Whole-orbit radiomics: machine learning-based multi- and fused- region radiomics signatures for intravenous glucocorticoid response prediction in thyroid eye disease.

BACKGROUND: Radiomics analysis of orbital magnetic resonance imaging (MRI) shows preliminary potential for intravenous glucocorticoid (IVGC) response prediction of thyroid eye disease (TED). The current region of interest segmentation contains only a single organ as extraocular muscles (EOMs). It would be of great value to consider all orbital soft tissues and construct a better prediction model. METHODS: In this retrospective study, we enrolled 127 patients with TED that received 4·5 g IVGC therapy and had complete follow-up examinations. Pre-treatment orbital T2-weighted imaging (T2WI) was acquired for all subjects. Using multi-organ segmentation (MOS) strategy, we contoured the EOMs, lacrimal gland (LG), orbital fat (OF), and optic nerve (ON), respectively. By fused-organ segmentation (FOS), we contoured the aforementioned structures as a cohesive unit. Whole-orbit radiomics (WOR) models consisting of a multi-regional radiomics (MRR) model and a fused-regional radiomics (FRR) model were further constructed using six machine learning (ML) algorithms. RESULTS: The support vector machine (SVM) classifier had the best performance on the MRR model (AUC = 0·961). The MRR model outperformed the single-regional radiomics (SRR) models (highest AUC = 0·766, XGBoost on EOMs, or LR on OF) and conventional semiquantitative imaging model (highest AUC = 0·760, NaiveBayes). The application of different ML algorithms for the comparison between the MRR model and the FRR model (highest AUC = 0·916, LR) led to different conclusions. CONCLUSIONS: The WOR models achieved a satisfactory result in IVGC response prediction of TED. It would be beneficial to include more orbital structures and implement ML algorithms while constructing radiomics models. The selection of separate or overall segmentation of orbital soft tissues has not yet attained its final optimal result.

Diagnosis of dysthyroid optic neuropathy: combined value of orbital MRI and intracranial visual pathway diffusion kurtosis imaging.

OBJECTIVES: To evaluate the combined performance of orbital MRI and intracranial visual pathway diffusion kurtosis imaging (DKI) in diagnosing dysthyroid optic neuropathy (DON). METHODS: We retrospectively enrolled 61 thyroid-associated ophthalmopathy (TAO) patients, including 25 with DON (40 eyes) and 36 without DON (72 eyes). Orbital MRI-based apical muscle index (MI), diameter index (DI) of the optic nerve (ON), area index (AI) of the ON, apparent diffusion coefficient (ADC) and signal intensity ratio (SIR) of the ON, DKI-based kurtosis fractional anisotropy (KFA) and mean kurtosis (MK) of the optic tract (OT), optic radiation (OR), and Brodmann areas (BAs) 17, 18, and 19 were measured and compared between groups. The diagnostic performances of models were evaluated using receiver operating characteristic curve analyses and compared using the DeLong test. RESULTS: TAO patients with DON had significantly higher apical MI, apical AI, and SIR of the ON, but significantly lower ADC of the ON than those without DON (p < 0.05). Meanwhile, the DON group exhibited significantly lower KFA across the OT, OR, BA17, BA18, and BA19 and lower MK at the OT and OR than the non-DON group (p < 0.05). The model integrating orbital MRI and intracranial visual pathway DKI parameters performed the best in diagnosing DON (AUC = 0.926), with optimal diagnostic sensitivity (80%) and specificity (94.4%), followed by orbital MRI combination (AUC = 0.890), and then intracranial visual pathway DKI combination (AUC = 0.832). CONCLUSION: Orbital MRI and intracranial visual pathway DKI can both assist in diagnosing DON. Combining orbital and intracranial imaging parameters could further optimize diagnostic efficiency. CLINICAL RELEVANCE STATEMENT: The novel finding could bring novel insights into the precise diagnosis and treatment of dysthyroid optic neuropathy, accordingly, contributing to the improvement of the patients' prognosis and quality of life in the future. KEY POINTS: • Orbital MRI and intracranial visual pathway diffusion kurtosis imaging can both assist in diagnosing dysthyroid optic neuropathy. • Combining orbital MRI and intracranial visual pathway diffusion kurtosis imaging optimized the diagnostic efficiency of dysthyroid optic neuropathy.

Immune-related visual dysfunction in thyroid eye disease: a combined orbital and brain neuroimaging study.

