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Venous-phase chest CT with reduced contrast medium dose: Utilization of spectral low keV monoenergetic images improves image quality
European Journal of Radiology 122 (2020) 108756
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European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad
Research article
Venous-phase chest CT with reduced contrast medium dose: Utilization of spectral low keV monoenergetic images improves image quality
T
Tilman Hickethiera,*, Jan Robert Kroegera, Simon Lennartza, Jonas Doernera, David Maintza, De-Hua Changa,b a b
Department of Radiology, University Hospital of Cologne, Kerpener-Str. 62, 50973, Cologne, Germany Department of Radiology, University Medical Center Heidelberg, Im Neuenheimer Feld 400, Heidelberg, Germany
A R T I C LE I N FO
A B S T R A C T
Keywords: Dual energy Dual layer CT Chest Contrast media reduction Low contrast agent dose
Purpose: Intravenous contrast administration is crucial in many CT examinations but also poses a potential risk to the patient. Monoenergetic images (MonoE) of dual-energy CT systems can virtually increase iodine attenuation and might improve image quality (IQ) if contrast dose is reduced. In this study, we investigated the influence of MonoE on lymph node (LN) delineation and IQ in chest CT examinations with significantly reduced contrast dose (50 %) of a novel dual-layer CT (DLCT). Method: 30 patients with clinically indicated reduced contrast dose underwent venous-phase chest DLCT scans. Conventional polyenergetic (PolyE) and MonoE images at 40 keV were calculated. The contrast difference of hilar lymph nodes (LN-CD) to the adjacent right pulmonary artery, their signal-to-noise (SNR) and contrast-tonoise-ratio (CNR) were determined. Subjective IQ was evaluated by 2 readers with respect to LN delineation and overall contrast enhancement (CE) using a 5-point-Likert-scale. Results: LN-CD, SNR and CNR were significantly higher in MonoE than in PolyE images (LN-CD 92.3 ± 37.9 vs. 33.1 ± 14.5 HU, SNR 8.4 ± 3.4 vs. 4.0 ± 1.2, CNR 9.2 ± 6.3 vs. 2.6 ± 1.5; all p < 0.01). The LN delineation (3.7 ± 0.9 vs.1.8 ± 0.7; p < 0.01) and the CE (3.9 ± 0.7 vs. 2.3 ± 0.7; p < 0.01) were rated significantly better for MonoE than for PolyE images. There was no MonoE examination classified as non-diagnostic. Conclusions: Subjective and objective IQ parameters can be significantly improved for venous-phase chest CT examinations with reduced contrast doses by utilization of low-keV MonoE reconstructions. All MonoE images provided sufficient overall CE and therefore reduced contrast doses might be considered in a wider range of DLCT examinations and patients.
1. Introduction The administration of intravenous contrast media (CM) is an integral element of many CT examination protocols. However, CM administration is also accompanied by a low but proven risk for adverse reactions, in particular allergic reactions [1] and contrast-induced nephropathy [2]. Therefore, the need for CM administration should always be scrutinized and the lowest adequate dose should be used [3,4]. However, there is no general consensus on a certain ideal contrast media dose [5–7]. In order to adress this problem, several studies have shown that the amount of CM can be reduced by utilization of lower tube voltages due to the approximation to the iodine K-edge [8–15]. In the last decade,
dual-energy CT (DECT) systems became available, which allow to calculate monoenergetic images and thus enable a virtual reduction in tube voltage with comparable results [16–18]. Recently, a detector based dual-energy technique, the dual-layer CT (DLCT), was introduced providing dual-energy information and the possibility to calculate monoenergetic images for every scan [19]. Using this novel DLCT, a first study has suggested that CM dose reductions of 50 % with preserved image quality are feasible [20]. Consequently, a DLCT protocol with reduced CM dose was implemented at our hospital for examinations without need for dynamic contrast media information (i.e. singlephase examinations) and for patients at risk for adverse CM reactions. For chest CT this mainly includes examinations to evaluate thoracic lymph nodes, which only partly rely on the contrast-enhancement
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Corresponding author at: University Hospital of Cologne, Kerpener Str. 62, 50937, Köln Germany. E-mail addresses: [email protected] (T. Hickethier), [email protected] (J.R. Kroeger), [email protected] (S. Lennartz), [email protected] (J. Doerner), [email protected] (D. Maintz), [email protected] (D.-H. Chang). https://doi.org/10.1016/j.ejrad.2019.108756 Received 31 July 2019; Received in revised form 6 November 2019; Accepted 18 November 2019 0720-048X/ © 2019 Elsevier B.V. All rights reserved.
