Comparison study of image quality at various radiation doses for CT venography using advanced modeled iterative reconstruction.

OBJECTIVE: We compared the image quality according to the radiation dose on computed tomography (CT) venography at 80 kVp using advanced modeled iterative reconstruction for deep vein thrombus and other specific clinical conditions considering standard-, low-, and ultralow-dose CT.
METHODS: In this retrospective study, 105 consecutive CT venography examinations were included using a third-generation dual-source scanner in the dual-source mode in tubes A (reference mAs, 210 mAs at 70%) and B (reference mAs, 90 mAs at 30%) at a fixed 80 kVp. Two radiologists independently reviewed each observation of standard- (100% radiation dose), low- (70%), and ultralow-dose (30%) CT. The objective quality of large veins and subjective image quality regarding lower-extremity veins and deep vein thrombus were compared between images according to the dose. In addition, the CT dose index volumes were displayed from the images.
RESULTS: From the patients, 24 presented deep vein thrombus in 69 venous segments of CT examinations. Standard-dose CT provided the lowest image noise at the inferior vena cava and femoral vein compared with low- and ultralow-dose CT (p < 0.001). There were no differences regarding subjective image quality between the images of popliteal and calf veins at the three doses (e.g., 3.8 ± 0.7, right popliteal vein, p = 0.977). The image quality of the 69 deep vein thrombus segments showed equally slightly higher scores in standard- and low-dose CT (4.0 ± 0.2) than in ultralow-dose CT (3.9 ± 0.4). The CT dose index volumes were 4.4 ± 0.6, 3.1 ± 0.4, and 1.3 ± 0.2 mGy for standard-, low-, and ultralow-dose CT, respectively.
CONCLUSIONS: Low- and ultralow-dose CT venography at 80 kVp using an advanced model based iterative reconstruction algorithm allows to evaluate deep vein thrombus and perform follow-up examinations while showing an acceptable image quality and reducing the radiation dose.

Introduction

Venous thromboembolism is the third main cause of cardiovascular disease [1], and its incidence has sharply increased over the last two decades [2]. It occurs in two forms, deep vein thrombosis (DVT) and pulmonary embolism. DVT is often related with recurrent venous thromboembolism and pulmonary embolism according to the disease process [3]. Disease recurrence occurs in 20–36% of the DVT patients as the disease progresses [4, 5]. Chronic venous change, venous bleeding, and death are the major consequences that may occur during the clinical course of DVT. Along with ultrasonography, computed tomography (CT) venography of the lower extremity is common for DVT diagnosis and follow-up.

There are many studies in the literature investigating radiation dose reduction with low tube voltages and advanced model based reconstruction [6-10]. We are contributing to this space by specifically looking at the image quality of DVT segments, chronic venous change, stent placement, and metal artifacts affecting the vein segments on low- and standard-dose CT venography. Nevertheless, such conditions are often encountered in clinical practice when radiologists review CT venograms.

Iterative reconstruction has been developed using statistical algorithms, and model-based iterative reconstruction algorithms have been recently introduced [11]. In addition, advanced modeled iterative reconstruction (ADMIRE; Siemens Healthineers, Forchheim, Germany) is a model-based algorithm that decreases raw data noise and enables radiation dose reduction with maintaining the image quality of CT scans. Dual-source CT scanners can blend or divide raw data acquired from each tube, allowing the generation of images at different radiation doses in a single CT examination [12, 13]. In this study, we compared the image quality according to radiation dose on CT venography at 80 kVp using ADMIRE regarding specific clinical conditions and considering standard-, low-, and ultralow-dose CT that using ADMIRE promotes dose reduction while maintaining the image quality.

Materials and methods

Study design

This retrospective study was approved by the Gil Medical Center institutional review board. The requirement for informed consent was waived given the retrospective nature of this study. The CT scans were performed using standard-dose radiation without additional dose exposure.

Patients

One hundred ten CT venography examinations were performed in a tertiary care center for either DVT diagnosis or follow-up between May 2019 and September 2020. The CT protocol of 5 examinations was different from that of the others and excluded from this study. Thus, 105 examinations from 100 patients (48 men, 52 women; mean age, 63.5 years; 18–94 years) were considered (). The clinical characteristics of the patients are listed in .

Flowchart of patient inclusion.

(a) Inclusion process. (b) study design.

Protocol

The patients underwent CT venography examinations from the T12 vertebra to the feet. To obtain the contrast-enhanced images, 1.5 mL/kg according to the body weight (maximum, 150 mL) of contrast media (Iohexol 350 mgI/mL—Bonorex 350; Central Medical Services, Seoul, Republic of Korea) at a flow rate of 3 mL/s was injected in each patient followed by 30 mL of 0.9% saline solution at the same flow rate. The CT scans were performed with a 192-slice CT scanner (SOMATOM Force; Siemens Healthineers, Erlangen, Germany) in the dual-source mode in tubes A (reference mAs, 210 mAs at 70%) and B (reference mAs, 90 mAs at 30%) using tube current modulation (CARE Dose 4D, Siemens Healthineers) at a fixed 80 kVp tube voltage in . The pitch was 0.6, and the rotation time was 0.5 s. The images were obtained using standard- (A and B tube data), low- (tube A data), and ultralow-dose (tube B data) CT, obtaining three image sets. To produce the specific split of the radiation dose (mAs) between each tube detector, the CT scanner needs a dual energy research license. The images were reconstructed with axial slice thickness of 5 mm using ADMIRE at strength level 3. From the reports in [3] and our preliminary examinations between March and April 2019, we designed the CT dose index volume (CTDIvol) at the ultralow dose to be approximately 1.5 mGy.

