Hybrid cardiac imaging in coronary artery disease

Dr Albert Flotats
Associate Professor of Nuclear Medicine, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain.

Dr Birger Hesse
Department of Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen, Denmark

Current multidetector computed tomography (MDCT) is an attractive non-invasive alternative to invasive coronary angiography (ICA), as it provides an angiographic visualisation of the coronary arteries with reasonably high temporal and spatial resolution.1  

On the other hand, myocardial perfusion imaging (MPI) with single photon emission computed tomography (SPECT) or positron emission tomography (PET) provides an assessment of the haemodynamic relevance of coronary artery disease (CAD) and predicts short- and long-term prognosis.2,3,4

Recent development of software and hardware has made possible the integration of these imaging modalities in the so-called hybrid imaging.5,6 There is increasing evidence of improved diagnostic accuracy for the non-invasive assessment of CAD with the combined use of cardiac-computed tomographic angiography (CCTA) and MPI.7-10

However, there is still debate about which patients should undergo such combined examination in relation to clinical effectiveness, costs, and radiation exposure, and if software-based fusion of images obtained separately would be a useful alternative.11

Hybrid imaging
Although the use of attenuation correction (AC) and the detection of the coronary artery calcium (CAC) with the integration of CT have improved the diagnostic accuracy and the interpretive confidence of SPECT MPI,12-15 the genuine basis of hybrid imaging – i.e. SPECT or PET combined with CT – is to provide an accurate spatial alignment between the anatomic and physiologic datasets into one fused image that provides information beyond that achievable with either stand-alone or side-by-side interpretation of the data sets, and beyond the information derived from AC and the measurement of calcified atherosclerotic plaque burden.

Hybrid cardiac SPECT/CT7 or PET/CT imaging16 performed in one session has been proposed for dual system scanners equipped with MDCT. In hybrid imaging, MPI and CT data sets both contribute to the image information, reducing the number of equivocal results17 and providing more quickly diagnostics, an advantage for the patients and the treating institutions as well.

Hybrid scanners are not used routinely in cardiac imaging because of the difficulty in predicting a priori which patients would benefit from hybrid scanning. In addition, it has been suggested that only 15-30% of patients will benefit from hybrid cardiac imaging and that these patients cannot be identified on beforehand.18 Therefore, a sequential diagnostic approach is often applied in clinical practice, with additional scans (CCTA or MPI) performed only if the results of the initial modality are equivocal. However, when CCTA is performed first, about 50% of the patients will need perfusion imaging.19,20

Hybrid MPI and CCTA with reliable image co-registration and fusion of three-dimensional information of myocardial regions onto their subtending coronary arteries can accurately allocate the culprit lesion in multivessel CAD, which is particularly important because the so-called standard distribution of myocardial perfusion territories does not match with the genuine coronary anatomy in more than half of the cases.21,22

Combining anatomical with perfusion data also helps to identify and correctly register possible subtle irregularities in myocardial perfusion. Furthermore, the reduced sensitivity of CCTA in distal coronary segments and side branches can be offset by the MPI information. On the other hand, CCTA improves the detection of multivessel CAD, which is one of the main pitfalls of semiquantitative MPI.

Finally, the assessment of regional myocardial perfusion and viability, together with the coronary artery tree, eliminates uncertainties in the relationship of perfusion defects, scar regions and diseased coronary arteries in watershed regions. This may be particularly helpful in patients with multiple perfusion abnormalities and multivessel CAD, including previous revascularisation procedures.
More accurate

CCTA when used in combination with MPI not only provides complementary information about the presence, extent, and composition of atherosclerosis, but, importantly, also results in improved risk stratification compared with the use of MPI alone.23

Different studies have underscored the incremental diagnostic accuracy of co-registration and fusion of MPI and CCTA data acquired on a stand-alone basis over side-by-side interpretation.8,9,24 Stand-alone CCTA tends to overestimate coronary stenoses, and a normal semiquantitative MPI is a poor discriminator of patients with subclinical or ’not flow-limiting’ CAD. The combination of CCTA with MPI allows identification of false-
positive CCTA findings and false-negative MPI studies.

Despite its excellent negative predictive value regarding exclusion of CAD, CCTA is not reliable for the exclusion of myocardial ischemia. The specificity and positive predictive value of stand-alone CCTA are particularly suboptimal in the presence of motion artefacts or severe coronary calcifications. On the other hand, balanced ishaemia in multiple vessel disease may be presented as normal in semiquantitative MPI and thus be false-negative in severe CAD.

