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Purpose Cerebral DSA is a routine procedure with few complications. However, it is associated with presumably clinically inapparent lesions detectable on diffusion-weighted MRI imaging (DWI lesions). However, there are insufficient data regarding incidence, etiology, clinical relevance, and longitudinal development of these lesions. This study prospectively evaluated subjects undergoing elective diagnostic cerebral DSA for the occurrence of DWI lesions, potentially associated clinical symptoms and risk factors, and longitudinally monitored the lesions using state-of-the-art MRI. Materials and Methods Eighty-two subjects were examined by high-resolution MRI within 24 h after elective diagnostic DSA and lesion occurrence was qualitatively and quantitatively evaluated. Subjects’ neurological status was assessed before and after DSA by clinical neurological examination and a perceived deficit questionnaire. Patient-related risk factors and procedural DSA data were documented. Subjects with lesions received a follow-up MRI and were questioned for neurological deficits after a median of 5.1 months. Results After DSA, 23(28%) subjects had a total of 54 DWI lesions. Significantly associated risk factors were number of vessels probed, intervention time, age, arterial hypertension, visible calcified plaques, and less examiner experience. Twenty percent of baseline lesions converted to persistent FLAIR lesions at follow-up. After DSA, none of the subjects had a clinically apparent neurological deficit. Self-perceived deficits were nonsignificantly higher at follow-up. Conclusion Cerebral DSA is associated with a considerable number of postinterventional lesions, some persisting as scars in brain tissue. Presumably because of the small lesion size and inconsistent location, no clinically apparent neurological deficits have been observed. However, subtle self-perceived changes may occur. Therefore, special attention is needed to minimize avoidable risk factors.

Cerebrovascular diseases can impair blood circulation and oxygen extraction from the blood. The effective oxygen diffusivity (EOD) of the capillary bed is a potential biomarker of microvascular function that has gained increasing interest, both for clinical diagnosis and for elucidating oxygen transport mechanisms. Models of capillary oxygen transport link EOD to measurable oxygen extraction fraction (OEF) and cerebral blood flow (CBF). In this work, we confirm that two well established mathematical models of oxygen transport yield nearly equivalent EOD maps. Furthermore, we propose an easy-to-implement and clinically applicable multiparametric magnetic resonance imaging (MRI) protocol for quantitative EOD mapping. Our approach is based on imaging OEF and CBF with multiparametric quantitative blood oxygenation level dependent (mq-BOLD) MRI and pseudo-continuous arterial spin labeling (pCASL), respectively. We evaluated the imaging protocol by comparing MRI-EOD maps of 12 young healthy volunteers to PET data from a published study in different individuals. Our results show comparably good correlation between MRI- and PET-derived cortical EOD, OEF and CBF. Importantly, absolute values of MRI and PET showed high accordance for all three parameters. In conclusion, our data indicates feasibility of the proposed MRI protocol for EOD mapping, rendering the method promising for future clinical evaluation of patients with cerebrovascular diseases.

Acute ischemic stroke and subarachnoid hemorrhage due to a ruptured intracranial aneurysm are cerebrovascular emergencies, in which interventional neuroradiological therapeutic procedures play a crucial role. Profound knowledge about indication based on current guidelines and treatment approaches with their advantages and disadvantages are the basis of an evidence-based therapeutic decision. This article aims to provide an empirical overview for everyday practical situations.Der akute ischämische Schlaganfall sowie eine Subarachnoidalblutung durch ein rupturiertes intrakranielles Aneurysma sind zwei unterschiedliche zerebrovaskuläre Notfälle, bei denen interventionell-neuroradiologische Therapieverfahren eine zentrale Rolle spielen. Fundierte Kenntnisse über die leitlinienbasierte Indikationsstellung und das jeweilige Vorgehen bei der endovaskulären Behandlung mit deren Vor- und Nachteilen sind Grundlage einer evidenzbasierten Therapieentscheidung. Dieser Artikel soll eine empirische Übersicht für alltägliche Praxissituationen bieten.