European Journal of Radiology 122 (2020) 108756
T. Hickethier, et al.
subcutaneous fat. The LN signal-to-noise ratio (LN SNR) was calculated as LN attenuation divided by the image noise. The LN contrast difference was defined as the LN attenuation (in HU) subtracted by the attenuation of the adjacent rMPA. The LN contrast-to-noise ratio (LN CNR) was calculated as LN contrast difference divided by the image noise. The relation coefficients between PolyE and MonoE LN SNR and CNR were assessed using linear regression equations analysis.
information [21–26]. In this current study, we retrospectively evaluated quantitative and qualitative image quality parameters of the first 30 examinations with this low CM dose protocol in order to estimate the potential of DLCT examinations in the context of reduced contrast agent amount since there is still no comparable information for this novel DECT technique. 2. Material and methods 2.1. Study population
2.4. Qualitative image analysis
The study population comprised 30 patients (16 male, 14 female; mean age 61.5 ± 13.5 years). They were referred from July 2016 to December 2017 to CT examinations of the chest with clinical decision to use a low CM dose protocol based on the specific assessment focus and individual risk stratification (e.g. known contrast medium allergy or impaired renal function). Consultation of the local ethics committee (Ethics Commission of Cologne University’s Faculty of Medicine; Application number 19–1240) was obtained and a specific approval was waived due to the retrospective design of the study based on preexisting examinations. In our institute, contrast-enhanced examinations on patients with a body weight of 55–120 kg are performed with a standardized amount of contrast medium (60 ml for venouse-phase chest examinations). Patients weighing below or above these limits receive a body weight-adapted amount of contrast medium. For this study, only patients who received the standardized amount of contrast medium were considered.
Two readers (both with 6 years' experience) independently evaluated the subjective delineation of the hilar lymph nodes and the overall contrast enhancement using a 5-point Likert scale (1: lymph nodes hardly distinguishable from adjacent structures / insufficient overall contrast enhancement; 2: lymph nodes perceivable but border to adjacent structures unclear / limited overall contrast enhancement; 3: lymph nodes clearly distinguishable from adjacent structures but exact margin unclear / fair overall contrast enhancement; 4: lymph node extent clear with only negligibly remaining impairment of margin delineation / good overall contrast enhancement; 5: lymph node margins perfectly definable / excellent overall contrast enhancement). After a joint training session, the subjective image analysis was performed randomly in a blinded manner.
2.5. Statistical analysis GraphPad Prism (version 8.1.0 for Macintosh, GraphPad Software, San Diego, California USA) was used for the statistical analyses. All data are given as mean ± standard deviation (SD). Data was tested for normality using the D'Agostino-Pearson omnibus K2 test. Parametric data (quantitative image parameters) was analyzed using paired t-tests (since only two groups were compared). Nonparametric data (subjective image quality scores) was analyzed using Wilcoxon matchedpairs signed rank tests. The interreader agreement for the subjective image scores was assessed using weighted Cohen's kappa. The values were interpreted according to Landis and Koch [27]. Statistical significance was defined as p ≤ 0.05.
2.2. CT acquisition parameters All examinations were performed using a 128-row dual-layer CT system (IQon; Philips GmbH, Hamburg, Germany). Patients were scanned supine during inspirational breath-hold in cranio-caudal direction. A clinical routine protocol for reduced contrast agent dose was used. It includes venous phase imaging of the chest obtained after a bolus application of 30 ml (instead of 60 ml) non-ionic, iodinated contrast media (350 mg Iohexol/mL; Accupaque 350; GE Healthcare GmbH, Solingen, Germany) injected via an antecubital vein at a flow rate of 4 ml/s followed by a 60 ml saline chaser. Bolus-tracking technique was activated in all cases, starting the examination with a 15 s scan delay after a trigger threshold of 150 Hounsfield units (HU) had been reached within a region of interest (ROI) placed in the descending aorta. The following scanning parameters were used for all scans: collimation 2 × 64 × 0.625 mm; rotation time 0.33 s; pitch 1.14; tube current - 120 kVp, matrix - 512 × 512; dose modulation type: DoseRight 3D-DOM (Philips GmbH, Hamburg, Germany). All images were reconstructed in axial orientation with a slice thickness of 2 mm and an increment of 1 mm using a dedicated spectral reconstruction algorithm with a strength level of 4 (comparable to hybrid iterative reconstructions methods, e.g. iDose4 (Philips GmbH, Hamburg, Germany)) and a constant kernel (Spectral B; Philips GmbH, Hamburg, Germany). Conventional 120 kV PolyE and MonoE images at 40 keV were reconstructed. All image analyses were performed offline on a dedicated workstation (IntelliSpace Portal 6.5; Philips GmbH, Hamburg, Germany).
