Macro- and microvascular contributions to cerebral structural alterations in patients with asymptomatic carotid artery stenosis.

Atherosclerosis can underly internal carotid artery stenosis (ICAS), a major risk factor for ischemic stroke, as well as small vessel disease (SVD). This study aimed to investigate hemodynamics and structural alterations associated with SVD in ICAS patients. 28 patients with unilateral asymptomatic ICAS and 30 age-matched controls underwent structural (T1-/T2-weighted and diffusion tensor imaging [DTI]) and hemodynamic (pseudo-continuous arterial spin labeling and dynamic susceptibility contrast) magnetic resonance imaging. SVD-related alterations were assessed using free water (FW), FW-corrected DTI, and peak-width of skeletonized mean diffusivity (PSMD). Furthermore, cortical thickness, cerebral blood flow (CBF), and capillary transit time heterogeneity (CTH) were analyzed. Ipsilateral to the stenosis, cortical thickness was significantly decreased in the posterior dorsal cingulate cortex (p = 0.024) and temporal pole (p = 0.028). ICAS patients exhibited elevated PSMD (p = 0.005), FW (p < 0.001), and contralateral alterations in FW-corrected DTI metrics. We found significantly lateralized CBF (p = 0.011) and a tendency for lateralized CTH (p = 0.067) in the white matter (WM) related to ICAS. Elevated PSMD and FW may indicate a link between SVD and WM changes. Contralateral alterations were seen in FW-corrected DTI, whereas hemodynamic and cortical changes were mainly ipsilateral, suggesting SVD might influence global brain changes concurrent with ICAS-related hemodynamic alterations.

Stronger influence of systemic than local hemodynamic-vascular factors on resting-state BOLD functional connectivity.

Correlated fluctuations in the blood oxygenation level dependent (BOLD) signal of resting-state functional MRI (i.e., BOLD-functional connectivity, BOLD-FC) reflect a spectrum of neuronal and non-neuronal processes. In particular, there are multiple hemodynamic-vascular influences on BOLD-FC on both systemic (e.g., perfusion delay) and local levels (e.g., neurovascular coupling). While the influence of individual factors has been studied extensively, combined and comparative studies of systemic and local hemodynamic-vascular factors on BOLD-FC are scarce, notably in humans. We employed a multi-modal MRI approach to investigate and compare distinct hemodynamic-vascular processes and their impact on homotopic BOLD-FC in healthy controls and patients with unilateral asymptomatic internal carotid artery stenosis (ICAS). Asymptomatic ICAS is a cerebrovascular disorder, in which neuronal functioning is largely preserved but hemodynamic-vascular processes are impaired, mostly on the side of stenosis. Investigated indicators for local hemodynamic-vascular processes comprise capillary transit time heterogeneity (CTH) and cerebral blood volume (CBV) from dynamic susceptibility contrast (DSC) MRI, and cerebral blood flow (CBF) from pseudo-continuous arterial spin labeling (pCASL). Indicators for systemic processes are time-to-peak (TTP) from DSC MRI and BOLD lags from functional MRI. For each of these parameters, their influence on BOLD-FC was estimated by a comprehensive linear mixed model. Equally across groups, we found that individual mean BOLD-FC, local (CTH, CBV, and CBF) and systemic (TTP and BOLD lag) hemodynamic-vascular factors together explain 40.7% of BOLD-FC variance, with 20% of BOLD-FC variance explained by hemodynamic-vascular factors, with an about two-times larger contribution of systemic versus local factors. We conclude that regional differences in blood supply, i.e., systemic perfusion delays, exert a stronger influence on BOLD-FC than impairments in local neurovascular coupling.

Incidence, Clinical Significance, and Longitudinal Signal Characteristics of Ischemic Lesions Related to Diagnostic Cerebral Catheter Angiography.

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.

[Acute cerebrovascular events-fundamentals]. / Akutes zerebrovaskuläres Ereignis ­ das kleine Einmaleins.

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.

