A signature of structural MRI features at 3 Tesla allows an accurate characterization of orbital cavernous venous malformation.

OBJECTIVES: To differentiate OCVM from other orbital lesions using structural MRI. METHODS: This IRB-approved a historical-prospective cohort single-center analysis of a prospective cohort that included consecutive adult patients presenting with an orbital lesion undergoing a 3T MRI before surgery from December 2015 to May 2021. Two readers blinded to all data read all MRIs assessing structural MRI characteristics. A univariate analysis followed by a stepwise multivariate analysis identified structural MRI features showing the highest sensitivity and specificity when diagnosing OCVM. RESULTS: One hundred ninety-one patients with 30/191 (16%) OCVM and 161/191 (84%) other orbital lesions were included. OCVM were significantly more likely to present with a higher signal intensity than that of the cortex on T2WI: 26/29 (89.7%) versus 28/160 (17.5%), p < 0.001, or with a chemical shift artifact (CSA): 26/29 (89.7%) versus 16/155 (10.3%), p < 0.001, or to present with a single starting point of enhancement, as compared to other orbital lesions: 18/29 (62.1%) versus 4/159 (2.5%), p = 0.001. The step-wise analysis identified 2 signatures increasing performances. Signature 1 combined a higher signal intensity than that of the cortex on T2WI and a CSA. Signature 2 included these two features and the presence of a single starting point of enhancement. Sensitivity, specificity, and accuracy were 0.83, 0.94, and 0.92 for signature 1 and 0.97, 0.93, and 0.93 for signature 2, respectively. CONCLUSION: Structural MRI yields high sensitivity and specificity when diagnosing OCVM. KEY POINTS: • Structural MRI shows high sensitivity and specificity when diagnosing orbital cavernous venous malformation. • We identified two signatures combining structural MRI features which might be used easily in routine clinical practice. • The combination of higher signal intensity of the lesion as compared to the cortex on T2WI and of a chemical shift artifact yields a sensitivity and specificity of 0.83 and 0.94 for the diagnosis of orbital cavernous venous malformation, respectively.

Intravoxel incoherent motion (IVIM) 3 T MRI for orbital lesion characterization.

OBJECTIVES: To determine the diagnostic accuracy of MRI intravoxel incoherent motion (IVIM) when characterizing orbital lesions, which is challenging due to a wide range of locations and histologic types. METHODS: This IRB-approved prospective single-center study enrolled participants presenting with an orbital lesion undergoing a 3-T MRI prior to surgery from December 2015 to July 2019. An IVIM sequence with 15 b values ranging from 0 to 2000 s/mm2 was performed. Two neuroradiologists, blinded to clinical data, individually analyzed morphological MRIs. They drew one region of interest inside each orbital lesion, providing apparent diffusion coefficient (ADC), true diffusion coefficient (D), perfusion fraction (f), and pseudodiffusion coefficient (D*) values. T test, Mann-Whitney U test, and receiver operating characteristic curve analyses were performed to discriminate between orbital lesions and to determine the diagnostic accuracy of the IVIM parameters. RESULTS: One hundred fifty-six participants (84 women and 72 men, mean age 54.4 ± 17.5 years) with 167 orbital lesions (98/167 [59%] benign lesions including 54 orbital inflammations and 69/167 [41%] malignant lesions including 32 lymphomas) were included in the study. ADC and D were significantly lower in malignant than in benign lesions: 0.8 × 10-3 mm2/s [0.45] versus 1.04 × 10-3 mm2/s [0.33], p < 0.001, and 0.75 × 10-3 mm2/s [0.40] versus 0.98 × 10-3 mm2/s [0.42], p < 0.001, respectively. D* was significantly higher in malignant lesions than in benign ones: 12.8 × 10-3 mm2/s [20.17] versus 7.52 × 10-3 mm2/s [7.57], p = 0.005. Area under curve was of 0.73, 0.74, 0.72, and 0.81 for ADC, D, D*, and a combination of D, f, and D*, respectively. CONCLUSIONS: Our study showed that IVIM might help better characterize orbital lesions. KEY POINTS: • Intravoxel incoherent motion (IVIM) helps clinicians to assess patients with orbital lesions. • Intravoxel incoherent motion (IVIM) helps clinicians to characterize orbital lymphoma versus orbital inflammation. • Management of patients becomes more appropriate.

