Subtraction coronary CT angiography with iterative reconstruction: a feasibility study of coronary calcium subtraction

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1 Subtraction coronary CT angiography with iterative reconstruction: a feasibility study of coronary calcium subtraction Poster No.: C-1756 Congress: ECR 2013 Type: Scientific Exhibit Authors: R. Tanaka, K. Yoshioka, K. Muranaka, M. Suzuki, S. Ehara; Iwate/ JP Keywords: Cardiac, CT, CT-Angiography, Diagnostic procedure, Arteriosclerosis, Calcifications / Calculi, Dosimetric comparison DOI: /ecr2013/C-1756 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 23

2 Purpose Coronary Computed Tomography Angiography (CCTA) allows detection of stenotic coronary artery lesions with high diagnostic accuracy[1; 2]. However, despite improvements in CT technology, extensive calcifications are uninterpretable or their severity is overestimate[3]. Therefore, patients with high calcium scores[1; 3; 4] cannot be reliably evaluated with CCTA and referral to other imaging modalities such as invasive coronary angiography is frequently recommended[5]. Recently, using a 320-detector row scanner, we developed subtraction CCTA which is a new method that allows subtraction of calcium from the CCTA images[6]. Briefly, two CCTA datasets - one with and one without contrast - are acquired in a single breath-hold. Afterwards, the noncontrast image dataset is subtracted from the contrast-enhanced CCTA study, thereby effectively removing calcium from the images. Using coronary calcium subtraction, patients may be evaluated with CT despite having a high calcium score. To minimize misregistration artifacts, we developed a dedicated volumetric CT digital subtraction angiography approach for optimal post-processing. In this study, we explore the feasibility of subtraction CCTA in patients with high calcium scores, and evaluate its potential to improve the interpretation of calcified segments as compared to conventional CCTA, using invasive coronary angiography as the gold standard. Methods and Materials Patient population and study protocol Eleven patients, referred for non-invasive CCTA followed by invasive coronary angiography, were enrolled. Patients were eligible for the subtraction CCTA protocol if they had a coronary calcium score >400 Agatston Units. Quantitative coronary angiography Invasive coronary angiography was performed according to standard techniques. Vascular access was obtained using the modified Seldinger technique, and the procedure was performed with a 4-F catheter. Quantitative assessment was performed by an observer blinded to CCTA using an offline software program (QAngio XA version 7.1, Medis medical imaging systems, Leiden, The Netherlands). Coronary arteries were divided into 17 segments according to the modified American Heart Association classification. QCA was performed in segments exceeding 20% luminal narrowing on Page 2 of 23

3 visual assessment. Significant stenosis was defined as #50% lumen reduction in the angiographic view with the most severe luminal narrowing. Coronary CT Angiography The imaging protocol for subtraction CCTA is illustrated in Fig. 1. Fig. 1: Acquisition protocol for subtraction CTCA References: Dept. of Radiology, Iwate Medical University - Iwate/JP All scans were performed using a 320-detector row CT scanner (Aquilion ONE, Toshiba Medical Systems, Otawara, Japan) with 0.5-mm detector elements and a rotation time of 350 ms. Software version was 4.74, which includes a novel dose reduction technology (Adaptive Iterative Dose Reduction 3D, AIDR 3D, Toshiba Medical Systems, Otawara, Japan). Unless contraindicated, patients with a heart rate #65 bpm received beta-blocking medication prior to scanning. First, coronary calcium scoring was performed using 120 kv and 300 ma. Coronary calcium score was immediately calculated after acquisition on the console using the Agatston method, and in case of a coronary calcium score >400, patients underwent the subtraction CCTA protocol, as shown in Fig. 1. For coronary enhancement, contrast medium (Iohexol 350, Daiichi Sankyo Company, Limited, Tokyo, Japan) was injected through the right antecubital vein at a rate of 0.07 x body weight (BW) ml/s in 10 s, followed by a saline chaser bolus of 30 ml. To determine the scan start time, a test bolus of 0.07 x BW x 3 ml was used, followed by a saline chaser bolus of BW x 0.25 ml. Both CCTA scans were performed during a single heart beat, with a maximum coverage of 16 cm. Prospective ECG-triggering was used with the exposure window depending of the heart rate. Tube voltage was set at 120 kv. Target noise for tube current selection was set at 28 HU. After acquisition, datasets were reconstructed with a slice thickness of 0.5 mm and a reconstruction interval of 0.5 mm. Page 3 of 23

