Detection of Myocardial Ischemia using Real-Time Myocardial Contrast Echocardiography

Abstract: Echocardiography is an ideal clinical method for obtaining information about morphology and function of the heart. Echocardiography is more accessible, mobile and inexpensive compared to other imaging techniques and has become the perhaps most used diagnostic method in cardiology during recent years. To assess myocardial ischemia, different types of stress echocardiography have been available, where mainly wall motion analysis at rest and stress has been used to evaluate the presence and extent of ischemia. During the last few years, second generation contrast agents have become clinically available. This has improved image quality in echocardiography, which, combined with new ultrasound technical developments, has made it possible to obtain echocardiographic images of myocardial perfusion. When this myocardial contrast echocardiography technique is carried out in real-time, as in the studies of this thesis, it is labelled real-time perfusion (RTP). RTP in combination of adenosine stress (RTP-ASE) has the potential to become a valuable clinical tool to evaluate myocardial ischemia. If proven as accurate as other clinically and scientifically accepted methods, such as 99mTc-sestamibi single-photon emission computed tomography (SPECT), RTP-ASE might become an alternative method. Compared to SPECT, it is more accessible, mobile, inexpensive, and without radiation, compared to dobutamine-atropine stress echocardiography (DSE) it is more tolerable and swifter, and it is more accurate than exercise ECG. In all studies of this thesis, we performed RTP-ASE in patients with known or suspected stable coronary artery disease (CAD), admitted to adenosine SPECT evaluation. Adenosine was infused to provoke relative regional hypo-perfusion in ischemic myocardial territories. Using a SONOS 5500 echocardiography machine, patients underwent RTP imaging during Sonovue infusion, before and throughout the adenosine stress, also used for SPECT. RTP images were stored for later, blinded, off-line analysis. In studies III and IV, the commercially available software Qontrast was used to generate parametric images of myocardial perfusion and quantitative values of perfusion replenishment from RTP-ASE image loops. Method of reference for the ischemia evaluation in the thesis was the presence or absence of reversible ischemia at SPECT. The left ventricular myocardium was divided into three territories corresponding to the distribution territories of the three main coronary arteries; left anterior descending (LAD), left circumflex (LCx) and right coronary artery (RCA). In studies I and II, we investigated the feasibility of RTP-ASE for the detection of ischemia using visual interpretation of RTP-ASE loops acquired at rest and stress. Study III was carried out to examine the value of quantitatively generated parametric perfusion images from RTP-ASE loops, in detecting myocardial ischemia. In study IV, the usefulness of quantitative detection of myocardial ischemia from RTP-ASE loops was assessed. Data comparing quantitative measurements of perfusion replenishment from RTP-ASE images at rest and stress were used as markers of ischemia. The results from the studies in this thesis suggest that visual evaluation of ischemia from RTP-ASE images, using angio-mode as well as high resolution grey scale mode, is accurate and feasible. It is therefore a clinically useful method in patients with known or suspected stable CAD. Quantification of ischemia or parametric imaging for ischemia evaluation using Qontrast, are not yet suitable for clinical use, as judged by the findings of this thesis. However, since further technical development can be expected, quantitative assessment of myocardial perfusion may well be a clinically useful method in the near future.

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