Review / Cardiovascular Imaging

Evolution of Cardiac Computed Tomography: Where Do We Stand?

Yasmin S. Hamirani, MD and Matthew J. Budoff, MD
Yasmin S. Hamirani, MD and Matthew J. Budoff, MD
Cardiovascular imaging has experienced widespread popularity and growth over the past decade. When integrated into clinical practice it promotes prompt, efficient, and cost-effective patient care. Noninvasive coronary angiography has been a challenge due to rapid cardiac motion, small vessel size and the tortuous anatomic configuration, but with advances in the cardiac computed tomography (CCT), it is now possible to view the coronary artery lumen with sufficient diagnostic accuracy, thus allowing the selective use of more expensive and invasive procedures such as invasive coronary angiography. CCT has undergone tremendous improvement, and now with faster gantry rotation, better z-axis spatial resolution, thin collimations and simultaneous acquisition of 64–320 slices, high-quality images are obtained with lower contrast doses and shorter breath-hold times. This has been a key to higher success and diagnostic rates. The aim of this article is to discuss the rapid development of CCT, its current applications and future implications. Development of Cardiac Computed Tomography Scanners The computed tomographic (CT) system was invented in 1972 by Sir Godfrey Newbold Hounsfield.1 Allan McLeod Cormack of Tufts University independently invented the same process and they shared a Nobel Prize in medicine in 1979.2 The first scanner, known as the EMI Scanner (Electric and Musical Industries, London, United Kingdom), took several hours to acquire the raw data and several days to produce the images and was limited to making tomographic sections of the brain. The first CT system that could make images of any part of the body was the scanner designed by Robert S. Ledley, DDS, at Georgetown University.3 Noninvasive coronary angiography was first described for CT in 1995 using electron-beam computed tomography (EBCT).4 Since then, scanners from different manufacturers that vary in their technical specifications have rapidly improved in terms of image quality. The multi-row detector scanners (MDCT) have better spatial, but lower temporal, resolution compared to EBCT. With the current 64–320 detector-row MDCT, high resolution and high temporal resolution can be obtained simultaneously. The temporal resolution of the MDCT scanner, which increases the ability to freeze images within the cardiac cycle, reduces motion artifacts, allows identification of an additional reconstruction window within the cardiac cycle, enhances the system’s performance when assessing left ventricular function and reduces the scanning time. The temporal resolution ranges from 165–210 milliseconds (ms) for a single beat with half-scan reconstruction (gantry rotation time of 330–420 ms).5–7 The 64 detectors yield a 3-dimensional dataset: for example, near-isotropic voxels of 0.35 x 0.35 x 0.5 mm3 can be rotated in any given plane without loss of resolution. With the dual-source CT (Siemens, Erlangen, Germany), the temporal resolution has decreased to 83 ms. The newly released high-definition CT (CT750 HD, GE Healthcare, Waukesha, Wisconsin) uses the first new detector material in 20 years. This detector material, by changing the molecular structure of real garnets, features a scintillator that is proposed to deliver images 100 times faster, with up to 33% greater detail through the body and up to 47% greater detail in the heart. Improved spatial resolution enhances the ability to visualize smaller coronary artery branches, increases the ability to quantitate calcium and analyze the lumen better by reducing the blooming artifact, reduces the blooming effect of stents, allows better visualization of the stent lumen, and also provides improved plaque definition with better potential quantification. Limiting factors of cardiac computed tomography. Certain factors limit the diagnostic capability of CCT, the most important of which are arrhythmias or heart-rate variability. Atrial fibrillation is a contraindication to CCT due to significant artifacts leading to blurred and nondiagnostic images. In case of faster heart rates, beta blockade is routinely used before the scans (to decrease the heart rate to Clinical Applications of Cardiac Computed Tomography 1. Coronary artery calcium scanning. The Multi-Ethnic Study of Atherosclerosis (MESA) and several other studies have clearly shown that a greater coronary artery calcium score (CACS), as measured using cardiac