4 Coronary calcium subtraction Coronary calcium subtraction was performed using a dedicated algorithm [Volumetric CT Digital Subtraction Angiography] available on the scanner console. Global non-rigid registration followed by local rigid registration is performed to obtain the subtraction CCTA images. Of note, the registration process is locally optimized for each part of the coronary tree. Image evaluation On the console, dedicated software (Plaque View) was used to generate curved multiplanar reconstructions (cmpr) and cross-sectional reconstructions. The obtained images (both subtraction images and original contrast images) were subsequently transferred to a dedicated workstation (Zio M900; Ziosoft, Tokyo, Japan) for further analysis and reporting. First, the conventional contrast-enhanced images without application of coronary calcium subtraction were evaluated for image quality and the presence of significant stenosis, defined as #50% luminal narrowing. The evaluation was done by two experienced observers, blinded to invasive coronary angiography data but aware of the clinical history of the patient. The caliper measurements were done using cross-sectional images. Coronary arteries were divided into 17 segments according to the modified American Heart Association classification. Only segments with calcifications, and thus target segments for coronary calcium subtraction were evaluated. First image quality was assessed, as previously described, using a 4-point scale. Each segment was graded as 1. uninterpretable (evaluation not possible), 2. poor (severe artifacts limiting adequate evaluation of the segment (low reader confidence)), 3. moderate (some artifacts present, but interpretation possible (moderate reader confidence), or 4. good (good image quality without artifacts (high reader confidence). Scores 1 and 2 were considered to reflect non-diagnostic image quality while scores 3 and 4 were considered to reflect diagnostic image quality. Next, the presence of significant stenosis (#50% stenosis) was determined. Page 4 of 23

5 In a separate session, the same observers performed an identical analysis of the available subtraction images. During this session, both the conventional contrastenhanced and subtraction images were used to allow verification of the subtraction images with the original contrast-enhanced images. Image quality and the presence of significant stenosis were determined as described above. Data and statistical analysis Data were evaluated on a segment level. Only segments with coronary calcifications and where the coronary calcium subtraction method had been applied were evaluated. Average image quality scores between conventional and subtraction CCTA were compared using paired t-test. The frequency of diagnostic image quality versus nondiagnostic image quality was compared using the chi-square test. Invasive coronary angiography in combination with QCA served as the gold standard. The diagnostic accuracies (sensitivity, specificity, positive predictive value, negative predictive value) of conventional and subtraction CCTA for the detection of #50% stenosis on QCA were calculated. To assess diagnostic accuracy, the area under the receiver operating characteristic curve (AUC) was calculated for conventional CCTA and subtraction CCTA. All statistical tests were performed using PASW statistics 18 (SPSS, Inc.) for Microsoft Windows. The effective radiation dose was estimated based on the dose-length product (DLP, mgy x cm) using the formula effective radiation dose = DLP x k, where k = msv x mgy -1-1 x cm, which is recommended by the European Working Group for Guidelines on Quality Criteria in CT and the American Association of Physicists in Medicine. Images for this section: Fig. 1: Acquisition protocol for subtraction CTCA Page 5 of 23

6 Results In total, eleven patients underwent subtraction CCTA and invasive coronary angiography. Patient characteristics are specified in Table 1. Page 6 of 23

