Automatic Assessment of Coronary Artery Calcium Score from Contrast-Enhanced 256-Row Coronary Computed Tomography Angiography

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1 Automatic Assessment of Coronary Artery Calcium Score from Contrast-Enhanced 256-Row Coronary Computed Tomography Angiography Ronen Rubinshtein, MD a, *, David A. Halon, MBChB a, Tamar Gaspar, MD b, Basil S. Lewis, MD a, and Nathan Peled, MD b The coronary artery calcium score (CS), an independent predictor of cardiovascular events, can be obtained from a stand-alone nonenhanced computed tomography (CT) scan (CSCT) or as an additional nonenhanced procedure before contrast-enhanced coronary CT angiography (CCTA). We evaluated the accuracy of a novel fully automatic tool for computing CS from the CCTA examination. One hundred thirty-six consecutive symptomatic patients (aged years, 40% female) without known coronary artery disease who underwent both 256-row CSCT and CCTA were studied. Original scan reconstruction (slice thickness) was maintained (3 mm for CSCT and 0.67 mm for CCTA). CS was computed from CCTA by an automatic tool (COR Analyzer, rcadia Medical Imaging, Haifa, Israel) and compared with CS results obtained by standard assessment of nonenhanced CSCT (HeartBeat CS, Philips, Cleveland, Ohio). We also compared both methods for classification into 5 commonly used CS categories (0, 1 to 10, 11 to 100, 101 to 400, >400 Agatston units). All scans were of diagnostic quality. CS obtained by the COR Analyzer from CCTA classified 111 of 136 (82%) of patients into identical categories as CS by CSCT and 24 of remaining 25 into an adjacent category. Overall, CS values from CCTA showed high correlation with CS values from CSCT (Spearman rank correlation [ 0.95, p <0.0001). In conclusion, CS values automatically computed from 256-row CCTA correlated highly with standard CS values obtained from nonenhanced CSCT. CS obtained directly from CCTA may obviate the need for an additional scan and attendant radiation. Ó 2014 Elsevier Inc. All rights reserved. (Am J Cardiol 2014;113:7e11) In patients referred for coronary computed tomography angiography (CCTA) a coronary artery calcium score (CS) is commonly calculated as a separate nonenhanced scan (CSCT) before CCTA in view of the large body of prognostic data related to the CS. 1 Elevated CS is associated with increased prevalence of obstructive coronary artery disease and elevated risk of adverse cardiac events in both asymptomatic and symptomatic subjects 1e3 and may be preferable to other risk-assessment tools in clinical practice. 4 To limit radiation exposure and address a specific clinical scenario, the procedure may be limited to a single scan depending on the clinical scenario: CCTA for symptomatic patients or stand-alone CSCT for asymptomatic patients. Until recently, the high attenuation from contrast medium within the coronary vessel lumen precluded assessment of CS from CCTA with standard CS software. 4 Moreover, CS from CCTA might yield CS values different from those derived from conventional CSCT. In this study, we Departments of a Cardiovascular Medicine and b Radiology, Lady Davis Carmel Medical Center and the Ruth and Bruce Rappaport School of Medicine, Technion Israel Institute of Technology, Haifa, Israel. Manuscript received June 4, 2013; revised manuscript received and accepted August 19, See page 10 for disclosure information. *Corresponding author: Tel: (þ972) ; fax: (þ972) address: ronenrub@clalit.org.il (R. Rubinshtein). evaluated the accuracy of a novel fully automatic tool for computing CS directly from CCTA. Methods This retrospective, single-center study was approved by the institutional review board with waiver of informed consent. The cohort included consecutive adults (aged >21 years) in sinus rhythm, without previously diagnosed coronary artery disease and none of the exclusion criteria (listed subsequently) who were referred to our institution by their treating physician for 256-slice CCTA during a 2- month period. Study exclusion criteria were known stenosis (and/or previous revascularization) or CCTA exclusion criteria (unable to cooperate, pregnancy, iodine allergy, renal function impairment, creatinine clearance <60 ml/ min). A structured interview on the day of CCTA detailed common risk factors: (1) diabetes mellitus (patient history and/or treatment with insulin or oral hypoglycemic agents), (2) hypercholesterolemia, (3) systemic hypertension, (4) family history of coronary artery disease (in first-degree relatives <55 [male] or <65 [female] years of age), and (5) smoking history. All scans were performed using a 256-row scanner (Brilliance ict, Philips Healthcare, Cleveland, Ohio), which has a longitudinal coverage of 8 cm, variable rotation time (minimum 0.27 seconds) and a 120-kW generator. CS (in Agatston units, AU) was assessed initially as a CSCT using /13/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved.