CT, is a strong predictor of an increased rate of coronary heart disease (CHD) events and provides additional predictive information beyond that afforded by traditional risk-factor assessment in four major American ethnic groups.16 Patients with an increased CACS are approximately ten times more likely to suffer a cardiac event over the next 3–5 years. The correlation between MDCT and EBCT is fair-to-good, depending on the study.17,18 As a result of improved resolution, the latest 64-MDCT systems offer an even higher degree of correlation with EBCT, and CAC can be accurately quantified and followed over time.19 CACS has also been shown to help improve patient compliance with statin therapy.20 2. Cardiac computed tomography and diagnosis of coronary artery disease (CAD). Recent advancements in MDCT, which offers better temporal and spatial resolution, have led to higher sensitivity and specificity in diagnosing significant coronary artery stenosis (> 50%) on invasive coronary angiography. The negative predictive value (NPV) for significant stenoses with cardiac computed tomographic angiography (CTA) has been uniformly high (98–99%) using a 64-slice scanner.21–23 A meta-analysis of 23 studies using 64-slice MDCT was published by Hamon et al.24 The per-patient sensitivity and specificity for significant stenosis on pooled analysis were 98% and 88%, respectively, while in 21 studies, the per-segment sensitivity and specificity in pooled analysis were 90% and 96%, respectively. Specificity was noticed to be reduced in the presence of CAC, i.e., 73% versus 87% for >70% stenosis on invasive angiography for severe-to-moderate CAC. Three multicenter comparison trials of MDCT with invasive coronary angiography have been reported to date. The first multicenter trial, ACCURACY,25 evaluated 230 patients at 16 centers. Patient-based analysis demonstrated the sensitivity, specificity, positive predictive value (PPV) and NPV for ≥ 50% or ≥ 70% stenosis were 95%, 83%, 64% and 99%, respectively, and 94%, 83%, 48% and 99%, respectively. In the presence of a CAC score > 400, specificity was significantly reduced. CorE-64,26 another multicenter study, included 291 patients. On patient-based analysis, CorE-64 results showed that sensitivity, specificity, PPV and NPV for > 50% stenosis on CTA were 85%, 90%, 91% and 83%, respectively. Meijaboon et al,27in a study of 360 symptomatic patients with acute or stable angina and a high prevalence of > 50% stenosis on invasive angiography (68%), found the sensitivity, specificity, PPV and NPV on patient-based analysis for detecting those with significant CAD on CTA of 99%, 64%, 86% and 97%, respectively, while for segment-based analysis, the respective percentages were 88%, 90%, 47% and 99%. In symptomatic patients with CAD, apart from detecting apparent coronary stenosis, the physiologic significance of such lesions is important to diagnose, since it adds prognostic relevance to such lesions. Perfusion imaging. Perfusion imaging by MDCT is in its preliminary stages. Viability imaging by MDCT is based on the “delayed enhancement” phenomenon in CMR to detect myocardial scar versus viability.28 Manken et al29 compared CMR delayed enhancement with MDCT images acquired in a conventional and post-processed manner and found a high degree of correlation (kappa: 0.75–0.85). The timings for acquiring MDCT images for perfusion are under research as well. One study30 of 19 patients found no difference in the extent of infarct measurement if performed either at 5 minutes or 10 minutes after contrast injection. Similarly, a study by Habis et al31 of patients immediately after invasive angiography without iodine reinjection performed MDCT and then CMR within 10 ± 4 days. Myocardial infarct size assessed by the two methods were highly correlated (r = 0.94; p 3. Cardiac computed tomography and “triple rule-out” in the emergency department. Approximately 8 million people in the United States visit the emergency department (ED) per year for chest pain,32 with annual costs of $10–12 billion.33 Many of these patients fall into the low-risk category. Three emergent causes of chest pain that ED physicians are most concerned about misdiagnosing are acute myocardial infarction (MI), pulmonary embolus and aortic dissection (Figure 1), i.e., “triple rule-out”. MDCT is well-suited to detect all of these conditions and this can be done in one scan or multiple images. A study published in 200634 examined 373 ED patients suspected of having aortic dissection who underwent MDCT scanning. This study revealed a sensitivity of 99%, a specificity of 100%, a PPV of 100%, a NPV of 99.7% and an accuracy of 99.5% for the diagnosis of any aortic pathology. Another study35 randomized patients with acute chest pain to MDCT or standard care. It looked specifically at patients who were classified as low-risk on admission to the ED, citing the high NPV of MDCT as an advantage in such a population. ED use of MDCT resulted in lower costs, faster discharge and lower subsequent visits for chest pain patients than nuclear imaging. Multicenter randomized trials are currently underway. 