Quality-based pharmacokinetic model selection on DCE-MRI for characterizing orbital lesions.

BACKGROUND: Although several studies have evaluated dynamic contrast-enhanced (DCE) MRI in the orbit, showing its utility when detecting and diagnosing orbital lesions, none have evaluated the pharmacokinetic models. PURPOSE: To provide a quality-based pharmacokinetic model selection for characterizing orbital lesions using DCE-MRI at 3.0T. STUDY TYPE: Prospective. POPULATION: From December 2015 to April 2017, 151 patients with an orbital lesion underwent MRI prior to surgery, including a high temporal resolution DCE sequence, divided into one training and one test dataset with 100 and 51 patients, respectively. FIELD STRENGTH/SEQUENCE: 3T/DCE. ASSESSMENT: Six different pharmacokinetic models were tested. STATISTICAL TESTS: Univariate and multivariate analyses were performed using Wilcoxon-2-sample tests and a logistic regression to compare parameters between malignant and benign tumors for each pharmacokinetic model for the whole cohort. Receiver operating characteristic (ROC) curve analyses were performed on the training dataset to determine area under curve (AUC) and optimal cutoff values for each pharmacokinetic model, then validated on the test dataset to calculate sensitivity, specificity, and accuracy. RESULTS: Regardless of the model, tissue blood flow and tissue blood volume values were significantly higher in malignant vs. benign lesions: 103.8-195.1 vs. 65-113.8, P [<10-4 -2.10-4 ] and 21.3-36.9 vs. 15.6-33.6, P [<10-4 -0.03] respectively. Extracellular volume fraction and permeability-surface area product or transfer constant appeared to be less relevant: 17.3-27.5 vs. 22.8-28.2, P [0.01-0.7], 1.7-4.9, P [0.2-0.9] and 9.5-38.8 vs. 8.1-22.8, P [<10-4 -0.6], respectively. ROC curves showed no significant differences in AUC between the different models. The two-compartment exchange (2CX) model ranked first for quality. DATA CONCLUSION: DCE MRI pharmacokinetic model-derived parameters appeared to be useful for discriminating benign from malignant orbital lesions. The 2CX model provided the best quality of modeling and should be recommended. Perfusion-related DCE parameters appeared to be significantly more relevant to the diagnostic process. Level of Evidence 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1514-1525.

Repeatability of apparent diffusion coefficient and intravoxel incoherent motion parameters at 3.0 Tesla in orbital lesions.

OBJECTIVES: To evaluate repeatability of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) parameters in the orbit. METHODS: From December 2015 to March 2016, 22 patients were scanned twice using an IVIM sequence with 15b values (0-2,000 s/mm2) at 3.0T. Two readers independently delineated regions of interest in an orbital mass and in different intra-orbital and extra-orbital structures. Short-term test-retest repeatability and inter-observer agreement were assessed using the intra-class correlation coefficient (ICC), the coefficient of variation (CV) and Bland-Altman limits of agreements (BA-LA). RESULTS: Test-retest repeatability of IVIM parameters in the orbital mass was satisfactory for ADC and D (mean CV 12% and 14%, ICC 95% and 93%), poor for f and D*(means CV 43% and 110%, ICC 90% and 65%). Inter-observer repeatability agreement was almost perfect in the orbital mass for all the IVIM parameters (ICC = 95%, 93%, 94% and 90% for ADC, D, f and D*, respectively). CONCLUSIONS: IVIM appeared to be a robust tool to measure D in orbital lesions with good repeatability, but this approach showed a poor repeatability of f and D*. KEY POINTS: • IVIM technique is feasible in the orbit. • IVIM has a good-acceptable repeatability of D (CV range 12-25 %). • IVIM interobserver repeatability agreement is excellent (ICC range 90-95 %). • f or D* provide higher test-retest and interobserver variabilities.

Diagnostic Performance of Dynamic Contrast-Enhanced 3T MR Imaging for Characterization of Orbital Lesions: Validation in a Large Prospective Study.

