Unravelling the collagen network of the arterial wall

Although the extracellular matrix (ECM) is the key determinant of the mechanical behavior and stability of tissue, remarkably little is known on this tissue component. Most biomedical research on the human aorta focuses on biochemical analysis of tissues or the properties of specific cells in the aorta. We show that a physics-based approach can yield important complementary insight. By measuring the mechanical response of the ECM by AFM and imaging it with multi-photon microscopy, we show that the spatial organization of the network structure of collagen fibers plays an important role. First we show how aneurysms, a local dilatation of the arterial wall, are caused by profound defects in collagen network. The collagen fibers in het healthy aorta are organized in a loose braiding of collagen ribbons, while the aneurysmatic tissue show dramatically altered collagen architectures with loss of the collagen knitting. Evaluation by AFM shows how this altered network could explain the failure of the tissue. In a follow-up study, we examine the effects of enzymatic digestion of the ECM of the aortic wall. By starting with real tissue and selectively removing different elements, we are able to measure the contribution of the different constituents of the ECM to the mechanical properties of the whole tissue. We also show how the content of neutrophils is able to mimic the observed change in mechanical response from a healthy aorta to an aneurysm. Finally we will show first results on the disease of atherosclerosis, another common vascular disease. The collagen structure of the cap changes during the growth of the atherosclerotic plaque and we discuss its mechanical implications. This study gives key insights in the failure mechanism of two common pathologies and provides biomedical researchers a new, physics-oriented view to organs, with implications for the study of wound healing, myocardial infarction and cancer cell migration.LEI Universiteit LeidenThe Netherlands SmartMix, NIMIC partner organizationsCondensed Matter Condensed Physic

Reply to comment on: Distinct differences in anterior chamber configuration and peripheral aberrations in negative dysphotop

Neuro Imaging Researc

Effect of anatomical differences and intraocular lens design on negative dysphotopsia

Purpose: To assess the effect of ocular anatomy and intraocular lens (IOL) design on negative dysphotopsia (ND).Setting: Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands.Design: Ray-tracing study based on clinical data.Methods: Ray-tracing simulations were performed to assess the effect of anatomical differences and differences in IOL design on the peripheral retinal illumination. To that end, eye models that incorporate clinically measured anatomical differences between eyes of patients with ND and eyes of pseudophakic controls were created. The anatomical differences included pupil size, pupil centration, and iris tilt. The simulations were performed with different IOL designs, including a simple biconvex IOL design and a more complex clinical IOL design with a convex-concave anterior surface. Both IOL designs were analyzed using a clear edge and a frosted edge. As ND is generally considered to be caused by a discontinuity in peripheral retinal illumination, this illumination profile was determined for each eye model and the severity of the discontinuity was compared between eye models.Results: The peripheral retinal illumination consistently showed a more severe discontinuity in illumination with ND-specific anatomy. This difference was the least pronounced, 8%, with the frosted edge clinical IOL and the most pronounced, 18%, with the clear edge biconvex IOL.Conclusions: These results show that small differences in the ocular anatomy or IOL design affect the peripheral retinal illumination. Therewith, they can increase the severity of ND by up to 18%. Copyright (c) 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of ASCRS and ESCRSOphthalmic researc

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

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

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

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

Eye muscle MRI in myasthenia gravis and other neuromuscular disorders

Introduction:MRI of extra-ocular muscles (EOM) in patients with myasthenia gravis (MG) could aid in diagnosis and provide insights in therapy-resistant ophthalmoplegia. We used quantitative MRI to study the EOM in MG, healthy and disease controls, including Graves’ ophthalmopathy (GO), oculopharyngeal muscular dystrophy (OPMD) and chronic progressive external ophthalmoplegia (CPEO).Methods:Twenty recently diagnosed MG (59±19yrs), nineteen chronic MG (51±16yrs), fourteen seronegative MG (57±9yrs) and sixteen healthy controls (54±13yrs) were included. Six CPEO (49±14yrs), OPMD (62±10yrs) and GO patients (44±12yrs) served as disease controls. We quantified muscle fat fraction (FF), T2water and volume. Eye ductions and gaze deviations were assessed by synoptophore and Hess-charting.Results:Chronic, but not recent onset, MG patients showed volume increases (e.g. superior rectus and levator palpebrae [SR+LPS] 985±155 mm3 compared to 884±269 mm3 for healthy controls, p 3, p 3, p p water were found.Interpretation:We observed small increases in EOM volume and FF in chronic MG compared to healthy controls. Surprisingly, we found no atrophy in MG, even in patients with long-term ophthalmoplegia. This implies that even long-term ophthalmoplegia in MG does not lead to secondary structural myopathic changes precluding functional recovery.Biological, physical and clinical aspects of cancer treatment with ionising radiatio

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

Neutrophil-mediated experimental metastasis is enhanced by VEGFR inhibition in a zebrafish xenograft model

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