MR-based follow-up after brachytherapy and proton beam therapy in uveal melanoma.

PURPOSE: MRI is increasingly used in the diagnosis and therapy planning of uveal melanoma (UM). In this prospective cohort study, we assessed the radiological characteristics, in terms of anatomical and functional imaging, of UM after ruthenium-106 plaque brachytherapy or proton beam therapy (PBT) and compared them to conventional ultrasound. METHODS: Twenty-six UM patients were evaluated before and 3, 6 and 12 months after brachytherapy (n = 13) or PBT (n = 13). Tumour prominences were compared between ultrasound and MRI. On diffusion-weighted imaging, the apparent diffusion value (ADC), and on perfusion-weighted imaging (PWI), the time-intensity curves (TIC), relative peak intensity and outflow percentages were determined. Values were compared between treatments and with baseline. RESULTS: Pre-treatment prominences were comparable between MRI and ultrasound (mean absolute difference 0.51 mm, p = 0.46), but larger differences were observed post-treatment (e.g. 3 months: 0.9 mm (p = 0.02)). Pre-treatment PWI metrics were comparable between treatment groups. After treatment, brachytherapy patients showed favourable changes on PWI (e.g. 67% outflow reduction at 3 months, p < 0.01). After PBT, significant perfusion changes were observed at a later timepoint (e.g. 38% outflow reduction at 6 months, p = 0.01). No consistent ADC changes were observed after either treatment, e.g. a 0.11 × 10-3mm2/s increase 12 months after treatment (p = 0.15). CONCLUSION: MR-based follow-up is valuable for PBT-treated patients as favourable perfusion changes, including a reduction in outflow, can be detected before a reduction in size is apparent on ultrasound. For brachytherapy, a follow-up MRI is of less value as already 3 months post-treatment a significant size reduction can be measured on ultrasound.

A Comparison of 3 T and 7 T MRI for the Clinical Evaluation of Uveal Melanoma.

BACKGROUND: Magnetic resonance imaging (MRI) is increasingly being used in the diagnosis and treatment planning of uveal melanoma (UM), the most common primary intraocular tumor. Initially, 7 T MRI was primarily used, but more recently these techniques have been translated to 3 T, as it is more commonly available. PURPOSE: Compare the diagnostic performance of 3 T and 7 T MRI of UM. STUDY TYPE: Prospective. POPULATION: Twenty-seven UM patients (19% female). FIELD STRENGTH/SEQUENCE: 3 T: T1- and T2-weighted three-dimensional (3D) spin echo (SE) and multi-slice (MS) SE, 7 T: T1-weighted 3D gradient echo (GE), T2-weighted 3D SE and MS SE, 3 T and 7 T GE dynamic contrast-enhanced. T1 weighted images: acquired before and after Gadolinium (Gd) administration. ASSESSMENT: For all sequences, scan and diagnostic quality was quantified using a 5-point Likert scale. Signal intensities on T1 and T2 relative to choroid and eye muscle respectively were assessed as well as the tumor prominence. Finally, the perfusion time-intensity curves (TICs) were classified as plateau, progressive, or wash-out. STATISTICAL TESTS: Image quality scores were compared between both field strengths using Wilcoxon signed-rank and McNemar tests. Paired t-tests and Bland-Altman were used for comparing tumor prominences. P < 0.05 was considered statistically significant. RESULTS: Image quality was comparable between 3 T and 7 T, for 3DT1, 3DT2, 3DT1Gd (P = 0.86; P = 0.34; P = 0.78, respectively) and measuring tumor dimensions (P = 0.40). 2DT1 and 2DT2 image quality were rated better on 3 T compared to 7 T. Most UM had the same relative signal intensities at 3 T and 7 T on T1 (17/21) and T2 (13/17), and 16/18 diagnostic TICs received the same classification. Tumor prominence measurements were similar between field strengths (95% confidence interval: -0.37 mm to 0.03 mm, P = 0.097). DATA CONCLUSION: Diagnostic performance of the evaluated 3 T protocol proved to be as capable as 7 T, with the addition of 3 T being superior in assessing tumor growth into nearby anatomical structures compared to 7 T. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

MR imaging characteristics of uveal melanoma with histopathological validation.

