New Virtual Contrast Enhancement Boost Technique Can Reduce the Dose of Intravenous Contrast Medium Used in Angiotomography of the Abdominal Aorta

doi:10.21203/rs.3.rs-4940251/v1

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New Virtual Contrast Enhancement Boost Technique Can Reduce the Dose of Intravenous Contrast Medium Used in Angiotomography of the Abdominal Aorta

https://doi.org/10.21203/rs.3.rs-4940251/v1

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Purpose: This study aims to evaluate the image quality of computed tomography (CT) angiograms obtained using a virtual contrast augmentation technique, adding an iodine map to the contrast-enhanced images, obtained through a digital subtraction technique, reducing the dose of intravenous iodinated contrast medium compared to the conventional institutional standard technique.

Methods: This prospective investigation enrolled patients previously diagnosed with abdominal aortic aneurysms, who underwent two successive computed tomography angiographies (CTAs) of the aorta. One CTA was performed employing the virtual contrast enhancement boost technique with a 40% decrease in the intravenous contrast medium dose, while the other adhered to the conventional protocol without any reduction in contrast medium volume. After imaging, both qualitative and quantitative assessments were conducted to evaluate the opacification level of the aorta and its branching vessels.

Results: The study analyzed 28 examinations from 14 subjects (two per participant). Qualitative analysis revealed that image quality was deemed adequate for diagnostic purposes, with nearly all arterial segments in both protocols rated as good or excellent. Although no statistically significant differences were detected, the average attenuation across all arterial segments in the angiograms exhibited a trend towards higher values in the virtual contrast enhancement boost technique, compared to the conventional protocol. Similarly, the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) demonstrated comparable levels between the two methodologies.

Conclusion: The application of virtual contrast enhancement in the acquisition of CT angiograms of the aorta maintains comparable image quality, while reducing the dosage of intravenous contrast medium in 40%. This approach suggests a potential for optimizing contrast use in vascular imaging, aligning with goals related to patient safety and radiological efficiency.

Tomography

X-ray computed

Angiography

Aortic aneurysm

Contrast media

Computed tomography angiography.

The advent of multidetector computed tomography (MDCT) has solidified computed tomography angiography (CTA) as the modality of choice for the evaluation of aortic diseases and their branches [1]. Nonetheless, the methodology necessitates recurrent intravenous administration of iodinated contrast medium, which is associated with potential complications including hypersensitivity reactions and contrast-induced nephropathy [2]. The risk of nephropathy is contingent upon the patient's estimated glomerular filtration rate (eGFR), with those presenting an eGFR below 30 mL/min/1.73m² classified as high risk, and those with eGFR values between 30 and 44 mL/min/1.73m² as moderate risk [3, 4]. Despite the historical overestimation of nephropathy risk post-contrast medium administration, its potential occurrence in patients with predisposing factors such as diabetes and advanced age, who are frequently subjected to CTA for aortic diseases, cannot be disregarded [5, 6].

The global shortages of contrast media during 2021/22, exacerbated by the COVID-19 pandemic, have highlighted the critical need for judicious use of these resources from both economic and environmental perspectives. Various CTA protocols aiming at enhancing vascular opacification or reducing contrast volume without compromising image quality have been explored, including low kVp CTA [7], dual-source CT [8, 9], and the virtual contrast enhancement boost technique. However, the efficacy of a digital subtraction imaging technique, termed virtual contrast enhancement boost technique, in reducing the dose of intravenous contrast medium for CTA of the aorta remains uninvestigated in the English literature.

The virtual contrast enhancement boost technique, which involves retrospective enhancement of contrast on CT images through an iodine map generated by subtracting a non-contrast CT image from a contrast-enhanced CT image, has shown promise in enhancing contrast and aiding in the diagnostic detection of conditions such as type II endoleaks post-endovascular treatment of aortic aneurysms and improving portal vein image quality [10].

This study aims to evaluate the clinical feasibility of the virtual contrast enhancement boost technique, combined with a reduced dose of intravenous contrast medium, for the assessment of aortic diseases. It will compare the image quality of this innovative approach with the conventional CTA acquisition method, which employs a standard dose of intravenous contrast medium, without the use of the virtual contrast enhancement boost technique.

This prospective study compared CT angiograms acquired from the same patient, in different moments, using different techniques. Informed consent was obtained from all participants, and the study received approval from the local institutional review board as well as the national research ethics committee.