Background Carotid artery stenosis can impair cerebral hemodynamics especially within watershed areas (WSAs) between vascular territories. WSAs can shift because of collateral flow, which may be an indicator for increased hemodynamic implications and hence higher risk for ischemic stroke. However, whether revascularization treatment can reverse the spatial displacement of individual WSAs (iWSAs) and impaired hemodynamics remains unknown. Hypothesis That iWSAs spatially normalize because of hemodynamic improvement resulting from revascularization treatment. Study Type Prospective. Population Sixteen patients with unilateral, high‐grade carotid artery stenosis confirmed by duplex ultrasonography and 17 healthy controls. Field strength/Sequences A 3 T‐magnetization‐prepared rapid acquisition gradient echo (MPRAGE), gradient‐echo echo planar dynamic susceptibility contrast (DSC), and fluid‐attenuated inversion recovery (FLAIR) sequences. Additionally, contrast‐enhanced 3D gradient echo magnetic resonance angiography (MRA) and diffusion‐tensor imaging (DTI) spin‐echo echo planar imaging were performed. Assessment iWSAs were delineated by a recently proposed procedure based on time‐to‐peak maps from DSC perfusion MRI, which were also used to evaluate perfusion delay. We spatially compared iWSAs and perfusion delay before and after treatment (endarterectomy or stenting). Additionally, the Circle of Willis collateralization status was evaluated, and basic cognitive testing was conducted. Statistical Tests Statistical tests included two‐sample t‐tests and Chi‐squared tests. A P value < 0.05 was considered to be statistically significant. Results After revascularization, patients showed a significant spatial shift of iWSAs and significantly reduced perfusion delay ipsilateral to the stenosis. Spatial shift of iWSA (P = 0.007) and cognitive improvement (P = 0.013) were more pronounced in patients with poor pre‐existing collateralization. Controls demonstrated stable spatial extent of iWSAs (P = 0.437) and symmetric perfusion delays between hemispheres over time (P = 0.773). Data Conclusion These results demonstrate the normalization of iWSA and impaired hemodynamics after revascularization in patients with high‐grade carotid artery stenosis. Level of Evidence 2 Technical Efficacy Stage 2, publishedVersion

Improved understanding of complex hemodynamic impairments in asymptomatic internal carotid artery stenosis (ICAS) is crucial to better assess stroke risks. Multimodal MRI is ideal for measuring brain hemodynamics and has the potential to improve diagnostics and treatment selections. We applied MRI-based perfusion and oxygenation-sensitive imaging in ICAS with the hypothesis that the sensitivity to hemodynamic impairments will improve within individual watershed areas (iWSA). We studied cerebral blood flow (CBF), cerebrovascular reactivity (CVR), relative cerebral blood volume (rCBV), relative oxygen extraction fraction (rOEF), oxygen extraction capacity (OEC) and capillary transit-time heterogeneity (CTH) in 29 patients with asymptomatic, unilateral ICAS (age 70.3 ± 7.0 y) and 30 age-matched healthy controls. In ICAS, we found significant impairments of CBF, CVR, rCBV, OEC, and CTH (strongest lateralization ΔCVR = –24%), but not of rOEF. Although the spatial overlap of compromised hemodynamic parameters within each patient varied in a complex manner, most pronounced changes of CBF, CVR and rCBV were detected within iWSAs (strongest effect ΔCVR = +117%). At the same time, CTH impairments were iWSA independent, indicating widespread dysfunction of capillary-level oxygen diffusivity. In summary, complementary MRI-based perfusion and oxygenation parameters offer deeper perspectives on complex microvascular impairments in individual patients. Furthermore, knowledge about iWSAs improves the sensitivity to hemodynamic impairments.