PURPOSE: To evaluate the magnetic resonance imaging (MRI) characteristics of uveal melanoma (UM), to compare them with fundoscopy and ultrasound (US), and to validate them with histopathology. METHODS: MR images from 42 UM were compared with US and fundoscopy, and on 14 enucleated cases with histopathology. RESULTS: A significant relationship between the signal intensity on T1 and pigmentation on histopathology was found (p=0.024). T1 hyperintense UM were always moderately or strongly pigmented on histopathology, while T1-hypointense UM were either pigmented or non-pigmented. Mean apparent diffusion coefficient (ADC) of the UM was 1.16 ± 0.26 × 10-3 mm2/s. Two-thirds of the UM had a wash-out and the remaining a plateau perfusion time-intensity curve (TIC). MRI was limited in evaluating the basal diameter of flat tumors. US tends to show larger tumor prominence (0.5mm larger, p=0.008) and largest basal diameter (1.4mm larger, p<0.001). MRI was good in diagnosing ciliary body involvement, extrascleral extension, and optic nerve invasion, but limited on identifying scleral invasion. An increase of tumor prominence was associated with lower ADC values (p=0.030) and favored a wash-out TIC (p=0.028). An increase of tumor ADC correlated with a plateau TIC (p=0.011). CONCLUSIONS: The anatomical and functional MRI characteristics of UM were comprehensively assessed. Knowing the MRI characteristics of UM is important in order to confirm the diagnosis and to differentiate UM from other intra-ocular lesions and because it has implications for treatment planning. MRI is a good technique to evaluate UM, being only limited in case of flat tumors or on identifying scleral invasion.

Eye-specific quantitative dynamic contrast-enhanced MRI analysis for patients with intraocular masses.

OBJECTIVE: Dynamic contrast enhanced (DCE)-MRI is currently not generally used for intraocular masses as lesions are small, have an inhomogeneous T1 and the eye is prone to motion. The aim of this paper is to address these eye-specific challenges, enabling accurate ocular DCE-MRI. MATERIALS & METHODS: DCE-MRI of 19 uveal melanoma (UM) patients was acquired using a fat-suppressed 3D spoiled gradient echo sequence with TWIST (time-resolved angiography with stochastic trajectories sequence). The analysis consisted of a two-step registration method to correct for both head and eye motion. A T1 map was calculated to convert signal intensities to concentrations. Subsequently, the Tofts model was fitted voxel wise to obtain Ktrans and ve. RESULTS: Registration significantly improved the concentration curve quality (p < 0.001). The T1 of melanotic lesions was significantly lower than amelanotic lesions (888 ms vs 1350 ms, p = 0.03). The average achieved B1+ in the lesions was 91%. The average Ktrans was 0.46 min-1 (range 0.13-1.0) and the average ve was 0.22 (range 0.10-0.51). CONCLUSION: Using this eye-specific analysis, DCE of intraocular masses is possible which might aid in the diagnosis, prognosis and follow-up of UM.

CT and MR imaging of orbital inflammation.

PURPOSE: Orbital inflammation can be idiopathic or in the context of a specific disease and it can involve different anatomical orbital structures. On imaging, inflammatory disease is frequently mistaken for infection and malignant tumors, and its underlying cause is often not determined. Through this article we aim to improve orbital inflammation diagnosis and underlying inflammatory diseases recognition. METHODS: The imaging protocols and characteristics of orbital inflammation were reviewed. RESULTS: A decision tree for the evaluation of these patients is provided. First, a combination of clinical and radiological clues is used to recognize inflammation, in particular to differentiate it both from orbital infection and tumor. Subsequently, different radiological patterns are recognized, often allowing the differentiation of the several orbital inflammatory diseases. CONCLUSION: The use of adequate imaging protocols and subsequent evaluation allow the recognition of an orbital lesion as inflammatory and the diagnosis of the underlying inflammatory disease. All in all, a proper treatment can be established, and at times, a biopsy can be avoided.

Clinical evaluation of ultra-high-field MRI for three-dimensional visualisation of tumour size in uveal melanoma patients, with direct relevance to treatment planning.

