The role of MRI and CT for diagnosis and work-up in suspected ACS

Left-ventricular function: cine CMR

Cine CMR with its consistent image quality accurately identifies regional and global wall motion abnormalities. Typically, at least two cine slices can be acquired within a single breath-hold. While generally, contiguous stacks are recommended [11], [12], the acquisition of six long-axis views is faster and results are equally accurate [13]. Clearly defined regional wall motion abnormalities without associated wall thinning are consistent with recent ischemic injury, although cine imaging solely cannot exclude other etiologies. The same images allow for the assessment of regional or global systolic function, for a qualitative assessment of valvular function, pericardial effusion, and edema [14]. Figure 1 shows diastolic and systolic frames of a cine series in a patient with ACS. Overall, the left-ventricular function is a known prognostic marker in patients with ACS.

Figure 1:

Cine CMR images at end-diastole (upper row) and end-systole (middle row) in a patient with acute ischemia in the territory of the left anterior descending (LAD) coronary artery.

While there is only subtle dysfunction, the water-sensitive CMR images (lower low) show evidence of myocardial edema in the LAD territory (arrows).

Edema imaging

Edema imaging by CMR has become the most efficient clinical tool to verify the presence, extent, and location of acute myocardial injury. It has been known for more than 30 years that an acute ischemic injury, despite a rather small net increase of absolute tissue water content, significantly increases myocardial T2 signal [15]. More recently, edema has been identified as a strong diagnostic marker [16], which is specific for acute vs. chronic ischemic injury [17]. Dark-blood water-sensitive (“T2-weighted”) images with fat saturation are typically applied [18]. Myocardial edema in a coronary territory showing an ischemic distribution pattern (subendocardial or transmural) is very specific for acute ischemic injury. Figure 2 shows a typical example of a reperfused acute myocardial infarction (Figure 2). The absence of an associated high signal intensity in late gadolinium enhancement (LGE) indicates fully reversible injury, which is, for example, found in stress-induced cardiomyopathy (“takotsubo”). Of note, edema-sensitive CMR is the only available in-vivo technique to assess the myocardium for edema, the most accurate in-vivo marker for acute myocardial injury.

Figure 2:

CMR images in a patient with acute reperfused myocardial infarction after revascularization of the left circumflex (LCX) coronary artery.

The cine images in diastole (left upper panel) and systole (right upper panel) show mild hypokinesis of the inferolateral wall. The LGE image (left lower panel) indicates largely transmural irreversible injury (arrow), which corresponds to transmural edema in the same region (right lower panel, arrow).

However, its inherently low signal-to-noise ratio and susceptibility to motion artifacts can limit the quality of these images. More recently, T1 mapping [19], [20] and T2 mapping [21] have been introduced and may be more robust for detecting acute injury. While T1 mapping may show increased values in acute as well as in chronic stages of myocardial injury, T2 mapping detects mainly myocardial edema as result of an acute myocardial injury. Of note, recent controversial data indicated that T2 may show a transient (pseudo-) normalization about 24 h after the onset of ischemia [22].

Areas with low signal intensity in water-sensitive images may indicate myocardial hemorrhage which is a relatively frequent complication of acute coronary revascularization. The presence of a hypointense core also indicates an impaired prognosis [23].

Necrosis and scar imaging

Specific images acquired 10–30 min after the injection of gadolinium-based agents accurately visualize irreversible myocardial injury due to a delayed washout of the contrast agent from the extracellular compartment, a technique known as aforementioned late gadolinium enhancement (LGE) imaging. In the context of ACS, bright signal intensity in images, in which the signal intensity of tissue with normal washout kinetics is artificially set to very low values, indicates necrosis. LGE imaging is more sensitive than nuclear medicine techniques in detecting smaller infarcts and visualizes both, viable and non-viable tissue [24]. In acute myocardial infarction, areas of high signal intensity in LGE images may slightly overestimate the size of reperfused infarcts around 24 h after the event [25], likely due to reperfusion injury. It is important to keep in mind that if no water-sensitive CMR images are acquired, a clear discrimination from remote myocardial infarction is not possible. Figure 3 shows an example of an acute and a remote infarct in the same patient. Non-reperfused and late reperfused infarcts often show a very dark region within the infarcted area (Figure 4). This is a no-reflow zone that often reflects microvascular obstruction related to myocardial hemorrhage.

Figure 3:

CMR in a patient with acute and chronic infarction. The cine images in diastole (left upper panel) and systole (right upper panel) show largely preserved systolic function.

