One-stop combined coronary-craniocervical computed tomography angiography with low-dose body coverage using artificial intelligence iterative reconstruction: a clinically feasible solution to multi-territorial atherosclerosis diagnosis

Introduction

In a recent study (1), the feasibility of one-stop combined coronary-craniocervical computed tomography angiography (CTA) was validated with a high-speed wide-detector computed tomography (CT) system, allowing the value of this protocol to be assessed in the routine clinical setting for patients suspected of coronary artery disease (CAD) or craniocervical artery disease (CCAD). As a systemic disease, atherosclerosis often coexists in multiple territories (2-4) and progresses significantly in the short term (5-7). Given the intrinsic correlation among cardiovascular atherosclerosis (3,8), combining craniocervical arteries in the scan for coronary artery patients, or the way around, could help reveal abnormalities residing beyond the region of primary concern that would have not been detected at the time of the first examination. This falls in the concept of multi-territorial atherosclerosis, from which an immediate question may arise, i.e., about extending the range of this combined coronary-craniocervical CTA to a greater part of the body.

To include a body coverage would be able to account for the aorta, the iliofemoral arteries, and the renal arteries (RAs), etc., on which the prevalence of clinical and subclinical atherosclerosis is also known to be considerably high and has been studied using hybrid approaches involving various imaging modalities (2,4,9-11). Owing to the capability of rapid mode switching on the high-speed wide-detector CT system, the most straightforward way to do so, following the combined coronary-craniocervical CTA, is to append a scan technically similar to an aortic CTA except for the scheme of contrast medium administration, which has to be arranged with respect to the preceding scan in order to form one single efficient examination. The barrier, unfortunately, is the additional radiation dose. Using the routine exposure setting, e.g., about 20 mGy in terms of volume CT dose index (CTDI_vol) (12), the dose-length product (DLP) of an added body CTA is estimated to be around 1,217 mGy·cm, which is up to 192% of the combined coronary-craniocervical CTA.

The continuous effort seeking for low-dose CT has been substantially facilitated by the evolution of the image reconstruction algorithm. As enabled by the well-established hybrid iterative reconstruction (HIR), the radiation dose for aortic CTA has been lowered to 9.33 mGy in terms of CTDI_vol (13), by utilizing low tube voltage and low contrast dosage protocols (14,15). Considering the large longitudinal coverage of aortic CTA, however, the radiation dose is still considerably high. More recently, deep learning-based reconstruction (DLR) algorithms are being proposed with the potential of greater dose reduction while preserving the noise characteristics and diagnostic acceptability (16). Wang et al. have proven the feasibility of reducing the effective dose (ED) to less than 3 mSv on aortic CTA by using the DLR algorithm (17). The demonstrated ability on noise suppression and on vascular visualization in low-dose aortic CTA, naturally, would inspire us to explore something new.

The purpose of this study was to test the hypothesis that the latest CT image reconstruction technique would allow the combined coronary-craniocervical CTA to be extended to cover the body territory at a rather low cost of additional dose, and that such an increased practical feasibility would be of direct clinical value in detecting abnormalities beyond the coronary-craniocervical arteries, including but not limited to multi-territorial atherosclerosis. The CT reconstruction technique considered for investigation herein was a deep learning-based algorithm, namely artificial intelligence iterative reconstruction (AIIR; United Imaging Healthcare, Shanghai, China), which has proven highly efficient at low-dose settings (18-20). We present this article in accordance with the STARD reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-24-1545/rc).

Methods

Study design and patient enrollment

The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). This prospective study was approved by the Institutional Review Board of The Third Xiangya Hospital of Central South University (No. 23293). Written informed consent from all participants were obtained.