4. Cardiac computed tomography and coronary artery bypass grafts. Examination of patients with recurrent chest pain complaints after coronary artery bypass graft (CABG) surgery is another possible application of MDCT (Figure 2). Bypass grafts can usually be imaged with excellent quality because of their large caliber, relative lack of motion of at least their proximal portions and the higher contrast differential with the surrounding areas. The roadmap provides identification of number, location and types of bypass grafts. Metal clips are not a significant limitation, as thin slices reduce partial volume averaging. Native coronary arteries may sometimes be more of a challenge in CABG patients due to a lower contrast differential between the arteries, veins any calcifications and the contrast-enhanced myocardium. Under most circumstances, a confident interpretation can be made with a good correlation to cardiac catheterization.36–38 A meta-analysis of 12 studies39 (441 patients with 1,246 grafts) examined with 4-slice MDCT showed an overall sensitivity to detect bypass occlusion of 93% and a specificity of 96%. Two studies with 144 patients and 416 grafts examined with 16-slice MDCT showed improved sensitivity and specificity of 99% and 98%, respectively. Sixty-four-slice MDCT permits the evaluation of bypass patients with even higher diagnostic accuracy. Compared to previous scanner generations, the evaluation of the distal anastomosis site and the native coronary arteries is improved.40 Auguadro et al41 evaluated 40 bypass patients (118 grafts: 80 vein and 38 arterial conduits). A 100% diagnostic concordance was found between MDCT and invasive angiography. With regard to the native vessels, MDCT properly identified 80 of the 88 vessels (90%) described by angiography, whereas calcium deposits interfered with adequate detection in the remaining 8 cases. Kamohara et al,42 while assessing gastroepiploic arteries (GEA) using 64-slice MDCT on 30 CABG patients, found that the diameter of the middle of the GEA on MDCT correlated strongly with the actual internal diameter at the anastomotic site (r = 0.72; p 94%. 5. Cardiac computed tomography and assessment of coronary artery stents. The clinical incidence of restenosis after coronary stent implantation is about 20–35% for bare-metal stents (BMS) and 5–10% for drug-eluting stents (DES), but it can be higher in certain subsets of lesions such as long stenoses, bifurcation lesions or small-vessel lesions. Given the large number of patients who receive coronary artery stents, a noninvasive tool for the reliable detection of in-stent restenosis (ISR) would be clinically useful. Thus, there has been growing interest in the use of MDCT for the assessment of coronary artery stents (Figure 3). The new-generation MDCT scanners with high spatial and temporal resolution have high feasibility and diagnostic accuracy for the evaluation of coronary stents and the diagnosis of ISR. Although several reports have shown that MDCT may be used to evaluate stent patency, more precise evaluation of the lumen within the stent is markedly hindered by artificial enlargement of the metallic stent struts caused by blooming artifact. The impact of blooming and partial-volume artifact (stent producing artifacts by increasing the strut thickness) on the evaluation of structures inside stents is inversely related to stent diameter as well as stent type. In large-diameter coronary stents (> 3–3.5 mm) such as those in the left main coronary artery (LMCA), the proximal left anterior descending artery (LAD) or in bypass grafts, neointimal hyperplasia within the stent can be visualized on MDCT, demonstrating this modality’s potential for detection of ISR.47 Van Mieghem et al48 evaluated 74 patients scheduled for follow-up invasive angiography after LMCA stenting who underwent MDCT beforehand. Initially, a 16-slice MDCT scanner was used and afterwards, CT angiography was performed using a 64-slice MDCT scanner for all of the