Intracranial Atherosclerosis Assessed with 7-T MRI: Evaluation of Patients with Ischemic Stroke or Transient Ischemic Attack.

Background Intracranial atherosclerosis is an important cause of ischemic stroke and is associated with several vascular risk factors. Current imaging is mainly based on the assessment of luminal narrowing rather than abnormalities in the vessel wall. Purpose To investigate the relationship between vascular risk factors and atherosclerotic lesion burden of intracranial arteries assessed with vessel wall MRI at 7 T in participants with ischemic stroke or transient ischemic attack (TIA). Materials and Methods In this prospective study (trial identification number: NTR2119; www.trialregister.nl), study participants who presented with ischemic stroke or TIA of the anterior circulation between December 2009 and September 2017 underwent pre- and postcontrast 7-T vessel wall MRI within 3 months of symptom onset. All large arteries of the intracranial circulation were assessed for number, location, and enhancement of vessel wall lesions. Generalized estimating equations for Poisson regression were used to investigate the relationship between vascular risk factors and number or enhancement of vessel wall lesions. Results Ninety participants (52 men; mean age, 60 years) were evaluated. Increasing age (relative risk [RR], 1.02; 95% confidence interval [CI]: 1.01, 1.03), hypertension (RR, 1.46; 95% CI: 1.06, 2.02), diabetes mellitus (RR, 1.67; 95% CI: 1.20, 2.33), and a higher multivariable vascular risk score (Second Manifestations of Arterial Disease risk score) (RR, 1.01; 95% CI: 1.00, 1.02) were associated with a higher number of vessel wall lesions in the anterior circulation. Contrast material-enhancing vessel wall lesions were associated only with increasing age (RR, 1.03; 95% CI: 1.01, 1.05). No association was found between smoking and the number of vessel wall lesions. Conclusion Except for smoking, traditional common cardiovascular risk factors were associated with a higher number and enhancement of intracranial vessel wall lesions at 7-T MRI in individuals evaluated after ischemic stroke or transient ischemic attack. Published under a CC BY 4.0 license. Online supplemental material is available for this article.

Detecting Intracranial Vessel Wall Lesions With 7T-Magnetic Resonance Imaging: Patients With Posterior Circulation Ischemia Versus Healthy Controls.

BACKGROUND AND PURPOSE: Vessel wall magnetic resonance imaging sequences have been developed to directly visualize the intracranial vessel wall, enabling detection of vessel wall changes, including those that have not yet caused luminal narrowing. In this study, vessel wall lesion burden was assessed in patients with recent posterior circulation ischemia using 7T-magnetic resonance imaging and compared with matched healthy controls. METHODS: Fifty subjects (25 patients and 25 matched healthy controls) underwent 7T-magnetic resonance imaging with an intracranial vessel wall sequence before and after contrast administration. Two raters scored the presence and contrast enhancement of arterial wall lesions in individual segments of the circle of Willis and its primary branches. Total burden and distribution of vessel wall lesions and lesion characteristics (configuration, thickening pattern, and contrast enhancement) were compared both between and within both groups. RESULTS: Overall, vessel wall lesion burden and distribution were comparable between patients and controls. Regarding individual arterial segments, only vessel wall lesions in the posterior cerebral artery were more frequently observed in patients (18.0%) than in controls (5.4%; P=0.003). Many of these lesions showed enhancement, both in patients (48.9%) and in controls (43.5%; P=0.41). In patients, the proportion of enhancing lesions was higher in the posterior circulation (53.3%) than in the anterior circulation (20.6%; P=0.008). CONCLUSIONS: Although overall intracranial vessel wall lesion burden and contrast enhancement were comparable between patients with recent posterior circulation ischemia and healthy controls, this study also revealed significant differences between the 2 groups, suggesting an association between posterior circulation lesion burden/enhancement and ischemic events. CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl. Unique identifier: NTR5688.

High-resolution intracranial vessel wall MRI in an elderly asymptomatic population: comparison of 3T and 7T.

