Extracellular volume fraction based on dual-layer spectral computed tomography in assessment of gastric cancer: feasibility analysis of low-dose equilibrium phase scanning

Abstract

Background

The extracellular volume fraction (fECV) based on equilibrium phase iodine density images (IDIs) of dual-layer spectral detector computed tomography (DLCT) can be used in the assessment of gastric cancer (GC). However, obtaining the equilibrium phase images requires a higher radiation dose. The purpose of our study was to evaluate the feasibility of low-dose equilibrium phase scans on DLCT for fECV acquisition in histological grading assessment of GC.

Methods

A total of 86 gastric adenocarcinoma patients confirmed by surgical pathology were divided into two groups that underwent contrast-enhanced DLCT with routine-dose (120 kV/129 refmAs) and low-dose (120 kV/90 refmAs) equilibrium phases, respectively. The fECV values of GC lesions were measured from IDIs in the equilibrium phase. The radiation dose, image quality of the equilibrium phase images, and fECV values were compared between the low- and routine-dose groups. Then, the performance of the fECV in the two groups to distinguish histological grades of GC lesions was evaluated using a receiver operating characteristic (ROC) curve and the DeLong test. The fECV maps were reconstructed from the IDIs of the equilibrium phase.

Results

The radiation dose of the equilibrium phase and the accumulated dose in the low-dose group decreased by 54% and 34%, respectively, compared to the routine-dose group (both P<0.001). The image noise of equilibrium phase images was higher in the low-dose group than that in the routine-dose group (P<0.001) and the noise scores of the low-dose group were lower than those of the routine-dose group (P=0.003), whereas no significant differences were detected in the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), detail score, and fECV values between the two groups (P=0.243, 0.607, 0.861, and 0.301, respectively). The fECV values of high-grade GC lesions were higher than those of the low-grade lesions in the two groups (52.98%±8.06% vs. 38.31%±5.24%, P<0.001, and 51.94%±9.11% vs. 36.91%±5.26%, P=0.002). The fECV obtained in the low-dose group had a similar performance compared to the routine-dose group in histological grading assessment of GC [area under the curve (AUC): 0.871 vs. 0.879, Z=−0.148, P=0.882].

Conclusions

Contrast-enhanced DLCT with low-dose equilibrium phase scans in GC reduced the radiation dose while providing comparable image quality and performance of fECV in histological grading assessment to those of routine-dose scans.

Introduction

Gastric adenocarcinoma is a common malignant tumor that originates from the epithelial cells of the gastric mucosa (1). Currently, the incidence of gastric cancer (GC) ranks first among malignant gastrointestinal tumors in China (2). This cancer is usually diagnosed histologically after endoscopic biopsy and staged using contrast-enhanced computed tomography (CECT). However, considering the high molecular and phenotypical heterogeneity of GC, an endoscopic biopsy cannot evaluate tumors accurately and comprehensively due to the limitation of the sample size available for endoscopy (3,4). CECT can provide a detailed view of the entire anatomy and the tumor’s extent, but conventional CECT can only assess tumors from morphological features and does not completely reflect the pathological characteristics of GC (5). Therefore, some quantitative parameters based on computed tomography (CT) images are needed to compensate for the shortcomings of subjective visualization images and evaluate the tumor heterogeneity more deeply.

Extracellular volume fraction (fECV) can be used to quantitatively reflect the extracellular stroma of lesions, which plays a critical role in tumor formation, progression, invasion, and metastasis (6,7). Relevant studies have shown that the fECV values obtained based on imaging methods are consistent with the extracellular intercellular quality detected by tissue biopsy (8,9). Previous studies have confirmed the predictive value of fECV based on equilibrium-enhanced CT for pathological features and therapeutic response of GC (10,11). The fECV based on conventional CECT usually requires pre- and post-contrast images to calculate the spread of iodine contrast agent, sometimes leading to image misregistration (11). Dual-layer spectral detector CT (DLCT) is a promising imaging tool that allows noninvasive quantification of the fECV directly from the iodine density images (IDIs) of the equilibrium phase without requiring unenhanced images, which improves the accuracy and convenience of the measurement (12,13). However, obtaining the equilibrium phase images increases the radiation dose, which is hazardous to patients. In 1990, Naidich et al. (14) proposed the concept of low-dose CT, outlining that with the decrease in tube current, the radiation dose can be reduced to meet the diagnostic needs of radiologists while maintaining good image quality.

