Multimodal Registration Procedure for the Initial Spatial Alignment of a Retinal Video Sequence to a Retinal Composite Image

Accurate placement of lesions is crucial for the effectiveness and safety of a retinal laser photocoagulation treatment. Computer assistance provides the capability for improvements to treatment accuracy and execution time. The idea is to use video frames acquired from a scanning digital ophthalmoscope (SDO) to compensate for retinal motion during laser treatment. This paper presents a method for the multimodal registration of the initial frame from an SDO retinal video sequence to a retinal composite image, which may contain a treatment plan. The retinal registration procedure comprises the following steps: 1) detection of vessel centerline points and identification of the optic disc; 2) prealignment of the video frame and the composite image based on optic disc parameters; and 3) iterative matching of the detected vessel centerline points in expanding matching regions. This registration algorithm was designed for the initialization of a real-time registration procedure that registers the subsequent video frames to the composite image. The algorithm demonstrated its capability to register various pairs of SDO video frames and composite images acquired from patients.

A Hybrid Multimodal Non-Rigid Registration of MR Images Based on Diffeomorphic Demons

n this paper we present a novel hybrid approach for multimodal medical image registration based on diffeomorphic demons. Diffeomorphic demons have proven to be a robust and efficient way for intensity-based image registration. A very recent extension even allows to use mutual information (MI) as a similarity measure to registration multimodal images. However, due to the intensity correspondence uncertainty existing in some anatomical parts, it is difficult for a purely intensity-based algorithm to solve the registration problem. Therefore, we propose to combine the resulting transformations from both intensity-based and landmark-based methods for multimodal non-rigid registration based on diffeomorphic demons. Several experiments on different types of MR images were conducted, for which we show that a better anatomical correspondence between the images can be obtained using the hybrid approach than using either intensity information or landmarks alone.

A novel fusion toxin derived from an EpCAM-specific designed ankyrin repeat protein has potent antitumor activity

Designed ankyrin repeat proteins (DARPins) hold great promise as a new class of binding molecules to overcome the limitations of antibodies for biomedical applications. Here, we assessed the potential of an epithelial cell adhesion molecule (EpCAM)-specific DARPin (Ec4) for tumor targeting as a fusion toxin with Pseudomonas aeruginosa exotoxin A.

Multimodal therapy of functional gastrointestinal disorders

A multimodal approach is state-of-the art for effective treatment of functional gastrointestinal disorders (FGD) like irritable bowel syndrome and functional dyspepsia. Based on the now established view that the pathogenesis of FGD is multicausal, evidence-based therapeutic options comprise education about the nature of the disorder, dietary modifications, relaxation techniques, behavioral changes, and pharmacological treatments. These therapies are variously combined depending on the severity of the FGD and the individual needs of the patient. Our overview portrays the options for the therapy of FGD and proposes that these are best provided by an interdisciplinary team of primary care physicians, gastroenterologists, and psychosomatic medicine specialists.

Rapid fusion and syncytium formation of heterologous cells upon expression of the FGFRL1 receptor

The fusion of mammalian cells into syncytia is a developmental process that is tightly restricted to a limited subset of cells. Besides gamete and placental trophoblast fusion, only macrophages and myogenic stem cells fuse into multinucleated syncytia. In contrast to viral cell fusion, which is mediated by fusogenic glycoproteins that actively merge membranes, mammalian cell fusion is poorly understood at the molecular level. A variety of mammalian transmembrane proteins, among them many of the immunoglobulin superfamily, have been implicated in cell-cell fusion, but none has been shown to actively fuse cells in vitro. Here we report that the FGFRL1 receptor, which is up-regulated during the differentiation of myoblasts into myotubes, fuses cultured cells into large, multinucleated syncytia. We used luciferase and GFP-based reporter assays to confirm cytoplasmic mixing and to identify the fusion inducing domain of FGFRL1. These assays revealed that Ig-like domain III and the transmembrane domain are both necessary and sufficient to rapidly fuse CHO cells into multinucleated syncytia comprising several hundred nuclei. Moreover, FGFRL1 also fused HEK293 and HeLa cells with untransfected CHO cells. Our data show that FGFRL1 is the first mammalian protein that is capable of inducing syncytium formation of heterologous cells in vitro.

Real-Time Multimodal Retinal Image Registration for a Computer Assisted Laser Photocoagulation System

An algorithm for the real-time registration of a retinal video sequence captured with a scanning digital ophthalmoscope (SDO) to a retinal composite image is presented. This method is designed for a computer-assisted retinal laser photocoagulation system to compensate for retinal motion and hence enhance the accuracy, speed, and patient safety of retinal laser treatments. The procedure combines intensity and feature-based registration techniques. For the registration of an individual frame, the translational frame-to-frame motion between preceding and current frame is detected by normalized cross correlation. Next, vessel points on the current video frame are identified and an initial transformation estimate is constructed from the calculated translation vector and the quadratic registration matrix of the previous frame. The vessel points are then iteratively matched to the segmented vessel centerline of the composite image to refine the initial transformation and register the video frame to the composite image. Criteria for image quality and algorithm convergence are introduced, which assess the exclusion of single frames from the registration process and enable a loss of tracking signal if necessary. The algorithm was successfully applied to ten different video sequences recorded from patients. It revealed an average accuracy of 2.47 ± 2.0 pixels (∼23.2 ± 18.8 μm) for 2764 evaluated video frames and demonstrated that it meets the clinical requirements.