at baseline to 1.49 +/- 0.07s during HH. In patients, CBF values in the affected flow territory for the HH condition were increased relative to baseline CBF values and were within the physiological range (RA CBF=36.6 +/- 8.2mL/100g/min; HH CBF=45.2 +/- 13.9mL/100g/min). It can be concluded that hyperoxic (95% O-2) 3-T arterial blood T-1aHH=1.49 +/- 0.07s relative to a normoxic T-1a of 1.65s. Copyright (c) 2015 John Wiley & Sons, Ltd.

INTRODUCTION: Blood oxygenation‐level dependent (BOLD) magnetic resonance imaging signal changes in response to stimuli have been used to evaluate age‐related changes in neuronal activity. Contradictory results from these types of experiments have been attributed to differences in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO(2)). To clarify the effects of these physiological parameters, we investigated the effect of age on baseline CBF and CMRO(2). MATERIALS AND METHODS: Twenty young (mean ± sd age, 28 ± 3 years), and 45 older subjects (66 ± 4 years) were investigated. A dual‐echo pseudocontinuous arterial spin labeling (ASL) sequence was performed during normocapnic, hypercapnic, and hyperoxic breathing challenges. Whole brain and regional gray matter values of CBF, ASL cerebrovascular reactivity (CVR), BOLD CVR, oxygen extraction fraction (OEF), and CMRO(2) were calculated. RESULTS: Whole brain CBF was 49 ± 14 and 40 ± 9 ml/100 g/min in young and older subjects respectively (P

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Background and Purpose-Cerebral small-vessel disease and cerebral blood flow (CBF) are interrelated. However, the direction of the relationship is unknown, and longitudinal studies are scarce. We investigated the longitudinal relationship between CBF and white matter hyperintensities (WMHs) and lacunes, as representatives of cerebral small-vessel disease, in patients with manifest arterial disease. Methods-Within the Second Manifestations of Arterial Disease-Magnetic Resonance (SMART-MR) study, 1.5T brain magnetic resonance imaging, including an MR angiography, was obtained at baseline and after on approximate to 3.9 years of follow-up in 575 patients with manifest arterial disease (mean age, 57 +/- 10 years). Longitudinal associations of WMHs and lacunes with parenchymal CBF (pCBF; per 100-mL brain volume) were estimated using regression analyses, adjusted for age, sex, follow-up time, and baseline brain measures. Results-Baseline pCBF was not associated with progression of WMHs and lacunes over time. However, periventricular and deep WMHs at baseline were associated with decline in pCBF; mean (95% confidence interval) decline in pCBF per % intracranial volume increase in periventricular and deep WMH volume was -0.70 (-1.40 to -0.00) and -1.01 (-1.64 to -0.38) mL/min per 100-mL brain volume, respectively. These associations were partly explained by cardiovascular risk factors but remained significant for deep WMHs (mean decline [95% confidence interval] in pCBF per % intracranial volume increase in deep WMH volume was -0.92 [-1.56 to -0.28] mL/min per 100-mL brain volume). Lacunes were not associated with change in pCBF. Conclusions-In patients with manifest arterial disease, baseline periventricular and deep WMH volumes were associated with decline in pCBF over time, but baseline pCBF was not associated with progression of WMHs and lacunes over time.

