Pharmacokinetic modelling for the simultaneous assessment of perfusion and 18F-flutemetamol uptake in cerebral amyloid angiopathy using a reduced PET-MR acquisition time: Proof of concept

Abstract

Purpose: Cerebral 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.

Methods: Dynamic¹⁸F-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.

Results: The 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.

Conclusion: Pharmacokinetic (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.

Keywords: (18)F-flutemetamol uptake; Cerebral amyloid angiopathy; Magnetic resonance imaging; Perfusion; Pharmacokinetic modelling; Positron emission tomography.