Invest Clin 64(2): 142 - 150, 2023 https://doi.org/10.54817/IC.v64n2a01

Corresponding author: Junmiao Li. Department of Medical Imaging,Taizhou Municipal Hospital, Municipal Hospi-

tal Affiliated to Taizhou University, Jiaojiang District, Taizhou, Zhejiang, China. Email: ljmwylxt@163.com

Analysis of the value of dynamic computed

tomography (CT) examination in the

diagnosis of early lung cancer.

Liang Sheng, Liang Wu, Xianwu Xia and Junmiao Li

Department of Medical Imaging, Taizhou Municipal Hospital, Municipal Hospital

Affiliated to Taizhou University, Taizhou, Zhejiang, China.

Keywords: CT dynamic enhancement scan; early stage; diagnostic value; blood flow.

Abstract. Early diagnosis and treatment are vital to improving lung cancer

patients’ quality of life and survival rate. This study aimed to investigate the

value of dynamic enhanced scanning examination by computed tomography

(CT) in early lung cancer diagnosis. One hundred and twenty patients with

isolated lung nodules were selected to analyze this diagnostic method, using

pathological diagnostic results of cancer as the gold standard. Of the 120 pa-

tients with isolated pulmonary nodules, the diagnosis was confirmed by patho-

logical examination in 96 patients with early lung cancer (adenocarcinoma of

the lung) and 24 patients with benign lung lesions. The sensitivity, specificity,

accuracy, positive predictive value, and negative predictive value of CT dynamic

enhancement scans for the diagnosis of early-stage lung cancer were 93.75%,

83.33%, 91.67%, 95.74%, and 76.92%, respectively. Early-stage lung cancer had

significantly less blood volume and a noticeably shorter mean time to passage

than benign lung lesions (p<0.01). Blood flow and surface permeability were

higher in early-stage lung cancer than in benign lung lesions (p<0.05). The ar-

eas under the receiver operating characteristic (ROC) curves for blood volume,

blood flow, surface permeability, and mean time to passage for the diagnosis of

early-stage lung cancer were 0.737, 0.724, 0.779, and 0.946, respectively. In

conclusion, CT dynamic enhancement scan has good application value in diag-

nosing early lung cancer and is worth promoting in clinical practice.

CT examination and diagnosis of early lung cancer 143

Vol. 64(2): 142 - 150, 2023

Análisis del valor del escaneo dinámico realzado por tomografía

computarizada (TC) en el diagnóstico de cáncer de pulmón

temprano.

Invest Clin 2023; 64 (2): 142 – 150

Palabras clave: tomografía computarizada (TC) de realce dinámico; etapa temprana;

cáncer de pulmón; valor de diagnóstico; flujo sanguíneo.

Resumen. El diagnóstico y tratamiento tempranos son vitales para mejo-

rar la calidad de vida y la tasa de supervivencia de los pacientes con cáncer de

pulmón. Este estudio tuvo como objetivo investigar el valor del examen de esca-

neo dinámico realzado por tomografía computarizada (TC) en el diagnóstico de

cáncer de pulmón temprano. Ciento veinte pacientes con nódulos pulmonares

aislados fueron seleccionados para analizar este método diagnóstico, utilizando

los resultados del diagnóstico patológico de cáncer como el estándar de oro. De

los 120 pacientes con nódulos pulmonares aislados, el diagnóstico fue confir-

mado mediante un examen patológico en 96 pacientes con cáncer de pulmón

temprano (adenocarcinoma de pulmón) y 24 pacientes con lesiones pulmona-

res benignas. La sensibilidad, la especificidad, la precisión, el valor predictivo

positivo y el valor predictivo negativo de las tomografías computarizadas de re-

alce dinámico para el diagnóstico de cáncer de pulmón en etapa inicial fueron

respectivamente del 93,75%, 83,33%, 91,67%, 95,74% y 76,92%. El cáncer de

pulmón en etapa temprana tuvo un volumen de sangre de modo significativo

menor y un tiempo medio notablemente más corto hasta el paso que las lesio-

nes pulmonares benignas (p<0,01). El flujo sanguíneo y la permeabilidad de

la superficie fueron mayores en el cáncer de pulmón en etapa temprana que

en las lesiones pulmonares benignas (p<0,05). Las áreas bajo las curvas ROC

(Característica Operativa del Receptor) para el volumen de sangre, el flujo san-

guíneo, la permeabilidad de la superficie y el tiempo medio hasta el paso para

el diagnóstico de cáncer de pulmón en etapa temprana fueron respectivamente

0,737, 0,724, 0,779 y 0,946. En conclusión, la tomografía computarizada de

realce dinámico tiene un buen valor de aplicación diagnóstico temprano del

cáncer de pulmón y vale la pena promoverla en la práctica clínica.

