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,... Show moreUveal 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. Show less
Jaarsma-Coes, M.; Ferreira, T.A.G.; Marinkovic, M.; Luyten, G.P.M.; Beenakker, J.W.M. 2018
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... Show moreAlthough 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. Show less
The microarchitecture of different components of the extracellular matrix (ECM) is crucial to our understanding of the properties of a tissue. In the study presented here, we used a top-down... Show moreThe microarchitecture of different components of the extracellular matrix (ECM) is crucial to our understanding of the properties of a tissue. In the study presented here, we used a top-down approach to understand how the interplay among different fibers determines the mechanical properties of real tissues. By selectively removing different elements of the arterial wall, we were able to measure the contribution of the different constituents of the ECM to the mechanical properties of the whole tissue. Changes in the network structure were imaged with the use of two-photon microscopy. We used an atomic force microscope to measure changes in the mechanical properties by performing nanoindentation experiments. We show that although the removal of a key element of the ECM reduced the local stiffness by up to 50 times, the remaining tissue still formed a coherent network. We also show how this method can be extended to study the effects of cells on real tissues. This new (to our knowledge) way of studying the ECM will not only help physicists gain a better understanding of biopolymers, it will be a valuable tool for biomedical researchers studying processes such as wound healing and cervix ripening. Show less
