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Neuro Imaging Researc

Dose fractionation effects in primary and metastatic human uveal melanoma cell lines

PURPOSE: To investigate the effects of split-dose irradiation on primary and metastatic uveal melanoma cell lines, with a clonogenic survival assay. METHODS: Appropriate cell concentrations of four primary and four metastatic human uveal melanoma cell lines were cultured for irradiation with single doses and with two equal fractions separated by 5 hours. After irradiation, colony formation was allowed for 7 to 21 days. Two cutaneous melanomas were also tested for comparison. All survival curves were analyzed using the linear quadratic (LQ) model. Specific parameters for the intrinsic radiosensitivity (alpha-component, SF2), for the capacity of repair of DNA damage (beta-component), as well as the alpha/beta ratio were calculated. RESULTS: After single-dose irradiation a wide range in the values of the alpha- and beta-component was obtained for both primary and metastatic uveal melanomas, which resulted in a wide range of alpha/beta ratios. In contrast, calculations based on split-dose data, with which the beta-component could be estimated independent of the alpha-component, indicated that estimates for the capacity of sublethal DNA damage repair was very similar in all cell lines. This indicated that intrinsic factors dominated the radiosensitivity of these cell lines. Split-dose irradiation had little influence on the intrinsic radiosensitivity (alpha-component), but cell survival increased for all cell lines. For the two cutaneous melanomas comparable split-dose results were obtained. CONCLUSIONS: For both primary and metastatic uveal melanoma cell lines, data from single and fractionated doses indicate large variations in radiosensitivity, which are mainly dominated by the intrinsic radiosensitivities. Doses of approximately 8 Gy in five fractions would be sufficient to eradicate 10(9) cells (approximately 1 cm3) of the most radioresistant tumor cell lines, but this schedule is an overkill for the radiosensitive tumor cell lines. Based on specific morphologic and histologic tumor markers, more individualized dose fractionation schedules could improve the therapeutic ratio for uveal melanomas

MRI-based 3D retinal shape determination

Objective To establish a good method to determine the retinal shape from MRI using three-dimensional (3D) ellipsoids as well as evaluate its reproducibility.Methods and analysis The left eyes of 31 volunteers were imaged using high-resolution ocular MRI. The 3D MR-images were segmented and ellipsoids were fitted to the resulting contours. The dependency of the resulting ellipsoid parameters on the evaluated fraction of the retinal contour was assessed by fitting ellipsoids to 41 different fractions. Furthermore, the reproducibility of the complete procedure was evaluated in four subjects. Finally, a comparison with conventional two-dimensional (2D) methods was made.Results The mean distance between the fitted ellipsoids and the segmented retinal contour was 0.03 +/- 0.01 mm (mean +/- SD) for the central retina and 0.13 +/- 0.03 mm for the peripheral retina. For the central retina, the resulting ellipsoid radii were 12.9 +/- 0.9, 13.7 +/- 1.5 and 12.2 +/- 1.2 mm along the horizontal, vertical and central axes. For the peripheral retina, these radii decreased to 11.9 +/- 0.6, 11.6 +/- 0.4 and 10.4 +/- 0.7 mm, which was accompanied by a mean 1.8 mm posterior shift of the ellipsoid centre. The reproducibility of the ellipsoid fitting was 0.3 +/- 1.2 mm for the central retina and 0.0 +/- 0.1 mm for the peripheral retina. When 2D methods were used to fit the peripheral retina, the fitted radii differed a mean 0.1 +/- 0.1 mm from the 3D method.Conclusion An accurate and reproducible determination of the 3D retinal shape based on MRI is provided together with 2D alternatives, enabling wider use of this method in the field of ophthalmology.Neuro Imaging Researc

Cellular radiosensitivity of primary and metastatic human uveal melanoma cell lines