Functional connectivity (FC) derived from blood oxygenation level dependent (BOLD) functional magnetic resonance imaging at rest (rs-fMRI), is commonly interpreted as indicator of neuronal connectivity. In a number of brain disorders, however, metabolic, vascular, and hemodynamic impairments can be expected to alter BOLD-FC independently from neuronal activity. By means of a neurovascular coupling (NVC) model of BOLD-FC, we recently demonstrated that aberrant timing of cerebral blood flow (CBF) responses may influence BOLD-FC. In the current work, we support and extend this finding by empirically linking BOLD-FC with capillary transit time heterogeneity (CTH), which we consider as an indicator of delayed and broadened CBF responses. We assessed 28 asymptomatic patients with unilateral high-grade internal carotid artery stenosis (ICAS) as a hemodynamic lesion model with largely preserved neurocognitive functioning and 27 age-matched healthy controls. For each participant, we obtained rs-fMRI, arterial spin labeling, and dynamic susceptibility contrast MRI to study the dependence of left-right homotopic BOLD-FC on local perfusion parameters. Additionally, we investigated the dependency of BOLD-FC on CBF response timing by detailed simulations. Homotopic BOLD-FC was negatively associated with increasing CTH differences between homotopic brain areas. This relation was more pronounced in asymptomatic ICAS patients even after controlling for baseline CBF and relative cerebral blood volume influences. These findings match simulation results that predict an influence of delayed and broadened CBF responses on BOLD-FC. Results demonstrate that increasing CTH differences between homotopic brain areas lead to BOLD-FC reductions. Simulations suggest that CTH increases correspond to broadened and delayed CBF responses to fluctuations in ongoing neuronal activity.

Patients with asymptomatic, high-grade internal carotid artery stenosis often suffer from subtle cognitive impairments with unclear underlying neuro-cognitive mechanisms. Thus, we hypothesized that stenosis-related unilateral cerebral hypoperfusion leads to an ipsilateral attentional bias; 22 patients with asymptomatic, one-sided high-grade carotid stenosis and 24 age-matched healthy controls underwent pseudo-continuous arterial spin labeling to assess brain perfusion in the territory of the carotid arteries. Furthermore, a parametric assessment of attention functions was carried out on the basis of the computational Theory of Visual Attention. Both patients' perfusion and spatial attention were significantly more lateralized than those of healthy controls. Critically, both asymmetry indices were significantly correlated in patients, i.e. the stronger one-sided relative hypoperfusion, the stronger ipsilateral bias of attention. This association was specifically pronounced in parietal cortices and independent of white matter hyperintensities as a surrogate for cerebrovascular brain damage. Results provide evidence for a link between lateralized hypoperfusion and lateralized attentional weighting in asymptomatic, high-grade carotid stenosis. Data suggest that lateralized hypoperfusion with simultaneous spatial attentional bias might serve as a potential therapeutic target in one-sided carotid stenosis.

Oxygen extraction (OEF), oxidative metabolism (CMRO2), and blood flow (CBF) in the brain, as well as the coupling between CMRO2 and CBF due to cerebral autoregulation are fundamental to brain's health. We used a clinically feasible MRI protocol to assess impairments of these parameters in the perfusion territories of stenosed carotid arteries. Twenty-nine patients with unilateral high-grade carotid stenosis and thirty age-matched healthy controls underwent multi-modal MRI scans. Pseudo-continuous arterial spin labeling (pCASL) yielded absolute CBF, whereas multi-parametric quantitative blood oxygenation level dependent (mqBOLD) modeling allowed imaging of relative OEF and CMRO2. Both CBF and CMRO2 were significantly reduced in the stenosed territory compared to the contralateral side, while OEF was evenly distributed across both hemispheres similarly in patients and controls. The CMRO2-CBF coupling was significantly different between both hemispheres in patients, i.e. significant interhemispheric flow-metabolism uncoupling was observed in patients compared to controls. Given that CBF and CMRO2 are intimately linked to brain function in health and disease, the proposed easily applicable MRI protocol of pCASL and mqBOLD imaging might serve as a valuable tool for early diagnosis of potentially harmful cerebral hemodynamic and metabolic states with the final aim to select clinically asymptomatic patients who would benefit from carotid revascularization therapy.

Functional connectivity of blood oxygenation level dependent signal fluctuations (BOLD-FC) is decreased in Alzheimer’s disease (AD), and suggested to reflect reduced coherence in neural population activity; however, as both neuronal and vascular-hemodynamic processes underlie BOLD signals, impaired perfusion might also contribute to reduced BOLD-FC; 42 AD patients and 27 controls underwent simultaneous PET/MR imaging. Resting-state functional MRI assessed BOLD co-activity to quantify BOLD-FC, pulsed arterial spin labeling (pASL) assessed cerebral blood flow (CBF) as proxy for vascular hemodynamics, and 18F-fluorodeoxyglucose PET assessed glucose metabolism (GluMet) to index neuronal activity. Patients’ BOLD-FC, CBF, and GluMet were reduced within the same precuneal parietal regions. BOLD-FC was positively associated with mean CBF, specifically in patients and controlled for GluMet levels, suggesting that BOLD-FC reductions correlate with pASL-derived hypoperfusion in AD, independently from 18F-fluorodeoxyglucose PET-derived hypometabolism. Data indicate that impaired vascular hemodynamic processes contribute to reduced BOLD connectivity in AD.