7 Table 1 References: Dept. of Radiology, Iwate Medical University - Iwate/JP Page 7 of 23

8 Briefly, 91% was male and mean age was 69 ± 11 years. Average coronary calcium score was 1276 ± Invasive coronary angiography in combination with QCA revealed significant stenosis in all (100%) of patients. On a segmental basis, significant stenosis was observed in 16 of 55 evaluated segments. Average percentage stenosis was 76.2 ± 13.7%. Conventional CCTA The average image quality of conventional CCTA was 2.5 ± 0.6 (Fig. 2). Fig. 2: Average segmental image quality scores of conventional CCTA and subtraction CCTA. References: Dept. of Radiology, Iwate Medical University - Iwate/JP The AUC for conventional CCTA was (95% confidence interval [CI], to 0.885) for the diagnosis of a segment with coronary stenosis of 50% or more as assessed by QCA (Fig. 3). Page 8 of 23

9 Fig. 3: Area under the receiver operating characteristics curves of conventional CCTA and subtraction CCTA versus invasive coronary angiography. References: Dept. of Radiology, Iwate Medical University - Iwate/JP Segmental sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 93.8%, 48.7%, 42.9%, 95.0% and 61.8%, respectively (Table 2). Page 9 of 23

10 Table 2 References: Dept. of Radiology, Iwate Medical University - Iwate/JP Impact of subtraction CCTA The average image quality of subtraction CCTA in all segments was 3.1 ± 0.6 (Fig. 4) Page 10 of 23

11 Fig. 4: Percentage of segments with diagnostic versus non-diagnostic quality for conventional CCTA and subtraction CCTA. (Abbreviations: IQ: image quality) References: Dept. of Radiology, Iwate Medical University - Iwate/JP, which was significantly higher than conventional CCTA. Moreover, the percentage of segments with non-diagnostic image quality significantly decreased from 41.8% to 12.7% after coronary calcium subtraction (Fig. 4). The AUC for subtraction was (95% CI, to 1.000) for the diagnosis of a segment with coronary stenosis of 50% or more as assessed by QCA (Fig. 3). Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 93.8%, 59.0%, 48.4%, 95.8% and 69.1%, respectively (Table 2).A case example using coronary calcium subtraction is provided in Fig 5. Page 11 of 23

12 Fig. 5: A case example with coronary artery calcifications and coronary artery stenosis. References: Dept. of Radiology, Iwate Medical University - Iwate/JP Images for this section: Fig. 2: Average segmental image quality scores of conventional CCTA and subtraction CCTA. Page 12 of 23

13 Fig. 4: Percentage of segments with diagnostic versus non-diagnostic quality for conventional CCTA and subtraction CCTA. (Abbreviations: IQ: image quality) Page 13 of 23

14 Fig. 3: Area under the receiver operating characteristics curves of conventional CCTA and subtraction CCTA versus invasive coronary angiography. Page 14 of 23

