Simon’s research interests center around biomedical imaging. His major contributions have been in developing systems for positron emission tomography, for example in designing and building the first microPET scanner for small-animal imaging and as co-leader of the EXPLORER consortium which developed the world’s first total-body PET scanner.

He also has contributed to detector technology innovations for PET, conducted early biomedical studies using Cerenkov luminescence, and developed the first proof-of-concept hybrid PET/MRI (magnetic resonance imaging) systems. 

At KCL, Simon's primary role is to provide strategic leadership in the area of total-body PET imaging, as well as to support early career researchers through mentoring activities.