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Contrast medium injection protocols for coronary CT angiography: should contrast medium volumes be tailored to body weight or body surface area?
Clinical Radiology xxx (xxxx) xxx
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Contrast medium injection protocols for coronary CT angiography: should contrast medium volumes be tailored to body weight or body surface area? W.-H. Yin a, 1, Y.-T. Yu a, 1, Y. Zhang a, b, Y.-Q. An a, Z.-H. Hou a, Y. Gao a, H.-P. Wang a, B. Lu a, *, D. De Santis c, J.D. Rollins c, U.J. Schoepf c, d a Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China b Department of Radiology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, People’s Republic of China c Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC, USA d Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA
art icl e i nformat ion Article history: Received 16 August 2019 Accepted 6 December 2019
AIM: To compare the uniformity and image quality between contrast media injection protocols adjusted for patient body weight (BW) versus body surface area (BSA) during coronary computed tomography (CT) angiography (CCTA). MATERIALS AND METHODS: Consecutive patients (n¼489) with suspected coronary artery disease were randomised prospectively to one of two CCTA protocols. In the BW protocol (n¼245), patients received individualised iodine delivery rates (50 kg: 1 g/s; 51e60 kg: 1.2 g/ s; 61e70 kg: 1.4 g/s; 71e80 kg: 1.6 g/s; 81e90 kg: 1.8 g/s; 91e100 kg: 2 g/s; >100 kg: 2.2 g/s). In the BSA protocol (n¼244), patients received 9,600 mg iodine/m2 of contrast medium over 12 seconds. Attenuation and image noise were measured. Signal-to-noise ratio and contrast-tonoise ratio were calculated. Image quality was scored. Attenuation was assessed for correlation with BW and BSA using linear regression. RESULTS: There were no statistically significant differences in mean arterial attenuation (396.847.6 versus 395.842.2 HU, p¼0.804; 95% confidence interval: e7 to 9), image noise (25.25.8 versus 25.55.4 HU; p¼0.549), signal-to-noise ratio (16.74.4 versus 16.63.6; p¼0.902), contrast-to-noise ratio (25.15.8 versus 25.87.4; p¼0.258) or image quality scores (4.10.9 versus 40.9; p¼0.770) between the BW and BSA protocols. There was no correlation between BW and aortic attenuation or between BSA and aortic attenuation (p¼0.324 and 0.932, respectively).
* Guarantor and correspondent: B. Lu, Department of Radiology, Fuwai Hospital, #167 Bei-Li-Shi Street, Xi-Cheng District, Beijing, 100037, People’s Republic of China. Tel.: þ86 10 88322662; fax: þ86 10 68313012. E-mail address: [email protected] (B. Lu). 1 These authors contributed equally to this paper. https://doi.org/10.1016/j.crad.2019.12.005 0009-9260/Ó 2019 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Please cite this article as: Yin W-H et al., Contrast medium injection protocols for coronary CT angiography: should contrast medium volumes be tailored to body weight or body surface area?, Clinical Radiology, https://doi.org/10.1016/j.crad.2019.12.005
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CONCLUSION: The average contrast media attenuation and image quality was comparable between BW-adjusted protocol and BSA-adjusted protocol. Ó 2019 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Introduction Coronary computed tomography angiography (CCTA) is a robust minimally invasive diagnostic tool for the assessment of coronary artery disease (CAD; 50% luminal stenosis in a vessel).1 Contrary to the dramatic technical advancements of CT systems in the last decade, the optimal contrast medium (CM) injection protocol is still a matter of active investigation.2 Injecting a fixed amount of CM is the simplest and fastest approach to perform CCTA; however, in recent years a trend toward a patient-centred examination is taking place.3 In light of that, the CM injection is often tailored to the patient’s body weight (BW), while the iodine delivery rate (IDR) is also varied to achieve adequate contrast enhancement.4 Previous study has shown that such an approach could achieve consistent vascular enhancement despite its complexity.5 Nevertheless, patient factors other than BW, such as muscle mass, cardiac output, and hydration status, may influence contrast enhancement.6,7 Among them, body surface area (BSA) has been demonstrated as a reliable body parameter to achieve a consistent contrast enhancement in CCTA over a wide range of body sizes.5 Yanaga et al.7 investigated the effect on aortic enhancement of CM volume adjusted for BSA in aortic CT angiography, demonstrating that a BSA-based CM injection protocol provides adequate and consistent aortic enhancement regardless of BW; however, to the authors’ knowledge, a comparison between BW-based and BSA-based CM injection protocols in CCTA has not been reported to date. Thus, the purpose of the present study was to evaluate prospectively whether the image quality of BSA-based CM injection protocol is non-inferior to the widely accepted BW-based protocol in patients undergoing CCTA for suspected CAD.
Materials and Methods Study design and patient population This single-centre study was approved by the hospital’s Institutional Ethics Committee. The study was a prospective, randomised, non-inferiority trial. Between September 2018 and December 2018, 515 consecutive patients with suspected CAD who were scheduled to undergo clinically indicated CCTA due to chest pain, the presence of one or more CAD risk factors, or electrocardiographic abnormalities were approached prospectively. Inclusion criteria were age 30e85 years and a stable baseline cardiac sinus rhythm.
Exclusion criteria included known CAD, history of prior percutaneous intervention or bypass surgery, prior reaction to iodinated contrast materials, and impaired renal function (eGFR < 30 ml/min/1.73 m2).
CCTA acquisition All patients underwent CCTA on a second-generation dual-source CT system (Somatom Definition Flash, Siemens Healthineers, Forchheim, Germany) operating in single-energy mode. Acquisition parameters were 2640.6 mm detector collimation, 280 ms gantry rotation time, pitch of 3.4, and field of view of 200e250 mm. Heart rate was recorded during CCTA. Individuals with heart rate 60 beats/min were scanned with prospectively electrocardiogram (ECG)-triggered high-pitch spiral mode8 with a trigger phase at 60% of the R-R interval. Individuals with a heart rate between 60 and 70 beats/min were scanned with prospectively ECG-triggered sequential acquisition mode during mid diastole (70e80% of the R-R interval). Individuals with heart rates 70 beats/min were scanned with prospectively ECG-triggered sequential acquisition mode during end systole (35e45% of the R-R interval). The X-ray tube potential and tube current were tailored to the body mass index (BMI) as follows: 80 kV/400 mAs for BMI <20 kg/m2, 100 kV/370 mAs for 20 kg/m2 BMI <25 kg/m2, and 120 kV/320 mAs for BMI 25 kg/m2. Attenuation-based tube current modulation (CareDose 4D, Siemens) was applied. The time for scan initiation was established by means of an automated bolus-tracking technique (CareBolus, Siemens): a region of interest (ROI) was placed in the ascending aorta; after a 10-second delay, repetitive scans at 1-second intervals were performed, the trigger level was set at 100 HU, and an additional 6-second delay was set before commencing the angiographic acquisition CCTA study.8
CM injection protocols CM was injected via an 18-G access through an antecubital vein using a double-syringe power injector (Stellant, Medrad, Indianola, PA, USA). A triple-phase CM injection protocol was used, which consisted of undiluted CM (Ioversol 350 mg iodine/ml, Hengrui Medicine, Jiangsu, China) followed by a 30:70 mixture of CM and saline followed by a 20 ml saline flush. Therefore, the total CM volume was calculated as the volume of first phase plus 30% of the second phase. All patients were randomised 1:1 to either BW group or BSA group using a web-based randomisation system.9 In the BW group, each patient received an individualised IDR (g iodine/s) in the first phase (50 kg: 1 g iodine/s; 51e60 kg:
Please cite this article as: Yin W-H et al., Contrast medium injection protocols for coronary CT angiography: should contrast medium volumes be tailored to body weight or body surface area?, Clinical Radiology, https://doi.org/10.1016/j.crad.2019.12.005
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1.2 g iodine/s; 61e70 kg: 1.4 g iodine/s; 71e80 kg: 1.6 g iodine/s; 81e90 kg: 1.8 g iodine/s; 91e100 kg: 2 g iodine/s; >100 kg: 2.2 g iodine/s).