OBJECTIVES: To investigate the pathological interplay between immunity and the visual processing system (VPS) in thyroid eye disease (TED). METHODS: A total of 24 active patients (AP), 26 inactive patients (IP) of TED, and 27 healthy controls (HCs) were enrolled. Orbital magnetic resonance imaging (MRI) and resting-state functional MRI (rs-fMRI) were conducted for each participant. Multiple MRI parameters of the intraorbital optic nerve (ON) were assessed. The amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) were calculated. Correlation analyses were carried out on the above parameters and clinical characteristics. RESULTS: Visual functioning scores differentiated between the AP and IP groups. The ON subarachnoid space and ON sheath diameter were significantly higher in AP than in IP. Six vision-related brain regions were identified in TED patients compared with HCs, including right calcarine (CAL.R), right cuneus (CUN.R), left postcentral gyrus (PoCG.L), right middle temporal gyrus (MTG.R), left superior frontal gyrus (SFG.L), and left caudate (CAU.L). The brain activity of MTG.R, SFG.L, and CAU.L differentiated between the AP and IP groups. The correlation analysis revealed a close association among the vision-related brain regions, MRI parameters of ON, and clinical characteristics in AP and IP, respectively. CONCLUSIONS: Combined orbital and brain neuroimaging revealed abnormalities of the VPS in TED, which had a close correlation with immune statuses. Vision-related brain regions in TED might be possibly altered by peripheral immunity via a direct or indirect approach. CLINICAL RELEVANCE STATEMENT: The discovery of this study explained the disparity of visual dysfunction in TED patients with different immune statuses. With the uncovered neuroimaging markers, early detection and intervention of visual dysfunction could be achieved and potentially benefit TED patients. KEY POINTS: • Patients with different immune statuses of thyroid eye disease varied in the presentation of visual dysfunction. • The combined orbital and brain neuroimaging study identified six altered vision-related brain regions, which had a significant correlation with the MRI parameters of the intraorbital optic nerve and immunological characteristics. • Peripheral immunity might possibly give rise to alterations in the central nervous system part of the visual processing system via a direct or indirect approach.

Optical coherence tomography angiography in thyroid associated ophthalmopathy: a systematic review.

PURPOSE: To evaluate the evidence for alterations of blood flow, vascular and perfusion densities in the choroid, macula, peripapillary region, and the area surrounding the optic nerve head (ONH) in patients with thyroid-associated ophthalmopathy (TAO) based on changes of OCTA parameters. METHODS: A systematic review of Pubmed, Google Scholar, Scopus, WOS, Cochrane, and Embase databases, including quality assessment of published studies, investigating the alterations of OCTA parameters in TAO patients was conducted. The outcomes of interest comprised changes of perfusion and vascular densities in radial peripapillary capillary (RPC), ONH, superficial and deep retinal layers (SRL and DRL), choriocapillaris (CC) flow, and the extent of the foveal avascular zone (FAZ). RESULTS: From the total of 1253 articles obtained from the databases, the pool of papers was narrowed down to studies published until March 20th, 2024. Lastly, 42 studies were taken into consideration which contained the data regarding the alterations of OCTA parameters including choriocapillary vascular flow, vascular and perfusion densities of retinal microvasculature, SRL, and DRL, changes in macular all grid sessions, changes of foveal, perifoveal and parafoveal densities, macular whole image vessel density (m-wiVD) and FAZ, in addition to alterations of ONH and RPC whole image vessel densities (onh-wiVD and rpc-wiVD) among TAO patients. The correlation of these parameters with visual field-associated parameters, such as Best-corrected visual acuity (BCVA), Visual field mean defect (VF-MD), axial length (AL), P100 amplitude, and latency, was also evaluated among TAO patients. CONCLUSION: The application of OCTA has proven helpful in distinguishing active and inactive TAO patients, as well as differentiation of patients with or without DON, indicating the potential promising role of some OCTA measures for early detection of TAO with high sensitivity and specificity in addition to preventing the irreversible outcomes of TAO. OCTA assessments have also been applied to evaluate the effectiveness of TAO treatment approaches, including systemic corticosteroid therapy and surgical decompression.

Performance of T2 mapping in the staging of Graves' ophthalmopathy based on different region of interest selection methods.

BACKGROUND: Discriminating the stage of Graves' ophthalmopathy (GO) is crucial for clinical decision. Application of conventional T2-weighted imaging in the staging is still limited. PURPOSE: To evaluate the performance of T2 mapping based on two different regions of interest (ROIs) for staging GO. MATERIAL AND METHODS: In total, 56 GO patients were retrospectively enrolled and divided into two groups according to the clinical activity score (CAS). T2 relaxation time (T2RT) of extraocular muscle (EOM) on T2 mapping based on two different ROIs (T2RTROI-1: ROIs were drawn separately in the four EOMs; T2RTROI-2: ROI was drawn in the most inflamed EOM) was measured and compared between active and inactive groups. RESULTS: Both T2RTROI-1 and T2RTROI-2 values in the active GO were significantly higher than those of inactive GO (P <0.001). T2RTROI-1 and T2RTROI-2 values were positively correlated with CAS (rs=0.73, 0.69; P <0.001). When the T2RTROI-1 value of 83.3 ms and T2RTROI-2 value of 106.3 ms were used as cutoff values for staging GO, respectively, the best results were obtained with areas under the curve (AUCs) of 0.822 and 0.827. There was no significant difference for AUCs between T2RTROI-1 and T2RTROI-2 (P = 0.751). Excellent and good inter-observer agreements were achieved in quantitative measurements for T2RTROI-1 and T2RTROI-2 values, respectively, with intraclass correlation coefficients of 0.954 and 0.882. CONCLUSION: The T2RT values derived from two different ROIs were useful for assessment of disease activity. Taking reproducibility and diagnostic performance into consideration, T2RTROI-1 would be an ideal image biomarker for staging GO compared to T2RTROI-2.