The cerebral blood flow (CBF) or the delivery of nutrients to the brain tissue is essential for the viability of brain cells and is a necessity for the human body to perform physical and mental activities. Both under-and overperfusion of the brain tissue can cause substantial harm wherefore the CBF is very tightly regulated. Dilatation and constriction of arterioles contribute to this regulation which can be expressed by the cerebrovascular reactivity (CVR). Through the cerebral blood flow, essential nutrients such as glucose and oxygen are delivered to the brain tissue. The consumption of these nutrients can either be expressed by the cerebral metabolic rate of glucose (CMRGlc), the oxygen extraction fraction (OEF) or the cerebral metabolic rate of oxygen (CMRO2). The CBF, the CVR, the CMRGlc, the OEF, and the CMRO2, or the brain hemodynamic parameters, provide important information of the brain tissue’s health. For instance, in patients with steno-occlusive disease, they provide insight into the amount of stress the brain tissue is opposed to, and, they are reflective of maturation and aging processes. Fluorodeoxyglucose positron emission tomography (PET) and oxygen-15 PET are the gold standards to evaluate these parameters. But, the invasiveness of these techniques and the requirement of an onsite cyclotron in case of oxygen-15 PET have limited their application in clinical practice. This thesis focused on the development and application of alternative non-invasive techniques to evaluate the brain hemodynamic parameters. We demonstrated that arterial spin labeling (ASL) obtained CBF values in neonates reflect maturation and can predict adverse outcome in case of a perinatal ischemic event. Similar, T2-TRIR obtained OEF values were lower in these latter infants and could thus be indicative of adverse outcome. In the adult population we applied calibrated MRI, which combines ASL and blood oxygenation level-dependent (BOLD) measurements performed at hypercapnic and hyperoxic breathing, to obtain a full evaluation of all brain hemodynamic parameters. Although some technical issues still prohibit its translation to clinical practice, the technique seems to be promising in the evaluation of patients with steno-occlusive disease and in the investigation of the aging process. At last, as the amount of brain tissue in adults also provides important information regarding (pathological) aging, a fast volumetric CSF mapping technique was developed. This technique was consequently shown to be able to act as a surrogate for time-and post-processing intensive imaging (tools) which are now commonly used to evaluate brain atrophy. In conclusion, non-invasive imaging techniques to evaluate brain hemodynamics show great promise. The application of these techniques in clinical practice will be possible when some of the limitations, encountered in our clinical studies, are dealt with. Once optimized they will be of great value in the investigation of maturation and ageing processes, in therapeutic decision making in patients with ischemic or cerebrovascular disease, and in the prediction of outcome in patients with ischemic disease.

OBJECTIVE: Previous studies on cerebellar infarcts have been largely restricted to acute infarcts in patients with clinical symptoms, and cerebellar infarcts have been evaluated with the almost exclusive use of transversal MR images. We aimed to document the occurrence and 3D-imaging patterns of cerebellar infarcts presenting as an incidental finding on MRI. METHODS: We analysed the 1.5 Tesla MRI, including 3D T1-weighted datasets, of 636 patients (mean age 62 ± 9 years, 81% male) from the SMART-Medea study. Cerebellar infarct analyses included an assessment of size, cavitation and gliosis, of grey and white matter involvement, and of infarct topography. RESULTS: One or more cerebellar infarcts (mean 1.97; range 1-11) were detected in 70 out of 636 patients (11%), with a total amount of 138 infarcts identified, 135 of which showed evidence of cavitation. The average mean axial diameter was 7 mm (range 2-54 mm), and 131 infarcts (95%) were smaller than 20 mm. Hundred-thirty-four infarcts (97%) involved the cortex, of which 12 in combination with subcortical white matter. No infarcts were restricted to subcortical branches of white matter. Small cortical infarcts involved the apex of a deep (pattern 1) or shallow fissure (pattern 2), or occurred alongside one (pattern 3) or opposite sides (pattern 4) of a fissure. Most (87%) cerebellar infarcts were situated in the posterior lobe. CONCLUSIONS: Small cerebellar infarcts proved to be much more common than larger infarcts, and preferentially involved the cortex. Small cortical infarcts predominantly involved the posterior lobes, showed sparing of subcortical white matter and occurred in characteristic topographic patterns.

A 60-year-old woman with a history of hypertension presented with acute onset of left-sided weakness and drowsiness. Non-contrast CT at baseline and follow-up showed a focal high density lesion in the right middle cerebral artery, consistent with a calcified embolus. CT angiography confirmed its location.