Flow rate ðmL = sÞ ¼
Flow rate was calculated as follows
Image reconstruction
Flow Rate ðmL = sÞ ¼
IDR ðgI=sÞ 1000 CM concentration ðmgI=mLÞ
CM volume was calculated as follows
CM volume ðmlÞ ¼ flow rateðml = sÞ 12 s The second CM injection had a fixed duration of 6 seconds, with IDR and flow rate corresponding to those used in the first phase. Comprehensive CM injection parameters are reported in Table 1. For the BSA group, BSA was estimated using the following formula10: pffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi weight ðkgÞ height ðcmÞ BSA m2 ¼ 60 A fixed-duration injection protocol was used in order to reduce interpatient variability in aortic enhancement.11 In the first CM injection, 9,600 mg iodine/m2 of CM was administered over 12 seconds such that patients received CM volume according to the equation: CM volume（mL） ¼
9600 ðmgI=m2 Þ BSA ðm2 Þ CM concentration ðmgI=mLÞ
The corresponding flow rate was therefore calculated as: Flow rate ðmL = sÞ ¼
CM volume ðmLÞ 12 s
During the second CM injection, patients received 1,160 mg iodine/m2 of CM over a fixed duration of 6 seconds, such that: CM volume（mL） ¼
1160 ðmgI=m2 Þ BSA ðm2 Þ CM concentration ðmgI=mLÞ
Likewise, the corresponding flow rate for the second phase was calculated as: Table 1 Body weight (BW) injection protocol. Weight group
Iodine Flow rate delivery (ml/s) rate (g/s)
Volume (ml) phase 1
Volume (ml) phase 2
50 kg (n¼8) 60 kg (n¼43) 70 kg (n¼76) 80 kg (n¼65) 90 kg (n¼36) 100 kg (n¼13) >100 kg (n¼4)
1 1.2 1.4 1.6 1.8 2 2.2
35 41 48 55 61 68 76
17.4 20.4 24 27.6 30.6 34.2 37.8
2.9 3.4 4 4.6 5.1 5.7 6.3
CM volume ðmLÞ 0:3 6 s
All CCTA datasets were reconstructed with the following parameters: 0.75 mm section thickness, 0.5 mm slice increment, 200 mm field-of-view. Sinogram-affirmed iterative reconstruction (SAFIRE) strength level of 3 was used with a medium smooth-tissue convolution kernel (I26f). According to the previously described beneficial effects of a higher spatial resolution kernel on the evaluation of heavy calcifications, the higher frequency “I46f” algorithm was also included.8
Objective image quality analysis All CCTA image datasets were transferred to a workstation using syngo.via version VB10 (Siemens Healthineers, Forchheim, Germany). A single observer with 6 years of experience in CCTA performed the quantitative measurements, blinded to the CM injection protocol. On the axial plane, attenuation values and standard deviation (SD) were measured by drawing circular ROIs within the aortic root (size: 100 mm2) at the level of the right coronary artery ostium. Coronary artery attenuation values were measured within the left main coronary artery and at the level of the proximal and distal right coronary artery, carefully avoiding vessel wall and plaques. Coronary artery attenuation values were eventually averaged to obtain a single value. An additional ROI was placed within the pericardial fat in order to measure attenuation and SD. Image noise was defined as the SD of pericardial fat. To ensure data consistency, all measurements were performed in triplicate and subsequently averaged. Signal-to-noise ratio (SNR) and contrastto-noise ratio (CNR) were defined according to the following: SNR ¼
HUaorta noise
CNR ¼
HUvessels HUfat noise
Subjective image quality analysis Two observers with 5 and 6 years of experience in CCTA, respectively, independently assessed subjective image quality, blinded to the CM injection protocol. Images were evaluated on a per-segment level using the modified 18segment classification system of the Society of Cardiovascular Computed Tomography12 in random order, and with a preset window setting (window level 300 HU, width 800 HU), freely adjustable based on the reader’s preference. Observers were asked to grade the image quality using the following five-point scale: 1, non-diagnostic; 2, poor; 3, adequate (presence of artefacts not limiting detection of luminal stenosis); 4, good; and 5, excellent. Mean image quality scores 3 were deemed diagnostic.
Please cite this article as: Yin W-H et al., Contrast medium injection protocols for coronary CT angiography: should contrast medium volumes be tailored to body weight or body surface area?, Clinical Radiology, https://doi.org/10.1016/j.crad.2019.12.005
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Statistical analysis This study was a non-inferiority design. The primary endpoint was the uniformity of vessel enhancement, defined as the average magnitude of attenuation values. The sample size was determined by power analysis based on a type 2 error rate b¼0.2. Based on historical analysis a CT attenuation of 390 HU was assumed, with a standard deviation of approximately 80 HU.13 A difference of 30 HU in CT attenuation was prespecified and considered clinically relevant. Considering a 10% dropout rate, the study required 125 patients in each group. Data were analysed using commercially available software (SPSS 2007, SPSS for Windows, Version 16.0, Chicago, IL, USA). Continuous variables were expressed as meanSD while categorical variables were reported as frequencies or percentages. Differences between groups were compared using one-way analysis of variance; all pairs of groups were compared using Fisher’s least significant difference method. Normally distributed variables were compared using Student’s t-test for unpaired samples. The c2 test was used for categorical variables. The generalised linear model was used to analyse the effects of age, sex, BMI, and heart rate on vessel enhancement in both protocols. The Akaike information criterion was calculated for all models and most appropriate model was selected, with age, sex, BMI, and heart rate considered as confounding factors. Two-tailed p<0.05 was considered statistically significant.
venous access for the desired contrast medium delivery rate. Therefore, the final study cohort consisted of 489 patients who provided written informed consent. Patients were randomly assigned to undergo one of two CM protocols (Fig 1). All CCTA studies were successfully completed without complications. No patient in the BW or BSA protocol experienced CM extravasation or aborted injection secondary to patient symptoms. Data analysis was performed for 489 patients: 245 patients (148 males, mean age 59.212.5 years, age range 30e85 years) in the BW group, and 244 patients (135 males, mean age 59.811.3 years, age range 30e83 years) in the BSA group. There were no significant differences in patients’ age, sex distribution, BMI, or heart rate (all p0.272). In the BW group, tube voltage of 120, 100, and 80 kVp was performed in 130, 105, and 10 patients, respectively. In the BSA group, tube voltage of 120, 100, and 80 kVp was performed in 125, 108, and 11 patients, respectively. Patient characteristics, CT imaging details, and contrast agent administration parameters are summarised in Table 2.
CM volume and injection flow rate The CM volume and injection rate were comparable between the BW group (volume: 55.18.4 ml; rate: 4.10.6 ml/s) and the BSA group (volume: 54.46.6 ml; rate: 4.10.5 ml/s; all p0.218).
