Ultra-low-dose coronary artery calcium scoring using novel scoring thresholds for low tube voltage protocols—a pilot study

Ultra-low-dose coronary artery calcium scoring using novel scoring thresholds for low tube... Abstract Aims To determine if tube-adapted thresholds for coronary artery calcium (CAC) scoring by computed tomography at 80 kilovolt-peak (kVp) tube voltage and 70-kVp yield comparable results to the standard 120-kVp protocol. Methods and results We prospectively included 103 patients who underwent standard scanning with 120-kVp tube voltage and additional scans with 80 kVp and 70 kVp. Mean body mass index (BMI) was 27.9 ± 5.1 kg/m2. For the lowered tube voltages, we applied novel kVp-adapted thresholds for calculation of CAC scores and compared them with standard 120-kVp scans using intraclass correlation and Bland–Altman (BA) analysis. Furthermore, risk-class (CAC score 0/1–10/11–100/101–400/>400) changes were assessed. Median CAC score from 120-kVp scans was 212 (interquartile range 25–901). Thirteen (12.6%) patients had zero CAC. Using the novel kVp-adapted thresholds, CAC scores derived from 80-kVp scans showed excellent correlation (r = 0.994, P < 0.001) with standard 120-kVp scans with BA limits of agreement of −235 (−39.5%) to 172 (28.9%). Similarly, for 70-kVp scans, correlation was excellent (r = 0.972, P < 0.001) but with broader limits of agreement of −476 (−85.0%) to 270 (48.2%). Only 2 (2.8%) reclassifications were observed for the 80-kVp scans in patients with a BMI <30 kg/m2 (n = 71), and 2 (6.1%) for the 70-kVp scans in patients with a BMI <25 kg/m2 (n = 33). Mean effective radiation dose was 0.60 ± 0.07 millisieverts (mSv), 0.19 ± 0.02 mSv, and 0.12 ± 0.01 mSv for the 120-kVp, 80-kVp, and 70-kVp scans, respectively. Conclusion The present study suggests that CAC scoring with reduced peak tube voltage is accurate if kVp-adapted thresholds for calculation of CAC scores are applied while offering a substantial further radiation dose reduction. coronary artery calcium scoring, computed tomography, radiation dose, low-dose Introduction Coronary artery calcium (CAC) scoring by non-contrast cardiac computed tomography (CT) is a well-established predictor of coronary artery disease events and provides incremental information over standard coronary risk factors.1,2 A recent study reported on a very low mortality rate in patients with zero CAC which increased progressively with higher CAC score risk-classes (1–99, 100–399, and ≥400) over a long-term follow-up of up to 15 years.3 Although the radiation exposure from CAC scanning is low, the theoretical association of cancer caused by ionizing radiation raises concerns to the public and physicians likewise.4 In line with the basic principle of ‘as low as reasonably achievable (ALARA)’, radiation exposure from CAC scanning has steadily decreased in recent years and now lies in the range of ∼1–1.5 millisievert (mSv) in daily clinical routine.5 Meanwhile, however, radiation dose exposure from coronary CT angiography could be lowered much more substantially and, with latest-generation equipment, diagnostic image quality can now be routinely acquired using only a fraction of the dose necessary for obtaining CAC scores,6–8 emphasizing the need for further improvement in CAC scanning, where prior attempts towards lowering radiation dose were mainly focused on lowering tube currents.9,10 However, the greatest radiation dose reduction can be obtained by reducing peak tube voltage and past studies have shown a significant radiation dose reduction with 100 kilovoltage peak (kVp) scans.11,12 Yet lowering peak tube voltage remains challenging because tissue attenuation is closely related to photon energy, thus rendering the established thresholds for calculating CAC scores (i.e. Agatston scores) incomparable if peak tube voltages other than the standard 120 kVp are applied.11,12 In this pilot study, we aimed to determine whether CAC scoring based on CT scan protocols with peak tube voltages of 80-kVp and 70-kVp yields comparable results to the standard 120-kVp protocol if novel attenuation-based, and kVp-adapted thresholds are applied. Methods Patient population We prospectively included 105 patients without a history of revascularization or intracardiac defibrillator/pacemaker who were referred for clinically indicated single photon emission tomography and additional CAC scoring. CAC scoring was performed on the latest generation 256-slice CT scanner (Revolution CT, GE Healthcare, Waukesha, WI, USA). Of note, after inclusion of 13 patients with zero CAC, only patients with CAC score >0 were consecutively included afterwards. Two patients had to be excluded because of technical reasons not allowing reconstruction of some or all datasets. Thus, 103 patients were included in the final analysis. Scan protocols, image reconstruction, and image analysis All patients underwent the standard scanning protocol with 120 kVp and two additional scans with 80 kVp and 70 kVp immediately afterwards. Tube current was set to 200 milliampere (mA). All scans were performed in cranio-caudal direction during inspiratory breath-hold with prospective electrocardiogram (ECG)-triggering as previously reported.6 The scanning parameters included 256 × 0.625 mm collimation with a z-coverage of 12–16 cm and a display field of view of 25 cm with a slice thickness, and an increment of 2.5 mm was reconstructed. Gantry rotation time was 280 ms.6 Images were reconstructed using filtered back projection.13 With the exception of peak tube voltage, for each triplet of scans, the scanning parameters were identical. Values for effective radiation dose were calculated by multiplying the dose length product with a tube voltage dependent conversion factor (i.e. 0.0145 mSv × mGy−1 × cm−1 for 120 kVp and 0.0147 mSv × mGy−1 × cm−1 for 80 kVp and 70 kVp) as previously described.14 For every patient, the aortic root was examined at the level of the left main coronary artery on an axial image using a region of interest with a 20 mm diameter to measure mean attenuation (representing signal) and its standard deviation (SD) (representing noise) in Hounsfield units (HU) in order to calculate the signal-to-noise ratio (SNR). Novel kVp-adapted thresholds for CAC scoring X-ray attenuation is non-linearly and strongly dependent on the photon energy, which in turn depends on peak tube voltage used for CT imaging. For elements with a high effective atomic number (z) such as calcium, decreasing the photon energy (i.e. from 120 to 70 kVp) results in a substantial increase in CT attenuation number because of a higher absorption of calcium at low-photon energy levels. Therefore, the thresholds as established by Agatston et al.15 are not applicable to other tube currents. Attempting to overcome this limitation, we have mathematically derived novel thresholds for calculation of the CAC score for various peak tube voltage settings. From the initial study by Agatston et al.,15 it remains unclear what the exact material density of the reference plaque for establishing the scoring threshold was. By using linear attenuation coefficients derived from The National Institute of Standards and Technology (NIST) XCOM photon cross-sections database (Standard Reference Database 8, XGAM),16 we identified for the reference plaque a material composition containing phosphorus pentoxide (P2O5), calcium (Ca), magnesium oxide (MgO), hydrogen (H), carbon (C), and oxygen (O),17,18 with an attenuation coefficient of 0.1823 cm2/g which yields attenuation of 130 HU at 120-kV photon energy (Figure 1) while offering a composition of elements that are likely to constitute a coronary artery plaque. From these attenuation coefficients derived from the photon cross-sections database and taking into account differing attenuation for water at different kV, we calculated from the original thresholds the novel kVp-adapted thresholds for 70 kVp and 80 kVp assuming coherent scattering and a linear relationship between attenuation coefficients and photon energy in the relatively low energy spectrum of interest [i.e. between 10−2 and 10−1 megaelectron volts (MeV), Figure 1] by calculating the ratio between the attenuation coefficients at standard 120-kV photon energy vs. 100-kV, 80-kV, and 70-kV photon energies and have used this value as a coefficient to calculate the new thresholds from the original ones at each energy level. Our calculations led to the kVp-adapted thresholds for CAC scores given in Table 1. These thresholds for CAC score calculation with 70-kVp and 80-kVp scans were then validated in the present study population against the CAC scores derived from 120-kVp scans and based on the commonly used thresholds by Agatston et al.15 Table 1 Novel kVp-adapted thresholds Thresholds (HU) for lesion scores Tube voltage (kVp) 1 2 3 4 120 130–199 200–299 300–399 ≥400 100 145–222 223–334 335–446 ≥447 80 177–271 272–408 409–544 ≥545 70 207–318 319–477 478–636 ≥637 Thresholds (HU) for lesion scores Tube voltage (kVp) 1 2 3 4 120 130–199 200–299 300–399 ≥400 100 145–222 223–334 335–446 ≥447 80 177–271 272–408 409–544 ≥545 70 207–318 319–477 478–636 ≥637 Attenuation-based and kVp-adapted thresholds for calculation of CAC scores. Thresholds for 120 kVp are derived from Agatston et al.15 and represent the standard of reference. The calculated thresholds for 100 kVp are given for comparative purposes. In brief, according to the method developed by Agatston et al.,15 a total CAC score is calculated by applying for each region of interest drawn around a coronary lesion the above-mentioned lesions scores according to the maximal HU measured within this region, multiplying it with the area, and summing these scores for all CT slices. Note that the thresholds for applying any given score increase with decreasing kVp as lower kVp lead to higher HU for a given lesion. kVp, kilovolt-peak; HU, Hounsfield units. Table 1 Novel kVp-adapted thresholds Thresholds (HU) for lesion scores Tube voltage (kVp) 1 2 3 4 120 130–199 200–299 300–399 ≥400 100 145–222 223–334 335–446 ≥447 80 177–271 272–408 409–544 ≥545 70 207–318 319–477 478–636 ≥637 Thresholds (HU) for lesion scores Tube voltage (kVp) 1 2 3 4 120 130–199 200–299 300–399 ≥400 100 145–222 223–334 335–446 ≥447 80 177–271 272–408 409–544 ≥545 70 207–318 319–477 478–636 ≥637 Attenuation-based and kVp-adapted thresholds for calculation of CAC scores. Thresholds for 120 kVp are derived from Agatston et al.15 and represent the standard of reference. The calculated thresholds for 100 kVp are given for comparative purposes. In brief, according to the method developed by Agatston et al.,15 a total CAC score is calculated by applying for each region of interest drawn around a coronary lesion the above-mentioned lesions scores according to the maximal HU measured within this region, multiplying it with the area, and summing these scores for all CT slices. Note that the thresholds for applying any given score increase with decreasing kVp as lower kVp lead to higher HU for a given lesion. kVp, kilovolt-peak; HU, Hounsfield units. Figure 1 View largeDownload slide Plot of attenuation coefficients in relation to different photon energies for the reference plaque with a compound constituted as shown in the inlet. Note that the correlation is nearly linear in the in the relatively low energy spectrum of interest (i.e. in the range of 10−2 MeV). Figure 1 View largeDownload slide Plot of attenuation coefficients in relation to different photon energies for the reference plaque with a compound constituted as shown in the inlet. Note that the correlation is nearly linear in the in the relatively low energy spectrum of interest (i.e. in the range of 10−2 MeV). CAC scoring All datasets were transferred to a dedicated workstation (Advantage AW 4.4, GE Healthcare) running a prototype of a semi-automatic software for CAC scoring (SmartScore 4.0, GE Healthcare) allowing for manual adjustment of the attenuation-based thresholds for CAC scoring. All pixels with an attenuation