Clinical and demographic predictors of buccal fat pad volume in thyroid eye disease.

PURPOSE: To understand how thyroid eye disease (TED) impacts buccal fat pad (BFP) volume. METHODS: In this cohort study, computed tomography (CT) scans and charts of adult patients with and without TED were obtained from an institutional database. The primary outcome was BFP volume in cubic centimeters. Three independent, blinded observers analyzed scans using Horos, a free, open-source medical image viewing software. Bivariate and multivariable analyses were performed. We determined sample size using an effect size based on published reports of the minimum amount of fat excision needed to notice a clinical difference. Equivalence testing against upper and lower bounds set by the same effect size was conducted to assess practical significance of the results. RESULTS: Our sample was sufficient to detect a difference as large as 1.5cc with 95% power. 72 scans were included in our study, 24 TED patients and 48 controls. Mean BFP volume was not statistically different between TED patients and controls (3.96 cc vs 4.06 cc, p = .778). Analysis of covariance adjusting for relevant patient factors (age, sex, and BMI) also failed to find a significant difference between groups. Equivalence testing was significant (p < .001) and revealed the observed difference between groups was less than any clinically meaningful difference. For an effect size of 1.5cc, the data suggests there is a 5% risk of a false negative. CONCLUSIONS: TED was not associated with a significant difference in BFP volume, suggesting that the BFP is spared from TED-related soft-tissue expansion.

Whole-orbit-based multiparametric assessment of disease activity of thyroid eye disease on Dixon MRI.

PURPOSE: This study aimed to explore the diagnostic value of whole-orbit-based multiparametric assessment on Dixon MRI for the evaluation of the thyroid eye disease (TED) activity. METHODS: The retrospective study enrolled patients diagnosed as TED and obtained their axial and coronal Dixon MRI scans. Multiparameters were assessed, including water fraction (WF), fat fraction (FF) of extraocular muscles (EOMs), orbital fat (OF), and lacrimal gland (LG). The thickness of OF and herniation of LG were also measured. Univariable and multivariable logistic regression was applied to construct prediction models based on single or multiple structures. Receiver operating characteristic (ROC) curve analysis was also implemented. RESULTS: Univariable logistic analysis revealed significant differences in water fraction (WF) of the superior rectus (P = 0.018), fat fraction (FF) of the medial rectus (P = 0.029), WF of OF (P = 0.004), and herniation of LG (P = 0.012) between the active and inactive TED phases. Multivariable logistic analysis and corresponding receiver operating characteristic curve (ROC) analysis of each structure attained the area under the curve (AUC) values of 0.774, 0.771, and 0.729 for EOMs, OF, and LG, respectively, while the combination of the four imaging parameters generated a final AUC of 0.909. CONCLUSIONS: Dixon MRI may be used for fine multiparametric assessment of multiple orbital structures. The whole-orbit-based model improves the diagnostic performance of TED activity evaluation.

Teprotumumab for the Treatment of Active Thyroid Eye Disease.

BACKGROUND: Thyroid eye disease is a debilitating, disfiguring, and potentially blinding periocular condition for which no Food and Drug Administration-approved medical therapy is available. Strong evidence has implicated the insulin-like growth factor I receptor (IGF-IR) in the pathogenesis of this disease. METHODS: In a randomized, double-masked, placebo-controlled, phase 3 multicenter trial, we assigned patients with active thyroid eye disease in a 1:1 ratio to receive intravenous infusions of the IGF-IR inhibitor teprotumumab (10 mg per kilogram of body weight for the first infusion and 20 mg per kilogram for subsequent infusions) or placebo once every 3 weeks for 21 weeks; the last trial visit for this analysis was at week 24. The primary outcome was a proptosis response (a reduction in proptosis of ≥2 mm) at week 24. Prespecified secondary outcomes at week 24 were an overall response (a reduction of ≥2 points in the Clinical Activity Score plus a reduction in proptosis of ≥2 mm), a Clinical Activity Score of 0 or 1 (indicating no or minimal inflammation), the mean change in proptosis across trial visits (from baseline through week 24), a diplopia response (a reduction in diplopia of ≥1 grade), and the mean change in overall score on the Graves' ophthalmopathy-specific quality-of-life (GO-QOL) questionnaire across trial visits (from baseline through week 24; a mean change of ≥6 points is considered clinically meaningful). RESULTS: A total of 41 patients were assigned to the teprotumumab group and 42 to the placebo group. At week 24, the percentage of patients with a proptosis response was higher with teprotumumab than with placebo (83% [34 patients] vs. 10% [4 patients], P<0.001), with a number needed to treat of 1.36. All secondary outcomes were significantly better with teprotumumab than with placebo, including overall response (78% of patients [32] vs. 7% [3]), Clinical Activity Score of 0 or 1 (59% [24] vs. 21% [9]), the mean change in proptosis (-2.82 mm vs. -0.54 mm), diplopia response (68% [19 of 28] vs. 29% [8 of 28]), and the mean change in GO-QOL overall score (13.79 points vs. 4.43 points) (P≤0.001 for all). Reductions in extraocular muscle, orbital fat volume, or both were observed in 6 patients in the teprotumumab group who underwent orbital imaging. Most adverse events were mild or moderate in severity; two serious events occurred in the teprotumumab group, of which one (an infusion reaction) led to treatment discontinuation. CONCLUSIONS: Among patients with active thyroid eye disease, teprotumumab resulted in better outcomes with respect to proptosis, Clinical Activity Score, diplopia, and quality of life than placebo; serious adverse events were uncommon. (Funded by Horizon Therapeutics; OPTIC ClinicalTrials.gov number, NCT03298867, and EudraCT number, 2017-002763-18.).