Data analysis

All image analyses were performed using a picture archiving and communication system (PACS). The CT scans were independently reviewed by two radiologists with 10 and 13 years of experience. Diverging interpretations were reevaluated by the radiologists to reach a consensus. The 315 images (105 examinations × 3 image sets) were analyzed for the three dose levels with a washout period (6 weeks).

Subjective image quality analysis

A subjective image quality analysis was performed by the two radiologists, who were blinded to the radiation dose and patient’s information. The overall CT image quality and the segment image quality of the inferior vena cava (IVC), bilateral common iliac veins (CIVs), bilateral femoral veins (FVs), bilateral popliteal veins, and bilateral calf veins were scored using the following four-point scale: 1) poor, unacceptable subjective image noise with artifacts impeding diagnosis; 2) adequate, average image noise and acceptable information for diagnosis; 3) good, low image noise and necessary information for adequate diagnosis; and 4) excellent, very low image noise and optimal information for diagnosis [12]. A score of 1 was regarded unacceptable for diagnosis. Analogously, the venous contrast was graded using the following four-point scale: 1) poor, enhancement below adjacent muscular enhancement; 2) adequate, enhancement similar to surrounding muscle enhancement; 3) good, inhomogeneous enhancement, less intense than the corresponding artery but more than surrounding muscle; and 4) excellent, homogenous enhancement similar to the corresponding arterial enhancement.

The following conditions were analyzed regarding the evaluations and image quality: 1) acute DVT of lower-extremity vein segment, 2) May–Thurner syndrome, 3) chronic venous change, 4) in-stent restenosis in patients with uncovered or covered stent, 5) artifacts due to prosthesis, and 6) incidental findings (e.g., varicose vein). Acute DVT was diagnosed by the presence of complete or partial low-attenuation intraluminal filling defects on CT venograms for at least two consecutive axial images [14]. Chronic venous change (i.e., chronic-stage DVT) was diagnosed by the presence of decreased vessel caliber, fibrotic bands, recanalization, and thick eccentric walls [15]. Acute DVT was evaluated using the four-point scale used for the overall CT image quality. Stent and prosthesis artifacts were scored using the following four-point scale: 1) strong streak artifacts with nondiagnostic insufficient image quality, 2) severe artifacts causing uncertainty, 3) mild artifacts with adequate image evaluation, and 4) excellent image quality with no visible artifacts.

Objective image quality analysis

One blinded radiologist drew a circular region of interest (size, 1–3 cm2) at the specific levels of the three axial images using PACS. The levels were IVC and midportions of right FV. The mean and standard deviation in Hounsfield units of the region of interest (i.e., attenuation, image noise) were calculated.

Reference standards

Lesions from previous interventional venography for thrombectomy and/or ultrasound results and clinical date from electronic medical records were used.

Radiation dose

The CTDIvol and dose–length product were described on the CT dose report to analyze the radiation dose [6, 12].

Statistical analyses

The radiation dose and image analysis were compared between the three image sets using a one-way analysis of variance with post-hoc analysis and Bonferroni correction for multiple comparisons. A p-value below 0.05 was considered statistically significant. The statistical analyses were performed using SPSS version 21.0 (IBM, Armonk, NY, USA).

Results

The 100 patients who underwent the 105 examinations had a weight of 65.5±13.6 (range, 40.0–106.0 kg) and a body mass index of 24.8 ± 4.0 kg/m2 (range, 12.0–32.0 kg/m2) at the time of their corresponding examinations.

In the CT venography examinations, 24 patients presented DVT in 69 segments. Specifically, 10, 5, 4, 3, 1, and 1 patients showed DVT in 3, 2, 1, 5, 6, and 4 venous segments, respectively. In addition, 13 patients presented chronic venous change in 25 venous segments, while 10 patients presented varicose veins in 25 venous segments incidentally, and 17 patients presented the May–Thurner syndrome in 20 examinations. Moreover, 32 patients had a total of 48 metal prostheses affecting 77 venous segments with metal artifacts, corresponding to IVC filter (n = 10), internal fixation of bone (n = 8; femur, 6; tibia, 2), vertebroplasty (n = 7), posterior lumbar interbody fusion (n = 5), total hip replacement (THR; n = 4; left, 3; right, 1), and total knee replacement (TKR; n = 14; right, 7; left, 7). Seventeen patients had 18 stents (15 left CIV, 1 left FV, 2 right FV) appearing in 19 examinations (2 overlapping examinations).