The LGE image (left lower panel) indicates largely transmural irreversible injury in the territory of the left circumflex artery (arrow), which corresponds to transmural edema in the same region (right lower panel, arrow). The LGE image, however, also shows a scar in the anterior segment (arrowhead), with the same region appearing unremarkable in the edema-sensitive images (right lower panel). The combination of increased signal intensity in LGE images (scar) and largely normal signal intensity in edema-sensitive images is consistent with remote myocardial infarction.

Figure 4:

Late gadolinium enhancement image (4-chamber view) in a patient with acute, reperfused myocardial infarction of the LCX territory.

A large inferolateral region (arrowheads) including the subendocardial layer is surrounded by high signal intensity (arrows), typical for the large no-reflow zone often found in patients with late reperfusion and myocardial hemorrhage.

As an example for infarct-related complications, large transmural septal infarcts indicate a higher risk for an acute ventricular septal defect. Other complications detectable by CMR include pericarditis and pseudoaneurysms.

Cardiac CT

In the recent decades, CT has emerged as a valuable diagnostic modality in modern cardiovascular medicine as well as in emergency medicine. Especially in acute care, CT has two important features: 1) Its wide availability allows for the immediate examination of patients in most primary care hospital with emergency departments or chest pain units and not only in specialized tertiary centres. 2) The short scan durations enable the comprehensive assessment of critically ill patients.

Regarding ACS, two different acquisition protocols are of clinical interest. Coronary computed tomography angiography (CCTA) protocols for the assessment of the coronary arteries and triple rule out (TRO) protocols which also include the simultaneous examination of the thorax.

Coronary computed tomography angiography

The reliable evaluation of coronary arteries in clinical routine became possible over 10 years ago with the introduction of 64 multi-slice CT systems. Since then, the advances in scanner and post-processing technologies have led to a further improvement in diagnostic accuracy. State-of-the-art CT scanners attain spatial resolutions <0.25 mm and temporal resolutions <60 ms allowing for the examination of a broad variety of patients and clinical conditions.

While calcium scoring of the coronary calcified plaque burden is used for risk stratification, its utility in ACS is limited as about 5% of patients with occlusive but non-calcified CAD may be missed [26], [27]. In some cases, however, calcium scoring can serve as a gatekeeper for CCTA as a high burden of calcified plaques indicate the presence of a significant CAD and may impair the diagnostic quality of a subsequent CCTA significantly [28], [29].

CCTA features a high sensitivity and a negative predictive value up to 99% for significant CAD [30]. Thus, a normal CCTA excludes significant CAD with sufficient sensitivity and allows for a safe discharge of patients [31], [32]. Yet, the specificity of CCTA is limited due to its susceptibility to artifacts from calcified plaques or cardiac and respiratory motion. Especially high heart rates, arrhythmias, and poor patient conditions may lead to motion artifacts which impair the assessment of the coronary arteries. In consequence, CCTA is mostly applicable for patients presenting with chest pain with a low to intermediate risk for CAD whereas those with high probability should rather be assigned to other modalities. Furthermore, CCTA may be appropriate in patients with ambiguous findings or with symptoms resolving hours before presentation [8]. A recent meta-analysis showed that the use of CCTA for ACS in emergency departments can result in a cost reduction and length of stay compared to standard care whereas the number of invasive coronary angiographies and revascularizations increases [33]. While there are several studies focusing on the outcome of patients with stable angina assessed with CCTA, outcome data for patients presenting with ACS are still scarce.

Triple rule out

Aside from CAD, acute chest pain can be caused by other, potential life-threatening pathologies. TRO protocols are designed to provide sufficient contrast of the coronary arteries, pulmonary arteries as well as the thoracic aorta, in order to allow for the assessment of CAD, pulmonary embolism (PE), aortic dissection (AD) as well as pneumothorax and traumatic injuries by a single acquisition. Although the image quality of TRO protocols is similar to CCTA protocols, the exposure to radiation and the amount of contrast medium are higher [34]. Therefore, dedicated CT examinations are recommended if the differential diagnosis can be narrowed [8]. If the leading diagnosis is PE or AD, CT is recommended because of its high diagnostic accuracy [8], [35], [36]. However, if such a risk is low, the diagnostic benefit of a TRO protocol over a CCTA is small and its use rarely appears appropriate [8], [34]. Nevertheless, in patients with unclear leading diagnosis, who have a relevant risk for AD, CAD or PE, the use of TRO protocols may be of diagnostic value and therefore warranted. Figure 5 shows the diagnostic benefit of a TRO protocol in a patient with equivocal symptoms and biomarkers.