equal or above the lowest threshold (e.g. ≥130 HU for the standard 120-kVp scans) having an area ≥1 mm2 are automatically colour marked, and lesions are manually selected by creating a region of interest around all lesions found in a coronary artery (Figure 2). The software then calculates the CAC score, as previously described.13 In brief, a score for each region of interest is calculated by multiplying the density score (i.e. the thresholds) and the area of calcifications. A total CAC score is then determined by adding up the scores for each CT slice. Of note, the thresholds for CAC scoring are only applied to pixels with a density equal or larger than the lowest threshold and an area of ≥1 mm2. This eliminates single pixels with a density above the thresholds due to noise. For the 80-kVp and 70-kVp CAC scoring, the novel thresholds were manually entered in the prototype software version (SmartScore 4.0, GE Healthcare). All datasets were analysed by two experienced readers in random order and measurements from both readers were averaged. Figure 2 View largeDownload slide CAC scoring. Example of CAC scoring in an 86-year-old female patient with a BMI of 38 kg/m2 using images derived from a 120-kVp (A), 80-kVp (B), and 70-kVp (C) CT scan. Potential lesions are automatically colour marked (green) and manually allocated to a coronary artery, e.g. in this case to the left anterior descending artery (LAD, purple) and to the left circumflex artery (LCX, yellow). In this particular patient CAC analysis based on the 120-kVp, the 80-kVp, and the 70-kVp scans yielded scores of 362, 347, and 332 in the LAD and of 35, 16, and 10 in the LCX. Figure 2 View largeDownload slide CAC scoring. Example of CAC scoring in an 86-year-old female patient with a BMI of 38 kg/m2 using images derived from a 120-kVp (A), 80-kVp (B), and 70-kVp (C) CT scan. Potential lesions are automatically colour marked (green) and manually allocated to a coronary artery, e.g. in this case to the left anterior descending artery (LAD, purple) and to the left circumflex artery (LCX, yellow). In this particular patient CAC analysis based on the 120-kVp, the 80-kVp, and the 70-kVp scans yielded scores of 362, 347, and 332 in the LAD and of 35, 16, and 10 in the LCX. Based on the CAC score, each patient was allocated to a risk-class: 0, 1–10, 11–100, 101–400, and >400. Risk-class changes for CAC scores derived from 70-kVp and 80-kVp scans were assessed using as a reference the risk-class derived from standard 120-kVp scans. The study was approved by the local ethics committee (KEK-ZH-Nr. 2015-0072), and all patients provided written informed consent. Statistical analysis Quantitative variables are expressed as the mean ± SD or as median with interquartile range (IQR) if not normally distributed. Categorical variables are expressed as frequencies or percentages. The data were tested for normal distribution using the Kolmogorov–Smirnov test. CAC scores derived from 70-kVp and 80-kVp scans were compared with standard 120-kVp scans using intraclass correlation (ICC, absolute agreement) and Bland–Altman (BA) analysis. Sub-analyses were performed for patients with a CAC score ≤400 and ≤100 and for patients with a body mass index (BMI) <35 kg/m2, BMI <30 kg/m2, and BMI <25 kg/m2. Inter-reader agreement was assessed using ICC. Further, measurement of agreement between the different scans with regard to risk classification was tested with the kappa test and the 95% confidence interval is given. Quantitative analysis using reconstructions were compared using repeated-measures analysis of variance (ANOVA), and post hoc pairwise comparisons between were adjusted for multiple comparisons by the Bonferroni correction with a significance level of <0.05. The sample size of 105 patients was based on an equivalence power analysis assuming upper and lower equivalence limits of 25 Agatston units, with a two-sided significance of 0.05 and a power of 0.9. SPSS 22.0 (IBM Corporation, Armonk, NY, USA) software package was used for analysis. A P-value of <0.05 was considered statistically significant. Results Patient baseline characteristics and CAC score risk-classes derived from 120-kVp scans are given in Table 2. Signal, noise, and SNR for the three scan protocols are provided in Table 3. Median CAC score from 120-kVp scans was 212 (IQR 25–901). Using the novel kVp-adapted thresholds, CAC scores derived from 80-kVp scans showed an excellent correlation (r = 0.994, P < 0.001) compared with standard 120-kVp scans with BA analysis revealing a mean difference of −31 (−5.2%) and limits of agreement of −235 (−39.5%) to 172 (28.9%) (Figure 3). Similarly, for CAC scores derived from 70-kVp scans, correlation was excellent (r = 0.972, P < 0.001) but with marked underestimation of −103 (−18.4%) and broader BA limits of agreement of −476 (−85.0%) to 270 (48.2%) (Figure 4). A change in risk-class was observed in 7 (6.8%) patients and in 17 (16.5%) patients, notably mostly to a lower risk-class, after obtaining CAC scores from the 80-kVp and the 70-kVp scans, respectively. Agreement between CAC score-based risk classification derived from 80-kVp and 70-kVp scans as compared with standard 120-kVp scans are given in Tables 4 and 5, respectively. Inter-reader agreement was excellent with ICC coefficients of r = 1.0, r = 0.999, and r = 0.997 for the 120-kVp, the 80-kVp, and the 70-kVp scans, respectively (all P < 0.001) and with BA limits of agreement for the 120-kVp, the 80-kVp, and the 70-kVp scans of −60 (−9.8%) to 57 (9.3%), −115 (−19.8%) to 151 (26.1%), and −154 (−30.3) to 198 (39.0%), respectively. Mean effective radiation dose was 0.60 ± 0.07 mSv, 0.19 ± 0.02 mSv, and 0.12 ± 0.01 mSv for the 120-kVp, the 80-kVp, and the 70-kVp scans, respectively (P < 0.001). Table 2 Patient characteristics (n = 103) Male gender 70 (68) Age (years) 69 ± 10 Body weight (kg) 80 ± 16 (range 43–126) Body size (cm) 170 ± 8 (range 149–189) BMI (kg/m2) 27.9 ± 5.1 (range 17.8–41.2) Cardiovascular risk factors  Smoking 40 (38.8)  Diabetes mellitus 30 (29.1)  Hypertension 72 (69.9)  Dyslipidaemia 48 (46.6)  Positive family history 14 (13.6) Clinical symptoms  Asymptomatic 24 (23.3)  Typical angina pectoris 20 (19.4)  Atypical chest pain 21 (20.4)  Dyspnoea 21 (20.4)  Syncope 3 (2.9) Medication  Antiplatelet therapy 39 (37.8)  Beta-blocker 19 (18.4)  ACI/ARB 56 (54.4)  Statin 7 (6.8)  Oral anticoagulation 10 (9.7) CAC score risk-class  0 13 (12.6)  1–10 7 (6.8)  11–100 22 (21.4)  101–400 22 (21.4)  >400 39 (37.9) Male gender 70 (68) Age (years) 69 ± 10 Body weight (kg) 80 ± 16 (range 43–126) Body size (cm) 170 ± 8 (range 149–189) BMI (kg/m2) 27.9 ± 5.1 (range 17.8–41.2) Cardiovascular risk factors  Smoking 40 (38.8)  Diabetes mellitus 30 (29.1)  Hypertension 72 (69.9)  Dyslipidaemia 48 (46.6)  Positive family history 14 (13.6) Clinical symptoms  Asymptomatic 24 (23.3)  Typical angina pectoris 20 (19.4)  Atypical chest pain 21 (20.4)  Dyspnoea 21 (20.4)  Syncope 3 (2.9) Medication  Antiplatelet therapy 39 (37.8)  Beta-blocker 19 (18.4)  ACI/ARB 56 (54.4)  Statin 7 (6.8)  Oral anticoagulation 10 (9.7) CAC score risk-class  0 13 (12.6)  1–10 7 (6.8)  11–100 22 (21.4)  101–400 22 (21.4)  >400 39 (37.9) Values given are mean ± standard deviation or absolute numbers and percentages in brackets unless otherwise stated. BMI, body mass index; ACI/ARB, Angiotensin-converting enzyme-inhibitors/Angiotensin-receptor antagonist; CAC, coronary artery calcium. Table 2 Patient characteristics (n = 103) Male gender 70 (68) Age (years) 69 ± 10 Body weight (kg) 80 ± 16 (range 43–126) Body size (cm) 170 ± 8 (range 149–189) BMI (kg/m2) 27.9 ± 5.1 (range 17.8–41.2) Cardiovascular risk factors  Smoking 40 (38.8)  Diabetes mellitus 30 (29.1)  Hypertension 72 (69.9)  Dyslipidaemia 48 (46.6)  Positive family history 14 (13.6) Clinical symptoms  Asymptomatic 24 (23.3)  Typical angina pectoris 20 (19.4)  Atypical chest pain 21 (20.4)  Dyspnoea 21 (20.4)  Syncope 3 (2.9) Medication  Antiplatelet therapy 39 (37.8)  Beta-blocker 19 (18.4)  ACI/ARB 56 (54.4)  Statin 7 (6.8)  Oral anticoagulation 10 (9.7) CAC score risk-class  0 13 (12.6)  1–10 7 (6.8)  11–100 22 (21.4)  101–400 22 (21.4)  >400 39 (37.9) Male gender 70 (68) Age (years) 69 ± 10 Body weight (kg) 80 ± 16 (range 43–126) Body size (cm) 170 ± 8 (range 149–189) BMI (kg/m2) 27.9 ± 5.1 (range 17.8–41.2) Cardiovascular risk factors  Smoking 40 (38.8)  Diabetes mellitus 30 (29.1)  Hypertension 72 (69.9)  Dyslipidaemia 48 (46.6)  Positive family history 14 (13.6) Clinical symptoms  Asymptomatic 24 (23.3)  Typical angina pectoris 20 (19.4)  Atypical chest pain 21 (20.4)  Dyspnoea 21 (20.4)  Syncope 3 (2.9) Medication  Antiplatelet therapy 39 (37.8)  Beta-blocker 19 (18.4)  ACI/ARB 56 (54.4)  Statin 7 (6.8)  Oral anticoagulation 10 (9.7) CAC score risk-class  0 13 (12.6)  1–10 7 (6.8)  11–100 22 (21.4)  101–400 22 (21.4)  >400 39 (37.9) Values given are mean ± standard deviation or absolute numbers and percentages in brackets unless otherwise stated. BMI, body mass index; ACI/ARB, Angiotensin-converting enzyme-inhibitors/Angiotensin-receptor antagonist; CAC, coronary artery calcium. Table 3 Image noise and signal ANOVA Bonferroni post hoc tests 120 kVp vs. 80 kVp 80 kVp vs. 70 kVp 120 kVp vs. 70 kVp 120 kVp 80 kVp 70 kVp P-value P-value P-value P-value Signal (HU) 42.8 44.8 46.3 0.006 0.204 0.505 0.004 Noise (HU) 28.8 32.2 32.0 <0.001 <0.001 1.0 <0.001 SNR 1.5 1.4 1.4 0.018 0.014 0.465 0.466 ANOVA Bonferroni post hoc tests 120 kVp vs. 80 kVp 80 kVp vs. 70 kVp 120 kVp vs. 70 kVp 120 kVp 80 kVp 70 kVp P-value P-value P-value P-value Signal (HU) 42.8 44.8 46.3 0.006 0.204 0.505 0.004 Noise (HU) 28.8 32.2 32.0 <0.001 <0.001 1.0 <0.001 SNR 1.5 1.4 1.4 0.018 0.014 0.465 0.466 For signal mean values are given, for noise standard deviation is given. HU, Hounsfield units; SNR, signal-to-noise ratio. Table 3 Image noise and signal ANOVA Bonferroni post hoc tests 120 kVp vs. 80 kVp 80 kVp vs. 70 kVp 120 kVp vs. 70 kVp 120 kVp 80 kVp 70 kVp P-value P-value P-value P-value Signal (HU) 42.8 44.8 46.3 0.006 0.204 0.505 0.004 Noise (HU) 28.8 32.2 32.0 <0.001 <0.001 1.0 <0.001 SNR 1.5 1.4 1.4 0.018 0.014 0.465 0.466 ANOVA Bonferroni post hoc tests 120 kVp vs. 80 kVp 80 kVp vs. 70 kVp 120 kVp vs. 70 kVp 120 kVp 80 kVp 70 kVp P-value P-value P-value P-value Signal (HU) 42.8 44.8 46.3 0.006 0.204 0.505 0.004 Noise (HU) 28.8 32.2 32.0 <0.001 <0.001 1.0 <0.001 SNR 1.5 1.4 1.4 0.018 0.014 0.465 0.466 For signal mean values are given, for noise standard deviation is given. HU, Hounsfield units; SNR, signal-to-noise ratio. Table 4 Agreement of CAC score-based risk classification derived from 80-kVp scans as compared with standard 120-kVp scans 120 kVp 80 kVp CAC score 0 1–10 11–100 101–400 >400 0 13 1 0 0 0 1–10 0 5 3 0 0 11–100 0 1 19 1 0 101–400 0 0 0 21 1 >400 0 0 0 0 38 120 kVp 80 kVp CAC score 0 1–10 11–100 101–400 >400 0 13 1 0 0 0 1–10 0 5 3 0 0 11–100 0 1 19 1 0 101–400 0 0 0 21 1 >400 0 0 0 0 38 Measure of agreement kappa = 0.909. Table 4 Agreement of CAC score-based risk classification derived from 80-kVp scans as compared with standard 120-kVp scans 120 kVp 80 kVp CAC score 0 1–10 11–100 101–400 >400 0 13 1 0 0 0 1–10 0 5 3 0 0 11–100 0 1 19 1 0 101–400 0 0 0 21 1 >400 0 0 0 0 38 120 kVp 80 kVp CAC score 0 1–10 11–100 101–400 >400 0 13 1 0 0 0 1–10 0 5 3 0 0 11–100 0 1 19 1 0 101–400 0 0 0 21 1 >400 0 0 0 0 38 Measure of agreement kappa = 0.909. Table 5 Agreement of CAC score-based risk classification derived from 70-kVp scans as compared with standard 120-kVp scans 120 kVp 70 kVp CAC score 0 1–10 11–100 101–400 >400 0 13 2 2 0 0 1–10 0 4 5 0 0 11–100 0 1 15 4 0 101–400 0 0 0 18 3 >400 0 0 0 0 36 120 kVp 70 kVp CAC score 0 1–10 11–100 101–400 >400 0 13 2 2 0 0 1–10 0 4 5 0 0 11–100 0 1 15 4 0 101–400 0 0 0 18 3 >400 0 0 0 0 36 Measure of agreement kappa = 0.782. Table 5 Agreement of CAC score-based risk classification derived from 70-kVp scans as compared with standard 120-kVp scans 120 kVp 70 kVp CAC score 0 1–10 11–100 101–400 >400 0 13 