Altered dynamic brain activity and functional connectivity in thyroid-associated ophthalmopathy.

Although previous neuroimaging evidence has confirmed the brain functional disturbances in thyroid-associated ophthalmopathy (TAO), the dynamic characteristics of brain activity and functional connectivity (FC) in TAO were rarely concerned. The present study aims to investigate the alterations of temporal variability of brain activity and FC in TAO using resting-state functional magnetic resonance imaging (rs-fMRI). Forty-seven TAO patients and 30 age-, gender-, education-, and handedness-matched healthy controls (HCs) were enrolled and underwent rs-fMRI scanning. The dynamic amplitude of low-frequency fluctuation (dALFF) was first calculated using a sliding window approach to characterize the temporal variability of brain activity. Based on the dALFF results, seed-based dynamic functional connectivity (dFC) analysis was performed to identify the temporal variability of efficient communication between brain regions in TAO. Additionally, correlations between dALFF and dFC and the clinical indicators were analyzed. Compared with HCs, TAO patients displayed decreased dALFF in the left superior occipital gyrus (SOG) and cuneus (CUN), while showing increased dALFF in the left triangular part of inferior frontal gyrus (IFGtriang), insula (INS), orbital part of inferior frontal gyrus (ORBinf), superior temporal gyrus (STG) and temporal pole of superior temporal gyrus (TPOsup). Furthermore, TAO patients exhibited decreased dFC between the left STG and the right middle occipital gyrus (MOG), as well as decreased dFC between the left TPOsup and the right calcarine fissure and surrounding cortex (CAL) and MOG. Correlation analyses showed that the altered dALFF in the left SOG/CUN was positively related to visual acuity (r = .409, p = .004), as well as the score of QoL for visual functioning (r = .375, p = .009). TAO patients developed abnormal temporal variability of brain activity in areas related to vision, emotion, and cognition, as well as reduced temporal variability of FC associated with vision deficits. These findings provided additional insights into the neurobiological mechanisms of TAO.

Application of Multiparameter Quantitative Magnetic Resonance Imaging in the Evaluation of Graves' Ophthalmopathy.

BACKGROUND: Assessment of the activity of Graves' ophthalmopathy (GO) is difficult. Existing methods need improvement. PURPOSE: Investigate the application of multiparametric magnetic resonance imaging (MRI) in GO. STUDY TYPE: Retrospective. POPULATION: A total of 235 GO patients (age: 38.8 ± 13.4 years; 90 male; 96 active patients). FIELD STRENGTH/SEQUENCE: Short-tau inversion recovery (STIR) fast spin echo, multiecho spin echo T2 mapping and 3D T1-weighted fast field echo sequences at 3.0 T. ASSESSMENT: Two physicians assessed the mean and maximum signal intensity ratio of extraocular muscles to white matter (SIR), T2 relaxation time (T2RT), extraocular muscle area (EMA), fat fraction (FF), retrobulbar fat volume (RFV), and extraocular muscle volume (EMV). Clinical activity score (CAS) â‰§ 3 was in active stage. STATISTICAL TESTS: The optimal cut-off point of diagnostic efficacy was selected using receiver operating characteristic (ROC) curve analysis and evaluated using area under the curve (AUC), compared using Student's t test, analysis of variance or Kruskal-Wallis H test. The correlation used Pearson correlation analysis. The discriminant equation used a binary logistic regression analysis. P < 0.05 was considered statistically significant. RESULTS: The SIRmean, SIRmax, T2RTmean, T2RTmax, EMA, and EMV in active GO patients were significantly higher than those in inactive and were positively correlated with CAS (r = 0.276, 0.228, 0.438, 0.388, 0.502, and 0333, respectively). The FFmax of active patients was significantly lower than that of inactive patients and was negatively correlated with CAS (r = -0.44). Logistic regression analysis indicated that T2RTmean was independently associated with GO active periods and had good diagnostic performance (area under ROC curve = 0.736, sensitivity 70.7%, specificity 69.3%). T2RTmean â‰§ 74.295 could be a diagnostic cut-off for judging GO activity (sensitivity 55.3%). CONCLUSION: SIR, T2RT, EMV, and FF can quantitatively assess the activity and severity of GO and can potentially provide a basis for clinical judgment and selection of treatment options. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 2.