3. Results 3.1. Attenuation and image noise measurements The attenuation of the lymph nodes at the right lung hilum was significantly higher in MonoE images than in PolyE images (98.2 ± 30.1 vs. 54.3 ± 12.5 HU; p < 0.01). Likewise, the attenuation of the right main pulmonary artery was also significantly higher in MonoE images than in PolyE images (190.5 ± 36.7 vs. 87.4 ± 11.2 HU; p < 0.01). Image noise was slightly lower in MonoE images than in PolyE images, which also reached significance (11.8 ± 3.4 vs. 14.1 ± 3.4 HU; p < 0.01). Fig. 1 shows the above-mentioned results.
3.2. Lymph node contrast difference, SNR and CNR values Consequently, LN SNR values were significantly higher in MonoE images than in PolyE images (8.4 ± 3.4 vs. 4.0 ± 1.2; p < 0.01). The calculated lymph node contrast difference (LN CD) was also significantly higher for MonoE images than for PolyE images (92.3 ± 37.9 vs. 33.1 ± 14.5 HU; p < 0.01). As a result, the LN CNR values were likewise significantly higher for MonoE images than for PolyE images (9.2 ± 6.3 vs. 2.6 ± 1.5; p < 0.01). Fig. 2 shows the above-mentioned results. Additionally, linear regression analysis revealed a 2.1x higher SNR and 3.6x higher CNR for MonoE compared to PolyE data.
2.3. Quantitative image analysis All quantitative analyses were conducted by a reader with 6 years' experience and all measurements were performed at predefined positions. Circular regions of interest (ROIs) of at least 70 mm2 were placed in a lymph node (LN) at the right lung hilum, in the adjacent right main pulmonary artery (rMPA), in the infraspinatus muscle and the subcutaneous fat. Attenuation values (in Hounsfield Units; HU) and standard deviations (SD) were averaged and compared between both reconstruction types. Image noise was defined as SD of attenuation of the 2
European Journal of Radiology 122 (2020) 108756
T. Hickethier, et al.
Fig. 1. Graphical depiction of the attenuation of the hilar lymph nodes (striped, left y-axis) and the right main pulmonary artery (dotted, left y-axis) as well as the image noise (checkered, right y-axis; lower is superior) for both reconstruction types (PolyE light gray, MonoE dark gray) (n = 30 for each comparison). Asterisks indicate significant differences between MonoE and PolyE images (p < 0.05). Fig. 3. Graphical depiction of the qualitative image analysis: delineation of hilar lymph nodes (striped; higher is superior) as well as overall contrast enhancement (dotted; higher is superior) for both reconstruction types (PolyE light gray, MonoE dark gray) (n = 30 for each comparison). Asterisks indicate significant differences between MonoE and PolyE images (p < 0.05).
4. Discussion Our study shows quantitative and qualitative image quality improvements for venous-phase chest CT examinations with low contrast media dose using low keV monoenergetic images derived from a DLCT. It is the first study to provide data for this novel DECT technique based on which the use of reduced contrast medium doses could be extended to further indications. We found a significant increase in lymph node and, to a much greater extent, right main pulmonary artery attenuation for MonoE images, which resulted in an overall significantly increased contrast difference of these adjacent structures. Additionally, in line with previous studies on DLCT examinations of the chest [28], image noise was slightly lower in MonoE than in PolyE images. Paired with the increased lymph node contrast difference, this led to significantly higher CNR values in MonoE reconstructions. This is underlined by the linear regression analysis performed, which shows 2.1x higher SNR and 3.6x higher CNR for MonoE compared to PolyE data. These quantitative improvements in image quality were also reflected by the qualitative image analysis results. Both the delineation of hilar lymph nodes and the overall contrast enhancement were rated significantly better for MonoE images, with adequate results in these two categories despite the low contrast media dose. Our data are consistent with the results of previous studies, which found a significant increase in SNR and CNR values for low keV MonoE images of venous-phase abdominal examinations conducted with a different dual energy technique [16]. Another preclinical venous-phase abdominal study demonstrated that CNR values of PolyE images could be maintained in examinations with 50 % or, for hypovascular lesions, even 75 % reductions in contrast media dose if low keV MonoE images were used [17]. Likewise, a further study, in this case with regard to pediatric abdominal examinations, found that low keV MonoE images of examinations with reduced contrast media dose provide similar degrees of absolute and relative enhancement of abdominal organs compared to PolyE images with regular contrast media dose as well as a clinically acceptable image quality [18].
