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Multimodality CT imaging contributes to improving the diagnostic accuracy of solitary pulmonary nodules: a multi-institutional and prospective study

Gaowu Yan
Gaowu Yan
, 
Hongwei Li
Hongwei Li
, 
Xiaoping Fan
Xiaoping Fan
, 
Jiantao Deng
Jiantao Deng
, 
Jing Yan
Jing Yan
, 
Fei Qiao
Fei Qiao
, 
Gaowen Yan
Gaowen Yan
, 
Tao Liu
Tao Liu
, 
Jiankang Chen
Jiankang Chen
, 
Lei Wang
Lei Wang
, 
Yang Yang
Yang Yang
, 
Yong Li
Yong Li
, 
Linwei Zhao
Linwei Zhao
, 
Anup Bhetuwal
Anup Bhetuwal
, 
Morgan A. McClure
Morgan A. McClure
, 
Na Li
Na Li
 and 
Chen Peng
Chen Peng
   | Feb 17, 2023
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Article Category: Research Article
Published Online: Feb 17, 2023
Page range: 20 - 34
Received: Aug 15, 2022
Accepted: Dec 05, 2022
DOI: https://doi.org/10.2478/raon-2023-0008
© 2023 Gaowu Yan, Hongwei Li, Xiaoping Fan, Jiantao Deng, Jing Yan, Fei Qiao, Gaowen Yan, Tao Liu, Jiankang Chen, Lei Wang, Yang Yang, Yong Li, Linwei Zhao, Anup Bhetuwal, Morgan A. McClure, Na Li, Chen Peng, published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Figure 1

Flow chart of patient selection. SPNs = solitary pulmonary nodules
Flow chart of patient selection. SPNs = solitary pulmonary nodules

Figure 2

Technology roadmap of multimodality computed tomography (CT) imaging for evaluating solitary pulmonary nodules (SPNs). BF = blood flow; BV = blood volume; CECT = contrast enhanced CT; CTPI = CT perfusion imaging; DECT = dual-energy CT; IC = iodine concentration; MPR = multiplanar reconstruction; NECT = non-contrast enhanced CT; MTT = mean transit time; NIC = normalized iodine concentration; OL = iodine overlay; PS = permeability surface
Technology roadmap of multimodality computed tomography (CT) imaging for evaluating solitary pulmonary nodules (SPNs). BF = blood flow; BV = blood volume; CECT = contrast enhanced CT; CTPI = CT perfusion imaging; DECT = dual-energy CT; IC = iodine concentration; MPR = multiplanar reconstruction; NECT = non-contrast enhanced CT; MTT = mean transit time; NIC = normalized iodine concentration; OL = iodine overlay; PS = permeability surface

Figure 3

A solitary pulmonary nodule (SPN) with the size of 17.0 × 19.0 mm located in the middle lobe of right lung of a 59 years old male. Non-contrast enhanced CT (NECT), both upper (A) and (B) images, showed that there was sign of smooth margin, but without signs of lobulation, spiculation, vacuole, cavitation, air bronchogram, calcification, fat, pleural indentation, vessel convergence, or adjacent bronchial changes. Contrast enhanced CT (CECT) showed that there were mild and obvious enhancements in the arterial (C) and venous (D) phases, respectively. The patient was scanned with a CT-guided percutaneous lung biopsy procedure, and the pathological result showed chronic inflammatory disease. This SPN disappeared after a week of antibiotic therapy.
A solitary pulmonary nodule (SPN) with the size of 17.0 × 19.0 mm located in the middle lobe of right lung of a 59 years old male. Non-contrast enhanced CT (NECT), both upper (A) and (B) images, showed that there was sign of smooth margin, but without signs of lobulation, spiculation, vacuole, cavitation, air bronchogram, calcification, fat, pleural indentation, vessel convergence, or adjacent bronchial changes. Contrast enhanced CT (CECT) showed that there were mild and obvious enhancements in the arterial (C) and venous (D) phases, respectively. The patient was scanned with a CT-guided percutaneous lung biopsy procedure, and the pathological result showed chronic inflammatory disease. This SPN disappeared after a week of antibiotic therapy.