Preliminary Diffusion-Tensor Imaging Evidence for Trans-Synaptic Axonal Degeneration in Dysthyroid Optic Neuropathy Due to Thyroid-Associated Ophthalmopathy.

BACKGROUND: The mechanism driving dysthyroid optic neuropathy (DON) is unclear. Diffusion-tensor imaging (DTI) allows for noninvasively assessing the microstructure of the entire visual pathway and may facilitate a better understanding of the mechanism of DON. PURPOSE: To assess microstructural changes of the whole visual pathway and to investigate the potential mechanism of trans-synaptic damage（TSD） pathogenesis in DON with DTI. STUDY TYPE: Cross-sectional. POPULATION: Sixty-four patients with bilateral thyroid-associated ophthalmopathy (TAO), 30 with and 34 without DON, and 30 age- and sex-matched healthy controls (HCs). FIELD STRENGTH/SEQUENCE: 3 T/DTI (A single-shot diffusion-weighted echo-planar imaging sequence). ASSESSMENT: Differences in DTI parameters including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in each segment (optic nerve, tract, and radiation) of the entire visual pathway among the groups were compared. The parameters of visual evoked potentials (VEPs), visual field tests, and mean retinal nerve fiber layer (mRNFL) thickness on optical coherence tomography were also compared across patients. STATISTICAL TESTS: Student's t-test, chi-square test; ANOVA with post-hoc testing, interclass correlation coefficient, and correlation analysis. Significance level: P < 0.05. RESULTS: TAO patients with DON showed significantly reduced mRNFL thickness and abnormal VEPs. There was a tendency for gradually reduced FA and AD, and increased RD and MD from HCs, with non-DON to with DON in optic nerve and tract, statistically. For radiation, the RD and MD showed statistical increase, the AD and FA just showed numerical decrease (P = 0.119 and 0.059, respectively). For DON, the FA and MD of visual pathway segments showed correlations with abnormal VEPs. DATA CONCLUSION: DTI may be a useful tool for detecting microstructural changes in the entire visual pathway in DON. The changes in RNFL thickness and DTI parameters suggested TSD as a potential pathogenic mechanism of DON. EVIDENCE LEVEL: 4 Technical Efficacy: Stage 5.

Aberrant spontaneous brain activity in patients with thyroid-associated ophthalmopathy with and without optic neuropathy: a resting-state functional MRI study.

OBJECTIVES: To investigate the brain functional alterations in dysthyroid optic neuropathy (DON) by evaluating spontaneous neural activity, using functional magnetic resonance imaging (fMRI) with regional homogeneity (ReHo), and its relationship with ophthalmologic performance. METHODS: Forty-seven patients with thyroid-associated ophthalmopathy (TAO; 20 with DON, 27 with non-DON) and 33 age-, sex-, and education-matched healthy controls (HCs) underwent fMRI. ReHo values were compared using one-way analysis of variance (ANOVA) with post hoc pairwise comparisons (voxel-level p < 0.01, Gaussian random field correction, cluster-level p < 0.05). Correlations between ReHo values and ophthalmological metrics were assessed for DONs, with Bonferroni correction for multiple comparisons (p < 0.004). ROC curves were applied to evaluate the diagnostic performance of ReHo metrics. RESULTS: ReHo values were significantly lower in the left insula and right superior temporal gyrus, and higher in the left posterior cingulate cortex (LPCC), of DON than of non-DON patients. ReHo values were also significantly lower in the right middle temporal, left insula, and left precentral gyrus in DON than in HCs. Meanwhile, ReHo values were higher in LPCC in non-DON than in HCs. ReHo values correlated with ophthalmic examinations to varying degrees in DON. For distinguishing DON, the ReHo values in LPCC showed optimal individually (AUC = 0.843), the combination of the ReHo in both the left insula and LPCC performed better (AUC = 0.915). CONCLUSION: Spontaneous brain activity differed between TAO with and without DON, which may reflect the underlying pathological mechanism of DON. The ReHo index can be considered a diagnostic biomarker. CLINICAL RELEVANCE STATEMENT: Spontaneous brain activity in DON differed from that in TAO without DON, which may reflect the underlying pathological mechanism of DON. The ReHo index can be considered a diagnostic biomarker for early detection of DON. KEY POINTS: • Dysthyroid optic neuropathy (DON) affects brain activity, which contributes in the understanding of its visual dysfunction. • Regional homogeneity values differ between thyroid-associated ophthalmopathy with and without DON in various brain regions. • Regional homogeneity values can be used as a biomarker in the differential diagnosis of DON.

Quantitative assessment of extraocular muscles in Graves' ophthalmopathy using T1 mapping.