BACKGROUND AND PURPOSE: Orbital lesions are rare but serious. Their characterization remains challenging. Diagnosis is based on biopsy or surgery, which implies functional risks. It is necessary to develop noninvasive diagnostic tools. The goal of this study was to evaluate the diagnostic performance of dynamic contrast-enhanced MR imaging at 3T when distinguishing malignant from benign orbital tumors on a large prospective cohort. MATERIALS AND METHODS: This institutional review board-approved prospective single-center study enrolled participants presenting with an orbital lesion undergoing a 3T MR imaging before surgery from December 2015 to May 2021. Morphologic, diffusion-weighted, and dynamic contrast-enhanced MR images were assessed by 2 readers blinded to all data. Univariable and multivariable analyses were performed. To assess diagnostic performance, we used the following metrics: area under the curve, sensitivity, and specificity. Histologic analysis, obtained through biopsy or surgery, served as the criterion standard for determining the benign or malignant status of the tumor. RESULTS: One hundred thirty-one subjects (66/131 [50%] women and 65/131 [50%] men; mean age, 52 [SD, 17.1] years; range, 19-88 years) were enrolled. Ninety of 131 (69%) had a benign lesion, and 41/131 (31%) had a malignant lesion. Univariable analysis showed a higher median of transfer constant from blood plasma to the interstitial environment (K trans) and of transfer constant from the interstitial environment to the blood plasma (minute-1) (Kep) and a higher interquartile range of K trans in malignant-versus-benign lesions (1.1 minute-1 versus 0.65 minute-1, P = .03; 2.1 minute-1 versus 1.1 minute-1, P = .01; 0.81 minute-1 versus 0.65 minute-1, P = .009, respectively). The best-performing multivariable model in distinguishing malignant-versus-benign lesions included parameters from dynamic contrast-enhanced imaging, ADC, and morphology and reached an area under the curve of 0.81 (95% CI, 0.67-0.96), a sensitivity of 0.82 (95% CI, 0.55-1), and a specificity of 0.81 (95% CI, 0.65-0.96). CONCLUSIONS: Dynamic contrast-enhanced MR imaging at 3T appears valuable when characterizing orbital lesions and provides complementary information to morphologic imaging and DWI.

A Magnetic Resonance Imaging Radiomics Signature to Distinguish Benign From Malignant Orbital Lesions.

OBJECTIVES: Distinguishing benign from malignant orbital lesions remains challenging both clinically and with imaging, leading to risky biopsies. The objective was to differentiate benign from malignant orbital lesions using radiomics on 3 T magnetic resonance imaging (MRI) examinations. MATERIALS AND METHODS: This institutional review board-approved prospective single-center study enrolled consecutive patients presenting with an orbital lesion undergoing a 3 T MRI prior to surgery from December 2015 to July 2019. Radiomics features were extracted from 6 MRI sequences (T1-weighted images [WIs], DIXON-T2-WI, diffusion-WI, postcontrast DIXON-T1-WI) using the Pyradiomics software. Features were selected based on their intraobserver and interobserver reproducibility, nonredundancy, and with a sequential step forward feature selection method. Selected features were used to train and optimize a Random Forest algorithm on the training set (75%) with 5-fold cross-validation. Performance metrics were computed on a held-out test set (25%) with bootstrap 95% confidence intervals (95% CIs). Five residents, 4 general radiologists, and 3 expert neuroradiologists were evaluated on their ability to visually distinguish benign from malignant lesions on the test set. Performance comparisons between reader groups and the model were performed using McNemar test. The impact of clinical and categorizable imaging data on algorithm performance was also assessed. RESULTS: A total of 200 patients (116 [58%] women and 84 [42%] men; mean age, 53.0 ± 17.9 years) with 126 of 200 (63%) benign and 74 of 200 (37%) malignant orbital lesions were included in the study. A total of 606 radiomics features were extracted. The best performing model on the training set was composed of 8 features including apparent diffusion coefficient mean value, maximum diameter on T1-WIs, and texture features. Area under the receiver operating characteristic curve, accuracy, sensitivity, and specificity on the test set were respectively 0.869 (95% CI, 0.834-0.898), 0.840 (95% CI, 0.806-0.874), 0.684 (95% CI, 0.615-0.751), and 0.935 (95% CI, 0.905-0.961). The radiomics model outperformed all reader groups, including expert neuroradiologists (P < 0.01). Adding clinical and categorizable imaging data did not significantly impact the algorithm performance (P = 0.49). CONCLUSIONS: An MRI radiomics signature is helpful in differentiating benign from malignant orbital lesions and may outperform expert radiologists.

