IEEE TRANSACTIONS ON MEDICAL IMAGING, VOL. 23, NO. 9, SEPTEMBER 2004 1141 Registration of Real-Time 3-D Ultrasound Images of the Heart for Novel 3-D Stress Echocardiography Raj Shekhar*, Member, IEEE, Vladimir Zagrodsky, Member, IEEE, Mario J. Garcia, and James D. Thomas Abstract—Stress echocardiography is a routinely used clinical procedure to diagnose cardiac dysfunction by comparing wall mo- tion information in prestress and poststress ultrasound images. In- complete data, complicated imaging protocols and misaligned pre- stress and poststress views, however, are known limitations of con- ventional stress echocardiography. We discuss how the first two limitations are overcome via the use of real-time three-dimensional (3-D) ultrasound imaging, an emerging modality, and have called the new procedure “3-D stress echocardiography.” We also show that the problem of misaligned views can be solved by registration of prestress and poststress 3-D image sequences. Such images are misaligned because of variations in placing the ultrasound trans- ducer and stress-induced anatomical changes. We have developed a technique to temporally align 3-D images of the two sequences first and then to spatially register them to rectify probe placement error while preserving the stress-induced changes. The 3-D spatial registration is mutual information-based. Image registration used in conjunction with 3-D stress echocardiography can potentially improve the diagnostic accuracy of stress testing. Index Terms—Image registration, mutual information, stress echocardiography, three-dimensional ultrasound imaging. I. INTRODUCTION S TRESS echocardiography is a clinical procedure routinely used to diagnose myocardial ischemia. Early diagnosis of myocardial ischemia may save many lives by allowing narrowed coronary vessels to be reopened before the myocardium be- comes irreversibly scarred. Stress echocardiography measures the heart’s response to exercise or other forms of stress by com- paring resting and active phases of the wall of the left ventricle (LV) with conventional two-dimensional (2-D) ultrasound im- ages. A normal heart becomes hyperkinetic upon exercise; my- ocardial ischemia manifests itself as hypokinesis or akinesis [1]. Despite its frequent clinical utilization, conventional stress echocardiography has some fundamental limitations. Because stress-induced wall motion abnormalities are both transitory and time-dependent, the time window for acquiring images of the heart when under stress is extremely narrow (on the order of 1 Manuscript received September 3, 2003; revised April 19, 2004. This work was supported by the Whitaker Foundation research grant RG-01-0071. The Associate Editor resposible for coordinating the review of this paper and rec- ommending its publication was J. S. Duncan. Asterisk indicates corresponding author. *R. Shekhar is with the Department of Biomedical Engineering (ND20), Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland OH 44195 USA (e-mail: shekhar@bme.ri.ccf.org). V. Zagrodsky is with the Department of Biomedical Engineering, Lerner Re- search Institute of The Cleveland Clinic Foundation, Cleveland OH 44195 USA. M. J. Garcia and J. D. Thomas are with the Department of Cardiovascular Medicine of The Cleveland Clinic foundation, Cleveland OH 44195 USA. Digital Object Identifier 10.1109/TMI.2004.830527 min). A tradeoff then exists when using conventional 2-D ultra- sound in conjunction with stress testing. One must acquire sev- eral cine loops (2-D image sequences spanning a complete car- diac cycle) from different physical locations to view as much of the heart as possible; doing so, however, degrades the accuracy of wall motion information because the individual cine loops often do not reflect the same state of the “stressed” heart, and some loops may even fail to capture any abnormal wall motion. In practice, no more than three or four cine loops can be ac- quired in the time available. A second limitation of conventional stress echocardiography is that the 2-D views captured before and after stress may not correspond to the same cross-section of the heart. This limitation arises because of the sonographer’s inability to duplicate the lo- cation and orientation of the ultrasound probe between imaging sessions during a procedure that, by design, involves significant patient movement. Clinically, the term “foreshortening” is used to describe this phenomenon, which causes the LV to appear shrunken longitudinally in the poststress image in comparison to the prestress orientation. It is important that the identical re- gions of the LV are compared prestress and poststress for an accurate assessment of wall motion abnormality. Real-time three-dimensional (RT3D) imaging [2]–[4], a new development in ultrasound image acquisition, could address the aforementioned limitations of conventional stress echocardiog- raphy and thus improve its diagnostic power. RT3D Ultrasound, for the first time, has made it possible to image a beating LV in its entirety without gating, thus reducing image acquisition du- ration to the time of a single cardiac cycle (approximately 1-s or less). It is, therefore, natural to think of performing stress testing in conjunction with RT3D ultrasound – a combination we call three-dimensional (3-D) stress echocardiography. This procedure addresses the first limitation through rapid volumetric acquisition. Complete wall motion data for every part of the LV for a given stress level is gathered by RT3D ultrasound. Moreover, this procedure has the ability to capture any transient wall motion activity that may not be captured by all cine loops acquired at different times in conventional stress echocardiog- raphy. RT3D Ultrasound thus has the potential to collect com- plete and accurate wall motion information. Three-dimensional Stress echocardiography can also address the limitation of misaligned image planes. By registering prestress and poststress volumetric images retrospectively, the same anatomical plane from the prestress and poststress data can be presented to a physician for making a diagnosis. Conventional stress echocardiography cannot provide this ca- pability because it does not collect enough data to permit image registration. Furthermore, as we have shown, the availability 0278-0062/04$20.00 © 2004 IEEE