OBJECTIVE: To evaluate the performance of T1 mapping in the characterization of extraocular muscles (EOMs) of Graves' ophthalmopathy (GO) patients and investigate its feasibility in assessing the response to glucocorticoid therapy in active GO patients. METHODS: A total of 133 participants (78 active GO, 23 inactive GO, 18 Graves' disease (GD) patients, and 14 healthy volunteers) were consecutively enrolled from July 2018 to December 2020. Native T1 (nT1) and postcontrast T1 (cT1) values of EOMs were measured and compared. The variations in T1 mapping metrics of EOMs were compared pre/post glucocorticoid treatment in 23 follow-up active GO patients. Logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed. RESULTS: The nT1 of EOMs in GO patients was higher than that in GD patients and healthy volunteers. The nT1 of superior rectus (SR) in active GO was higher than that in inactive GO patients, and it could be used as a potential marker of GO activity (OR: 1.003; 95% CI: 1.001, 1.004), with a diagnostic sensitivity of 86.3% and specificity of 43.7%. Meanwhile, the cT1 of SR, inferior rectus (IR), and medial rectus (MR) in inactive GO patients were higher than those in active GO patients. The nT1 of EOMs achieved sufficient diagnostic performance in evaluating the response to glucocorticoid therapy for follow-up active GO patients (AUC, 0.797; sensitivity, 71.9%; specificity, 85.7%). CONCLUSIONS: T1 mapping could quantitatively assess the activity of GO and the response to glucocorticoid therapy in active GO patients and may even potentially reflect the fibrosis of EOMs. CLINICAL RELEVANCE STATEMENT: T1 values can reflect the pathological status of the extraocular muscle. T1 mapping could help to quantitatively assess the clinical activity of GO and the response to glucocorticoid therapy in active GO patients. KEY POINTS: • Graves' ophthalmopathy patients had greater nT1 of extraocular muscles than Graves' disease patients and healthy volunteers, and nT1 of the superior rectus could be a potential marker of Graves' ophthalmopathy activity. • The cT1 of extraocular muscles in inactive Graves' ophthalmopathy patients was higher than that in active Graves' ophthalmopathy patients, and it might be associated with muscle fibrosis. • nT1 of extraocular muscles could offer sufficient diagnostic performance in evaluating the response to glucocorticoid therapy for follow-up active Graves' ophthalmopathy patients.

Extraocular muscle volume index at the orbital apex with optic neuritis: a combined parameter for diagnosis of dysthyroid optic neuropathy.

OBJECTIVES: To evaluate the diagnostic performance of the extraocular muscle volume index at the orbital apex (AMI) and the signal intensity ratio (SIR) of the optic nerve in dysthyroid optic neuropathy (DON). METHODS: Clinical data and magnetic resonance imaging were collected retrospectively from 63 Graves' ophthalmopathy patients, including 24 patients with DON and 39 without DON. The volume of these structures was obtained by reconstructing their orbital fat and extraocular muscles. The SIR of the optic nerve and axial length of eyeball were also measured. The posterior 3/5 of the retrobulbar space volume was used as the orbital apex to compare parameters in patients with or without DON. Area under the receiver operating characteristic curve (AUC) analysis was used to select the morphological and inflammatory parameters with the highest diagnostic value. A logistic regression was performed to identify the risk factors of DON. RESULTS: One hundred twenty-six orbits (35 with DON and 91 without DON) were analyzed. Most of the parameters in DON patients were significantly higher than in non-DON patients. However, the SIR 3 mm behind the eyeball of the optic nerve and AMI had the highest diagnostic value in these parameters and are independent risk factors of DON by stepwise multivariate logistic regression analysis. Combining AMI and SIR had a higher diagnostic value than a single index. CONCLUSIONS: Combining AMI with SIR 3 mm behind the eyeball's orbital nerve can be a potential parameter for diagnosing DON. CLINICAL RELEVANCE STATEMENT: The present study provided a quantitative index based on morphological and signal changes to assess the DON, allowing clinicians and radiologists to monitor DON patients timely. KEY POINTS: The extraocular muscle volume index at the orbital apex (AMI) has excellent diagnostic performance for dysthyroid optic neuropathy. A signal intensity ratio (SIR) of 3 mm behind the eyeball has a higher AUC compared to other slices. Combining AMI and SIR has a higher diagnostic value than a single index.

Magnetic resonance imaging parameters on lacrimal gland in thyroid eye disease: a systematic review and meta-analysis.