Resting-state BOLD functional connectivity depends on the heterogeneity of capillary transit times in the human brain A combined lesion and simulation study about the influence of blood flow response timing.

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.

Hemodynamic MRI parameters to predict asymptomatic unilateral carotid artery stenosis with random forest machine learning.

Background: Internal carotid artery stenosis (ICAS) can cause stroke and cognitive decline. Associated hemodynamic impairments, which are most pronounced within individual watershed areas (iWSA) between vascular territories, can be assessed with hemodynamic-oxygenation-sensitive MRI and may help to detect severely affected patients. We aimed to identify the most sensitive parameters and volumes of interest (VOI) to predict high-grade ICAS with random forest machine learning. We hypothesized an increased predictive ability considering iWSAs and a decreased cognitive performance in correctly classified patients. Materials and methods: Twenty-four patients with asymptomatic, unilateral, high-grade carotid artery stenosis and 24 age-matched healthy controls underwent MRI comprising pseudo-continuous arterial spin labeling (pCASL), breath-holding functional MRI (BH-fMRI), dynamic susceptibility contrast (DSC), T2 and T2* mapping, MPRAGE and FLAIR. Quantitative maps of eight perfusion, oxygenation and microvascular parameters were obtained. Mean values of respective parameters within and outside of iWSAs split into gray (GM) and white matter (WM) were calculated for both hemispheres and for interhemispheric differences resulting in 96 features. Random forest classifiers were trained on whole GM/WM VOIs, VOIs considering iWSAs and with additional feature selection, respectively. Results: The most sensitive features in decreasing order were time-to-peak (TTP), cerebral blood flow (CBF) and cerebral vascular reactivity (CVR), all of these inside of iWSAs. Applying iWSAs combined with feature selection yielded significantly higher receiver operating characteristics areas under the curve (AUC) than whole GM/WM VOIs (AUC: 0.84 vs. 0.90, p = 0.039). Correctly predicted patients presented with worse cognitive performances than frequently misclassified patients (Trail-making-test B: 152.5s vs. 94.4s, p = 0.034). Conclusion: Random forest classifiers trained on multiparametric MRI data allow identification of the most relevant parameters and VOIs to predict ICAS, which may improve personalized treatments.

Imaging effective oxygen diffusivity in the human brain with multiparametric magnetic resonance imaging.

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.

Decreasing Spatial Variability of Individual Watershed Areas by Revascularization Therapy in Patients With High-Grade Carotid Artery Stenosis.

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.

Hemodynamic impairments within individual watershed areas in asymptomatic carotid artery stenosis by multimodal MRI.

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.

The stronger one-sided relative hypoperfusion, the more pronounced ipsilateral spatial attentional bias in patients with asymptomatic carotid stenosis.

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.

Characterizing white matter fiber orientation effects on multi-parametric quantitative BOLD assessment of oxygen extraction fraction.

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 T2* 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 ( T2*, T2, R2', rCBV, rOEF, where R2'=1/ T2*-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 R2' and rCBV effects, possibly suggesting applicability of rOEF as an oxygenation sensitive biomarker. However, unresolved issues warrant caution when applying mq-BOLD to WM.

Reduced blood oxygenation level dependent connectivity is related to hypoperfusion in Alzheimer's disease.

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.

Flow-metabolism uncoupling in patients with asymptomatic unilateral carotid artery stenosis assessed by multi-modal magnetic resonance imaging.

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.

Increased variability of watershed areas in patients with high-grade carotid stenosis.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Characterizing hypoxia in human glioma: A simultaneous multimodal MRI and PET study.

