Harmonizing brain magnetic resonance imaging methods for vascular contributions to neurodegeneration

Introduction Many consequences of cerebrovascular disease are identifiable by magnetic resonance imaging (MRI), but variation in methods limits multicenter studies and pooling of data. The European Union Joint Program on Neurodegenerative Diseases (EU JPND) funded the HARmoNizing Brain Imaging MEthodS for VaScular Contributions to Neurodegeneration (HARNESS) initiative, with a focus on cerebral small vessel disease. Methods Surveys, teleconferences, and an in-person workshop were used to identify gaps in knowledge and to develop tools for harmonizing imaging and analysis. Results A framework for neuroimaging biomarker development was developed based on validating repeatability and reproducibility, biological principles, and feasibility of implementation. The status of current MRI biomarkers was reviewed. A website was created at www.harness-neuroimaging.org with acquisition protocols, a software database, rating scales and case report forms, and a deidentified MRI repository. Conclusions The HARNESS initiative provides resources to reduce variability in measurement in MRI studies of cerebral small vessel disease

Cortical phase changes in Alzheimer's disease at 7T MRI:a novel imaging marker

AbstractBackgroundPostmortem studies have indicated the potential of high-field magnetic resonance imaging (MRI) to visualize amyloid depositions in the cerebral cortex. The aim of this study is to test this hypothesis in patients with Alzheimer's disease (AD).MethodsT2*-weighted MRI was performed in 16 AD patients and 15 control subjects. All magnetic resonance images were scored qualitatively by visual assessment, and quantitatively by measuring phase shifts in the cortical gray matter and hippocampus. Statistical analysis was performed to assess differences between groups.ResultsPatients with AD demonstrated an increased phase shift in the cortex in the temporoparietal, frontal, and parietal regions (P < .005), and this was associated with individual Mini-Mental State Examination scores (r = −0.54, P < .05).ConclusionIncreased cortical phase shift in AD patients demonstrated on 7-tesla T2*-weighted MRI is a potential new biomarker for AD, which may reflect amyloid pathology in the early stages

Early Magnetic Resonance Imaging and Cognitive Markers of Hereditary Cerebral Amyloid Angiopathy

BACKGROUND AND PURPOSE: Early markers for cerebral amyloid angiopathy (CAA) are largely unknown. We aimed to identify which MRI (performed at 7 tesla and 3 tesla) and cognitive markers are an early sign in (pre-)symptomatic subjects with Hereditary Cerebral Hemorrhage With Amyloidosis-Dutch type (HCHWA-D). METHODS: Twenty-seven DNA-proven Dutch type mutation carriers (15 symptomatic and 12 pre-symptomatic) (mean age of 45.9) and 33 controls (mean age of 45.6) were included. 7T and 3T MRI was performed, CAA and small vessel disease type MRI markers were estimated, and cognitive performance was assessed. Univariate general linear modeling analysis was used to assess the association between MRI markers and cognitive performance on the one hand, and on the other mutation status, adjusted for age, sex and education. RESULTS: In symptomatic patients, all established CAA MRI markers (microbleeds, intracerebral hemorrhages, subarachnoid hemorrhages, superficial siderosis, microinfarcts, volume of white matter hyperintensities (WMHs) and dilated perivascular spaces in centrum semiovale) were increased compared to controls (p<0.05). In pre-symptomatic subjects, the prevalence of microinfarcts and median volume of WMHs were increased in comparison to controls (p<0.05). Symptomatic patients performed worse on all cognitive domains, whereas pre-symptomatic subjects did not show differences in comparison with controls (p<0.05). CONCLUSIONS: WMHs and microinfarcts are more prevalent among pre-symptomatic subjects and precede cognitive and neuropsychiatric symptoms and intracerebral hemorrhages

Cortical phase changes measured using 7-T MRI in subjects with subjective cognitive impairment, and their association with cognitive function

Studies have suggested that, in subjects with subjective cognitive impairment (SCI), Alzheimer's disease (AD)-like changes may occur in the brain. Recently, an in vivo study has indicated the potential of ultra-high-field MRI to visualize amyloid-beta (Aβ)-associated changes in the cortex in patients with AD, manifested by a phase shift on T2*-weighted MRI scans. The main aim of this study was to investigate whether cortical phase shifts on T2*-weighted images at 7 T in subjects with SCI can be detected, possibly implicating the deposition of Aβ plaques and associated iron. Cognitive tests and T2*-weighted scans using a 7-T MRI system were performed in 28 patients with AD, 18 subjects with SCI and 27 healthy controls (HCs). Cortical phase shifts were measured. Univariate general linear modeling and linear regression analysis were used to assess the association between diagnosis and cortical phase shift, and between cortical phase shift and the different neuropsychological tests, adjusted for age and gender. The phase shift (mean, 1.19; range, 1.00–1.35) of the entire cortex in AD was higher than in both SCI (mean, 0.85; range, 0.73–0.99; p <0.001) and HC (mean, 0.94; range, 0.79–1.10; p <0.001). No AD-like changes, e.g. increased cortical phase shifts, were found in subjects with SCI compared with HCs. In SCI, a significant association was found between memory function (Wechsler Memory Scale, WMS) and cortical phase shift (β = –0.544, p = 0.007). The major finding of this study is that, in subjects with SCI, an increased cortical phase shift measured at high field is associated with a poorer memory performance, although, as a group, subjects with SCI do not show an increased phase shift compared with HCs. This increased cortical phase shift related to memory performance may contribute to the understanding of SCI as it is still unclear whether SCI is a sign of pre-clinical AD. </p

Amyloid imaging of dutch-type hereditary cerebral amyloid angiopathy carriers

Objective: To determine whether amyloid imaging with the positron emission tomography (PET) agent Pittsburgh compound B (PiB) can detect vascular β-amyloid (Aβ) in the essentially pure form of cerebral amyloid angiopathy associated with the Dutch-type hereditary cerebral amyloid angiopathy (D-CAA) mutation. Methods: PiB retention in a cortical composite of frontal, lateral, and retrosplenial regions (FLR) was measured by PiB-PET in 19 D-CAA mutation carriers (M+; 13 without neurologic symptoms, 6 with prior lobar intracerebral hemorrhage) and 17 mutation noncarriers (M−). Progression of PiB retention was analyzed in a subset of 18 serially imaged individuals (10 asymptomatic M+, 8 M−). We also analyzed associations between PiB retention and cerebrospinal fluid (CSF) Aβ concentrations in 17 M+ and 11 M− participants who underwent lumbar puncture and compared the findings to PiB-PET and CSF Aβ in 37 autosomal dominant Alzheimer disease (ADAD) mutation carriers. Results: D-CAA M+ showed greater age-dependent FLR PiB retention (p < 0.001) than M−, and serially imaged asymptomatic M+ demonstrated greater longitudinal increases (p = 0.004). Among M+, greater FLR PiB retention associated with reduced CSF concentrations of Aβ40 (r = −0.55, p = 0.021) but not Aβ42 (r = 0.01, p = 0.991). Despite comparably low CSF Aβ40 and Aβ42, PiB retention was substantially less in D-CAA than ADAD (p < 0.001). Interpretation: Increased PiB retention in D-CAA and correlation with reduced CSF Aβ40 suggest this compound labels vascular amyloid, although to a lesser degree than amyloid deposits in ADAD. Progression in PiB signal over time suggests amyloid PET as a potential biomarker in trials of candidate agents for this untreatable cause of hemorrhagic stroke. ANN NEUROL 2019