OBJECTIVES: Several intracranial vessel wall sequences have been described in recent literature, with either 3-T or 7-T magnetic resonance imaging (MRI). In the current study, we compared 3-T and 7-T MRI in visualising both the intracranial arterial vessel wall and vessel wall lesions. METHODS: Twenty-one elderly asymptomatic volunteers were scanned by 3-T and 7-T MRI with an intracranial vessel wall sequence, both before and after contrast administration. Two raters scored image quality, and presence and characteristics of vessel wall lesions. RESULTS: Vessel wall visibility was equal or significantly better at 7 T for the studied arterial segments, even though there were more artefacts hampering assessment. The better visualisation of the vessel wall at 7 T was most prominent in the proximal anterior cerebral circulation and the posterior cerebral artery. In the studied elderly asymptomatic population, 48 vessel-wall lesions were identified at 3 T, of which 7 showed enhancement. At 7 T, 79 lesions were identified, of which 29 showed enhancement. Seventy-one percent of all 3-T lesions and 59 % of all 7-T lesions were also seen at the other field strength. CONCLUSIONS: Despite the large variability in detected lesions at both field strengths, we believe 7-T MRI has the highest potential to identify the total burden of intracranial vessel wall lesions. KEY POINTS: • Intracranial vessel wall visibility was equal or significantly better at 7-T MRI • Most vessel wall lesions in the cerebral arteries were found at 7-T MRI • Many intracranial vessel wall lesions showed enhancement after contrast administration • Large variability in detected intracranial vessel wall lesions at both field strengths • Seven-tesla MRI has the highest potential to identify total burden of intracranial atherosclerosis.

Magnetic Resonance Imaging of Plaque Morphology, Burden, and Distribution in Patients With Symptomatic Middle Cerebral Artery Stenosis.

BACKGROUND AND PURPOSE: Intracranial atherosclerosis is a major cause of ischemic stroke worldwide. Intracranial vessel wall imaging is an upcoming field of interest to assess intracranial atherosclerosis. In this study, we investigated total intracranial plaque burden in patients with symptomatic middle cerebral artery stenosis, assessed plaque morphological features, and compared features of symptomatic and asymptomatic lesions using a 3T vessel wall sequence. METHODS: Nineteen consecutive Chinese patients with ischemic stroke and transient ischemic attack (mean age: 67 years; 7 females) with a middle cerebral artery stenosis were scanned at 3T magnetic resonance imaging; the protocol included a time-of-flight magnetic resonance angiography and the T1-weighted volumetric isotropically reconstructed turbo spin echo acquisition sequence before and after (83%) contrast administration. Chi-square tests were used to assess associations between different plaque features. Statistical significance was set at P<0.05. RESULTS: Vessel wall lesions were identified in 18 patients (95%), totaling 57 lesions in 494 segments (12% of segments). Lesions were located primarily in the anterior circulation (82%). Eccentric lesions were associated with a focal thickening pattern and concentric lesions with a diffuse thickening pattern (P<0.001). When differentiating between asymptomatic and symptomatic lesions, an association (P<0.05) was found between eccentricity and asymptomatic lesions, but not for enhancement or a specific thickening pattern. Symptomatic lesions did not have any specific morphological features. CONCLUSIONS: Our results lead to a 2-fold conclusion: (1) The classification system of both thickening pattern and distribution of the lesion can be simplified by using distribution pattern only and (2) differentiation between symptomatic and asymptomatic atherosclerotic lesions was possible using intracranial vessel wall imaging.

Relation between subcortical grey matter atrophy and conversion from mild cognitive impairment to Alzheimer's disease.

OBJECTIVE: To investigate whether subcortical grey matter atrophy predicts progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD), and to compare subcortical volumes between AD, MCI and controls. To assess the correlation between subcortical grey matter volumes and severity of cognitive impairment. METHODS: We included 773 participants with three-dimensional T1-weighted MRI at 3 T, made up of 181 controls, who had subjective memory symptoms with normal cognition, 201 MCIs and 391 AD. During follow-up (2.0 ± 0.9 years), 35 MCIs converted to AD (progressive MCI) and 160 MCIs remained stable (stable MCI). We segmented volumes of six subcortical structures of the amygdala, thalamus, caudate nucleus, putamen, globus pallidus and nucleus accumbens, and of the hippocampus, using FMRIBs integrated registration and segmentation tool. RESULTS: Analysis of variances, adjusted for sex and age, showed that all structures, except the globus pallidus, were smaller in AD than in controls. In addition, the amygdala, thalamus, putamen, nucleus accumbens and hippocampus were smaller in MCIs than in controls. Across groups, all subcortical greymatter volumes, except the globus pallidus, showed a positive correlation with cognitive function, as measured by Mini Mental State Examination (MMSE) (0.16

Hyaluronan accumulation and arrested oligodendrocyte progenitor maturation in vanishing white matter disease.