2 2 0 0 1–10 0 4 5 0 0 11–100 0 1 15 4 0 101–400 0 0 0 18 3 >400 0 0 0 0 36 120 kVp 70 kVp CAC score 0 1–10 11–100 101–400 >400 0 13 2 2 0 0 1–10 0 4 5 0 0 11–100 0 1 15 4 0 101–400 0 0 0 18 3 >400 0 0 0 0 36 Measure of agreement kappa = 0.782. Figure 3 View largeDownload slide Linear regression analysis (A) and Bland–Altman plot (B) comparing CAC scores derived from 80-kVp scans and from standard 120-kVp scans in all patients (n = 103). Bland–Altman limits of agreement were −235 to 172. CAC, coronary artery calcium. Figure 3 View largeDownload slide Linear regression analysis (A) and Bland–Altman plot (B) comparing CAC scores derived from 80-kVp scans and from standard 120-kVp scans in all patients (n = 103). Bland–Altman limits of agreement were −235 to 172. CAC, coronary artery calcium. Figure 4 View largeDownload slide Linear regression analysis (A) and Bland–Altman plot (B) comparing CAC scores derived from 70-kVp scans and from standard 120-kVp scans in all patients (n = 103). Bland–Altman limits of agreement were −476 to 270. CAC, coronary artery calcium. Figure 4 View largeDownload slide Linear regression analysis (A) and Bland–Altman plot (B) comparing CAC scores derived from 70-kVp scans and from standard 120-kVp scans in all patients (n = 103). Bland–Altman limits of agreement were −476 to 270. CAC, coronary artery calcium. In a sub-analysis of 64 (62.1%) patients with a CAC score ≤400, scores derived from 80-kVp scans showed an excellent correlation (r = 0.982, P < 0.001) compared with standard 120-kVp scans with BA analysis revealing a mean difference of −5 (−5.2%) and limits of agreement of −65 (−66.7%) to 55 (56.4%) (Figure 5). For CAC scores derived from 70-kVp scans, correlation was r = 0.917 (P < 0.001) with a mean difference of −28 (−33%) and BA limits of agreement of −134 (−157.8%) to 79 (93%). In this sub-analysis, a change in risk-class was observed in 6 (9.4%) patients and 14 (21.9%) patients, notably mostly to a lower risk-class, after obtaining CAC scores from the 80-kVp and the 70-kVp scans, respectively (see also Tables 4 and 5). In a further sub-analysis of 42 (40.8%) patients with a CAC score ≤100, scores derived from 80-kVp scans showed an excellent correlation (r = 0.958, P < 0.001) compared with standard 120-kVp scans with BA analysis revealing a mean difference of −3 (−10.6%) and limits of agreement of −24 (−102.7%) to 19 (81.2%) (Figure 6). For CAC scores derived from 70-kVp scans correlation was r = 0.853 (P < 0.001) with a mean difference of −13 (−54.0%) and BA limits of agreement of −58 (−298.3%) to 33 (169.7%). In this sub-analysis, a change in risk-class was observed in 5 (11.9%) patients and 10 (23.8%) patients, notably mostly to a lower risk-class, after obtaining CAC scores from the 80-kVp and the 70-kVp scans, respectively (see also Tables 4 and 5). Figure 5 View largeDownload slide Bland–Altman plot comparing CAC scores derived from 80-kVp scans and from standard 120-kVp scans in patients with CAC score ≤400 (n = 64). Bland–Altman limits of agreement were −65 to 55. CAC, coronary artery calcium. Figure 5 View largeDownload slide Bland–Altman plot comparing CAC scores derived from 80-kVp scans and from standard 120-kVp scans in patients with CAC score ≤400 (n = 64). Bland–Altman limits of agreement were −65 to 55. CAC, coronary artery calcium. Figure 6 View largeDownload slide Bland–Altman plot comparing CAC scores derived from 80-kVp scans and from standard 120-kVp scans in patients with CAC score ≤100 (n = 42). Bland–Altman limits of agreement were −24 to 19. CAC, coronary artery calcium. Figure 6 View largeDownload slide Bland–Altman plot comparing CAC scores derived from 80-kVp scans and from standard 120-kVp scans in patients with CAC score ≤100 (n = 42). Bland–Altman limits of agreement were −24 to 19. CAC, coronary artery calcium. In the 92 (89.3%) patients with BMI <35 kg/m2, scores derived from 80-kVp scans showed an excellent correlation (r = 0.997, P < 0.001) compared with standard 120-kVp scans with BA analysis revealing a mean difference of −22 (−3.6%) and limits of agreement of −172 (−27.8%) to 129 (20.9%). For CAC scores derived from 70-kVp scans correlation was r = 0.994 (P < 0.001) with a mean difference of −87 (−14.9%) and BA limits of agreement of −370 (−63.1%) to 196 (33.5%). Five (5.4%) patients and 14 (15.2%) patients in whom CAC scores were derived from 80-kVp and 70-kVp scans, respectively, changed the risk-class (Tables 6 and 7). In the 71 (68.9%) patients with a BMI <30 kg/m2, scores derived from 80-kVp scans showed an excellent correlation (r = 0.997, P < 0.001) compared with standard 120-kVp scans with BA analysis revealing a mean difference of −18 (−2.7%) and limits of agreement of −166 (−25.0%) to 130 (19.6%). For CAC scores derived from 70-kVp scans correlation was r = 0.995 (P < 0.001) with a mean difference of −78 (−12.3%) and BA limits of agreement of −364 (−57.5%) to 208 (32.9%). Two (2.8%) patients changed the risk-class observed for CAC scores derived from the 80-kVp scans but in 6 (8.5%) patients for CAC scores derived from the 70-kVp scans (Tables 8 and 9). Finally, in the 33 (32.0%) patients with a BMI <25 kg/m2, scores derived from 80-kVp scans showed an excellent correlation (r = 0.998, P < 0.001) compared with standard 120-kVp scans with BA analysis revealing a mean difference of −10 (−1.9%) and limits of agreement of −142 (−27.6%) to 122 (23.7%). For CAC scores derived from 70-kVp scans correlation was r = 0.998 (P < 0.001) with a mean difference of −51 (−10.3%) and BA limits of agreement of −303 (−61.3%) to 201 (40.7%). One (3.0%) patient and 2 (6.1%) patients, in whom CAC score was derived from 80-kVp and 70-kVp, respectively, changed the risk-class (Tables 10 and 11). Inter-reader agreement in this subgroup was excellent with ICC coefficients of r = 1.0 for all three scan protocols (P < 0.001). Table 6 Agreement of CAC score risk classes derived from 80-kVp scans as compared with standard 120-kVp scans in patients with BMI <35 kg/m2 (n = 92) 120 kVp 80 kVp CAC score 0 1–10 11–100 101–400 >400 0 11 1 0 0 0 1–10 0 5 2 0 0 11–100 0 1 17 0 0 101–400 0 0 0 20 1 >400 0 0 0 0 34 120 kVp 80 kVp CAC score 0 1–10 11–100 101–400 >400 0 11 1 0 0 0 1–10 0 5 2 0 0 11–100 0 1 17 0 0 101–400 0 0 0 20 1 >400 0 0 0 0 34 Measure of agreement kappa = 0.927. Table 6 Agreement of CAC score risk classes derived from 80-kVp scans as compared with standard 120-kVp scans in patients with BMI <35 kg/m2 (n = 92) 120 kVp 80 kVp CAC score 0 1–10 11–100 101–400 >400 0 11 1 0 0 0 1–10 0 5 2 0 0 11–100 0 1 17 0 0 101–400 0 0 0 20 1 >400 0 0 0 0 34 120 kVp 80 kVp CAC score 0 1–10 11–100 101–400 >400 0 11 1 0 0 0 1–10 0 5 2 0 0 11–100 0 1 17 0 0 101–400 0 0 0 20 1 >400 0 0 0 0 34 Measure of agreement kappa = 0.927. Table 7 Agreement of CAC score risk classes derived from 70-kVp scans as compared with standard 120-kVp scans in patients with BMI <35 kg/m2 (n = 92) 120 kVp 70 kVp CAC score 0 1–10 11–100 101–400 >400 0 11 2 1 0 0 1–10 0 4 4 0 0 11–100 0 1 14 3 0 101–400 0 0 0 17 3 >400 0 0 0 0 32 120 kVp 70 kVp CAC score 0 1–10 11–100 101–400 >400 0 11 2 1 0 0 1–10 0 4 4 0 0 11–100 0 1 14 3 0 101–400 0 0 0 17 3 >400 0 0 0 0 32 Measure of agreement kappa = 0.798. Table 7 Agreement of CAC score risk classes derived from 70-kVp scans as compared with standard 120-kVp scans in patients with BMI <35 kg/m2 (n = 92) 120 kVp 70 kVp CAC score 0 1–10 11–100 101–400 >400 0 11 2 1 0 0 1–10 0 4 4 0 0 11–100 0 1 14 3 0 101–400 0 0 0 17 3 >400 0 0 0 0 32 120 kVp 70 kVp CAC score 0 1–10 11–100 101–400 >400 0 11 2 1 0 0 1–10 0 4 4 0 0 11–100 0 1 14 3 0 101–400 0 0 0 17 3 >400 0 0 0 0 32 Measure of agreement kappa = 0.798. Table 8 Agreement of CAC score-based risk classification derived from 80-kVp scans as compared with standard 120-kVp scans in patients with BMI <30 kg/m2 (n = 71) 120 kVp 80 kVp CAC score 0 1–10 11–100 101–400 >400 0 8 0 0 0 0 1–10 0 4 1 0 0 11–100 0 1 14 0 0 101–400 0 0 0 15 0 >400 0 0 0 0 28 120 kVp 80 kVp CAC score 0 1–10 11–100 101–400 >400 0 8 0 0 0 0 1–10 0 4 1 0 0 11–100 0 1 14 0 0 101–400 0 0 0 15 0 >400 0 0 0 0 28 Measure of agreement kappa = 0.962. Table 8 Agreement of CAC score-based risk classification derived from 80-kVp scans as compared with standard 120-kVp scans in patients with BMI <30 kg/m2 (n = 71) 120 kVp 80 kVp CAC score 0 1–10 11–100 101–400 >400 0 8 0 0 0 0 1–10 0 4 1 0 0 11–100 0 1 14 0 0 101–400 0 0 0 15 0 >400 0 0 0 0 28 120 kVp 80 kVp CAC score 0 1–10 11–100 101–400 >400 0 8 0 0 0 0 1–10 0 4 1 0 0 11–100 0 1 14 0 0 101–400 0 0 0 15 0 >400 0 0 0 0 28 Measure of agreement kappa = 0.962. Table 9 Agreement of CAC score risk classes derived from 70-kVp scans as compared with standard 120-kVp scans in patients with BMI <30 kg/m2 (n = 71) 120 kVp 70 kVp CAC score 0 1–10 11–100 101–400 >400 0 8 0 0 0 0 1–10 0 4 3 0 0 11–100 0 1 12 1 0 101–400 0 0 0 14 1 >400 0 0 0 0 27 120 kVp 70 kVp CAC score 0 1–10 11–100 101–400 >400 0 8 0 0 0 0 1–10 0 4 3 0 0 11–100 0 1 12 1 0 101–400 0 0 0 14 1 >400 0 0 0 0 27 Measure of agreement kappa = 0.886. Table 9 Agreement of CAC score risk classes derived from 70-kVp scans as compared with standard 120-kVp scans in patients with BMI <30 kg/m2 (n = 71) 120 kVp 70 kVp CAC score 0 1–10 11–100 101–400 >400 0 8 0 0 0 0 1–10 0 4 3 0 0 11–100 0 1 12 1 0 101–400 0 0 0 14 1 >400 0 0 0 0 27 120 kVp 70 kVp CAC score 0 1–10 11–100 101–400 >400 0 8 0 0 0 0 1–10 0 4 3 0 0 11–100 0 1 12 1 0 101–400 0 0 0 14 1 >400 0 0 0 0 27 Measure of agreement kappa = 0.886. Table 10 Agreement of CAC score-based risk classification derived from 80-kVp scans as compared with standard 120-kVp scans in patients with BMI <25 kg/m2 (n = 33) 120 kVp 80 kVp CAC score 0 1–10 11–100 101–400 >400 0 2 0 0 0 0 1–10 0 3 0 0 0 11–100 0 1 8 0 0 101–400 0 0 0 9 0 >400 0 0 0 0 10 120 kVp 80 kVp CAC score 0 1–10 11–100 101–400 >400 0 2 0 0 0 0 1–10 0 3 0 0 0 11–100 0 1 8 0 0 101–400 0 0 0 9 0 >400 0 0 0 0 10 Measure of agreement kappa = 0.960. Table 10 Agreement of CAC score-based risk classification derived from 80-kVp scans as compared with standard 120-kVp scans in patients with BMI <25 kg/m2 (n = 33) 120 kVp 80 kVp CAC score 0 1–10 11–100 101–400 >400 0 2 0 0 0 0 1–10 0 3 0 0 0 11–100 0 1 8 0 0 101–400 0 0 0 9 0 >400 0 0 0 0 10 120 kVp 80 kVp CAC score 0 1–10 11–100 101–400 >400 0 2 0 0 0 0 1–10 0 3 0 0 0 11–100 0 1 8 0 0 101–400 0 0 0 9 0 >400 0 0 0 0 10 Measure of agreement kappa = 0.960. Table 11 Agreement of CAC score risk classes derived from 70-kVp scans as compared with standard 120-kVp scans in patients with BMI <25 kg/m2 (n = 33) 120 kVp 70 kVp CAC score 0 1–10 11–100 101–400 >400 0 2 0 0 0 0 1–10 0 3 1 0 0 11–100 0 1 7 0 0 101–400 0 0 0 9 0 >400 0 0 0 0 10 120 kVp 70 kVp CAC score 0 1–10 11–100 101–400 >400 0 2 0 0 0 0 1–10 0 3 1 0 0 11–100 0 1 7 0 0 101–400 0 0 0 9 0 >400 0 0 0 0 10 Measure of agreement kappa = 0.920. Table 11 Agreement of CAC score risk classes derived from 70-kVp scans as compared with standard 120-kVp scans in patients with BMI <25 kg/m2 (n = 33) 120 kVp 70 kVp CAC score 0 1–10 11–100 101–400 >400 0 2 0 0 0 0 1–10 0 3 1 0 0 11–100 0 1 7 0 0 101–400 0 0 0 9 0 >400 0 0 0 0 10 120 kVp 70 kVp CAC score 0 1–10 11–100 101–400 >400 0 2 0 0 0 0 1–10 0 3 1 0 0 11–100 0 1 7 0 0 101–400 0 0 0 9 0 >400 0 0 0 0 10 Measure of agreement kappa = 0.920. Of note, no misclassification from or to a zero CAC score was found for neither the 80-kVp nor the 70-kVp scans in the subpopulation with a BMI <30 kg/m2. Average CAC scores in each risk-class based on the 120-kVp classification and average differences in each risk-class (i.e. 80 kVp and 70 kVp compared with 120 kVp) are depicted in Table 12. Table 12 Average CAC score in each risk-class based on the 120-kVp classification and average differences in each risk-class (i.e. 80 kVp and 70 kVp compared with 120 kVp) CAC category Mean CAC score-based on 120 kVp Mean Δ CAC score 120 kVp 80 kVp 70 kVp 120 kVp–80 kVp 120 kVp–70 kVp 0 0 0 0 0 0 1–10 6 4 2 2 4 11–100 45 40 26 5 19 101–400 243 234 181 9 62 >400 1450 1377 1224 73 226 