Therefore, the present study aimed to evaluate the feasibility of low-dose scanning in the equilibrium phase of DLCT for obtaining the fECV in GC by comparing the image quality of equilibrium phase images and the diagnostic performance of fECV values in histological grade assessment between the low- and routine-dose groups. We present this article in accordance with the STARD reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-24-2013/rc).

Methods

Patient population

This study was approved by the independent Ethics Committee of the Affiliated Kunshan Hospital of Jiangsu University (No. 2022-03-037-K01). Each participant provided “Informed consent about contrast-enhanced CT”. The study was conducted according to the Declaration of Helsinki and its subsequent amendments. A total of 115 patients with newly diagnosed GC who underwent endoscopic biopsy in our hospital between March 2022 and June 2024 were prospectively enrolled. Among them, 107 patients with no contraindications (history of iodine allergy, pregnancy, and kidney dysfunction) to CECT were enrolled and randomly divided into two groups according to the number registered before the CT examination. The two groups comprised those who underwent contrast-enhanced DLCT scan with routine-dose (120 kV/129 refmAs) and low-dose (120 kV/90 refmAs) equilibrium phases, respectively. The inclusion criteria were as follows: (I) postoperative histological confirmation of gastric adenocarcinoma; (II) no prior antitumor therapy, including radiotherapy, chemotherapy, or targeted therapy; (III) abdominal DLCT performed within one month before surgery with complete imaging data available; (IV) comprehensive clinical data obtained, including hospital records, laboratory tests, surgical records, and pathological reports. The exclusion criteria were as follows: (I) patients with an unsuitable body mass index (BMI) of >25 kg/m²; (II) patients with other concurrent malignancies; (III) patients with inadequate stomach filling, poor image quality, or lesions too small to be clearly visualized on CT images; (IV) patients with incomplete DLCT image data. Finally, 86 gastric adenocarcinoma patients meeting the inclusion and exclusion criteria were enrolled, including two groups (44 and 42 cases) with routine-dose and low-dose equilibrium phases, respectively. Figure 1 illustrates the patient selection and grouping process for this study.

Figure 1.

Patient selection and grouping process. DLCT, dual-layer spectral detector computed tomography; BMI, body mass index.

The demographics and pathological data of the patients were obtained at the time of admission. The following data were recorded: age, gender, BMI, site of the tumor, histological grade, histological type, and pathological tumor-node (pTN) stage.

CT scanning technique and post-processing of images

The study was performed on SDCT scanners (IQon Spectral CT, Philips Health Systems, Amsterdam, Netherlands). The tube voltage/tube current was 120 kV/auto tube current (129 refmAs) in the unenhanced, arterial, and venous phases of all groups and in the equilibrium phase of the routine-dose group; it was a 120 kV/auto tube current (90 refmAs) in the equilibrium phase of the low-dose group. The other scanning parameters in all groups were as follows: 5 mm slice thickness, 0.5 seconds rotation time, and 512×512 matrix.

The patients were administered 0.75–1.0 L of water orally (within 10 min before starting the scanning) and another 0.25 L (immediately before scanning) to inflate the stomach wall. To reduce gastrointestinal motility, participants were intravenously administered 20 mg anisodamine (10 min before scanning). The ionic contrast medium (iohexol, Omnipaque 350, GE Healthcare, Chicago, IL, USA) was administered intravenously at a dose of 1.5 mL/kg body weight at a rate of 3.0–3.5 mL/s, followed by 10 mL of saline at the same rate. The arterial, venous, and equilibrium phase images were obtained at 33-, 70-, and 180-seconds after contrast injection, respectively.

Conventional dose mixed-energy images and spectral-based images (SBIs) were constructed using the raw data with a 1 mm slice thickness. Then, IDIs and the fECV maps were generated from the SBI data of the equilibrium phase using commercial software (IntelliSpace Portal version 9 and Clinical Science, Philips Healthcare).