Hypoxia plays an important role for the prognosis and therapy response of cancer. Thus, hypoxia imaging would be a valuable tool for pre-therapeutic assessment of tumor malignancy. However, there is no standard validated technique for clinical application available yet. Therefore, we performed a study in 12 patients with high-grade glioma, where we directly compared the two currently most promising techniques, namely the MR-based relative oxygen extraction fraction (MR-rOEF) and the PET hypoxia marker H-1-(3-[18 F]-fluoro-2-hydroxypropyl)-2-nitroimidazole ([18 F]-FMISO). MR-rOEF was determined from separate measurements of T2 , T2 * and relative cerebral blood volume (rCBV) employing a multi-parametric approach for quantification of the blood-oxygenation-level-dependent (BOLD) effect. With respect to [18 F]-FMISO-PET, besides the commonly used late uptake between 120 and 130 min ([18 F]-FMISO120-130 min ), we also analyzed the hypoxia specific uptake rate [18 F]-FMISO-k3 , as obtained by pharmacokinetic modeling of dynamic uptake data. Since pharmacokinetic modeling of partially acquired dynamic [18 F]-FMISO data was sensitive to a low signal-to-noise-ratio, analysis was restricted to high-uptake tumor regions. Individual spatial analyses of deoxygenation and hypoxia-related parameter maps revealed that high MR-rOEF values clustered in (edematous) peritumoral tissue, while areas with high [18 F]-FMISO120-130 min concentrated in and around active tumor with disrupted blood-brain barrier, i.e. contrast enhancement in T1 -weighted MRI. Volume-of-interest-based correlations between MR-rOEF and [18 F]-FMISO120-130 min as well as [18 F]-FMISO-k3 , and voxel-wise analyses in individual patients, yielded limited correlations, supporting the notion that [18 F]-FMISO uptake, even after 2 h, might still be influenced by perfusion while [18 F]-FMISO-k3 was severely hampered by noise. According to these results, vascular deoxygenation, as measured by MR-rOEF, and severe tissue hypoxia, as measured by [18 F]-FMISO, show a poor spatial correspondence. Overall, the two methods appear to rather provide complementary than redundant information about high-grade glioma biology.

Resting-State Connectivity of the Left Frontal Cortex to the Default Mode and Dorsal Attention Network Supports Reserve in Mild Cognitive Impairment.

Reserve refers to the phenomenon of relatively preserved cognition in disproportion to the extent of neuropathology, e.g., in Alzheimer's disease. A putative functional neural substrate underlying reserve is global functional connectivity of the left lateral frontal cortex (LFC, Brodmann Area 6/44). Resting-state fMRI-assessed global LFC-connectivity is associated with protective factors (education) and better maintenance of memory in mild cognitive impairment (MCI). Since the LFC is a hub of the fronto-parietal control network that regulates the activity of other networks, the question arises whether LFC-connectivity to specific networks rather than the whole-brain may underlie reserve. We assessed resting-state fMRI in 24 MCI and 16 healthy controls (HC) and in an independent validation sample (23 MCI/32 HC). Seed-based LFC-connectivity to seven major resting-state networks (i.e., fronto-parietal, limbic, dorsal-attention, somatomotor, default-mode, ventral-attention, visual) was computed, reserve was quantified as residualized memory performance after accounting for age and hippocampal atrophy. In both samples of MCI, LFC-activity was anti-correlated with the default-mode network (DMN), but positively correlated with the dorsal-attention network (DAN). Greater education predicted stronger LFC-DMN-connectivity (anti-correlation) and LFC-DAN-connectivity. Stronger LFC-DMN and LFC-DAN-connectivity each predicted higher reserve, consistently in both MCI samples. No associations were detected for LFC-connectivity to other networks. These novel results extend our previous findings on global functional connectivity of the LFC, showing that LFC-connectivity specifically to the DAN and DMN, two core memory networks, enhances reserve in the memory domain in MCI.

Intra-lesional spatial correlation of static and dynamic FET-PET parameters with MRI-based cerebral blood volume in patients with untreated glioma.

PURPOSE: 18F-fluorethyltyrosine-(FET)-PET and MRI-based relative cerebral blood volume (rCBV) have both been used to characterize gliomas. Recently, inter-individual correlations between peak static FET-uptake and rCBV have been reported. Herein, we assess the local intra-lesional relation between FET-PET parameters and rCBV. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Closed-Cell Stent-Assisted Coiling of Intracranial Aneurysms: Evaluation of Changes in Vascular Geometry Using Digital Subtraction Angiography.