Discriminating between IgG4-related orbital disease and other causes of orbital inflammation with intra voxel incoherent motion (IVIM) MR imaging at 3T.

PURPOSE: The purpose of this prospective study was to determine the capabilities of intravoxel incoherent motion (IVIM) MRI at 3 Tesla in discriminating between IgG4-related orbital disease (IgG4-ROD) and other causes of orbital inflammation. MATERIALS AND METHODS: Main selection criteria for the patients enrolled in this prospective study were age over 18 years and histopathologicaly proven orbital inflammatory lesion. MRI examinations were performed prior to surgery and treatment in all patients with suspected orbital inflammation. Two neuroradiologists, blinded to clinical data, independently analyzed structural MRI examinations and IVIM sequences obtained with 15 b values ranging from 0 to 2000 s/mm². Apparent diffusion coefficient (ADC), "true" diffusion coefficient (D), perfusion fraction (f) and pseudodiffusion coefficient (D*) values were calculated from all orbital lesions. Diagnostic capabilities of IVIM parameters were assessed using receiver operating-characteristic (ROC) curves and area under the curve (AUC). Sensitivity, specificity, and accuracy of IVIM parameters were calculated for the best threshold values and reported with their corresponding 95% confidence intervals (CI). RESULTS: Thirty-five patients (21 women and 14 men; mean age, 49.2 ± 13.75 [SD] years; age range: 23-77 years) with 48 orbital lesions were enrolled in the study. Fifteen patients (15/35; 43%) had IgG4-ROD and 20 (20/35; 57%) had other causes of orbital inflammation. Median D value was significantly greater in patients with IgG4-ROD (1 × 10-3 mm2/s; interquartile range [IQR]: 0.9 × 10-3; 1.2 × 10-3) as compared to patients with non IgG4-ROD (0.80 × 10-3 mm2/s; IQR: 0.7 × 10-3; 1 × 10-3) (P = 0.04). There was no significant difference for ADC, f or D*. Area under the curve were of 0.54, 0.73, 0.63 and 0.56 for ADC, D, f and D*, respectively. Optimal threshold derived from ROC curves for D was 0.87 × 10-3 mm2/s, yielding 92% sensitivity (95% CI: 62-100%) and 71% specificity (95% CI: 44-90%) for the diagnosis of IgG4-ROD. No differences in standard morphological MRI criteria were found between IgG4-ROD and non IgG4-ROD. CONCLUSION: Our study shows that IVIM MRI is a useful imaging technique to distinguish IgG4-ROD from other causes of orbital inflammation.

IgG4-related disease in patients with idiopathic orbital inflammation syndrome: data from the French SIOI prospective cohort.

PURPOSE: To better characterize IgG4-related disease (RD) in the setting of idiopathic orbital inflammation syndrome (IOIS). METHODS: National, multicentre, prospective, observational cohort study. Among the patients consecutively included in the French multicentre SIOI cohort, we selected those who underwent orbital and/or adnexal biopsy. Clinical, morphological and pathological findings at diagnosis were blindly analysed. Serum IgG4 levels at inclusion were measured and all available biopsy specimens were immunostained for IgG4 and IgG. Biopsy samples with more than 10 IgG4-positive plasma cells per high-power field and a IgG4+/IgG+ plasma cell ratio above 40% were scored as positive. IgG4-positive patients were then screened for comprehensive diagnostic criteria for IgG4-RD. RESULTS: Of the 87 patients included, 35 had histologically documented IOIS. Thirteen patients (37%) with a mean age at onset of 27 years (range 21-78) had IgG4-positive biopsies, among which 10 patients (77%) and 3 (23%, with IgG4 serum levels >1.35 g/L) were considered as having probable and definite IgG4-RD, respectively. The latter 13 patients more frequently fulfilled histological criteria for IgG4-RD (including plasmacytic infiltrate (p = 0.006), fibrosis (p = 0.0025) and periphlebitis (p = 0.075)) than IgG4-negative patients. Storiform fibrosis was exclusively found in orbital tissues from IgG4-positive patients (n = 3, 23%). Eosinophilia associated with recurrent sinusitis or asthma was a prominent feature in patients with definite IgG4-RD. CONCLUSIONS: More than one-third of patients with biopsy-proven IOIS satisfied criteria for IgG4-RD, but only a few had a definite type.