Received: 07-09-2022 Accepted: 23-10-2022

INTRODUCTION

Lung cancer originates from the bron-

chial mucosa epithelium, and its incidence

gradually increases. The early clinical symp-

toms of lung cancer are not obvious, and

about 2/3 of lung cancer patients are at an

advanced stage (stage III or IV) 1. Aggres-

sive radiotherapy, chemotherapy, or surgery

can cure and extend the survival time of pa-

tients with early-stage lung cancer. However,

patients with intermediate to advanced lung

cancer have poor outcomes, high mortality

rates, and a significantly lower quality of life 2.

Therefore, early detection and treat-

ment are the keys to improving lung cancer

144 Sheng et al.

Investigación Clínica 64(2): 2023

patients’ survival rate and quality of life. In

clinical practice, the diagnosis of early-stage

lung cancer depends mainly on imaging

data.

With the more frequent usage of imag-

ing techniques, more research concentrated

on detecting pulmonary nodules using com-

puted tomography (CT). CT enhancement

peaks and associated parameters are ob-

tained from CT dynamic enhancement scans

and analyzed for their diagnostic efficacy 3.

Due to the aggressive nature of malignant

tumors during the growth period, their mor-

phological features and enhancement modes

are commonly used for early diagnosis of

pulmonary nodules in the clinical practice.

Also, a series of radiomic studies based

on tissue analysis of lung nodules have been

considered for better interpretation of mor-

phological heterogeneity and irregular pro-

liferation of tumor cells than using tradi-

tional CT images 4,5. It was confirmed that

CT dynamic enhancement detection has

considerable value for identifying malignant

and benign nodules 6. Wang and Shan7 re-

ported that dynamic enhanced CT scanning

showed the ability to differentiate pulmo-

nary inflammatory pseudotumor, pulmonary

tuberculosis, and lung cancer, representing

its diagnostic value.

The blood supply in lung cancer is mark-

edly different from benign lesions due to tu-

mor angiogenesis, and the change in tissue

density after contrast injection is marked.

Some studies reported that malignant nod-

ules have higher blood flow, volume, and

mean transit time 8–10. Nevertheless, a study

showed that malignant lesions had lower

blood volume and mean transit time 11. In ad-

dition, the results of a meta-analysis showed

that blood volume is the best indicator and

marker for describing the blood supply, while

permeability surface has a high specificity in

quantifying the vascular permeability 4.

However, these studies focused on the

high stages of lung cancer. Therefore, inves-

tigation of CT parameters in early lung can-

cer patients is necessary.

In this study, the value of dynamic CT-

enhanced scanning examination in the diag-

nosis of early lung cancer was investigated.

MATERIALS AND METHODS

Subjects and study design

Patients with isolated pulmonary nod-

ules who attended our hospital from Janu-

ary 2017 to December 2020 were selected.

Inclusion criteria included that all patients

were pathologically confirmed, aged >18

years, without lymph node enlargement, and

underwent CT dynamic enhancement scans.

Exclusion criteria were that the quality of the

images was suboptimal and that the patient

had a combination of other malignancies.

According to the inclusion and exclusion

criteria, 96 patients with isolated pulmo-

nary nodules were included in this study, of

whom 68 were males and 28 were females.

Their ages ranged from 34 to 71 years, with

a mean age of (52.04 ± 5.12) years.

CT dynamic enhancement scan

All patients underwent CT dynamic en-

hancement scans and pathological examina-

tions. A SOMATOM Definition AS multi-layer

spiral CT machine from Siemens, Germany,

was employed as the CT dynamic enhance-

ment scanning equipment. A volume of 65

mL of iopamidol injected into the patient’s

elbow vein at a flow rate of 3 mL/s. Patients

were instructed to fast before the examina-

tion and adopt the correct breathing meth-

od for the iodine allergy test. The patient’s

lung lesion and a surrounding area of ap-

proximately 6 mm were scanned at 20, 80,

140, 200, and 260 s after the contrast injec-

tion, and the CT perfusion parameters were

calculated.