Results
Objective image quality analysis
Patient population
In the BW and BSA groups, considering age, sex, BMI, and heart rate as confounding factors, the lowest Akaike information criterion scores were 22,577.1 and 2,523.3, respectively. Using a generalised linear model, age, sex, BMI, and
Of 515 patients approached for participation, 24 patients refused to participate, and two patients had inadequate
Figure 1 Study enrolment flowchart. Consecutive patients (n¼515) were approached for participation. Of those, 489 patients were enrolled and underwent CCTA: 245 were randomly assigned to the BW protocol, and 244 to the BSA protocol. Please cite this article as: Yin W-H et al., Contrast medium injection protocols for coronary CT angiography: should contrast medium volumes be tailored to body weight or body surface area?, Clinical Radiology, https://doi.org/10.1016/j.crad.2019.12.005
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Table 2 Baseline demographic data and contrast dose in body weight (BW) and body surface area (BSA) protocols. Parameters Patient demographics Male-to-female ratio Age (years) Height (cm) Weight (kg) Body mass index (kg/m2) Heart rate (beats/min) No. of patients with CAD Scanning parameter Reference tube current (mAs) Tube voltage (120 kV:100 kV: 80 kV) Contrast medium injection protocol Contrast medium volume (ml) Flow rate in the first phase (ml/s)
BW group
BSA group
p-Values
148:97 59.212.5 166.98.0 71.412.7 25.63.7 64.59.5 55 (22.4)
135:109 59.811.3 1667.7 70.311.5 25.43.1 65.97.3 43 (17.6)
0.272 0.629 0.231 0.309 0.679 0.086 0.214
344.726.9 347.827.0 0.205 130:105:10 125:108:11 0.911
55.18.4 4.10.6
54.46.6 4.10.5
0.285 0.218
All parameters are expressed as mean standard deviation or n (%). CAD, coronary artery disease.
heart rate had no statistically significant effect on vessel enhancement (all p>0.05). Full objective image quality data are reported in Table 3. The BW protocol and BSA protocol returned comparable attenuation (396.847.6 versus 395.842.2 HU; p¼0.804), SNR (16.74.4 versus 16.63.6; p¼0.902), and CNR (25.15.8 versus 25.87.4; p¼0.258). Mean difference of CT attenuation between the BW and BSA protocols was 14.1, with no statistical significance (p¼0.804); 95% confidence interval was e7 to 9.0. The CT attenuation of four examinations was deemed not optimal in the BW group. Of these four, the CT attenuation of three patients was <300 HU, and >500 HU in the other. In comparison, no examination had a CT attenuation of <300 HU in the BSA group whereas one exceeded 500 HU. -vis To evaluate the robustness of image quality vis-a body size, the cohort was divided into lower and higher body mass index (BMI) groups. Because the mean BMI in this study was 25.48 kg/m2, this value was used as the cutoff threshold. No correlation was found between CT attenuation and BW or BSA in either the BW- or BSA-adjusted group (p¼0.324 and 0.932, respectively; Figs 2a and 3a). There was no correlation between weight and aortic attenuation in the low (p¼0.174 and 0.755, respectively) or high (p¼0.969 and 0.209, respectively) BMI sub-groups in either the BW- or BSA-adjusted group (Figs 2b and 3b). There was no significant difference in vascular attenuation between the low BMI group and high BMI group in either the BW- or BSA-
Table 3 Comparison of objective image quality parameters between in body weight (BW) and body surface area (BSA) protocol groups.
Attenuation Image noise Signal-to-noise ratio Contrast-to-noise ratio
BW group
BSA group
p-Values
396.847.6 25.25.8 16.74.4 25.1 5.8
395.842.2 25.55.4 16.63.6 25.87.4
0.804 0.549 0.902 0.258
Figure 2 Plot of CT attenuation versus BW in the BW group. (a) The regression formula was CT attenuation ¼ 425.55e0.403 (BW; blue line). There was no correlation between BW and CT attenuation (p¼0.324). Correlation is significant at the 0.01 level (two-tailed). (b) The regression formula of CT attenuation versus BW was CT attenuation ¼ 445.93e0.7445(BW) for the low BMI group (red line) and CT attenuation ¼ 397.04e0.0154(BW) for the high BMI group (purple line). There was no correlation between BW and CT attenuation in both low (p¼0.174) and high (p¼0.969) BMI groups.
adjusted group (398.651.2 versus 395.843.6 HU, p¼0.649; 398.143.7 versus 393.240.4 HU, p¼0.362, respectively; Figs 4 and 5).
Subjective image quality analysis For the purpose of assessing 50% luminal stenosis on a per-segment level, all of the examinations were deemed diagnostic. A total of 3,674 and 3,659 coronary artery segments were present in the BW and BSA groups, respectively (mean 15 segments per patient). Of these, 151 (4.1%) from the BW group and 146 segments (4%) from the BSA group were deemed non-diagnostic consistently by both observers: 66 (1.8%) and 59 (1.6%) segments could not be confidently evaluated due to “blooming” artefact from heavy calcification, while motion artefact affected 85 segments (2.3%) and 88 segments (2.4%) in the BW and BSA groups, respectively. Non-diagnostic image quality between the two groups did not reach statistical significance
Please cite this article as: Yin W-H et al., Contrast medium injection protocols for coronary CT angiography: should contrast medium volumes be tailored to body weight or body surface area?, Clinical Radiology, https://doi.org/10.1016/j.crad.2019.12.005
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Figure 3 Plot of CT attenuation versus BSA. There was no correlation between BSA and CT attenuation (p¼0.932). (a) The regression formula was CT attenuation ¼393.46 þ 1.2981(BSA; blue line). (b) The regression formula of CT attenuation versus BSA was CT attenuation ¼ 383.44 þ 8.5947(BSA) for the low BMI group (red line) and CT attenuation ¼ 447.88e28.953(BSA) for the high BMI group (yellow line). There was no correlation between BSA and CT attenuation in either low (p¼0.755) or high (p¼0.209) BMI groups.
Figure 4 Comparison of CT attenuation between low and high BMI groups within the BW and BSA groups (all p > 0.05).
(p¼0.813). Overall, image-quality scores on a per-segment level as determined by the readers were similar for the two protocol groups (p¼0.770, Table 4).
Discussion This study compares the contrast enhancement and image quality in CCTA with an individualised injection
protocol based on BW and BSA. By basing the CM application on either BW or BSA, the average enhancement and image quality was comparable between the two groups. No correlation was found between CT attenuation and BW or BSA in either group. The optimal vascular attenuation is approximately 350 HU in CCTA for detection of coronary artery stenosis.14 A lower vascular enhancement can aid the differentiation of the enhanced lumen from calcification,15 while higher vascular attenuations may be helpful in improving the visualisation of small coronary arteries.16 The vascular attenuation achieved in the present study was slightly lower than 400 HU in both protocols. Thus, both approaches provided adequate vessel opacification, which is essential to achieve a diagnostic CCTA examination. Body weight is the main patient-related determinant of vascular enhancement. Adjusting IDR to different weight categories is a sensible approach to contrast protocols.17 Lubbers et al.18 and Rengo et al.13 compared the effect of CM iodine concentration and osmolarity on contrast enhancement when injected at a constant IDR in CCTA. The results demonstrated that for a given IDR, CM with different concentrations or osmolarities achieve comparable vascular enhancement. BSA has been proposed as an alternative in determining the optimal CM volume in CCTA.5 In the present study, BSA was demonstrated to be an effective determinant of CM volume, providing adequate and consistent vascular enhancement. Interestingly, these results have been achieved in both low- and high-BMI groups, further validating the robustness of using BSA to estimate appropriate CM volume. The present investigation did not demonstrate significant differences in terms of vascular enhancement and image quality between the BSA and BW groups. These results are in accordance with Yanaga et al.,7 who prospectively investigated the effect on aortic enhancement of CM volumes adjusted for BSA and BW in CTA. The authors demonstrated that both approaches achieved comparable aortic enhancement. Nevertheless, Yanaga et al.7 also reported that BW had a significant effect on aortic enhancement in the BW-based CM injection protocol, while the aortic enhancement in the BSA group was not influenced by BW. This finding is discordant with the present results, which demonstrated no correlation between BW and vascular enhancement in the BW group. A possible explanation for this outcome could be found in the different injection protocols between the two studies. In fact, patients in the BW group had the CM injected at different IDRs based on their size, while Yanaga et al. administered CM at a fixed injection rate. Thus, the present injection protocol partially counteracted the well-established negative correlation between higher BMI and vascular attenuation.5 In the subgroup analysis based on BMI, no significant differences were found in vascular attenuation in two BMI subgroups in both patient groups, suggesting that both CM injection protocols are reliable and not negatively affected by a patient’s size; hence, either strategy can be applied in clinical practice, depending on the operator’s preferences,
Please cite this article as: Yin W-H et al., Contrast medium injection protocols for coronary CT angiography: should contrast medium volumes be tailored to body weight or body surface area?, Clinical Radiology, https://doi.org/10.1016/j.crad.2019.12.005
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Figure 5 CT images in four individuals representing patients from the low and high BMI groups subjected to the BW and BSA protocols. (a) A patient in the BW group weighing 55kg with BMI 19.7 kg/m2. CT attenuation of the ascending aorta was 391.7 HU. (b) A patient in the BW group; 90.1 kg, BMI 31.1 kg/m2, 390 HU. (c) A patient in BSA group; 60.2 kg, BMI 19.6 kg/m2, 396.8 HU. (d) A patient in BSA group; 95.5 kg, BMI 31.7 kg/ m2, 382.3 HU. Enhancement of the ascending aorta was adequate in four patients, and similar in low and high BMI patients subjected to the BW and BSA protocols.
