Clinical validation of SPECT attenuation correction using x-ray computed tomography– derived attenuation maps: Multicenter clinical trial with angiographic correlation Yasmin Masood, MD, a Yi-Hwa Liu, PhD, a Gordon DePuey, MD, b Raymond Taillefer, MD, c Luis I. Araujo, MD, d Steven Allen, MD, e Dominique Delbeke, MD, f Frank Anstett, g Aharon Peretz, g Mary-Jo Zito, CNMT, BS, a Vera Tsatkin, CNMT, MS, a and Frans J. Th. Wackers, MD a Background. Nonuniform attenuation artifacts cause suboptimal specificity of stress single photon emission computed tomography (SPECT) myocardial perfusion images. In phantoms, normal subjects, and patients suspected of having coronary artery disease (CAD), we evaluated a new hybrid attenuation correction (AC) system that combines x-ray computed tomography (CT) with conventional stress SPECT imaging. Methods and Results. The effect of CT-based AC was evaluated in phantoms by assessing homogeneity of normal cardiac inserts. AC improved homogeneity of normal cardiac phantoms from 11%  2% to 5%  1% (P < .001). Attenuation-corrected normal patient files were created from 37 normal subjects with a low likelihood (<3%) of CAD. The diagnostic performance of AC for detection of CAD was evaluated in 118 patients who had stress technetium 99m sestamibi or tetrofosmin stress SPECT imaging and coronary angiography. SPECT images with and without AC were interpreted by 4 blinded readers with different interpretative attitudes. Overall, AC improved the diagnostic performance of all readers, particularly the normalcy rate. The degree of improve- ment depended on interpretative attitude. Readers prone to high sensitivity or with less experience had the greatest gain in the normalcy rate, whereas a reader prone to higher specificity had improvements in sensitivity and specificity but not the normalcy rate. Importantly, improvement of one diagnostic variable was not associated with worsening of other variables. Conclusion. CT-based AC of SPECT images consistently improved overall diagnostic performance of readers with different interpretive attitudes and experience. CT-based AC is well suited for routine use in clinical practice. (J Nucl Cardiol 2005;12:676-86.) Key Words: Single photon emission computed tomography • computed x-ray tomography • attenuation correction • coronary artery disease Stress radionuclide myocardial perfusion imaging (MPI) by use of single photon emission computed tomography (SPECT) is widely used for the detection of coronary artery disease (CAD) and patient risk stratifi- cation. The clinical usefulness of stress SPECT imaging for detecting CAD is supported by ample evidence in the literature in numerous and varying patient populations. 1,2 However, despite considerable technical advances achieved during the last 10 to 15 years, specificity of conventional SPECT imaging has remained suboptimal because of breast and diaphragmatic attenuation arti- facts. 3,4 Hardware and software devices have been de- veloped to correct for nonuniform attenuation artifacts. The most widely used attenuation correction (AC) de- vices utilize scanning radioisotope line sources for ob- taining transmission maps. 5-7 Multiple clinical studies have demonstrated that AC devices improve diagnostic From the Cardiovascular Nuclear Imaging Laboratory, Yale University School of Medicine, New Haven, Conn a ; Department of Nuclear Medicine, St. Lukes-Roosevelt Hospital, New York, NY b ; Depart- ment of Nuclear Medicine, Hôtel Dieu de Montréal, Montréal, Québec, Canada c ; Department of Nuclear Medicine, University of Pennsylvania, Philadelphia, Pa d ; Department of Nuclear Medicine, Mercy Medical Center, Springfield, Mass e ; Department of Nuclear Medicine, Vanderbilt University, Nashville, Tenn f ; GE Healthcare, Waukesha, Wis. g This study was supported in part by an educational grant from GE Healthcare. Received for publication April 5, 2005; final revision accepted Aug 2, 2005. Reprint requests: Frans J. Th. Wackers, MD, Yale University School of Medicine, Cardiovascular Nuclear Imaging Laboratory, 333 Cedar St, Fitkin-3, New Haven, CT 06520; frans.wackers@yale.edu. 1071-3581/$30.00 Copyright © 2005 by the American Society of Nuclear Cardiology. doi:10.1016/j.nuclcard.2005.08.006 676