Overall, the diagnostic accuracy of fusion imaging is very high with a sensitivity, specificity, positive predictive value and negative predictive value of 76–96 %, 92–100 %, 77–100 %, and 84–99 %, respectively. The incremental value of fusion cardiac imaging lies in the accurate spatial co-localization of myocardial perfusion defects assessed by SPECT or PET and subtending coronary arteries (Fig. 10.1). However, there are some limitations which apply to these early clinical studies such as the difference in hybrid systems, the variable reference standard (either invasive coronary angiography alone or in combination with SPECT or FFR), the single-center design, as well as the small sample size.

In the first clinical study documenting the feasibility and clinical robustness of noninvasive fusion imaging after fusion of ¹³N-NH₃ PET with four-slice CCTA in 25 patients with CAD, the hybrid PET/CCTA images allowed identifying flow-limiting coronary lesions requiring a revascularization procedure (as defined by ICA and PET) with a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 90 %, 98 %, 82 %, and 99 %, respectively (Table 10.1) [13]. Similar results were documented in a study by Rispler and coworkers, who were able to show an increase in specificity (from 63 to 95 %) and PPV (from 31 to 77 %) with SPECT/CCTA compared to CCTA alone [14]. Another study by Sato and coworkers demonstrated a particular improvement in specificity and PPV by adding SPECT information in non-evaluable arteries on CCTA (from 80 to 92 % and from 69 to 85 %, respectively) [15]. Kajender and coworkers demonstrated in a study of 107 patients who underwent ¹⁵O-H₂O PET/64-slice CCTA that hybrid images increased the PPV significantly from 76 to 96 % compared to CCTA alone [16]. Moreover, in that study, the hemodynamic significance of ICA stenoses was confirmed by fractional flow reserve (FFR) in 18 of 40 patients providing a more comprehensive reference standard. Similarly, Schaap and coworkers showed an improvement of specificity from 62 and 79 % when using CCTA alone and SPECT alone, respectively, to a specificity of 95 % in a combined approach [17]. In a study using ¹⁵O-H₂O PET/64-slice CCTA on 120 patients with an intermediate likelihood for CAD, the diagnostic accuracy of quantitative ¹⁵O-H₂O PET/64-slice CCTA was superior to either ¹⁵O-H₂O PET or CCTA alone [18]. Finally, in a study by Thomassen and coworkers, the quantitative hybrid PET/CCTA imaging yielded an excellent sensitivity, specificity, positive predictive value, and negative predictive value of 91, 100, 100, and 92 % pointing out the benefit especially in increasing the positive predictive value, which was 71 % for CCTA alone and 87 % for SPECT alone [19].

These studies have documented the incremental diagnostic value of fusion imaging compared to one imaging modality alone. Furthermore, so far, there have been three studies which have specifically evaluated the additional value of fusion cardiac imaging over the side-by-side analysis of CCTA and myocardial perfusion images. In the first study, the number of lesions with equivocal hemodynamic relevance could be significantly reduced using SPECT/CCTA fusion compared with the side-by-side analysis in 38 patients with perfusion defects on SPECT [20]. In another study conducted by Santana and coworkers, a higher diagnostic performance for fused SPECT/CCTA imaging compared to the side-by-side analysis of SPECT and CCTA (p = 0.007) for the diagnosis of obstructive CAD on ICA could be demonstrated [21]. This was mainly true in patients with multivessel disease. Finally, Slomka and coworkers demonstrated an improved diagnostic value of cardiac fusion imaging mainly in the territories of the circumflex artery and the right coronary artery in a study implementing motion-frozen SPECT data and CCTA-guided SPECT contour and territory adjustments [22].

In summary, cardiac fusion imaging combining the anatomic information from CCTA with the functional information from myocardial perfusion imaging offers an incremental diagnostic value in the identification of hemodynamically significant coronary artery stenoses and thereby in guiding clinicians on the appropriate treatment (medical versus revascularization). The added value has not only been proven when comparing to one imaging modality alone, but also when comparing to the side-by-side analysis.