The overall image quality of the standard-, low-, and ultralow-dose CT scans were scored at 4.0 ± 0.1 (range, 3–4), 4.0 ± 0.2 (range, 3–4), and 3.5 ± 0.5 (range, 3–4), respectively. The differences in segmental image quality between images were the largest in the IVC (3.9 ± 0.4, 3.8 ± 0.4, 3.5 ± 0.6; p < 0.001), whereas no differences occurred between the three image sets for the popliteal and calf veins (3.8 ± 0.7, right popliteal vein; p = 0.977). The scores of venous segments from the three image sets were 2–4 (adequate–excellent), except for a few popliteal veins. All calf veins showed scores of 3–4 in the three image sets, except for a right calf vein that scored 2 for ultralow-dose CT. The venous contrast quality showed scores of 4.0 ± 0.1 (range, 3–4), 4.0 ± 0.1(range, 3–4), and 3.9 ± 0.7 (range, 3–4) for standard-, low-, and ultralow-dose CT, respectively. The detailed scores for the segments are described in .

The image quality of the 69 DVT segments showed higher scores for standard- and low-dose CT (4.0 ± 0.2) than for ultralow-dose CT (3.9 ± 0.4), as detailed in . All DVT segments for standard- and low-dose CT scored 3–4 () and only 2 segments (IVC) showed a score of 2 for ultralow-dose CT. Chronic venous change in 25 segments scored 4 for standard- and low-dose CT, and only 1 segment scored 3 for ultralow-dose CT. The varicose veins in 25 venous segments scored 4 on the three image sets.

CT venograms at 80 kVp of 81-year-old woman with DVT (body mass index, 26.1 kg/m2).

(a) Standard-dose (CTDIvol, 4.6 mGy; dose–length product—DLP, 557.3 mGy⋅cm), (b) low-dose (CTDIvol, 3.2 mGy; DLP, 390.1 mGy⋅cm), and (c) ultralow-dose (CTDIvol, 1.4 mGy; DLP, 167.2 mGy⋅cm) CT scans show acute DVT in both popliteal veins. The scores of venous segments from the three image sets were 4.

The 48 metal prostheses produced artifacts in 77 venous segments, as detailed in . The abovementioned 13 segments of popliteal veins (6 right popliteal veins and 7 left popliteal veins) showed identically poor scores of 1, being unsuitable for diagnosis due to the artifacts from the metal prostheses for TKR. In addition, 29 segments scored 2 for ultralow-dose CT and 3 segments scored 2 for standard- and low-dose CT. The 18 stents in 19 examinations (2 overlapping examinations for the same patient) from 17 patients scored 4 in the three image sets, as detailed in .

CT venograms at 80 kVp of 65-year-old man (body mass index, 21.8 kg/m2).

(a) Standard-dose (CTDIvol, 6.0 mGy; DLP, 836.2 mGy⋅cm), (b) low-dose (CTDIvol, 4.0 mGy; DLP, 585.3 mGy⋅cm), and (c) ultralow-dose (CTDIvol, 2.0 mGy; DLP, 250.9 mGy⋅cm) CT scans. The segmental image quality of the left external iliac vein scored 3 for low- and standard-dose CT. Metal artifacts caused by THR affected the left iliac vein evaluation, reducing the score to 2 for ultralow-dose CT.

The segments showed significantly higher image noise in the left femoral vein and IVC for ultralow-dose CT than for standard- and low-dose CT (p < 0.001). The noise levels in segments of the left femoral vein were 7.4 ± 2.5, 9.1 ± 3.1, and 11.1 ± 3.5 for standard-, low-, and ultralow-dose CT, respectively, while those of the IVC were 9.3 ± 2.3, 11.2 ± 2.6, and 16.3 ± 3.7, respectively. The differences in image noise between image sets were larger for the IVC than for the femoral vein. The objective image quality results are listed in .

The mean CTDIvol values for standard-, low-, and ultralow-dose CT were 4.4 ± 0.6, 3.1 ± 0.4, and 1.3 ± 0.2 mGy, respectively. The dose–length products for standard-, low-, and ultralow-dose CT were 567.9 ± 103.0, 397.5 ± 72.1, and 170.4 ± 30.9 mGy⋅cm, respectively. The mean CTDIvol and dose–length product for standard-dose CT showed significantly higher than those for low- and ultralow-dose CT (p < 0.001).

Discussion

Our study revealed similar subjective image quality for DVT, popliteal veins, calf veins, and metal artifacts on standard-, low-, and ultralow-dose CT venograms. Although standard-dose CT showed higher overall image quality than low- and ultralow-dose CT, reduced-dose CT venography (CTDIvol, 1.3 mGy) provided a suitable image quality to evaluate DVT and lower-extremity veins when applying ADMIRE at 80 kVp. Previous studies have reported that CT venography at 80 kVp can reduce the radiation dose while maintaining image quality [6, 8, 16]. However, a detailed analysis regarding specific segmental veins, DVT, or metal artifacts has not been conducted. In this study, we investigated whether reduced-dose CT affects clinically important factors for DVT diagnosis and venogram evaluation.