with no need for further refinement in an overweight population. Therefore, it is anticipated that the simple calculation of BW or BSA scales could be programmed to calculate both dose and injection rate automatically and program this information directly into a power injector. The present study presents some limitations. First, the iodine dose per BSA in the first and second phase was set at 9,600 mg iodine/m2 and 1,160 mg iodine/m,2 respectively. These were empirical values based on previous research and clinical experience that this amount provides consistent and adequate attenuation. Besides, the calculation of the body surface area is complicated in the daily clinical routine. Second, age, sex, BMI, and heart rate may all Table 4 Comparison of subjective image-quality scores.
Reader 1 Reader 2 Overall
BW group
BSA group
p-Values
4.10.9 4.11.0 4.10.9
41 41.1 40.9
0.667 0.688 0.770
BW, body weight; BSA, body surface area.
influence the results; however, the hierarchical analysis demonstrated no significant difference in such subgroups. Third, calculation of CM dose based on lean body weight has been proposed in previous study.19 Since lean body weight needs a body composition and analyser scale to measure body fat using complex calculations, this study did not explore whether a lean body weight protocol could improve the uniformity of enhancement compared with BW- or BSAbased protocols in CCTA. Fourth, the aim of the present study was to investigate luminal imaging, rather than to quantify coronary artery stenosis or plaque. Therefore, only CT attenuation, noise, SNR, and CNR were analysed in this study. Fifth, the patient cohort was limited in size, especially in the BW >100 kg (n¼4) or BW 50 kg (n¼8) groups. Additionally, in the BW 50 kg group, a tube voltage of 70 kVp could have been used.20 It is possible that with a larger patient population, portions of data may have achieved true statistical significance. The ideal situation would involve scanning the same patient using the two protocols and comparing the vessel enhancement; however, this was impractical in the clinical setting. Larger multicentre studies
Please cite this article as: Yin W-H et al., Contrast medium injection protocols for coronary CT angiography: should contrast medium volumes be tailored to body weight or body surface area?, Clinical Radiology, https://doi.org/10.1016/j.crad.2019.12.005
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would be desirable to minimise the effect of individual differences. In conclusion, the present study demonstrates that CM injection protocols based on BW or BSA could provide patient-to-patient uniformity of vascular enhancement and image quality, irrespective of patient size. Therefore, both BW-adjusted and BSA-adjusted injection protocols could be reliably used in CCTA.
Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements This study was granted by the Ministry of Science and Technology of China, National key research and development project (2016YFC1300403) and Fundamental Research Funds for the Central Universities (3332018063). U.J.S. is a consultant for and/or receives research support from Astellas, Bayer, GE, Guerbet, HeartFlow Inc., Medrad, and Siemens. The other authors have no industry relationships or conflicts of interest relevant to this investigation to disclose.
References 1. Schoepf UJ. Contrast media for coronary CT angiography: should an isoosmolar agent be used? Radiology 2018;286(1):81e2. 2. Bae KT. Intravenous contrast medium administration and scan timing at CT: considerations and approaches. Radiology 2010;256(1):32e61. 3. Albrecht MH, Nance JW, Schoepf UJ, et al. Diagnostic accuracy of low and high tube voltage coronary CT angiography using an X-ray tube potential-tailored contrast medium injection protocol. Eur Radiol 2018;28(5):2134e42. 4. De Santis D, Caruso D, Schoepf UJ, et al. Contrast media injection protocol optimization for dual-energy coronary CT angiography: results from a circulation phantom. Eur Radiol 2018;28(8):3473e81. 5. Bae KT, Seeck BA, Hildebolt CF, et al. Contrast enhancement in cardiovascular MDCT: effect of body weight, height, body surface area, body mass index, and obesity. AJR (Am J Roentgenol) Am J Roentgenol 2008;190(3):777e84.
6. Bae KT, Heiken JP, Brink JA. Aortic and hepatic contrast medium enhancement at CT: part I. Prediction with a computer model. Radiology 1998;207(3):647e55. 7. Yanaga Y, Awai K, Nakaura T, et al. Contrast material injection protocol with the dose adjusted to the body surface area for MDCT aortography. AJR (Am J Roentgenol) Am J Roentgenol 2010;194(4):903e8. 8. Yin WH, Lu B, Li N, et al. Iterative reconstruction to preserve image quality and diagnostic accuracy at reduced radiation dose in coronary CT angiography: an intraindividual comparison. JACC Cardiovasc Imag 2013;6(12):1239e49. 9. Yin WH, Lu B, Gao JB, et al. Effect of reduced x-ray tube voltage, low iodine concentration contrast medium, and sinogram-affirmed iterative reconstruction on image quality and radiation dose at coronary CT angiography: results of the prospective multicenter REALISE trial. J Cardiovasc Comput Tomogr 2015;9(3):215e24. 10. Mosteller RD. Simplified calculation of body-surface area. N Engl J Med 1987;317(17):1098. 11. Awai K, Hiraishi K, Hori S. Effect of contrast material injection duration and rate on aortic peak time and peak enhancement at dynamic CT involving injection protocol with dose tailored to patient weight. Radiology 2004;230(1):142e50. 12. Raff GL, Abidov A, Achenbach S, et al. SCCT guidelines for the interpretation and reporting of coronary computed tomographic angiography. J Cardiovasc Comput Tomogr 2009;3(2):122e36. 13. Rengo M, Dharampal A, Lubbers M, et al. Impact of iodine concentration and iodine delivery rate on contrast enhancement in coronary CT angiography: a randomized multicenter trial (CT-CON). Eur Radiol 2019;29(11):6109e18. 14. Fei X, Du X, Yang Q, et al. 64-MDCT coronary angiography: phantom study of effects of vascular attenuation on detection of coronary stenosis. AJR (Am J Roentgenol) Am J Roentgenol 2008;191(1):43e9. 15. Becker CR, Hong C, Knez A, et al. Optimal contrast application for cardiac 4-detector-row computed tomography. Invest Radiol 2003;38(11):690e4. 16. Cademartiri F, Mollet NR, van der Lugt A, et al. Intravenous contrast material administration at helical 16-detecter row CT coronary angiography: effect of iodine concentration on vascular attenuation. Radiology 2005;236(2):661e5. 17. Rutten A, Meijs MF, de Vos AM, et al. Biphasic contrast medium injection in cardiac CT: moderate versus high concentration contrast material at identical iodine flux and iodine dose. Eur Radiol 2010;20(8):1917e25. 18. Lubbers MM, Kock M, Niezen A, et al. Iodixanol versus iopromide at coronary CT angiography: lumen opacification and effect on heart rhythmdthe randomized IsoCOR Trial. Radiology 2018;286(1):71e80. 19. Awai K, Kanematsu M, Kim T, et al. The optimal body size index with which to determine iodine dose for hepatic dynamic CT: a prospective multicenter study. Radiology 2016;278(3):773e81. 20. Feng R, Tong J, Liu X, et al. High-pitch coronary CT angiography at 70 kVp adopting a protocol of low injection speed and low volume of contrast medium. Korean J Radiol 2017;18(5):763e72.
