With the development of personalized medicine and molecular targeting therapy, it is particularly important to determine the pathological type of lung cancer before starting treatment, because the efficacy of targeted drugs depends on the pathological subtype of lung cancer, For example, such as bevacizumab are effective in the treatment of AC, but it may lead to neutropenia and massive bleeding in patients with SCC [20, 21]. The diagnostic accuracy of peripheral lung squamous cell carcinoma and peripheral lung adenocarcinoma is very limited due to the overlap of imaging signs on conventional CT. The multi-parameter of spectral CT can effectively reflect the tissue composition and biological characteristics of the tumor, and has great potential in identifying tumor subtypes and differentiation degree [17]. Wang et al. [22] studied the spectral CT manifestations of AC and SCC and found that spectral CT can provide both qualitative and quantitative parameters of the lesion, which provides a new method for differentiating them.
In this study, we found that CT40keV, CT70keV, K70keV and IC in patients with P-AC in both AP and VP were higher than those in patients with P-SCC, which was consistent with the results of previous studies [23–25], indicating that the blood supply of AC was more abundant than that of SCC. According to the results of previous pathological studies [26], the capillary endothelial cells in normal tissues are tightly connected and the basement membrane is intact, and the contrast agent rarely penetrates into the intercellular space. However, a large number of new capillaries are formed in the tumor tissue, in which the capillary endothelial cells are loosely connected and the basement membrane is incomplete, so the contrast agent can easily penetrate into the intercellular space. Yazdani et al. [27] found that compared with SCC, AC is more likely to form rich and homogeneous cribriform capillaries, with greater microvessel density, and the maturity of neovascularization formed by SCC is not as good as that of AC. Neovascularization is more likely to be broken or blocked due to the rapid growth of tumor tissues. Therefore, the uptake of iodine contrast agent in AC is higher than that in SCC. According to histopathological analysis, AC is mainly composed of glandular structure, which contains rich interstiitium, loose internal structure and the number of cells per volume is large, while SCC is mainly composed of cancer nests, keratinocytes, intercellular bridges and other structures. The internal structure is dense and there are fewer tumor cells per volume [24], so the extent of the penetration of contrast agent will also be different.
The spectral curve reflects the change of the CT value of the lesion under different keV. We can judge the properties, homology and difference of lesions by analyzing the spectral curve of lesions, and it also can reflect the absorption of the contrast agent in the lesion [25]. The results showed that the slope of different energy intervals are different, and the CT value of tissues will decrease with the increase of energy, and the CT value of different energy levels representing the mass absorption coefficient of lesions at different energy levels [28]. In this study, the curve is steep in the range of 40 ~ 70 keV, and the curve is flat in the range of 70 ~ 100 keV. This is related to the larger the X absorption coefficient and the more X-ray attenuation at low energy. In this study, the slope of spectral curve between 40 and 70 keV was selected as the quantitative analysis index. The results showed that the K70keV of AC was higher than SCC during both AP and VP, and the difference was statistically significant, which was consistent with the research results of other scholars [25]. The slope of spectral curve reflects the intensity of lesion enhancement, so it is considered that AC absorbs more iodine contrast agents than SCC, and contrast agents enhance the difference of mass absorption coefficient between the two groups of lesions.
The effective atomic number (Zeff) can directly reflect the atomic number of the compound inside the lesion. If the X-ray attenuation coefficient of the atomic number of an element is the same as that of the compound, then the atomic number of the element is the atomic number of the substance [26]. According to this feature, the composition and properties of compounds can be identified [17], especially those with similar densities and CT values. Some studies have shown that the Zeff can accurately describe the histological characteristics of the lesion and distinguish the material components [24, 29, 30]. In this study, the Zeff of P-AC was greater than that of P-SCC during both AP and VP, and the difference was statistically significant. This may be due to the different pathological tissue types, the material composition and cell metabolic activity of the lesions are also different. And the Zeff with enhanced scan is related to the uptake dose of contrast agents by the lesions, which leads to the difference of Zeff between the P-AC and P-SCC [31].
According to ROC curve analysis, the combination of all parameters in AP and VP showed higher sensitivity (88%) and specificity (84%) Compared with the quantitative parameters alone during AP or VP in distinguishing P-SCC and P-AC, and the diagnostic efficiency of the AP is higher than that of VP. Zhang et al. [7] who found that quantitative parameters in VP had greater significance in differentiating SCC and AC than in AP. However, Jia et al. [25] found that the quantitative parameters of the two phases had no significant difference in distinguishing SCC from AC. The difference between the above studies may be due to the fact that each quantitative parameter is related to the uptake of contrast agents by the lesions, which may be affected by the dose of contrast agent, the enhanced scanning time of each phase, and the patient's hemodynamic status, resulting in different Research results [31]. It may also be due to the samples included in these studies is small or the lack of distinction between lung cancer types, such as peripheral and central squamous cell carcinomas, which may affect the results between different parameters. At present, our study with the largest sample to distinguish P-AC and P-SCC. Therefore, our results are more accurate and generalized.
There are several limitations in this study. First, this study was a retrospective study, which may lead to sampling bias. Secondly, this study focuses on differentiating P-SCC and P-AC, and other histological subtypes of lung cancer were not included. In future studies, more lung cancer subtypes will be included to draw broader conclusions. Finally, in order to reduce the radiation dose, the patients were not scanned for the delayed phase. Therefore, more studies are needed to confirm whether the quantitative parameters during the delay period can differentiate P-SCC and P-AC.