Watershed areas (WSAs) of the brain are most susceptible to acute hypoperfusion due to their peripheral location between vascular territories. Additionally, chronic WSA-related vascular processes underlie cognitive decline especially in patients with cerebral hemodynamic compromise. Despite of high relevance for both clinical diagnostics and research, individual in vivo WSA definition is fairly limited to date. Thus, this study proposes a standardized segmentation approach to delineate individual WSAs by use of time-to-peak (TTP) maps and investigates spatial variability of individual WSAs. We defined individual watershed masks based on relative TTP increases in 30 healthy elderly persons and 28 patients with unilateral, high-grade carotid stenosis, being at risk for watershed-related hemodynamic impairment. Determined WSA location was confirmed by an arterial transit time atlas and individual super-selective arterial spin labeling. We compared spatial variability of WSA probability maps between groups and assessed TTP differences between hemispheres in individual and group-average watershed locations. Patients showed significantly higher spatial variability of WSAs than healthy controls. Perfusion on the side of the stenosis was delayed within individual watershed masks as compared to a watershed template derived from controls, being independent from the grade of the stenosis and collateralization status of the circle of Willis. Results demonstrate feasibility of individual WSA delineation by TTP maps in healthy elderly and carotid stenosis patients. Data indicate necessity of individual segmentation approaches especially in patients with hemodynamic compromise to detect critical regions of impaired hemodynamics.

Relative oxygen extraction fraction (rOEF) is a fundamental indicator of cerebral metabolic function. An easily applicable method for magnetic resonance imaging (MRI) based rOEF mapping is the multi-parametric quantitative blood oxygenation level dependent (mq-BOLD) approach with separate acquisitions of transverse relaxation times [Formula: see text] and T2 and dynamic susceptibility contrast (DSC) based relative cerebral blood volume (rCBV). Given that transverse relaxation and rCBV in white matter (WM) strongly depend on nerve fiber orientation, mq-BOLD derived rOEF is expected to be affected as well. To investigate fiber orientation related rOEF artefacts, we present a methodological study characterizing anisotropy effects of WM as measured by diffusion tensor imaging (DTI) on mq-BOLD in 30 healthy volunteers. Using a 3T clinical MRI-scanner, we performed a comprehensive correlation of all parameters ([Formula: see text], T2, [Formula: see text], rCBV, rOEF, where [Formula: see text]=1/[Formula: see text]–1/T2) with DTI-derived fiber orientation towards the main magnetic field (B0). Our results confirm strong dependencies of transverse relaxation and rCBV on the nerve fiber orientation towards B0, with anisotropy-driven variations up to 37%. Comparably weak orientation-dependent variations of mq-BOLD derived rOEF (3.8%) demonstrate partially counteracting influences of [Formula: see text] and rCBV effects, possibly suggesting applicability of rOEF as an oxygenation sensitive biomarker. However, unresolved issues warrant caution when applying mq-BOLD to WM.

Thirty untreated glioma patients (27 high-grade) underwent simultaneous PET/MRI on a 3 T hybrid scanner obtaining structural and dynamic susceptibility contrast sequences. Static FET-uptake and dynamic FET-slope were correlated with rCBV within tumour hotspots across patients and intra-lesionally using a mixed-effects model to account for inter-individual variation. Furthermore, maximal congruency of tumour volumes defined by FET-uptake and rCBV was determined.While the inter-individual relationship between peak static FET-uptake and rCBV could be confirmed, our intra-lesional, voxel-wise analysis revealed significant positive correlations (median r = 0.374, p 0.0001). Similarly, significant inter- and intra-individual correlations were observed between FET-slope and rCBV. However, rCBV explained only 12% of the static and 5% of the dynamic FET-PET variance and maximal overlap of respective tumour volumes was 37% on average.Our results show that the relation between peak values of MR-based rCBV and static FET-uptake can also be observed intra-individually on a voxel basis and also applies to a dynamic FET parameter, possibly determining hotspots of higher biological malignancy. However, just a small part of the FET-PET signal variance is explained by rCBV and tumour volumes determined by the two modalities showed only moderate overlap. These findings indicate that FET-PET and MR-based rCBV provide both congruent and complimentary information on glioma biology.

