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01 juli 2023, Contains fulltext : 293781.pdf (Publisher’s version ) (Open Access), The acquisition of intravoxel incoherent motion (IVIM) data and diffusion tensor imaging (DTI) data from the brain can be integrated into a single measurement, which offers the possibility to determine orientation-dependent (tensorial) perfusion parameters in addition to established IVIM and DTI parameters. The purpose of this study was to evaluate the feasibility of such a protocol with a clinically feasible scan time below 6 min and to use a model-selection approach to find a set of DTI and IVIM tensor parameters that most adequately describes the acquired data. Diffusion-weighted images of the brain were acquired at 3 T in 20 elderly participants with cerebral small vessel disease using a multiband echoplanar imaging sequence with 15 b-values between 0 and 1000 s/mm(2) and six non-collinear diffusion gradient directions for each b-value. Seven different IVIM-diffusion models with 4 to 14 parameters were implemented, which modeled diffusion and pseudo-diffusion as scalar or tensor quantities. The models were compared with respect to their fitting performance based on the goodness of fit (sum of squared fit residuals, chi(2) ) and their Akaike weights (calculated from the corrected Akaike information criterion). Lowest chi(2) values were found using the model with the largest number of model parameters. However, significantly highest Akaike weights indicating the most appropriate models for the acquired data were found with a nine-parameter IVIM-DTI model (with isotropic perfusion modeling) in normal-appearing white matter (NAWM), and with an 11-parameter model (IVIM-DTI with additional pseudo-diffusion anisotropy) in white matter with hyperintensities (WMH) and in gray matter (GM). The latter model allowed for the additional calculation of the fractional anisotropy of the pseudo-diffusion tensor (with a median value of 0.45 in NAWM, 0.23 in WMH, and 0.36 in GM), which is not accessible with the usually performed IVIM acquisitions based on three orthogonal diffusio

01 juli 2023, Item does not contain fulltext, Cerebral small vessel disease (SVD) is common during ageing and can present as stroke, cognitive decline, neurobehavioural symptoms, or functional impairment. SVD frequently coexists with neurodegenerative disease, and can exacerbate cognitive and other symptoms and affect activities of daily living. Standards for Reporting Vascular Changes on Neuroimaging 1 (STRIVE-1) categorised and standardised the diverse features of SVD that are visible on structural MRI. Since then, new information on these established SVD markers and novel MRI sequences and imaging features have emerged. As the effect of combined SVD imaging features becomes clearer, a key role for quantitative imaging biomarkers to determine sub-visible tissue damage, subtle abnormalities visible at high-field strength MRI, and lesion-symptom patterns, is also apparent. Together with rapidly emerging machine learning methods, these metrics can more comprehensively capture the effect of SVD on the brain than the structural MRI features alone and serve as intermediary outcomes in clinical trials and future routine practice. Using a similar approach to that adopted in STRIVE-1, we updated the guidance on neuroimaging of vascular changes in studies of ageing and neurodegeneration to create STRIVE-2.

01 september 2023, Contains fulltext : 296150.pdf (Publisher’s version ) (Open Access), BACKGROUND: Preeclampsia, a hypertensive pregnancy disorder, is a leading cause of maternal and fetal morbidity and mortality, with remote cardio- and cerebrovascular implications. After preeclampsia, women may report serious disabling cognitive complaints, especially involving executive function, but the extent and time course of these complaints are unknown. OBJECTIVE: This study aimed to determine the impact of preeclampsia on perceived maternal cognitive functioning decades after pregnancy. STUDY DESIGN: This study is part of a cross-sectional case-control study named Queen of Hearts (ClinicalTrials.gov Identifier: NCT02347540), a collaboration study of 5 tertiary referral centers within the Netherlands investigating long-term effects of preeclampsia. Eligible participants were female patients aged ≥18 years after preeclampsia and after normotensive pregnancy between 6 months and 30 years after their first (complicated) pregnancy. Preeclampsia was defined as new-onset hypertension after 20 weeks of gestation along with proteinuria, fetal growth restriction, or other maternal organ dysfunction. Women with a history of hypertension, autoimmune disease, or kidney disease before their first pregnancy were excluded. Attenuation of higher-order cognitive functions, that is, executive function, was measured with the Behavior Rating Inventory of Executive Function for Adults. Crude and covariate-adjusted absolute and relative risks of clinical attenuation over time after (complicated) pregnancy were determined with moderated logistic and log-binomial regression. RESULTS: This study included 1036 women with a history of preeclampsia and 527 women with normotensive pregnancies. Regarding overall executive function, 23.2% (95% confidence interval, 19.0-28.1) of women experienced clinically relevant attenuation after preeclampsia, as opposed to 2.2% (95% confidence interval, 0.8-6.0) of controls immediately after childbirth (adjusted relative risk, 9.20 [95% confidence inte