PURPOSE: To investigate the radiosensitivity of uveal melanoma cell lines by a clonogenic survival assay, to improve the efficiency of the radiation regimen. METHODS: Four primary and four metastatic human uveal melanoma cell lines were cultured in the presence of conditioned medium. After single-dose irradiation (0-12 Gy), colonies were allowed to form for 6 to 14 days. Two cutaneous melanomas cell lines were also tested for comparison. The survival curves were analyzed by the linear quadratic (LQ) model, and the surviving fraction at a dose of 2 Gy (SF(2)), the SF at 10 Gy (SF(10)), the ratio of initial irreparably damaged DNA (alpha-coefficient) to the capacity to repair sublethally damaged DNA (beta-coefficient), and the plating efficiency were calculated. RESULTS: The melanomas displayed a wide range of initial irreparable DNA damage (alpha-component), as well as a capacity for repair of sublethal DNA damage (beta-component), which ultimately resulted in a wide range of alpha/beta ratios. These findings were similar in both primary and metastatic melanomas and were comparable with data obtained from two cutaneous melanomas. CONCLUSIONS: Cell lines obtained from primary and metastatic human uveal melanomas displayed a wide range of radiosensitivity, similar to that published for cutaneous melanomas. Translating these data to the clinical setting indicates that a fractionated dose of 8 to 10 Gy administered in three to four fractions, as currently delivered in many centers, should be sufficient to eradicate tumors of approximately 1 cm(3)

Two-year results after combined phacoemulsification and iris-fixated phakic intraocular lens removal

Purpose To describe and present results after a technique for cataract surgery combined with explantation of an iris-fixated phakic intraocular lens (IF-pIOL).Methods The medical records of all patients, who had undergone cataract surgery combined with IF-pIOL explantation and subsequent implantation of a posterior chamber IOL by the Single Incision Technique (SIT), were reviewed. Data collection included preoperative and postoperative corrected distance visual acuity (CDVA), manifest refraction, and endothelial cell density (ECD) up to a follow-up time of 24 months.Results Fifty myopic eyes (34 patients) and 9 hyperopic eyes (6 patients) had undergone a SIT procedure mainly because of cataract (67%). Postoperative CDVA improved in both the myopic eyes to 0.16 +/- 0.37 logMAR, as in the hyperopic eyes to - 0.10 +/- 0.55 logMAR with no eyes having loss of Snellen lines. Mean postoperative spherical equivalent was - 0.34 +/- 0.72 D and - 0.10 +/- 0.55 D, respectively. ECD loss 6 months after surgery was 5% and remained stable thereafter.Conclusion SIT for combined phacoemulsification and IF-pIOL removal yields good visual and refractive results and is a safe procedure in regard to ECD loss. The technique has advantages over the conventional procedure and is easy to perform.Neuro Imaging Researc

Evaluation of intraocular lens position and retinal shape in negative dysphotopsia using high-resolution magnetic resonance imaging

Purpose: To assess potential relationships of intraocular lens (IOL) position and retinal shape in negative dysphotopsia (ND). Setting: Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands. Design: Case-control study. Methods: High-resolution ocular magnetic resonance imaging (MRI) scans were performed in patients with ND and pseudophakic controls, and subsequently used to determine the displacement and tilt of the in-the-bag IOL about the pupil and iris. In addition, anterior segment tomography was used to assess the iris-IOL distance. Furthermore, the retinal shape was quantified from the MRI scans by fitting an ellipse to the segmented inner boundary of the retina. Both the IOL position and retinal shape were compared between groups to assess their potential role in the etiology of ND. Results: In total, 37 patients with ND and 26 pseudophakic controls were included in the study. The mean displacement and tilt of the IOL were less than 0.1 mm and 0.5 degrees, respectively, in both groups and all directions. The corresponding mean iris-IOL distance was 1.1 mm in both groups. Neither of these values differed statistically significantly between groups (all P values >.6). The retinal shape showed large variations but was not statistically significantly different between the groups in both the left-right (P = .10) and the anterior-posterior (P = .56) directions. Conclusions: In this study, the in-the-bag IOL position and retinal shape did not statistically significantly differ between patients with ND and the general pseudophakic population. Given the large variation in retinal shape between subjects, however, it could still be an important factor in a multifactorial origin of ND.Neuro Imaging Researc

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 3Neuro Imaging Researc

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 x 10(-3) mm(2)/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.Neuro Imaging Researc