patients. Among patients with technically adequate scans (n = 70), MDCT correctly identified all patients with ISR, but misclassified 5 patients without ISR (false-positives). Overall, the accuracy of MDCT for detection of angiographic ISR was 93%. The sensitivity, specificity, PPV and NPV values were 100%, 91%, 67% and 100%, respectively. When analysis was restricted to patients with LMCA stents, with or without extension into a single major side branch, the accuracy was 98%. When both branches of the left main bifurcation were stented, the accuracy was 83%. For the assessment of stent diameter and area, MDCT showed good correlation with intravascular ultrasound (IVUS) (r = 0.78 and 0.73, respectively). An IVUS threshold value ≥ 1 mm was identified to reliably detect in-stent neointimal hyperplasia with MDCT. Andreini et al49 used 64-slice MDCT on 100 patients with previously implanted coronary stents followed by invasive angiography. The feasibility of stent visualization was 95%. Thirty-four of 39 cases of ISR (87%) were correctly detected and localized by remaining stented lesions. Sensitivity, specificity, PPV and NPV of MDCT for ISR identification were 87%, 98%, 92% and 96%, respectively. There was good correlation between percent stenosis evaluated by MDCT versus quantitative coronary angiography (QCA) and IVUS (r = 0.794, p 6. Cardiac computed tomography diagnosis of cardiomyopathy and analysis of cardiac function. CCT can be used to diagnose and differentiate between ischemic, dilated and hypertrophic cardiomyopathy (CMP) as well as to diagnose right ventricular (RV) pathology and aortic aneurysms. Budoff et al52 evaluated CAC testing in 125 patients with CMP of unclear etiology to determine ischemic versus dilated etiology, resulting in a sensitivity of 99% and a specificity of 83% compared to invasive angiography. Compared to nuclear stress imaging (NSI) in 56 patients, NSI was found to have a sensitivity and specificity of 97% and 18%, respectively, while an EBCT CAC score of > 0 Agatston units (AU) had a sensitivity and specificity of 97% and 68%, respectively, for differentiating ischemic from nonischemic CMP.53 Andreini et al54 using 16-slice MDCT on 61 patients with dilated CMP of unknown etiology and detected a sensitivity, specificity, PPV and NPV of 99%, 96.2%, 81.2% and 99.8%, respectively, in the diagnosis of ischemic CMP (coronary artery stenosis on invasive angiography of > 50%). Cornily,55 using 16-slice MDCT on 36 patients, found a sensitivity and a NPV of 100% in diagnosing CMP of ischemic etiology in patients with a CAC score of 7. Cardiac computed tomography and analysis of coronary anomalies and congenital heart disease. Up to 5.6% of the general population has some sort of coronary arterial anomaly involving the origin, course or termination of a vessel.65 Presently, MDCT shows coronary vessels more clearly than CMR. It helps in the identification of abnormal origins or unusual angulations of the coronary artery ostia, which saves time in the invasive cardiac catheterization laboratory and in the successful engagement of coronary artery catheters (Figure 5). Patients in whom the proximal segment of an anomalous coronary artery courses between the aorta and the pulmonary artery are at an increased risk of sudden cardiac death.66 Whether an anomalous coronary artery follows such a malignant “interarterial course”, or whether it courses in benign fashion in front of the pulmonary artery or behind the aorta, can be determined with very high accuracy by CTA and with much greater ease than by invasive coronary angiography. While echocardiography continues to be the mainstay of congenital heart disease (CHD) imaging, CMR and CTA have taken on increasing roles in the diagnosis of CHD in infants, children and, importantly, in adults who may have limited echocardiographic windows, especially if postoperative. CMR is certainly limited67 compared to CTA, with lower spatial resolution, artifacts due to metal such as coils, higher cost, limited availability, contraindication in patients with pacemakers, increased need for general anesthesia in younger children and longer time required for image acquisition precluding imaging of critically ill, thermally unstable and uncooperative pediatric patients. When anatomic information about blood vessels (especially aorta (Figure 6A), pulmonary arteries, collaterals and pulmonary veins) is desired, CTA can provide this information within seconds. Septal defects like atrial septal defect (ASD) and ventricular septal defect (VSD) can be detected