01 september 2023, Item does not contain fulltext, Blood-brain barrier (BBB) is known to be impaired in cerebral small vessel disease (SVD), and is measurable by dynamic-contrast enhancement (DCE)-MRI. In a cohort of 69 patients (42 sporadic, 27 monogenic SVD), who underwent 3T MRI, including DCE and cerebrovascular reactivity (CVR) sequences, we assessed the relationship of BBB-leakage hotspots to SVD lesions (lacunes, white matter hyperintensities (WMH), and microbleeds). We defined as hotspots the regions with permeability surface area product highest decile on DCE-derived maps within the white matter. We assessed factors associated with the presence and number of hotspots corresponding to SVD lesions in multivariable regression models adjusted for age, WMH volume, number of lacunes, and SVD type. We identified hotspots at lacune edges in 29/46 (63%) patients with lacunes, within WMH in 26/60 (43%) and at the WMH edges in 34/60 (57%) patients with WMH, and microbleed edges in 4/11 (36%) patients with microbleeds. In adjusted analysis, lower WMH-CVR was associated with presence and number of hotspots at lacune edges, and higher WMH volume with hotspots within WMH and at WMH edges, independently of the SVD type. In conclusion, SVD lesions frequently collocate with high BBB-leakage in patients with sporadic and monogenic forms of SVD.

01 juli 2023, Contains fulltext : 294519.pdf (Publisher’s version ) (Open Access), OBJECTIVES: Pre-eclampsia has been associated with cardiovascular, cerebrovascular and/or psychological complaints. Signs of altered brain morphology and more white-matter hyperintensities (WMHs) during and shortly after pre-eclampsia have been observed in some, but not all, studies. We compared volumes of cerebral structures and the number of WMHs between formerly pre-eclamptic women and those with normotensive gestational history and assessed the effect of age on brain volumes. METHODS: Structural 7-Tesla magnetic resonance imaging of the brain was performed in 59 formerly pre-eclamptic women (aged 37 ± 6 years, 0.5-16 years postpartum) and 20 women with a history of normotensive pregnancy (aged 39 ± 5 years, 1-18 years postpartum). Fazekas scores were obtained to assess WMH load. Volumes of the whole brain, gray and white matter, brain lobes, and ventricular and pericortical cerebrospinal fluid (CSF) spaces were calculated after semiautomatic segmentation. Group differences were analyzed using ANCOVA and Bayes factors. Results were adjusted for age, educational attainment, presence of current hypertension and total intracranial volume. The effect of age on cerebral volumes was analyzed using linear regression analysis. RESULTS: No changes in global and local brain volumes were observed between formerly pre-eclamptic and control women. Also, no difference in WMH load was observed. Independent of pre-eclamptic history, gray-matter volume significantly decreased with age, while ventricular and pericortical CSF space volumes significantly increased with age. CONCLUSIONS: Volumetric changes of the cerebrum are age-related but are independent of pre-eclamptic history in the first two decades after childbirth. No evidence of greater WMH load after pre-eclampsia was found. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