15 Table 1 Page 15 of 23

16 Table 2 Fig. 5: A case example with coronary artery calcifications and coronary artery stenosis. Page 16 of 23

17 Conclusion Conclusion CCTA is increasingly used as a non-invasive alternative for the visualization of the coronary arteries. The diagnostic performance of CCTA using 64-detector row CT and beyond to detect significant coronary artery stenosis has been reported in many studies[1; 2; 7-13]. However, the presence of severe calcifications in the coronary arteries interferes with the assessment of the lumen[3; 14]. A multicenter study called the ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) study reported a significant reduction of specificity when the calcium score exceeded 400[1]. A significant decline in specificity with increasing calcium scores was confirmed by a recent meta-analysis of 19 eligible studies[4]. Not surprisingly therefore, high calcium scores are in general considered to present a relative contraindication for CCTA. ndeed, the appropriate use criteria for cardiac CT by ASSF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR published in 2010 present a threshold level, where the indication for CCTA in suspected coronary artery disease changes from "appropriate to "uncertain" above a calcium score of 400[5]. Accordingly, there is a clear need to improve image quality and diagnostic interpretation in the presence of calcifications. A potential solution for this problem could be offered by coronary calcium subtraction. Successful removal of calcium could allow more effective assessment of luminal stenosis and thus improve specificity[6]. Successful subtraction CT has been reported previously for the purpose of bone removal[15]. Based on these results, we considered that calcification removal is theoretically also achievable when the potential misregistration between precontrast and postcontrast datasets is minimized. Therefore, in this study, we planned pre- and post-contrast scanning in a single breath-hold. For this purpose, the peak time of the contrast was calculated with the test injection method. Also, we used a dedicated algorithm (Volumetric CT Digital Subtraction Angiography) for the image subtraction process. A previous report of subtraction CCTA used the two breath-hold method[6]. In this approach, the pre- and post-contrast scans are obtained during separate breath-holds. Although the individual breath-holds are shorter, the likelihood of misregistration between the two datasets is increased. Using this two breath-hold method, an average image quality score of 2.4 was seen[6]. In the current study based on single breath-hold subtraction CCTA, we observed an average image quality score of 3.1. Importantly, this average was significantly greater than the average image quality score (2.5) of conventional contrast-enhanced CCTA (Fig. 3), indicating a reduction of beam-hardening artifacts from the severe calcifications. In a next step, diagnostic accuracy was assessed, using invasive coronary angiography as the gold standard. Using only the conventional CCTA images, particularly specificity was low due to a high number of false positive Page 17 of 23

18 readings. With the subtraction method, patency of the lumen, initially obscured by severe calcifications, could become visible. The number of false positive studies was slightly reduced, resulting in an about 10% improvement of specificity without any changes in sensitivity. While in these highly calcified segments the AUC of conventional CCTA was 0.741, the AUC of subtraction CCTA improved significantly to Accordingly, these preliminary findings show the potential of coronary calcium subtraction to improve the efficacy of CCTA in the presence of calcifications. Radiation dose of CCTA is a major concern. With the recent introduction of iterative image reconstruction techniques scanning with less radiation dose has become possible[16-18]. The mean estimated effective radiation dose was 5.21 msv and its range was msv. These values included both precontrast and postcontrast CCTA scanning and are similar to reported doses obtained with conventional CCTA by 64-slice CT[13; 19-21]. Radiation dose was kept low by performing intensive heart rate control, followed by the scanning with prospective ECG-gating in one heart beat. Also zaxis scan range was kept as low as possible. Additional optimization of the subtraction acquisition protocol is expected to allow further dose reduction. Finally, the current study was done using an initial version of the subtraction algorithm. Optimization of this subtraction algorithm is currently ongoing with the aim to further enhance the accuracy and clinical usefulness of this promising new tool. As a conclusion, in patients with extensive calcifications, coronary calcium subtraction has the potential to improve evaluation of calcified segments on CCTA. Images for this section: Page 18 of 23

19 Fig. 3: Area under the receiver operating characteristics curves of conventional CCTA and subtraction CCTA versus invasive coronary angiography. Page 19 of 23

20 Fig. 4: Percentage of segments with diagnostic versus non-diagnostic quality for conventional CCTA and subtraction CCTA. (Abbreviations: IQ: image quality) Page 20 of 23