Introduction: A main obstacle that impedes standardized clinical and research applications of arterial spin labeling (ASL), is the substantial differences between the commercial implementations of ASL from major MRI vendors. In this study, we compare a single identical 2D gradient-echo EPI pseudo-continuous ASL (PCASL) sequence implemented on 3T scanners from three vendors (General Electric Healthcare, Philips Healthcare and Siemens Healthcare) within the same center and with the same subjects. Material and methods: Fourteen healthy volunteers (50% male, age 26.4 +/- 4.7 years) were scanned twice on each scanner in an interleaved manner within 3 h. Because of differences in gradient and coil specifications, two separate studies were performed with slightly different sequence parameters, with one scanner used across both studies for comparison. Reproducibility was evaluated by means of quantitative cerebral blood flow (CBF) agreement and inter-session variation, both on a region-of-interest (ROI) and voxel level. In addition, a qualitative similarity comparison of the CBF maps was performed by three experienced neuro-radiologists. Results: There were no CBF differences between vendors in study 1 (p > 0.1), but there were CBF differences of 2-19% between vendors in study 2 (p < 0.001 in most gray matter ROIs) and 10-22% difference in CBF values obtained with the same vendor between studies (p < 0.001 in most gray matter ROIs). The inter-vendor inter-session variation was not significantly larger than the intra-vendor variation in all (p > 0.1) but one of the ROIs (p < 0.001). Conclusion: This study demonstrates the possibility to acquire comparable cerebral CBF maps on scanners of different vendors. Small differences in sequence parameters can have a larger effect on the reproducibility of ASL than hardware or software differences between vendors. These results suggest that researchers should strive to employ identical labeling and readout strategies in multi-center ASL studies.

INTRODUCTION: Blood oxygenation-level dependent (BOLD) magnetic resonance imaging signal changes in response to stimuli have been used to evaluate age-related changes in neuronal activity. Contradictory results from these types of experiments have been attributed to differences in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2 ). To clarify the effects of these physiological parameters, we investigated the effect of age on baseline CBF and CMRO2 . MATERIALS AND METHODS: Twenty young (mean ± sd age, 28 ± 3 years), and 45 older subjects (66 ± 4 years) were investigated. A dual-echo pseudocontinuous arterial spin labeling (ASL) sequence was performed during normocapnic, hypercapnic, and hyperoxic breathing challenges. Whole brain and regional gray matter values of CBF, ASL cerebrovascular reactivity (CVR), BOLD CVR, oxygen extraction fraction (OEF), and CMRO2 were calculated. RESULTS: Whole brain CBF was 49 ± 14 and 40 ± 9 ml/100 g/min in young and older subjects respectively (P

This review provides a summary statement of recommended implementations of arterial spin labeling (ASL) for clinical applications. It is a consensus of the ISMRM Perfusion Study Group and the European ASL in Dementia consortium, both of whom met to reach this consensus in October 2012 in Amsterdam. Although ASL continues to undergo rapid technical development, we believe that current ASL methods are robust and ready to provide useful clinical information, and that a consensus statement on recommended implementations will help the clinical community to adopt a standardized approach. In this review, we describe the major considerations and trade-offs in implementing an ASL protocol and provide specific recommendations for a standard approach. Our conclusion is that as an optimal default implementation, we recommend pseudo-continuous labeling, background suppression, a segmented three-dimensional readout without vascular crushing gradients, and calculation and presentation of both label/control difference images and cerebral blood flow in absolute units using a simplified model. Magn Reson Med 73:102-116, 2015. (c) 2014 Wiley Periodicals, Inc.

This review provides a summary statement of recommended implementations of arterial spin labeling (ASL) for clinical applications. It is a consensus of the ISMRM Perfusion Study Group and the European ASL in Dementia consortium, both of whom met to reach this consensus in October 2012 in Amsterdam. Although ASL continues to undergo rapid technical development, we believe that current ASL methods are robust and ready to provide useful clinical information, and that a consensus statement on recommended implementations will help the clinical community to adopt a standardized approach. In this review, we describe the major considerations and trade-offs in implementing an ASL protocol and provide specific recommendations for a standard approach. Our conclusion is that as an optimal default implementation, we recommend pseudo-continuous labeling, background suppression, a segmented three-dimensional readout without vascular crushing gradients, and calculation and presentation of both label/control difference images and cerebral blood flow in absolute units using a simplified model. Magn Reson Med 73:102-116, 2015. (c) 2014 Wiley Periodicals, Inc.