and quantified for further management. It can detect LV thrombus and patent ductus arteriosus (PDA). In the study by Beier et al68 of 162 patients with CHD (mean age 16 ± 18 years) who underwent EBCT and transthoracic echocardiography (TTE), 667 findings were analyzed and stratified for age and anatomic categories. EBCT and TTE findings were correlated in patients 8. Cardiac computed tomography and plaque imaging. Plaque classification has been established by Schroeder and colleagues. Substantially different mean densities of 419 ± 194 Hounsfield units (HU), 91 ± 21 HU and 14 ± 26 HU, respectively, can be detected in calcified, intermediate and soft plaques (with IVUS serving as a standard of reference).69 Recently, Kunimasa et al demonstrated that low-density coronary plaques detected with 16-slice MDCT were observed significantly more often in patients presenting with acute coronary syndromes as compared to those with stable CAD.70 In 26 patients, the sensitivity of noncalcified and calcified plaques was 96.6% and 92.6%, respectively, with mean CT densities for soft, mixed and calcified plaques of 79 ± 34 HU (range, 7–149 Hu), 90 ± 27 HU (range, 22–154 HU), and 772 ± 251 HU (range, 295–1,325 HU), respectively.71 Pundziute et al72 showed a good correlation between such semiquantitative classification of coronary plaque and IVUS findings in 50 patients. In their study, 32% of mixed plaques by CT contained “thin-cap fibroatheroma” by IVUS criteria, as compared with 13% and 8% of noncalcified and calcified plaques, respectively. Data on plaque imaging with MDCT are limited and prospective studies are required to determine whether MDCT can indeed play a role in the identification of patients at elevated risk for coronary events based on plaque distribution and type. Moreover, further distinction between low-density plaques in fibrous and lipid content appears infeasible, as their signal intensities on MDCT overlap significantly. It may be possible in the future to detect and follow subclinical atherosclerosis in asymptomatic individuals and to follow the effect of lipid-lowering treatment, but its benefit and utility are yet to be shown by large multicentered trials. 9. Cardiac computed tomography and electrophysiology. CTA can accurately define coronary venous anatomy.73,74 The anatomy of the cardiac venous system is important for certain electrophysiologic procedures such as LV epicardial lead placement for cardiac resynchronization therapy.75,76 CTA can provide information about the presence of a Besian valve, which may cause difficulty when advancing guiding catheters into the coronary sinus ostium.76 By documenting the exact location of the esophagus, CTA helps prevent complications such as atrio-esophageal fistulae. Pericardial adipose tissue can be identified along with low-attenuation trabeculations, scalloping of the RV free wall, intramyocardial fat deposits and reduced RV motion. This might be comparable to cardiac MRI for RV dysplasia77 (Figure 6B). 10. Cardiac computed tomography and heart transplant patients. The potential efficacy of CTA for detecting cardiac allograft vasculopathy was assessed in a report of 53 heart transplant recipients with a 16-slice MDCT system.78 For detection of coronary stenosis > 50%, the sensitivity was 83%, the specificity was 95%, the PPV was 71%, the NPV was 95% and accuracy was 93%. Conclusion Cardiac computed tomography has undergone tremendous advancement since 1995. Multiple comparison studies with other noninvasive imaging modalities have proven its diagnostic efficacy, not only in regard to coronary artery imaging, but also for other noncoronary cardiac applications. Radiation exposure has been proactively addressed, and with prospective imaging, radiation exposure is reduced to levels below annual background radiation levels (3–5 mSev). Further developments are underway in the area of perfusion and coronary plaque imaging. CTA is potentially useful in assessing for plaque progression and as a tool to simultaneously evaluate the coronary lesion and reveal its functional significance. From the Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, California. The authors report no conflicts of interest regarding the content herein. Manuscript submitted June 10, 2009 and final version accepted June 16, 2009. Address for correspondence: Matthew J. Budoff, MD, FACC, FAHA, Los Angeles Biomedical Research Institute at Harbor-UCLA, 1124 W. Carson St., Torrance, CA 90502. E-mail: mbudoff@labiomed.org
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