Measurement of fECV

The fECV values were measured in the IDIs of the equilibrium phase by two senior radiologists experienced in abdominal radiology independently, with reference to the endoscopic results. The plane of maximal GC lesion was selected, and a region of interest (ROI) was drawn to encompass the whole lesion, avoiding the regions of necrosis, cystic degeneration, and hemorrhage. A circular ROI (range 50–100 mm²) was drawn within the aorta in the same plane as the GC lesion. The average iodine density (ID) values of each ROI were recorded, and the values measured by the two observers were averaged to represent each ROI. The fECV values were calculated as follows (10):

$$\text{fECV=}\left(1-\text{Hct}\right)\times \frac{{\text{ID}}_{\text{cancer}}}{{\text{ID}}_{\text{aorta}}}\times \text{100\%}$$ [1]

ID_cancer: the ID value of GC lesions; ID_aorta: the ID value of the aorta; Hct: hematocrit value within 2 days before or after DLCT examination.

Radiation dose

CT dose index (CTDI), CT dose-length product (DLP), and effective dose (ED) were used to evaluate the radiation dose of patients. The CTDI and DLP of each patient were recorded during the scans, and the ED value was calculated by multiplying the DLP by a conversion factor specific to abdominal imaging. The conversion factor for abdominal CT used in this study was 0.015 mSv/mGycm (15).

Image quality evaluation

The quantitative evaluation was performed by a radiologist with 10 years of experience in abdominal CT, who was blinded to the scanning parameters of the equilibrium phase. The measurements were performed on conventional iDose mixed-energy images of the equilibrium phase in routine-dose and low-dose groups. The plane of maximal GC lesion was selected, and the ROI was drawn, encompassing the whole lesion and avoiding the regions of necrosis, cystic degeneration, and hemorrhage. Three circular ROIs (range 20–50 mm²) were selected from the erector spinae and subcutaneous fat of the anterior abdominal wall at the same plane as the GC lesions. The CT attenuation value and standard deviation (SD) of the ROIs were recorded, and the average value of the three ROIs was calculated. Then, these values were used to calculate the noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) of the images using the following formula:

$$\text{Image\hspace{0.17em}noise}={\text{SD}}_{\text{cancer}}$$ [2]

SD_cancer: SD of GC lesions.

$$\text{SNR=}\frac{\text{CTcancer}}{\text{SDfat}}$$ [3]

CT_cancer: average CT attenuation value of GC lesions; SD_fat: SD of subcutaneous fat.

$$\text{CNR=}\frac{\text{CTcancer}-\text{CTmuscle}}{\text{SDfat}}$$ [4]

CT_cancer: average CT attenuation value of GC lesions; CT_muscle: average CT attenuation value of the erector spinae; SD_fat: SD of subcutaneous fat.

The qualitative evaluation was performed by two radiologists with >10 years of experience in abdominal CT in a double-blinded manner. When the score results of two radiologists were inconsistent, a third radiologist scored again, and the majority score was used. The qualitative image assessment was conducted in two steps: (I) a training session and (II) an assessment session. In the training session, the readers reviewed the averaged image quality of mixed-energy images in the routine-dose equilibrium phase in 20 patients (13 men; median age, 73 years; median BMI, 22.60 kg/m²) not included in these participants. The averaged image noise and the image details identified during the training session served as the reference for subsequent visual analyses. In the assessment session, the two independent observers qualitatively assessed the image noise and image detail of the equilibrium phase mixed-energy images in the routine-dose and low-dose groups. The equilibrium phase images were presented in a randomized order within a predefined soft tissue window [window width: 240 Hounsfield units (HU); window level: 40 HU]. Observers were permitted to adjust the window level and width freely during their evaluation. The specific scoring method is as follows (15):

1. Noise score: score 1, significant increase in image noise; score 2, mild increase in image noise; score 3, image noise comparable to CT images observed in the training session; score 4, mild decrease in image noise; and score 5, significant decrease in image noise.

2. Detail score: score 1, poor recognition for anatomical structures or lesion details; score 2, slightly decreased recognition for anatomical structures or lesion details; score 3, recognition for anatomical structures or lesion details comparable to that observed in the training session; score 4, slightly better recognition for anatomical structures or lesion details; and score 5, substantially better recognition for anatomical structures or lesion details.