Figure 4

A solitary pulmonary nodule (SPN) with the size of 25.0 × 27.0 mm located in the superior lobe of left lung of a 61 years old female evaluated by CT perfusion imaging (CTPI). Blood volume (BV) (A), blood flow (BF) (B), mean transit time (MTT) (C), and permeability surface (PS) (D) for the SPN were 6.16 ml/100 g, 34.16 ml/100 g/min, 10.94 s, and 25.97 ml/100 g/min, respectively. Pathology of the SPN after the surgery confirmed the diagnosis of an adenocarcinoma.
A solitary pulmonary nodule (SPN) with the size of 25.0 × 27.0 mm located in the superior lobe of left lung of a 61 years old female evaluated by CT perfusion imaging (CTPI). Blood volume (BV) (A), blood flow (BF) (B), mean transit time (MTT) (C), and permeability surface (PS) (D) for the SPN were 6.16 ml/100 g, 34.16 ml/100 g/min, 10.94 s, and 25.97 ml/100 g/min, respectively. Pathology of the SPN after the surgery confirmed the diagnosis of an adenocarcinoma.

Figure 5

Receiver operating characteristic curve for distinguishing benign from malignant nodules using CT perfusion imaging parameter of permeability surface (PS).
Receiver operating characteristic curve for distinguishing benign from malignant nodules using CT perfusion imaging parameter of permeability surface (PS).

Figure 6

A solitary pulmonary nodule (SPN) with the size of 24.0 × 26.0 mm located in the superior lobe of left lung of a 57 years old female evaluated by arterial (A) and venous phases (B) of dual-energy CT (DECT). Iodine concentration at the arterial phase (aIC), Iodine concentration at the venous phase (vIC), normalized iodine concentration at the arterial phase (aNIC), and normalized iodine concentration at the venous phase (vNIC) were 2.409 mg/mL, 10.23 mg/mL, 0.17 (2.409/14.18), 0.53 (10.23/19.18) respectively. Pathology of the SPN after the surgery confirmed the diagnosis of an adenocarcinoma.
A solitary pulmonary nodule (SPN) with the size of 24.0 × 26.0 mm located in the superior lobe of left lung of a 57 years old female evaluated by arterial (A) and venous phases (B) of dual-energy CT (DECT). Iodine concentration at the arterial phase (aIC), Iodine concentration at the venous phase (vIC), normalized iodine concentration at the arterial phase (aNIC), and normalized iodine concentration at the venous phase (vNIC) were 2.409 mg/mL, 10.23 mg/mL, 0.17 (2.409/14.18), 0.53 (10.23/19.18) respectively. Pathology of the SPN after the surgery confirmed the diagnosis of an adenocarcinoma.

Figure 7

Receiver operating characteristic curves for distinguishing benign from malignant nodules using dual-energy CT parameters. aOL = Iodine overlay at the arterial phase (AUC = 0.636); vOL = Iodine overlay at the venous phase (AUC = 0.638); aIC = Iodine concentration at the arterial phase (AUC = 0.657); vIC = Iodine concentration at the venous phase (area under the curve [AUC] = 0.703); aNIC = normalized iodine concentration at the arterial phase (AUC = 0.728); vNIC = normalized iodine concentration at the venous phase (AUC = 0.790); all p values < 0.05
Receiver operating characteristic curves for distinguishing benign from malignant nodules using dual-energy CT parameters. aOL = Iodine overlay at the arterial phase (AUC = 0.636); vOL = Iodine overlay at the venous phase (AUC = 0.638); aIC = Iodine concentration at the arterial phase (AUC = 0.657); vIC = Iodine concentration at the venous phase (area under the curve [AUC] = 0.703); aNIC = normalized iodine concentration at the arterial phase (AUC = 0.728); vNIC = normalized iodine concentration at the venous phase (AUC = 0.790); all p values < 0.05

