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Baseline Multiparametric Volumetric T2RT Histogram Analysis: Can It Be Used to Predict Therapy Response in Patients with Thyroid Associated Ophthalmopathy (TAO) Undergoing Intravenous Methylprednisolone1radiology, The Affliated Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, WuHan, China, 2The Affliated Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, WuHan, China
Synopsis
Prompt recognition the characteristics of extraocular muscles (EOMs) representing responding to intravenous methylprednisolone pulses (ivMP) is crucial for identifying optimal, patient-tailored treatment options in the era of personalized, precision medicine for thyroid-associated ophthalmopathy (TAO). This study attempts to predict the therapy response using the baseline histogram features of EOMs from volumetric T2 relaxion time (T2RT) texture analysis. Multivariate logistic regression analysis suggested that 90th and 95th percentile T2RT, skewness, entropy and inhomogeneity were significant predictors of ivMP response. Volumetric T2RT histogram analysis is a feasible and promising tool for predicting the response of ivMP therapy in patients with TAO.
Introduction & Purpose:
Management of thyroid-associated ophthalmopathy (TAO) is of challenge and dilemma, largely for the variety of treatment regimens, emerging novel treatment options, unsatisfied therapy response and balance between benefit and harm from therapy1-2. Which raised a higher requirement for the evaluation of therapy response in the era of personalized, precision medicine. Corticosteroids remains the mainstay for majority of TAO patients, intravenous methylprednisolone pulses (ivMP) seemed more effective and better tolerated regimen among them3. Prediction and evaluation of the response to ivMP therapy is extremely essential for clinical management of TAO, which is help to better identify patients who will truly benefit from ivMP and provides better grounds for evidence-based tailored therapeutic strategy to reduce the risk of progression to sever sight-threatening disease. Existing measurements no matter the ophthalmic examinations or imaging can’t be adopted as a unifying clinically applicable system to reliably identify disease and accurately measure therapeutic outcomes. Albeit the orbital MRI imaging become increasingly prominent in TAO for its capability in objectively and directly assessing the orbit tissue. The current imaging modalities were either semi-quantitative means or based on the morphologic alterations, which were incapable of assess the treatment response effectively. Texture analysis (TA) can detect a lot of intrinsic microscopic information of tissues contained in medical images.Volumetric T2RT histogram analysis, may be an ideal method can improve sampling bias and quantify the inhomogeneity within tissues. This study aims to use the baseline volumetric T2RT histogram parameters of EOMs to predict the therapeutic response of ivMP in TAO patients.Methods:
45 TAO patients who were treated with ivMP were included. They were divided by efficacy into responsive group and unresponsive group. Baseline histogram-derived T2RT parameters of involved EOMs were analyzed by univariate analyses and were used to fit a multivariable logistic regression model. Receiver operating characteristic (ROC) curves were conducted to discriminate the performance of this model and determine Youden index-based cutoff values.Results:
The responsive group had a significant higher value in higher percentiles (75th, 90th, and 95th) T2RT, SD, skewness, entropy and inhomogeneity (P<0.05) than unresponsive group(Figure1). Multivariate logistic regression analysis showed that 90th, 95th percentile, skewness, entropy and inhomogeneity were significant predictors of ivMP response(Figure3). The logistic regression model combining the five histogram features achieved a highest area under the ROC (AUC, 0.884; 95% CI, 0.847–0.914; P < 0.001), and the corresponding sensitivity and specificity were 82.81% and 79.06%(Figure2).Discussion:
TAO is a progressive disease, it is difficult to identify whether or which patient would be beneficial to immunosuppressive therapy by clinical assessment alone. The combination of T2mapping technique and histogram-derived texture analysis can assess the EOMs comprehensively. It acts as a microscopic approach to reflect the coexistence of complex biological components including interstitial edema, proliferation of lymphocytes, immature plasma cells, and occasional dense fibrous scar tissue within EOM.
The current study employed pre-treatment T2RT histogram analysis of EOMs to predict the response of ivMP. The preliminary demonstrated that: (1) in patients giving favorable response, the value of higher percentile (75th, 90th and 95th) T2RT, skewness, entropy, and inhomogeneity of EOMs were pronouncedly higher than those in the patients without good response;(2) the entropy alone can be used as an independent predict factor to predict therapy response, combination of 90th and 95th percentile T2RT, skewness, entropy and inhomogeneity can better predict the therapy response with a highest AUC.
The glucocorticoids mainly interfere with the binding of lymphocytes or a lymphokine to retroocular fibroblasts in TAO4. In T2RT histogram, the T2RT values were listed in an increasing number from the left to right, the 90th and 95th percentile T2RT located in the rightmost areas in the histogram, which represent the highest T2RT and the most inflammatory edema part in the EOM. The entropy describes the irregularity or complexity of the distribution of a parameter of interest’s distribution. The skewness measures the asymmetry of the histogram distributions and inhomogeneity quantifies the heterogeneity of a parametric distribution. The entropy, skewness and inhomogeneity jointly reflect the complexity of the tissue components5, the higher the value the more diverse and complex the components, indicating the myopathy is in an active proliferative phase. In this active phase, the methylprednisolone can exert its targeting therapy function.
Conclusion:
The emerging quantitative analysis method-T2RT histogram analysis-may be of fundamental importance in selecting appropriate TAO patients to ivMP. Which is helpful for the clinicians to choose the appropriate treatment or to adjust therapeutic strategies such as radiation in time to develop a more individualized treatment for TAO patients.Acknowledgements
This work was supported by grants from the National Natural Science Foundation of China (No.81771793, 81301192)References
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2.Wiersinga WM. Advances in treatment of active, moderate-to-severe Graves' ophthalmopathy. The lancet Diabetes & endocrinology 2017; 5(2): 134-42.
3.Brauer VF, Scholz GH. Treatment of Graves' ophthalmopathy with oral or intravenous corticosteroids. Medizinische Klinik (Munich, Germany : 1983). 2004;99(2):71-6.
4.Sisson JC, Kirchick H, Kothary P. Inhibition of glycosaminoglycans production in retrobulbar fibroblast cultures by ethacrynic acid and hydrocortisone. The Journal of clinical endocrinology and metabolism. 1974;38(5):777-82.
5.Rosenkrantz AB, Ream JM, Nolan P, Rusinek H, Deng FM, Taneja SS. Prostate Cancer: Utility of Whole-Lesion Apparent Diffusion Coefficient Metrics for Prediction of Biochemical Recurrence After Radical Prostatectomy. AJR Am J Roentgenol. 2015;205(6):1208-14.
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