BACKGROUND: Hypertension alters the structure and function of cerebral blood vessels, and is an important risk factor for stroke and cerebral small vessel disease (cSVD). However, the pathophysiological process is not yet well understood. This study aimed to investigate the relationship between the pulsatility measures in small perforating arteries and hypertension, since hypertension-induced arterial stiffening may lead to a higher blood flow pulsatility and lower damping.METHODS: We examined 28 patients with essential hypertension and 25 age-and sex-matched healthy controls (mean age: 63.4, range: 43-81 years, 26 males). Blood flow velocity waveforms were acquired in the lenticulostriate arteries (LSAs) and the middle cerebral artery using phase-contrast MRI at 7 Tesla. Several cSVD markers were scored. The velocity and pulsatility measures were compared between the hypertensives and controls.RESULTS: A higher pulsatility index (PI) in the LSAs and a lower damping factor (DF) was found in the hypertensive compared to the normotensive group (P=0.015, P=0.015, respectively), but no association was found for the PI in the middle cerebral artery. Higher systolic and mean arterial pressures were associated with higher PI in the LSA and DF. For diastolic blood pressure, only an association with a lower DF was found. Adjusting for cSVD score did not alter these relationships.CONCLUSIONS: This study shows a higher PI in the LSAs and a lower DF in subjects with hypertension, independent of cSVD presence. This supports the hypothesis that hypertension-induced arterial remodeling may alter the intracerebral blood flow velocity profiles, which could eventually contribute to cerebral tissue damage.

12 mei 2022, Item does not contain fulltext, Background: Neuroimaging markers of cerebral small vessel disease (SVD) are common in older individuals, but the pathophysiological mechanisms causing these lesions remain poorly understood. Although hypertension is a major risk factor for SVD, the direct causal effects of increased blood pressure are unknown. The Hyperintense study is designed to examine cerebrovascular and structural abnormalities, possibly preceding SVD, in young adults with hypertension. These patients undergo a diagnostic work-up that requires patients to temporarily discontinue their antihypertensive agents, often leading to an increase in blood pressure followed by a decrease once effective medication is restarted. This allows examination of the effects of blood pressure increase and decrease on the cerebral small vessels. Methods: Hyperintense is a prospective observational cohort study in 50 hypertensive adults (18–55 years) who will temporarily discontinue antihypertensive medication for diagnostic purposes. MRI and clinical data is collected at four timepoints: before medication withdrawal (baseline), once antihypertensives are largely or completely withdrawn (T = 1), when patients have restarted medication (T = 2) and reached target blood pressure and 1 year later (T = 3). The 3T MRI protocol includes conventional structural sequences and advanced techniques to assess various aspects of microvascular integrity, including blood-brain barrier function using Dynamic Contrast Enhanced MRI, white matter integrity, and microperfusion. Clinical assessments include motor and cognitive examinations and blood sampling.Discussion: The Hyperintense study will improve the understanding of the pathophysiological mechanisms following hypertension that may cause SVD. This knowledge can ultimately help to identify new targets for treatment of SVD, aimed at prevention or limiting disease progression.

Background: Lesions of cerebral small vessel disease, such as white matter hyperintensities (WMHs) in individuals with cardiometabolic risk factors, interfere with the trajectories of the white matter and eventually contribute to cognitive decline. However, there is no consensus yet about the precise underlying topological mechanism.Purpose: To examine whether WMH and cognitive function are associated and whether any such association is mediated or explained by structural connectivity measures in an adult population. In addition, to investigate underlying local abnormalities in white matter by assessing the tract-specific WMH volumes and their tract-specific association with cognitive function.Materials and Methods: In the prospective type 2 diabetes-enriched population-based Maastricht Study, structural and diffusion-tensor MRI was performed (December 2013 to February 2017). Total and tract-specific WMH volumes; network measures; cognition scores; and demographic, cardiovascular, and lifestyle characteristics were determined. Multivariable linear regression and mediation analyses were used to investigate the association of WMH volume, tract-specific WMH volumes, and network measures with cognitive function. Associations were adjusted for age, sex, education, diabetes status, and cardiovascular risk factors.Results: A total of 5083 participants (mean age, 59 years +/- 9 [standard deviation]; 2592 men; 1027 with diabetes) were evaluated. Larger WMH volumes were associated with stronger local (standardized beta coefficient, 0.065; PConclusion: White matter hyperintensity volume, local network efficiency, and information processing speed scores are interrelated, and local network properties explain lower cognitive performance due to white matter network alterations. (C) RSNA, 2020