The largest score differences in subjective image quality between standard-, low-, and ultralow-dose CT were found in the abdominal area corresponding to the segmental images of the IVC. Such differences originate from the theory that large solid organs (e.g., lower abdomen) require a high tube current using automatic tube current modulation according to the longitudinal (z-axis) mAs modulation [17]. On the other hand, the tube current can be reduced without a significant increase in the overall image noise in small body regions. Hence, CT scans of extremity veins show less beam attenuation than those of the abdomen, and CT scans of lower-extremity veins reflect suitable diagnostic image quality even when using low tube current for ultralow-dose CT. As a result, popliteal and calf veins showed no differences in segmental image quality between standard- and ultralow-dose CT. As the development of most DVT cases occurs in lower extremities with venous abnormality, our results support the use of reduced-dose CT venography applying ADMIRE at 80 kVp.

Lower CT tube voltages yield reduced radiation exposure but increased image noise [18]. Nevertheless, iterative reconstruction algorithms can minimize noise and provide a more acceptable image quality than filtered back-projection. Recent model-based iterative reconstruction algorithms enable direct reconstruction from raw data. However, previous studies have reported that model-based iterative reconstruction is time-consuming during its early stage [6, 19, 20], being unsuitable for the clinical workflow. In contrast, ADMIRE allows real-time CT scan reconstruction, contributing to the adoption of reconstruction in clinical settings. Moreover, advances in hardware equipped with Stellar detectors (Siemens Healthineers), which can reduce electronic noise by blending an analog digital converter chip to directly deliver a digital signal, can foster image quality while reducing the radiation dose for CT imaging at 80 kVp [21].

A concern about iterative reconstruction was related to the masking or underestimation of small lesions due to lesions with a low attenuation difference compared with surrounding tissue [22]. However, model-based iterative reconstruction provides more accuracy than statistical iterative reconstruction in the detection of small lesions in the abdomen while reducing radiation dose and maintaining the image quality [23, 24]. Similarly, our results showed a comparable subjective image quality of small lesions (e.g., DVT, metal artifacts, stents) in lower extremities between standard- and low-dose CT.

Metal artifacts can degrade small lesion detection on CT scans [25]. Although most segmental veins showed acceptable/excellent image quality in the images with the 47 metal prostheses, 13 prostheses led to poor subjective image quality regardless of the radiation dose. These 13 prostheses correspond to TKR and affected the image quality in the popliteal veins. Thus, popliteal vein thrombosis may be underestimated in patients with metal prostheses in the knee joint regardless of the radiation dose. In these cases, ultrasound may be more suitable for accurate DVT diagnosis than CT venography.

This study has some limitations. First, this was a retrospective study considering CT venography examinations, which has a selection bias. Second, the examinations were conducted on relatively only a patient with severe obesity, which undermines imaging quality. The results of our study do not directly translate to the severely obese patients. Third, we did not analyze interobserver variability for subjective image analysis or diagnostic performance for DVT detection. Fourth, we selected fixed 80 kVp and compared between specific radiation doses. Selection of automatic kVp change or fixed kVp is possible in Siemens CT. However, using the specific split of the tube dose in a dual source mode, we can only select a specific kVp (i.e, cannot use automatic kVp change). Finally, image quality compared to that using other tube voltages (e.g., 70, 90, and 100 kVp) or other image reconstruction methods (i.e., filtered back projection) was not assessed. These limitations hinder the generalization of our results toward the widespread use of low-dose CT venography.

Overall, our results suggest the low- and ultralow-dose CT venography at 80 kVp using ADMIRE show acceptable image quality for DVT evaluation and follow-up.

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26 May 2021

PONE-D-21-10760

Comparison study of image quality at various radiation doses for CT venography using advanced modeled iterative reconstruction

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Additional Editor Comments:

The reviewers raised the major concerns about the feasibility of CT protocol and the lack of comparison of bench-mark methods, such as FBP. The latter may be necessary to establish that the model-based iterative reconstruction algorithm (ADMIRE) is essential for low-dose CT venogram. In addition, the readers' experience and performance difference should be provided for the subjective evaluation. Addressing these issues would greatly improve the significance of the paper.

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Reviewer #2: No

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Reviewer #1: A review of the paper titled “Comparison study of image quality at various radiation doses for CT venography using advanced modeled iterative reconstruction”

Thank for letting me review this work! It is good to see we can go lower in dose using this scanner/recon for these indications and not suffer issues.

General Comments:

1. The abstract needs some attention. The conclusion statement says “using a reconstruction algorithm allows” I think you need to say “using an advanced model based iterative reconstruction algorithm”

2. It is not clear from the abstract that you compare regular and lower dose non advanced recon to lower dose advanced recon. You need to do this to support your conclusions to prove it was the advanced recon that enabled the dose reduction. Or else how to do we know the overall dose was just set too high? I assume you did this in the paper itself, but reading the abstract itself, this important study design point is not clear. For example, I can scan at 100 mGy using FBP and then cut it to 50 mGy and use ADMIRE. But concluding ADMIRE allowed a reduction w/o issues for diagnostic purposes is flawed…I would need to show at 50 mGy with FBP I performed worse.

1. Introduction: I don’t think this sentence means what you intend “The radiation exposure during CT venography is becoming an increasing concern 67 because the mean dose level rises when a patient requires multiple CT examinations during the 68 disease process of pulmonary embolism (chest CT) or given the recurrency of DVT” There is no reason for the mean dose the pt gets to change, I think you mean their cumulative effective dose is rising as they get more and more scans? Using CED as a motivation for dose reduction is kind of controversial, an exam, if indicated and appropriate should be given w/o concern for stochastic cancer risk. This is the position of the American College of Radiology and the American Association of Physicists in Medicine.