Observation indicators

The diagnostic value of CT dynamic en-

hancement scans for early lung cancer was

analyzed using pathological findings as the

gold standard, including sensitivity, speci-

ficity, accuracy, and positive and negative

CT examination and diagnosis of early lung cancer 145

Vol. 64(2): 142 - 150, 2023

predictive values. CT dynamic enhancement

scans were performed for patients with early

lung cancer, whose diagnosis was confirmed

by a histological study on the sample re-

moved by biopsy through bronchoscopy.

CT perfusion parameters, which includ-

ed blood flow, volume, surface permeability,

and mean time to passage, were compared

between patients with early-stage lung can-

cer and benign lung nodules. Based on the

Patlak analysis method, reflux can be calcu-

lated from the maximum slope of the tissue

concentration-time curve or its peak height

normalized to the arterial input function.

According to this theoretical model, the ex-

change between blood and tissue can be well

described by a Patlak diagram, which shows

the tissue-to-blood concentration ratio ver-

sus the AUC (area under the curve) ratio of

the blood-to-blood concentration curve. For

different time values, if the data fits this the-

oretical model, the graph will be a line with

a slope equal to the blood vacuum per unit

volume (permeability) and an interval equal

to the relative blood volume of the tissue.

Statistical analysis

The SPSS 22.0 was used for the statisti-

cal analysis of the data. The measurement

data were expressed as mean ± standard

deviation (x ± SD), and the t-test was used

for comparison between groups. The statis-

tical data were expressed as the number of

cases and the rate (%), and the χ2 test was

used for comparison between groups. The di-

agnostic value of the perfusion parameters

was assessed using the receiver operating

characteristic (ROC) curve. The difference

was considered statistically significant at

p<0.05.

RESULTS

Pathological findings

Among 120 patients with isolated lung

nodules, 96 patients were diagnosed with

early-stage lung cancer (adenocarcinoma

of the lung) by pathological examination-

Twenty-five patients of those were classified

as stage 0 of TNM (Tumor-Node-Metastasis)

staging system, 44 patients were classified

as stage I A, and 27 patients were classified

as stage I B. There were 24 patients with be-

nign lung lesions, including 11 with pneu-

monia and 13 with tuberculosis (Table 1).

Demographic of patients

Out of 21 patients in TNM stage 0M, 17

patients were men, and eight were women.

Also, out of 44 patients in TNM stage I A,

30 were men, and 14 were women; out of 27

patients in TNM stage I B, 21 were men, and

six were women. There were no significant

differences in terms of gender in the three

stages of the disease.

The average age of patients in TNM stage

0M was 54.05 ± 6.4 years. Moreover, the aver-

age age of patients in TNM stage I A and TNM

stage I B stages were 52.03 ± 3.1 and 55 ±

4.2, respectively, and the patients of the three

stages were significantly different in terms of

average age (p ≤ 0.03) (Table 2).

Diagnostic value of CT dynamic

enhancement scans for early-stage

lung cancer

The sensitivity, specificity, accuracy,

positive predictive value, and negative predic-

tive value of CT dynamic enhancement scans

for the diagnosis of early-stage lung can-

cer were 93.75% (90/96), 83.33% (20/24),

Table 1

Pathological findings

Early-stage lung cancer Benign lung lesions

TNM stage 0 TNM stage I A TNM stage I B pneumonia tuberculosis

Cases 25 44 27 11 13

146 Sheng et al.

Investigación Clínica 64(2): 2023

91.67% (110/120), 95.74% (90/94) and

76.92% (20/26), respectively.

Comparison of parameters of early-stage

lung cancer and benign lung lesions

The blood volume of early-stage lung

cancer was significantly lower than that of

benign lung lesions, and the mean time to

passage was significantly shorter than that

of benign lung lesions, and all differences

were statistically significant (p<0.01). Both

blood flow and surface permeability were

higher in early-stage lung cancer than in be-

nign lung lesions, and the differences were

statistically significant (p<0.05). There

were no statistically significant differences

in lesion size and proportion of solid nodules

when comparing early-stage lung cancer and

benign lung lesions (p>0.05) (Fig. 1).