Contains fulltext : 235711.pdf (Publisher’s version ) (Open Access), Cerebrospinal fluid (CSF) enhancement on T2-weighted post-contrast fluid-attenuated inversion recovery (pcT2wFLAIR) images is a relatively unknown neuroradiological marker for gadolinium-based contrast agent extravasation due to blood-brain barrier (BBB) disruption. We systematically reviewed human studies reporting on CSF enhancement on pcT2wFLAIR images to provide a comprehensive overview of prevalence of this new biomarker in healthy and diseased populations as well as its etiology and optimal detection methodology. We extracted information on the prevalence of CSF enhancement, its vascular risk factor and neuroimaging correlates, and methodological attributes of each study. Forty-four eligible studies were identified. By pooling data, we found that the prevalence of CSF enhancement was 82% (95% confidence interval (CI) 80-89) in meningitis (4 studies, 65 patients), 73% (95%CI 62-81) in cases with (post-) acute intracerebral hemorrhage (2 studies, 77 cases), 64% (95% CI 54-73) in cases who underwent surgery for aneurysm treatment (2 studies, 99 patients), 40% (95% CI 30-51) in cases who underwent surgery for carotid artery disease treatment (3 studies, 76 patients), 27% (95% CI 25-30) in cases with acute ischemic stroke (9 studies, 1148 patients), 21% (95% CI 17-23) in multiple sclerosis (6 studies, 897 patients), and 13% (95% CI 7-21) in adult controls (4 studies, 112 cases). Presence of CSF enhancement was associated with higher age in eleven studies, with lobar cerebral microbleeds in one study, and with cerebral atrophy in four studies. PcT2wFLAIR imaging represents a promising method that can provide novel perspectives on BBB leakage into CSF compartments, with the potential to reveal important new insights into the pathophysiological mechanisms of varying neurological diseases.

Contains fulltext : 199954.pdf (publisher's version ) (Open Access), Background and Purpose: Hypertensive vasculopathy and cerebral amyloid angiopathy are the two most common forms of cerebral small vessel disease. Both forms are associated with the development of primary intracerebral hemorrhage, but the pathophysiological mechanisms underlying spontaneous vessel rupture remain unknown. This work constitutes a systematic review on blood-brain barrier dysfunction in the etiology of spontaneous intracerebral hemorrhage due to cerebral small vessel disease. Methods: We searched Medline (1946-2018) and Embase (1974-2018) for animal and human studies reporting on blood-brain barrier dysfunction associated with intracerebral hemorrhage or cerebral microbleeds. Results: Of 26 eligible studies, 10 were animal studies and 16 were in humans. The authors found indications for blood-brain barrier dysfunction in all four animal studies addressing hypertensive vasculopathy-related intracerebral hemorrhage (n = 32 hypertensive animals included in all four studies combined), and in four of six studies on cerebral amyloid angiopathy-related intracerebral hemorrhage (n = 47). Of the studies in humans, five of six studies in patients with cerebral amyloid angiopathy-related intracerebral hemorrhage (n = 117) and seven out of nine studies examining intracerebral hemorrhage with mixed or unspecified underlying etiology (n = 489) found indications for blood-brain barrier dysfunction. One post-mortem study in hypertensive vasculopathy-related intracerebral hemorrhage (n = 82) found no evidence for blood-brain barrier abnormalities. Conclusions: Signs of blood-brain barrier dysfunction were found in 20 out of 26 studies. Blood-brain barrier integrity deserves further investigation with a view to identification of potential treatment targets for spontaneous intracerebral hemorrhage.