As illustrated in Figure 1, patients who were scheduled for combined coronary-craniocervical CTA between March and October 2023 were considered for enrollment (group A), where a low-dose body CTA was added immediately following the original combined coronary-craniocervical CTA. All patients were informed of the associated risks of the added radiation exposure and contrast administration. Only patients with consent were included. The few under 40 years old were excluded because the added scan would place radiation on reproductive organs. Patients with clear clinical indication or known history of body arterial issues were also excluded because routine-dose aortic CTA should be taken. A retrospective set of routine-dose aortic CTA with a consistent scan range (group B) was additionally collected to form a reference for comparison with the low-dose body CTA in terms of image quality, radiation dose, and contrast volume.

Figure 1 Flowchart illustrating the study design. Group A: prospectively enrolled patients for extended CTA; group B: retrospectively collected patients who underwent routine-dose aortic CTA. CTA, computed tomography angiography; BMI, body mass index.

Extended CTA protocol

All CTA examinations were performed using a 320-row CT (uCT960+; United Imaging Healthcare). The one-stop combined coronary-craniocervial CTA protocol, as detailed in the previous study, consisted of a cranioverical CTA scan in caudocranial direction and helical mode and an electrocardiography (ECG)-gated prospective coronary CTA scan in axial mode (1). With a short interval of 4–5 s for table translation from the heart to the shoulder and for the switching from axial to helical scanning mode, a low-dose helical body CTA followed immediately, starting from above the subclavian fossa down to below the symphysis pubis. Specifically, the body CTA also covered the region from the subclavian to the aortic arch for ensuring the image quality of subclavian and brachiocephalic arteries, which may stand in the beam-hardening artifacts caused by the dense contrast medium in the subclavian vein at the time of combined coronary-craniocervical CTA (21-23).

The scanning parameters for the low-dose body CTA were kept in consistency with routine aortic CTA except for the rotation time and the reduced tube current: 100 kVp, automated tube current modulation (reference level: 30 mAs), 0.96 pitch, 80 mm detector collimation, and 0.25 s rotation time. Of note that the rotation time must not vary across the entire examination, i.e., the cranoicervical CTA, the coronary CTA, and the added body CTA, when three scans were integrated into one combined protocol, denoted as “extended CTA” for short though out the text. The scheme of contrast medium administration was configured to be variable-flow-rate in order to cope with the added scan coverage, where the flow rate of the first bolus was determined by the body mass index (BMI) of the patient, i.e., flow rate = BMI × 0.22 mL/s, contrast volume = flow rate × 15 s, followed by 20 mL contrast and 40 mL saline flush at 4 mL/s. A region of interest (ROI) was set on the descending aorta for bolus-tracking, using a triggering threshold of 180 Hounsfield unit (HU).

The coronary-craniocervcial CTA images were reconstructed at 0.5-mm slice thickness and interval using the HIR algorithm (Karl 3D; United Imaging Healthcare). Low-dose body CTA images were reconstructed at 1-mm slice thickness and interval using the AIIR. The retrospectively collected routine-dose aortic CTA images had been obtained with HIR.

Image quality evaluation

The resulting image quality of the low-dose body CTA was first evaluated in a subjective manner by two radiologists and then in an objective manner by comparing to the reference data of routine-dose aortic CTA.

The diagnostic acceptability of low-dose body CTA images was evaluated independently by two cardiovascular radiologists (P.R. and Q.L.). The overall image quality was assessed using a 5-point Likert scale, with 1 for diagnostically unacceptable and 5 for excellent, in respect to the arterial visualization, image noise, and diagnostic confidence. Images with a score ≥3 were considered adequate for diagnosis.