Comparison of CT perfusion parameters

for early-stage lung cancer at different

TNM stages

The differences in blood flow, surface

permeability, and mean time to passage were

not statistically significant when comparing

patients with TNM stage 0, stage IA and stage

IB early-stage lung cancer (p>0.05) (Fig. 2).

Diagnostic efficacy of CT perfusion

parameters for early-stage lung cancer

The areas under the ROC curves of

blood volume, blood flow, surface permeabil-

ity, and mean time to passage for the diag-

nosis of early-stage lung cancer were 0.737,

0.724, 0.779, and 0.946, respectively. Sur-

face permeability had the highest sensitivity

of 92.5% for diagnosing early-stage lung can-

cer and the highest specificity of 99.5% for

diagnosing early-stage lung cancer by mean

time to passage (Table 3).

DISCUSSION

Diagnostic imaging is critical for the de-

tection and staging of lung cancer. Standard

clinical imaging examinations are conven-

tional chest scans and dynamic enhancement

CT 12. Performing a plain chest examination

on a patient usually requires a continuous

change of position to ensure that the exami-

nation is completed. However, it can worsen

the patient’s lung pain, leading to poor com-

pliance. Therefore, in practice, this option is

not chosen for most patients 13 The CT dy-

namic enhancement scanning technique with

non-overlapping images allows for precise

detection of small early lesions, timely detec-

tion of enlarged mediastinal lymph nodes,

and determination of the extent of tumor in-

vasion of the pleura and surrounding blood

vessels, leading to the correct staging of lung

cancer 14. In addition, relevant studies have

shown that dynamic CT-enhanced scanning

techniques can be used as an effective adjunc-

tive diagnostic tool for early lung cancer in

clinical practice 15.

The results of this study showed that the

sensitivity, specificity, accuracy, and positive

and negative predictive values of CT dynamic

enhancement scans for the diagnosis of ma-

lignant lesions were all at a high level. This

Table 2

Characteristics of the three groups with different pathological findings.

Characteristics TNM stage 0M TNM stage I A TNM stage I B p-value

Gender

Male 17 30 21 0.07*

Female 8 14 6

Age (y) 54.05 ± 6.4 52.03 ± 3.1 55 ± 4.2 0.03**

*p-value calculated based on chi-square, ** p-value calculated based on One-way ANOVA.

CT examination and diagnosis of early lung cancer 147

Vol. 64(2): 142 - 150, 2023

is because the imaging features in the early

diagnosis of lung cancer are manifested by

lobar signs, burr signs, vascular collection

signs, and bronchial inflation signs, which

are absent in patients with benign nodules.

These phenomena allow the identification

of benign and malignant nodules and can

improve the accuracy of diagnosis of early-

stage lung cancer. The lobar sign is caused

by the lack of clear cut and heterogeneity

of the tumor margins, which is caused by re-

stricted growth 16.

56.25%

54.17%

Blood volume

(ml/100 g)

Blood Flow

[ml/(100· min)]

Surface permeability

[ml/(100· min)]

Average pass

time(s)

Lesion diameter

(cm)

Solid nodules

[n(%)]

120

Parameters between early stage lung cancer

and benign lung lesions

early stage lung cance

benign lung lesions

Fig. 1. Comparison of parameters between early-stage lung cancer and benign lung lesions *p<0.05.

Blood Flow

[ml/(100· min)]

Surface permeability

[ml/(100· min)]

Average pass

time(s)

100

120

CT perfusion parameters for early stage lung cancer

at different TNM stages

0 stage

ⅠA stag e

ⅡB stag e

Fig. 2. Comparison of CT perfusion parameters for early-stage lung cancer at different TNM stages.

56.25%

54.17%

Blood volume

(ml/100 g)

Blood Flow

[ml/(100· min)]

Surface permeability

[ml/(100· min)]

Average pass

time(s)

Lesion diameter

(cm)

Solid nodules

[n(%)]

120

Parameters between early stage lung cancer

and benign lung lesions

early stage lung cance

benign lung lesions

148 Sheng et al.

Investigación Clínica 64(2): 2023

Most tumor cells grow invasively along

the alveolar wall and lymphatic vessels, re-

sulting in localized venous stasis and burr.