Fig. 2. Graphical depiction of the lymph node contrast difference (CD) (striped, left y-axis; higher is superior) as well as the LN SNR (dotted, right y-axis; higher is superior) and CNR (checkered, right y-axis; higher is superior) values for both reconstruction types (PolyE light gray, MonoE dark gray) (n = 30 for each comparison). Asterisks indicate significant differences between MonoE and PolyE images (p < 0.05).
3.3. Qualitative image analysis The interreader agreement for the subjective image analysis was very good for both evaluated parameters and both reconstruction types (LN Delineation PolyE 0.869, MonoE 0.802, Overall contrast enhancement PolyE 0.813, MonoE 0.821; data is not shown in a separate figure). The delineation of hilar lymph nodes was rated significantly better for MonoE images than for PolyE images (MonoE mean score 3.7 ± 0.9, median score 4 vs. PolyE mean score 1.8 ± 0.7, median score 2; p < 0.01). Likewise, the overall contrast enhancement was also rated significantly better for MonoE images than for PolyE images (MonoE mean score 3.9 ± 0.7, median score 4 vs. PolyE mean score 2.3 ± 0.7, median score 2; p < 0.01). In all MonoE reconstructions there were no examinations rated as limited or insufficient overall contrast enhancement. Fig. 3 shows the above-mentioned results and Fig. 4 gives an example images of the improved subjective and objective image quality parameters in MonoE reconstructions. 3
European Journal of Radiology 122 (2020) 108756
T. Hickethier, et al.
Fig. 4. Conventional polyenergetic (left) and 40 keV monoenergetic reconstructions (right) of identical raw data. Additional coronal images were calculated for demonstration purposes. Hilar lymph nodes were marked with arrows in MonoE images. Subjective image quality and objective image parameters were superior in MonoE images compared to the PolyE images (LN Delineation 4 vs. 3 / Overall contrast enhancement 4 vs. 2 / LN CNR 5.8 vs. 1.9).
transferability to other chest CT indications and therefore the individual demand of each examination must be assessed before low CM dose protocols can be safely considered. In addition, only the data of patients who received a standardized amount of contrast medium were evaluated in the current study. Although this shows the feasibility of venous-phase chest DLCT examinations with reduced contrast medium doses, the minimum amount of contrast medium required as well as the influence of body weight-adapted contrast medium administration cannot be clarified on the basis of these data and should be the subject of further studies.
In addition to the above-mentioned reduction in the risk potential posed by the administration of contrast medium to patients, decreased contrast media doses would also lead to significant cost reductions, with prices for 1 ml of contrast agent quantified at up to $0.95 [29,30]. Due mainly to its retrospective nature, our study has several limitations. First, there is no control group, as the reduced CM dose protocol was chosen individually based on clinical considerations and individual risk stratification. Therefore, only a comparison between PolyE and MonoE images of the same examinations with reduced CM dose was possible. However, in our study, there were no MonoE reconstructions classified as limited or insufficient overall contrast enhancement, so a reduced CM dose might be considered in a broader range of patients. Secondl, only chest CT examinations were included in this current study. Abdominal examinations may rely more on dynamic contrast-enhancement information (e.g. for the evaluation of hepatic neoplasms) and the use of low CM dose protocols must be evaluated separately for them. Third, the consecutive inclusion of all patients who have received a low CM dose chest CT examination potentially leads to a selection bias. Additionally, there was only a limited number of of assessment focuses in our study without consideration of specific thoracic pathologies. These two aspects mentioned above reduce the
5. Conclusion Our study provides the first retrospective data on venous-phase chest CT examinations with reduced contrast medium doses conducted using a novel DLCT. If low keV MonoE reconstructions are used, subjective and objective image quality can be significantly improved in comparison to conventional PolyE images. Additionally, all MonoE images provided sufficient overall contrast enhancement and therefore a reduced contrast media dose might be considered in a wider range of DLCT examinations. 4
European Journal of Radiology 122 (2020) 108756
T. Hickethier, et al.
Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/ or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Consultation of the local ethics committee was obtained and a specific approval was waived due to the retrospective design of the study based on pre-existing examinations.