CAC category Mean CAC score-based on 120 kVp Mean Δ CAC score 120 kVp 80 kVp 70 kVp 120 kVp–80 kVp 120 kVp–70 kVp 0 0 0 0 0 0 1–10 6 4 2 2 4 11–100 45 40 26 5 19 101–400 243 234 181 9 62 >400 1450 1377 1224 73 226 Table 12 Average CAC score in each risk-class based on the 120-kVp classification and average differences in each risk-class (i.e. 80 kVp and 70 kVp compared with 120 kVp) CAC category Mean CAC score-based on 120 kVp Mean Δ CAC score 120 kVp 80 kVp 70 kVp 120 kVp–80 kVp 120 kVp–70 kVp 0 0 0 0 0 0 1–10 6 4 2 2 4 11–100 45 40 26 5 19 101–400 243 234 181 9 62 >400 1450 1377 1224 73 226 CAC category Mean CAC score-based on 120 kVp Mean Δ CAC score 120 kVp 80 kVp 70 kVp 120 kVp–80 kVp 120 kVp–70 kVp 0 0 0 0 0 0 1–10 6 4 2 2 4 11–100 45 40 26 5 19 101–400 243 234 181 9 62 >400 1450 1377 1224 73 226 Discussion This is the first in vivo study demonstrating the feasibility and accuracy of CAC scoring with reduced peak tube voltages of 80 kVp and 70 kVp using kVp-adapted thresholds. Compared with standard 120-kVp CAC scanning, lower peak tube voltages of 80 kVp and 70 kVp led to a mean radiation dose of 0.19 mSv and 0.12 mSv, respectively, representing a reduction of 68% and 80%, compared with the standard 120-kVp protocol which resulted in a radiation dose exposure of 0.60 mSv. There was an only minimal underestimation of the CAC scores as compared with the standard 120-kVp protocol with narrower absolute BA limits of agreement for lower CAC scores and lower BMI. Underestimation was marked and limits of agreement were broader with increasing CAC scores and BMI. However, in high-risk patients with a CAC score >400, a broader variation may well be acceptable due to the lower reclassification rate, and therefore, without any impact on adjustment in treatment strategies. Risk-class changes were rare and mainly observed in patients with high BMI, most probably due to the greater degree of tissue attenuation and increased image noise in this subgroup.19 This notion is corroborated in particular by the findings of a distinct outlier (see Figures 3 and 4) with a BMI of 35 kg/m2 and marked abdominal obesity in whom the entire inferior left ventricular wall was severely attenuated in the low tube voltage scans, rendering the coronary calcifications practically undetectable, hence resulting in a substantial underestimation of the CAC scores. The fact that only a few reclassifications were observed for CAC scores derived from 80-kVp in patients with a BMI <35 kg/m2 and for scores derived from 70-kVp in patients with a BMI <30 kg/m2 and with no misclassifications from or to a zero CAC score in the subpopulation with a BMI <30 kg/m2, suggests the potential use of a BMI-adapted peak tube voltage approach in daily clinical routine where 120-kVp, 80-kVp, and 70-kVp scans are used for patients with a BMI ≥30 kg/m2, <30 kg/m2, and <25 kg/m2, respectively. However, while the present pilot study includes a population with a relatively broad range of BMI, the sample size may not be large enough to give recommendations to change clinical practice as of yet. However, it offers suggestions to be validated in larger cohorts. A few prior studies have assessed CAC scanning with reduced peak tube voltage. In the study of Jakobs et al.,20 radiation dose was reduced by 65% by applying an 80-kVp protocol compared with the standard 120-kVp protocol. However, the study did not assess Agatston scores but rather the calcium mass derived from the scan—a parameter that is not widely used for risk stratification in clinical routine. Furthermore, retrospective ECG-gating was used, yielding mean radiation dose exposures of 0.72 mSv with the 80-kVp protocol. In a more recent study, Tesche et al.21 could demonstrate excellent agreement between a standard 120-kVp and a tin-filtration 100-kVp protocol, yielding accurate Agatston scores with very few misclassifications at a low mean radiation dose exposure of only 0.19 ± 0.05 with the new protocol. While the approach suggested by Tesche et al. is unquestionably interesting, it’s generalizability remains limited because the applied tin-filtration is a vendor-specific tool. By contrast, our study theoretically paves the way for ultra-low-dose CAC scoring independent of site- or vendor-specific prerequisites. In a further study by Nakazato et al., 60 consecutive patients were scanned with standard 120 kVp and with 100 kVp. In this study, however, only the lower threshold of 130 HU was adapted to 100 kVp for CAC scoring by simply calculating the ratio of attenuation of a plaque at 100 kVp over its attenuation at 120 kVp. By contrast, our approach is based on a mathematical model enabling adaption not only of the lowest but of all thresholds and potentially for any given peak tube voltage, which may yield more accurate results because CAC scoring is based not only on the lowest threshold but also incorporates the scores 2–4, which accounts for substantial deviation from the true total score if the thresholds for these higher scores are not properly adapted to the tube voltage in use. However, a direct comparison with the results from Nakazato et al.12 is difficult, due to the limited range of CAC as compared with the present study. Moreover, while tube current was increased by 30% in the study by Nakazato et al., it remained unchanged for all scans in the present study, contributing to a further reduction in effective radiation exposure. Marwan et al. also reduced peak tube voltage from ECG-triggered high-pitch 120-kVp to 100-kVp protocol and could significantly reduce radiation dose from 0.3 mSv to 0.2 mSv. CAC scores measured from 100-kVp scans while maintaining the 130 HU thresholds were overestimated when compared with the standard protocol of 120 kVp. However, agreement improved when a threshold of 147 HU was applied for the 100-kVp protocol. Similar to our study, a minority of patients (3.4%) were reclassified to a different risk-class if CAC scores were obtained from a 100-kVp scan, although this was observed towards a higher risk-class which is to be expected if only the lowest threshold is adapted. This is in contrast to our results where reclassification was mostly seen towards lower risk-classes. This might be due to the fact that on the one hand, in the study by Nakazato et al.12 and Marwan et al.11 only the lower threshold of 130 HU was adapted to 147 HU, while our novel thresholds are increasingly higher than the original thresholds at 120 kVp with decreasing tube voltage, thus compensating for the higher plaque attenuation at lower photon energies. On the other hand, increasing noise at lower tube voltages while using a fixed tube current may have led to a shift towards underestimation. Finally, in the present study, all patients were included in the final analysis, regardless of image noise. This reflects an intention-to-diagnose approach and stands in contrast with the previous study by Marwan et al. where patients were excluded due to excessive image noise. Of note, our calculated lower threshold of 145 HU for a 100-kVp protocol is very similar the 147 HU threshold proposed in the above-mentioned studies.11,12 Furthermore, our calculated lower threshold of 177 HU for the 80-kVp protocol is comparable to a phantom study suggesting a threshold of 187 HU.22 Some recent studies have applied iterative reconstruction in order to reduce image noise at lower tube currents,23–25 while other studies have suggested that the application of iterative reconstruction algorithms on 120-kVp scans has per se an impact on CAC measurements, generally leading to underestimation of CAC scores.13,26,27 In the present study, we have used a fixed tube current and have refrained from applying iterative reconstruction algorithms so as not to introduce a confounder. Future studies will need to clarify if the use of iterative reconstruction algorithms confers added value for ultra-low-dose CAC scoring at very low peak tube voltages. If this was the case, the results of the present study may pave the way for even more reduction in radiation dose exposure as it would allow additional lowering of the tube current while applying iterative reconstruction for compensation of increasing noise. Although our results suggest that CAC protocols with low tube voltage offer a substantial potential of radiation dose reduction, it should be taken into consideration that this is achieved in a setting of sub-millisievert exposure and it remains an issue of ongoing debate whether ionizing radiation of this magnitude is of any clinical relevance on the patient level.28 Against this background, it is up to debate whether a decline in accuracy brought upon by applying an ultra-low-dose CAC protocol is justified. However, CAC scoring is mainly a tool for risk stratification and the results from this pilot study suggests a very low rate of reclassifications particularly if a BMI-adapted approach is applied. Considering the fact that the number of CT examinations for CAC assessment is constantly increasing, any further reduction of radiation exposure may translate into a reduced radiation-related risk not only on a patient but also on a population-level, justifying the trade-off between image quality and radiation exposure while following the principle of ALARA as suggested by a recent European report.28 Limitations It may be perceived as a limitation that we have refrained from including more patients with a zero CAC score. However, we felt that it was imperative for a pilot study with a limited patient population to include patients with a broad range of CAC scores to validate our thresholds for CAC scoring even at the upper range of CAC scores which may be encountered in clinical routine. Consecutive inclusion of patients would have led to a large proportion of the sampled population having zero CAC scores, rendering an assessment of accuracy difficult. Hence, the number of patients with a CAC score of zero was prospectively limited. Furthermore, as the focus of this pilot study was to assess the validity of the novel thresholds which are only dependent on tube voltage, we have refrained from applying other adjustments such as adaption of the tube current to BMI so as not to introduce an additional confounder. Moreover, by using a 200 mA tube current for the standard of reference, it is unlikely that it was negatively affected by noise at tube voltages of 120-kVp even in patients with a high BMI. Finally, it may be argued that the thresholds presented in this study are imperfect because they are based on assumptions with regard to the plaque composition that was used by Agatston et al.15 However, it is difficult to comment on the magnitude of such potential imperfection and it seems impossible to find a perfect solution because aside from requiring new thresholds, lowering the tube voltage in CT scanning inevitably at the same time introduces increased image noise which in turn affects CAC scoring as well. The latter is reflected by the observation that a BMI-adapted protocol yields more accurate results. Conclusions The present pilot study suggests that CAC scoring with reduced peak tube voltage is accurate if kVp-adapted thresholds for calculation of CAC scores are applied while offering a radiation dose reduction of up to 80%. Conflict of interest: The University Hospital Zurich holds a research agreement with GE Healthcare. 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Strategies for radiation dose reduction in nuclear cardiology and cardiac computed tomography imaging: a report from the European Association of Cardiovascular Imaging (EACVI), the Cardiovascular Committee of European Association of Nuclear Medicine (EANM), and the European Society of Cardiovascular Radiology (ESCR) . Eur Heart J 2018 ; 39 : 286 – 96 . Google Scholar PubMed Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Heart Journal – Cardiovascular Imaging Oxford University Press

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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.