Please cite this article as: Yin W-H et al., Contrast medium injection protocols for coronary CT angiography: should contrast medium volumes be tailored to body weight or body surface area?, Clinical Radiology, https://doi.org/10.1016/j.crad.2019.12.005
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Clinical Radiology journal homepage: www.clinicalradiologyonline.net
Contrast medium injection protocols for coronary CT angiography: should contrast medium volumes be tailored to body weight or body surface area? W.-H. Yin a, 1, Y.-T. Yu a, 1, Y. Zhang a, b, Y.-Q. An a, Z.-H. Hou a, Y. Gao a, H.-P. Wang a, B. Lu a, *, D. De Santis c, J.D. Rollins c, U.J. Schoepf c, d a Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China b Department of Radiology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, People’s Republic of China c Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC, USA d Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA
art icl e i nformat ion Article history: Received 16 August 2019 Accepted 6 December 2019
AIM: To compare the uniformity and image quality between contrast media injection protocols adjusted for patient body weight (BW) versus body surface area (BSA) during coronary computed tomography (CT) angiography (CCTA). MATERIALS AND METHODS: Consecutive patients (n¼489) with suspected coronary artery disease were randomised prospectively to one of two CCTA protocols. In the BW protocol (n¼245), patients received individualised iodine delivery rates (50 kg: 1 g/s; 51e60 kg: 1.2 g/ s; 61e70 kg: 1.4 g/s; 71e80 kg: 1.6 g/s; 81e90 kg: 1.8 g/s; 91e100 kg: 2 g/s; >100 kg: 2.2 g/s). In the BSA protocol (n¼244), patients received 9,600 mg iodine/m2 of contrast medium over 12 seconds. Attenuation and image noise were measured. Signal-to-noise ratio and contrast-tonoise ratio were calculated. Image quality was scored. Attenuation was assessed for correlation with BW and BSA using linear regression. RESULTS: There were no statistically significant differences in mean arterial attenuation (396.847.6 versus 395.842.2 HU, p¼0.804; 95% confidence interval: e7 to 9), image noise (25.25.8 versus 25.55.4 HU; p¼0.549), signal-to-noise ratio (16.74.4 versus 16.63.6; p¼0.902), contrast-to-noise ratio (25.15.8 versus 25.87.4; p¼0.258) or image quality scores (4.10.9 versus 40.9; p¼0.770) between the BW and BSA protocols. There was no correlation between BW and aortic attenuation or between BSA and aortic attenuation (p¼0.324 and 0.932, respectively).
* Guarantor and correspondent: B. Lu, Department of Radiology, Fuwai Hospital, #167 Bei-Li-Shi Street, Xi-Cheng District, Beijing, 100037, People’s Republic of China. Tel.: þ86 10 88322662; fax: þ86 10 68313012. E-mail address: [email protected] (B. Lu). 1 These authors contributed equally to this paper. https://doi.org/10.1016/j.crad.2019.12.005 0009-9260/Ó 2019 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Please cite this article as: Yin W-H et al., Contrast medium injection protocols for coronary CT angiography: should contrast medium volumes be tailored to body weight or body surface area?, Clinical Radiology, https://doi.org/10.1016/j.crad.2019.12.005
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CONCLUSION: The average contrast media attenuation and image quality was comparable between BW-adjusted protocol and BSA-adjusted protocol. Ó 2019 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Introduction Coronary computed tomography angiography (CCTA) is a robust minimally invasive diagnostic tool for the assessment of coronary artery disease (CAD; 50% luminal stenosis in a vessel).1 Contrary to the dramatic technical advancements of CT systems in the last decade, the optimal contrast medium (CM) injection protocol is still a matter of active investigation.2 Injecting a fixed amount of CM is the simplest and fastest approach to perform CCTA; however, in recent years a trend toward a patient-centred examination is taking place.3 In light of that, the CM injection is often tailored to the patient’s body weight (BW), while the iodine delivery rate (IDR) is also varied to achieve adequate contrast enhancement.4 Previous study has shown that such an approach could achieve consistent vascular enhancement despite its complexity.5 Nevertheless, patient factors other than BW, such as muscle mass, cardiac output, and hydration status, may influence contrast enhancement.6,7 Among them, body surface area (BSA) has been demonstrated as a reliable body parameter to achieve a consistent contrast enhancement in CCTA over a wide range of body sizes.5 Yanaga et al.7 investigated the effect on aortic enhancement of CM volume adjusted for BSA in aortic CT angiography, demonstrating that a BSA-based CM injection protocol provides adequate and consistent aortic enhancement regardless of BW; however, to the authors’ knowledge, a comparison between BW-based and BSA-based CM injection protocols in CCTA has not been reported to date. Thus, the purpose of the present study was to evaluate prospectively whether the image quality of BSA-based CM injection protocol is non-inferior to the widely accepted BW-based protocol in patients undergoing CCTA for suspected CAD.
Materials and Methods Study design and patient population This single-centre study was approved by the hospital’s Institutional Ethics Committee. The study was a prospective, randomised, non-inferiority trial. Between September 2018 and December 2018, 515 consecutive patients with suspected CAD who were scheduled to undergo clinically indicated CCTA due to chest pain, the presence of one or more CAD risk factors, or electrocardiographic abnormalities were approached prospectively. Inclusion criteria were age 30e85 years and a stable baseline cardiac sinus rhythm.
Exclusion criteria included known CAD, history of prior percutaneous intervention or bypass surgery, prior reaction to iodinated contrast materials, and impaired renal function (eGFR < 30 ml/min/1.73 m2).
CCTA acquisition All patients underwent CCTA on a second-generation dual-source CT system (Somatom Definition Flash, Siemens Healthineers, Forchheim, Germany) operating in single-energy mode. Acquisition parameters were 2640.6 mm detector collimation, 280 ms gantry rotation time, pitch of 3.4, and field of view of 200e250 mm. Heart rate was recorded during CCTA. Individuals with heart rate 60 beats/min were scanned with prospectively electrocardiogram (ECG)-triggered high-pitch spiral mode8 with a trigger phase at 60% of the R-R interval. Individuals with a heart rate between 60 and 70 beats/min were scanned with prospectively ECG-triggered sequential acquisition mode during mid diastole (70e80% of the R-R interval). Individuals with heart rates 70 beats/min were scanned with prospectively ECG-triggered sequential acquisition mode during end systole (35e45% of the R-R interval). The X-ray tube potential and tube current were tailored to the body mass index (BMI) as follows: 80 kV/400 mAs for BMI <20 kg/m2, 100 kV/370 mAs for 20 kg/m2 BMI <25 kg/m2, and 120 kV/320 mAs for BMI 25 kg/m2. Attenuation-based tube current modulation (CareDose 4D, Siemens) was applied. The time for scan initiation was established by means of an automated bolus-tracking technique (CareBolus, Siemens): a region of interest (ROI) was placed in the ascending aorta; after a 10-second delay, repetitive scans at 1-second intervals were performed, the trigger level was set at 100 HU, and an additional 6-second delay was set before commencing the angiographic acquisition CCTA study.8
CM injection protocols CM was injected via an 18-G access through an antecubital vein using a double-syringe power injector (Stellant, Medrad, Indianola, PA, USA). A triple-phase CM injection protocol was used, which consisted of undiluted CM (Ioversol 350 mg iodine/ml, Hengrui Medicine, Jiangsu, China) followed by a 30:70 mixture of CM and saline followed by a 20 ml saline flush. Therefore, the total CM volume was calculated as the volume of first phase plus 30% of the second phase. All patients were randomised 1:1 to either BW group or BSA group using a web-based randomisation system.9 In the BW group, each patient received an individualised IDR (g iodine/s) in the first phase (50 kg: 1 g iodine/s; 51e60 kg:
Please cite this article as: Yin W-H et al., Contrast medium injection protocols for coronary CT angiography: should contrast medium volumes be tailored to body weight or body surface area?, Clinical Radiology, https://doi.org/10.1016/j.crad.2019.12.005
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1.2 g iodine/s; 61e70 kg: 1.4 g iodine/s; 71e80 kg: 1.6 g iodine/s; 81e90 kg: 1.8 g iodine/s; 91e100 kg: 2 g iodine/s; >100 kg: 2.2 g iodine/s).