For objective assessment, two radiologists (R.G. and S.P.) measured six arterial segments using circular ROI of different sizes: 30 mm² on the subclavian artery (SA) at the level of thoracic inlet, 100 mm² on the thoracic aorta (TA) at the level of tracheal bifurcation, 80 mm² on the abdominal aorta (AA) at the level of porta hepatis, 5 mm² on the proximal of RA, 20 mm² on the common iliac artery (CIA) at the level of 1 cm distal to the aortic bifurcation, 10 mm² on the internal iliac artery (IIA)and 15 mm² on the external iliac artery (EIA) at the level of 1 cm distal to the common iliac bifurcation. The ROIs were placed as large as possible on each arterial segment while avoiding vessel edges, plaques, thrombi, and artifacts. The image signal and image noise, which were defined as the mean CT value (µ) and standard deviation (SD) of the ROIs on arteries, respectively, were measured to calculate signal-to-noise ratio (SNR) using SNR=μarterySDartery. ROIs were also placed on the muscle at each of the six levels to calculate contrast-to-noise ratio (CNR) using CNR=μartery−μmuscleSDmuscle. The measurement and calculation were repeated on three continuous levels to obtain an average.

CTA diagnosis

Diagnostic reading was performed and interpreted by other two radiologists (P.R. and Q.L.) on three vascular territories, i.e., coronary, craniocervical, and body. Consensus was obtained by negotiation as discrepancy occurred. Atherosclerosis in coronary arteries was evaluated according to the CAD-RADS™ (24). Atherosclerosis in craniocervical arteries was evaluated via NASCET (25) and categorized into mild stenosis (<50%), moderate stenosis (50–69%), severe stenosis (70–99%), and occlusion (100%). Atherosclerosis in body arteries was graded in the same stenosis categories as for craniocervical arteries. The degree of stenosis on coronary, craniocervical, and body territories was each reported as the highest of all lesions detected therein. Non-atherosclerotic vascular disease (e.g., aneurysm, thrombus, or dissection) and extravascular abnormalities were considered incidental findings. Of note, only incidental findings detected by the added low-dose body CTA were taken into account, which would have been missed if the examination had been restricted to coronary-craniocervical CTA.

To further characterize the impact of body CTA, the changes introduced to subsequent clinical management according to the guideline for aortic disease (26) were categorized as: risk factor modification; additional medications; additional operative therapy (vascular interventions or vascular surgery); additional operative therapy and medications.

Statistically analysis

All statistical analyses were performed using SPSS (version 20.0, SPSS Inc.). Continuous variables were expressed as mean ± SD, and categorical variables were expressed as counts. The distribution of gender was analyzed with the Chi-squared test. For data with a normal distribution, the Student’s t-test was used to assess the statistical significance of the difference between the two groups; otherwise, the Mann-Whitney U test was used. A P value of <0.05 was considered statistically significant. Kappa value was used to quantify the inter-reader agreement on subjective image quality assessment, which was interpreted as excellent (>0.80), good (0.61–0.80), moderate (0.41–0.60), inadequate (0.21–0.40), and poor (<0.21). The intraclass correlation coefficient (ICC) was used to evaluate the interreader agreement on objective image quality, which was interpreted as excellent (0.91–1.00), good (0.76–0.90), moderate (0.51–0.75), and poor (<0.51).

Results

Patient demographics

A total of 100 patients were prospectively enrolled in group A to take the additional low-dose body CTA. The retrospective group B for comparison, i.e., routine-dose aortic CTA, also included 100 patients. As listed in Table 1, there were no significant differences in age, gender or BMI between the two groups (all P>0.05).

Radiation dose and contrast dosage

As listed in Table 2, the ED of low-dose body CTA was roughly 15% of the routine-dose aortic CTA (1.6±0.6 vs. 10.3±2.6 mSv, P<0.001), while the contrast volume for the added low-dose body CTA was about 30% of the routine-dose aortic CTA (25.4±0.5 vs. 86.0±12.1 mL, P<0.001). The ED of the combined coronary-craniocervical CTA was 5.9±0.7 mSv and the contrast medium volume was 74.9±7.1 mL. As a result, the total ED for the extended CTA (7.5±1.0 mSv) was 27% higher than the combined coronary-craniocervical CTA and the total volume of contrast medium (100.3±7.6 mL) was 34% higher.