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Abstract

Abstract Aims To determine if tube-adapted thresholds for coronary artery calcium (CAC) scoring by computed tomography at 80 kilovolt-peak (kVp) tube voltage and 70-kVp yield comparable results to the standard 120-kVp protocol. Methods and results We prospectively included 103 patients who underwent standard scanning with 120-kVp tube voltage and additional scans with 80 kVp and 70 kVp. Mean body mass index (BMI) was 27.9 ± 5.1 kg/m2. For the lowered tube voltages, we applied novel kVp-adapted thresholds for calculation of CAC scores and compared them with standard 120-kVp scans using intraclass correlation and Bland–Altman (BA) analysis. Furthermore, risk-class (CAC score 0/1–10/11–100/101–400/>400) changes were assessed. Median CAC score from 120-kVp scans was 212 (interquartile range 25–901). Thirteen (12.6%) patients had zero CAC. Using the novel kVp-adapted thresholds, CAC scores derived from 80-kVp scans showed excellent correlation (r = 0.994, P < 0.001) with standard 120-kVp scans with BA limits of agreement of −235 (−39.5%) to 172 (28.9%). Similarly, for 70-kVp scans, correlation was excellent (r = 0.972, P < 0.001) but with broader limits of agreement of −476 (−85.0%) to 270 (48.2%). Only 2 (2.8%) reclassifications were observed for the 80-kVp scans in patients with a BMI <30 kg/m2 (n = 71), and 2 (6.1%) for the 70-kVp scans in patients with a BMI <25 kg/m2 (n = 33). Mean effective radiation dose was 0.60 ± 0.07 millisieverts (mSv), 0.19 ± 0.02 mSv, and 0.12 ± 0.01 mSv for the 120-kVp, 80-kVp, and 70-kVp scans, respectively. Conclusion The present study suggests that CAC scoring with reduced peak tube voltage is accurate if kVp-adapted thresholds for calculation of CAC scores are applied while offering a substantial further radiation dose reduction. coronary artery calcium scoring, computed tomography, radiation dose, low-dose Introduction Coronary artery calcium (CAC) scoring by non-contrast cardiac computed tomography (CT) is a well-established predictor of coronary artery disease events and provides incremental information over standard coronary risk factors.1,2 A recent study reported on a very low mortality rate in patients with zero CAC which increased progressively with higher CAC score risk-classes (1–99, 100–399, and ≥400) over a long-term follow-up of up to 15 years.3 Although the radiation exposure from CAC scanning is low, the theoretical association of cancer caused by ionizing radiation raises concerns to the public and physicians likewise.4 In line with the basic principle of ‘as low as reasonably achievable (ALARA)’, radiation exposure from CAC scanning has steadily decreased in recent years and now lies in the range of ∼1–1.5 millisievert (mSv) in daily clinical routine.5 Meanwhile, however, radiation dose exposure from coronary CT angiography could be lowered much more substantially and, with latest-generation equipment, diagnostic image quality can now be routinely acquired using only a fraction of the dose necessary for obtaining CAC scores,6–8 emphasizing the need for further improvement in CAC scanning, where prior attempts towards lowering radiation dose were mainly focused on lowering tube currents.9,10 However, the greatest radiation dose reduction can be obtained by reducing peak tube voltage and past studies have shown a significant radiation dose reduction with 100 kilovoltage peak (kVp) scans.11,12 Yet lowering peak tube voltage remains challenging because tissue attenuation is closely related to photon energy, thus rendering the established thresholds for calculating CAC scores (i.e. Agatston scores) incomparable if peak tube voltages other than the standard 120 kVp are applied.11,12 In this pilot study, we aimed to determine whether CAC scoring based on CT scan protocols with peak tube voltages of 80-kVp and 70-kVp yields comparable results to the standard 120-kVp protocol if novel attenuation-based, and kVp-adapted thresholds are applied. Methods Patient population We prospectively included 105 patients without a history of revascularization or intracardiac defibrillator/pacemaker who were referred for clinically indicated single photon emission tomography and additional CAC scoring. CAC scoring was performed on the latest generation 256-slice CT scanner (Revolution CT, GE Healthcare, Waukesha, WI, USA). Of note, after inclusion of 13 patients with zero CAC, only patients with CAC score >0 were consecutively included afterwards. Two patients had to be excluded because of technical reasons not allowing reconstruction of some or all datasets. Thus, 103 patients were included in the final analysis. Scan protocols, image reconstruction, and image analysis All patients underwent the standard scanning protocol with 120 kVp and two additional scans with 80 kVp and 70 kVp immediately afterwards. Tube current was set to 200 milliampere (mA). All scans were performed in cranio-caudal direction during inspiratory breath-hold with prospective electrocardiogram (ECG)-triggering as previously reported.6 The scanning parameters included 256 × 0.625 mm collimation with a z-coverage of 12–16 cm and a display field of view of 25 cm with a slice thickness, and an increment of 2.5 mm was reconstructed. Gantry rotation time was 280 ms.6 Images were reconstructed using filtered back projection.13 With the exception of peak tube voltage, for each triplet of scans, the scanning parameters were identical. Values for effective radiation dose were calculated by multiplying the dose length product with a tube voltage dependent conversion factor (i.e. 0.0145 mSv × mGy−1 × cm−1 for 120 kVp and 0.0147 mSv × mGy−1 × cm−1 for 80 kVp and 70 kVp) as previously described.14 For every patient, the aortic root was examined at the level of the left main coronary artery on an axial image using a region of interest with a 20 mm diameter to measure mean attenuation (representing signal) and its standard deviation (SD) (representing noise) in Hounsfield units (HU) in order to calculate the signal-to-noise ratio (SNR). Novel kVp-adapted thresholds for CAC scoring X-ray attenuation is non-linearly and strongly dependent on the photon energy, which in turn depends on peak tube voltage used for CT imaging. For elements with a high effective atomic number (z) such as calcium, decreasing the photon energy (i.e. from 120 to 70 kVp) results in a substantial increase in CT attenuation number because of a higher absorption of calcium at low-photon energy levels. Therefore, the thresholds as established by Agatston et al.15 are not applicable to other tube currents. Attempting to overcome this limitation, we have mathematically derived novel thresholds for calculation of the CAC score for various peak tube voltage settings. From the initial study by Agatston et al.,15 it remains unclear what the exact material density of the reference plaque for establishing the scoring threshold was. By using linear attenuation coefficients derived from The National Institute of Standards and Technology (NIST) XCOM photon cross-sections database (Standard Reference Database 8, XGAM),16 we identified for the reference plaque a material composition containing phosphorus pentoxide (P2O5), calcium (Ca), magnesium oxide (MgO), hydrogen (H), carbon (C), and oxygen (O),17,18 with an attenuation coefficient of 0.1823 cm2/g which yields attenuation of 130 HU at 120-kV photon energy (Figure 1) while offering a composition of elements that are likely to constitute a coronary artery plaque. From these attenuation coefficients derived from the photon cross-sections database and taking into account differing attenuation for water at different kV, we calculated from the original thresholds the novel kVp-adapted thresholds for 70 kVp and 80 kVp assuming coherent scattering and a linear relationship between attenuation coefficients and photon energy in the relatively low energy spectrum of interest [i.e. between 10−2 and 10−1 megaelectron volts (MeV), Figure 1] by calculating the ratio between the attenuation coefficients at standard 120-kV photon energy vs. 100-kV, 80-kV, and 70-kV photon energies and have used this value as a coefficient to calculate the new thresholds from the original ones at each energy level. Our calculations led to the kVp-adapted thresholds for CAC scores given in Table 1. These thresholds for CAC score calculation with 70-kVp and 80-kVp scans were then validated in the present study population against the CAC scores derived from 120-kVp scans and based on the commonly used thresholds by Agatston et al.15 Table 1 Novel kVp-adapted thresholds Thresholds (HU) for lesion scores Tube voltage (kVp) 1 2 3 4 120 130–199 200–299 300–399 ≥400 100 145–222 223–334 335–446 ≥447 80 177–271 272–408 409–544 ≥545 70 207–318 319–477 478–636 ≥637 Thresholds (HU) for lesion scores Tube voltage (kVp) 1 2 3 4 120 130–199 200–299 300–399 ≥400 100 145–222 223–334 335–446 ≥447 80 177–271 272–408 409–544 ≥545 70 207–318 319–477 478–636 ≥637 Attenuation-based and kVp-adapted thresholds for calculation of CAC scores. Thresholds for 120 kVp are derived from Agatston et al.15 and represent the standard of reference. The calculated thresholds for 100 kVp are given for comparative purposes. In brief, according to the method developed by Agatston et al.,15 a total CAC score is calculated by applying for each region of interest drawn around a coronary lesion the above-mentioned lesions scores according to the maximal HU measured within this region, multiplying it with the area, and summing these scores for all CT slices. Note that the thresholds for applying any given score increase with decreasing kVp as lower kVp lead to higher HU for a given lesion. kVp, kilovolt-peak; HU, Hounsfield units. Table 1 Novel kVp-adapted thresholds Thresholds (HU) for lesion scores Tube voltage (kVp) 1 2 3 4 120 130–199 200–299 300–399 ≥400 100 145–222 223–334 335–446 ≥447 80 177–271 272–408 409–544 ≥545 70 207–318 319–477 478–636 ≥637 Thresholds (HU) for lesion scores Tube voltage (kVp) 1 2 3 4 120 130–199 200–299 300–399 ≥400 100 145–222 223–334 335–446 ≥447 80 177–271 272–408 409–544 ≥545 70 207–318 319–477 478–636 ≥637 Attenuation-based and kVp-adapted thresholds for calculation of CAC scores. Thresholds for 120 kVp are derived from Agatston et al.15 and represent the standard of reference. The calculated thresholds for 100 kVp are given for comparative purposes. In brief, according to the method developed by Agatston et al.,15 a total CAC score is calculated by applying for each region of interest drawn around a coronary lesion the above-mentioned lesions scores according to the maximal HU measured within this region, multiplying it with the area, and summing these scores for all CT slices. Note that the thresholds for applying any given score increase with decreasing kVp as lower kVp lead to higher HU for a given lesion. kVp, kilovolt-peak; HU, Hounsfield units. Figure 1 View largeDownload slide Plot of attenuation coefficients in relation to different photon energies for the reference plaque with a compound constituted as shown in the inlet. Note that the correlation is nearly linear in the in the relatively low energy spectrum of interest (i.e. in the range of 10−2 MeV). Figure 1 View largeDownload slide Plot of attenuation coefficients in relation to different photon energies for the reference plaque with a compound constituted as shown in the inlet. Note that the correlation is nearly linear in the in the relatively low energy spectrum of interest (i.e. in the range of 10−2 MeV). CAC scoring All datasets were transferred to a dedicated workstation (Advantage AW 4.4, GE Healthcare) running a prototype of a semi-automatic software for CAC scoring (SmartScore 4.0, GE Healthcare) allowing for manual adjustment of the attenuation-based thresholds for CAC scoring. All pixels with an attenuation equal