Hybrid imaging has shown that non-evaluable, severely calcified vessels especially benefit from further testing due to their relatively high likelihood of obstructive disease, whereas non-evaluable vessels with motion artefacts (particularly in the right coronary artery) do not usually have haemodynamic significance.10 Image fusion is of particular value in lesions of distal segments, diagonal braches, right coronary artery and left circumflex artery.8,9

Quantitative PET in combination with CT has recently been compared with ICA, including measurement of fractional flow reserve when appropriate and feasible, in patients with stable chest pain with moderate pretest likelihood of CAD.20 Although both stand-alone PET and CT provided excellent exclusion of CAD, false-positive findings were not uncommon. Hybrid imaging was significantly more accurate than CTA or PET alone.20

The effective patient radiation dose from MPI and cardiac CT varies widely depending on the protocol, instrumentation, and patient size. With the latest technology, the complete hybrid examination can be performed with a radiation dose of ≤15mSv in the average patient size.25,26,27

Clinical use
The clinical use of imaging should depend on the pretest likelihood of CAD. Because software registration can reliably bring MPI and CCTA data acquired on different scanners into appropriate alignment, for most sites the practical current 
approach for overall clinical effectiveness and 
the minimisation of the cost and radiation dose may be the sequential scanning, facilitated by software tools for automatic image registration and fusion.24

In the sites with appropriate infrastructure and tracer availability, single-session hybrid imaging is likely to be preferred, as it gives obvious benefits for the patients. For symptomatic patients without known CAD and low-to-moderate pretest likelihood of disease (i.e. <50% likelihood), typically young and middle-aged patients, CCTA would probably be essential to practically exclude CAD.

When findings are normal, further diagnostic tests are avoided. However, abnormal or equivocal findings have to be confirmed or rejected by MPI or ICA. Thus, hybrid imaging leads to a more rapid diagnosis in these patients and with a higher normality rate, resulting in a reduction of the number of patients referred for ICA.11

A rapid imaging protocol based on stepwise use of low-dose CTCA, stress-only MPI and rest MPI according to positive or equivocal findings was recently published. The mean duration of a complete examination for this patient group with low-to-intermediate pretest likelihood was less than one hour, and the mean radiation dose was calculated to be 4.8mSv. The accuracy compared to invasive angiography was 95%.19

MPI might be a better first-line test compared with CCTA in patients with higher pretest likelihood of disease (i.e. >50% likelihood), characteristically those with known CAD or older age, likely to have extensive CAC,28 and patients with known or suspected microvascular endothelial dysfunction, e.g. diabetics.10 CCTA can be added in presence of equivocal MPI findings suggestive of artefacts, microvascular disease or multivessel disease. Also in these patients, hybrid imaging improves diagnostic accuracy, providing a complete evaluation of haemodynamic relevance of coronary stenoses and assessment of viability in territories subtended by occluded arteries. The accurate spatial association of coronary stenoses and perfusion defects allows evaluation of haemodynamic properties of even fairly small coronary branches, allowing for timely and appropriate treatment.

For asymptomatic patients with moderate pretest likelihood of disease, hybrid imaging cannot be recommended. CAC imaging has been suggested as a reasonable choice for refining the risk stratification.29

Conclusions
The integration of anatomic and physiologic imaging modalities in hybrid imaging has produced important improvement in the study of patients with known or suspected CAD, allowing:

• 
Detection and quantification of the burden of the extent of calcified and non-calcified plaques
• 
Quantification of vascular reactivity and endothelial dysfunction
• 
Identification of flow-limiting coronary stenoses
• Assessment of myocardial viability.

Thus, hybrid imaging has incremental diagnostic and prognostic value beyond that of either device alone and that of side-by-side analysis in patients at intermediate risk for CAD. Hybrid imaging appears to improve both the identification of the culprit vessel and the diagnostic confidence for categorising intermediate lesions and equivocal perfusion defects.

However, the clinical impact and incremental value of integrated imaging need to be evaluated and confirmed in larger cohorts and multicentre investigations with hard endpoints (morbidity, mortality) as the gold standard. Moreover, increased imaging costs associated with logistics in hybrid imaging must be taken into consideration. With current technology, radiation dose by hybrid imaging is less important for symptomatic patients in a total risk assessment.

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