BACKGROUND: Thyroid eye disease is an extrathyroidal manifestation of Graves' disease and is associated with dry eye disease. This is the first systematic review and meta-analysis to evaluate the role of magnetic resonance imaging lacrimal gland parameters in thyroid eye disease diagnosis, activity grading, and therapeutic responses prediction. METHODS: Up to 23 August, 2022, 504 studies from PubMed and Cochrane Library were analyzed. After removing duplicates and imposing selection criteria, nine eligible studies were included. Risk of bias assessment was done. Meta-analyses were performed using random-effect model if heterogeneity was significant. Otherwise, fixed-effect model was used. Main outcome measures include seven structural magnetic resonance imaging parameters (lacrimal gland herniation, maximum axial area, maximum coronal area, maximum axial length, maximum coronal length, maximum axial width, maximum coronal width), and three functional magnetic resonance imaging parameters (diffusion tensor imaging-fractional anisotropy, diffusion tensor imaging-apparent diffusion coefficient or mean diffusivity, diffusion-weighted imaging-apparent diffusion coefficient). RESULTS: Thyroid eye disease showed larger maximum axial area, maximum coronal area, maximum axial length, maximum axial width, maximum coronal width, diffusion tensor imaging-apparent diffusion coefficient/ mean diffusivity, and lower diffusion tensor imaging-fractional anisotropy than controls. Active thyroid eye disease showed larger lacrimal gland herniation, maximum coronal area, diffusion-weighted imaging-apparent diffusion coefficient than inactive. Lacrimal gland dimensional (maximum axial area, maximum coronal area, maximum axial length, maximum axial width, maximum coronal width) and functional parameters (diffusion tensor imaging-apparent diffusion coefficient, diffusion tensor imaging-apparent diffusion coefficient) could be used for diagnosing thyroid eye disease; lacrimal gland herniation, maximum coronal area, and diffusion-weighted imaging-apparent diffusion coefficient for differentiating active from inactive thyroid eye disease; diffusion tensor imaging parameters (diffusion tensor imaging-fractional anisotropy, diffusion tensor imaging-mean diffusivity) and lacrimal gland herniation for helping grading and therapeutic responses prediction respectively. CONCLUSIONS: Magnetic resonance imaging lacrimal gland parameters can detect active thyroid eye disease and differentiate thyroid eye disease from controls. Maximum coronal area is the most effective indicator for thyroid eye disease diagnosis and activity grading. There are inconclusive results showing whether structural or functional lacrimal gland parameters have diagnostic superiority. Future studies are warranted to determine the use of magnetic resonance imaging lacrimal gland parameters in thyroid eye disease.

Quantitative assessment of the intraorbital segment of the optic nerve in patients with thyroid orbitopathy using diffusion tensor imaging.

BACKGROUND: It is difficult to detect optic nerve changes in patients with thyroid-associated ophthalmopathy (TAO) before the development of optic neuropathy. PURPOSE: To detect changes in the intraorbital segment of the optic nerve in patients with TAO using diffusion tensor imaging (DTI) and determine any correlations with disease severity. MATERIAL AND METHODS: A total of 74 participants (17 normal, 22 mild, and 35 moderate-severe TAO) were organized to be given 3-T DTI to measure fractional anisotropy (FA) and mean diffusivity (MD) for the orbital segments of their optic nerves. All underwent ophthalmological examinations for visual acuity, intraocular pressure, exophthalmos, and fundoscopy, and were assessed based on the Clinical Activity Score (CAS). Univariate analysis of variance and Pearson's correlation coefficients were carried out. RESULTS: Patients with moderate-to-severe TAO had significantly lower FA values and higher MD values (P < 0.05). FA values were negatively correlated with CAS but had no obvious correlations with the degree of exophthalmos. MD values had no obvious correlations with CAS or the degree of exophthalmos. CONCLUSION: DTI parameters of the intraorbital optic nerves were significantly altered in moderate-to-severe patients before onset of clinical optic nerve dysfunction and may, therefore, be used as an imaging biomarker for assessing the disease.

A novel method of measuring proptosis with computed tomography.

BACKGROUND: Computed tomography (CT) can avoid interference factors and has been imported into some software to measure proptosis clinically as the golden standard. PURPOSE: To establish a new method for semi-automatically measuring the proptosis on CT and evaluate its accuracy and reproducibility. MATERIAL AND METHODS: A total of 50 orbital CT images were collected of healthy individuals, 25 patients with Graves ophthalmopathy (GO), and 25 patients with orbital fracture (OF). A new image processing software, MedrawHDC, was developed to semi-automatically measure the proptosis (MedrawHDC method). The classic radiological (CR) method (measuring proptosis with the software called Mimics) and MedrawHDC method were applied in all three groups (measured by observer S). Hertel's exophthalmometer (HE) method was also applied in the GO group. Moreover, two other observers were asked to measure the proptosis using MedrawHDC, to evaluate its reproducibility. RESULTS: The MedrawHDC method was highly consistent with the CR method in measuring proptosis (normal group: intraclass correlation coefficient [ICC] = 0.989; GO group: ICC = 0.979; OF group: ICC = 0.979). In the GO group, the value of proptosis measured by two radiological methods were consistent with that measured by the HE method (CR method: ICC = 0.703; MedrawHDC method: ICC = 0.697). Bland-Altman plots showed similar results. The measurements obtained by three observers were highly reproducible (ICC = 0.995). CONCLUSION: The newly established MedrawHDC method, with high accessibility, convenience, and repeatability, is reliable in assessing proptosis. It shows high potential for wide application, having clinical value for scientific evaluation of proptosis.

Differential effects of teprotumumab treatment based on fat-to-muscle ratio in patients with thyroid eye disease.

