Myocardial Perfusion Imaging – Recent Advances and Applications
Realtime myocardial contrast echocardiography (RTMCE) is an emerging technique capable of rapidly assessing myocardial perfusion at the capillary level using gas-filled microbubbles (<10μm) that are encapsulated with lipid, albumin or biocompatible polymers, thus generating an ultrasound signal to allow visualisation of perfusion.12,13
capillary circulation and persist within the systemic circulation.14
These microbubbles are able to traverse the pulmonary The
contrast enhancement observed after intravenous injection of microbubbles reflects capillary cross-sectional area. With RTMCE, a high-mechanical-index impulse (flash impulse) can be given to clear the myocardial capillaries of microbubbles (known as the destruction phase). The subsequent rate of contrast replenishment (correlating with flow velocity) and the plateau ultrasound intensity (representing cross-sectional area) can be used to calculate changes in the volume of blood flow. The replenishment kinetics is curvilinear, with the relationship between time (t) and signal intensity (y) expressed to an exponential function of y = A(1–e-βt), where A is the plateau intensity reflecting blood volume within the systemic capillaries and β is the mean flux rate of blood flow. Relative blood flow can be calculated by the product of blood volume and velocity (A x β),15 correlated well with quantitative PET perfusion in humans.16
which has With
continuous dobutamine and microbubble infusion, echocardiography images are taken before, during and after the flash impulse; areas with abnormal subendocardial replenishment of myocardial contrast represent perfusion defects.15,17
In addition to diagnosing ischaemia and evaluating blood flow, RTMCE can be useful in determining the extent of myocardial viability in patients with chronic ischaemic cardiomyopathy with low-dose dobutamine. Viability predicted by RTMCE was shown to correlate well with CMRI.18
Other studies have shown RTMCE to provide prognostic
information regarding left ventricular (LV) function recovery, death and heart failure.19–22
In a retrospective study of 788 patients
undergoing dobutamine RTMCE, the three-year event-free survival rate was 95% for patients with normal myocardial perfusion and wall motion and 82% for those with normal wall motion but abnormal perfusion, suggesting incremental prognostic value of both wall motion and perfusion.6
Studies have shown reduced specificity for CAD compared with wall motion,23,24
mainly due to attenuation of ultrasound beam and lack of
standardisation of myocardial contrast echocardiography protocols. However, when these variables are corrected, the higher resolution (≤1mm) seen on echo has been shown to detect perfusion defects not visualised by SPECT imaging (10–11mm).25,26
Sensitivity to detect CAD
with RTMCE in both dobutamine and treadmill exercise ranged between 85 and 99% in a study population of 254 patients.27
In October 2007, the US Food and Drug Administration (FDA) issued a black box warning on the echocardiography contrast agents Definity® and Optison® after reports of serious cardiopulmonary reactions within 30 minutes following administration in high-risk patients.28 However, studies since then have shown that ultrasound contrast agents are not associated with short-term or long-term risk of death
or MI.29,30
Currently, many echocardiography laboratories are still
employing the use of echo contrast except for those with severe pulmonary hypertension and known intracardiac shunts.
The advent of realtime 3D echocardiography (RT3DE) technology has provided volumetric imaging and quantification of myocardial
EUROPEAN CARDIOLOGY
Cadmium zinc telluride (CZT) is an alloy of cadmium telluride and zinc telluride that was incorporated into the SPECT system due to its high atomic number, leading to higher detector efficiency compared with NaI(Tl). Other detector crystals in development include cadmium telluride (CdTe), silicon strip detector, charge-coupled
33
Detector Crystals
Detector crystals in SPECT convert gamma-ray photons into electrical signals, which are then used to form 3D images from multiple projections. Image quality is dependent on the properties of these detectors. Desired detectors have high intrinsic efficiency, energy and spatial resolution.35
Traditionally, sodium iodide crystals doped with
thallium, NaI(Tl), have been used in most SPECT systems. However, other detector crystals are in development due to NaI(Tl)’s low spatial and energy resolution.
perfusion.31 Iwakura et al. have shown that RT3DE can be used to
assess subendocardial perfusion, and that this technique predicts infarct size and functional recovery more precisely than 2D myocardial contrast echocardiography.32
However, limitations of
RT3DE include the need for post-acquisition processing, lower spatial resolution leading to subendocardial artefacts and lack of quantitative measurement using replenishment curves as in 2D myocardial contrast echocardiography. Future advances in technology are needed to resolve these limitations.
Single-photon-emission Computed Tomography
SPECT is a widely available nuclear technique to assess myocardial perfusion using radiotracers such as thallium-201 (TI-201) or technetium-99m (Tc-99m). Images of regional myocardial blood flow (MBF) are obtained at rest and during stress. In the presence of significant coronary artery stenosis, heterogeneous myocardial perfusion occurs when comparing rest with stress, and the difference is detected by SPECT. Although SPECT is very sensitive, it has suffered from limitations including long image acquisition, low image resolution, reduced specificity due to soft-tissue attenuation and use of radioactive material. Recent advances in image reconstruction, detector crystals, new vasodilator agents, new hardware and incorporation of other imaging modalities have aimed to increase sensitivity or reduce patient side effects while maintaining image resolution and decreasing acquisition time.
Image Reconstruction
Current myocardial perfusion SPECT (MPS) is performed by standard dual-head scintillation cameras with collimators in 90º detector geometry and image reconstruction based on a standard filtered-back projection (FBP) algorithm, which back-projects 2D images into a virtual 3D space. However, FBP requires longer scanning time,
is
susceptible to motion artefacts, and has lower resolution due to increased noise. For example, wide-beam reconstruction (WBR) by UltraSPECT uses iterative image reconstruction that enables simultaneous resolution and contrast recovery combined with improved signal-to-noise ratio. WBR requires much less data input compared with FBP and can achieve similar-quality images by using half-projection at 6º, half the radiation dose or half the acquisition time. This technique has been compared with FBP by Borges-Neto et al. and other groups, who have shown highly significant correlations between variables including LV ejection fraction (LVEF), end-systolic and -diastolic volumes, summed rest score (SRS), summed stress score (SSS) and summed difference score (SDS).33,34
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