Patients were consecutively assigned to two groups at the time of their first CTA, with one group first undergoing CTA according to the conventional protocol and the second according to the virtual contrast enhancement boost protocol, and vice versa for the second group. The interval between exams was maintained within clinically recommended duration for follow-up after endovascular or surgical treatment of an abdominal aortic aneurysm.

Patient Population

Patients were recruited by vascular surgeons from an angiology and vascular surgery outpatient clinic. Eligibility criteria included individuals over 18 years of age who had undergone surgical or endovascular treatment for an abdominal aortic aneurysm and for whom it was recommended follow up with at least two CTAs of the abdominal aorta at intervals ranging from 6 months to 1 year post-operatively. Exclusion criteria encompassed contraindications to intravenous iodinated contrast use, such as severe allergic reactions or kidney failure, and pregnancy. Serum creatinine levels were monitored before and after CTAs to assess renal function. The patient’s weight was measured before each CTAs.

Image Acquisition

Images were acquired using a 320-detector row CT scanner. The same concentration of intravenous iodinated contrast medium was administered via an antecubital vein in the upper right limb using an automatic injector in all image acquisitions. The exams evaluated the abdominal aorta, iliac arteries, and proximal segments of the femoral arteries, with a non-contrast stage performed on the upper abdomen and pelvis using a low dose protocol. The timing for contrast-enhanced image acquisition was triggered by reaching a specific contrast density threshold in the abdominal aorta (180 HU).

For exams employing the virtual contrast enhancement boost technique, the volume of intravenous contrast medium was reduced by 40% (Table 1), following the equipment manufacturer's guidelines, with a proportional reduction in injection flow rate to maintain the same total injection time as the standard protocol (Table 2) .

Table 1

Intravenous iodinated contrast material injection protocol for CTA with virtual contrast enhancement boost technique. (CTA = angiotomography)
Weight	Contrast volume (injection flow)
< 55kg	43mL (2,4mL/sec)
56–65kg	49mL (2,7mL/sec)
66–85kg	54mL (3mL/sec)
86–90kg	60mL (3,3mL/sec)

Table 2

Intravenous iodinated contrast material injection protocol for CTA with standard acquisition. (CTA = angiotomography)
Weight	Contrast volume (injection flow)
< 55kg	72mL (4,0mL/sec)
56–65kg	81mL (4,5mL/sec)
66–85kg	90mL (5,0mL/sec)
86–90kg	99mL (5,5mL/sec)

Postprocessing

Images with 1.0 mm thickness and 0.8 cm increment were analyzed on a workstation equipped with a picture archiving and communication system (PACS) using 3D volume rendering, multiplanar reformating and maximum intensity projection for three-dimensional reconstructions.

Image Analyses

Two experienced radiologists in vascular imaging (5 years and 17 years of experience) conducted blinded and randomized qualitative and quantitative analyses of the images. The quality of arterial opacification was assessed using a four-point scale [11], and quantitative analysis involved the measurement of the mean vascular attenuation in Hounsfield Units (HU) using a region of interest (ROI) positioned centrally in the vessel.

Radiation dose comparisons were based on the dose-length product (DLP) reported by the scanner.

Statistical analyses

Statistical analyses were performed using tests for continuous (mean and standard deviation and compared using the paired Student's t-test), categorical (frequency tables and percentages), and ordinal variables (McNemar test). The concordance between observers was evaluated using Kendall's coefficient of concordance.

Patient Characteristics

Nineteen individuals were initially included in the study. Five of them were excluded, one due to kidney failure and four due to impossibility of scheduling the exam. Fourteen patients were included in the analysis after exclusions. Five of them were women and nine were men, with an average age of 73.7 years. All patients underwent two serial CTAs of the abdominal aorta, with intervals of 6 to 12 months between acquisitions.

Contrast Volume and Flow

A significant reduction in the volume and flow rate of intravenous contrast medium was observed in exams utilizing the virtual contrast enhancement boost technique − 56 mL (43-65mL interval) - compared to the standard protocol − 101,8 mL (70–140 mL interval), demonstrating the feasibility of reducing contrast medium usage (Table 3).

Table 3

Comparison of intravenous contrast medium volume and flow rate between protocols
Objective parameters	Standard protocol		Virtual contrast enhancement boost protocol
	Mean	Interval	Mean	Interval
Intravenous contrast medium volume (mL)	101,8	70–140	56,4	43 - 65
Intravenous contraste médium flow rate (mL/s)	4,5	4–5	3,11	2,4 − 3,6

Concordance between Observers

High concordance was noted in the qualitative analyses of arterial opacification, indicating consistent image quality assessments by the evaluators across both imaging protocols (Table 4).