BACKGROUND: Stent-assisted coil embolization (SACE) plays an important role in the treatment of intracranial aneurysms. The purpose of this study was to investigate geometrical changes caused by closed-cell design stents in bifurcation and sidewall aneurysms. METHODS: 31 patients with 34 aneurysms underwent SACE with closed-cell design stents. Inflow angle α, determined by aneurysm neck and afferent vessel, and angle between afferent and efferent vessel close to (δ1), respectively, more remote from the aneurysm neck (δ2) were graphically determined in 2D angiography projections. RESULTS: Stent assisted coiling resulted in a significant increase of all three angles from a mean value (±SEM) of α = 119° (±6.5°) pretreatment to 130° (±6.6°) posttreatment (P ≤ .001), δ1 = 129° (±6.4°) to 139° (±6.1°), (P ≤ .001) and δ2 = 115° (±8.4°) to 126° (±7.5°), (P ≤ .01). Angular change of δ1 in AcomA aneurysms was significant greater compared to sidewall aneurysms (26°±4.9° versus 8°± 2.3°, P ≤ .05). The initial angle of δ1 and δ2 revealed a significantly inverse relationship to the angle increase (δ1: r = -0.41, P ≤ .05 and δ2: r = -0.47, P ≤ .01). Moreover, angle δ1 was significantly higher in unruptured compared to ruptured aneurysms (135°±7.1° versus 103°±10.8°, P ≤ .05). CONCLUSION: Stent deployment modulates the geometry of the aneurysm-vessel complex, which may lead to favorable hemodynamic changes more similar to unruptured than to ruptured aneurysms. Our findings also suggest that the more acute-angled aneurysm-vessel anatomy, the larger the angular change. Further studies are needed to investigate whether these changes improve the clinical outcome.

Disrupted Intrinsic Networks Link Amyloid-ß Pathology and Impaired Cognition in Prodromal Alzheimer's Disease.

Amyloid-ß pathology (Aß) and impaired cognition characterize Alzheimer's disease (AD); however, neural mechanisms that link Aß-pathology with impaired cognition are incompletely understood. Large-scale intrinsic connectivity networks (ICNs) are potential candidates for this link: Aß-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 Aß-pathology with impaired cognition via impaired intrinsic connectivity. Pittsburgh compound B (PiB)-positron emission tomography reflecting in vivo Aß-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 Aß-pathology and cognitive impairment. Data provide evidence that disrupted intrinsic network connectivity links Aß-pathology with cognitive impairment in early AD.

Within-patient correspondence of amyloid-ß and intrinsic network connectivity in Alzheimer's disease.

There is striking overlap between the spatial distribution of amyloid-ß 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-ß and intrinsic connectivity, and indeed there is evidence in patients for the detrimental effects of amyloid-ß 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-ß exceeds these tightly circumscribed areas, suggesting that previous studies may have underestimated the negative impact of amyloid-ß on intrinsic connectivity. We hypothesized that the known positive baseline correlation between patterns of amyloid-ß and intrinsic connectivity may mask the larger extent of the negative effects of amyloid-ß on connectivity. Crucially, a test of this hypothesis requires the within-patient comparison of intrinsic connectivity and amyloid-ß distributions. Here we compared spatial patterns of amyloid-ß-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-ß and intrinsic connectivity patterns were positively correlated in the default mode and several fronto-parietal attention networks, confirming that amyloid-ß 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-ß-plaque concentration in regions of high connectivity co-varied negatively with intrinsic connectivity, indicating that amyloid-ß pathology adversely reduces connectivity anywhere in an affected network as a function of local amyloid-ß-plaque concentration. The local negative association between amyloid-ß 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-ß on intrinsic connectivity in heteromodal networks is underestimated by conventional analyses. Moreover, our results provide first within-patient evidence for correspondent patterns of amyloid-ß and intrinsic connectivity, with the distribution of amyloid-ß pathology following functional connectivity gradients within and across intrinsic networks.