Ergometer stress can be performed with either a (supine) scanner mounted bicycle ergometer or a treadmill near or in the scanner room. With supine cycling, it can be challenging to achieve target physiological responses. Treadmills offer a more physiological exercise regime but require rapid transfer of patients onto the scanner for imaging. Recently, an MR compatible treadmill has been described, which can be located immediately adjacent to the scanner with shortened transfer times [3].

Dobutamine directly stimulates β1 and β2 receptors in the heart, leading to a dose-related increase in heart rate, blood pressure and myocardial contractility.

Dobutamine stress CMR testing is performed using standard protocols in which the dose of intravenous dobutamine is determined by the patient’s bodyweight. Dobutamine is administered in increments of 5–10 μg/kg/min to a maximum of 40 μg/kg/min until the target heart rate, calculated as ((220-age) × 0.85), is reached. If required to achieve the target heart rate, intravenous atropine may be added up to a maximal dose of 2 mg.

Because of the inability to use the electrocardiogram for ischemia detection, close monitoring of the patient is mandatory: ischemia detection relies on patient symptoms, physical signs and imaging findings. At each dobutamine stress level, a series of cine images is acquired and reviewed by the examiner immediately after data acquisition. The presence of new or worsening wall motion abnormalities is a termination criterion alongside other published criteria (Table 14.2) [4].

Vasodilator stress (see next section as well as the chapter on Perfusion for more details) can in principle be used for the induction of ischemic wall motion abnormalities, but has a significantly lower diagnostic accuracy for the detection of CAD [2]. The use of vasodilator stress to detect ischemic wall motion changes is not advised.

Adenosine induces direct coronary arteriolar vasodilation through activation of the A2A receptor, but it is also activates A1, A2b, and A3 receptors, which leads to the side effects of adenosine infusion such as atrio-vertricular block, peripheral vasodilation (causing flushing sensation) and bronchospasm (causing chest discomfort). A modest increase in heart rate and often a small drop in systemic blood pressure are also observed. Adenosine is administered as a continuous intravenous infusion at a standard dose of 140 mcg/kg/min. Maximal hyperemia is typically reached at 3 min of infusion and image acquisition can begin. In the absence of any of these signs and symptoms, many investigators now recommend increasing the adenosine dose to 170 or 210 mcg/kg/min to overcome an assumed failure of full adenosine effect. Such as failure may be mediated by caffeine, which is a competitive antagonist of the adenosine receptor, if patients have failed to adhere to the recommended scan preparation.

Dipyridamole is an indirect coronary vasodilator that increases intravascular adenosine levels through inhibition of intracellular reuptake and deamination of adenosine. It is administered intravenously at a dose of 0.56 mg/kg over a 4-min period and induces hyperemia for more than 15 min.

The more recently approved regadenoson is a selective A2A adenosine receptor agonist although it also has some effect on the A1, A2B and A3 adenosine receptors. Regadenoson is injected as a rapid (10 s) intravenous bolus of 5 mL (0.4 mg), followed by a saline flush. Regadenoson reaches its maximal effect within 1–4 min. In CMR, regadenoson stress imaging therefore commences at approximately 2–4 min. A key advantage of regadenoson over adenosine is the upfront bolus injection, so that only one cannula is needed, and a better side effect profile through more selective A2A receptor affinity. For example, first degree AV block occurs in 3 % with regadenoson (7 % with adenosine) and second degree AV block in 0.1 % (1 % with adenosine). It does however lead to a higher increase in heart rate (more than 40 bpm in 5 % vs 3 % for adenosine), which in some cases may result in reduced image quality.

Dobutamine increases regional myocardial blood flow in response to its positive inotropic and chronotropic stimulation, which lead to increased oxygen demand. Vascular beds supplied by significantly stenosed coronary arteries have a reduced perfusion reserve and when oxygen demand exceeds supply, hypoxia and ischemia ensues, demonstrated on perfusion imaging as an area of reduced contrast uptake. Perfusion CMR during dobutamine stress faces challenges of high heart rates and higher risk profile than vasodilator imaging.

Physiological stress with an ergometer or treadmill can in principle also be used in perfusion CMR, although remains a research application.