Flow rate ðmL = sÞ ¼
Flow rate was calculated as follows
Image reconstruction
Flow Rate ðmL = sÞ ¼
IDR ðgI=sÞ 1000 CM concentration ðmgI=mLÞ
CM volume was calculated as follows
CM volume ðmlÞ ¼ flow rateðml = sÞ 12 s The second CM injection had a fixed duration of 6 seconds, with IDR and flow rate corresponding to those used in the first phase. Comprehensive CM injection parameters are reported in Table 1. For the BSA group, BSA was estimated using the following formula10: pffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi weight ðkgÞ height ðcmÞ BSA m2 ¼ 60 A fixed-duration injection protocol was used in order to reduce interpatient variability in aortic enhancement.11 In the first CM injection, 9,600 mg iodine/m2 of CM was administered over 12 seconds such that patients received CM volume according to the equation: CM volume（mL） ¼
9600 ðmgI=m2 Þ BSA ðm2 Þ CM concentration ðmgI=mLÞ
The corresponding flow rate was therefore calculated as: Flow rate ðmL = sÞ ¼
CM volume ðmLÞ 12 s
During the second CM injection, patients received 1,160 mg iodine/m2 of CM over a fixed duration of 6 seconds, such that: CM volume（mL） ¼
1160 ðmgI=m2 Þ BSA ðm2 Þ CM concentration ðmgI=mLÞ
Likewise, the corresponding flow rate for the second phase was calculated as: Table 1 Body weight (BW) injection protocol. Weight group
Iodine Flow rate delivery (ml/s) rate (g/s)
Volume (ml) phase 1
Volume (ml) phase 2
50 kg (n¼8) 60 kg (n¼43) 70 kg (n¼76) 80 kg (n¼65) 90 kg (n¼36) 100 kg (n¼13) >100 kg (n¼4)
1 1.2 1.4 1.6 1.8 2 2.2
35 41 48 55 61 68 76
17.4 20.4 24 27.6 30.6 34.2 37.8
2.9 3.4 4 4.6 5.1 5.7 6.3
CM volume ðmLÞ 0:3 6 s
All CCTA datasets were reconstructed with the following parameters: 0.75 mm section thickness, 0.5 mm slice increment, 200 mm field-of-view. Sinogram-affirmed iterative reconstruction (SAFIRE) strength level of 3 was used with a medium smooth-tissue convolution kernel (I26f). According to the previously described beneficial effects of a higher spatial resolution kernel on the evaluation of heavy calcifications, the higher frequency “I46f” algorithm was also included.8
Objective image quality analysis All CCTA image datasets were transferred to a workstation using syngo.via version VB10 (Siemens Healthineers, Forchheim, Germany). A single observer with 6 years of experience in CCTA performed the quantitative measurements, blinded to the CM injection protocol. On the axial plane, attenuation values and standard deviation (SD) were measured by drawing circular ROIs within the aortic root (size: 100 mm2) at the level of the right coronary artery ostium. Coronary artery attenuation values were measured within the left main coronary artery and at the level of the proximal and distal right coronary artery, carefully avoiding vessel wall and plaques. Coronary artery attenuation values were eventually averaged to obtain a single value. An additional ROI was placed within the pericardial fat in order to measure attenuation and SD. Image noise was defined as the SD of pericardial fat. To ensure data consistency, all measurements were performed in triplicate and subsequently averaged. Signal-to-noise ratio (SNR) and contrastto-noise ratio (CNR) were defined according to the following: SNR ¼
HUaorta noise
CNR ¼
HUvessels HUfat noise
Subjective image quality analysis Two observers with 5 and 6 years of experience in CCTA, respectively, independently assessed subjective image quality, blinded to the CM injection protocol. Images were evaluated on a per-segment level using the modified 18segment classification system of the Society of Cardiovascular Computed Tomography12 in random order, and with a preset window setting (window level 300 HU, width 800 HU), freely adjustable based on the reader’s preference. Observers were asked to grade the image quality using the following five-point scale: 1, non-diagnostic; 2, poor; 3, adequate (presence of artefacts not limiting detection of luminal stenosis); 4, good; and 5, excellent. Mean image quality scores 3 were deemed diagnostic.
Please cite this article as: Yin W-H et al., Contrast medium injection protocols for coronary CT angiography: should contrast medium volumes be tailored to body weight or body surface area?, Clinical Radiology, https://doi.org/10.1016/j.crad.2019.12.005
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Statistical analysis This study was a non-inferiority design. The primary endpoint was the uniformity of vessel enhancement, defined as the average magnitude of attenuation values. The sample size was determined by power analysis based on a type 2 error rate b¼0.2. Based on historical analysis a CT attenuation of 390 HU was assumed, with a standard deviation of approximately 80 HU.13 A difference of 30 HU in CT attenuation was prespecified and considered clinically relevant. Considering a 10% dropout rate, the study required 125 patients in each group. Data were analysed using commercially available software (SPSS 2007, SPSS for Windows, Version 16.0, Chicago, IL, USA). Continuous variables were expressed as meanSD while categorical variables were reported as frequencies or percentages. Differences between groups were compared using one-way analysis of variance; all pairs of groups were compared using Fisher’s least significant difference method. Normally distributed variables were compared using Student’s t-test for unpaired samples. The c2 test was used for categorical variables. The generalised linear model was used to analyse the effects of age, sex, BMI, and heart rate on vessel enhancement in both protocols. The Akaike information criterion was calculated for all models and most appropriate model was selected, with age, sex, BMI, and heart rate considered as confounding factors. Two-tailed p<0.05 was considered statistically significant.
venous access for the desired contrast medium delivery rate. Therefore, the final study cohort consisted of 489 patients who provided written informed consent. Patients were randomly assigned to undergo one of two CM protocols (Fig 1). All CCTA studies were successfully completed without complications. No patient in the BW or BSA protocol experienced CM extravasation or aborted injection secondary to patient symptoms. Data analysis was performed for 489 patients: 245 patients (148 males, mean age 59.212.5 years, age range 30e85 years) in the BW group, and 244 patients (135 males, mean age 59.811.3 years, age range 30e83 years) in the BSA group. There were no significant differences in patients’ age, sex distribution, BMI, or heart rate (all p0.272). In the BW group, tube voltage of 120, 100, and 80 kVp was performed in 130, 105, and 10 patients, respectively. In the BSA group, tube voltage of 120, 100, and 80 kVp was performed in 125, 108, and 11 patients, respectively. Patient characteristics, CT imaging details, and contrast agent administration parameters are summarised in Table 2.
CM volume and injection flow rate The CM volume and injection rate were comparable between the BW group (volume: 55.18.4 ml; rate: 4.10.6 ml/s) and the BSA group (volume: 54.46.6 ml; rate: 4.10.5 ml/s; all p0.218).