OBJECTIVES: To assess the tumour dimensions in uveal melanoma patients using 7-T ocular MRI and compare these values with conventional ultrasound imaging to provide improved information for treatment options. MATERIALS AND METHODS: Ten uveal melanoma patients were examined on a 7-T MRI system using a custom-built eye coil and dedicated 3D scan sequences to minimise eye-motion-induced image artefacts. The maximum tumour prominence was estimated from the three-dimensional images and compared with the standard clinical evaluation from 2D ultrasound images. RESULTS: The MRI protocols resulted in high-resolution motion-free images of the eye in which the tumour and surrounding tissues could clearly be discriminated. For eight of the ten patients the MR images showed a slightly different value of tumour prominence (average 1.0 mm difference) compared to the ultrasound measurements, which can be attributed to the oblique cuts through the tumour made by the ultrasound. For two of these patients the more accurate results from the MR images changed the treatment plan, with the smaller tumour dimensions making them eligible for eye-preserving therapy. CONCLUSION: High-field ocular MRI can yield a more accurate measurement of the tumour dimensions than conventional ultrasound, which can result in significant changes in the prescribed treatment.

Magnetic Resonance Imaging in the Clinical Care for Uveal Melanoma Patients-A Systematic Review from an Ophthalmic Perspective.

Conversely to most tumour types, magnetic resonance imaging (MRI) was rarely used for eye tumours. As recent technical advances have increased ocular MRI's diagnostic value, various clinical applications have been proposed. This systematic review provides an overview of the current status of MRI in the clinical care of uveal melanoma (UM) patients, the most common eye tumour in adults. In total, 158 articles were included. Two- and three-dimensional anatomical scans and functional scans, which assess the tumour micro-biology, can be obtained in routine clinical setting. The radiological characteristics of the most common intra-ocular masses have been described extensively, enabling MRI to contribute to diagnoses. Additionally, MRI's ability to non-invasively probe the tissue's biological properties enables early detection of therapy response and potentially differentiates between high- and low-risk UM. MRI-based tumour dimensions are generally in agreement with conventional ultrasound (median absolute difference 0.5 mm), but MRI is considered more accurate in a subgroup of anteriorly located tumours. Although multiple studies propose that MRI's 3D tumour visualisation can improve therapy planning, an evaluation of its clinical benefit is lacking. In conclusion, MRI is a complementary imaging modality for UM of which the clinical benefit has been shown by multiple studies.

Comparison of Magnetic Resonance Imaging-Based and Conventional Measurements for Proton Beam Therapy of Uveal Melanoma.

OBJECTIVE: Conventionally, ocular proton therapy (PT) is planned using measurements obtained by an ophthalmologist using ultrasound, fundoscopy, biometry, and intraoperative assessments. Owing to the recent advances in magnetic resonance imaging (MRI) of uveal melanoma (UM), it is possible to acquire high-resolution 3-dimensional images of the eye, providing the opportunity to incorporate MRI in ocular PT planning. In this study, we described how these measurements can be obtained using MRI, compared the MRI-based measurements with conventional ophthalmic measurements, and identified potential pitfalls for both modalities. DESIGN: Cross-sectional study. SUBJECTS: Data from 23 consecutive patients with UM treated with PT were retrospectively evaluated. METHODS: Magnetic resonance imaging-based measurements of axial length, tumor height and basal diameter, and marker-tumor distances were compared with the conventional ophthalmic measurements, and discrepancies were evaluated in a multidisciplinary setting. MAIN OUTCOME MEASURES: Tumor prominence and basal diameters on MRI and ultrasound, axial length on MRI and biometry, tumor-marker distances on MRI and measured intraoperatively. RESULTS: The mean absolute differences of the tumor height and basal diameter measurements between ultrasound and MRI were 0.57 mm and 1.44 mm, respectively. Larger absolute differences in height and basal diameter were observed when the full tumor extent was not visible on ultrasound (0.92 mm and 1.67 mm, respectively) compared with when the full tumor extent was visible (0.44 mm and 1.15 mm, respectively). When the full tumor was not visible on ultrasound, MRI was considered more reliable. Tumor-marker distances measured using MRI and intraoperative techniques differed < 1 mm in 55% of the markers. For anteriorly located and mushroom-shaped tumors (25% of the markers), MRI provided more accurate measurements. In flat UM (15% of the markers), however, it was difficult to delineate the tumor on MRI. The mean absolute difference in axial length between optical biometry and MRI was 0.50 mm. The presence of the tumor was found to influence optical biometry in 15 of 22 patients; the remaining patients showed a better agreement (0.30 mm). Magnetic resonance imaging-based biometry was considered more reliable in patients with UM. CONCLUSIONS: Magnetic resonance imaging allowed for the 3-dimensional assessment of the tumor and surrounding tissue. In specific patients, it provided a more reliable measurement of axial length, tumor dimensions, and marker-tumor distances and could contribute to a more accurate treatment planning. Nevertheless, a combined evaluation remains advised, especially for flat UM.