Signal enhancement of MRI contrast agents is predominantly the result of their effect on the T₁ relaxation times of their surrounding tissues. Myocardial perfusion CMR pulse sequences therefore need to be strongly T₁-weighted. Given the short TR required for fast data acquisition, T₁-weighting in perfusion CMR is most commonly achieved with saturation recovery methods, i.e. by applying a 90-degree preparation pulse prior to the read-out pulse sequence. Saturation recovery methods are robust to heart rate variation, which is the reason why they have replaced previously used inversion recovery methods. The saturation time (TS) needs to be long enough to establish a high T1-contrast before the read-out sequence is employed and in most clinically used pulse sequences is around 100 ms. As for other MRI applications, the relationship between contrast agent concentration and signal is not linear, in particular at higher contrast doses and with longer TS. Shorter TS values and contrast agent doses may therefore be desirable if quantitative perfusion imaging analysis is planned – rarely the case in current clinical practice. Shorter TS also allows longer read out, usually allowing the acquisition of images with higher in-plane resolution, or acquisition of more slices within the constraints of each RR interval.

For signal readout, a wide variety of methods is in use, often vendor and institution specific. Most commonly, fast spoiled gradient echo methods (GRE), echo planar imaging (EPI), balanced Steady State Free Precession (bSSFP) pulse sequences or hybrids of these methods are used. Often, these readout schemes are combined with parallel acquisition techniques or image undersampling to shorten acquisition times and improve spatial resolution.

See Fig. 14.4 for typical myocardial perfusion CMR pulse sequences.

A fast gradient echo (FGRE) read-out sequence utilises a very short repetition time TR (<10 ms) and echo time TE (<5 ms), combined with a small flip angle of around 20–30°, resulting in a pulse sequence with predominant T1-weighting. A 90° preparation-pulse applied before the FGRE read-out increases image contrast. Since a very short TR is used, myocardial tissue or blood that stays in the slice becomes saturated (spoiling effect). Signal in FGRE therefore depends on the flow of blood to generate contrast. In clinical practice, FGRE pulse sequences are attractive because they are relatively robust to dark rim artifact.

This technique generates multiple gradient echoes following one rf pulse by quickly alternating the direction of frequency encoding gradients forming an echo train. The successive frequency gradients are interspersed by small phase encoding gradients to fill different lines of k-space within each heartbeat. However, T2* decay throughout the echo train causes image degredation with long echo trains. Thus a hybrid-EPI (also known as segmented EPI) technique is generally used in perfusion imaging where a number of shorter echo trains are acquired by applying multiple rf pulses. This reduces the destructive effect of T2* weighting, improving the image quality while maintaining part of the acceleration advantage provided by the EPI technique.

Balanced Steady State Free Precession (bSSFP) gradient echo sequences are constructed to protect the transverse magnetization from being spoiled but returned into phase at the end of each TR period when the next rf pulse is applied. Thus, the bSSFP sequence reverses the signal de-phased by the applied gradients by means of additional balancing gradients to re-phase the MR signal before each subsequent rf pulse. After a number of repetitions this gives rise to a steady state condition where the transverse magnetization from two or more successive repetition periods incorporate to give a much greater signal. Since the transverse magnetization is generated from multiple TR combination, the magnetization signal amplitude and consequently signal to noise ratio (SNR) for bSSFP is much higher in comparison to spoiled gradient echo. The increased signal permits the employment of higher receiver bandwidths, resulting in a shorter TE and TR compared to spoiled gradient echo pulse sequences and therefore improved imaging efficiency. However, if the magnetic field is not homogenous, the transverse magnetization from several TRs can destroy each other rather than sum together in areas of magnetic field inhomogeneity, causing a higher susceptibility to dark banding artifacts in comparison to spoiled FGRE. Shimming and keeping TR as short as possible are therefore crucial when bSSFP is used for myocardial perfusion CMR. Unlike spoiled gradient echo sequences, the contrast nature of bSSFP sequences is related to the tissue’s T2/T1 ratio, therefore fluid and fat in particular appearing as brighter than other tissues.