2. Introduction: I think there a lot of papers out there for this, please cite more (I went to google scholar and found several on the first page of results you don’t cite on this topic) and consider changing the verbiage/tone of this paragraph, to something more like “there are many papers in the literature looking at dose reduction with lower kV and advanced model based recons…we are contributing to this space by looking specifically at …

a. “Few 69 studies have reported the reduction of the average radiation dose for CT venography using low 70 tube voltages, mono-energy CT, and iterative reconstruction algorithms”

3. There is no stat testing for the reader scores/ Just for the noise measurements?

4. The paper concludes it is recon method that enables the low dose visualization, but we cannot conclude this from your methods. The scores seem to basically be the same or just differ by 1 point from low to high dose, with more variation being pt to pt. I think in order to support that the lower dose was enabled by advanced recon, you must prove to us the images are not fit for diagnostic purposes if the ADMIRE recon was not used?

Specific Comments:

1. In the CT protocol section, can you elaborate on what the 70 and 30% refer to? Was the actual mAs equal to what you have listed, or was 70 and 30% used?

Reviewer #2: In this manuscript, the author evaluated image quality of three radiation dose levels for CT venography. The results showed low- and ultralow-dose CT venography at 80 kV had acceptable image quality.

Comments

1) My biggest question is that how it was possible for the author to run the Siemens Force scanner with both tubes at 80 kV and different tube currents. For Siemens Force scanner, all the clinical protocols using two sources are in either dual-energy mode or dual-source mode. The dual-energy mode has one tube high kV and one tube low kV. In dual-source mode, both tubes are using the same tube current. Did the author use some special service mode or collaborate with Siemens to config the protocols? Otherwise, it is not possible to scan using the protocols described in the manuscript.

2) Line 42. CT dose index volume is not “calculated” but displayed on the dose page. I don’t think there was any calculation about CTDIvol in the manuscript.

3) The abstract needs to mention the special setup of the protocols using dual-source CT.

4) Have the author tried the CarekV, an automatic kV selection tool used by Siemens CT? How does it compare to 80 kV method used in the manuscript?

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Reviewer #1: No

Reviewer #2: No

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2 Jul 2021

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: No

Reviewer #2: No

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

4. Is the manuscript presented in an intelligible fashion and written in standard English?

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Reviewer #1: Yes

Reviewer #2: Yes

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: A review of the paper titled “Comparison study of image quality at various radiation doses for CT venography using advanced modeled iterative reconstruction”

Thank for letting me review this work! It is good to see we can go lower in dose using this scanner/recon for these indications and not suffer issues.

General Comments:

1. The abstract needs some attention. The conclusion statement says “using a reconstruction algorithm allows” I think you need to say “using an advanced model based iterative reconstruction algorithm”

Response: Thank you for your comment. We have changed the abstract as suggested “Low- and ultralow-dose CT venography at 80 kVp using an advanced model based iterative reconstruction algorithm” (R1-1).

2. It is not clear from the abstract that you compare regular and lower dose non advanced recon to lower dose advanced recon. You need to do this to support your conclusions to prove it was the advanced recon that enabled the dose reduction. Or else how to do we know the overall dose was just set too high? I assume you did this in the paper itself, but reading the abstract itself, this important study design point is not clear. For example, I can scan at 100 mGy using FBP and then cut it to 50 mGy and use ADMIRE. But concluding ADMIRE allowed a reduction w/o issues for diagnostic purposes is flawed…I would need to show at 50 mGy with FBP I performed worse.

Response: Thank you for your comment. We were routinely inspecting the lower extremity CT venography using ADMIRE on a CT machine (Force). At that time, we conducted using caredose at 300 reference mAs when carekVp was set at 80kVp. It would have been a superior study comparing images with FBP reconstructing and those with ADMIRE regarding dose reduction. However, raw data work will be needed to reconstruct FBP images in comparison with ADMIRE images. We did not perform the work. We have added the limitation of the study in the manuscript (R1-2). Currently, major CT vendors introduced iterative reconstruction algorithms for clinical routine, which evolved rapidly into increasingly advanced reconstruction algorithms. Most dose-reduction strategies remained in the domain of decreasing tube current or tube voltage while iterative reconstruction algorithms insure an acceptable diagnostic image quality. Therefore, we focused on dose reduction study of intraindividual comparison using ADMIRE.

1. Introduction: I don’t think this sentence means what you intend “The radiation exposure during CT venography is becoming an increasing concern 67 because the mean dose level rises when a patient requires multiple CT examinations during the 68 disease process of pulmonary embolism (chest CT) or given the recurrency of DVT” There is no reason for the mean dose the pt gets to change, I think you mean their cumulative effective dose is rising as they get more and more scans? Using CED as a motivation for dose reduction is kind of controversial, an exam, if indicated and appropriate should be given w/o concern for stochastic cancer risk. This is the position of the American College of Radiology and the American Association of Physicists in Medicine.