Contains fulltext : 183400.pdf (publisher's version ) (Open Access), Introduction: Autism spectrum disorder (ASD) is mainly characterized by functional and communication impairments as well as restrictive and repetitive behavior. The leading hypothesis for the neural basis of autism postulates globally abnormal brain connectivity, which can be assessed using functional magnetic resonance imaging (fMRI). Even in the absence of a task, the brain exhibits a high degree of functional connectivity, known as intrinsic, or resting-state, connectivity. Global default connectivity in individuals with autism versus controls is not well characterized, especially for a high-functioning young population. The aim of this study is to test whether high-functioning adolescents with ASD (HFA) have an abnormal resting-state functional connectivity. Materials and Methods: We performed spatial and temporal analyses on resting-state networks (RSNs) in 13 HFA adolescents and 13 IQ- and age-matched controls. For the spatial analysis, we used probabilistic independent component analysis (ICA) and a permutation statistical method to reveal the RSN differences between the groups. For the temporal analysis, we applied Granger causality to find differences in temporal neurodynamics. Results: Controls and HFA display very similar patterns and strengths of resting-state connectivity. We do not find any significant differences between HFA adolescents and controls in the spatial resting-state connectivity. However, in the temporal dynamics of this connectivity, we did find differences in the causal effect properties of RSNs originating in temporal and prefrontal cortices. Conclusion: The results show a difference between HFA and controls in the temporal neurodynamics from the ventral attention network to the salience-executive network: a pathway involving cognitive, executive, and emotion-related cortices. We hypothesized that this weaker dynamic pathway is due to a subtle trigger challenging the cognitive state prior to the resting state.

Contains fulltext : 195452.pdf (publisher's version ) (Open Access)

Contains fulltext : 170424.pdf (publisher's version ) (Closed access), Cerebral small vessel disease (cSVD) and amyloid-beta (Abeta) deposition often co-exist in (prodromal) dementia, and both types of pathology have been associated with neurodegeneration. We examined whether cSVD and Abeta have independent or interactive effects on hippocampal volume (HV) in a memory clinic population. We included 87 individuals with clinical diagnoses of Alzheimer's disease (AD) (n = 24), mild cognitive impairment (MCI) (n = 26), and subjective cognitive complaints (SCC) (n = 37). cSVD magnetic resonance imaging markers included white matter hyperintensity (WMH) volume, lacunar infarct presence, and microbleed presence. Abeta pathology was assessed as cerebrospinal fluid-derived Abeta1 - 42 levels and dichotomized into normal or abnormal, and HV was determined by manual volumetric measurements. A linear hierarchical regression approach was applied for the detection of additive or interaction effects between cSVD and Abeta on HV in the total participant group (n = 87) and in the non-demented group (including SCC and MCI individuals only, n = 63). The results revealed that abnormal Abeta and lacunar infarct presence were independently associated with lower HV in the non-demented individuals. Interestingly, Abeta and WMH pathology interacted in the non-demented individuals, such that WMH had a negative effect on HV in individuals with abnormal CSF Abeta42 levels, but not in individuals with normal CSF Abeta42 levels. These associations were not present when individuals with AD were included in the analyses. Our observations suggest that relatively early on in the disease process older individuals with abnormal Abeta levels are at an increased risk of accelerated disease progression when concomitant cSVD is present.

AIM: To increase our insight in the neuronal mechanisms underlying cognitive side-effects of antiepileptic drug (AED) treatment.METHODS: The relation between functional magnetic resonance-acquired brain network measures, AED use, and cognitive function was investigated. Three groups of patients with epilepsy with a different risk profile for developing cognitive side effects were included: A "low risk" category (lamotrigine or levetiracetam, n = 16), an "intermediate risk" category (carbamazepine, oxcarbazepine, phenytoin, or valproate, n = 34) and a "high risk" category (topiramate, n = 5). Brain connectivity was assessed using resting state functional magnetic resonance imaging and graph theoretical network analysis. The Computerized Visual Searching Task was used to measure central information processing speed, a common cognitive side effect of AED treatment.RESULTS: Central information processing speed was lower in patients taking AEDs from the intermediate and high risk categories, compared with patients from the low risk category. The effect of risk category on global efficiency was significant (P < 0.05, ANCOVA), with a significantly higher global efficiency for patient from the low category compared with the high risk category (P < 0.05, post-hoc test). Risk category had no significant effect on the clustering coefficient (ANCOVA, P > 0.2). Also no significant associations between information processing speed and global efficiency or the clustering coefficient (linear regression analysis, P > 0.15) were observed.CONCLUSION: Only the four patients taking topiramate show aberrant network measures, suggesting that alterations in functional brain network organization may be only subtle and measureable in patients with more severe cognitive side effects.