[13]
[14]
Declaration of Competing Interest [15]
No conflicts of interest were declared. Acknowledgements
[16]
Research related to this project was partially funded under a research agreement between University Hospital of Cologne and Philips Healthcare. David Maintz is on the speakers’ bureau for Philips Healthcare.
[17]
[18]
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Contents lists available at ScienceDirect
European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad
Research article
Venous-phase chest CT with reduced contrast medium dose: Utilization of spectral low keV monoenergetic images improves image quality
T
Tilman Hickethiera,*, Jan Robert Kroegera, Simon Lennartza, Jonas Doernera, David Maintza, De-Hua Changa,b a b
Department of Radiology, University Hospital of Cologne, Kerpener-Str. 62, 50973, Cologne, Germany Department of Radiology, University Medical Center Heidelberg, Im Neuenheimer Feld 400, Heidelberg, Germany
A R T I C LE I N FO
A B S T R A C T
Keywords: Dual energy Dual layer CT Chest Contrast media reduction Low contrast agent dose
Purpose: Intravenous contrast administration is crucial in many CT examinations but also poses a potential risk to the patient. Monoenergetic images (MonoE) of dual-energy CT systems can virtually increase iodine attenuation and might improve image quality (IQ) if contrast dose is reduced. In this study, we investigated the influence of MonoE on lymph node (LN) delineation and IQ in chest CT examinations with significantly reduced contrast dose (50 %) of a novel dual-layer CT (DLCT). Method: 30 patients with clinically indicated reduced contrast dose underwent venous-phase chest DLCT scans. Conventional polyenergetic (PolyE) and MonoE images at 40 keV were calculated. The contrast difference of hilar lymph nodes (LN-CD) to the adjacent right pulmonary artery, their signal-to-noise (SNR) and contrast-tonoise-ratio (CNR) were determined. Subjective IQ was evaluated by 2 readers with respect to LN delineation and overall contrast enhancement (CE) using a 5-point-Likert-scale. Results: LN-CD, SNR and CNR were significantly higher in MonoE than in PolyE images (LN-CD 92.3 ± 37.9 vs. 33.1 ± 14.5 HU, SNR 8.4 ± 3.4 vs. 4.0 ± 1.2, CNR 9.2 ± 6.3 vs. 2.6 ± 1.5; all p < 0.01). The LN delineation (3.7 ± 0.9 vs.1.8 ± 0.7; p < 0.01) and the CE (3.9 ± 0.7 vs. 2.3 ± 0.7; p < 0.01) were rated significantly better for MonoE than for PolyE images. There was no MonoE examination classified as non-diagnostic. Conclusions: Subjective and objective IQ parameters can be significantly improved for venous-phase chest CT examinations with reduced contrast doses by utilization of low-keV MonoE reconstructions. All MonoE images provided sufficient overall CE and therefore reduced contrast doses might be considered in a wider range of DLCT examinations and patients.
1. Introduction The administration of intravenous contrast media (CM) is an integral element of many CT examination protocols. However, CM administration is also accompanied by a low but proven risk for adverse reactions, in particular allergic reactions [1] and contrast-induced nephropathy [2]. Therefore, the need for CM administration should always be scrutinized and the lowest adequate dose should be used [3,4]. However, there is no general consensus on a certain ideal contrast media dose [5–7]. In order to adress this problem, several studies have shown that the amount of CM can be reduced by utilization of lower tube voltages due to the approximation to the iodine K-edge [8–15]. In the last decade,
dual-energy CT (DECT) systems became available, which allow to calculate monoenergetic images and thus enable a virtual reduction in tube voltage with comparable results [16–18]. Recently, a detector based dual-energy technique, the dual-layer CT (DLCT), was introduced providing dual-energy information and the possibility to calculate monoenergetic images for every scan [19]. Using this novel DLCT, a first study has suggested that CM dose reductions of 50 % with preserved image quality are feasible [20]. Consequently, a DLCT protocol with reduced CM dose was implemented at our hospital for examinations without need for dynamic contrast media information (i.e. singlephase examinations) and for patients at risk for adverse CM reactions. For chest CT this mainly includes examinations to evaluate thoracic lymph nodes, which only partly rely on the contrast-enhancement
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Corresponding author at: University Hospital of Cologne, Kerpener Str. 62, 50937, Köln Germany. E-mail addresses: [email protected] (T. Hickethier), [email protected] (J.R. Kroeger), [email protected] (S. Lennartz), [email protected] (J. Doerner), [email protected] (D. Maintz), [email protected] (D.-H. Chang). https://doi.org/10.1016/j.ejrad.2019.108756 Received 31 July 2019; Received in revised form 6 November 2019; Accepted 18 November 2019 0720-048X/ © 2019 Elsevier B.V. All rights reserved.