Vanishing white matter disease is a genetic leukoencephalopathy caused by mutations in eukaryotic translation initiation factor 2B. Patients experience a slowly progressive neurological deterioration with episodes of rapid clinical worsening triggered by stress. The disease may occur at any age and leads to early death. Characteristic neuropathological findings include cystic degeneration of the white matter with feeble, if any, reactive gliosis, dysmorphic astrocytes and paucity of myelin despite an increase in oligodendrocytic density. These features have been linked to a maturation defect of astrocytes and oligodendrocytes. However, the nature of the link between glial immaturity and the observed neuropathological features is unclear. We hypothesized that the defects in maturation and function of astrocytes and oligodendrocytes are related. Brain tissue of seven patients with genetically proven vanishing white matter disease was investigated using immunohistochemistry, western blotting, quantitative polymerase chain reaction and size exclusion chromatography. The results were compared with those obtained from normal brain tissue of age-matched controls, from chronic demyelinated multiple sclerosis lesions and from other genetic and acquired white matter disorders. We found that the white matter of patients with vanishing white matter disease is enriched in CD44-expressing astrocyte precursor cells and accumulates the glycosaminoglycan hyaluronan. Hyaluronan is a major component of the extracellular matrix, and CD44 is a hyaluronan receptor. We found that a high molecular weight form of hyaluronan is overabundant, especially in the most severely affected areas. Comparison between the more severely affected frontal white matter and the relatively spared cerebellum confirms that high molecular weight hyaluronan accumulation is more pronounced in the frontal white matter than in the cerebellum. High molecular weight hyaluronan is known to inhibit astrocyte and oligodendrocyte precursor maturation and can explain the arrested glial progenitor maturation observed in vanishing white matter disease. In conclusion, high molecular weight species of hyaluronan accumulate in the white matter of patients with vanishing white matter disease, and by inhibiting glial maturation and proper function, they may be a major determinant of the white matter pathology and lack of repair.

Intracranial arterial wall imaging: Techniques, clinical applicability, and future perspectives.

PURPOSE: To review the current state of the art and future development of intracranial vessel wall imaging. METHODS: Recent literature review and expert opinion about intracranial arterial wall imaging. RESULTS: Intracranial large artery diseases represent an important cause of stroke and vascular cognitive impairment worldwide. Our traditional understanding of intracranial large artery diseases is based on the observation of luminal narrowing or occlusion with angiographic or ultrasound techniques. Recently, novel imaging techniques have made the intracranial artery wall accessible for noninvasive visualization. The main advantage of vessel-wall imaging as compared to conventional imaging techniques for visualization of intracranial arteries is the ability to detect vessel wall changes even before they get to cause any significant luminal stenosis. This diagnostic capacity is provoking a revolutionary change in the way we see the intracranial circulation. In this article, we will review the current state of magnetic resonance imaging and computed tomography-based intracranial arterial wall imaging, focusing on technical considerations and their clinical applicability. Moreover, we will provide the readers with our vision on the future development of vessel-wall imaging techniques. CONCLUSION: Intracranial arterial wall imaging methods are gaining increasing potential to impact the diagnosis and treatment of patients with cerebrovascular diseases.

Short-term mechanisms influencing volumetric brain dynamics.

With the use of magnetic resonance imaging (MRI) and brain analysis tools, it has become possible to measure brain volume changes up to around 0.5%. Besides long-term brain changes caused by atrophy in aging or neurodegenerative disease, short-term mechanisms that influence brain volume may exist. When we focus on short-term changes of the brain, changes may be either physiological or pathological. As such determining the cause of volumetric dynamics of the brain is essential. Additionally for an accurate interpretation of longitudinal brain volume measures by means of neurodegeneration, knowledge about the short-term changes is needed. Therefore, in this review, we discuss the possible mechanisms influencing brain volumes on a short-term basis and set-out a framework of MRI techniques to be used for volumetric changes as well as the used analysis tools. 3D T1-weighted images are the images of choice when it comes to MRI of brain volume. These images are excellent to determine brain volume and can be used together with an analysis tool to determine the degree of volume change. Mechanisms that decrease global brain volume are: fluid restriction, evening MRI measurements, corticosteroids, antipsychotics and short-term effects of pathological processes like Alzheimer's disease, hypertension and Diabetes mellitus type II. Mechanisms increasing the brain volume include fluid intake, morning MRI measurements, surgical revascularization and probably medications like anti-inflammatory drugs and anti-hypertensive medication. Exercise was found to have no effect on brain volume on a short-term basis, which may imply that dehydration caused by exercise differs from dehydration by fluid restriction. In the upcoming years, attention should be directed towards studies investigating physiological short-term changes within the light of long-term pathological changes. Ultimately this may lead to a better understanding of the physiological short-term effects of pathological processes and may aid in early detection of these diseases.