Image quality of low-dose body CTA

All the low-dose body CTA images were deemed adequate for diagnosis by both radiologists with good agreement (κ=0.75), where score 4 accounted for 6.5% and score 5 accounted for 93.5%. A representative image dataset of combined coronary-craniocervical CTA and the added low-dose body CTA was shown in Figure 2A, with more diagnostic details provided in Figure 2B. The major branches of the aorta were visualized with strong opacification and sharp boundary, where the image noise was negligible and the calcifications were conspicuous. In Figure 2A, specifically, the initial segment of the right common carotid artery was obscured by the severe beam-hardening artifacts from the dense contrast medium in the right subclavian vein during coronary-craniocervical CTA, while shown continuous in the subsequent body CTA when the contrast medium had been diluted by the saline flush.

Figure 2 Extended CTA images acquired on a 75-year-old male patient with multi-territorial atherosclerosis. The hyperrealistic rendering of combined coronary-craniocevical CTA and added low-dose aortic CTA after bone subtraction is shown in panel (A), with a discontinuous carotid artery in the coronary-craniocervical CTA (yellow arrow) but a continuous carotid artery in the low-dose body CTA (green arrow). The maximum intensity projection of added low-dose body CTA is shown in panel (B), with axial images at six levels: ① subclavian, ② thoracic, ③ abdominal, ④ renal, ⑤ common iliac, and ⑥ IIA & EIA. CTA, computed tomography angiography; IIA, internal iliac artery; EIA, external iliac artery.

Quantitative image quality analysis was shown in Figure 3. The CT values of low-dose body CTA were slightly higher than routine-dose aortic CTA, with statistical significance on CIA, IIA, and EIA segments (all P<0.05) but without statistical significance on SA, TA, AA, and RA (all P>0.05). The differences in CT values between the two groups were resulted from the different contrast administration scheme, given that stronger enhancement was achieved with the increased contrast volume and prolonged injection duration during low-dose body CTA (27). Compared to routine-dose aortic CTA, image noise in low-dose body CTA was significantly reduced by the AIIR algorithm, resulting in significantly higher SNRs and CNRs on all segments in low-dose body CTA (all P<0.05). Moderate to excellent inter-reader agreement was obtained, with the ICC ranging from 0.73 to 0.96.

Figure 3 Comparisons of CT value (A), noise (B), SNR (C), and CNR (D) between added low-dose body CTA and routine-dose aortic CTA. Asterisk “*” indicates statistical significance (P<0.05), and “ns” indicates statistical non-significance (P≥0.05). CT, computed tomography; HU, Hounsfield unit; SA, subclavian artery; TA, thoracic aorta; AA, abdominal aorta; RA, renal artery; CIA, common iliac artery; IIA, internal iliac artery; EIA, external iliac artery; SNR, signal-to-noise ratio; CNR, contrast-to-noise ratio; CTA, computed tomography angiography.

Atherosclerosis diagnosis of extended CTA

In total, 82 out of the 100 participants referred for combined coronary-craniocervical CTA were diagnosed with atherosclerosis, of which 20 patients were diagnosed with CAD or CCAD and the remaining 62 with both CAD and CCAD. Attributed to the added low-dose body CTA, additional atherosclerosis in body arteries was found in 73 (73%) patients. As summarized in Figure 4A, among the 73 patients with atherosclerosis in body arteries, 85% (62/73) presented mild stenosis, 10% (7/73) moderate stenosis, 4% (3/73) severe stenosis, and 1% (1/73) showed an occlusion at the left CIA. Regarding plaque subtypes as shown in Figure 4B, 52% patients (38/73) were identified with only calcified plaques, 47% (34/73) with both calcified and non-calcified plaques, and 1% (1/73) with only non-calcified plaques. In these patients with neither clinical indication nor history of atherosclerosis in body arteries, the subclinical atherosclerosis in body arteries was predominantly comprised of calcified components and presented as mild stenosis.