2 8 The American Journal of Cardiology ( Table 1 Patient characteristics (n ¼ 136) Variable Age (yrs) Female gender 55 (40%) Diabetes mellitus 31 (23%) Hyperlipidemia* 90 (66%) Hypertension 65 (48%) Family history for coronary disease 29 (21%) Smoker 42 (31%) * Total serum cholesterol level 5 mmol/l or treatment with lipidlowering drugs. blood pressure >140/90 mm Hg or treatment with antihypertensive medication. Table 3 Classification of patients into calcium score categories* by (noncontrast) calcium score computed tomography and (contrast-enhanced) coronary computed tomography angiography No. of Patients in Each CS Category Using CSCT No. of patients in each CS category using CCTA 0 1e10 11e e400 > e e e > * CS categories are presented in Agatston units. Table 2 Coronary computed tomography angiography (256-slice) scan data Heart rate (beats/min), mean SD (range) 61 9 (44e85) Contrast material (ml), mean SD (range) (50e100) Dose length product (mgy cm), (232e1,716) mean SD (range) Step-and-shoot mode, n 38 of 136 (28%) prospective electrocardiographic (ECG) triggering, tube voltage of 120 kv and a tube current of 55 mas as standard (100 mas in obese patients). CCTA was performed with either prospectively triggered step-and-shoot scans (Step & Shoot Cardiac, Philips Healthcare) or with helical retrospective ECG gating. Oral and/or intravenous b blockers were used to lower heart rate when >70 beats/min. Sublingual nitroglycerine (0.4 mg) was given before CCTA to all patients with systolic blood pressure of 110 mm Hg and no clinical contraindications, and a contrast enhanced scan was then performed using a bolus of ml (range 50 to 100) Iohexol (Omnipaque 350 mg I/ml, GE Healthcare, Princeton, New Jersey) injected into an antecubital vein at a flow rate of 5 to 6 ml/s, followed by a mixed 50% contrast/saline injection and then a 20- to 30-ml saline chaser bolus. Both modes of scans were performed at 120 kv with a slice collimation of mm with a dynamic dual focal spot (providing 256-slice acquisition) and a rotation time of 0.27 or 0.33 seconds. Helical scans (retrospective ECG gating) were performed with an effective tube current (rotation time product normalized by the pitch) in the range of 900 to 1,500 mas depending on body mass index and body habitus and a pitch of 0.14 to ECG based tube-current modulation was used with retrospective gating. The step-and-shoot scans were performed in patients with stable heart rhythm and heart rate <65 beats/ min with a tube current e x-ray on time product of 160 to 300 mas. Radiation exposure was assessed as dose-lengthproduct (product of scan length and CT dose index [CTDI vol ]). Reconstruction was performed using a window centered at 75% of the R-R interval as default. For heart rates >70 beats/min, an earlier reconstruction phase (usually 45%) was frequently used with retrospective gating. Standard CS was obtained by assessment of CSCT using semiautomatic software (HeartBeat CS) available on the Extended Brilliance Workstation (EBW, Philips Figure 1. Bland Altman analysis demonstrating good correlation between coronary artery calcium (CAC) score values obtained from traditional calcium score computed tomography and coronary computed tomography angiography (using the COR Analyzer). PCt ¼ percent. Healthcare). Traditional CS scoring on a nonenhanced scan involves (1) reconstruction of images with 3-mm slice thickness, (2) calcium segmentation, performed semiautomatically by selecting all pixels >130 HU in the coronary arteries, and (3) Scoring (by the software), measured slice by slice by summing the 2-dimensional area of each lesion in the slice multiplied by a factor determined by the maximal intensity of the calcium lesion in that slice. Reconstruction of CCTA images were initially performed with a slice thickness of 0.67 mm and spacing (z axis) of 0.4 mm. The reconstructed images were then sent to the COR Analyzer II workstation. The COR Analyzer software (rcadia Medical Imaging, Haifa, Israel) is a fully automatic tool developed to diagnose coronary stenosis from CCTA. The software classifies the coronary artery system into 3 main arteries and 10 coronary segments. Each artery is classified by the software to 1 of 3 categories: significantly stenotic (50% diameter stenosis), without significant stenosis (<50%), or indecisive (expert reading required). Additionally, the software version tested in the current study includes an additional module (COR CS module) that uses a novel algorithm involving the following steps to allow CS assessment from CCTA: (1) calcium segmentation is performed by comparing images to a model of intensity distribution within the artery lumen. The model is adaptive

3 Coronary Artery Disease/Obtaining Calcium Score from Coronary CT Angiography 9 Figure 2. Calcium scoring (left anterior descending plaque) in the same patient using traditional (nonenhanced) CSCT (top 2 images) and an automatic tool (COR Analyzer) used for CCTA (lower 2 images). to the local vessel geometry and to the local contrast intensity and noise estimation. (2) A virtual CS (nonenhanced, 3-mm slice thickness) study is simulated on the basis of the original CCTA, and segmented calcium (this step is patent pending) is marked. (3) The standard Agatston scoring is applied to the virtual CS study. The total CS score is then presented in Agatston units. Baseline characteristics and imaging and scanning parameters were recorded using descriptive statistics. CS obtained from CSCT (with traditional semiautomatic analysis) and that from CCTA (using