Histological grade assessment

The GC lesions were classified according to histological grade as grade 1 (well-differentiated, glandular formation >95%), grade 2 (moderately differentiated, glandular formation between 50% and 95%), and grade 3 (poorly differentiated, glandular formation <50%). Following the two-level classification system for digestive system tumors proposed by the World Health Organization in 2019 (16), patients were further divided into a low-grade group (G1 and G2) and a high-grade group (G3).

Statistical analysis

The continuous variables were expressed as mean ± SD or median [interquartile range (IQR)]. The categorical variables were summarized using counts (percentages). The comparisons between the two groups were analyzed using an independent-samples t-test or Mann-Whitney U test for continuous variables. The chi-square test was used for comparisons between groups for categorical variables. Receiver operating characteristic (ROC) curve analysis and DeLong test were conducted to assess the diagnostic performance of fECV values determined from the routine- and low-dose groups to distinguish high-grade GC lesions from low-grade lesions. A P<0.05 indicated a statistically significant difference. The inter-rater agreement between two radiologists was assessed using an intraclass correlation coefficient (ICC) analysis. The ICC value was interpreted as follows: 0–0.5 slight, 0.5–0.75 moderate, 0.75–0.9 good, and >0.9 almost perfect agreement. All statistical analyses were performed using the software SPSS 19.0 (IBM Corp., Armonk, NY, USA) and MedCalc version 15.0 (MedCalc Software, Ostend, Belgium).

Results

Clinicopathological data of patients in low- and routine-dose groups

A total of 86 patients were enrolled in the low- and routine-dose groups (age range, 39–88 years; median age, 72.5 years; female/male, 26/60; BMI, 19.24–24.85 kg/m²; median BMI, 22.86 kg/m²), including 42 tubular adenocarcinomas, 25 signet-ring cell carcinomas, and 19 mucinous adenocarcinomas.

No significant differences were observed in age, gender, BMI, site of the tumor, histological grade, histological type, and pTN stage between the low- and routine-dose groups (Table 1, all P>0.05).

Table 1. Clinicopathological data of patients in low- and routine-dose groups.

Parameter	Low-dose group (n=42)	Routine-dose group (n=44)	t/χ2	P
Age (years)	69.59±11.12	69.45±11.65	0.014	0.989
Gender (male)	28/42	32/44	1.251	0.263
BMI (kg/m2)	22.87±1.58	22.01±1.48	1.764	0.086
Site of tumor			4.300	0.116
Cardia or fundus	14 (33.33)	16 (36.36)
Body of stomach	10 (23.81)	9 (20.45)
Antrum or pylorus	12 (28.57)	12 (27.27)
Overlapping sites	6 (14.29)	7 (15.91)
Histological grade			0.404	0.525
Low-grade	26 (61.90)	30 (68.18)
High-grade	16 (38.10)	14 (31.82)
Histological type			0.291	0.865
Tubular adenocarcinoma	20 (47.62)	22 (50.00)
Signet-ring cell carcinoma	13 (30.95)	12 (27.27)
Mucous adenocarcinoma	9 (21.43)	10 (22.73)
pTN stage			0.904	0.825
I	7 (16.67)	9 (20.45)
II	14 (33.33)	15 (34.10)
III	16 (38.10)	17 (38.64)
IV	5 (11.90)	3 (6.82)

t/χ² values corresponding to mean ± standard deviation and n (%) were obtained by independent-samples t-test and chi-square test, respectively, and the corresponding P values were derived. P<0.05 indicates a significant difference. BMI, body mass index; pTN, pathological tumor-node.

Comparison of radiation dose, image quality, and fECV values between low- and routine-dose groups

The tube current range and CTDI of equilibrium phases were 68–101 mAs and 8.0±1.33 mGy in the low-dose group, 119–203 mAs and 13.97±3.33 mGy in the routine-dose group. The accumulated DLP and ED and the DLP and ED of the equilibrium phase in the routine-dose group were higher than those in the low-dose group (Table 2 part 1, all P<0.001), decreased by 34% and 54% compared to the routine-dose group, respectively.

Table 2. Radiation dose, image quality, and fECV values in low- and routine-dose groups.