Relations between location and type of intracranial atherosclerosis and parenchymal damage.

The aim of this study was to assess the relation between location and type of intracranial atherosclerosis (ICAS) and cortical microinfarcts (CMIs) and macroinfarcts in 18 patients presenting with ischemic stroke (n = 12) or transient ischemic attack (TIA) (n = 6) using 7 tesla MR imaging. The protocol included: 3D T2-weighted FLAIR and 3D T1-weighted Magnetization-Preparation Inversion Recovery Turbo Spin Echo sequence. ICAS lesions and infarcts were scored by two raters. The relation between ICAS lesions, calculated ratios of ICAS lesion characteristics, location, and infarcts were examined using linear regression analyses. A total number of 75 ICAS lesions (all patients), 101 CMIs (78% of patients), and 31 macroinfarcts (67% of patients) were found. Seventy-six and sixty-five percent of the CMIs and macroinfarcts, respectively, were found in the same vascular territory as the ICAS lesions (p = 0.977, p = 0.167, respectively). A positive correlation existed between the number of macroinfarcts and CMIs (p < 0.05). In patients with macroinfarcts, we found more concentric (p < 0.01) and diffuse (p < 0.05) type of ICAS lesions. A high prevalence of brain tissue lesions, both macroinfarcts and CMIs, were found in patients with ICAS. Macroinfarcts were found to be related to specific ICAS lesion types. The type of ICAS lesion seems to be promising as a marker for ICAS patients at higher risk of future infarcts.

Qualitative Evaluation of a High-Resolution 3D Multi-Sequence Intracranial Vessel Wall Protocol at 3 Tesla MRI.

BACKGROUND AND PURPOSE: Intracranial vessel wall imaging using MRI has great potential as a clinical method for assessing intracranial atherosclerosis. The purpose of the current study was to compare three 3T MRI vessel wall sequences with different contrast weightings (T1w, PD, T2w) and dedicated sagittal orientation perpendicular to the middle cerebral artery, to the reconstructed sagittal image from a transverse 3D T1w volumetric isotropically reconstructed turbo spin-echo acquisition (VIRTA), and provide a clinical recommendation. MATERIALS AND METHODS: The above-mentioned sequences were acquired in 10 consecutive Chinese ischemic stroke or TIA patients (age: 68 years, sex: 4 females) with angiographic-confirmed MCA stenosis at 3T. Institutional review board approval was obtained. Two raters qualitatively scored all images on overall image quality, presence of artifacts, and visibility of plaques. Data were compared using Repeated measures ANOVA and Sidak's adjusted post hoc tests. RESULTS: All sequences except the T2w sequence were able to depict the walls of the large vessels of the Circle of Willis (p<0.05). T1w sagittal oblique VIRTA showed significantly more artifacts (p<0.01). Peripherally located plaques were sometimes missed on the sagittal sequences, but could be appreciated on the transverse T1w VIRTA. CONCLUSION: With the 3T multi-sequence vessel wall protocol we were able to assess the intracranial plaque with two different image contrast weightings. The sequence of preference to include in a clinical protocol would be the transverse 3D T1w VIRTA based on absence of artifacts, larger coverage including the whole Circle of Willis, and excellent lesion depiction.

More atrophy of deep gray matter structures in frontotemporal dementia compared to Alzheimer's disease.