Table 4

Measurements of attenuation in arterial lumen
Objective analysis	Standard protocol		Virtual contrast enhancement boost protocol
Objective analysis	Mean	SD	Mean	SD	P value
Attenuation of the suprarenal abdominal aorta	375,7	92,86	396,57	75,32	0,177
Attenuation of the infrarenal abdominal aorta	392,57	97,74	406	74,61	0,438
Attenuation of the right common iliac artery	389,43	97,39	406,86	75,02	0,316
Attenuation of the left common iliac artery	360	86,97	386,92	81,26	0,318
Attenuation of the right external iliac artery	380,93	108,77	408,14	76,06	0,186
Attenuation of the left external iliac artery	376,38	104,53	377,92	73,72	0,943
Attenuation of the right common femoral artery	388,86	95,15	409,86	72,34	0,245
Attenuation of the left common femoral artery	375,57	101,73	395,64	86,96	0,243
Attenuation of the right superficial femoral artery	398,14	105,99	417,93	83,02	0,336
Attenuation of the left superficial femoral artery	378,57	110,45	392,21	87,92	0,506

SD: standard deviation.

Image Quality

No statistically significant difference in image quality was observed between the standard and virtual contrast enhancement boost techniques, with the majority of arterial segments receiving scores indicative of good or excellent diagnostic quality (Table 4).

Despite there being no statistically significant difference between results from the two approaches when done the objective evaluation, the arterial lumen ROI measures showed greater mean attenuation in the CTA exams performed utilizing the virtual contrast enhancement boost technique in all the segments examined. The mean values were 382.51HU (CI 95% 369–398 HU) for CTAs with standard protocol, and 399.80HU (CI 95% 392.2-417.9 HU) for the CTAs performed with the virtual contrast enhancement boost protocol.

Radiation Dose, Noise, Signal-to-Noise Ratio, and Contrast-to-Noise Ratio

Comparisons of radiation dose, image noise, SNR, and CNR revealed no significant differences between the standard and virtual contrast enhancement boost protocols (Table 5).

Table 5

Comparison of Noise, Signal-to-Noise Ratio, and Contrast-to-Noise Ratio
	Standard protocol		Virtual contrast enhancement boost protocol
	Mean	SD	Mean	SD	P value
Noise	17,5	3,1	16,9	5,1	0,670
Signal-to-Noise Ratio (SNR)	22,0	7,0	25,5	8,7	0,186
Contrast-to-Noise Ratio (CNR)	19,2	6,5	22,7	8,1	0,135

In this investigation, computed tomography angiographies (CTAs) utilizing a virtual contrast enhancement boost technique alongside a 40% reduction in the volume of intravenous contrast medium, yielded image quality on par with those obtained through a conventional imaging acquisition protocol. This study points to the clinical efficacy of this innovative approach in diminishing the volume of contrast medium administered to patients, while obtaining similar results.

Quantitative scrutiny within this research revealed that the mean attenuation values of the region of interest (ROI) within the arterial lumen were not smaller and actually marginally elevated in CTAs conducted using the virtual contrast enhancement boost technique compared to the conventional approach, with values of 399.8 versus 382.5 Hounsfield Units (HU) respectively. However, it is crucial to acknowledge that both methodologies yielded an average arterial opacification level deemed adequate for diagnostic purposes, surpassing 300 HU [1].

Regarding image noise, no significant difference was observed between the CTAs performed under the standard protocol and those executed using the virtual contrast enhancement boost technique. This outcome was anticipated, considering that radiation dosage was automatically calibrated using the same technique across both groups, facilitating the comparability of results between the two studies.

The Signal-to-Noise Ratio (SNR) and Contrast-to-Noise Ratio (CNR) in CTAs conducted with the virtual contrast enhancement boost protocol were slightly superior to those observed in CTAs performed under the standard protocol. This indicates the virtual contrast enhancement boost technique's effectiveness in enhancing vascular contrast information using an iodine-based intravenous contrast medium, thereby augmenting signal and contrast without a proportional increase in noise. Similarly, a retrospective study assessing contrast enhancement of the portal vein in CTAs, contrasting images generated with and without the virtual contrast enhancement boost technique, reported enhanced SNR and CNR in the group utilizing the virtual contrast enhancement boost technique [12].

Additionally, another investigation employing the virtual contrast enhancement boost tool for pulmonary vessel examination discovered increased attenuation in the pulmonary artery trunk and subsegmental pulmonary arteries compared to the traditional technique, alongside improved SNR and CNR [13].