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subcutaneous fat. The LN signal-to-noise ratio (LN SNR) was calculated as LN attenuation divided by the image noise. The LN contrast difference was defined as the LN attenuation (in HU) subtracted by the attenuation of the adjacent rMPA. The LN contrast-to-noise ratio (LN CNR) was calculated as LN contrast difference divided by the image noise. The relation coefficients between PolyE and MonoE LN SNR and CNR were assessed using linear regression equations analysis.
information [21–26]. In this current study, we retrospectively evaluated quantitative and qualitative image quality parameters of the first 30 examinations with this low CM dose protocol in order to estimate the potential of DLCT examinations in the context of reduced contrast agent amount since there is still no comparable information for this novel DECT technique. 2. Material and methods 2.1. Study population
2.4. Qualitative image analysis
The study population comprised 30 patients (16 male, 14 female; mean age 61.5 ± 13.5 years). They were referred from July 2016 to December 2017 to CT examinations of the chest with clinical decision to use a low CM dose protocol based on the specific assessment focus and individual risk stratification (e.g. known contrast medium allergy or impaired renal function). Consultation of the local ethics committee (Ethics Commission of Cologne University’s Faculty of Medicine; Application number 19–1240) was obtained and a specific approval was waived due to the retrospective design of the study based on preexisting examinations. In our institute, contrast-enhanced examinations on patients with a body weight of 55–120 kg are performed with a standardized amount of contrast medium (60 ml for venouse-phase chest examinations). Patients weighing below or above these limits receive a body weight-adapted amount of contrast medium. For this study, only patients who received the standardized amount of contrast medium were considered.
Two readers (both with 6 years' experience) independently evaluated the subjective delineation of the hilar lymph nodes and the overall contrast enhancement using a 5-point Likert scale (1: lymph nodes hardly distinguishable from adjacent structures / insufficient overall contrast enhancement; 2: lymph nodes perceivable but border to adjacent structures unclear / limited overall contrast enhancement; 3: lymph nodes clearly distinguishable from adjacent structures but exact margin unclear / fair overall contrast enhancement; 4: lymph node extent clear with only negligibly remaining impairment of margin delineation / good overall contrast enhancement; 5: lymph node margins perfectly definable / excellent overall contrast enhancement). After a joint training session, the subjective image analysis was performed randomly in a blinded manner.
2.5. Statistical analysis GraphPad Prism (version 8.1.0 for Macintosh, GraphPad Software, San Diego, California USA) was used for the statistical analyses. All data are given as mean ± standard deviation (SD). Data was tested for normality using the D'Agostino-Pearson omnibus K2 test. Parametric data (quantitative image parameters) was analyzed using paired t-tests (since only two groups were compared). Nonparametric data (subjective image quality scores) was analyzed using Wilcoxon matchedpairs signed rank tests. The interreader agreement for the subjective image scores was assessed using weighted Cohen's kappa. The values were interpreted according to Landis and Koch [27]. Statistical significance was defined as p ≤ 0.05.
2.2. CT acquisition parameters All examinations were performed using a 128-row dual-layer CT system (IQon; Philips GmbH, Hamburg, Germany). Patients were scanned supine during inspirational breath-hold in cranio-caudal direction. A clinical routine protocol for reduced contrast agent dose was used. It includes venous phase imaging of the chest obtained after a bolus application of 30 ml (instead of 60 ml) non-ionic, iodinated contrast media (350 mg Iohexol/mL; Accupaque 350; GE Healthcare GmbH, Solingen, Germany) injected via an antecubital vein at a flow rate of 4 ml/s followed by a 60 ml saline chaser. Bolus-tracking technique was activated in all cases, starting the examination with a 15 s scan delay after a trigger threshold of 150 Hounsfield units (HU) had been reached within a region of interest (ROI) placed in the descending aorta. The following scanning parameters were used for all scans: collimation 2 × 64 × 0.625 mm; rotation time 0.33 s; pitch 1.14; tube current - 120 kVp, matrix - 512 × 512; dose modulation type: DoseRight 3D-DOM (Philips GmbH, Hamburg, Germany). All images were reconstructed in axial orientation with a slice thickness of 2 mm and an increment of 1 mm using a dedicated spectral reconstruction algorithm with a strength level of 4 (comparable to hybrid iterative reconstructions methods, e.g. iDose4 (Philips GmbH, Hamburg, Germany)) and a constant kernel (Spectral B; Philips GmbH, Hamburg, Germany). Conventional 120 kV PolyE and MonoE images at 40 keV were reconstructed. All image analyses were performed offline on a dedicated workstation (IntelliSpace Portal 6.5; Philips GmbH, Hamburg, Germany).