AIM: To increase our insight in the neuronal mechanisms underlying cognitive side-effects of antiepileptic drug (AED) treatment.METHODS: The relation between functional magnetic resonance-acquired brain network measures, AED use, and cognitive function was investigated. Three groups of patients with epilepsy with a different risk profile for developing cognitive side effects were included: A "low risk" category (lamotrigine or levetiracetam, n = 16), an "intermediate risk" category (carbamazepine, oxcarbazepine, phenytoin, or valproate, n = 34) and a "high risk" category (topiramate, n = 5). Brain connectivity was assessed using resting state functional magnetic resonance imaging and graph theoretical network analysis. The Computerized Visual Searching Task was used to measure central information processing speed, a common cognitive side effect of AED treatment.RESULTS: Central information processing speed was lower in patients taking AEDs from the intermediate and high risk categories, compared with patients from the low risk category. The effect of risk category on global efficiency was significant (P < 0.05, ANCOVA), with a significantly higher global efficiency for patient from the low category compared with the high risk category (P < 0.05, post-hoc test). Risk category had no significant effect on the clustering coefficient (ANCOVA, P > 0.2). Also no significant associations between information processing speed and global efficiency or the clustering coefficient (linear regression analysis, P > 0.15) were observed.CONCLUSION: Only the four patients taking topiramate show aberrant network measures, suggesting that alterations in functional brain network organization may be only subtle and measureable in patients with more severe cognitive side effects.

Brain activation differences of reading-related processes between dyslexic and normal reading children were localized with functional magnetic resonance imaging (MRI). The children performed tasks that varied in visuospatial, orthographic, phonologic, and semantic processing demands. Enhanced activation of the left extrastriate cortex was found during all tasks in the dyslexic group. During orthographic processing, dyslexic children predominantly showed activation in the right prefrontal cortex, as also occurred during the visuo-spatial task. Normal readers also showed activation in the left prefrontal cortex. Dyslexic readers showed less activation of both the temporal and the prefrontal cortex during phonologic processing. The results suggest that dyslexic readers fail to use brain areas that are normally specialized in language processing, but rather use areas that underlie visuospatial processing.

INTRODUCTION: Focal cortical dysplasia (FCD) is a congenital malformation of cortical development that often leads to medically refractory epilepsy. Focal resection can be an effective treatment, but is challenging as the surgically relevant abnormality may exceed the MR-visible lesion. The aim of the current study is to develop methodology to characterize the profile of functional connectivity around FCDs using resting-state functional MRI and in the individual patient. The detection of aberrant connectivity may provide a means to more completely delineate the clinically relevant lesion.MATERIALS AND METHODS: Fifteen FCD patients (age, mean±SD: 31±11 years; 11 males) and 16 matched healthy controls (35±9 years; 7 males) underwent structural and functional imaging at 3 Tesla. The cortical surface was reconstructed from the T1-weighted scan and the registered functional MRI data was spatially normalized to a common anatomical standard space employing the gyral pattern. Seed-based functional connectivity was determined in all subjects for all dysplasia locations. A single patient was excluded based on an aberrant FCD seed time series. Functional connectivity as a function of geodesic distance (along the cortical surface) was compared between the individual patients and the homotopic normative connectivity profiles derived from the controls.RESULTS: In 12/14 patients, aberrant profiles of functional connectivity were found, which demonstrated both hyper- and hypoconnectivity as well as combinations. Abnormal functional connectivity was typically found (also) beyond the lesion visible on structural MRI, while functional connectivity profiles not related to a lesion appeared normal in patients.CONCLUSION: This novel functional MRI technique has potential for delineating functionally aberrant from normal cortex beyond the structural lesion in FCD, which remains to be confirmed in future research.