Eye Tracker Accuracy: Quantitative Evaluation of the Invisible Eye Center Location

Purpose. We present a new method to evaluate the accuracy of an eye tracker based eye localization system. Measuring the accuracy of an eye tracker's primary intention, the estimated point of gaze, is usually done with volunteers and a set of fixation points used as ground truth. However, verifying the accuracy of the location estimate of a volunteer's eye center in 3D space is not easily possible. This is because the eye center is an intangible point hidden by the iris. Methods. We evaluate the eye location accuracy by using an eye phantom instead of eyes of volunteers. For this, we developed a testing stage with a realistic artificial eye and a corresponding kinematic model, which we trained with {\mu}CT data. This enables us to precisely evaluate the eye location estimate of an eye tracker. Results. We show that the proposed testing stage with the corresponding kinematic model is suitable for such a validation. Further, we evaluate a particular eye tracker based navigation system and show that this system is able to successfully determine the eye center with sub-millimeter accuracy. Conclusions. We show the suitability of the evaluated eye tracker for eye interventions, using the proposed testing stage and the corresponding kinematic model. The results further enable specific enhancement of the navigation system to potentially get even better results

Eye tracking based navigation for proton beam therapy

Cancers of the eye, so-called ocular tumors, are a severe disease that may lead to blindness or even death if left untreated. A possibility to remove the tumor from the body of the patient is a so-called enucleation surgery, the removal of the eye. However, it is a drastic action and oncologists usually try to avoid it. Another treatment option is the therapy with protons. The actual proton therapy to treat ocular tumors is very successful and non-invasive. However, the navigation method that is applied for this kind of therapy requires a pre-treatment surgery, where radio-opaque clips are sutured onto the affected eyeball. These clips are used during the actual treatment to align the diseased eye with two orthogonal X-ray units. Hence, the overall treatment is invasive. The work at hand presents an alternative, completely non-invasive navigation method based on eye tracking technology. We present a new treatment scheme with a first eye tracking prototype integrated into the treatment facility at Paul Scherrer Institute (PSI). This system together with a patient specific eye model enables the medical physicist to align the patient’s eye such that the tumor gets accurately treated by the proton beam. Further, we present a second, improved eye tracking system. This time, we propose a stereo eye tracker, which only uses one physical camera to save physical space. We combine a stereo eye tracking algorithm with a clever arrangement of two planar mirrors and a single camera to get high accuracy, precision, and a compact design altogether. Finally, we present a method to quantitatively evaluate the proposed navigation system. Verifying the accuracy of the location estimate of a volunteer’s eye center is not easily possible. This is because the eye center is an intangible point, that does not correspond to an anatomical structure. Our evaluation method is based on an eye phantom on microstages and a corresponding kinematic model. Our research and development may lead to an ocular tumor treatment which will be safer, more cost-effective, and more accessible to patients suffering from this serious disease

The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article

Eye Tracker Accuracy: Quantitative Evaluation of the Invisible Eye Center Location

PURPOSE:We present a new method to evaluate the accuracy of an eye tracker-based eye localization system. Measuring the accuracy of an eye tracker's primary intention, the estimated point of gaze, is usually done with volunteers and a set of fixation points used as ground truth. However, verifying the accuracy of the location estimate of a volunteer's eye center in 3D space is not easily possible. This is because the eye center, the center of corneal curvature, is an intangible point. METHODS:We evaluate the eye location accuracy by using an eye phantom instead of eyes of volunteers. For this, we developed a testing stage with a realistic artificial eye and a corresponding kinematic model, which we trained with [Formula: see text] data. This enables us to precisely evaluate the eye location estimate of an eye tracker. RESULTS:We show that the proposed testing stage with the corresponding kinematic model is suitable for such a validation. Further, we evaluate a particular eye tracker-based navigation system and show that this system is able to successfully determine the eye center with a mean accuracy of 0.68 mm. CONCLUSION:We show the suitability of the evaluated eye tracker for eye interventions, using the proposed testing stage and the corresponding kinematic model. The results further enable specific enhancements of the navigation system to potentially get even better results

With Gaze Tracking Towards Noninvasive Eye Cancer Treatment

We present a new gaze tracking-based navigation scheme for proton beam radiation of intraocular tumors and we show the technical integration into the treatment facility. Currently, to treat a patient with such a tumor, a medical physicist positions the patient and the affected eye ball such that the radiation beam targets the tumor. This iterative eye positioning mechanism requires multiple X-rays, and radio-opaque clips previously sutured on the target eyeball. We investigate a possibility to replace this procedure with a noninvasive approach using a 3-D model-based gaze tracker. Previous work does not cover a comparably extensive integration of a gaze tracking device into a state-of-the-art proton beam facility without using additional hardware, such as a stereo optical tracking system. The integration is difficult because of limited available physical space, but only this enables to quantify the overall accuracy. We built a compact gaze tracker and integrated it into the proton beam radiation facility of the Paul Scherrer Institute in Villigen, Switzerland. Our results show that we can accurately estimate a healthy volunteer's point of gaze, which is the basis for the determination of the desired initial eye position. The proposed method is the first crucial step in order to make the proton therapy of the eye completely noninvasive

Clostridium perfringens beta-toxin induces necrostatin-inhibitable, calpain-dependent necrosis in primary porcine endothelial cells