or above the lowest threshold (e.g. ≥130 HU for the standard 120-kVp scans) having an area ≥1 mm2 are automatically colour marked, and lesions are manually selected by creating a region of interest around all lesions found in a coronary artery (Figure 2). The software then calculates the CAC score, as previously described.13 In brief, a score for each region of interest is calculated by multiplying the density score (i.e. the thresholds) and the area of calcifications. A total CAC score is then determined by adding up the scores for each CT slice. Of note, the thresholds for CAC scoring are only applied to pixels with a density equal or larger than the lowest threshold and an area of ≥1 mm2. This eliminates single pixels with a density above the thresholds due to noise. For the 80-kVp and 70-kVp CAC scoring, the novel thresholds were manually entered in the prototype software version (SmartScore 4.0, GE Healthcare). All datasets were analysed by two experienced readers in random order and measurements from both readers were averaged. Figure 2 View largeDownload slide CAC scoring. Example of CAC scoring in an 86-year-old female patient with a BMI of 38 kg/m2 using images derived from a 120-kVp (A), 80-kVp (B), and 70-kVp (C) CT scan. Potential lesions are automatically colour marked (green) and manually allocated to a coronary artery, e.g. in this case to the left anterior descending artery (LAD, purple) and to the left circumflex artery (LCX, yellow). In this particular patient CAC analysis based on the 120-kVp, the 80-kVp, and the 70-kVp scans yielded scores of 362, 347, and 332 in the LAD and of 35, 16, and 10 in the LCX. Figure 2 View largeDownload slide CAC scoring. Example of CAC scoring in an 86-year-old female patient with a BMI of 38 kg/m2 using images derived from a 120-kVp (A), 80-kVp (B), and 70-kVp (C) CT scan. Potential lesions are automatically colour marked (green) and manually allocated to a coronary artery, e.g. in this case to the left anterior descending artery (LAD, purple) and to the left circumflex artery (LCX, yellow). In this particular patient CAC analysis based on the 120-kVp, the 80-kVp, and the 70-kVp scans yielded scores of 362, 347, and 332 in the LAD and of 35, 16, and 10 in the LCX. Based on the CAC score, each patient was allocated to a risk-class: 0, 1–10, 11–100, 101–400, and >400. Risk-class changes for CAC scores derived from 70-kVp and 80-kVp scans were assessed using as a reference the risk-class derived from standard 120-kVp scans. The study was approved by the local ethics committee (KEK-ZH-Nr. 2015-0072), and all patients provided written informed consent. Statistical analysis Quantitative variables are expressed as the mean ± SD or as median with interquartile range (IQR) if not normally distributed. Categorical variables are expressed as frequencies or percentages. The data were tested for normal distribution using the Kolmogorov–Smirnov test. CAC scores derived from 70-kVp and 80-kVp scans were compared with standard 120-kVp scans using intraclass correlation (ICC, absolute agreement) and Bland–Altman (BA) analysis. Sub-analyses were performed for patients with a CAC score ≤400 and ≤100 and for patients with a body mass index (BMI) <35 kg/m2, BMI <30 kg/m2, and BMI <25 kg/m2. Inter-reader agreement was assessed using ICC. Further, measurement of agreement between the different scans with regard to risk classification was tested with the kappa test and the 95% confidence interval is given. Quantitative analysis using reconstructions were compared using repeated-measures analysis of variance (ANOVA), and post hoc pairwise comparisons between were adjusted for multiple comparisons by the Bonferroni correction with a significance level of <0.05. The sample size of 105 patients was based on an equivalence power analysis assuming upper and lower equivalence limits of 25 Agatston units, with a two-sided significance of 0.05 and a power of 0.9. SPSS 22.0 (IBM Corporation, Armonk, NY, USA) software package was used for analysis. A P-value of <0.05 was considered statistically significant. Results Patient baseline characteristics and CAC score risk-classes derived from 120-kVp scans are given in Table 2. Signal, noise, and SNR for the three scan protocols are provided in Table 3. Median CAC score from 120-kVp scans was 212 (IQR 25–901). Using the novel kVp-adapted thresholds, CAC scores derived from 80-kVp scans showed an excellent correlation (r = 0.994, P < 0.001) compared with standard 120-kVp scans with BA analysis revealing a mean difference of −31 (−5.2%) and limits of agreement of −235 (−39.5%) to 172 (28.9%) (Figure 3). Similarly, for CAC scores derived from 70-kVp scans, correlation was excellent (r = 0.972, P < 0.001) but with marked underestimation of −103 (−18.4%) and broader BA limits of agreement of −476 (−85.0%) to 270 (48.2%) (Figure 4). A change in risk-class was observed in 7 (6.8%) patients and in 17 (16.5%) patients, notably mostly to a lower risk-class, after obtaining CAC scores from the 80-kVp and the 70-kVp scans, respectively. Agreement between CAC score-based risk classification derived from 80-kVp and 70-kVp scans as compared with standard 120-kVp scans are given in Tables 4 and 5, respectively. Inter-reader agreement was excellent with ICC coefficients of r = 1.0, r = 0.999, and r = 0.997 for the 120-kVp, the 80-kVp, and the 70-kVp scans, respectively (all P < 0.001) and with BA limits of agreement for the 120-kVp, the 80-kVp, and the 70-kVp scans of −60 (−9.8%) to 57 (9.3%), −115 (−19.8%) to 151 (26.1%), and −154 (−30.3) to 198 (39.0%), respectively. Mean effective radiation dose was 0.60 ± 0.07 mSv, 0.19 ± 0.02 mSv, and 0.12 ± 0.01 mSv for the 120-kVp, the 80-kVp, and the 70-kVp scans, respectively (P < 0.001). Table 2 Patient characteristics (n = 103) Male gender 70 (68) Age (years) 69 ± 10 Body weight (kg) 80 ± 16 (range 43–126) Body size (cm) 170 ± 8 (range 149–189) BMI (kg/m2) 27.9 ± 5.1 (range 17.8–41.2) Cardiovascular risk factors  Smoking 40 (38.8)  Diabetes mellitus 30 (29.1)  Hypertension 72 (69.9)  Dyslipidaemia 48 (46.6)  Positive family history 14 (13.6) Clinical symptoms  Asymptomatic 24 (23.3)  Typical angina pectoris 20 (19.4)  Atypical chest pain 21 (20.4)  Dyspnoea 21 (20.4)  Syncope 3 (2.9) Medication  Antiplatelet therapy 39 (37.8)  Beta-blocker 19 (18.4)  ACI/ARB 56 (54.4)  Statin 7 (6.8)  Oral anticoagulation 10 (9.7) CAC score risk-class  0 13 (12.6)  1–10 7 (6.8)  11–100 22 (21.4)  101–400 22 (21.4)  >400 39 (37.9) Male gender 70 (68) Age (years) 69 ± 10 Body weight (kg) 80 ± 16 (range 43–126) Body size (cm) 170 ± 8 (range 149–189) BMI (kg/m2) 27.9 ± 5.1 (range 17.8–41.2) Cardiovascular risk factors  Smoking 40 (38.8)  Diabetes mellitus 30 (29.1)  Hypertension 72 (69.9)  Dyslipidaemia 48 (46.6)  Positive family history 14 (13.6) Clinical symptoms  Asymptomatic 24 (23.3)  Typical angina pectoris 20 (19.4)  Atypical chest pain 21 (20.4)  Dyspnoea 21 (20.4)  Syncope 3 (2.9) Medication  Antiplatelet therapy 39 (37.8)  Beta-blocker 19 (18.4)  ACI/ARB 56 (54.4)  Statin 7 (6.8)  Oral anticoagulation 10 (9.7) CAC score risk-class  0 13 (12.6)  1–10 7 (6.8)  11–100 22 (21.4)  101–400 22 (21.4)  >400 39 (37.9) Values given are mean ± standard deviation or absolute numbers and percentages in brackets unless otherwise stated. BMI, body mass index; ACI/ARB, Angiotensin-converting enzyme-inhibitors/Angiotensin-receptor antagonist; CAC, coronary artery calcium. Table 2 Patient characteristics (n = 103) Male gender 70 (68) Age (years) 69 ± 10 Body weight (kg) 80 ± 16 (range 43–126) Body size (cm) 170 ± 8 (range 149–189) BMI (kg/m2) 27.9 ± 5.1 (range 17.8–41.2) Cardiovascular risk factors  Smoking 40 (38.8)  Diabetes mellitus 30 (29.1)  Hypertension 72 (69.9)  Dyslipidaemia 48 (46.6)  Positive family history 14 (13.6) Clinical symptoms  Asymptomatic 24 (23.3)  Typical angina pectoris 20 (19.4)  Atypical chest pain 21 (20.4)  Dyspnoea 21 (20.4)  Syncope 3 (2.9) Medication  Antiplatelet therapy 39 (37.8)  Beta-blocker 19 (18.4)  ACI/ARB 56 (54.4)  Statin 7 (6.8)  Oral anticoagulation 10 (9.7) CAC score risk-class  0 13 (12.6)  1–10 7 (6.8)  11–100 22 (21.4)  101–400 22 (21.4)  >400 39 (37.9) Male gender 70 (68) Age (years) 69 ± 10 Body weight (kg) 80 ± 16 (range 43–126) Body size (cm) 170 ± 8 (range 149–189) BMI (kg/m2) 27.9 ± 5.1 (range 17.8–41.2) Cardiovascular risk factors  Smoking 40 (38.8)  Diabetes mellitus 30 (29.1)  Hypertension 72 (69.9)  Dyslipidaemia 48 (46.6)  Positive family history 14 (13.6) Clinical symptoms  Asymptomatic 24 (23.3)  Typical angina pectoris 20 (19.4)  Atypical chest pain 21 (20.4)  Dyspnoea 21 (20.4)  Syncope 3 (2.9) Medication  Antiplatelet therapy 39 (37.8)  Beta-blocker 19 (18.4)  ACI/ARB 56 (54.4)  Statin 7 (6.8)  Oral anticoagulation 10 (9.7) CAC score risk-class  0 13 (12.6)  1–10 7 (6.8)  11–100 22 (21.4)  101–400 22 (21.4)  >400 39 (37.9) Values given are mean ± standard deviation or absolute numbers and percentages in brackets unless otherwise stated. BMI, body mass index; ACI/ARB, Angiotensin-converting enzyme-inhibitors/Angiotensin-receptor antagonist; CAC, coronary artery calcium. Table 3 Image noise and signal ANOVA Bonferroni post hoc tests 120 kVp vs. 80 kVp 80 kVp vs. 70 kVp 120 kVp vs. 70 kVp 120 kVp 80 kVp 70 kVp P-value P-value P-value P-value Signal (HU) 42.8 44.8 46.3 0.006 0.204 0.505 0.004 Noise (HU) 28.8 32.2 32.0 <0.001 <0.001 1.0 <0.001 SNR 1.5 1.4 1.4 0.018 0.014 0.465 0.466 ANOVA Bonferroni post hoc tests 120 kVp vs. 80 kVp 80 kVp vs. 70 kVp 120 kVp vs. 70 kVp 120 kVp 80 kVp 70 kVp P-value P-value P-value P-value Signal (HU) 42.8 44.8 46.3 0.006 0.204 0.505 0.004 Noise (HU) 28.8 32.2 32.0 <0.001 <0.001 1.0 <0.001 SNR 1.5 1.4 1.4 0.018 0.014 0.465 0.466 For signal mean values are given, for noise standard deviation is given. HU, Hounsfield units; SNR, signal-to-noise ratio. Table 3 Image noise and signal ANOVA Bonferroni post hoc tests 120 kVp vs. 80 kVp 80 kVp vs. 70 kVp 120 kVp vs. 70 kVp 120 kVp 80 kVp 70 kVp P-value P-value P-value P-value Signal (HU) 42.8 44.8 46.3 0.006 0.204 0.505 0.004 Noise (HU) 28.8 32.2 32.0 <0.001 <0.001 1.0 <0.001 SNR 1.5 1.4 1.4 0.018 0.014 0.465 0.466 ANOVA Bonferroni post hoc tests 120 kVp vs. 80 kVp 80 kVp vs. 70 kVp 120 kVp vs. 70 kVp 120 kVp 80 kVp 70 kVp P-value P-value P-value P-value Signal (HU) 42.8 44.8 46.3 0.006 0.204 0.505 0.004 Noise (HU) 28.8 32.2 32.0 <0.001 <0.001 1.0 <0.001 SNR 1.5 1.4 1.4 0.018 0.014 0.465 0.466 For signal mean values are given, for noise standard deviation is given. HU, Hounsfield units; SNR, signal-to-noise ratio. Table 4 Agreement of CAC score-based risk classification derived from 80-kVp scans as compared with standard 120-kVp scans 120 kVp 80 kVp CAC score 0 1–10 11–100 101–400 >400 0 13 1 0 0 0 1–10 0 5 3 0 0 11–100 0 1 19 1 0 101–400 0 0 0 21 1 >400 0 0 0 0 38 120 kVp 80 kVp CAC score 0 1–10 11–100 101–400 >400 0 13 1 0 0 0 1–10 0 5 3 0 0 11–100 0 1 19 1 0 101–400 0 0 0 21 1 >400 0 0 0 0 38 Measure of agreement kappa = 0.909. Table 4 Agreement of CAC score-based risk classification derived from 80-kVp scans as compared with standard 120-kVp scans 120 kVp 80 kVp CAC score 0 1–10 11–100 101–400 >400 0 13 1 0 0 0 1–10 0 5 3 0 0 11–100 0 1 19 1 0 101–400 0 0 0 21 1 >400 0 0 0 0 38 120 kVp 80 kVp CAC score 0 1–10 11–100 101–400 >400 0 13 1 0 0 0 1–10 0 5 3 0 0 11–100 0 1 19 1 0 101–400 0 0 0 21 1 >400 0 0 0 0 38 Measure of agreement kappa = 0.909. Table 5 Agreement of CAC score-based risk classification derived from 70-kVp scans as compared with standard 120-kVp scans 120 kVp 70 kVp CAC score 0 1–10 11–100 101–400 >400 0 13 2 2 0 0 1–10 0 4 5 0 0 11–100 0 1 15 4 0 101–400 0 0 0 18 3 >400 0 0 0 0 36 120 kVp 70 kVp CAC score 0 1–10 11–100 101–400 >400 0 13 2 2 0 0 1–10 0 4 5 0 0 11–100 0 1 15 4 0 101–400 0 0 0 18 3 >400 0 0 0 0 36 Measure of agreement kappa = 0.782. Table 5 Agreement of CAC score-based risk