Small Choroidal Melanoma Revealed by a Large Extrascleral Extension.

AIMS: Orbital extraocular extension of choroidal melanoma is very rare with small melanomas. We report the case of a patient whose small choroidal melanoma was initially overlooked and was revealed by a large extrascleral extension. METHODS: A 48-year-old Caucasian woman presented with sudden total visual loss in the right eye. Multicolor imaging of the fundus showed right optic disc edema and an orange and green lesion near the optic disc. The diagnosis of unilateral optic neuritis was made. Magnetic resonance imaging showed an extraocular mass adjacent to the optic nerve; on ultrasound, this mass was acoustically hollow and a small intraocular component was visible. RESULTS: Choroidal melanoma with a large extrascleral extension was diagnosed (T4eN0M0, stage IIIC according to the AJCC 7th TNM classification, 2010). The size of the extraocular nodule was 13 × 5 mm. Treatment consisted of enucleation followed by adjuvant external beam orbital radiotherapy. Tumor analysis showed a mixed cell type melanoma with monosomy 3. The patient developed liver metastasis 10 months after local treatment. CONCLUSION: Extraocular extension of choroidal melanoma can occur with small lesions. Prognosis is generally poor according to AJCC TNM. This case is a reminder that fundus examination may reveal the nature of the mass in some patients with orbital tumors.

Successful use of infliximab therapy in sight-threatening corticosteroid-resistant Vogt-Koyanagi-Harada disease.

PURPOSE: To report an experience with infliximab in severe corticosteroid-resistant Vogt-Koyanagi-Harada (VKH) disease. DESIGN: Interventional case series. METHODS: The medical records of 2 adult patients were reviewed. RESULTS: Both patients had a visual acuity reduced to hand motion perception bilaterally after 1 month of high-dose corticosteroid therapy, due to multiple exudative retinal detachment involving the fovea. Visual acuity and OCT findings improved immediately after the first infliximab infusion, retinal detachments fully resolved after 1 month and visual acuity returned to normal within 6 months. Despite a negative pretreatment screening, one patient developed multivisceral tuberculosis, which led to infliximab discontinuation after the 7th infusion and was cured by a 9-month ambulatory antibiotic regimen. The other patient received 11 well-tolerated infliximab infusions. Respectively, 9 and 4 months after infliximab discontinuation both patients had normal vision and OCT findings. CONCLUSION: Infliximab showed tremendous therapeutic efficacy in sight-threatening corticosteroid-resistant VKH disease.

Angiographic and optical coherence tomography characteristics of recent myopic choroidal neovascularization.

PURPOSE: To analyze the contribution of fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD OCT) to the diagnosis of recent choroidal neovascularization (CNV) associated with high myopia. DESIGN: Retrospective, observational case series. METHODS: Ninety eyes of 73 highly myopic patients (refractive error ≥-6 diopters) with CNV in 1 or both eyes were included. Epidemiologic features, refractive error, fundus examination, fluorescein angiography, and SD OCT findings at onset of CNV were analyzed. RESULTS: Mean age at onset of CNV was 54.4 ± 14 years. CNV was bilateral in 17 of 73 cases. Mean refractive error was -13.9 ± 5.2 diopters. Myopic CNV was associated more frequently with patchy or geographic atrophy (P = .019). CNV was associated with exudative features on fluorescein angiography in 82% of cases (64/78), and on SD OCT in 48.6% of cases (36/74). There was no agreement about signs of active CNV between these 2 imaging methods (κ = 25.7 ± 10%; P = .0044). CNV area was significantly smaller in younger patients (<55 years) than in older patients (0.57 mm(2) vs 1.21 mm(2), respectively; P = .023). CONCLUSIONS: Exudative features of myopic CNV are more obvious on FA than on SD OCT, suggesting that fluorescein angiography should be performed when new-onset myopic CNV is suspected. Myopic CNV occurring in older patients (≥55 years) is larger than those seen in younger patients and resembles CNV associated with age-related macular degeneration. This suggests an overlap between myopic CNV in older patients and age-related macular degeneration.