Clostridium perfringens β-toxin (CPB) is a β-barrel pore-forming toxin and an essential virulence factor of C. perfringens type C strains, which cause fatal hemorrhagic enteritis in animals and humans. We have previously shown that CPB is bound to endothelial cells within the intestine of affected pigs and humans, and that CPB is highly toxic to primary porcine endothelial cells (pEC) in vitro. The objective of the present study was to investigate the type of cell death induced by CPB in these cells, and to study potential host cell mechanisms involved in this process. CPB rapidly induced lactate dehydrogenase (LDH) release, propidium iodide uptake, ATP depletion, potassium efflux, a marked rise in intracellular calcium [Ca(2+)]i, release of high-mobility group protein B1 (HMGB1), and caused ultrastructural changes characteristic of necrotic cell death. Despite a certain level of caspase-3 activation, no appreciable DNA fragmentation was detected. CPB-induced LDH release and propidium iodide uptake were inhibited by necrostatin-1 and the two dissimilar calpain inhibitors PD150606 and calpeptin. Likewise, inhibition of potassium efflux, chelation of intracellular calcium and treatment of pEC with cyclosporin A also significantly inhibited CPB-induced LDH release. Our results demonstrate that rCPB primarily induces necrotic cell death in pEC, and that necrotic cell death is not merely a passive event caused by toxin-induced membrane disruption, but is propagated by host cell-dependent biochemical pathways activated by the rise in intracellular calcium and inhibitable by necrostatin-1, consistent with the emerging concept of programmed necrosis ("necroptosis")

Clostridium perfringens Beta-Toxin Induces Necrostatin-Inhibitable, Calpain-Dependent Necrosis in Primary Porcine Endothelial Cells

International audienceClostridium perfringens β-toxin (CPB) is a β-barrel pore-forming toxin and an essential virulence factor of C. perfringens type C strains, which cause fatal hemorrhagic enteritis in animals and humans. We have previously shown that CPB is bound to endothelial cells within the intestine of affected pigs and humans, and that CPB is highly toxic to primary porcine endothelial cells (pEC) in vitro. The objective of the present study was to investigate the type of cell death induced by CPB in these cells, and to study potential host cell mechanisms involved in this process. CPB rapidly induced lactate dehydrogenase (LDH) release, propidium iodide uptake, ATP depletion, potassium efflux, a marked rise in intracellular calcium [Ca(2+)]i, release of high-mobility group protein B1 (HMGB1), and caused ultrastructural changes characteristic of necrotic cell death. Despite a certain level of caspase-3 activation, no appreciable DNA fragmentation was detected. CPB-induced LDH release and propidium iodide uptake were inhibited by necrostatin-1 and the two dissimilar calpain inhibitors PD150606 and calpeptin. Likewise, inhibition of potassium efflux, chelation of intracellular calcium and treatment of pEC with cyclosporin A also significantly inhibited CPB-induced LDH release. Our results demonstrate that rCPB primarily induces necrotic cell death in pEC, and that necrotic cell death is not merely a passive event caused by toxin-induced membrane disruption, but is propagated by host cell-dependent biochemical pathways activated by the rise in intracellular calcium and inhibitable by necrostatin-1, consistent with the emerging concept of programmed necrosis ("necroptosis")

Morphological changes and LDH release induced by rCPB in pEC.

<p>(A) pEC were either left untreated (white) or exposed to rCPB or staurosporine (200 nM) for 4 h. Cell morphology was visualized using phase contrast microscopy. (B) Changes in total cell number (determined using automated cell counter) of pEC after 2, 4 and 16 h incubation with control medium, rCPB at indicated concentrations, neutralized rCPB using monoclonal anti-CPB antibodies, or staurosporine. Bar graphs represent the mean ± SEM of n = 3–6 independent experiments. Statistical difference to control cells was assessed by 1-way ANOVA and Dunnnet post-hoc test. *P<0.05, **P<0.01, †P<0.001. (C) The supernatants of pEC cultures from B were analyzed for LDH activity to determine LDH release after different times of exposure. Bar graph shows summary of results from 3 to 6 independent experiments expressed as percentage of activity compared to lysed control cells ( = 100%). Statistical difference to non-treated control cells was assessed by 1-way ANOVA and Dunnnet post-hoc test. *P<0.05, **P<0.01, †P<0.001.</p

pEC exposed to rCPB do not exhibit apoptotic but typical features of necrotic cell death.

<p>(A) Presence of cleaved caspase 3 was assessed by Western blotting at different time points after exposure to 30 ng/ml rCPB or staurosporine. Tubulin was used as loading control. Representative results of 3 independent experiments. (B) Internucleosomal DNA fragmentation was assessed after 16 h of exposure to rCPB. Staurosporine was used as a control for apoptosis, while incubation with 5 mM of H₂O₂ or freeze thawing served as controls for necrosis. Representative results of 3 independent experiments. (C) Intracellular ATP levels were determined at the indicated time points. Results represent mean ± SEM of 3 independent experiments. Statistical difference to untreated control cells was assessed by 2-way ANOVA and Bonferroni multiple comparisons test. *P<0.05, **P<0.01, †P<0.001, ††P<0.0001. (D) Cytoplasmic translocation of HMGB-1 (red) was detectable by immunofluorescence in pEC already 30 min after exposure to 30 ng/ml rCPB. Control cells incubated with toxin-free medium exhibit typical nuclear localization. Nuclear counterstain with Hoechst 33258 (blue). (E) Electron microscopic image of pEC 6 h after incubation with 30 ng/ml rCPB. Cells exhibit small irregular clumps of chromatin abutting to the nuclear membrane (asterisk), swelling of cell organelles with disappearance of the elongated mitochondria with cristae (arrows), and plasma membrane discontinuities (arrowhead).</p