Solitary pulmonary nodules evaluated with CT perfusion imaging

Parameters* Benign SPNs (n = 118) Malignant SPNs (n = 167) P values
BF (ml/100 g/min) 49.34 (27.78, 72.81) 58.44 (24.91, 80.47) 0.1022
BV (ml/100 g) 4.79 (2.87, 7.66) 4.84 (2.90, 7.74) 0.1829
MTT (s) 6.71 (3.05, 9.58) 7.66 (3.83, 10.54) 0.2034
PS (ml/100 g/min) 8.89 (4.94, 12.45) 14.37 (11.50, 16.29) < 0.0001

Solitary pulmonary nodules evaluated with dual-energy CT

Parameters AUC Threshold Sensitivity Specificity 95% CI P values
aOL (HU) 0.636 13.89 70.66 61.02 0.577–0.692 < 0.001
vOL (HU) 0.638 12.79 59.88 72.03 0.580–0.694 < 0.001
aIC (mg/ml) 0.657 0.65 67.66 69.49 0.599–0.712 < 0.001
vIC (mg/ml) 0.703 0.85 68.86 71.19 0.646–0.755 < 0.001
aNIC 0.728 0.12 67.66 74.58 0.672–0.778 < 0.001
vNIC 0.790 0.35 75.45 80.51 0.738–0.836 0.0001

Step-wise approach of multimodality CT imaging for evaluating solitary pulmonary nodules14647

1. Solid
Density 2. Subsolid
3. Round or oval
Shape 4. Triangular or polygonal
5. Smooth
Margins 6. Lobulated
7. Spiculated
Non-contrast enhanced CT 8. Fat
Internal characteristics 9. Calcification
10. Cavitation
11. Pleural retraction
12. Air bronchogram
Some complex findings 13. Bubble like lucencies (pseudocavitation)
14. Cystic airspace
15. Vascular convergence
Contrast enhanced CT Parameter (s) 16. Degree of enhancement
CT perfusion imaging Parameter (s) 17. Permeability surface
Dual-energy CT Parameter (s) 18. Normalized iodine concentration at the venous phase

Solitary pulmonary nodules (SPNs) evaluated with dual-energy CT

Parameters* Benign SPNs (n = 118) Malignant SPNs (n = 167) P Values
aOL (HU) 13.24 (10.97, 21.58) 19.58 (13.29, 26.07) < 0.0001
vOL (HU) 11.09 (10.09, 14.86) 14.99 (10.59, 23.98) < 0.0001
aIC (mg/ml) 0.69 (0.47, 0.985) 1.13 (0.70, 1.56) < 0.0001
vIC (mg/ml) 0.55 (0.44, 1.00) 0.97 (0.50, 1.46) < 0.0001
aNIC 0.10 (0.06, 0.13) 0.18 (0.11, 0.25) < 0.0001
vNIC 0.23 (0.13, 0.32) 0.54 (0.43, 0.65) < 0.0001

Pathological results of the 285 solitary pulmonary nodules (SPNs) included in this study

SPNs Pathology Datum (%)
Benign SPNs (n = 118)
Tuberculosis 46 (29.0%)
Acute and chronic inflammation 32 (27.1%)
Inflammatory pseudotumor 14 (11.9%)
Hamartoma 9 (7.6%)
Pulmonary sclerosing hemangioma 6 (5.1%)
Sequestration 4 (3.4%)
Bronchogenic cyst 3 (2.5%)
Rheumatoid arthritis 2 (1.7%)
Granulomatosis with polyangiitis 2 (1.7%)
Malignant SPNs (n = 167)
Primary pulmonary carcinoma 116 (69.5%)
Solitary metastasis 23 (13.8%)
Primary lung neuroendocrine tumor 21 (12.6%)
Primary pulmonary lymphoma 7 (4.2%)

Solitary pulmonary nodules evaluated with multimodality CT imaging

Methods* Sensitivity (%) Specificity (%) Accuracy (%) PPV (%) NPV (%)
Method A 83.23 63.56 75.09 76.37 72.82 %
Method B 85.63 67.80 78.25 79.01 76.92 %
Method C 84.43 66.10 76.84 77.90 75.00 %
Method A+B 94.61 74.58 86.32 84.04 90.72 %
Method A+C 92.81 77.97 86.67 85.64 88.46 %
Method B+C 95.81 81.36 89.82 87.91 93.20 %
Method A+B+C 97.60 88.14 93.68 92.09 96.30 %