The application of the virtual contrast enhancement boost technique in conjunction with model-based iterative reconstruction (MBIR) has also been shown to enhance abdominal image quality over other reconstruction methods [14].

Alternative techniques to the virtual contrast enhancement boost, aimed at reducing the dosage of intravenous contrast media in CTAs, include double energy acquisition with image reconstruction at optimal energy levels to augment contrast attenuation, albeit potentially increasing radiation dosage due to dual energy acquisitions at the same site [15, 16]. Another mentioned technique is the low kilovoltage single energy acquisition, which, while increasing contrast attenuation, may also elevate noise and image artifacts, resulting in diminished SNR and CNR [1, 17].

In the current study, a slight increase in radiation dosage was noted in CTAs employing the virtual contrast enhancement boost technique compared to the standard protocol, though this difference was not statistically significant. Several factors were reviewed to elucidate this minor discrepancy in radiation dosage, including tomographic acquisitions, which were consistent across all studies, and an analysis of patient weight variation in relation to radiation dose, which showed no correlation. Adjustments made during image acquisition, such as isocenter positioning and coverage in the Z-axis, could potentially explain the slight variance in radiation dose.

Qualitative analysis by both evaluators in this study found nearly all analyzed segments, under both protocols, to possess opacification levels deemed good or excellent for diagnostic purposes. Only three segments were rated as having moderate image quality when evaluated using the virtual contrast enhancement boost technique, yet upon further analysis, factors such as beam hardening artifacts could have influenced these assessments.

Our study also adapted contrast media injection flow rate in accordance with the reduced volume of intravenous contrast medium used in the virtual contrast enhancement boost technique, maintaining consistent injection duration all tomographic acquisitions. This approach is supported by principles of arterial contrast media enhancement, which state that arterial enhancement is directly proportional to the contrast media injection rate, increases cumulatively with longer injection durations, and is inversely proportional to cardiac output [18].

The capability to perform CTAs with opacification quality akin to the standard technique, while utilizing a reduced dose of intravenous contrast medium, represent a significant clinical advantage. This is particularly relevant in light of the recent global shortage of contrast media, underscoring the importance of judicious usage of this resource, reinforcing the value of the virtual contrast enhancement boost technique in maintaining high-quality tomographic studies with reduced contrast media volumes.

The study's limitations to be acknowledged are, first, the small sample size, comprising fourteen patients and resulting in twenty eight comparative CT angiography (CTA) studies. Yet, this limitation is at least partially mitigated by the study's approach of testing each patient twice, using the same equipment, thereby controlling most variables. This intra-patient comparison ensures a high degree of internal validity, allowing for a precise evaluation of the virtual contrast enhancement technique versus the standard protocol. Second, the risk of ineffective blinding during image evaluation, while notable, is somewhat intrinsic to studies comparing imaging techniques. The distinct visual outputs of the standard and virtual contrast enhancement protocols can inadvertently reveal the method used to evaluators, potentially introducing bias. However, this limitation is inherent to the nature of imaging technique comparisons and does not detract significantly from the study's value. Future studies could address this by incorporating a broader pool of evaluators and more objective image quality assessment criteria.

In essence, despite these limitations, the study's design—particularly the controlled, within-subject comparison—provides a solid foundation for assessing the efficacy of the virtual contrast enhancement technique. This approach underscores the potential benefits of the technique, especially in reducing contrast media volume while maintaining diagnostic image quality.

The virtual contrast enhancement boost technique represents a significant advancement in computed tomography angiography of the aorta, enabling the acquisition of high-quality images with a 40% reduction in intravenous contrast medium usage, comparable to those images obtained with the conventional imaging protocol. This finding highlight the potential of the virtual contrast enhancement boost technique to contribute to more secure, sustainable and efficient imaging practices, particularly in face of global contrast media shortages. Further research with larger patient cohorts is warranted to validate these results and explore the full potential of this innovative imaging technique.

Author Contribution

All authors designed the study. J.N., L.B.S.V., A.T., M.M.A.S acquired data and performed statistical analyses. J.N., G.S. and A.T. drafted the initial manuscript. All authors critically reviewed and revised the manuscript. All authors approved the final manuscript.

Acknowledgement

The authors express our sincere gratitude to Rosemeire Pereira Bezerra who contribute to the execution of this study.

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No competing interests reported.

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New Virtual Contrast Enhancement Boost Technique Can Reduce the Dose of Intravenous Contrast Medium Used in Angiotomography of the Abdominal Aorta

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