Response: Thank you for your comment. We have removed the sentence as suggested (R1-3)

2. Introduction: I think there a lot of papers out there for this, please cite more (I went to google scholar and found several on the first page of results you don’t cite on this topic) and consider changing the verbiage/tone of this paragraph, to something more like “there are many papers in the literature looking at dose reduction with lower kV and advanced model based recons…we are contributing to this space by looking specifically at …

a. “Few 69 studies have reported the reduction of the average radiation dose for CT venography using low 70 tube voltages, mono-energy CT, and iterative reconstruction algorithms”

Response) Thank you for your comment. We have changed the introduction and added several references as suggested (R1-4, There are many studies in the literature investigating at radiation dose reduction with low tube voltages and advanced model based reconstruction. We are contributing to this space by specifically looking at..).

3. There is no stat testing for the reader scores/ Just for the noise measurements?

Response: Thank you for your comment. Two radiologists reviewed subjective image analysis (i.e. scores) in consensus. We did not analyze interobserver variability. We only measured attenuation and image noise. Therefore, we added the limitation of this study in the manuscript (R1-5). We analyzed differences of subjective image quality and image noise of three image sets using a one-way analysis of variance with post-hoc analysis and Bonferroni correction.

4. The paper concludes it is recon method that enables the low dose visualization, but we cannot conclude this from your methods. The scores seem to basically be the same or just differ by 1 point from low to high dose, with more variation being pt to pt. I think in order to support that the lower dose was enabled by advanced recon, you must prove to us the images are not fit for diagnostic purposes if the ADMIRE recon was not used?

Response: Thank you for your comment. We did not analyze diagnostic performance for DVT detection or compare between images with filtered back projection and those with ADMIRE. We have added our study’s limitation (we did not analyze diagnostic performance for DVT detection) and change in the conclusion (~ADMIRE show acceptable image quality for DVT evaluation~, R1-6).

Specific Comments:

1. In the CT protocol section, can you elaborate on what the 70 and 30% refer to? Was the actual mAs equal to what you have listed, or was 70 and 30% used?

Response: We used 70% and 30% reference mAs, compared with reference mAs on standard CT. The actual mAs also showed 70% and 30% ratio (low-dose and ultralow-dose), compared with standard dose CT.

Reviewer #2: In this manuscript, the author evaluated image quality of three radiation dose levels for CT venography. The results showed low- and ultralow-dose CT venography at 80 kV had acceptable image quality.

Comments

1) My biggest question is that how it was possible for the author to run the Siemens Force scanner with both tubes at 80 kV and different tube currents. For Siemens Force scanner, all the clinical protocols using two sources are in either dual-energy mode or dual-source mode. The dual-energy mode has one tube high kV and one tube low kV. In dual-source mode, both tubes are using the same tube current. Did the author use some special service mode or collaborate with Siemens to config the protocols? Otherwise, it is not possible to scan using the protocols described in the manuscript.

Response: Thank you for your comment. To perform the specific split of the tube dose (mAs) between tube detector A and B, the CT scanner requires a dual energy research license. We added the feature in the material and method (R2-1).

2) Line 42. CT dose index volume is not “calculated” but displayed on the dose page. I don’t think there was any calculation about CTDIvol in the manuscript.

Response: Thank you for your comment. We changed the word, as “displayed” (R2-2).

3) The abstract needs to mention the special setup of the protocols using dual-source CT.

Response: Thank you for your comment. We added the protocol in methods section, “in the dual-source mode in tubes A (reference mAs, 210 mAs at 70%) and B (reference mAs, 90 mAs at 30%) at a fixed 80 kVp” (R2-3).

4) Have the author tried the CarekV, an automatic kV selection tool used by Siemens CT? How does it compare to 80 kV method used in the manuscript?

Response: Thank you for your comment. In Siemens CT, selection of automatic kVp or fixed kVp is possible. However, using the specific split of the tube dose in a dual source mode, we select a specific kVp (i.e, did not use automatic kVp change). Therefore, we selected fixed 80 kVp and compared between specific radiation doses.

2 Aug 2021

PONE-D-21-10760R1

Comparison study of image quality at various radiation doses for CT venography using advanced modeled iterative reconstruction

PLOS ONE

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Reviewer #1: The authors have addressed my concerns. The major issue I had was that we cannot claim it was the advanced recon that allowed the dose reduction, I think the authors have changed the paper's verbiage to account for the fact their study never compared FBP low dose to ADMIRE low dose directly. Thanks.

Reviewer #2: (No Response)

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Reviewer #1: Yes: Timothy P Szczykutowicz

Reviewer #2: No

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5 Aug 2021

Editor

Please re-address the comment 4 of Reviewer 2 about CarekV from last review. Since CarekV is a standard package on the scanner for the same purpose of this study, please add some discussion about the limitation of this study if the experiment suggested by the reviewer can't be conducted.

Response: Thank you for your comment. We have added the limitation as suggested “Fourth, we selected fixed 80 kVp and compared between specific radiation doses. Selection of automatic kVp change or fixed kVp is possible in Siemens CT. However, using the specific split of the tube dose in a dual source mode, we can only select a specific kVp (i.e, cannot use automatic kVp change).” (Editor).

