Combination of multiple MRI techniques for brain metastases
Traditional magnetic resonance diagnosis of brain metastases is performed by routine MRI and enhanced examination, and the signals of brain metastases and edema around the tumor are observed. That is, the MRI shows that the brain metastases are slightly low or low signal intensity on T1 WI, high signal intensity on T2WI, equal or slightly low signal intensity on T1 WI and high signal intensity on T2WI in the edema area around the tumor. The reason is tumor cells have a relatively high water content compared with normal white matter. By MR-enhanced scans, brain metastases had characteristic of uniform enhancement, uneven enhancement, nodular or annular enhancement, and more clearly showed partially hidden lesions. The edemas around the tumor are not enhanced. When brain metastases intratumoral hemorrhage occur, complicated by hypertension, some lesions showed high or slightly high signal on T1WI.
The DWI and its ADC signals were used to observe the degree of edema of lung cancer and its surrounding edema. when high DWI signal and decreased ADC value appear, it reflected the changes of microscopic structure of brain metastasis, and showed certain characteristics to the surrounding area of the tumor. So it can effectively improve the accuracy of diagnosis and differential diagnosis of lung cancer brain metastases. This is well validated in this set of data[6].
SWI showed tumor and peripheral blood supply, intratumoral hemorrhage, non-invasive detection of differences in magnetic sensitivity between tissues, reflecting blood oxygen levels in tissues. In this group of data, 26 cases of brain metastases and 15 cases of gliomas, SWI images showed a low intra-tumor signal and connected with the blood supply artery. Cases of brain metastases and gliomas with intratumoral hemorrhage were excluded by SWI images to avoid affecting CEST MTR results[7,8].
Using ASL with PLD=2.0, it is possible to determine the changes in blood-brain barrier permeability and the loss of cerebral blood flow regulation during the evolution of brain metastases and gliomas[9].
The role of 3.0T MR CEST
In the experiment, T1WI, T2WI, T2 FLAIR, T1WI+C, DWI, SWI, ASL of 3.0T MRI were used to verify and observe the metastatic tumor group, glioma group and normal group. Using the GRE EPI CEST sequence of ASSET technology, the 3.5ppm (MTR) map were obtained by APT software with the quantitative analysis of the corresponding region. Then, the CEST technique and clinical application value of 3.0T magnetic resonance lung cancer brain metastasis were discussed. The aim is to develop a non-invasive and accurate molecular imaging MRI research program based on CEST for lung cancer brain metastases. The results showed the characteristics of CEST signal in lung cancer brain metastasis. The focal parenchymal areas and edema areas of the metastatic tumor group were reddish yellow and greenish blue. The MTR value was lower than that of the glioma group, which was higher than the normal group. But the non-lesional areas of the metastatic tumor group were greenish blue. The MTR value is higher than glioma group, normal group. The MTR values of the edema and non-lesional areas are similar. In addition, these value were higher than those in the normal group, which were mainly in the substantial region (Figures 1, 2, 3, and 4) [10,11].
This is related to the mechanism of brain metastases derived from hematogenous metastasis. The tumor cells circulate in various parts of the body with blood, including the parts of the brain where no metastatic lesions have been found. Thus the MTR value of the metastatic tumor lesions is significantly increased. And the MTR value in the edema areas, and the non-lesional areas are increase.
When the brain metastases are accompanied by hemorrhage, the high MTR value of the parenchymal area, and the signal in the focal parenchymal areasis uneven. This is related to the oxygenated hemoglobin content, the deoxyhemoglobin content, and the necrosis of the tumor parenchyma in different periods after hemorrhage. Conventional sequences combined with SWI and ASL can verify it. when SWI showed old bleeding with a significantly low signal, the MTR value reach more than 80% increase. Although the parenchymal areas are all increased, the differences between individuals and regions are large, which may be related to the coexistence of new and old hemorrhage in the metastatic tumor and necrosis in the tumor [7,8]. CEST can detect blood products (deoxyhemoglobin, methemoglobin, ferritin, and hemosiderin) that cause hemorrhage and a significant increase in MTR. It may also be related to changes in tissue pH during the evolution of brain metastatic tumors, which requires further data validation. In order to avoid the interference of bleeding, the cases of intratumoral bleeding were not included in the data of this group.
