Glioma grading has an extremely important influence on the prognosis of patients. Therefore, the correct classification of glioma before and during surgery has important guiding significance for selecting surgical plans and predicting prognosis. Intraoperative ultrasound has become an important surgical auxiliary method in the field of neurosurgery and has the advantages of real-time positioning, simple operation, no radiation damage, and portability. At the same time, a variety of new ultrasound techniques have been gradually applied in craniocerebral neurosurgery. In this study, the value of B-mode ultrasound performance, SWE and SMI in glioma pathological grading was studied.
In our study, a total of 49 patients were enrolled to study the B-mode characteristics between HGG and LGG. We observed that tumor morphology, border, internal echo, cystic degeneration and calcification showed a certain trend of difference, but the difference was not significant, which may be due to tumor heterogeneity and relatively limited sample size. However, the degree of edema around the tumors of HGG and LGG has a significant statistical difference, which may be due to the rapid growth of HGG, poor differentiation of neovascularization in the tumor accompanied by increased vascular permeability, and difficulty in establishing venous collateral circulation, leading to edema of surrounding normal brain tissue. At the same time, the growth process of a tumor often leads to the destruction of the blood-brain barrier, leading to more obvious edema.(30).
SWE does not require external pressure, and the shear wave velocity of the tissue provides an estimate of the stiffness of the tissue in meters per second or is converted to Young's modulus in kilopascals. Compared with strain elastography, the elastic value of shear-wave elastography can be evaluated quantitatively and reproducibly. In our study, the elasticity of HGG and LGG was different between tumor regions and peritumoral tissues. For tumor regions, HGG was harder than LGG, which was similar to the results of previous MRI- and ultrasound-related studies(31, 32). For LGG, the hardness of peritumoral tissue was significantly lower than that of the tumor regions, while for HGG, there was no difference between them. The reason for the low stiffness of HGG may be that the rapid growth of tumors may lead to the lack of adequate nutrient supply of the tumor, leading to the coexistence of partial solid tumors, necrosis, hemorrhagic and cystic degeneration, leading to relatively low stiffness(33). For peritumoral tissues, the elasticity value of HGG is lower, probably because HGG is often accompanied by more severe peritumoral edema, which leads to a decrease in the hardness of the surrounding normal brain tissue.According to our study, SWE can serve as an important tool for differentiating LGG and HGG with good sensitivity (88.9%) and specificity (73.5%). The cutoff value for distinguishing LGG and HGG was 12.95 kPa, which was consistent with the previous related research results of 12.1 kPa(9). To be more specific, stiffness measurements are invaluable in helping surgeons quantitatively distinguish between LGG and HGG. This differentiation is important because tumor grade is closely related to prognosis and treatment strategy.
SMI is an innovative Doppler technology that can display low-velocity vessels and describe diseased microvessels in more detail than traditional CDFI. SMI is a safe and low-cost alternative to CEUS, which has been widely used in the thyroid, breast, prostate, uterine appendages, etc(34–39). Our study applied SMI to distinguish between HGG and LGG and found different vascularity patterns in intratumoral and peritumoral tissues. Compared with LGG, the internal vasculature of HGG is relatively distorted, and the peritumoral vessels are mainly vertically penetrating. Neoangiogenesis is the essential condition and root cause of tumor growth and metastasis. Angiogenic growth factor expression levels were shown to influence tumor progression. Angiogenic factors in glioma are upregulated by various mechanisms, such as oncogene activation, loss of tumor suppressor gene function, and/or a hypoxic microenvironment, leading to vascular structural disorders, lumen dilation, irregular arrangement, irregular branching, and high permeability(40). The neogenesis and structural abnormalities of microvessels increased significantly with the increase of malignant degree, so the blood vessels of HGG were more distorted and abundant. Meanwhile, the tumor vascular system is highly permeable to plasma and plasma proteins, leading to local edema and plasma extravascular coagulation, which may explain the more pronounced peritumoral edema in tumors with higher malignancy(41, 42).
Through further regression analysis, we found that the elasticity value of SWE and the tumor parenchymal vascularity patterns of the tumor were clearly correlated with the diagnosis of HGG. The AUC diagnostic performance of the regression model is better than that of the SWE Young's modulus alone. The evaluation of B-mode, hardness and vascularity of the tumor could be more conducive to the classification and evaluation of glioma grade. These ultrasonographic features should be considered comprehensively when determining the grade of glioma by intraoperative ultrasonography.
This study also has some limitations. First of all, the sample size is relatively small and only supratentorial superficial tumors were enrolled, so it is necessary to expand the sample for further research on the efficacy of SWE and SMI. Secondly, this study only analyzed the ability of B-mode ultrasound, SWE, and SMI to differentiate HGG from LGG, and further study is needed to evaluate the value of accurate localization of tumor boundaries and residual tumor assessment. In summary, IoUS, especially SWE, and SMI are beneficial for the differentiation of HGG and LGG and may help optimize clinical surgical procedures. The use of SWE and SMI for ultrasound monitoring in neurosurgery provides a wide range of information for precision surgery and may become a useful neurosurgical instrument in the near future.