Abstract
PurposeCerebral amyloid angiopathy (CAA) is a cerebral small vessel disease associated with perivascular β-amyloid deposition. CAA is also associated with strokes due to lobar intracerebral haemorrhage (ICH). 18F-flutemetamol amyloid ligand PET may improve the early detection of CAA. We performed pharmacokinetic modelling using both full (0–30, 90–120 min) and reduced (30 min) 18F-flutemetamol PET-MR acquisitions, to investigate regional cerebral perfusion and amyloid deposition in ICH patients. MethodsDynamic18F-flutemetamol PET-MR was performed in a pilot cohort of sixteen ICH participants; eight lobar ICH cases with probable CAA and eight deep ICH patients. A model-based input function (mIF) method was developed for compartmental modelling. mIF 1-tissue (1-TC) and 2-tissue (2-TC) compartmental modelling, reference tissue models and standardized uptake value ratios were assessed in the setting of probable CAA detection. ResultsThe mIF 1-TC model detected perfusion deficits and 18F-flutemetamol uptake in cases with probable CAA versus deep ICH patients, in both full and reduced PET acquisition time (all P < 0.05). In the reduced PET acquisition, mIF 1-TC modelling reached the highest sensitivity and specificity in detecting perfusion deficits (0.87, 0.77) and 18F-flutemetamol uptake (0.83, 0.71) in cases with probable CAA. Overall, 52 and 48 out of the 64 brain areas with 18F-flutemetamol-determined amyloid deposition showed reduced perfusion for 1-TC and 2-TC models, respectively. ConclusionPharmacokinetic (1-TC) modelling using a 30 min PET-MR time frame detected impaired haemodynamics and increased amyloid load in probable CAA. Perfusion deficits and amyloid burden co-existed within cases with CAA, demonstrating a distinct imaging pattern which may have merit in elucidating the pathophysiological process of CAA.
Highlights
Cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease characterised by the deposition of β-amyloid protein in cortical and leptomeningeal arterial walls, which is common in healthy elderly and in people with dementia (Neuropathology Group, 2001)
Dynamic18F-flutemetamol positron emission tomography (PET)-MR was performed in a pilot cohort of sixteen intracerebral haemorrhage (ICH) participants; eight lobar ICH cases with probable CAA and eight deep ICH patients
Cognition assessments were performed for all participants prior to PET-MR imaging, to identify cases with probable CAA and patients with deep ICH with similar history of cognitive impairment, given that
Summary
Cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease characterised by the deposition of β-amyloid protein in cortical and leptomeningeal arterial walls, which is common in healthy elderly and in people with dementia (Neuropathology Group, 2001). Recent studies showed that amyloid-positron emission tomography (PET) can differentiate probable CAA from healthy elderly and patients with deep ICH, which is generally due to hypertension (Charidimou et al, 2017, 2018). Another study did not show a difference in amyloid-PET uptake between patients with probable CAA and healthy controls (Baron et al, 2014). A recent study assessed a surrogate measure of cerebral perfusion using standardised uptake value ratios (SUVR) analysis from an early phase 11C-Pittsburgh compound B (11C-PiB) time frame, reporting reduced SUVR in participants with probable CAA against age-matched controls (Farid et al, 2015). Whether any increases in the amyloid-PET uptake may be associated with cerebral perfusion differences in a distinct pattern in probable CAA, is currently unknown
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