GO is an autoimmune inflammatory disease of the orbit. Early diagnosis of the orbital tissues (active or inactive phase) is critical in deciding the best treatment option .
Previous radiological studies of GO were mainly concentrated on extraocular muscles. However, the LG is one of the most prevalently involved peripheral organs in GO [16, 17]. Go patients usually present with ocular discomforts, such as abnormal tear secretion . Some studies have indicated that oxidative stress markers, cytokines, and growth factors are elevated in GO patients’ tear fluid and positively correlated with CAS [19–21]. Although a few imaging studies in recent years have shown that LG herniation and MRI quantitative parameters were related to GO activity, the accuracy of predicting GO activity may be further improved. The aim of this study was to establish and validate a new prediction model based on MRI quantitative parameters and objective clinical manifestations for predicting the GO stage.
T2-mapping is a kind of multi-echo spin-echo pulse sequence. By drawing ROI, the T2 value could be acquired by quantifying water content and collagen tissue . Some studies have shown that the T2 value is valuable in the early evaluation of cartilage degeneration and myocardial disease [23, 24]. Moreover, the T2 value of LG is a good indicator for GO staging . In our study, the T2 value of LG (especially in model I and II) resulted as the best predictor for GO staging. Furthermore, the T2 value of LG in the GO active phase was significantly higher than that in the inactive phase, reflecting inflammatory edema of LG.
DWI is a functional MRI technique that is increasingly applied in GO staging, therapeutic evaluation, and prognostic estimation [10, 25]. The DWI signal reflects the degree of diffusivity of water molecules. Also, ADC value provides quantified information on physiologic tissue characteristics. Compared to traditional Echo-Planar Imaging (EPI) DWI, Turbo Spin-Echo (TSE) DWI could provide distortion-free images with a similar signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) . Therefore, in this study, the coronal TSE DWI sequence was adopted to enable the bilateral LG to be clearly displayed, and the ROI can be accurately delineated on the ADC map. No significant statistical difference was found in ADC values of LG between the active and inactive groups, which was inconsistent with some previous studies . Further research is needed to determine whether the result is related to sample size, machine model, or B values.
DCE-MRI quantitative parameters were calculated based on the extended Tofts model, which reflects the microcirculation and hemodynamics of the tissue . Ktrans, Kep, Ve, Vp, and IAUC did not show statistical differences between the active and inactive groups, nor did they result as valuable variables in Model I and II. In a previous report on DCE-MRI of LG, only Ktrans and Kep were significantly different between the two groups . Although LG size and herniation have been reported to be useful for staging GO, regrettably, no significant differences between the inactive and active phases were found in our study regarding the internal microcirculation of LG.
In this study, we combined sex, age, and objective clinical data with imaging parameters. We found that in Model I (that included patient age, sex, and imaging parameters), sex was a good independent predictor. A previous study suggested that an active GO phase is often seen in male patients compared to females . It is speculated that this may be due to the high proportion of smoking among male subjects . It has been documented that GO tends to be more severe in men, and smoking is the most important modifiable risk factor for GO . Yet, the mechanism by which smoking adversely affects GO is unclear. Oxygen-free radical generation, enhanced production of cytokines, hypoxia in orbit, and stimulation of adipogenesis have all been associated with smoking .
In Model II, age, history of treatment, interorbital distance, MRD-1, and MRD-2 all showed all good value in predicting the GO stage. A previous study found that the mean age of patients with moderate to severe GO was significantly higher than that of patients with mild GO, thus suggesting that age is a relevant factor affecting the severity of GO . In our case, the average age of the GO active group was significantly higher than that of the inactive group, which was consistent with previous studies. It is not difficult to understand that moderate to severe GO is usually in the active stage, and CAS is higher than that of the inactive stage, active stage is more common in the elderly. Moreover, most of patients who received the treatment of I123, corticosteroids, or radiotherapy were sensitive to treatment and in the inactive phase at the time of visit, while most of the untreated patients were still in the active phase at the time of visit. Additionally, the accurate measurement and evaluation of interorbital distance, MRD1, and MRD-2, were conducive to staging GO. The AUC of Model II was 0.928, and that of Model I was 0.832. Thus, it was concluded that patient demographics and MRI parameters were not sufficient for GO staging prediction, and ophthalmic clinical indicators measured by ophthalmologists could be used to better establish the model.
Although CAS itself is an exact value, the 7 CAS indicators are obtained using the subjective judgment of evaluators. In this study, we investigated new methods to evaluate the objective items (clinical and imaging data) of each CAS indicator. Among the newly added variables in Model II compared to Model I, we found that swelling of eyelids, redness of the conjunctiva, swelling of the conjunctiva, swelling of caruncle or plica, and spontaneous retrobulbar pain in CAS could be predicted by demographics, objective ocular manifestations, and quantitative MRI measurements of the lacrimal gland. Based on this, considering these 5 CAS indicators, we tried to use objective indicators and MRI parameters to replace the subjective clinical judgment of CAS. The result section partially presented the substitution formula of the 5 indicators that could be verified and optimized in the subsequent related research. Future studies should also explore the other two transformation methods that failed to achieve objective substitution indicators in this study.
This study has a few limitations. This is a cross-sectional study with small sample size. In addition, indicators of patients were collected before treatment and did not involve the analysis and prediction of intervention methods and efficacy.
In this study, various MRI parameters of LG, patient demographics, and clinical indicators of GO patients were creatively combined to establish a prediction model for GO staging, acihieving satisfactory results. The value of introducing clinical indicators was also proved by the improvement of model AUC. On this basis, this study achieved the substitution of objectification of 5 CAS evaluation indexes, providing a new idea for improving the objectification level of GO data collection.
To sum up, our preliminary data suggest that sex and the T2-mapping value of LG could be useful indicators for predicting the phase of GO. Finally, the objective replacement of the CAS index provides a new idea for multi-center GO diagnosis and treatment and quantitative research.