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Response: Thank you for your comment.

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Reviewer #1: The authors have addressed my concerns. The major issue I had was that we cannot claim it was the advanced recon that allowed the dose reduction, I think the authors have changed the paper's verbiage to account for the fact their study never compared FBP low dose to ADMIRE low dose directly. Thanks.

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Reviewer #1: Yes: Timothy P Szczykutowicz

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Response 1~7): Thank you for your helpful comment.

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10 Aug 2021

Comparison study of image quality at various radiation doses for CT venography using advanced modeled iterative reconstruction

PONE-D-21-10760R2

Dear Dr. Park,

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23 Aug 2021

PONE-D-21-10760R2

Comparison study of image quality at various radiation doses for CT venography using advanced modeled iterative reconstruction

Dear Dr. Park:

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Table 1

Patient characteristics.

Parameter	Value
Patients (Male)	100 (48)
Age (years)	63.5 ± 16.2
Height (cm)	162.1 ± 10.6
Weight (kg)	65.5 ± 13.6
Body mass index	24.8 ± 4.0
<18.5 (underweight)	10
18.5–24.9 (normal)	41
25–29.9 (overweight)	40
30–34.9 (moderately obese)	8
35–39.9 (severely obese)	1

Note. Data are means ± standard deviations.

Table 2

Subjective and objective image quality of standard-, low-, and ultralow-dose CT venography scans.

	Standard	Low	Ultralow
Subjective image quality
Overall image quality	4.0 ± 0.1	4.0 ± 0.2	3.5 ± 0.5
Segmental vein quality
Inferior vena cava	3.9 ± 0.4	3.8 ± 0.4	3.5 ± 0.6
Right common iliac vein	3.9 ± 0.2	3.9 ± 0.3	3.8 ± 0.5
Left common iliac vein	3.9 ± 0.3	3.9 ± 0.3	3.8 ± 0.5
Right femoval vein	4.0 ± 0.3	4.0 ± 0.3	3.9 ± 0.4
Left femoral vein	3.9 ± 0.3	3.9 ± 0.3	3.8 ± 0.4
Right popliteal vein	3.8 ± 0.7	3.8 ± 0.7	3.8 ± 0.7
Left popliteal vein	3.8 ± 0.7	3.8 ± 0.7	3.8 ± 0.7
Right calf vein	3.9 ± 0.3	3.9 ± 0.3	3.9 ± 0.5
Left calf vein	3.9 ± 0.2	3.9 ± 0.2	3.9 ± 0.5
Hounsfield unit
Attenuation
Inferior vena cava	196.1 ± 31.2	195.0 ± 33.0	197.4 ± 31.6
Left femoral vein	183.4 ± 29.0	185.0 ± 28.9	181.0 ± 29.1
Image noise
Inferior vena cava	9.3 ± 2.3	11.2 ± 2.6	16.3 ± 3.7
Left femoral vein	7.4 ± 2.5	9.1 ± 3.1	11.1 ± 3.5

Note. Data are means ± standard deviations.

Table 3

Subjective image quality of DVT segments on standard-, low-, and ultralow-dose CT venography scans.

Patient No.	Age /sex	Venous segment	Standard	Low	Ultralow
1	F/81	Both calf vein	4	4	4
2	M/52	LT PV, LT calf vein	4	4	4
3	M/71	RT FV	4	4	3
		RT PV, RT calf vein	4	4	4
4	M/37	Both FV, Both PV	4	4	4
5	M/43	RT PV, RT calf vein	4	4	4
6	F/48	LT FV, LT PV, LT calf vein	4	4	4
7	M/72	RT FV, RT PV, RT calf vein	4	4	4
8	F/60	LT PV, LT calf vein	4	4	4
9	M/60	RT FV, RT PV, RT calf vein	4	4	4
10	M/70	LT FV, LT PV, LT calf vein	4	4	4
11	F/84	LT EIV	4	4	4
		LT FV	3	3	3
12	F/81	Both FV, both PV, both calf vein	4	4	4
13	M/65	RT FV	4	4	3
		Both calf vein	4	4	4
14	M/68	IVC	3	3	2
15	M/60	RT FV, RT PV, RT calf vein	4	4	4
16	M/58	LT FV, LT PV, LT calf vein	4	4	4
17	F/57	LT calf vein	4	4	4
18	F/44	RT FV, RT PV, RT calf vein	4	4	4
19	M/71	RT FV	4	4	3
		Both PV, both calf vein	4	4	4
20	M/43	IVC	3	3	2
		RT CIV, both EIV, RT FV	4	4	4
21	F/78	LT CIV, LT EIV	4	4	3
		LT FV, LT PV, LT calf vein	4	4	4
22	M/36	LT CIV	4	4	4
23	M/68	LT calf vein	4	4	4
24	M/70	LT FV, LT PV, LT calf vein	4	4	4

Abbreviations: F, female; M, male; LT, left; RT, right; IVC, inferior vena cava; CIV, common iliac vein; FV, femoral veins; PV, popliteal vein.

Table 4

Subjective image quality of venous segments in 32 patients with metal prostheses on standard-, low-, and ultralow-dose CT venography.

