Clinical Value of Energy Spectrum Curves of Dual-energy CT in Evaluating Pathological Grading of Gastric Adenocarcinoma

Backgroud: Accurate diagnosis of cancer staging and pathological differentiation are critical for the formulation of individualized treatment and prognosis of gastric cancer. It is vital to explore non-invasive preoperative imaging techniques to evaluate the pathological differentiation degree of gastric cancer tissues, and provide better diagnostic basis and decision-making reference for treatment. The purpose of this study was to explore the clinical value of energy spectrum curves of dual-source dual-energy CT in the quantitative evaluation of different pathological grades of gastric adenocarcinoma. Methods: A total of 62 patients with 1 well, 25 moderately and 36 poorly differentiated gastric adenocarcinomas pathologically confirmed by surgery were collected, and they underwent dual-source dual-energy CT plain scanning and enhanced scanning before operation. Dual-Energy software was used to measure the slope of the energy spectrum curves (λ) in arterial and venous phases after image reconstruction. Patients were divided into two groups according to the pathological results, including well and moderately differentiated gastric adenocarcinoma group and poorly differentiated gastric adenocarcinoma group. Data of each group were analyzed by independent sample t-test. The receiver operating characteristic curve was plotted to evaluate the diagnostic efficiency of the corresponding parameters. Results: There were significant differences in λ values of 40-50keV, 40-60keV, 40-80keV, 40-90keV, 40-100keV, 40-120keV, 40-130keV, 40-140keV and 40-150keV energy ranges in venous phase between the well and moderately differentiated group and poorly differentiated group (P<0.05), but no significant differences in λ values of different energy ranges in arterial phase between the two groups (P>0.05). And the area under curve in 40-3


Introduction
Gastric cancer is the most common malignant tumor of digestive tract with the third highest mortality rate among cancer-related mortality rates [1]. There are about 1 million new-onset cases of gastric cancer every year. There are regional differences in survival and prognosis of patients with gastric cancer, mainly due to differences in staging criteria. Accurate diagnosis of cancer staging and pathological differentiation is of great significance to the formulation of individualized treatment and prognosis of gastric cancer [2,3,4]. The clinical diagnosis of gastric cancer is mainly based on gastroscopy and a definite diagnosis of the pathological differentiation degree of gastric adenocarcinoma mainly depends on postoperative pathological examinations. However, some advanced patients who cannot tolerate surgery and gastroscopy were failed to make a definite diagnosis of the degree of pathological differentiation. Therefore, it is of great clinical significance to actively explore non-invasive preoperative imaging methods to evaluate the pathological differentiation degree of gastric cancer tissues, and to provide more diagnostic basis and decision-making reference for clinical treatment.
Computer tomography(CT) staging and endoscopic ultrasonography (EUS) staging of gastric cancer were independently classified by the Alliance Against Cancer and the 8th edition American joint committee on cancer (AJCC) TNM staging system [5,6,7].
In clinical practice, CT examination has become the main means of T staging of gastric cancer before treatment because of its simplicity, rapidity and objective image advantages [8]. Dual-source CT uses two sets of independent tube detector systems, which can simultaneously obtain the data of substances under high and low energy X-ray, and obtain the attenuation data of substances on X-ray under different energies. Quantitative parameters derived from spectral imaging data on the basis of dual-energy CT have proven to be useful for the diagnosis and staging of gastric cancer [9,10]. The purpose of this study was to explore the clinical value of energy spectrum curve of dual-source CT in the quantitative evaluation of gastric adenocarcinoma with different degrees of differentiation.

Patients
The retrospective study was approved by our Hospital Ethics Committee and the informed consent was waived. 134 Patients with gastric adenocarcinoma pathologically confirmed by surgery in our hospital from May 2018 to September 2018 were collected. 73 patients were included consecutively according to the following inclusion criteria: ① Patients undergo surgery after routinely dual-source dual-energy CT scans, with complete clinical data, pathological results; ② Interval shorter than 1 week between dual-source CT scan and surgery; ③ No radiotherapy, chemotherapy and other anti-cancer treatments were performed before enhanced CT scanning; ④ Scanning mode and imaging parameters are in accordance with the unified standard, and iodine contrast agents of the same manufacturer and concentration are used. Of the 73 retrieved patients, 11 were subsequently excluded for the exclusion criteria: ①Distant metastasis or no surgical indication; ②Suboptimal image quality for interpretation or image acquired from other institutions; ③Patients with poor gastric filling and poor lesion display. Finally, a total of 62 cases of gastric adenocarcinoma were included, including 46 males and 16 females (range, 33-86 years; mean age, 65.41±9.73 years). The patients were divided into three groups according to differentiation status: well, moderately and poorly differentiation. Of the 62 gastric adenocarcinomas, one was highly differentiated adenocarcinoma, 25 were moderately differentiated adenocarcinomas and 36 were poorly differentiated adenocarcinomas ( Figure 1).

