The common ABCA4 variant p.Asn1868ile shows nonpenetrance and variable expression of stargardt disease when present in trans with severe variants

PURPOSE. To assess the occurrence and the disease expression of the common p.Asn1868Ile variant in patients with Stargardt disease (STGD1) harboring known, monoallelic causal ABCA4 variants. METHODS. The coding and noncoding regions of ABCA4 were sequenced in 67 and 63 STGD1 probands respectively, harboring monoallelic ABCA4 variants. In case p.Asn1868Ile was detected, segregation analysis was performed whenever possible. Probands and affected siblings harboring p.Asn1868Ile without additional variants in cis were clinically evaluated retrospe

Real-time visualization of heterotrimeric G protein Gq activation in living cells

Contains fulltext : 97296.pdf (publisher's version ) (Open Access)BACKGROUND: Gq is a heterotrimeric G protein that plays an important role in numerous physiological processes. To delineate the molecular mechanisms and kinetics of signalling through this protein, its activation should be measurable in single living cells. Recently, fluorescence resonance energy transfer (FRET) sensors have been developed for this purpose. RESULTS: In this paper, we describe the development of an improved FRET-based Gq activity sensor that consists of a yellow fluorescent protein (YFP)-tagged Ggamma2 subunit and a Galphaq subunit with an inserted monomeric Turquoise (mTurquoise), the best cyan fluorescent protein variant currently available. This sensor enabled us to determine, for the first time, the kon (2/s) of Gq activation. In addition, we found that the guanine nucleotide exchange factor p63RhoGEF has a profound effect on the number of Gq proteins that become active upon stimulation of endogenous histamine H1 receptors. The sensor was also used to measure ligand-independent activation of the histamine H1 receptor (H1R) upon addition of a hypotonic stimulus. CONCLUSIONS: Our observations reveal that the application of a truncated mTurquoise as donor and a YFP-tagged Ggamma2 as acceptor in FRET-based Gq activity sensors substantially improves their dynamic range. This optimization enables the real-time single cell quantification of Gq signalling dynamics, the influence of accessory proteins and allows future drug screening applications by virtue of its sensitivity

Deep learning-based ultrasound transducer induced CT metal artifact reduction using generative adversarial networks for ultrasound-guided cardiac radioablation

In US-guided cardiac radioablation, a possible workflow includes simultaneous US and planning CT acquisitions, which can result in US transducer-induced metal artifacts on the planning CT scans. To reduce the impact of these artifacts, a metal artifact reduction (MAR) algorithm has been developed based on a deep learning Generative Adversarial Network called Cycle-MAR, and compared with iMAR (Siemens), O-MAR (Philips) and MDT (ReVision Radiology), and CCS-MAR (Combined Clustered Scan-based MAR). Cycle-MAR was trained with a supervised learning scheme using sets of paired clinical CT scans with and without simulated artifacts. It was then evaluated on CT scans with real artifacts of an anthropomorphic phantom, and on sets of clinical CT scans with simulated artifacts which were not used for Cycle-MAR training. Image quality metrics and HU value-based analysis were used to evaluate the performance of Cycle-MAR compared to the other algorithms. The proposed Cycle-MAR network effectively reduces the negative impact of the metal artifacts. For example, the calculated HU value improvement percentage for the cardiac structures in the clinical CT scans was 59.58%, 62.22%, and 72.84% after MDT, CCS-MAR, and Cycle-MAR application, respectively. The application of MAR algorithms reduces the impact of US transducer-induced metal artifacts on CT scans. In comparison to iMAR, O-MAR, MDT, and CCS-MAR, the application of developed Cycle-MAR network on CT scans performs better in reducing these metal artifacts

CT Scan Based Patient-Specific Transperineal Ultrasound Probe Setups for Image Guided Radiotherapy [Conference abstract]

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Pseudo-CT scan creation using registration of transabdominal ultrasound volumes of a prostate cancer patient