Patient No.	Age /sex	Metal prosthesis	Affecting venous segment	Standard	Low	Ultralow
1	F/81	S1 VP	RT CIV	4	4	4
			LT CIV	4	3	3
2	M/71	IVC filter	IVC	3	3	3
3	F/48	IVC filter	IVC	3	3	3
4	F/69	T12 VP	IVC	3	3	2
5	M/59	L4-5 PLIF	IVC, both CIV	3	3	2
6	F/62	L3-5 PLIF	Both CIV	3	3	2
		RT TKR	RT PV	2	2	2
7	M/79	L3-5 PLIF	Both CIV	4	3	2
		IVC filter	IVC	3	3	3
8	F/84	LT femur IF	LT FV	3	3	3
9	M/68	L3-5 PLIF	Both CIV	4	3	3
		IVC filter	IVC	3	3	2
		LT THR	LT EIV, LT FV	3	3	3
10	M/83	L2 VP	IVC	3	3	3
11	F/88	T12 VP	IVC	4	4	4
12	M/57	RT tibia IF	RT calf vein	2	2	2
13	F/80	IVC filter	IVC	3	3	3
14	F/88	IVC filter	IVC	3	3	3
15	F/85	RT TKR	RT PV	1	1	1
			RT calf vein	3	3	2
		LT TKR	LT PV	1	1	1
			LT calf vein	3	3	2
16	M/43	IVC filter	IVC	3	3	3
17	F/67	L5-S1 PLIF	Both CIV	3	3	3
		RT TKR	RT PV	1	1	1
			RT calf vein	3	3	2
		LT TKR	LT PV	1	1	1
			LT calf vein	3	3	2
18	M/73	IVC filter	IVC	3	3	3
19	F/84	T12/L3 VP	IVC	4	4	3
		RT TKR	RT PV	1	1	1
			RT calf vein	3	3	2
		LT TKR	LT PV	1	1	1
			LT calf vein	3	3	2
20	F/30	LT femur IF	LT FV	4	3	3
21	M/65	LT THR	LT EIV, LT FV	3	3	2
22	F/84	RT THR	RT EIV, RT FV	3	3	2
23	M/71	IVC filter	IVC	3	3	3
		RT femur IF	RT FV	3	3	3
24	F/76	RT TKR	RT PV	1	1	1
			RT calf vein	3	3	2
		LT TKR	LT PV	1	1	1
			LT calf vein	3	3	2
25	F/94	IVC filter	IVC	3	3	3
		RT TKR	RT PV	1	1	1
			RT calf vein	3	3	2
		LT TKR	LT PV	1	1	1
			LT calf vein	3	3	2
26	M/28	RT femur IF	RT FV	2	2	2
			RT PV	3	3	3
27	F/66	RT TKR	RT PV	1	1	1
			RT calf vein	3	3	3
		LT TKR	LT PV	1	1	1
			LT calf vein	3	3	3
28	M/36	LT femur IF	LT FV	3	3	2
			LT PV	3	3	3
29	F/70	L1-5 VP	IVC	3	3	3
			Both CIV	3	3	2
		LT THR	LT EIV, LT FV	3	3	3
		RT tibia IF	RT PV, RT calf vein	3	3	3
30	M/76	LT femur IF	LT FV	3	3	3
31	F/80	LT TKR	LT PV	1	1	1
			LT calf vein	3	3	3
32	F/86	T12 VP	IVC	3	3	3

Abbreviations: F, female; M, male; VP, vertebroplasty; PLIF, posterior lumbar interbody fusion; TKR, total knee replacement; THR, total hip replacement; IF, internal fixation; LT, left; RT, right; IVC, inferior vena cava; CIV, common iliac vein; FV, femoral veins; PV, popliteal vein.

Table 5

Subjective image quality of venous segments in 17 patients with stent placement.

Patient No.	Age /sex	Venous segment	Stent patency	Standard	Low	Ultralow
1	F/48	LT CIV	ISR	4	4	4
2	F/59	LT CIV	Patent	4	4	4
3–1), 2)	F/60	LT CIV	ISR	4	4	4
4	F/51	LT CIV	ISR	4	4	4
5	F/49	LT CIV	ISR	4	4	4
6	M/79	RT FV	ISR	4	4	4
7	M/68	RT FV	ISR	4	4	4
8	F/88	LT CIV	ISR	4	4	4
9	M/47	LT CIV	Patent	4	4	4
10–1), 2)	F/62	LT CIV	ISR	4	4	4
11	F/80	LT CIV	ISR	4	4	4
12	M/43	LT CIV	ISR	4	4	4
13	F/68	LT CIV	Patent	4	4	4
14	F/30	LT CIV	ISR	4	4	4
15	F/78	LT CIV	Occlusion	4	4	4
16	M/36	LT CIV, LT FV	Occlusion	4	4	4
17	F/80	LT CIV	Patent	4	4	4

* 3–1), 2) and 10–1), 2) indicate that each patient underwent two examinations, respectively.

Abbreviations: F, female; M, male; LT, left; RT, right; CIV, common iliac vein; FV, femoral veins; ISR, in-stent restenosis.