classification derived from 70-kVp scans as compared with standard 120-kVp scans 120 kVp 70 kVp CAC score 0 1–10 11–100 101–400 >400 0 13 2 2 0 0 1–10 0 4 5 0 0 11–100 0 1 15 4 0 101–400 0 0 0 18 3 >400 0 0 0 0 36 120 kVp 70 kVp CAC score 0 1–10 11–100 101–400 >400 0 13 2 2 0 0 1–10 0 4 5 0 0 11–100 0 1 15 4 0 101–400 0 0 0 18 3 >400 0 0 0 0 36 Measure of agreement kappa = 0.782. Figure 3 View largeDownload slide Linear regression analysis (A) and Bland–Altman plot (B) comparing CAC scores derived from 80-kVp scans and from standard 120-kVp scans in all patients (n = 103). Bland–Altman limits of agreement were −235 to 172. CAC, coronary artery calcium. Figure 3 View largeDownload slide Linear regression analysis (A) and Bland–Altman plot (B) comparing CAC scores derived from 80-kVp scans and from standard 120-kVp scans in all patients (n = 103). Bland–Altman limits of agreement were −235 to 172. CAC, coronary artery calcium. Figure 4 View largeDownload slide Linear regression analysis (A) and Bland–Altman plot (B) comparing CAC scores derived from 70-kVp scans and from standard 120-kVp scans in all patients (n = 103). Bland–Altman limits of agreement were −476 to 270. CAC, coronary artery calcium. Figure 4 View largeDownload slide Linear regression analysis (A) and Bland–Altman plot (B) comparing CAC scores derived from 70-kVp scans and from standard 120-kVp scans in all patients (n = 103). Bland–Altman limits of agreement were −476 to 270. CAC, coronary artery calcium. In a sub-analysis of 64 (62.1%) patients with a CAC score ≤400, scores derived from 80-kVp scans showed an excellent correlation (r = 0.982, P < 0.001) compared with standard 120-kVp scans with BA analysis revealing a mean difference of −5 (−5.2%) and limits of agreement of −65 (−66.7%) to 55 (56.4%) (Figure 5). For CAC scores derived from 70-kVp scans, correlation was r = 0.917 (P < 0.001) with a mean difference of −28 (−33%) and BA limits of agreement of −134 (−157.8%) to 79 (93%). In this sub-analysis, a change in risk-class was observed in 6 (9.4%) patients and 14 (21.9%) patients, notably mostly to a lower risk-class, after obtaining CAC scores from the 80-kVp and the 70-kVp scans, respectively (see also Tables 4 and 5). In a further sub-analysis of 42 (40.8%) patients with a CAC score ≤100, scores derived from 80-kVp scans showed an excellent correlation (r = 0.958, P < 0.001) compared with standard 120-kVp scans with BA analysis revealing a mean difference of −3 (−10.6%) and limits of agreement of −24 (−102.7%) to 19 (81.2%) (Figure 6). For CAC scores derived from 70-kVp scans correlation was r = 0.853 (P < 0.001) with a mean difference of −13 (−54.0%) and BA limits of agreement of −58 (−298.3%) to 33 (169.7%). In this sub-analysis, a change in risk-class was observed in 5 (11.9%) patients and 10 (23.8%) patients, notably mostly to a lower risk-class, after obtaining CAC scores from the 80-kVp and the 70-kVp scans, respectively (see also Tables 4 and 5). Figure 5 View largeDownload slide Bland–Altman plot comparing CAC scores derived from 80-kVp scans and from standard 120-kVp scans in patients with CAC score ≤400 (n = 64). Bland–Altman limits of agreement were −65 to 55. CAC, coronary artery calcium. Figure 5 View largeDownload slide Bland–Altman plot comparing CAC scores derived from 80-kVp scans and from standard 120-kVp scans in patients with CAC score ≤400 (n = 64). Bland–Altman limits of agreement were −65 to 55. CAC, coronary artery calcium. Figure 6 View largeDownload slide Bland–Altman plot comparing CAC scores derived from 80-kVp scans and from standard 120-kVp scans in patients with CAC score ≤100 (n = 42). Bland–Altman limits of agreement were −24 to 19. CAC, coronary artery calcium. Figure 6 View largeDownload slide Bland–Altman plot comparing CAC scores derived from 80-kVp scans and from standard 120-kVp scans in patients with CAC score ≤100 (n = 42). Bland–Altman limits of agreement were −24 to 19. CAC, coronary artery calcium. In the 92 (89.3%) patients with BMI <35 kg/m2, scores derived from 80-kVp scans showed an excellent correlation (r = 0.997, P < 0.001) compared with standard 120-kVp scans with BA analysis revealing a mean difference of −22 (−3.6%) and limits of agreement of −172 (−27.8%) to 129 (20.9%). For CAC scores derived from 70-kVp scans correlation was r = 0.994 (P < 0.001) with a mean difference of −87 (−14.9%) and BA limits of agreement of −370 (−63.1%) to 196 (33.5%). Five (5.4%) patients and 14 (15.2%) patients in whom CAC scores were derived from 80-kVp and 70-kVp scans, respectively, changed the risk-class (Tables 6 and 7). In the 71 (68.9%) patients with a BMI <30 kg/m2, scores derived from 80-kVp scans showed an excellent correlation (r = 0.997, P < 0.001) compared with standard 120-kVp scans with BA analysis revealing a mean difference of −18 (−2.7%) and limits of agreement of −166 (−25.0%) to 130 (19.6%). For CAC scores derived from 70-kVp scans correlation was r = 0.995 (P < 0.001) with a mean difference of −78 (−12.3%) and BA limits of agreement of −364 (−57.5%) to 208 (32.9%). Two (2.8%) patients changed the risk-class observed for CAC scores derived from the 80-kVp scans but in 6 (8.5%) patients for CAC scores derived from the 70-kVp scans (Tables 8 and 9). Finally, in the 33 (32.0%) patients with a BMI <25 kg/m2, scores derived from 80-kVp scans showed an excellent correlation (r = 0.998, P < 0.001) compared with standard 120-kVp scans with BA analysis revealing a mean difference of −10 (−1.9%) and limits of agreement of −142 (−27.6%) to 122 (23.7%). For CAC scores derived from 70-kVp scans correlation was r = 0.998 (P < 0.001) with a mean difference of −51 (−10.3%) and BA limits of agreement of −303 (−61.3%) to 201 (40.7%). One (3.0%) patient and 2 (6.1%) patients, in whom CAC score was derived from 80-kVp and 70-kVp, respectively, changed the risk-class (Tables 10 and 11). Inter-reader agreement in this subgroup was excellent with ICC coefficients of r = 1.0 for all three scan protocols (P < 0.001). Table 6 Agreement of CAC score risk classes derived from 80-kVp scans as compared with standard 120-kVp scans in patients with BMI <35 kg/m2 (n = 92) 120 kVp 80 kVp CAC score 0 1–10 11–100 101–400 >400 0 11 1 0 0 0 1–10 0 5 2 0 0 11–100 0 1 17 0 0 101–400 0 0 0 20 1 >400 0 0 0 0 34 120 kVp 80 kVp CAC score 0 1–10 11–100 101–400 >400 0 11 1 0 0 0 1–10 0 5 2 0 0 11–100 0 1 17 0 0 101–400 0 0 0 20 1 >400 0 0 0 0 34 Measure of agreement kappa = 0.927. Table 6 Agreement of CAC score risk classes derived from 80-kVp scans as compared with standard 120-kVp scans in patients with BMI <35 kg/m2 (n = 92) 120 kVp 80 kVp CAC score 0 1–10 11–100 101–400 >400 0 11 1 0 0 0 1–10 0 5 2 0 0 11–100 0 1 17 0 0 101–400 0 0 0 20 1 >400 0 0 0 0 34 120 kVp 80 kVp CAC score 0 1–10 11–100 101–400 >400 0 11 1 0 0 0 1–10 0 5 2 0 0 11–100 0 1 17 0 0 101–400 0 0 0 20 1 >400 0 0 0 0 34 Measure of agreement kappa = 0.927. Table 7 Agreement of CAC score risk classes derived from 70-kVp scans as compared with standard 120-kVp scans in patients with BMI <35 kg/m2 (n = 92) 120 kVp 70 kVp CAC score 0 1–10 11–100 101–400 >400 0 11 2 1 0 0 1–10 0 4 4 0 0 11–100 0 1 14 3 0 101–400 0 0 0 17 3 >400 0 0 0 0 32 120 kVp 70 kVp CAC score 0 1–10 11–100 101–400 >400 0 11 2 1 0 0 1–10 0 4 4 0 0 11–100 0 1 14 3 0 101–400 0 0 0 17 3 >400 0 0 0 0 32 Measure of agreement kappa = 0.798. Table 7 Agreement of CAC score risk classes derived from 70-kVp scans as compared with standard 120-kVp scans in patients with BMI <35 kg/m2 (n = 92) 120 kVp 70 kVp CAC score 0 1–10 11–100 101–400 >400 0 11 2 1 0 0 1–10 0 4 4 0 0 11–100 0 1 14 3 0 101–400 0 0 0 17 3 >400 0 0 0 0 32 120 kVp 70 kVp CAC score 0 1–10 11–100 101–400 >400 0 11 2 1 0 0 1–10 0 4 4 0 0 11–100 0 1 14 3 0 101–400 0 0 0 17 3 >400 0 0 0 0 32 Measure of agreement kappa = 0.798. Table 8 Agreement of CAC score-based risk classification derived from 80-kVp scans as compared with standard 120-kVp scans in patients with BMI <30 kg/m2 (n = 71) 120 kVp 80 kVp CAC score 0 1–10 11–100 101–400 >400 0 8 0 0 0 0 1–10 0 4 1 0 0 11–100 0 1 14 0 0 101–400 0 0 0 15 0 >400 0 0 0 0 28 120 kVp 80 kVp CAC score 0 1–10 11–100 101–400 >400 0 8 0 0 0 0 1–10 0 4 1 0 0 11–100 0 1 14 0 0 101–400 0 0 0 15 0 >400 0 0 0 0 28 Measure of agreement kappa = 0.962. Table 8 Agreement of CAC score-based risk classification derived from 80-kVp scans as compared with standard 120-kVp scans in patients with BMI <30 kg/m2 (n = 71) 120 kVp 80 kVp CAC score 0 1–10 11–100 101–400 >400 0 8 0 0 0 0 1–10 0 4 1 0 0 11–100 0 1 14 0 0 101–400 0 0 0 15 0 >400 0 0 0 0 28 120 kVp 80 kVp CAC score 0 1–10 11–100 101–400 >400 0 8 0 0 0 0 1–10 0 4 1 0 0 11–100 0 1 14 0 0 101–400 0 0 0 15 0 >400 0 0 0 0 28 Measure of agreement kappa = 0.962. Table 9 Agreement of CAC score risk classes derived from 70-kVp scans as compared with standard 120-kVp scans in patients with BMI <30 kg/m2 (n = 71) 120 kVp 70 kVp CAC score 0 1–10 11–100 101–400 >400 0 8 0 0 0 0 1–10 0 4 3 0 0 11–100 0 1 12 1 0 101–400 0 0 0 14 1 >400 0 0 0 0 27 120 kVp 70 kVp CAC score 0 1–10 11–100 101–400 >400 0 8 0 0 0 0 1–10 0 4 3 0 0 11–100 0 1 12 1 0 101–400 0 0 0 14 1 >400 0 0 0 0 27 Measure of agreement kappa = 0.886. Table 9 Agreement of CAC score risk classes derived from 70-kVp scans as compared with standard 120-kVp scans in patients with BMI <30 kg/m2 (n = 71) 120 kVp 70 kVp CAC score 0 1–10 11–100 101–400 >400 0 8 0 0 0 0 1–10 0 4 3 0 0 11–100 0 1 12 1 0 101–400 0 0 0 14 1 >400 0 0 0 0 27 120 kVp 70 kVp CAC score 0 1–10 11–100 101–400 >400 0 8 0 0 0 0 1–10 0 4 3 0 0 11–100 0 1 12 1 0 101–400 0 0 0 14 1 >400 0 0 0 0 27 Measure of agreement kappa = 0.886. Table 10 Agreement of CAC score-based risk classification derived from 80-kVp scans as compared with standard 120-kVp scans in patients with BMI <25 kg/m2 (n = 33) 120 kVp 80 kVp CAC score 0 1–10 11–100 101–400 >400 0 2 0 0 0 0 1–10 0 3 0 0 0 11–100 0 1 8 0 0 101–400 0 0 0 9 0 >400 0 0 0 0 10 120 kVp 80 kVp CAC score 0 1–10 11–100 101–400 >400 0 2 0 0 0 0 1–10 0 3 0 0 0 11–100 0 1 8 0 0 101–400 0 0 0 9 0 >400 0 0 0 0 10 Measure of agreement kappa = 0.960. Table 10 Agreement of CAC score-based risk classification derived from 80-kVp scans as compared with standard 120-kVp scans in patients with BMI <25 kg/m2 (n = 33) 120 kVp 80 kVp CAC score 0 1–10 11–100 101–400 >400 0 2 0 0 0 0 1–10 0 3 0 0 0 11–100 0 1 8 0 0 101–400 0 0 0 9 0 >400 0 0 0 0 10 120 kVp 80 kVp CAC score 0 1–10 11–100 101–400 >400 0 2 0 0 0 0 1–10 0 3 0 0 0 11–100 0 1 8 0 0 101–400 0 0 0 9 0 >400 0 0 0 0 10 Measure of agreement kappa = 0.960. Table 11 Agreement of CAC score risk classes derived from 70-kVp scans as compared with standard 120-kVp scans in patients with BMI <25 kg/m2 (n = 33) 120 kVp 70 kVp CAC score 0 1–10 11–100 101–400 >400 0 2 0 0 0 0 1–10 0 3 1 0 0 11–100 0 1 7 0 0 101–400 0 0 0 9 0 >400 0 0 0 0 10 120 kVp 70 kVp CAC score 0 1–10 11–100 101–400 >400 0 2 0 0 0 0 1–10 0 3 1 0 0 11–100 0 1 7 0 0 101–400 0 0 0 9 0 >400 0 0 0 0 10 Measure of agreement kappa = 0.920. Table 11 Agreement of CAC score risk classes derived from 70-kVp scans as compared with standard 120-kVp scans in patients with BMI <25 kg/m2 (n = 33) 120 kVp 70 kVp CAC score 0 1–10 11–100 101–400 >400 0 2 0 0 0 0 1–10 0 3 1 0 0 11–100 0 1 7 0 0 101–400 0 0 0 9 0 >400 0 0 0 0 10 120 kVp 70 kVp CAC score 0 1–10 11–100 101–400 >400 0 2 0 0 0 0 1–10 0 3 1 0 0 11–100 0 1 7 0 0 101–400 0 0 0 9 0 >400 0 0 0 0 10 Measure of agreement kappa = 0.920. Of note, no misclassification from or to a zero CAC score was found for neither the 80-kVp nor the 70-kVp scans in the subpopulation with a BMI <30 kg/m2. Average CAC scores in each risk-class based on the 120-kVp classification and average differences in each risk-class (i.e. 80 kVp and 70 kVp compared with 120 kVp) are depicted in Table 12. Table 12 Average CAC score in each risk-class based on the 120-kVp classification and average differences