Conventional MRI is one of the most important imaging examine for gliomas, and the grade of gliomas is usually evaluated by several aspects such as contrast enhancement, cortical involvement, lesions margin, tumor infiltration, mass effect, necrosis and so on[17-20]. However, conventional MRI offers only anatomical and morphological characteristic through visual comparison, which cannot obtain quantitative information. Synthetic MRI which is not affected by the scanner settings, inhomogeneity of the B1-field and coil sensitivity profile provided with additional quantitive information about gliomas grading. We retrospectively explored the diagnostic performance of synthetic MRI in evaluating gliomas grading and tumor proliferative activity.
In general, HGGs are more aggressiveness compared with LGGs. The intratumoral histological heterogeneity in gliomas can reflect tumor grading. Histologically, HGGs are different from LGGs in respect of nuclear anaplasia, mitoses, cellularity, neovascularization, and necrosis. Some MRI techniques have been reported to help quantify the features of gliomas. Conventional MRI after contrast enhancement showed that the destruction of BBB was more severe in HGGs than LGGs. DWI reflected the cellularity of gliomas which HGGs show higher cell density. CBV, as an indicator for the tumor neovascularization, reflected the difference of tumor neovascularity between HGGs and LGGs using perfusion MRI. Furthermore, some studies revealed that the concentration of mobile proteins and peptides were higher in HGGs than LGGs[3, 25]. T1 relaxation time, as a basic parameter of MRI, was mainly influenced by interstitial water content[26, 27]. All of these factors may lead to differences in T1 relaxation time between HGGs and LGGs. In our study, the average values of T1-pre were significantly higher in the group of HGGs compared with the group of LGGs, which may be helpful to distinguish HGGs from LGGs. Whereas, the sensitivity (69.2%) and specificity (65.0%) of grading diagnosis based on T1-pre values alone were relatively low.
The injection of contrast agent can better highlight the destruction of BBB. In general, the areas of contrast enhancement on T1-weighted images represent the breakdown of BBB which is usually associated with higher tumor grading[20, 28]. In addition, the degree of malignancy in gliomas is positively associated with massive angiogenesis that provides nutrients for the growth and metabolism of tumor tissues, and promotes tumor cell division and proliferation. These may lead to different changes in T1 relaxation time after enhancement. Our study showed that T1-Gd, rT1-Gd and ΔT1 differed significantly between the group of HGGs and the group of LGGs (P＜0.05) and the group of HGGs had lower T1-Gd, rT1-Gd and higher ΔT1 than the group of LGGs. Similar to our study, Su et al  scored tumor according to enhancement quality (1=none, 2=mild/minimal, 3=marked/avid) on conventional MRI and found that enhancement quality was significantly different between HGGs and LGGs and the contrast enhancement was more pronounced in HGGs compared with LGGs. In conventional MRI, contrast-enhanced detection was based on subjective comparison of T1-weighted images before and after enhancement. Synthetic MRI can quantitatively measure the T1 relaxation time before and after enhancement and obtain the ΔT1 which more objectively and accurately describes the degree of enhancement. Therefore, synthetic MRI is more advantageous for gliomas grading. ΔT1 values showed the highest diagnostic value (area under curve: 0.804) for gliomas grading, and the optical cut-off value was 277.88ms, sensitivity was 96.2% and specificity was 60.0%. In other word, when ΔT1≥277.88ms, the grading diagnosis tended to favor HGGs. In addition, both the values of T1-Gd and rT1-Gd had relatively high sensitivity (T1-Gd: 88.5%; rT1-Gd: 100%).
Ki-67 LI is positively associated with cellular proliferation and malignancy of tumor[16, 31, 32], which is no exception in gliomas. In our study, we found that the Ki-67 LI was positively correlated with tumor grading, and T1 relaxation time was positively correlated with gliomas grading. Therefore, we speculated that there would be certain differences in T1 relaxation time for gliomas with different proliferative activity.
Olsen et al investigated the relationship between proliferation activity and T1,T2 relaxation time in four human melanoma xenograft lines including A-07,D-12,R-18,U-25, and they found that T1 and T2 relaxation time of high proliferative activity tumor were higher than low proliferative activity tumor. In our study, we found that Ki-67 LI was positively correlated with T1-pre. After injecting the contrast agent, Ki-67 LI was negatively correlated with T1-Gd, rT1-Gd and positively correlated with ΔT1, Chang et al explored the correlation between cell density and MR signal intensity in glioblastoma, and they found that the signal intensity of T1-postcontrast subtraction by subtracting coregistration-normalized T1-precontrast volumes from T1-postcontrast volumes was positively correlated with cell density (r=0.69). Therefore, T1 relaxation time is expected to be an imaging indicator to express the proliferative activity for gliomas.
Hattingen et al emphasized the important of T2 relaxation time which allowed to detect tumor progression in glioblastoma much earlier compared with conventional MRI. In our study, we failed to find the clinical value of T2 relaxation time in predicting gliomas grade and tumor proliferative activity. Kern et al found that T2 values were higher in grade III gliomas compared with grade II gliomas, whereas the results were not statistically significant. Therefore, the application of T2 relaxation time in gliomas needs further exploration.
Synthetic MRI is a morphologic MRI that can provide quantitative values of T1 and T2. In our study, T1 relaxation time was helpful to differentiate HGGs and LGGs and to predict tumor proliferative activity. The gold standard for gliomas grade and tumor proliferative activity is based on surgical removal or biopsy, however, due to the tumor heterogeneity, the pathological results can only reflect the grading and proliferative activity of the specimens taken, rather than the whole tumor[8, 22].Therefore,T1 relaxation time, which was associated with gliomas grading and Ki-67 LI, may be useful to provide more information for biopsy ,as well as to determine the range of radiation exposure field for radiotherapy.
However, there are still several limitations to this study. Firstly, the number of patients is relatively small and larger samples sizes are needed to confirm these results in the future. Secondly, the selection of ROI cannot accurately correspond to the sampling of pathological specimens, so that the results may be biased to some extent.