Magnetic resonance imaging reveals possible cause of diplopia after Baerveldt glaucoma implantation.

PURPOSE: To assess if ocular motility impairment, and the ensuing diplopia, after Baerveldt Glaucoma device (BGI) implantation, is related to the presence of a large fluid reservoir (bleb), using Magnetic Resonance Imaging (MRI). METHODS: In a masked observational study (CCMO-registry number: NL65633.058.18), the eyes of 30 glaucoma patients with (n = 12) or without diplopia (n = 18) who had previously undergone BGI implantation were scanned with a 7 Tesla MRI-scanner. The substructures of the BGI-complex, including both blebs and plate, were segmented in 3D. Primary outcomes were a comparison of volume and height of the BGI-complex between patients with and without diplopia. Comparisons were performed by using an unpaired t-test, Fisher's Exact or Mann-Whitney test. Correlations were determined by using Spearman correlation. RESULTS: The median volume and height of the BGI-complex was significantly higher in patients with compared to patients without diplopia (p = 0.007 and p = 0.025, respectively). Six patients had an excessively large total bleb volume (median of 1736.5mm3, interquartile range 1486.3-1933.9mm3), four of whom experienced diplopia (33% of the diplopia patients). Fibrotic strands through the BGI plate, intended to limit the height of the bleb, could be visualized but were not related to diplopia (75% versus 88%; p = 0.28). CONCLUSIONS: With MRI, we show that in a significant number of diplopia cases a large bleb is present in the orbit. Given the large volume of these blebs, they are a likely explanation of the development of diplopia in at least some of the patients with diplopia after BGI implantation. Additionally, the MR-images confirm the presence of fibrotic strands. As these strands are also visible in patients with a large bleb, they are apparently not sufficient to restrict the bleb height.

The Economic Value of MR-Imaging for Uveal Melanoma.

OBJECTIVE: Uveal melanoma (UM) is the most common primary intra-ocular tumour. Treatment is determined by tumour size and location. Generally, smaller tumours are eligible for brachytherapy unless they are located close to posterior pole. Larger tumours are enucleated or undergo proton beam therapy (PBT), which is more expensive than brachytherapy and less available. Accuracy of tumour size determination is critical for accurate planning and delivery of treatment, particularly to ensure tumour coverage, critical structure sparing, and for the choice of treatment modality. This is particularly the case for tumour dimensions that are close to the cut-off point for a specific type of treatment: in the case of the brachytherapy protocol at our institution, 6-8 mm. Ultrasound is conventionally used, but magnetic resonance imaging (MRI) has recently become an additional available tool. Although more expensive, it enables more accurate measurements and is particularly useful in combination with clinical fundus examination, fundus photography and ultrasound. Our aim in this paper was to determine the economic value of MRI for UM treatment. METHODS: We retrospectively analysed 60 patients' MRI scans acquired as part of a study or for clinical care. For each patient, we assessed whether the extra cost of an MRI generated economic benefit or change in optimal treatment. RESULTS: MRI indicated a smaller tumour prominence than US in 10% of patients with intermediate tumour size, resulting in a change from PBT to brachytherapy. The costs of MRI, €200-€1000, are significantly lower than the higher costs of PBT compared to brachytherapy, €24,000 difference. In addition, the annual total economic burden of severe vision impairment associated with eye removal is €10,000. Furthermore, for patients where ultrasound was impossible due to previous surgery, MRI enabled eye-preserving treatment. CONCLUSION: An additional MRI for specific patients with UM improves economic value as it enables less expensive treatment in a sufficient percentage of patients to compensate for the MRI costs. Value is increased in terms of quality of care as it enables for some a treatment option which spares more vision.