in each risk-class (i.e. 80 kVp and 70 kVp compared with 120 kVp) CAC category Mean CAC score-based on 120 kVp Mean Δ CAC score 120 kVp 80 kVp 70 kVp 120 kVp–80 kVp 120 kVp–70 kVp 0 0 0 0 0 0 1–10 6 4 2 2 4 11–100 45 40 26 5 19 101–400 243 234 181 9 62 >400 1450 1377 1224 73 226 CAC category Mean CAC score-based on 120 kVp Mean Δ CAC score 120 kVp 80 kVp 70 kVp 120 kVp–80 kVp 120 kVp–70 kVp 0 0 0 0 0 0 1–10 6 4 2 2 4 11–100 45 40 26 5 19 101–400 243 234 181 9 62 >400 1450 1377 1224 73 226 Table 12 Average CAC score in each risk-class based on the 120-kVp classification and average differences in each risk-class (i.e. 80 kVp and 70 kVp compared with 120 kVp) CAC category Mean CAC score-based on 120 kVp Mean Δ CAC score 120 kVp 80 kVp 70 kVp 120 kVp–80 kVp 120 kVp–70 kVp 0 0 0 0 0 0 1–10 6 4 2 2 4 11–100 45 40 26 5 19 101–400 243 234 181 9 62 >400 1450 1377 1224 73 226 CAC category Mean CAC score-based on 120 kVp Mean Δ CAC score 120 kVp 80 kVp 70 kVp 120 kVp–80 kVp 120 kVp–70 kVp 0 0 0 0 0 0 1–10 6 4 2 2 4 11–100 45 40 26 5 19 101–400 243 234 181 9 62 >400 1450 1377 1224 73 226 Discussion This is the first in vivo study demonstrating the feasibility and accuracy of CAC scoring with reduced peak tube voltages of 80 kVp and 70 kVp using kVp-adapted thresholds. Compared with standard 120-kVp CAC scanning, lower peak tube voltages of 80 kVp and 70 kVp led to a mean radiation dose of 0.19 mSv and 0.12 mSv, respectively, representing a reduction of 68% and 80%, compared with the standard 120-kVp protocol which resulted in a radiation dose exposure of 0.60 mSv. There was an only minimal underestimation of the CAC scores as compared with the standard 120-kVp protocol with narrower absolute BA limits of agreement for lower CAC scores and lower BMI. Underestimation was marked and limits of agreement were broader with increasing CAC scores and BMI. However, in high-risk patients with a CAC score >400, a broader variation may well be acceptable due to the lower reclassification rate, and therefore, without any impact on adjustment in treatment strategies. Risk-class changes were rare and mainly observed in patients with high BMI, most probably due to the greater degree of tissue attenuation and increased image noise in this subgroup.19 This notion is corroborated in particular by the findings of a distinct outlier (see Figures 3 and 4) with a BMI of 35 kg/m2 and marked abdominal obesity in whom the entire inferior left ventricular wall was severely attenuated in the low tube voltage scans, rendering the coronary calcifications practically undetectable, hence resulting in a substantial underestimation of the CAC scores. The fact that only a few reclassifications were observed for CAC scores derived from 80-kVp in patients with a BMI <35 kg/m2 and for scores derived from 70-kVp in patients with a BMI <30 kg/m2 and with no misclassifications from or to a zero CAC score in the subpopulation with a BMI <30 kg/m2, suggests the potential use of a BMI-adapted peak tube voltage approach in daily clinical routine where 120-kVp, 80-kVp, and 70-kVp scans are used for patients with a BMI ≥30 kg/m2, <30 kg/m2, and <25 kg/m2, respectively. However, while the present pilot study includes a population with a relatively broad range of BMI, the sample size may not be large enough to give recommendations to change clinical practice as of yet. However, it offers suggestions to be validated in larger cohorts. A few prior studies have assessed CAC scanning with reduced peak tube voltage. In the study of Jakobs et al.,20 radiation dose was reduced by 65% by applying an 80-kVp protocol compared with the standard 120-kVp protocol. However, the study did not assess Agatston scores but rather the calcium mass derived from the scan—a parameter that is not widely used for risk stratification in clinical routine. Furthermore, retrospective ECG-gating was used, yielding mean radiation dose exposures of 0.72 mSv with the 80-kVp protocol. In a more recent study, Tesche et al.21 could demonstrate excellent agreement between a standard 120-kVp and a tin-filtration 100-kVp protocol, yielding accurate Agatston scores with very few misclassifications at a low mean radiation dose exposure of only 0.19 ± 0.05 with the new protocol. While the approach suggested by Tesche et al. is unquestionably interesting, it’s generalizability remains limited because the applied tin-filtration is a vendor-specific tool. By contrast, our study theoretically paves the way for ultra-low-dose CAC scoring independent of site- or vendor-specific prerequisites. In a further study by Nakazato et al., 60 consecutive patients were scanned with standard 120 kVp and with 100 kVp. In this study, however, only the lower threshold of 130 HU was adapted to 100 kVp for CAC scoring by simply calculating the ratio of attenuation of a plaque at 100 kVp over its attenuation at 120 kVp. By contrast, our approach is based on a mathematical model enabling adaption not only of the lowest but of all thresholds and potentially for any given peak tube voltage, which may yield more accurate results because CAC scoring is based not only on the lowest threshold but also incorporates the scores 2–4, which accounts for substantial deviation from the true total score if the thresholds for these higher scores are not properly adapted to the tube voltage in use. However, a direct comparison with the results from Nakazato et al.12 is difficult, due to the limited range of CAC as compared with the present study. Moreover, while tube current was increased by 30% in the study by Nakazato et al., it remained unchanged for all scans in the present study, contributing to a further reduction in effective radiation exposure. Marwan et al. also reduced peak tube voltage from ECG-triggered high-pitch 120-kVp to 100-kVp protocol and could significantly reduce radiation dose from 0.3 mSv to 0.2 mSv. CAC scores measured from 100-kVp scans while maintaining the 130 HU thresholds were overestimated when compared with the standard protocol of 120 kVp. However, agreement improved when a threshold of 147 HU was applied for the 100-kVp protocol. Similar to our study, a minority of patients (3.4%) were reclassified to a different risk-class if CAC scores were obtained from a 100-kVp scan, although this was observed towards a higher risk-class which is to be expected if only the lowest threshold is adapted. This is in contrast to our results where reclassification was mostly seen towards lower risk-classes. This might be due to the fact that on the one hand, in the study by Nakazato et al.12 and Marwan et al.11 only the lower threshold of 130 HU was adapted to 147 HU, while our novel thresholds are increasingly higher than the original thresholds at 120 kVp with decreasing tube voltage, thus compensating for the higher plaque attenuation at lower photon energies. On the other hand, increasing noise at lower tube voltages while using a fixed tube current may have led to a shift towards underestimation. Finally, in the present study, all patients were included in the final analysis, regardless of image noise. This reflects an intention-to-diagnose approach and stands in contrast with the previous study by Marwan et al. where patients were excluded due to excessive image noise. Of note, our calculated lower threshold of 145 HU for a 100-kVp protocol is very similar the 147 HU threshold proposed in the above-mentioned studies.11,12 Furthermore, our calculated lower threshold of 177 HU for the 80-kVp protocol is comparable to a phantom study suggesting a threshold of 187 HU.22 Some recent studies have applied iterative reconstruction in order to reduce image noise at lower tube currents,23–25 while other studies have suggested that the application of iterative reconstruction algorithms on 120-kVp scans has per se an impact on CAC measurements, generally leading to underestimation of CAC scores.13,26,27 In the present study, we have used a fixed tube current and have refrained from applying iterative reconstruction algorithms so as not to introduce a confounder. Future studies will need to clarify if the use of iterative reconstruction algorithms confers added value for ultra-low-dose CAC scoring at very low peak tube voltages. If this was the case, the results of the present study may pave the way for even more reduction in radiation dose exposure as it would allow additional lowering of the tube current while applying iterative reconstruction for compensation of increasing noise. Although our results suggest that CAC protocols with low tube voltage offer a substantial potential of radiation dose reduction, it should be taken into consideration that this is achieved in a setting of sub-millisievert exposure and it remains an issue of ongoing debate whether ionizing radiation of this magnitude is of any clinical relevance on the patient level.28 Against this background, it is up to debate whether a decline in accuracy brought upon by applying an ultra-low-dose CAC protocol is justified. However, CAC scoring is mainly a tool for risk stratification and the results from this pilot study suggests a very low rate of reclassifications particularly if a BMI-adapted approach is applied. Considering the fact that the number of CT examinations for CAC assessment is constantly increasing, any further reduction of radiation exposure may translate into a reduced radiation-related risk not only on a patient but also on a population-level, justifying the trade-off between image quality and radiation exposure while following the principle of ALARA as suggested by a recent European report.28 Limitations It may be perceived as a limitation that we have refrained from including more patients with a zero CAC score. However, we felt that it was imperative for a pilot study with a limited patient population to include patients with a broad range of CAC scores to validate our thresholds for CAC scoring even at the upper range of CAC scores which may be encountered in clinical routine. Consecutive inclusion of patients would have led to a large proportion of the sampled population having zero CAC scores, rendering an assessment of accuracy difficult. Hence, the number of patients with a CAC score of zero was prospectively limited. Furthermore, as the focus of this pilot study was to assess the validity of the novel thresholds which are only dependent on tube voltage, we have refrained from applying other adjustments such as adaption of the tube current to BMI so as not to introduce an additional confounder. Moreover, by using a 200 mA tube current for the standard of reference, it is unlikely that it was negatively affected by noise at tube voltages of 120-kVp even in patients with a high BMI. Finally, it may be argued that the thresholds presented in this study are imperfect because they are based on assumptions with regard to the plaque composition that was used by Agatston et al.15 However, it is difficult to comment on the magnitude of such potential imperfection and it seems impossible to find a perfect solution because aside from requiring new thresholds, lowering the tube voltage in CT scanning inevitably at the same time introduces increased image noise which in turn affects CAC scoring as well. The latter is reflected by the observation that a BMI-adapted protocol yields more accurate results. Conclusions The present pilot study suggests that CAC scoring with reduced peak tube voltage is accurate if kVp-adapted thresholds for calculation of CAC scores are applied while offering a radiation dose reduction of up to 80%. Conflict of interest: The University Hospital Zurich holds a research agreement with GE Healthcare. 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Journal

European Heart Journal – Cardiovascular ImagingOxford University Press

Published: Dec 1, 2018

References

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