Figure 4 Degree of stenosis (A) and plaque subtypes (B) of atherosclerosis detected in body arteries by the added low-dose body CTA among the enrolled 100 patients. CTA, computed tomography angiography.

In detail, it can be found in Figure 5 that 22% patients (4/18) with neither CAD nor CCAD were diagnosed with body arterial atherosclerosis. As for patients with CAD or CCAD and patients with both CAD and CCAD, the prevalence of body arterial atherosclerosis increased to 85% (17/20) and 84% (52/62), respectively. Despite the high prevalence of atherosclerosis in body arteries among all patients (73%, 73/100), atherosclerosis was most commonly present as mild stenosis (85%, 62/73). Moderate stenosis, severe stenosis, and occlusion were all found in patients with both CAD and CCAD. That is, higher the burden of CAD or CCAD in coronary-craniovervial arteries, higher the incidence and severity of atherosclerosis in body arteries.

Figure 5 Prevalence and degree of atherosclerotic stenosis detected in body arteries by the added low-dose body CTA, grouped by the diagnosis outcome of coronary-craniocervical CTA. CAD, coronary artery disease; CCAD, craniocervical artery disease; CTA, computed tomography angiography.

Incidental findings

A total of 44 incidental findings in 26 patients were detected by the added low-dose body CTA. As summarized in Table 3, incidental vascular abnormalities were detected in eight patients, with three aortic aneurysms, two aortic intramural hematomas, one aortic ulcer, and ten aortic ulcers accompanied by mural thrombi. The powerful noise suppressing ability of the AIIR algorithm at low-dose level allowed the low-dose body CTA to manage to reveal extravascular abnormalities, with 28 findings in 21 patients, e.g., cysts, calculi, dropsy, and tumor. Despite the indeterminate malignancy of tumor in the added low-dose body CTA, these findings did provide valuable and probably timely hints for further examination.

In addition, it should be noted that, although thyroid nodules were fairly identifiable in craniocervical CTA, the diagnostic performance was improved by the AIIR in the added low-dose body CTA. On the one hand, thyroids were contrast-enhanced during the added low-dose body CTA, as shown in Figure 6, making the presence of hypoattenuating nodules more obvious on the background of hyperattenuating thyroids. On the other hand, the suppression of streak artifacts by the AIIR algorithm also helps to improve lesion conspicuity. The diagnostic confidence for thyroid nodules was therefore remarkably increased with the added low-dose body CTA, where stronger evidence of image indication was made available.

Figure 6 Images of combined coronary-craniocervical CTA (A) and added low-dose body CTA (B) at the level of the thyroid. The thyroid nodules (yellow circles) were blurry in panel (A) due to streak artifacts and insufficient contrast between thyroid nodules to the gland, but were clearly visualized in panel (B) with suppressed artifacts and improved contrast. CTA, computed tomography angiography.

Impact on clinical management

The clinically relevant findings on body arteries had changed the clinical management of 38% patients (38/100). The four patients with neither CAD nor CCAD but body arterial atherosclerosis, which presented as mild stenosis, were referred for aggressive lifestyle modification and preventive pharmacotherapy, e.g., antihypertensive, antidiabetic, and lipid-lowering agents. A total of 27 patients were given the recommendation for additional medications, e.g., antiplatelet agents, anticoagulant agents, or both. One patient was referred for endovascular abdominal aortic repair due to the abdominal aneurysm. Another six patients were referred for additional operative therapy and medications, e.g., percutaneous transluminal angioplasty or stent implementation, as well as antiplatelet agents for severe iliac stenosis.

Discussion

In this study, we explored the feasibility of adding a low-dose body CTA to the combined coronary-craniocervical CTA by using the AIIR algorithm and investigated its potential clinical value. The main findings are as follows: the image quality of the added low-dose body CTA was superior to that of the routine-dose aortic CTA at a significantly lower cost of radiation dose and contrast medium; the added low-dose body CTA revealed a high prevalence of additional atherosclerosis in body arteries for patients who were referred for combined coronary-craniocervical CTA; clinical management of 38% patients was changed as a result of the additional vascular abnormalities detected by the added low-dose body CTA.

