Background
The quantifications of myocardial blood flow (MBF) and coronary flow reserve (CFR) are useful approaches for evaluating the functional severity of coronary artery disease (CAD) [
1,
2].
15O-water positron emission tomography (PET) is considered the gold standard method for the quantification of MBF, because it is the only method using a freely diffusible tracer with a 100% extraction fraction [
3,
4]. However, MBF quantification using PET/computed tomography (CT) with three-dimensional (3D) data acquisition presents technical challenges due to increased scattering. Accordingly, PET/CT MBF measurements using
15O-water should be validated by comparing CAD patients and an age-matched healthy control group. The aim of this study was to evaluate the diagnostic potential of MBF and CFR measurements using
15O-water PET/CT with 3D data acquisition.
Discussion
We assessed the feasibility of MBF and CFR estimated by 15O-water PET/CT with the 3D acquisition mode. A strong inter-observer correlation of MBF and CFR in all subjects was found, and there was little variability of regional MBF and CFR obtained from the healthy control group. The regional MBF and CFR showed a highly homogenous distribution in the healthy volunteers, suggesting that the registration of CT and the dosage of 15O-water were appropriate. The CFR in the patients was significantly lower compared to the age-matched control group.
PET is the most reliable method to quantify MBF and CFR, and these quantifications can be applied to the functional severity of coronary stenosis. They can also provide prognostic information about patients with CAD and the coronary risk factors for cardiac events [
1,
11]. Supportive evidence has been reported mostly by using a stand-alone PET scanner with two-dimensional (2D) acquisition to quantify MBF and CFR [
9,
12]. Roelants et al. directly compared the MBFs between 2D and 3D acquisition modes in dogs with
15O-water and
13N-ammonia using a stand-alone PET scanner. They concluded that quantification of MBF with 3D acquisition provides results similar to those obtained with the 2D technique, despite a lower activity being injected [
13]. In cases of combined PET/CT scans, a misregistration of the PET and CT due to respiratory or cardiac motion and gross physical movement of the patient causes a reduction of the MBF [
14,
15].
15O-water is known as an ideal PET tracer for the quantification of MBF because of the high extraction fraction. However,
15O-water has a limited image quality because it is an inert, freely diffusible tracer [
4]. Several automatic and manual methods have been proposed for corrections of the misalignment. Automatic methods were reported; the methods used mostly
13N-NH
3 with high uptake in the myocardium [
16‐
18]. Rajaram et al. reported that the optimal registration of PET and CT was a useful method to avoid this artifact in
82Rb PET/CT [
6]. As our present findings showed high homogeneity of the regional MBF in the control group, our manual registration method is suitable for
15O-water PET/CT.
Tsukamoto et al. reported the values of MBF and CFR obtained from 2D data acquisition using
15O-water PET in patients with backgrounds similar to the present study’s patients [
19]. In their control group, the estimated MBF at rest, MBF at stress, and CFR were 0.91 ± 0.16 ml/min/g, 3.66 ± 0.81 ml/min/g, and 4.06 ± 0.81, respectively. In the stenotic regions of their CAD group, the estimated MBF at rest, MBF at stress, and CFR were 0.96 ± 0.22 (ml/min/g), 2.19 ± 0.96 (ml/min/g), and 2.35 ± 0.89, respectively. Those data are equivalent to our results from 3D data acquisition.
The quantification of MBF and CFR using PET provides additional diagnostic value for the detection of CAD and can reliably exclude multivessel CAD with very high relative predictive values [
20‐
22]. Our present findings showed that the CFR in stenotic region tended to be lower compared to the non-stenotic region, which is similar to previous reports. The Agatston score and myocardial perfusion imaging are independent predictors. A hybrid PET/CT scanner allows both the integrated assessment of the physiological capacity of blood flow with the CFR and the quantification of the atherosclerotic burden with the Agatston score, which may improve the risk assessment of CAD [
23,
24].
A CFR value gives the information of microvascular dysfunction in addition to flow-limiting coronary artery stenosis [
1,
11]. Several coronary risk factors such as obesity, diabetes, dyslipidemia, hypertension, renal dysfunction, and smoking are known to adversely affect microvascular function [
25‐
27]. In the present study, the CFR values of the age-matched healthy volunteers were 1.7 times higher than those of the patients even without significant stenosis, which is thought to be related to the high frequencies of hypertension, diabetes mellitus, and smoking history in CAD patients.
This study has some methodological limitations. The sample size was relatively small. However, smaller sample sizes used in previous physiological studies were found to have sufficient power to confirm new methods. The healthy volunteers were not examined via invasive CAG. We also cannot compare 2D and 3D acquisition data because the current PET/CT scanner can obtain data only via 3D acquisition.
Acknowledgements
We thank Shigeo Oomagari, MSc, for his technical expertise, and Eriko Suzuki for her administrative support of this study. This study was supported in part by a grant from the Japan Society for the Promotion of Science (JSPS) KAKENHI (#16 K10264) and bythe Takeda Science Foundation (M.N.). Only non-Philips employees had control of the data and information that might present a conflict of interest for the authors who are Philips employees.