Amyloid-β pathology (Aβ) and impaired cognition characterize Alzheimer's disease (AD); however, neural mechanisms that link Aβ-pathology with impaired cognition are incompletely understood. Large-scale intrinsic connectivity networks (ICNs) are potential candidates for this link: Aβ-pathology affects specific networks in early AD, these networks show disrupted connectivity, and they process specific cognitive functions impaired in AD, like memory or attention. We hypothesized that, in AD, regional changes of ICNs, which persist across rest- and cognitive task-states, might link Aβ-pathology with impaired cognition via impaired intrinsic connectivity. Pittsburgh compound B (PiB)-positron emission tomography reflecting in vivo Aβ-pathology, resting-state fMRI, task-fMRI, and cognitive testing were used in patients with prodromal AD and healthy controls. In patients, default mode network's (DMN) functional connectivity (FC) was reduced in the medial parietal cortex during rest relative to healthy controls, relatively increased in the same region during an attention-demanding task, and associated with patients' cognitive impairment. Local PiB-uptake correlated negatively with DMN connectivity. Importantly, corresponding results were found for the right lateral parietal region of an attentional network. Finally, structural equation modeling confirmed a direct influence of DMN resting-state FC on the association between Aβ-pathology and cognitive impairment. Data provide evidence that disrupted intrinsic network connectivity links Aβ-pathology with cognitive impairment in early AD.

The cortical distribution of amyloid-β plaques in Alzheimer’s disease strikingly resembles frontal-parietal intrinsic functional connectivity networks. Using a novel method to trace the distribution of amyloid-β plaques within single patients, Myers et al. reveal a marked negative effect on intrinsic connectivity in several networks that have not typically been investigated., There is striking overlap between the spatial distribution of amyloid-β pathology in patients with Alzheimer’s disease and the spatial distribution of high intrinsic functional connectivity in healthy persons. This overlap suggests a mechanistic link between amyloid-β and intrinsic connectivity, and indeed there is evidence in patients for the detrimental effects of amyloid-β plaque accumulation on intrinsic connectivity in areas of high connectivity in heteromodal hubs, and particularly in the default mode network. However, the observed spatial extent of amyloid-β exceeds these tightly circumscribed areas, suggesting that previous studies may have underestimated the negative impact of amyloid-β on intrinsic connectivity. We hypothesized that the known positive baseline correlation between patterns of amyloid-β and intrinsic connectivity may mask the larger extent of the negative effects of amyloid-β on connectivity. Crucially, a test of this hypothesis requires the within-patient comparison of intrinsic connectivity and amyloid-β distributions. Here we compared spatial patterns of amyloid-β-plaques (measured by Pittsburgh compound B positron emission tomography) and intrinsic functional connectivity (measured by resting-state functional magnetic resonance imaging) in patients with prodromal Alzheimer’s disease via spatial correlations in intrinsic networks covering fronto-parietal heteromodal cortices. At the global network level, we found that amyloid-β and intrinsic connectivity patterns were positively correlated in the default mode and several fronto-parietal attention networks, confirming that amyloid-β aggregates in areas of high intrinsic connectivity on a within-network basis. Further, we saw an internetwork gradient of the magnitude of correlation that depended on network plaque-load. After accounting for this globally positive correlation, local amyloid-β-plaque concentration in regions of high connectivity co-varied negatively with intrinsic connectivity, indicating that amyloid-β pathology adversely reduces connectivity anywhere in an affected network as a function of local amyloid-β-plaque concentration. The local negative association between amyloid-β and intrinsic connectivity was much more pronounced than conventional group comparisons of intrinsic connectivity would suggest. Our findings indicate that the negative impact of amyloid-β on intrinsic connectivity in heteromodal networks is underestimated by conventional analyses. Moreover, our results provide first within-patient evidence for correspondent patterns of amyloid-β and intrinsic connectivity, with the distribution of amyloid-β pathology following functional connectivity gradients within and across intrinsic networks.