However, signs of pneumonia may also be

present in pneumonic nodules, which can

lead to misdiagnosis. The CT dynamic en-

hancement scan examination method is

simple, quick, and has non-invasive charac-

teristics, which can detect the whole range

and location of lung lesions with clear im-

ages and high diagnostic accuracy, indicat-

ing that CT dynamic enhancement scan can

be used for the diagnosis of lung cancer to

effectively reduce the misdiagnosis rate and

improve the diagnostic efficiency.

If the differential diagnosis cannot be

made based on the imaging features of early

lung cancer, the diagnosis can be accom-

plished by blood flow parameters. The results

of this study showed that early-stage lung

cancer had significantly less blood volume,

significantly shorter mean time to passage,

and higher blood flow and surface perme-

ability than benign lung lesions. In contrast,

the differences in blood volume, blood flow,

surface permeability, and mean time to pas-

sage were not statistically significant when

comparing patients with early-stage lung

cancer at different TNM stages. These re-

sults suggest that CT flow parameters can

be used clinically to differentiate between

benign and malignant lung lesions but are of

less diagnostic value for clinical TNM stag-

ing, which is caused by the lymphatic return

and lymphatic volume of malignant lesions.

During a CT dynamic enhancement scan,

the patient’s lymphatic reflux slows, and the

lymphatic volume decreases, affecting con-

trast flow due to lymphatic lesions in clinical

malignancies. In contrast, the endothelial

space of the capillaries widens, and there are

various inter endothelial channels, which

leads to a loss of basement membrane and,

therefore, a high blood flow in the vessels.

Some studies have found that CT perfu-

sion parameters such as blood volume, blood

flow, surface permeability, and passage time

during CT dynamic enhancement scans are

of high diagnostic value for early lung cancer

17,18. However, fewer studies have separately

accounted for their sensitivity and specific-

ity. In this study, we found that the mean

time to passage was of high diagnostic value

for early-stage lung cancer by plotting ROC

curves.

In conclusion, CT dynamic enhance-

ment scan has high application value in di-

agnosing early lung cancer and is worthy of

clinical promotion. However, the number of

cases included in this study was small, and

there is a need to expand the sample size in

future studies to eliminate statistical errors.

In addition, it is necessary to further ana-

lyze the intrinsic association between peak

CT enhancement and lung cancer pathogen-

esis in conjunction with some immunohis-

tochemical indicators to elucidate the ad-

junctive clinical significance of CT dynamic

enhancement scanning technology.

Limitation

One of the limitations of the study is

that it was conducted in a single hospital.

Therefore, it is recommended to carry out

Table 3

Diagnostic efficacy of CT perfusion parameters for early-stage lung cancer.

Parameters Area under

the curve

95%CI Optimal cut-off

value

Sensitivity

(%)

Specificity

(%)

Blood volume 0.74 0.60~0.88 13.15 85.0 65.0

Blood Flow 0.72 0.60~0.85 72.11 81.3 60.0

Surface permeability 0.78 0.66~0.89 27.27 92.5 50.0

Average pass time 0.95 0.89~0.99 10.64 85.0 99.5

CT examination and diagnosis of early lung cancer 149

Vol. 64(2): 142 - 150, 2023

similar studies in several hospitals or medi-

cal centers in the future.

Funding

Exploration of personalized screening

and graded diagnosis and treatment plans

for early lung cancer in Zhejiang Province

based on big data and artificial intelligence

(Project No: 2022C35008).

Competing Interests

The authors declared that they have no

competing interests.

Authors’ Contribution

LS, LW and JL contributed to the con-

ception of the study; LS, XX and JL per-

formed the experiment; LW contributed

significantly to the analysis and manuscript

preparation; LS and JL performed the data

analyses and wrote the manuscript; XX

helped perform the analysis with construc-

tive discussions.

Authors’ ORCID Number

• Liang Sheng: 0000-0003-0620-4779

• Liang Wu: 0000-0002-1247-4583

• Xianwu Xia: 0000-0003-3508-0816

• Junmiao Li: 0000-0001-8890-6242

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