the COR Analyzer) were compared using Bland Altman analysis and (nonparametric) Spearman rank correlation. We also compared both methods for classification into 5 commonly used CS categories (0, 1 to 10, 11 to 100, 101 to 400, and >400 AU). A p value <0.05 was considered significant. Statistical analysis was performed using Statistix 8 software package (Analytical Software, Tallahassee, Florida). Results One hundred thirty-six patients met study inclusion criteria and underwent both CSCT and CCTA. Their baseline characteristics are presented in Table 1. All scans were of diagnostic quality, and CCTA scanning parameters are presented in Table 2. Mean CS from traditional nonenhanced CSCT was AU (range 0 to 2,384, median ¼ 63, interquartile range ¼ 3, 276). Mean CS by CCTA using the COR Analyzer was AU (range 0 to 2,351, median ¼ 72, interquartile range ¼ 4, 301). The COR Analyzer analysis of the CCTA classified 111 of 136 patients (82%) into identical CS categories as the standard CSCT analysis and 24 of the remaining 25 into an adjacent CS category (Table 3). Thus a good correlation was maintained for all CS categories (regardless of scanning mode). Overall, CS values from CCTA and CSCT correlated well (Spearman rank correlation ¼ 0.95, p <0.0001), and Bland Altman analysis showed good correlation for all CS values (Figures 1 and 2). Discussion The study showed that total CS score can be calculated from contrast-enhanced CCTA using a novel algorithm and fully automatic tool (COR Analyzer). The CS correlated well with CS values obtained from traditional (nonenhanced) CSCT. Our findings imply that CS can be obtained accurately and automatically from CCTA using novel software without the need for an additional scan. Preliminary attempts to track calcium deposits in the coronary arteries in vivo and in vitro from contrast-enhanced scans yielded conflicting results. 5e8 It was suggested that a threshold value of 320 HU might be used, 9 but there are inherent limitations in using a simple fixed intensity threshold value from CCTA as opposed to the extensively validated 130-HU threshold used for CSCT. 10 Contrast intensity changes between studies and within a single study. Some calcified plaques may have a lower intensity than contrast for some lumen pixels in the same artery cross section. This limitation may be especially prominent and may introduce significant bias in the lower CS categories. Furthermore, because traditional calcium scoring is the product of the summed 2-dimensional area of all lesions in the slice and a factor determined by the maximal intensity of the calcium lesion in that slice, 10 thinner reconstruction slice thickness (as in CCTA) might result in higher calcium intensities leading to higher CS values when applying the standard Agatston scoring scheme to CCTA. Thus, using a fixed threshold cut-off value, it is likely that total CS values from 0.67-mm slice thickness reconstruction (as in

4 10 The American Journal of Cardiology ( CCTA) would be higher than a score constructed from 3- mm slice thickness reconstruction generated from CSCT. The novel algorithm used in this study was developed to overcome these limitations of CCTA-based calcium scoring. The COR Analyzer algorithm tries to overcome these limitations by using a 3-step approach (detailed in Methods). Our results support the findings of a preliminary report, 11 but extend these to a patient cohort with a wider range of CS and thus demonstrate that accuracy was maintained over a wider range of subjects than previously reported. In addition, the findings show that this 3-step approach yields similar CS values from CCTA to those obtained from traditional CSCT at all ranges of CS. The addition of the CS to CCTA data adds a risk assessment component to stenosis detection derived from CCTA based on large patient databases. 12 Importantly, this added information is cost-free and does not require additional radiation. Whether this extra information available from CCTA will lead to more frequent use of CCTA for screening asymptomatic patients at risk remains unknown. Current appropriate-use criteria clearly define the use of CCTA for screening of asymptomatic patients as inappropriate. 13 However, the ongoing reduction in radiation exposure now available with CCTA scanning (using iterative reconstruction, prospective triggering, low tube voltage, and other methods) and the improved risk assessment with automatically included CS values might tip the balance of risk-to-benefit ratio toward broader use of CCTA in selected asymptomatic patients for the purpose of risk assessment and possibly primary prevention. It is clear that even nonobstructive coronary atherosclerotic plaques by CCTA (calcified and noncalcified) are associated with increased risk of cardiovascular events. 14,15 It is therefore possible that combining lumen assessment from CCTA with the extensively validated calcium scoring in the same examination could have incremental prognostic value. However, ours was a relatively small, single-center study, and the findings need to be validated in prospective trials. 16 CS values may also be obtained from CCTA even when the CCTA is of low image quality. A zero calcium score, although not excluding obstructive coronary artery disease CAD, 17 especially in the acute setting, is still associated with low risk for future adverse events 18 and may obviate the need for further testing. Disclosures The authors have no conflicts of interest to disclose. 1. 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