Parameter	Low-dose group (n=42)	Routine-dose group (n=44)	t/Z	P
Radiation dose
DLPaccumulated (mGycm)	2,705.39±406.95	4,088.36±544.22	−9.101	<0.001*
EDaccumulated (mSv)	40.58±6.10	61.33±8.16	−9.101	<0.001*
DLPequilibrium (mGycm) equilibrium	408.30 (393.13, 424.50)	883.75 (847.68, 940.18)	−7.700	<0.001*
EDequilibrium (mSv)	6.12 (5.90, 6.37)	13.26 (12.72, 41.10)	−7.700	<0.001*
Image quality
Image noise (HU)	11.52±2.27	8.24±1.90	4.940	<0.001*
SNR	11.18±4.31	12.80±4.31	−1.187	0.243
CNR	4.23±2.37	3.88±1.86	0.519	0.607
Noise score	2.75±1.15	3.55±1.15	−3.107	0.003*
Details score	3.35±1.25	3.40±1.30	−0.175	0.861
fECV (%)	40.80±10.74	43.09±9.31	−1.041	0.301

t/Z values were corresponding to mean ± standard deviation and median (interquartile range) were obtained by independent-samples t-test and Mann-Whitney U test, respectively, and the corresponding P values were derived. *P<0.05 indicates a significant difference. CNR, contrast-to-noise ratio; DLP_accumulated, accumulated dose-length product of all phases; DLP_equilibrium, dose-length product of equilibrium phase; ED_accumulated, accumulated effective dose of all phases; ED_equilibrium, effective dose of equilibrium phase; fECV, extracellular volume fraction; SNR, signal-to-noise ratio.

No significant difference was detected in SNR, CNR, and detail scores between low- and routine-dose groups (all P>0.05), whereas the image noise scores of the low-dose group were higher than those of the routine-dose group, and the noise scores of the low-dose group were lower than those of the routine-dose group (Table 2 part 2, both P<0.05). The agreement on the noise score and detail score between the two radiologists was good (ICC =0.837 and 0.876, respectively, both P<0.001).

There was no statistically significant difference in the fECV values of GC lesions between the low- and routine-dose groups (Table 2 part 3, P>0.05). The fECV values measured by the two radiologists were in good agreement (ICC =0.828, P<0.001). The fECV values of high-grade GC lesions were higher than those of low-grade lesions in the two groups (Table 3, both P<0.05) (Figures 2,3). The ROC curve analysis showed that the area under the curve (AUC) of fECV to differentiate the high-grade GC lesions from low-grade ones between the low- and routine-dose groups were similar (Z=−0.148, P=0.882), as well as the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy (Table 4, Figure 2).

Table 3. Comparison of fECV determined from low- and routine-dose groups between high- and low-grade GC lesions.

Group	High-grade	Low-grade	t	P
fECVroutine-dose (%)	52.98±8.06	38.31±5.24	3.993	<0.001
fECVlow-dose (%)	51.94±9.11	36.91±5.26	3.386	0.002

t values corresponding to mean ± standard deviation were obtained using independent samples t-test, and the corresponding P values were derived. P<0.05 indicated a significant difference. fECV_routine-dose, fECV_low-dose, extracellular volume fraction determined from the low- and routine-dose groups; fECV, extracellular volume fraction; GC, gastric cancer.

Figure 2.

The ROC curves and box plots of fECV values determined from low- and routine-dose groups. (A,C) The ROC curves display the diagnostic performance of fECV in low- and routine-dose groups to distinguish high- from low-grade GC lesions. (B,D) The box plots showed the differences in fECV values between high- and low-grade GC lesions in low- and routine-dose groups. fECV_routine-dose, fECV_low-dose, extracellular volume fraction determined from the low- and routine-dose groups. AUC, area under the curve; fECV, extracellular volume fraction; GC, gastric cancer; HG, high-grade; LG, low-grade; ROC, receiver operating characteristic.

Figure 3.

The scatter plot of fECV values in different histological grades. (A) The distribution of fECV values determined from routine-dose groups in different histological grades. (B) The distribution of fECV values determined from low-dose groups in different histological grades. fECV_routine, fECV_low, extracellular volume fraction determined from the low- and routine-dose groups. fECV, extracellular volume fraction; HG, high-grade; LG, low-grade.

Table 4. The diagnostic performance of fECV determined from low- and routine-dose groups for histological grade assessment of GC.

