**5. CT myocardial perfusion**

current can be decreased in the remaining phase, resulting in a radiation dose lowered up to 50% [29, 30]. Under certain circumstances, it is possible to perform cCTA by prospective ECG triggering and sequential scanning. Patients with a low and stable heart rhythm and without an indication for functional testing are qualified for this technique in line with SCCT guidelines [31]. This attempt could reduce the radiation dose to 70–80% [29, 32]. Both options are optimal if either a scanner with 256 or more slices or a DSCT is used. Furthermore, use of DSCT enables further decrease due to its higher pitch rates at higher heart rates, since multisegment reconstruction is not necessary [33, 34]. Additional reduction is accomplished by a tube voltage of 100 kV or even 80 kV instead of the usual 120 kV, which can be performed depending on the patient's body mass [30, 31]. The image postprocessing technique of iterative reconstruction (chapter 3.2) also contributes to reduction of radiation dose. With all these measures taken into consideration, cCTA reached radiation doses lower than 4 mSv, therefore being in the range of the average yearly background radiation dose, in certain conditions even

Nowadays, two methods of image reconstruction are in use, analytical filtered back projection (FBP) and iterative reconstruction (IR). The initially used technique was indeed the more complex IR [37], but soon its use was limited by the computational power of erstwhile processors. The method was displaced by FBP, which still is the most widely used technique nowadays. In FBP, the measured intensity is described as an integral function, and the reconstruction data is obtained through solution of the resulting equations, which is called back projection. Additionally, a filter component compensates low-pass signals. If a higher spatial resolution is required, the filter can be adjusted accordingly. However, this adaptation of the filter causes

a higher image noise, since image sharpness and image noise are proportional [38].

IR seeks to solve this problem, and since nowadays, not only CT hardware but also software underwent enormous advances, complex computational operations are more and more available. Iterative reconstruction accomplishes the back projection through the comparison of two components; a simulated first image estimation on the one hand and the actual measured projection on the other hand. Both images are automatically compared and, in case of discrepancy, the estimation is altered and another comparison is made until a default condition is achieved [38]. The underlying complex mathematical algorithms are propriety of the respective companies. Not only was IR able to break the correlation between image noise and spatial resolution, but it does so while simultaneously reducing the applied radiation dose up to 40–70%, while maintaining or even increasing subjective image quality and diagnostic accuracy [39–42].

The first attempts in evaluating atherosclerotic plaques via CT have already been made 1985 [43], but this approach did not gain acceptance due to insufficient resolution and image quality. Nowadays, with a spatial resolution up to 400 μm, noninvasive detection and characterization

in submillisievert range [35, 36].

**4. Plaque characterization**

**3.2. Image reconstruction**

202 Interventional Cardiology

Due to high sensitivity and negative predictive value [54, 55], cCTA is at present an accepted diagnostic tool in detecting CAD in patients with low pretest probability [9]. However, the major limitation of cCTA remains in its low specificity and positive predictive value and the missing correlation of detected lesions and their physiological significance [56–58].

Challenge for novel diagnostic methods is to provide data about the anatomical and functional assessment of coronary stenosis. Myocardial perfusion derived from computed tomography (CTMP) is a recent instrument in diagnosis of ischemia. Compared to other functional tests, CTMP offers the substantial advantage that it is performed during ordinary cCTA. CTMP is a "one-stop shop" approach to close the gap between anatomical and functional assessment within a single imaging and could additionally limit false-positive results of cCTA [6].

Underlying principles of CTMP is the distribution and enhancement of iodinated contrast agent within the myocardium. The iodinated contrast agent is used as an indicator for myocardial blood flow and myocardial blood volume, based on the principles of the indicator-dilution theory. Myocardial areas with reduced amounts of contrast agent are indicating perfusion defects [59].

### **5.1. Image acquisition and protocols**

Like other functional imaging methods, ordinary acquisition of CTMP consists of three sequences: a rest acquisition, an acquisition under pharmacological stress, and an acquisition of late enhancement. This approach is used to evaluate the reversibility of the ischemia [6].