3. Results 3.1. Attenuation and image noise measurements The attenuation of the lymph nodes at the right lung hilum was significantly higher in MonoE images than in PolyE images (98.2 ± 30.1 vs. 54.3 ± 12.5 HU; p < 0.01). Likewise, the attenuation of the right main pulmonary artery was also significantly higher in MonoE images than in PolyE images (190.5 ± 36.7 vs. 87.4 ± 11.2 HU; p < 0.01). Image noise was slightly lower in MonoE images than in PolyE images, which also reached significance (11.8 ± 3.4 vs. 14.1 ± 3.4 HU; p < 0.01). Fig. 1 shows the above-mentioned results.
3.2. Lymph node contrast difference, SNR and CNR values Consequently, LN SNR values were significantly higher in MonoE images than in PolyE images (8.4 ± 3.4 vs. 4.0 ± 1.2; p < 0.01). The calculated lymph node contrast difference (LN CD) was also significantly higher for MonoE images than for PolyE images (92.3 ± 37.9 vs. 33.1 ± 14.5 HU; p < 0.01). As a result, the LN CNR values were likewise significantly higher for MonoE images than for PolyE images (9.2 ± 6.3 vs. 2.6 ± 1.5; p < 0.01). Fig. 2 shows the above-mentioned results. Additionally, linear regression analysis revealed a 2.1x higher SNR and 3.6x higher CNR for MonoE compared to PolyE data.
2.3. Quantitative image analysis All quantitative analyses were conducted by a reader with 6 years' experience and all measurements were performed at predefined positions. Circular regions of interest (ROIs) of at least 70 mm2 were placed in a lymph node (LN) at the right lung hilum, in the adjacent right main pulmonary artery (rMPA), in the infraspinatus muscle and the subcutaneous fat. Attenuation values (in Hounsfield Units; HU) and standard deviations (SD) were averaged and compared between both reconstruction types. Image noise was defined as SD of attenuation of the 2
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Fig. 1. Graphical depiction of the attenuation of the hilar lymph nodes (striped, left y-axis) and the right main pulmonary artery (dotted, left y-axis) as well as the image noise (checkered, right y-axis; lower is superior) for both reconstruction types (PolyE light gray, MonoE dark gray) (n = 30 for each comparison). Asterisks indicate significant differences between MonoE and PolyE images (p < 0.05). Fig. 3. Graphical depiction of the qualitative image analysis: delineation of hilar lymph nodes (striped; higher is superior) as well as overall contrast enhancement (dotted; higher is superior) for both reconstruction types (PolyE light gray, MonoE dark gray) (n = 30 for each comparison). Asterisks indicate significant differences between MonoE and PolyE images (p < 0.05).
4. Discussion Our study shows quantitative and qualitative image quality improvements for venous-phase chest CT examinations with low contrast media dose using low keV monoenergetic images derived from a DLCT. It is the first study to provide data for this novel DECT technique based on which the use of reduced contrast medium doses could be extended to further indications. We found a significant increase in lymph node and, to a much greater extent, right main pulmonary artery attenuation for MonoE images, which resulted in an overall significantly increased contrast difference of these adjacent structures. Additionally, in line with previous studies on DLCT examinations of the chest [28], image noise was slightly lower in MonoE than in PolyE images. Paired with the increased lymph node contrast difference, this led to significantly higher CNR values in MonoE reconstructions. This is underlined by the linear regression analysis performed, which shows 2.1x higher SNR and 3.6x higher CNR for MonoE compared to PolyE data. These quantitative improvements in image quality were also reflected by the qualitative image analysis results. Both the delineation of hilar lymph nodes and the overall contrast enhancement were rated significantly better for MonoE images, with adequate results in these two categories despite the low contrast media dose. Our data are consistent with the results of previous studies, which found a significant increase in SNR and CNR values for low keV MonoE images of venous-phase abdominal examinations conducted with a different dual energy technique [16]. Another preclinical venous-phase abdominal study demonstrated that CNR values of PolyE images could be maintained in examinations with 50 % or, for hypovascular lesions, even 75 % reductions in contrast media dose if low keV MonoE images were used [17]. Likewise, a further study, in this case with regard to pediatric abdominal examinations, found that low keV MonoE images of examinations with reduced contrast media dose provide similar degrees of absolute and relative enhancement of abdominal organs compared to PolyE images with regular contrast media dose as well as a clinically acceptable image quality [18].