Group	AUC (95% CI)	SEN	SPE	PPV	NPV	ACC	Cut-off
fECVroutine-dose	0.879 (0.778–0.980)	0.807	0.917	0.961	0.642	0.818	>38.77
fECVlow-dose	0.871 (0.753–0.989)	0.774	0.889	0.960	0.533	0.800	>35.85

fECV_routine-dose, fECV_low-dose, extracellular volume fraction determined from the low- and routine-dose groups. 95% CI, 95% confidence interval; ACC, accuracy; AUC, area under the curve; fECV, extracellular volume fraction; GC, gastric cancer; NPV, negative predictive value; PPV, positive predictive value; SEN, sensitivity; SPE, specificity.

In the fECV maps, high-grade GC lesions were shown in orange or red, and the low-grade lesions were shown in green or yellow. An fECV map can visually reflect the histological grade of GC. The visual contrast between GC lesions with different histological grades in fECV maps for the low- and routine-dose groups was comparable (Figures 4,5).

Figure 4.

iDose mixed energy images, IDIs of equilibrium phase, and fECV maps with routine-dose scans, and corresponding pathological images. (A-D) Female, 65 years old. iDose mixed energy images of equilibrium phase: the tumor located in the gastric cardia and fundus showed a localized mass with mild enhancement (long arrow) (A). IDIs of equilibrium phase: the ID_cancer (green ROI) and ID_aorta (white ROI) were 1.62 and 2.39 mg/mL, respectively. The Hct was 19.1% and the fECV value was calculated as 54.85% (B). fECV map: the tumor in the gastric cardia and fundus was shown in orange and red (long arrow) (C). Pathological images (HE staining ×100): high-grade gastric adenocarcinoma (D). (E-H) Male, 59 years old. iDose mixed energy images of equilibrium phase: the tumor located in the gastric body showed irregular gastric wall thickening with moderate enhancement (thick arrow) (E). IDIs of equilibrium phase: the ID_cancer (green ROI) and ID_aorta (white ROI) were 2.22 and 3.02 mg/mL, respectively. The Hct was 48.2% and the fECV value was calculated as 38.07% (F). fECV map: the tumor in the gastric body was shown in yellow and green (thick arrow) (G). Pathological images (HE staining ×100): low-grade gastric adenocarcinoma (H). fECV, extracellular volume fraction; Hct, hematocrit; HE, hematoxylin and eosin; ID, iodine density; IDIs, iodine density images; ROI, region of interest.

Figure 5.

iDose mixed energy images, IDIs of equilibrium phase, and fECV maps with low-dose scans, and corresponding pathological images. (A-D) Male, 82 years old. iDose mixed energy images of equilibrium phase: the tumor located in the gastric cardia and fundus showed a localized mass with moderate enhancement (long arrow) (A). IDIs of equilibrium phase: the ID_cancer (green ROI) and ID_aorta (white ROI) were 1.84 and 2.29 mg/mL, respectively. The Hct was 34.9% and the fECV value was calculated as 52.31% (B). fECV map: the tumor in the gastric cardia and fundus was shown in red (long arrow) (C). Pathological images (HE staining ×100): high-grade gastric adenocarcinoma (D). (E-H) Male, 68 years old. iDose mixed energy images of equilibrium phase: the tumor located in the gastric cardia and fundus showed a localized mass with mild enhancement (thick arrow) (E). IDIs of equilibrium phase: The ID_cancer (green ROI) and ID_aorta (white ROI) were 1.07 and 2.69 mg/mL, respectively. The Hct was 40.9% and the fECV value was calculated as 23.51% (F). fECV map: the tumor in the gastric cardia and fundus was shown in yellow and green (thick arrow) (G). Pathological images (HE staining ×100): low-grade gastric adenocarcinoma (H). fECV, extracellular volume fraction; Hct, hematocrit; HE, hematoxylin and eosin; ID, iodine density; IDIs, iodine density images; ROI, region of interest.

Discussion

This study first adopted the low-dose scanning in the equilibrium phase of DLCT to obtain fECV values in GC patients by decreasing the reference tube current (refmAs) of automatic tube current modulation (ATCM). The results showed that low-dose scanning in the equilibrium phase substantially reduced the radiation dose while providing similar fECV values and comparable performance of fECV in histological grading assessment of GC to routine-dose scanning without significantly affecting the image quality.