Pairwise comparison of AUC of dual energy CT parameters in 285 patients with solitary pulmonary nodules

Parameters* Z statistic P value
aOL vs vOL 0.0995 0.9207
aOL vs aIC 0.813 0.4162
aOL vs vIC 2.485 0.0129
aOL vs aNIC 3.171 0.0015
aOL vs vNIC 5.170 < 0.0001
vOL vs aIC 0.702 0.4829
vOL vs vIC 2.567 0.0103
vOL vs aNIC 3.280 0.0010
vOL vs vNIC 5.345 < 0.0001
aIC vs vIC 2.034 0.0420
aIC vs aNIC 2.755 0.0059
aIC vs vNIC 4.728 < 0.0001
vIC vs aNIC 1.036 0.3001
vIC vs vNIC 3.227 0.0013
aNIC vs vNIC 2.708 0.0068

Patient characteristics in 285 patients with solitary pulmonary nodules

Characteristics Pathology
 P value
Benign SPNs (n = 118) Malignant SPNs (n = 167)
Gender*
Male 56 (47.46%) 96 (57.49%)
Female 62 (52.54%) 71 (42.51%) 0.1170
Age (years)# 50.84 ± 19.60 52.93 ± 20.30 0.3952
Smoking status*
Yes 52 (44.07%) 81 (48.50%)
No 66 (55.93%) 86 (51.50%) 0.4721
Tumor history*
Yes 17 (14.41%) 28 (16.77%)
No 101 (85.59%) 139 (83.23%) 0.6245
Tumor biomarkers*
Normal 103 (87.29%) 139 (83.23%) 0.4026
Abnormal 15 (12.71%) 28 (16.77%)

Non-enhanced computed tomography (NECT) in evaluating solitary pulmonary nodules (SPNs) with various categories in 285 patients

Items Category I Category II Category III Category IV Category V
Benign SPNs (n = 118) 39 9 48 22 0
Malignant SPNs (n = 167) 0 5 54 19 89

Solitary pulmonary nodules evaluated with non-contrast enhanced CT

CT findings* Benign SPNs (n = 118) Malignant SPNs (n = 167) P Values
Smooth margin
Yes 84 (71.19%) 49 (29.34%) < 0.0001
No 34 (28.81%) 118 (70.66%)
Lobulated sign
Yes 29 (24.58%) 115 (68.86%)
No 89 (75.42%) 52 (31.14%) < 0.0001
Spiculated sign
Yes 25 (21.19%) 108 (78.81%)
No 93 (64.67%) 59 (35.33%) < 0.0001
Vacuole sign
Yes 13 (11.02%) 38 (22.75%) 0.0120
No 105 (88.98%) 129 (77.25%)
Cavity sign
Yes 9 (7.63%) 16 (9.58%)
No 109 (92.37%) 151 (90.42%) 0.6727
Air bronchogram
Yes 33 (27.97%) 56 (33.53%) 0.3643
No 85 (72.03%) 111 (66.47%)
Calcification
Yes 10 (8.47%) 6 (3.59%)
No 108 (91.53%) 161 (96.41%) 0.1149
Fat
Yes 6 (5.08%) 4 (2.40%) 0.3277
No 112 (94.92%) 163 (97.60%)
Pleural indentation
Yes 25 (21.19%) 89 (53.29%) < 0.0001
No 93 (78.81%) 78 (46.71%)
Vessel convergence
Yes 33 (27.97%) 84 (50.30%) 0.0002
No 85 (72.03%) 83 (49.70%)
Adjacent bronchial changes
Yes 26 (22.03%) 43 (25.75%) 0.4867
No 92 (77.97%) 124 (74.25%)
Location
Upper and middle lobes 53 (44.92%) 79 (47.31%) 0.7186
Inferior lobe 65 (55.08%) 88 (52.69%)
Size (mm)
15–20 29 (24.58%) 46 (27.54%) 0.5883
20–30 89 (75.42%) 121 (72.46%)
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