MR and CT Imaging of the Normal Eyelid and its Application in Eyelid Tumors.

T-staging of most eyelid malignancies includes the assessment of the integrity of the tarsal plate and orbital septum, which are not clinically accessible. Given the contribution of MRI in the characterization of orbital tumors and establishing their relations to nearby structures, we assessed its value in identifying different eyelid structures in 38 normal eyelids and evaluating tumor extension in three cases of eyelid tumors. As not all patients can receive an MRI, we evaluated those same structures on CT and compared both results. All eyelid structures were identified on MRI and CT, except for the conjunctiva on both techniques and for the tarsal muscles on CT. Histopathology confirmed the MRI findings of orbital septum invasion in one patient, and the MRI findings of intact tarsus and orbital septum in another patient. Histopathology could not confirm or exclude tarsal invasion seen on MRI on two patients. Although imaging the eyelid is challenging, the identification of most eyelid structures is possible with MRI and, to a lesser extent, with CT and can, therefore, have an important contribution to the T-staging of eyelid tumors, which may improve treatment planning and outcome.

MRI enables accurate diagnosis and follow-up in uveal melanoma patients after vitrectomy.

Uveal melanoma (UM), the most common primary intraocular tumour, is often complicated by exudative retinal detachment (RD). Sometimes, this exudative RD is mistaken for a rhegmatogenous detachment and is subsequently treated with vitrectomy with silicone oil (SiOil) tamponade. As SiOil prevents ultrasound imaging, the diagnosis, treatment planning and/or follow-up of UM underlying the detachment are often severely hindered by the SiOil. We aim to develop and evaluate new MRI methods to image UM patients with a SiOil tamponade and evaluate this in vivo. A dedicated MRI protocol for 3 and 7 T was developed and subsequently evaluated in three patients. The MRI protocol developed was evaluated in three patients. In the first patient, SiOil hindered follow-up and therefore MRI was indicated. No tumour recurrence was found after two follow-up scans. The second and third patient underwent vitrectomy with SiOil for assumed rhegmatogenous RD in another hospital, during which a mass was found. In these cases, MRI was used to determine whether the lesion was UM and perform measurements to plan brachytherapy treatment. In general, the proposed workflow is more complicated on 7 T than on 3 T as the off-resonance effects scale linearly with field strength. For example, the shimming procedure needed modifications at 7 T, whereas at 3 T, the automatic shimming sufficed. However, at 7 T, higher resolution images were obtained compared with 3 T (0.6 vs. 0.8 mm). A dedicated MRI protocol enables high-resolution imaging of vitrectomized eyes with SiOil tamponade, enabling treatment planning or follow-up in UM patients.

MRI of Uveal Melanoma.

Uveal Melanoma (UM) is the most common primary malignant ocular tumor. The high soft tissue contrast and spatial resolution, and the possibility of generating 3D volumetric and functional images, make Magnetic Resonance Imaging (MRI) a valuable diagnostic imaging technique in UM. Current clinical MRI protocols, however, are not optimized for UM and therefore lack the quality for accurate assessments. We therefore developed a dedicated protocol at a 3 Tesla MRI, using an eye coil, consisting of multi-slice 2D sequences, different isotropic sequences and diffusion and perfusion-weighted images. This protocol was prospectively evaluated in 9 uveal melanoma patients. The multi-slice 2D sequences had the highest in-plane resolution, being the most suited for lesion characterization and local extension evaluation. The isotropic 3D Turbo-Spin Echo (TSE) sequences were the most suitable for accurate geometric measurements of the tumor and are therefore important for therapy planning. Diffusion and perfusion-weighted images aid in differentiating benign from malignant lesions and provide quantitative measures on tumor hemodynamics and cellularity, which have been reported to be effective in predicting and assessing treatment outcome. Overall, this dedicated MRI protocol provides high-quality imaging of UM, which can be used to improve its diagnosis, treatment planning, and follow-up.