Results
Objective image quality analysis
Patient population
In the BW and BSA groups, considering age, sex, BMI, and heart rate as confounding factors, the lowest Akaike information criterion scores were 22,577.1 and 2,523.3, respectively. Using a generalised linear model, age, sex, BMI, and
Of 515 patients approached for participation, 24 patients refused to participate, and two patients had inadequate
Figure 1 Study enrolment flowchart. Consecutive patients (n¼515) were approached for participation. Of those, 489 patients were enrolled and underwent CCTA: 245 were randomly assigned to the BW protocol, and 244 to the BSA protocol. Please cite this article as: Yin W-H et al., Contrast medium injection protocols for coronary CT angiography: should contrast medium volumes be tailored to body weight or body surface area?, Clinical Radiology, https://doi.org/10.1016/j.crad.2019.12.005
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Table 2 Baseline demographic data and contrast dose in body weight (BW) and body surface area (BSA) protocols. Parameters Patient demographics Male-to-female ratio Age (years) Height (cm) Weight (kg) Body mass index (kg/m2) Heart rate (beats/min) No. of patients with CAD Scanning parameter Reference tube current (mAs) Tube voltage (120 kV:100 kV: 80 kV) Contrast medium injection protocol Contrast medium volume (ml) Flow rate in the first phase (ml/s)
BW group
BSA group
p-Values
148:97 59.212.5 166.98.0 71.412.7 25.63.7 64.59.5 55 (22.4)
135:109 59.811.3 1667.7 70.311.5 25.43.1 65.97.3 43 (17.6)
0.272 0.629 0.231 0.309 0.679 0.086 0.214
344.726.9 347.827.0 0.205 130:105:10 125:108:11 0.911
55.18.4 4.10.6
54.46.6 4.10.5
0.285 0.218
All parameters are expressed as mean standard deviation or n (%). CAD, coronary artery disease.
heart rate had no statistically significant effect on vessel enhancement (all p>0.05). Full objective image quality data are reported in Table 3. The BW protocol and BSA protocol returned comparable attenuation (396.847.6 versus 395.842.2 HU; p¼0.804), SNR (16.74.4 versus 16.63.6; p¼0.902), and CNR (25.15.8 versus 25.87.4; p¼0.258). Mean difference of CT attenuation between the BW and BSA protocols was 14.1, with no statistical significance (p¼0.804); 95% confidence interval was e7 to 9.0. The CT attenuation of four examinations was deemed not optimal in the BW group. Of these four, the CT attenuation of three patients was <300 HU, and >500 HU in the other. In comparison, no examination had a CT attenuation of <300 HU in the BSA group whereas one exceeded 500 HU. -vis To evaluate the robustness of image quality vis-a body size, the cohort was divided into lower and higher body mass index (BMI) groups. Because the mean BMI in this study was 25.48 kg/m2, this value was used as the cutoff threshold. No correlation was found between CT attenuation and BW or BSA in either the BW- or BSA-adjusted group (p¼0.324 and 0.932, respectively; Figs 2a and 3a). There was no correlation between weight and aortic attenuation in the low (p¼0.174 and 0.755, respectively) or high (p¼0.969 and 0.209, respectively) BMI sub-groups in either the BW- or BSA-adjusted group (Figs 2b and 3b). There was no significant difference in vascular attenuation between the low BMI group and high BMI group in either the BW- or BSA-
Table 3 Comparison of objective image quality parameters between in body weight (BW) and body surface area (BSA) protocol groups.
Attenuation Image noise Signal-to-noise ratio Contrast-to-noise ratio
BW group
BSA group
p-Values
396.847.6 25.25.8 16.74.4 25.1 5.8
395.842.2 25.55.4 16.63.6 25.87.4
0.804 0.549 0.902 0.258
Figure 2 Plot of CT attenuation versus BW in the BW group. (a) The regression formula was CT attenuation ¼ 425.55e0.403 (BW; blue line). There was no correlation between BW and CT attenuation (p¼0.324). Correlation is significant at the 0.01 level (two-tailed). (b) The regression formula of CT attenuation versus BW was CT attenuation ¼ 445.93e0.7445(BW) for the low BMI group (red line) and CT attenuation ¼ 397.04e0.0154(BW) for the high BMI group (purple line). There was no correlation between BW and CT attenuation in both low (p¼0.174) and high (p¼0.969) BMI groups.
adjusted group (398.651.2 versus 395.843.6 HU, p¼0.649; 398.143.7 versus 393.240.4 HU, p¼0.362, respectively; Figs 4 and 5).
Subjective image quality analysis For the purpose of assessing 50% luminal stenosis on a per-segment level, all of the examinations were deemed diagnostic. A total of 3,674 and 3,659 coronary artery segments were present in the BW and BSA groups, respectively (mean 15 segments per patient). Of these, 151 (4.1%) from the BW group and 146 segments (4%) from the BSA group were deemed non-diagnostic consistently by both observers: 66 (1.8%) and 59 (1.6%) segments could not be confidently evaluated due to “blooming” artefact from heavy calcification, while motion artefact affected 85 segments (2.3%) and 88 segments (2.4%) in the BW and BSA groups, respectively. Non-diagnostic image quality between the two groups did not reach statistical significance
Please cite this article as: Yin W-H et al., Contrast medium injection protocols for coronary CT angiography: should contrast medium volumes be tailored to body weight or body surface area?, Clinical Radiology, https://doi.org/10.1016/j.crad.2019.12.005
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Figure 3 Plot of CT attenuation versus BSA. There was no correlation between BSA and CT attenuation (p¼0.932). (a) The regression formula was CT attenuation ¼393.46 þ 1.2981(BSA; blue line). (b) The regression formula of CT attenuation versus BSA was CT attenuation ¼ 383.44 þ 8.5947(BSA) for the low BMI group (red line) and CT attenuation ¼ 447.88e28.953(BSA) for the high BMI group (yellow line). There was no correlation between BSA and CT attenuation in either low (p¼0.755) or high (p¼0.209) BMI groups.
Figure 4 Comparison of CT attenuation between low and high BMI groups within the BW and BSA groups (all p > 0.05).
(p¼0.813). Overall, image-quality scores on a per-segment level as determined by the readers were similar for the two protocol groups (p¼0.770, Table 4).
Discussion This study compares the contrast enhancement and image quality in CCTA with an individualised injection
protocol based on BW and BSA. By basing the CM application on either BW or BSA, the average enhancement and image quality was comparable between the two groups. No correlation was found between CT attenuation and BW or BSA in either group. The optimal vascular attenuation is approximately 350 HU in CCTA for detection of coronary artery stenosis.14 A lower vascular enhancement can aid the differentiation of the enhanced lumen from calcification,15 while higher vascular attenuations may be helpful in improving the visualisation of small coronary arteries.16 The vascular attenuation achieved in the present study was slightly lower than 400 HU in both protocols. Thus, both approaches provided adequate vessel opacification, which is essential to achieve a diagnostic CCTA examination. Body weight is the main patient-related determinant of vascular enhancement. Adjusting IDR to different weight categories is a sensible approach to contrast protocols.17 Lubbers et al.18 and Rengo et al.13 compared the effect of CM iodine concentration and osmolarity on contrast enhancement when injected at a constant IDR in CCTA. The results demonstrated that for a given IDR, CM with different concentrations or osmolarities achieve comparable vascular enhancement. BSA has been proposed as an alternative in determining the optimal CM volume in CCTA.5 In the present study, BSA was demonstrated to be an effective determinant of CM volume, providing adequate and consistent vascular enhancement. Interestingly, these results have been achieved in both low- and high-BMI groups, further validating the robustness of using BSA to estimate appropriate CM volume. The present investigation did not demonstrate significant differences in terms of vascular enhancement and image quality between the BSA and BW groups. These results are in accordance with Yanaga et al.,7 who prospectively investigated the effect on aortic enhancement of CM volumes adjusted for BSA and BW in CTA. The authors demonstrated that both approaches achieved comparable aortic enhancement. Nevertheless, Yanaga et al.7 also reported that BW had a significant effect on aortic enhancement in the BW-based CM injection protocol, while the aortic enhancement in the BSA group was not influenced by BW. This finding is discordant with the present results, which demonstrated no correlation between BW and vascular enhancement in the BW group. A possible explanation for this outcome could be found in the different injection protocols between the two studies. In fact, patients in the BW group had the CM injected at different IDRs based on their size, while Yanaga et al. administered CM at a fixed injection rate. Thus, the present injection protocol partially counteracted the well-established negative correlation between higher BMI and vascular attenuation.5 In the subgroup analysis based on BMI, no significant differences were found in vascular attenuation in two BMI subgroups in both patient groups, suggesting that both CM injection protocols are reliable and not negatively affected by a patient’s size; hence, either strategy can be applied in clinical practice, depending on the operator’s preferences,
Please cite this article as: Yin W-H et al., Contrast medium injection protocols for coronary CT angiography: should contrast medium volumes be tailored to body weight or body surface area?, Clinical Radiology, https://doi.org/10.1016/j.crad.2019.12.005
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Figure 5 CT images in four individuals representing patients from the low and high BMI groups subjected to the BW and BSA protocols. (a) A patient in the BW group weighing 55kg with BMI 19.7 kg/m2. CT attenuation of the ascending aorta was 391.7 HU. (b) A patient in the BW group; 90.1 kg, BMI 31.1 kg/m2, 390 HU. (c) A patient in BSA group; 60.2 kg, BMI 19.6 kg/m2, 396.8 HU. (d) A patient in BSA group; 95.5 kg, BMI 31.7 kg/ m2, 382.3 HU. Enhancement of the ascending aorta was adequate in four patients, and similar in low and high BMI patients subjected to the BW and BSA protocols.