PTBE will make the tumor occupying effect more obvious, further increase intracranial pressure and worsen clinical symptoms. In MRI, the signal of edema around the tumor of brain metastases is varies. This is not only related to the macroscopic factors such as the specificity of the nervous system, the location of the brain metastases and the degree of malignancy, but also VEGF and its receptors, AQP-4, MMP-9, IL-6, HIF-1a and other molecular organisms factors [5,12]. In this data, VEGF and AQP-4 results showed high levels of high expression. Especially in cases with peri-tumoral edema, AQP-4 was highly expressed in brain tissue surrounding brain metastatic tumors, not within metastatic tumors. This explains why the MTR value of CEST in brain metastases is increased, and the MTR value in the edema and non-focal areas is more pronounced in cases with bleeding, which may also promote angiogenesis with VEGF. It is related to factors such as the destruction of the blood-brain barrier. The edema around the tumor is related to the malignant degree of the tumor. The edema around the tumor caused by the malignant tumor destroying the blood-brain barrier is mainly angiogenic. And the edema mainly invades the white matter of the brain, and the liquid with a small amount of protein is damaged due to the damage of the blood-brain barrier, and accumulate around the tumor. The degree and extent of edema around the tumor are related to the structure and characteristics of the brain tissue itself. For example, edema in the cortex, basal ganglia, and thalamus is not easy to occur. The edema in the white matter area is more obvious, but not in the brain stem. In this group of data, this was also verified that 8 cases of edema-free brain metastases occurred in the basal ganglia and thalamus.
The MTR values in the focal parenchymal areasof the glioma group were higher than that of the metastatic tumor group. In addition, the lesion parenchyma and edema area were red, reddish yellow, and their boundary was unclear. The non-lesional area was greenish blue, and not different from the normal group with no increment.
The MTR values in the focal parenchymal areas of the metastatic tumor group were higher than those in the edema area and the non-focal area. The MTR values in the edema areas, and the non-lesional areas were similar, which were slightly higher than normal.
In this paper, CEST mainly reflects not only the metabolism of free protein and peptide molecules, but also the tumor activity and its progress from the molecular level[13-19]. The MTR values in the edema areas of the glioma group are increased, which is consistent with the tumor surrounding the brain and the surrounding edema of the tumor. However, brain metastases do not invade, but compression, the secondary edema of brain metastases occurs, which is differentiated from the original tumors in the brain. CEST has certain advantages in sensitivity and accurate display of anatomical structure. It can visually observe the abundant free protein or polypeptide molecules in brain metastases. Moreover, it is important for its treatment and prognosis that early diagnosis and comprehensive evaluation of the scope of brain metastases and its surrounding anatomical structure [13,19-22].
Case selection principles and limitations
As a material basis of life, proteins are closely related to various forms of life activities. Protein accounts for 16% to 20% of body weight, and its amide proton content is high[13,19-22]. The lung cancer brain metastasis and high-grade gliomas in this study have abnormal metabolism of intracellular proteins and peptides in their own disease course. This is the material basis of CEST effect in APT imaging, which is used to distinguish between parenchymal and necrotic areas, surrounding edema area, etc.
Brain metastases account for 10% to 15% of intracranial tumors, and lung cancer brain metastases account for 30%-40%[4]. This is also the reason why the experimental data cases are included in the above diseases.
The purpose of this experiment was to verify the CEST imaging effect. All of the selected brain metastases were lung cancer. Because the brain metastases of different types of lung cancer, brain metastases of different degrees, edema and edema size were not analyzed. So this brings the limitations of analysis, and will refine the research in the future work.
At present, there are still some cases of low signal-to-noise ratio and unsatisfactory contrast in CEST image quality. Combined with conventional sequence and enhanced examination, a certain degree of registration and correction are profitable to display and distinguish lesions, and analyze brain metastases. The regional signal and its MTR value can distinguish lesion parenchyma, necrosis and peripheral edema (Figures 2, 3, 4).
The experimental group will further collect data, expand the range of disease types, randomly select data, and analyze specificity and sensitivity. At the same time ,we will in-depth study the fast APT imaging sequences, and strive to use the fast imaging sequence software package. So as to reduce the series of interference signals caused by the EPI sequence, realize the intelligent CEST-APT imaging, and provide intelligent and accurate molecular imaging diagnosis information for the research of brain diseases.
Conclusions
The CEST sequence and APT software using ASSET and GRE-EPI techniques obtain pseudo-color images and reflect protein metabolism. The metastatic area and edema area of the metastatic tumor group were reddish yellow and greenish blue. The MTR value was lower than that of the glioma group, which was higher than that of the normal group. The non-focal area was greenish blue, and the MTR value was higher than that of the glioma group and the normal group.
Combined with the sequence of sweep, enhancement, DWI/DKI, SWI, ASL/PWI and MRS, the MTR image color resolution and MTR value of CEST 3.5ppm acyl protons can be used to observe the distribution and metabolic changes of brain metastases and realize early diagnosis of brain metastases and assessment of the outcome of molecular imaging of lesions.
Of course, the clinical application of CEST technology is still in the research stage, and further optimization is needed. It is believed that with the deepening of research, its clinical application value will become more and more extensive.