Fig. 2. Graphical depiction of the lymph node contrast difference (CD) (striped, left y-axis; higher is superior) as well as the LN SNR (dotted, right y-axis; higher is superior) and CNR (checkered, right y-axis; higher is superior) values for both reconstruction types (PolyE light gray, MonoE dark gray) (n = 30 for each comparison). Asterisks indicate significant differences between MonoE and PolyE images (p < 0.05).
3.3. Qualitative image analysis The interreader agreement for the subjective image analysis was very good for both evaluated parameters and both reconstruction types (LN Delineation PolyE 0.869, MonoE 0.802, Overall contrast enhancement PolyE 0.813, MonoE 0.821; data is not shown in a separate figure). The delineation of hilar lymph nodes was rated significantly better for MonoE images than for PolyE images (MonoE mean score 3.7 ± 0.9, median score 4 vs. PolyE mean score 1.8 ± 0.7, median score 2; p < 0.01). Likewise, the overall contrast enhancement was also rated significantly better for MonoE images than for PolyE images (MonoE mean score 3.9 ± 0.7, median score 4 vs. PolyE mean score 2.3 ± 0.7, median score 2; p < 0.01). In all MonoE reconstructions there were no examinations rated as limited or insufficient overall contrast enhancement. Fig. 3 shows the above-mentioned results and Fig. 4 gives an example images of the improved subjective and objective image quality parameters in MonoE reconstructions. 3
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Fig. 4. Conventional polyenergetic (left) and 40 keV monoenergetic reconstructions (right) of identical raw data. Additional coronal images were calculated for demonstration purposes. Hilar lymph nodes were marked with arrows in MonoE images. Subjective image quality and objective image parameters were superior in MonoE images compared to the PolyE images (LN Delineation 4 vs. 3 / Overall contrast enhancement 4 vs. 2 / LN CNR 5.8 vs. 1.9).
transferability to other chest CT indications and therefore the individual demand of each examination must be assessed before low CM dose protocols can be safely considered. In addition, only the data of patients who received a standardized amount of contrast medium were evaluated in the current study. Although this shows the feasibility of venous-phase chest DLCT examinations with reduced contrast medium doses, the minimum amount of contrast medium required as well as the influence of body weight-adapted contrast medium administration cannot be clarified on the basis of these data and should be the subject of further studies.
In addition to the above-mentioned reduction in the risk potential posed by the administration of contrast medium to patients, decreased contrast media doses would also lead to significant cost reductions, with prices for 1 ml of contrast agent quantified at up to $0.95 [29,30]. Due mainly to its retrospective nature, our study has several limitations. First, there is no control group, as the reduced CM dose protocol was chosen individually based on clinical considerations and individual risk stratification. Therefore, only a comparison between PolyE and MonoE images of the same examinations with reduced CM dose was possible. However, in our study, there were no MonoE reconstructions classified as limited or insufficient overall contrast enhancement, so a reduced CM dose might be considered in a broader range of patients. Secondl, only chest CT examinations were included in this current study. Abdominal examinations may rely more on dynamic contrast-enhancement information (e.g. for the evaluation of hepatic neoplasms) and the use of low CM dose protocols must be evaluated separately for them. Third, the consecutive inclusion of all patients who have received a low CM dose chest CT examination potentially leads to a selection bias. Additionally, there was only a limited number of of assessment focuses in our study without consideration of specific thoracic pathologies. These two aspects mentioned above reduce the
5. Conclusion Our study provides the first retrospective data on venous-phase chest CT examinations with reduced contrast medium doses conducted using a novel DLCT. If low keV MonoE reconstructions are used, subjective and objective image quality can be significantly improved in comparison to conventional PolyE images. Additionally, all MonoE images provided sufficient overall contrast enhancement and therefore a reduced contrast media dose might be considered in a wider range of DLCT examinations. 4
European Journal of Radiology 122 (2020) 108756
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Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/ or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Consultation of the local ethics committee was obtained and a specific approval was waived due to the retrospective design of the study based on pre-existing examinations.
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Declaration of Competing Interest [15]
No conflicts of interest were declared. Acknowledgements
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Research related to this project was partially funded under a research agreement between University Hospital of Cologne and Philips Healthcare. David Maintz is on the speakers’ bureau for Philips Healthcare.
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