The value of fECV in assessing histological grade has been substantiated by studies conducted on colorectal cancer (17). The current study reached a similar conclusion in gastric adenocarcinoma: an increased fECV suggested a higher histological grade, which correlates with greater aggressiveness and poorer prognosis. Several prior studies have corroborated this observation. Nishimuta et al. (11) showed that GC with higher fECV values was more prone to vascular invasion and infiltration growth patterns. The study by Chen et al. (10) indicated that the higher the fECV value of GC, the worse its response to immunotherapy. The fECV is the sum of the intravascular space and the extracellular matrix outside the vessel, which can reflect both the growth of tumor blood vessels and the degree of fibrosis in the extracellular matrix, thereby providing a more comprehensive reflection of the tumor microenvironment (18). Therefore, the higher the malignancy of gastric adenocarcinoma, the more immature the vascular network within the tumor with thin-walled vessels and richer new blood vessels, which leads to increased blood flow and vascular permeability, resulting in more contrast agent entering the interstitial space, thereby leading to a higher fECV value (19).

According to previous studies, the refmAs of ATCM determined the scanning dose and image quality (20). Therefore, in this study, routine refmAs (129 mAs) was selected in the routine sequences (unenhanced, arterial, and venous phases) for GC evaluation to ensure excellent image quality and diagnostic requirements, but low-dose scanning (refmAs: 90 mAs) was adopted in the equilibrium phase, which was only used to obtain fECV values. The refmAs setting for the low-dose scanning was selected according to the previous study (21), which showed that when refmAs was reduced by 10–40%, which in turn decreased the radiation dose, maintaining the diagnostic image quality of abdominal CT. Therefore, this study chose to reduce refmAs by 30% according to the above research results, that is, from 129 mAs to 90 mAs. Although image noise in the low-dose images was increased due to low refmAs, no significant effect was detected on the image contrast and the display of GC lesions because the gastric cavity was filled with sufficient water and surrounded by the adipose tissue for tissue contrast. This phenomenon was consistent with that of the previous study (21). To date, no studies have been carried out on low-dose scanning in the measurement of fECV values. In the present study, low-dose scanning was first used in the equilibrium phase to obtain fECV, and its diagnostic performance for histological grading assessment of GC was equivalent to that achieved with routine-dose scanning. Furthermore, the clarity and contrast of low-dose fECV maps were found to be comparable to those of routine-dose fECV maps, effectively identifying the histological grades of GC lesions. Moreover, the fECV values measured by the two radiologists had good consistency, indicating a high reproducibility of the method. Therefore, the fECV based on low-dose IDIs in the equilibrium phase of DLCT is expected to become a new imaging indicator in the evaluation of GC.

Nevertheless, the present study has some limitations. First, it was a single-center study with a small sample size, and the enrolled cases for different groups were not the same set to avoid repeat scanning, but randomization was adopted for uniform clinicopathological characteristics across the groups. Secondly, only one reference mAs value (90 mAs) was selected for low-dose scanning in this study. The most suitable refmAs for low-dose scanning should be verified in later studies by setting different refmAs. Finally, given that the primary objective of this study was to assess the feasibility of low-dose scanning models for fECV acquisition, individuals with a BMI greater than 25 kg/m² were excluded, as low-dose protocols are generally not recommended for this population. However, this exclusion introduced selection bias in evaluating the value of fECV; therefore, it is essential to include such individuals in future studies on fECV.

Conclusions

Low-dose equilibrium phase scanning of DLCT can reduce the radiation dose while preserving the image quality and is employed to acquire fECV, which is expected to become a new imaging indicator in GC assessment.

Supplementary

The article’s supplementary files as

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted according to the Declaration of Helsinki and its subsequent amendments. This study was approved by the Ethics Committee of Affiliated Kunshan Hospital of Jiangsu University (No. 2022-03-037-K01). Each participant signed “Informed consent about contrast-enhanced CT”.

Data Sharing Statement

Available at https://qims.amegroups.com/article/view/10.21037/qims-24-2013/dss

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DOI: 10.21037/qims-24-2013