with no need for further refinement in an overweight population. Therefore, it is anticipated that the simple calculation of BW or BSA scales could be programmed to calculate both dose and injection rate automatically and program this information directly into a power injector. The present study presents some limitations. First, the iodine dose per BSA in the first and second phase was set at 9,600 mg iodine/m2 and 1,160 mg iodine/m,2 respectively. These were empirical values based on previous research and clinical experience that this amount provides consistent and adequate attenuation. Besides, the calculation of the body surface area is complicated in the daily clinical routine. Second, age, sex, BMI, and heart rate may all Table 4 Comparison of subjective image-quality scores.
Reader 1 Reader 2 Overall
BW group
BSA group
p-Values
4.10.9 4.11.0 4.10.9
41 41.1 40.9
0.667 0.688 0.770
BW, body weight; BSA, body surface area.
influence the results; however, the hierarchical analysis demonstrated no significant difference in such subgroups. Third, calculation of CM dose based on lean body weight has been proposed in previous study.19 Since lean body weight needs a body composition and analyser scale to measure body fat using complex calculations, this study did not explore whether a lean body weight protocol could improve the uniformity of enhancement compared with BW- or BSAbased protocols in CCTA. Fourth, the aim of the present study was to investigate luminal imaging, rather than to quantify coronary artery stenosis or plaque. Therefore, only CT attenuation, noise, SNR, and CNR were analysed in this study. Fifth, the patient cohort was limited in size, especially in the BW >100 kg (n¼4) or BW 50 kg (n¼8) groups. Additionally, in the BW 50 kg group, a tube voltage of 70 kVp could have been used.20 It is possible that with a larger patient population, portions of data may have achieved true statistical significance. The ideal situation would involve scanning the same patient using the two protocols and comparing the vessel enhancement; however, this was impractical in the clinical setting. Larger multicentre studies
Please cite this article as: Yin W-H et al., Contrast medium injection protocols for coronary CT angiography: should contrast medium volumes be tailored to body weight or body surface area?, Clinical Radiology, https://doi.org/10.1016/j.crad.2019.12.005
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would be desirable to minimise the effect of individual differences. In conclusion, the present study demonstrates that CM injection protocols based on BW or BSA could provide patient-to-patient uniformity of vascular enhancement and image quality, irrespective of patient size. Therefore, both BW-adjusted and BSA-adjusted injection protocols could be reliably used in CCTA.
Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements This study was granted by the Ministry of Science and Technology of China, National key research and development project (2016YFC1300403) and Fundamental Research Funds for the Central Universities (3332018063). U.J.S. is a consultant for and/or receives research support from Astellas, Bayer, GE, Guerbet, HeartFlow Inc., Medrad, and Siemens. The other authors have no industry relationships or conflicts of interest relevant to this investigation to disclose.
References 1. Schoepf UJ. Contrast media for coronary CT angiography: should an isoosmolar agent be used? Radiology 2018;286(1):81e2. 2. Bae KT. Intravenous contrast medium administration and scan timing at CT: considerations and approaches. Radiology 2010;256(1):32e61. 3. Albrecht MH, Nance JW, Schoepf UJ, et al. Diagnostic accuracy of low and high tube voltage coronary CT angiography using an X-ray tube potential-tailored contrast medium injection protocol. Eur Radiol 2018;28(5):2134e42. 4. De Santis D, Caruso D, Schoepf UJ, et al. Contrast media injection protocol optimization for dual-energy coronary CT angiography: results from a circulation phantom. Eur Radiol 2018;28(8):3473e81. 5. Bae KT, Seeck BA, Hildebolt CF, et al. Contrast enhancement in cardiovascular MDCT: effect of body weight, height, body surface area, body mass index, and obesity. AJR (Am J Roentgenol) Am J Roentgenol 2008;190(3):777e84.
6. Bae KT, Heiken JP, Brink JA. Aortic and hepatic contrast medium enhancement at CT: part I. Prediction with a computer model. Radiology 1998;207(3):647e55. 7. Yanaga Y, Awai K, Nakaura T, et al. Contrast material injection protocol with the dose adjusted to the body surface area for MDCT aortography. AJR (Am J Roentgenol) Am J Roentgenol 2010;194(4):903e8. 8. Yin WH, Lu B, Li N, et al. Iterative reconstruction to preserve image quality and diagnostic accuracy at reduced radiation dose in coronary CT angiography: an intraindividual comparison. JACC Cardiovasc Imag 2013;6(12):1239e49. 9. Yin WH, Lu B, Gao JB, et al. Effect of reduced x-ray tube voltage, low iodine concentration contrast medium, and sinogram-affirmed iterative reconstruction on image quality and radiation dose at coronary CT angiography: results of the prospective multicenter REALISE trial. J Cardiovasc Comput Tomogr 2015;9(3):215e24. 10. Mosteller RD. Simplified calculation of body-surface area. N Engl J Med 1987;317(17):1098. 11. Awai K, Hiraishi K, Hori S. Effect of contrast material injection duration and rate on aortic peak time and peak enhancement at dynamic CT involving injection protocol with dose tailored to patient weight. Radiology 2004;230(1):142e50. 12. Raff GL, Abidov A, Achenbach S, et al. SCCT guidelines for the interpretation and reporting of coronary computed tomographic angiography. J Cardiovasc Comput Tomogr 2009;3(2):122e36. 13. Rengo M, Dharampal A, Lubbers M, et al. Impact of iodine concentration and iodine delivery rate on contrast enhancement in coronary CT angiography: a randomized multicenter trial (CT-CON). Eur Radiol 2019;29(11):6109e18. 14. Fei X, Du X, Yang Q, et al. 64-MDCT coronary angiography: phantom study of effects of vascular attenuation on detection of coronary stenosis. AJR (Am J Roentgenol) Am J Roentgenol 2008;191(1):43e9. 15. Becker CR, Hong C, Knez A, et al. Optimal contrast application for cardiac 4-detector-row computed tomography. Invest Radiol 2003;38(11):690e4. 16. Cademartiri F, Mollet NR, van der Lugt A, et al. Intravenous contrast material administration at helical 16-detecter row CT coronary angiography: effect of iodine concentration on vascular attenuation. Radiology 2005;236(2):661e5. 17. Rutten A, Meijs MF, de Vos AM, et al. Biphasic contrast medium injection in cardiac CT: moderate versus high concentration contrast material at identical iodine flux and iodine dose. Eur Radiol 2010;20(8):1917e25. 18. Lubbers MM, Kock M, Niezen A, et al. Iodixanol versus iopromide at coronary CT angiography: lumen opacification and effect on heart rhythmdthe randomized IsoCOR Trial. Radiology 2018;286(1):71e80. 19. Awai K, Kanematsu M, Kim T, et al. The optimal body size index with which to determine iodine dose for hepatic dynamic CT: a prospective multicenter study. Radiology 2016;278(3):773e81. 20. Feng R, Tong J, Liu X, et al. High-pitch coronary CT angiography at 70 kVp adopting a protocol of low injection speed and low volume of contrast medium. Korean J Radiol 2017;18(5):763e72.
Please cite this article as: Yin W-H et al., Contrast medium injection protocols for coronary CT angiography: should contrast medium volumes be tailored to body weight or body surface area?, Clinical Radiology, https://doi.org/10.1016/j.crad.2019.12.005