Clinical Validation of Computed Tomography derived Myocardial Perfusion
Imaging : a Hybrid PET/CT Study (ContRaSt)

The prevalence of Chronic Coronary Syndromes (CCS) ranges from 5-7% in women
aged 45-64 years to 10-12% in women aged 65-84 and from 4-7% in men aged 45-64
years to 12-14% in men aged 65-843. Although acute coronary symptoms are a
clear indication for intervention, stable CCS requires thorough diagnosis. In
fact, the COURAGE trial demonstrated that in CCS coronary revascularization as
an initial management strategy, without functional assessment of coronary
stenosis, offers no benefits over optimal pharmacologic therapy alone in
reducing mortality4. According to the current guidelines, the presence of
significant myocardial ischemia, during stress, is the most important
indication to perform revascularization. There is a variety of non-invasive and
invasive methods to assess myocardial ischemia.
Novel hybrid imaging modalities using SPECT/CT, PET/CT, MRI and CT (including
coronary computed tomography angiography-CCTA and MPI-CT) facilitate
non-invasive assessment of ischemia. Hybrid imaging is a technique combining
both functional and anatomical assessment of coronary arteries and thus holds
much promise for future clinical applications. So far, PET, MRI and SPECT have
become established tools to detect myocardial perfusion defects5,6. Recently
anatomical assessment with CT also has shown its diagnostic value in CCS. In
patients with suspected CCS, studies using 64-slice CT have shown sensitivities
of 98-99% and specificities of 82-89% as well as negative predictive values of
99-100% for the identification of patients with at least one coronary artery
stenosis found on ICA7,8. MPI-CT can also be used as a quicker, cheaper tool
compared to PET and SPECT, however MPI-CT is still in research phase and needs
clinical validation. The benefit of MPI-CT is combining both morphology
(coronary stenosis) and functionality (myocardial perfusion) in a single CT
setting, because of relatively low cost of CT and wider availability as
compared with SPECT/CT and PET/CT.
The first adenosine stress MPI-CT was performed in 2005 by Kurata9. Since then,
several trials have established the significance of myocardial MPI-CT compared
to reference standards as SPECT, ICA (with or without FFR) and stress perfusion
MRI10-16.
15O-water PET-CT is a well-established reference modality to assess myocardial
perfusion. The following study will employ the latest state-of-the-art digital
PET-CT scanner to validate MPI-CT. The Biograph Vision PET-CT at the institute
will be used to perform rest 15O-water PET-CT and Siemens SOMATOM Force will be
used to perform rest MPI-CT. As a next step we plan to validate rest MPI-CT
against gold standard 15O-water PET-CT.
As a first step we propose to compare rest MPI-CT results with rest 15O-water
PET-CT. The hypothesis is that MBF based on rest MPI-CT calculated from dynamic
CCTA is as accurate as gold standard rest 15O-water PET-CT.
If rest MPI-CT will be as accurate as rest 15O-water PET-CT to detect ischemia,
the aim is to use this data in a next research proposal where we will compare
the stress phase of MPI CT and 15O-water PET-CT. Finally, the application of
complete MPI-CT consisting of stress and rest phase, may improve patient*s
safety during the CCS diagnosis and significantly decrease the costs of
diagnosis.

Primary objective:

1. Is the MBF based on rest MPI-CT as accurate as gold standard rest 15O-water
PET-CT?

Proof-of-conccept

The main risk of the study is the exposition to a higher radiation dose
(1mSv of 15O-water-PET vs. 6.3 mSv of MPI-CT). The benefit of MPI-CT is
combining both morphology (coronary stenosis) and functionality (myocardial
perfusion) in a single CT setting, because of relatively low cost, wider
availability and faster acquisition time as compared with SPECT/CT and PET /CT
for the detection of functional ischemia.