2.1 Study population
This study was performed in a single university center and was approved by our institutional review board. Written informed consent was obtained from all patients.
All patients with clinical suspicion of CAD and after a cardiological evaluation were prospectively included.
Exclusion criteria were: 1) patients with unstable angina, 2) patients with severe renal failure (eGFR < 30 mL/min/1.73m2) or other contraindications for iodinated contrast material (i.e.previous allergic reaction), 3) heart rate > 85 bpm with contraindications to the use of β-blocker, 4) presence of arrhythmia or atrial fibrillation, 5) unstable clinical condition, 6) inability to perform a breath-hold.
2.2 CCTA protocol
All patients underwent low-kV CCTA protocol combined with prospective ECG-gated technique by using a 256-MDCT scanner (iCT Elite, Philips Medical Systems, Best, The Netherlands), a dual-mode scout (on the coronal and sagittal plane) to select the acquisition volume with the lowest scan length according to the patient’s anatomy.
The 80kV setting increased to 100kV for patients with BMI over 30, automated tube-current modulation, with a pre-set value depending on the patient's shape and geometry from the scout image, and a dose right index of 7 was used to reduce the total radiation dose. The other scan parameters were as follows: collimation 128 x 0.625; rotation time 0.27 sec; thickness 0.67 mm; increment 0.335 mm; FOV 250 mm; matrix 512 x 512.
CT data were acquired with step & shoot acquisition with a prospective ECG-triggered axial acquisition, selecting the 78% (± 3%) of the cardiac cycle (R-R interval).
In each patient, an 18-gauge intravenous catheter was placed in an antecubital vein of the upper limb, and a contrast medium was injected using an automatic double-syringe injector (Medrad Stellant, Pittsburgh, PA, USA). We used a standardized dose of contrast medium volume of 70 ml (Iobidtritol 350 – Xenetix, Guerbet, Aulnay, France), with a flow rate of 4.5 mL/s followed by saline flushing (volume 50 ml, flow rate 4.5 mL/s).
If the baseline heart rate (HR) was > 65 beats per minute (BPM) and patients had no contraindications for β-blockers, metoprolol (5–20 mg) was injected intravenously before the examination.
The start of scanning was obtained for each patient by using a bolus-tracking technique, with a trigger area manually placed at the proximal ascending aorta with 120 HU as threshold and 8 s as a delay.
All raw data were reconstructed with the standard filter "Cardiac Routine" with both algorithms: MBIR (IMR, Level 1, Philips Healthcare, Cleveland, OH, USA) and IR (iDose4, Level 4, Philips Healthcare, Cleveland, OH, USA). CCTA protocol is summarized in Table 1.
Table 1
– Scanning parameters and reconstruction algorithms used
CT scan parameters
|
MBIR
|
IR
|
Tube-voltage (kV)
|
80
|
Tube-current (mAs*)
|
Automated
|
Gantry rotation time (s)
|
0.27
|
Detector configuration
|
128 × 0.625
|
FOV (mm)
|
250
|
Thickness; increment (mm)
|
0.67/0.34
|
1.0/1.0
|
CM volume (mL); flow rate (mL/s)
|
60/4.5
|
60/4.5
|
2.3 Image analysis
Images were processed on a dedicated workstation (IntelliSpace Portal 9.0, Philips) to compute multiplanar reconstructions (MPR), maximum intensity projections (MIP), and volume rendering (VR) images. The CAD-RADS assessment categories and modifiers (10), quantitative and qualitative images analyses were performed by two radiologists with 4 (reader 1) and 7 years of experience (reader 2) in CCTA, CTA, and 3D vascular images interpretation, blinded each other and to clinical data.
Qualitative image evaluation
The diagnostic image quality of the ascending aorta and the coronary arteries (RCA, CTk, LAD, and LCx) was evaluated using a 5-point Likert scale for coronary CTA by the two readers, based on the presence of motion artifacts and image noise influencing subjective image quality, as follows: 5 = excellent image quality, 4 = good image quality, 3 = acceptable image quality, 2 = below-average image quality, 1 = poor image quality (13).
Quantitative image evaluation
Each study was evaluated using the CAD-RADS lexicon based on the degree of maximum coronary stenosis among vessel segments larger than 1.5 mm in diameter. All vessels were evaluated with a scoring system from 0 to 5, as follows: 0 = absence of atherosclerosis, 1 = minimal stenosis or plaque with no stenosis (1–24%), 2 = mild stenosis (25–49%), 3 = moderate stenosis (50–69%), 4A = severe stenosis (60–79%) or 4B = left main > 50% or 3 vessel obstructive (> 70%), 5 = total occlusion (100%).
Moreover, CAD-RADS categories can be completed by modifiers as follows: N = non-diagnostic study, S = presence of a stent, G = presence of graft, and V = presence of vulnerable plaque (10).
We measured vessel contrast enhancement (mean attenuation value, HU) and image noise, determined as the standard deviation of the attenuation values (SD) (Fig. 1), by manually placing a circular region of interest (ROI) in the center of the vascular lumen in ascending aorta (AO), in the proximal segment of right coronary artery (RCA), common trunk (CTk), left anterior descending (LAD) and left circumflex (LCx).
We computed the signal-to-noise ratio (SNR) using the formula where HUA is the mean attenuation of the coronary artery (at each proximal segment) and SDA is the standard deviation of the HU values. Finally, we also evaluated the contrast resolution by calculating the contrast-to-noise ratio (CNR) using the formula: where HUA is the attenuation of the proximal tract of coronary arteries and the ascending aorta and HUB and SDB are the attenuation and standard deviation of the adjacent adipose tissue, as reported in the paper by C.H. Park et al (12).
Finally, for each patient examined with CCTA, we checked the presence of ICA as the reference standard, to confirm the diagnostic value.
2.4 Radiation dose
CT dose index (CTDIvol, mGy) and CT dose-length product (DLP, mGy·cm) were registered for all examinations. We also computed the effective dose (ED), using the formula ED = k × DLP, where k is the region-specific normalized effective dose (mSv/mGycm) derived from the paper by Deak et al (14). A k value of 0.0146 mSv/mGy-1·cm-1 (14) was currently used for estimating the effective dose from cardiovascular imaging procedures for adult patients.
2.5 Statistical analysis
Continuous variables were expressed as means and standard deviations and compared by using the Mann-Whitney test or t-Student’s test, when appropriate.
The agreement between the two readers was assessed using the Cohen kappa or Weighted kappa coefficients (0.00-0.20 indicates slight agreement; 0.21–0.40, fair agreement; 0.41–0.60, moderate agreement; 0.61–0.80, substantial agreement; and 0.81-1.00, almost perfect agreement), in case of 2 or more than 2 categorical variables, respectively.
The comparison between the continuous variables measured by the two readers was assessed with Spearman correlation and the Bland-Altman Limits of Agreement (LoA) with the 95%CIs.
A p-value < 0.05 was considered significant. The analysis was performed using SPSS software (v 26.0, SPSS Inc, Chicago, Illinois).