17 Nov 20. Featured Paper

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

Link to paper on NeuroImage.

Authors

Giorgos Papanastasiou, Mark A. Rodrigues, Chengjia Wang, Kerstin Heurling, Christophe Lucatelli, Rustam Al-Shahi Salman, Joanna M. Wardlaw, Edwin J.R. van Beek, Gerard Thompson

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) & reduced (30 min) ¹⁸F-flutemetamol PET-MR acquisitions, to investigate regional cerebral perfusion & 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 & eight deep ICH patients.

A model-based input function (mIF) method was developed for compartmental modelling.

mIF 1-tissue (1-TC) & 2-tissue (2-TC) compartmental modelling, reference tissue models & standardized uptake value ratios were assessed in the setting of probable CAA detection.

Results: The mIF 1-TC model detected perfusion deficits & ¹⁸F-flutemetamol uptake in cases with probable CAA versus deep ICH patients, in both full & reduced PET acquisition time (all P < 0.05).

In the reduced PET acquisition, mIF 1-TC modelling reached the highest sensitivity & specificity in detecting perfusion deficits (0.87, 0.77) & ¹⁸F-flutemetamol uptake (0.83, 0.71) in cases with probable CAA.

Overall, 52 & 48 out of the 64 brain areas with ¹⁸F-flutemetamol-determined amyloid deposition showed reduced perfusion for 1-TC & 2-TC models, respectively.

Conclusion: Pharmacokinetic (1-TC) modelling using a 30 min PET-MR time frame detected impaired haemodynamics & increased amyloid load in probable CAA.

Perfusion deficits & 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

• 18F-flutemetamol uptake
• Cerebral amyloid angiopathy
• Magnetic resonance imaging
• Perfusion
• Pharmacokinetic modelling
• Positron emission tomography