Figure 5:

Triple rule out study of a patient who presented with unclear leading diagnosis and inconclusive biomarkers at the chest pain unit.

The CCT revealed a massive pulmonary embolism (arrows) as well as a severe stenosis of the proximal LAD (asterisk).

The so-called quadruple rule out protocols extent the longitudinal scan coverage of TRO protocols to the skull base to allow for the assessment of the neck and intracranial arteries. Although rarely used, these protocols may be of avail in patients with syncope or suspected ischemic cerebrovascular events.

CCT image acquisition

CCT scans should be performed on CT systems with at least 64 slices, if available, to allow for a reliable detection of coronary artery stenosis. Prior to the scan, nitrates are administered to improve the accessibility of the coronary tree. Furthermore, β-blockers may be given to reduce the heart rate and thereby improve image quality and allow for the application of advanced dose reduction acquisition protocols.

CCT requires synchronization with cardiac motion and is attained by ECG-gating. In retrospective protocols, the image acquisition comprises the whole cardiac cycle resulting in a lower susceptibility to artifacts due to arrhythmias. In addition, they allow for dynamic measurements, e.g. for the assessment of stroke volumes and ejection fractions. Yet, these protocols are associated with a considerable radiation exposure for the patient. In prospective protocols the acquisition is performed at a prespecified point of the cardiac cycle, mostly in the end-diastolic or end-systolic phase, leading to significant radiation dose reductions. In addition, state-of-the-art CT scanners offer special acquisition modes as high volume axial modes or high-pitch spiral dual source protocols. In combination with advanced reconstruction algorithms radiation doses below 1.0 mSv for CCTA can be reached [37], [38].

As the distribution of the contrast medium after the injection depends on individual factors such as cardiac output, which may vary significantly between patients, bolus timing or triggering techniques are usually applied. For bolus timing, a small test bolus is injected and dynamic measurements of the X-ray attenuation are performed in one or several regions of interests (ROI) to estimate the time/time to peak of the contrast medium arrival. This time is used to optimize the delay between contrast medium injection and start of the image acquisition of the subsequent actual scan. For bolus triggering, the entire volume of the contrast medium is injected and the scan is triggered once a threshold value is reached in a specified ROI.

Specific cardiac reconstruction algorithms are applied to generate images from the acquired raw data. Various signal processing algorithms (kernels) are employed to optimize the visualization of different anatomical structures. In general, “soft” kernels are most suitable for soft tissues and the coronary vessels whereas “sharp” or “hard” kernels are better suitable for calcified plaques or coronary stent assessment. Advanced iterative reconstruction algorithms, which have been introduced in CCT in the recent years, reduce image noise and artifacts resulting in an improved image quality. Consequently, they may allow for significant dose reductions for CCTA in clinical routine [39].

Advanced technologies

While CCTA allows for the detailed assessment of the morphology of coronary artery stenosis, it does not provide information about their hemodynamic significance. This issue is addressed by two recently introduced techniques: virtual fractional flow reserve derived from CCTA (vFFR_CT) and stress CT perfusion.

The fractional flow reserve (FFR), which is measured with a pressure wire at invasive coronary angiography, is the current reference standard to evaluate the rheological severity of a coronary artery stenosis. In vFFR_CT computational fluid dynamics are applied to anatomical models based on the prior acquired CCTA study to estimate the FFR. First studies demonstrated a higher diagnostic accuracy for the identification of hemodynamic relevant stenosis compared to CCTA [40], [41]. Yet, vFFR_CT requires a CCTA studies with a sufficient image quality which is a crucial point in ACS patients. To date, several issues have to be solved before this technique can be implemented in clinical routine, as 20% of scans are rejected because of insufficient image quality and a the computing algorithm is still not disclosed [42]. Thus, vFFR_CT is presently not feasible in patients with ACS.

In stress CT perfusion protocols, vasodilators such as adenosine or regadenoson are applied in addition to contrast medium to assess for myocardial perfusion deficits. In static CT perfusion imaging, a single acquisition is performed during first-pass contrast enhancement whereas in dynamic CT perfusion imaging several consecutive image acquisitions are conducted. The latter allows for a more reliable acquisition of the peak attenuation and the quantification of hemodynamic parameters as the myocardial blood flow. However, dynamic CT perfusion imaging is associated with a significantly higher radiation exposure than static CT perfusion imaging. Stress CT perfusion has shown to improve the diagnostic accuracy of CCTA for the identification of physiological relevant coronary stenosis in several trials [43], [44]. Yet some issues still have to be solved before they can be implemented in clinical routine [45].