With saving 85% of the radiation dose when compared to routine-dose aortic CTA, body arteries were covered at a radiation cost of 1.6 mSv through the low-dose body CTA. In some previous studies, the ED of low-dose aortic CTA studies using model-based (17,28), deep learning-based (29,30) reconstruction algorithms, or both (31), was higher than our protocol, ranging from 2.6 to 4.4 mSv. Another low-dose aortic CTA study using a 70-kVp protocol combined with AIIR, reported a similar ED of 1.58 mSv (18). While one study reported an ED of 0.4 mSv using a 70-kVp high-pitch aortic CTA protocol without advanced reconstruction algorithms, the image quality was inferior to the routine-dose protocol and the scan coverage was limited from aortic arch to RAs (32). By using the AIIR algorithm in this study, the image quality of low-dose body CTA was more than adequate for diagnosis, with SNRs and CNRs even higher than routine-dose aortic CTA. As such, the combined coronary-craniocervcial CTA extended with low-dose body coverage would enable effective detection of multi-territorial atherosclerosis.

Multi-territorial atherosclerosis in previous studies (2,4,9,33) was commonly evaluated segmentally with ultrasound, non-contrast coronary calcium CT, magnetic resonance, or a hybrid multi-modal imaging approach, which was inconvenient and time-consuming. Despite the availability of multiple alternative imaging modalities for multi-territorial atherosclerosis evaluation, CTA has the greatest advantage for detecting atherosclerosis. A whole-body approach to atherosclerosis evaluation in a single CTA examination using a 64-slice CT had been proposed over 10 years ago (34). However, it had not been widely applied because of the high radiation dose of over 15 mSv per patient. Until now, there have been limited studies to evaluate multi-territorial atherosclerosis using CTA (35-37), out of concern for radiation exposure and contrast dosage. Enabled by high-speed wide-detector CT, combined coronary-craniocervical CTA has been proven feasible with a reduced radiation dose than conventional 64-row CT (1). By using the advanced AIIR algorithm in this study, the scan range was further extended with low-dose body coverage, requiring an additional radiation dose of only 1.6 mSv and resulting in a total radiation dose of 7.5 mSv for extended CTA, which is much lower than previous studies with similar scan coverage.

However, there were still several limitations to the present study. Firstly, the image quality of the low-dose body CTA was not evaluated within the same patient group as the reference dataset, which was retrospectively collected instead. Secondly, as the AIIR algorithm is vendor-specific, our extended CTA protocol may not be suitable for implementation in all institutions. Alternative reconstruction algorithms can be employed, but the resulting image texture appearance and the required radiation dose for ensuring diagnostically acceptable image quality may vary between algorithms. Thirdly, the AIIR algorithm and low-dose settings were not applied in the combined coronary-craniocervical CTA since the diagnostic performance far outweighed the radiation dose in the coronary-craniocervical territories.

Conclusions

In conclusion, the one-stop-shop extended CTA, by adding a low-dose body CTA to the combined coronary-craniocervical CTA, was clinically feasible, technically efficient, and of great value in clinical decision-making. Using the AIIR, the scan coverage was further extended at only little cost of radiation dose and contrast medium, enabling lesion detection beyond the coronary-craniocervical territories, especially for multi-territorial atherosclerosis diagnosis. As such, it is worth recommending the extended CTA for patients suspected of CAD or CCAD as a solution to the comprehensive diagnosis of multi-territorial atherosclerosis.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STARD reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-24-1545/rc

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-1545/coif). W.Z. and G.Z. are employed scientific researchers with the Central Research Institute of United Imaging Healthcare. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Institutional Review Board of The Third Xiangya Hospital of Central South University (No. 23293). Written informed consent from all participants was obtained.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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