21 References 1 Budoff MJ, Dowe D, Jollis JG, et al. (2008) Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: results from the prospective multicenter ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial. J Am Coll Cardiol 52(21): Miller JM, Rochitte CE, Dewey M, et al. (2008) Diagnostic performance of coronary angiography by 64-row CT. N Engl J Med 359(22): Vavere AL, Arbab-Zadeh A, Rochitte CE, et al. (2011) Coronary artery stenoses: accuracy of 64-detector row CT angiography in segments with mild, moderate, or severe calcification--a subanalysis of the CORE-64 trial. Radiology 261(1): Abdulla J, Pedersen KS, Budoff M, Kofoed KF (2012) Influence of coronary calcification on the diagnostic accuracy of 64-slice computed tomography coronary angiography: a systematic review and meta-analysis. Int J Cardiovasc Imaging 28(4): Mark DB, Berman DS, Budoff MJ, et al. (2010) ACCF/ACR/AHA/NASCI/SAIP/ SCAI/SCCT 2010 expert consensus document on coronary computed tomographic angiography: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents. Circulation 121(22): Yoshioka K, Tanaka R, Muranaka K (2012) Subtraction coronary CT angiography for calcified lesions. Cardiol Clin 30(1): Andreini D, Pontone G, Bartorelli AL, et al. (2010) Comparison of the diagnostic performance of 64-slice computed tomography coronary angiography in diabetic and non-diabetic patients with suspected coronary artery disease. Cardiovasc Diabetol 9:80 8 Bayrak F, Guneysu T, Gemici G, et al. (2008) Diagnostic performance of 64slice computed tomography coronary angiography to detect significant coronary artery stenosis. Acta Cardiol 63(1): Hamon M, Morello R, Riddell JW (2007) Coronary arteries: diagnostic performance of 16- versus 64-section spiral CT compared with invasive coronary angiography--metaanalysis. Radiology 245(3): Shabestari AA, Abdi S, Akhlaghpoor S, et al. (2007) Diagnostic performance of 64channel multislice computed tomography in assessment of significant coronary artery disease in symptomatic subjects. Am J Cardiol 99(12): Page 21 of 23

22 11 Christiaens L, Duchat F, Boudiaf M, et al. (2012) Impact of 64-slice coronary CT on the management of patients presenting with acute chest pain: results of a prospective two-centre study. Eur Radiol 22(5): Meijboom WB, Mollet NR, Van Mieghem CA, et al. (2007) 64-Slice CT coronary angiography in patients with non-st elevation acute coronary syndrome. Heart 93(11): Dewey M, Hoffmann H, Hamm B (2007) CT coronary angiography using 16 and 64 simultaneous detector rows: intraindividual comparison. Rofo 179(6): Abbara S, Arbab-Zadeh A, Callister TQ, et al. (2009) SCCT guidelines for performance of coronary computed tomographic angiography: a report of the Society of Cardiovascular Computed Tomography Guidelines Committee. J Cardiovasc Comput Tomogr 3(3): Watanabe Y, Kashiwagi N, Yamada N, et al. (2008) Subtraction 3D CT angiography with the orbital synchronized helical scan technique for the evaluation of postoperative cerebral aneurysms treated with cobalt-alloy clips. AJNR Am J Neuroradiol 29(6): Wang R, Schoepf UJ, Wu R, et al. (2012) Image quality and radiation dose of low dose coronary CT angiography in obese patients: sinogram affirmed iterative reconstruction versus filtered back projection. Eur J Radiol 81(11): Oda S, Utsunomiya D, Funama Y, et al. (2012) A hybrid iterative reconstruction algorithm that improves the image quality of low-tube-voltage coronary CT angiography. AJR Am J Roentgenol 198(5): Ebersberger U, Tricarico F, Schoepf UJ, et al. (2013) CT evaluation of coronary artery stents with iterative image reconstruction: improvements in image quality and potential for radiation dose reduction. Eur Radiol 23(1): Zhang T, Luo Z, Wang D, et al. (2011) Radiation dose in coronary artery angiography with 320-detector row CT and its diagnostic accuracy: comparison with 64-detector row CT. Minerva Med 102(4): Xie Z, Wang J, Ding G, Song W, Xu K, Ren K (2012) Radiation Dose Study of 64Slice Spiral Ct Coronary Angiography: A Paired Design. Radiat Prot Dosimetry 21 Geleijns J, Joemai RM, Dewey M, et al. (2011) Radiation exposure to patients in a multicenter coronary angiography trial (CORE 64). AJR Am J Roentgenol 196(5): Page 22 of 23

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