Adenosine is used during the pharmacological stress acquisition for dilation of the coronary arteries with a dose ratio of 140 μg kg−1 min−1. This leads to a decrease of the perfusion pressure. However, compensatory dilatation of obstructed arteries is limited. Reversible ischemia is the result of decreased perfusion reserves within these vessels. This pathophysiological phenomenon is called the "steal-effect." After 2–3 min of continuous administration of adenosine with monitoring of ECG, pulse oximetry, and blood pressure, iodinated contrast agent is injected and image acquisition starts [6]. Beyond the application of iodinated contrast agent during rest and stress acquisition and adenosine during stress acquisition, beta blockers, and nitrates were administered immediately before the examination to avoid motion artifacts and to improve image quality [59]. Contraindication (e.g., contrast agent allergy, severe COPD, severe aortic valve stenosis) should be taken into consideration regarding suitability of the patient. After 5–10 min of administration of contrast agent, a delayed acquisition can provide information about nonviable myocardium [6]. Myocardial areas of ischemia or infarction are described based on the American Heart Association segmental model [14].

Regarding comparability of studies and deeper understanding, it should be noted that there is a static myocardial blood pool imaging method during first pass and apart from it a dynamic myocardial perfusion method over several time points of myocardial iodine distribution. Development in computed tomography offers with dual-energy CT a further static perfusion method. For example, differences between these techniques apply on the direct assessment of quantitative perfusion parameters or radiation exposure [6, 60].

#### **5.2. Radiation exposure**

Radiation dose of a comprehensive protocol containing rest, stress, delayed enhancement, and calcium scoring have generally been reported in the range of 12–14 mSv. This is comparable to the radiation dose during SPECT examination [6]. Modified protocols in research contain considerably lower radiation. Feuchtner et al. achieved high accuracy (sensitivity 96%, specificity 88%, PPV 93%, and NPV 94%) in a stress approach and reported radiation dose of 2.5 mSv for cCTA and perfusion imaging with pharmacological stress [61]. Radiation doses for CTMP can be expected to decrease further, as radiation doses <1 mSv on cCTA studies are still state of the art [61].

#### **5.3. Clinical setting**

As mentioned in the introduction of this chapter, CT myocardial perfusion offers additional functional data of the myocardial blood supply. In contrast, ordinary cCTA only provides anatomical evaluation of the heart. Combined cCTA plus CTMP provides incremental diagnostic value compared with cCTA alone to assess the status of the myocardial blood supply and for the detection of significant coronary stenosis [6, 57, 58].

Compared with other functional noninvasive methods such as single photon emission computed tomography (SPECT) or cardiac magnetic resonance perfusion imaging (cMRI), CTMP is a recent technology.

SPECT is a nuclear imaging technique with tracer substances, such as thallium-201 or technetium-99. Myocardial enhancement of this tracer differs in damaged myocardium. A rotating gamma camera enables three-dimensional tomographic reconstruction [6]. According to current guidelines of the American Heart Association and American College of Cardiology, SPECT is used for the diagnosis of CAD, risk stratification, myocardial viability, and left ventricular function [62]. Rest and stress SPECT acquisitions allow evaluation of ischemic reversibility.

Cardiac magnetic resonance imaging (cMRI) offers anatomical information and a variety of functional aspects, such as assessment of myocardial perfusion during rest and stress acquisition and myocardial viability. SPECT has lower temporal and spatial resolution than cMRI [6]. The large CE-MARC trial led to higher sensitivity with cMRI than with SPECT and postulated cost-effectiveness and more use of this method [63, 64]. Patients with devices such as cardiac pacemakers or internal cardiac defibrillator (ICD) are often associated with great effort, regarding cMRI requirements. For patients with a tendency to claustrophobia, cMRI is potentially not the adequate examination due to long acquisition time [65]. On the other hand, cMRI is advantageous because of no ionizing radiation.

CT myocardial perfusion or other functional techniques are not reasonable in each clinical question compared to ordinary cCTA for ruling out CAD. In a situation of acute chest pain in a patient with low pretest probability of CAD, an extensive stress examination (irrespective of the imaging technique) is potentially not indicated due to prolonged examination. The availability in case of short-term request of such a comprehensive examination represents a further doubtful aspect in the clinical setting. However, CT myocardial perfusion has the potential to overcome these obstacles.