BACKGROUND: The involvement of frontostriatal circuits in frontotemporal dementia (FTD) suggests that deep gray matter structures (DGM) may be affected in this disease. OBJECTIVE: We investigated whether volumes of DGM structures differed between patients with behavioral variant FTD (bvFTD), Alzheimer's disease (AD), and subjective complaints (SC) and explored relationships between DGM structures, cognition, and neuropsychiatric functioning. METHODS: For this cross-sectional study, we included 24 patients with FTD and matched them based on age, gender, and education at a ratio of 1:3 to 72 AD patients and 72 patients with SC who served as controls. Volumes of hippocampus, amygdala, thalamus, caudate nucleus, putamen, globus pallidus, and nucleus accumbens were estimated by automated segmentation of 3D T1-weighted MRI. MANOVA with Bonferroni adjusted post-hoc tests was used to compare volumes between groups. Relationships between volumes, cognition, and neuropsychiatric functioning were examined using multivariate linear regression and Spearman correlations. RESULTS: Nucleus accumbens and caudate nucleus discriminated all groups, with most severe atrophy in FTD. Globus pallidus volumes were smallest in FTD and discriminated FTD from AD and SC. Hippocampus, amygdala, thalamus, and putamen were smaller in both dementia groups compared to SC. Associations between amygdala and memory were found to be different in AD and FTD. Globus pallidus and nucleus accumbens were related to attention and executive functioning in FTD. CONCLUSION: Nucleus accumbens, caudate nucleus, and globus pallidus were more severely affected in FTD than in AD and SC. The associations between cognition and DGM structures varied between the diagnostic groups. The observed difference in volume of these DGM structures supports the idea that next to frontal cortical atrophy, DGM structures, as parts of the frontal circuits, are damaged in FTD rather than in AD.

High-resolution postcontrast time-of-flight MR angiography of intracranial perforators at 7.0 Tesla.

BACKGROUND AND PURPOSE: Different studies already demonstrated the benefits of 7T for precontrast TOF-MRA in the visualization of intracranial small vessels. The aim of this study was to assess the performance of high-resolution 7T TOF-MRA after the administration of a gadolinium-based contrast agent in visualizing intracranial perforating arteries. MATERIALS AND METHODS: Ten consecutive patients (7 male; mean age, 50.4 ± 9.9 years) who received TOF-MRA at 7T after contrast administration were retrospectively included in this study. Intracranial perforating arteries, branching from the parent arteries of the circle of Willis, were identified on all TOF-MRA images. Provided a TOF-MRA before contrast administration was present, a direct comparison between pre- and postcontrast TOF-MRA was made. RESULTS: It was possible to visualize intracranial perforating arteries branching off from the entire circle of Willis, and their proximal branches. The posterior cerebral artery (P1 and proximal segment of P2) appeared to have the largest number of visible perforating branches (mean of 5.1 in each patient, with a range of 2-7). The basilar artery and middle cerebral artery (M1 and proximal segment M2) followed with a mean number of 5.0 and 3.5 visible perforating branches (range of 1-9 and 1-8, respectively). Venous contamination in the postcontrast scans sometimes made it difficult to discern the arterial or venous nature of a vessel. CONCLUSION: High-resolution postcontrast TOF-MRA at 7T was able to visualize multiple intracranial perforators branching off from various parts of the circle of Willis and proximal intracranial arteries. Although confirmation in a larger study is needed, the administration of a contrast agent for high-resolution TOF-MRA at 7T seems to enable a better visualization of the distal segment of certain intracranial perforators.

Patterns of intracranial vessel wall changes in relation to ischemic infarcts.

OBJECTIVE: In this retrospective case series study, we used 7.0 tesla MRI to describe patterns of intracranial vessel wall abnormalities in relation to ischemic infarcts in 9 patients with different intracranial vessel wall pathologies. METHODS: A patient-specific clinical imaging protocol was obtained after regular clinical workup, including a fluid-attenuated inversion recovery and an intracranial vessel wall sequence before and after contrast administration using 7.0 tesla MRI. An attempt was made to describe patterns by grouping the patients by intracranial vessel wall abnormalities (eccentric or concentric; enhancing or nonenhancing), then on the presence of macroinfarcts and cortical microinfarcts (CMIs), and lastly on type of macroinfarct (lacunar, small macroinfarct, or large macroinfarct). RESULTS: Intracranial vessel wall abnormalities were identified in all patients, totaling 45 lesions, 12 of which enhanced after contrast administration. CMIs were found in 5 patients. Two patients had eccentric, enhancing wall thickening but differed based on presence or absence of CMIs. Four patients also had eccentric but nonenhancing wall thickening, 2 of whom showed CMIs. The 2 patients lacking CMIs could be subdivided based on the type of macroinfarct. Concentric, enhanced wall thickening was observed in 2 patients with CMIs who differed regarding macroinfarct types. One patient with previous vasculitis showed concentric, nonenhancing wall thickening. CONCLUSION: Our results suggest that the combination of intracranial vessel wall abnormalities and infarct type is related to different stroke etiologies.