Dual-source CT scan
Dual-source dual-energy CT scanner SOMATOM Force was used. Routine plain scanning covering the entire stomach region was performed firstly for each patient in a supine position, followed by three-phase enhanced scanning by using dualenergy mode, including arterial phase, venous phase and delayed phase. During enhanced scanning, a high-pressure syringe was used to inject 370 mg I/ml iopromide (1.2 ml/kg), a non-ionic contrast agent, into the antecubital vein (Ultravist, Bayer Healthcare Co., Ltd.) at a rate of 2.5-3.5 ml/s, subsequently 20 ml of saline was injected at the same rate. The automatic trigger mode was adopted in

Quantitative Dual-Energy CT Parameters
Post-processing was performed on the Dual-Energy workstation. An oval or rounded region of interest (ROI) about 0.2-0.4cm 2 drew by one radiologist, avoiding necrosis, calcification, blood vessel as much as possible, was traced in the most obvious enhancement area of the largest diameter of the tumor lesions on a single axial image. After the ROI was traced, the system automatically generated a scatter plot and a spectral curve. The following information was extracted from each lesion and sent for statistical analysis: HU (Hounsfield unit) at each x-ray beam value between 40keV and 150keV (with steps of 10keV).
The slope of the spectral Hounsfield unit curve (λ, in Hounsfield unit per kiloelectron-volt), which is defined as the difference between the CT value at two different energy divided by the energy difference, was calculated. For instance, as follows: where HU 40keV represents the CT value measured on 40keV images and HU 150keV stands for the CT value measured on 150keV images. Totally, 11 λ values were acquired from a spectrum curve, details are provided in Table 1 and Table 2. λ values were measured on both arterial and venous phase contrast-enhanced images.
Statistical analysis SPSS 22.0 software was used for statistical analysis. According to the pathological results, the patients were divided into two groups, including well and moderately differentiated gastric adenocarcinoma group and poorly differentiated gastric adenocarcinoma group. Measurement data were expressed by mean ± standard deviation. For data conforming to normal distribution, t-test was used for homogeneous variance; corrected t-test was used for heterogeneity of variance. The receiver operating characteristic (ROC) curve was drawn, the area under curve (AUC) was calculated, and diagnostic efficiency of each index was analyzed. P < 0.05 was considered as significant difference.

Clinical data
Of the 62 patients, there were 26 cases of well and moderately differentiated gastric adenocarcinomas, including 22 males with an average age of 67.33 ± 7.26 years, and 4 females with an average age of 65.50 ± 13.92 years; there were 36 cases of poorly differentiated adenocarcinoma, including 24 males with an average age of 64.88 ± 8.59 years, and 12 females with an average age of 63.08 ± 14.11 years. There were no significant differences in age and gender between the two groups.
Comparison of λvalues between the well and moderately differentiated group and poorly differentiated group According to observation and comparison, it can be seen that energy spectrum curves of all gastric adenocarcinomas in arterial phases ( Figure 2) and venous phases ( Figure 3) were descending. The curves in 40keV-110keV energy range varied greatly and those in 110keV-190keV energy range tended to be flat in arterial and venous phases. (Figure 4).
The λ values of poorly differentiated gastric adenocarcinoma group in arterial phase were higher than those of well and moderately differentiated gastric adenocarcinoma group in different energy ranges, but there was no significant difference between the two groups ( Table 1)

Discussion
As we all known, the clinical diagnosis of gastric cancer is mainly based on gastroscopy, and the degree of pathological differentiation mainly depends on postoperative pathological examinations, but there were differences in biological behavior, chemotherapy sensitivity [11] and neoadjuvant therapy sensitivity among different differentiated types of gastric adenocarcinoma. Therefore, evaluating the differentiated types of gastric adenocarcinoma before operation, chemotherapy or neoadjuvant therapy has certain clinical significance for individualized treatment and precise treatment of patients. In the present study, dual-source CT scanning technology was used to explore the energy spectrum curve of different energy ranges in evaluating the pathological differentiation of gastric adenocarcinoma, which had important practical significance and clinical value in guiding clinical diagnosis, treatment and prognosis evaluation.
Lesions are showed by conventional CT scanning due to the difference of CT values mostly. Although it can clearly show the location, size, shape, density and enhancement characteristics of the lesions, it has limited ability to differentiate and diagnose substances [12]. Dual-source CT scanning can simultaneously obtain the data of substances under high and low energy X-ray, obtain the attenuation data of substances under different energies, and form the energy spectrum curve of substances. The energy spectrum curve is that the CT value of ROI varies with the change of photon energy, the average CT value and standard deviation in each energy range from 40 to 190keV can be obtained on the energy spectrum curve, which reflects the attenuation characteristics and dynamic changes of substances in different energy ranges [13]. Because the energy spectrum curves of different substances show differences, differences of the energy spectrum curves in different tissue sources, characteristics and components can be estimated, which enables the differential diagnosis. It can be inferred that the energy spectrum curve can be used to differentiate the origin of tumors, benign and malignant tumors, and tumors with different differentiation degrees, moreover, the energy spectrum curve can be quantitatively analyzed to provide new diagnostic ideas [14][15].
In the present study, the energy spectrum curve rates of poorly differentiated gastric adenocarcinoma in venous phase were significantly higher than those of well and moderately differentiated gastric adenocarcinoma in 40-50keV, 40-60keV, 40-80keV, 40-90keV, 40-100keV, 40-120keV, 40-130keV, 40-140keV and 40-150keV energy ranges, and the diagnostic efficiency was the highest in 40-120keV energy range. Previous studies on blood perfusion in gastric cancer showed that the vascular permeability-surface value of undifferentiated gastric cancer was higher than that of differentiated gastric cancer [16], the lower the degree of differentiation, the higher the blood volume. In this study, the slope of energy spectrum curve of gastric adenocarcinoma lesions with poorer differentiation was higher, and there was a negative correlation, which indirectly proved that with the decrease of pathological differentiation of gastric cancer, the local enhancement of    Patient with poorly differentiated gastric adenocarcinoma(A1) and moderately differentiated The results showed that the energy spectrum curve of poorly differentiated gastric adenocar AUCs of ROC curve analysis in different energy ranges in venous phase. The AUC in λ of 40-1