The longitudinal relaxation time of blood is a crucial parameter for quantification of cerebral blood flow by arterial spin labeling and is one of the main determinants of the signal-to-noise ratio of the resulting perfusion maps. Whereas at low and medium magnetic field strengths (B(0) ), its in vivo value is well established; at ultra-high field, this is still uncertain. In this study, longitudinal relaxation time of blood in the sagittal sinus was measured at 1.5 T, 3 T, and 7 T. A nonselective inversion pulse preceding a Look-Locker echo planar imaging sequence was performed to obtain the inversion recovery curve of venous blood. The results showed that longitudinal relaxation time of blood at 7 T was ∼ 2.1 s which translates to an anticipated 33% gain in the signal-to-noise ratio in arterial spin labeling experiments due to T(1) relaxation alone compared with 3 T. In addition, the linear relationship between longitudinal relaxation time of blood and B(0) was confirmed. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.

Intra- and multicenter reproducibility of currently used arterial spin labeling (ASL) methods were assessed at three imaging centers in the Netherlands, equipped with Philips 3TMR scanners. Six healthy participants were scanned twice at each site. The imaging protocol consisted of continuous ASL (CASL), pseudo-continuous ASL (p-CASL) with and without background suppression, pulsed ASL (PASL) with single and multiple inversion times (TIs), and selective ASL for segmentation. Reproducibility was expressed in terms of the coefficient of repeatability and the repeatability index. Voxelwise analysis of variance was performed, yielding brain maps that reflected regional variability. Intra- and multicenter reproducibility were comparable for all methods, except for single TI PASL, with better intracenter reproducibility (F-test of equality of two variances, P

We describe the field demonstration of astrobiology instruments and research methods conducted in and from the Mars Desert Research Station (MDRS) in Utah during the EuroGeoMars campaign 2009 coordinated by ILEWG, ESA/ESTEC and NASA Ames, with the contribution of academic partners. We discuss the entire experimental approach from determining the geological context using remote sensing, in situ measurements, sorties with sample collection and characterization, analysis in the field laboratory, to the post sample analysis using advanced laboratory facilities. We present the rationale for terrestrial field campaigns to strengthen astrobiology research and the link between in situ and orbital remote sensing data. These campaigns are supporting the preparation for future missions such as Mars Science Laboratory, ExoMars or Mars Sample Return. We describe the EuroGeoMars 2009 campaign conducted by MDRS crew 76 and 77, focused on the investigation of surface processes in their geological context. Special emphasis was placed on sample collection and pre-screening using in-situ portable instruments. Science investigations included geological and geochemical measurements as well as detection and diagnostic of water, oxidants, organic matter, minerals, volatiles and biota. EuroGeoMars 2009 was an example of a Moon-Mars field research campaign dedicated to the demonstration of astrobiology instruments and a specific methodology of comprehensive measurements from selected sampling sites. We discuss in sequence: the campaign objectives and trade-off based on science, technical or operational constraints. This includes remote sensing data and maps, and geological context; the monitoring of environmental parameters; the geophysical context and mineralogy studies; geology and geomorphology investigations; geochemistry characterization and subsurface studies. We describe sample handling (extraction and collection) methods, and the sample analysis of soils and rocks performed in the MDRS laboratory using close inspection, initial petrological characterization, microscopy, Visible-NIR spectrometry, Raman spectrometry, X-ray diffraction/X-ray fluorescence spectrometry, soil analysis, electrochemical and biological measurements. The results from post-mission analysis of returned samples using advanced facilities in collaborator institutes are described in companion papers in this issue. We present examples of in-situ analysis, and describe an example investigation on the exploration and analysis of endolithic microbial mats (from reconnaissance, in-situ imaging, sampling, local analysis to post-mission sample analysis). © 2011 Cambridge University Press.