PURPOSE: To characterize the distribution of fat-to-muscle ratio (FMR) across patients with thyroid eye disease (TED) and to assess the association between FMR and therapeutic response to teprotumumab. METHODS: A retrospective cohort study of patients completing a full course of teprotumumab for TED between January 2020 and March 2022 at a single tertiary referral center. Patients without baseline orbital imaging were excluded. Quantitative analysis of FMR was performed by manual segmentation of patients' imaging using OsiriX software. The primary outcome measure was change in clinical measurement of proptosis. Linear regression modelled change in proptosis against FMR. Statistical significance was set at p < .05. RESULTS: Twenty-two patients (3 M:19F) were included with a mean age of 49.4 ± 15.5 years. The FMR ranged from 1.11 to 6.54, mean 3.15 ± 1.30. The data did not deviate from a normal distribution (Shapiro-Wilk test for normality, p = .18). Pre- and post-treatment average proptosis measurements were 21.72 ± 3.56 mm and 18.81 ± 3.07 mm, respectively. Univariable linear regression demonstrated a 0.78 ± 0.36 mm greater reduction in proptosis for every 1 unit decrease in FMR (p = .038). CONCLUSIONS: Contrary to the traditional dichotomous characterization of TED into type 1 and type 2 phenotypes, orbital FMR may represent a continuum of disease manifestation, more closely following a normal rather than bimodal distribution. Furthermore, pre-treatment FMR is associated with response to teprotumumab; those with lower FMR experiencing a greater reduction in proptosis. This has implications for patient selection and counselling regarding the expected treatment outcome.

Lateral orbital wall anomaly in a patient with thyroid eye disease.

An isolated defect in the lateral orbital wall is an uncommon occurrence, although cases of orbital floor, roof, and medial wall spontaneous dehiscence have been described in the literature. Here, we describe a lateral orbital wall defect in a patient with thyroid eye disease - which may be related to bony remodeling or may represent a rare congenital anomaly. Computed tomography (CT) prior to decompression surgery revealed a defect in the left lateral orbital wall. At the time of orbital decompression, prolapse of buccal fat into the orbit was noted once the subperiosteal plane was entered along the lateral orbital wall in the area of this bony defect. Literature review revealed only a few previous reports of lateral wall abnormalities, including two involving the inferior orbital fissure; one other case was associated with Down syndrome, and other reports consist of sphenoid hypoplasia associated with neurofibromatosis.

T2 -Weighted MR Imaging-Derived Radiomics for Pretreatment Determination of Therapeutic Response to Glucocorticoid in Patients With Thyroid-Associated Ophthalmopathy: Comparison With Semiquantitative Evaluation.

BACKGROUND: MR imaging has been applied to determine therapeutic response to glucocorticoid (GC) before treatment in thyroid-associated ophthalmopathy (TAO), while the performance was still poor. PURPOSE: To investigate the value of T2 -weighted imaging (T2 WI)-derived radiomics for pretreatment determination of therapeutic response to GC in TAO patients, and compare its diagnostic performance with that of semiquantitative parameters. STUDY TYPE: Retrospective. POPULATION: A total of 110 patients (49 ± 12 years; male/female, n = 48/62; responsive/unresponsive, n = 62/48), divided into training (n = 78) and validation (n = 32) cohorts. FIELD STRENGTH/SEQUENCE: 3.0 T, T2 -weighted fast spin echo. ASSESSMENT: W.C. and H.H. (6 and 10 years of experience, respectively) performed the measurements. Maximum, mean, and minimum signal intensity ratios (SIRs) of extraocular muscle (EOM) bellies were collected to construct a semiquantitative imaging model. Radiomics features from volumes of interest covering EOM bellies were extracted and three machine learning-based (logistic regression [LR]; decision tree [DT]; support vector machine [SVM]) models were built. STATISTICAL TESTS: The diagnostic performances of models were evaluated using receiver operating characteristic curve analyses, and compared using DeLong test. Two-sided P < 0.05 was considered statistically significant. RESULTS: The responsive group showed higher minimum signal intensity ratio (SIRmin ) of EOMs than the unresponsive group (training: 1.46 ± 0.34 vs. 1.18 ± 0.39; validation: 1.44 ± 0.33 vs. 1.19 ± 0.20). In both cohorts, LR-based radiomics model demonstrated good diagnostic performance (area under the curve [AUC] = 0.968, 0.916), followed by DT-based (AUC = 0.933, 0.857) and SVM-based models (AUC = 0.919, 0.855). All three radiomics models outperformed semiquantitative imaging model (SIRmin : AUC = 0.805) in training cohort. In validation cohort, only LR-based radiomics model outperformed that of SIRmin (AUC = 0.745). The nomogram integrating LR-based radiomics signature and disease duration further elevated the diagnostic performance in validation cohort (AUC: 0.952 vs. 0.916, P = 0.063). DATA CONCLUSION: T2 WI-derived radiomics of EOMs, together with disease duration, provides a promising noninvasive approach for determining therapeutic response before GC administration in TAO patients. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 4.