A crucial step in radiotherapy workflows is patient setup. The patients’ position prior to each treatment fraction (TX) must be as similar as possible to the simulation CT scan (CTsim), as the treatment plan was based on this scan. Even when the patient seems correctly aligned externally, internal tissue distributions might have changed. Delivery of the initial treatment plan might then result in suboptimal dose depositions. As frequent CT scan (CTtx) acquisition for treatment plan verification is not feasible, we propose to create instead pseudo-CT scans using simulation ultrasound (USsim) to treatment ultrasound (UStx) registratio

Patient-specific transperineal ultrasound probe setups for image guided radiotherapy

Despite the many advantages of ultrasound (US) imaging (e.g. safety and high - contrast soft tissue imaging) the use of US in image guided radiotherapy (IGRT) workflows is not widespread. This can primarily be attributed to the need of a s killed operator for US volume acquisition. We introduce an algorithm that provides the operator with a patient - specific probe setup that allows good anatomical structure visualization based on clinical requirements. This can potentially minimize operator dependence or even remove the need of the skilled operator

Various approaches for pseudo-CT scan creation based on ultrasound to ultrasound deformable image registration between different treatment time points for radiotherapy treatment plan adaptation in prostate cancer patients

The purpose of this study was to evaluate eight possible approaches to create pseudo-CT images for radiotherapy (RT) treatment re-planning. These re-planning CT scans would normally require a separate CTscan session. If important changes occur in patient's anatomy between simulation (SIM) and treatment (TX) stages, 3D ultrasound (US) images acquired at the two stages, available in US guided RT workflows, can be used to produce a deformation field. Proof of concept research showed that the application of this deformation field to the SIM CT image yields a pseudo-CT which can be more representative of the patient at TX than SIM CT. Co-registered CT and US volumes acquired at five different time points during the RT course of a prostate cancer patient were combined into data pairs, providing ground truth CTimages (CTtx). Eight different methods were explored to create the deformation field that was used to produce the pseudo-CT scan. Anatomical structure comparison and gamma index calculations were used to compare the similarity of the pseudo-CT volumes and the reference TX CT volumes. In five out of ten data pairs, all the eight approaches resulted in the creation of a pseudo-CT equally or more similar to the TX CTthan the SIM CT within the region of interest, with an average improvement of 54.1% (range: 5.1%-126.5%) in dice similarity coefficient (DSC) and 32.3% (range: 0.3%-52.6%) in gamma index. For the remaining data pairs, four up to seven approaches resulted in an improvement in both DSC (range: 4.3%-54%) and gamma index (range: 0.8%-41.3%). In conclusion, at least four out of eight explored approaches resulted in more representative pseudo-CT images in all the data pairs. In particular, the approaches in which an initial rigid alignment was combined with deformable registration performed best

The Use of Ultrasound Imaging in the External Beam Radiotherapy Workflow of Prostate Cancer Patients

External beam radiotherapy (EBRT) is one of the curative treatment options for prostate cancer patients. The aim of this treatment option is to irradiate tumor tissue, while sparing normal tissue as much as possible. Frequent imaging during the course of the treatment (image guided radiotherapy) allows for determination of the location and shape of the prostate (target) and of the organs at risk. This information is used to increase accuracy in radiation dose delivery resulting in better tumor control and lower toxicity. Ultrasound imaging is harmless for the patient, it is cost-effective, and it allows for real-time volumetric organ tracking. For these reasons, it is an ideal technique for image guidance during EBRT workflows. Review papers have been published in which the use of ultrasound imaging in EBRT workflows for different cancer sites (prostate, breast, etc.) was extensively covered. This new review paper aims at providing the readers with an update on the current status for prostate cancer ultrasound guided EBRT treatments

Evaluation of Optical Localization in the Visible Band for Ultrasound Guidance in Radiotherapy Using A Robotic Arm

In many medical fields, spatial localization of devices is of paramount importance to e.g. deliver treatments correctly or to perform accurate diagnostic evaluations. Among the different technologies available, optical localization in the visible band of the spectrum offers many advantages: minimum interference with other instruments, flexibility in position of the devices used and extra features such as patient/operator surface tracking or vital signs monitoring. Its application in the domain of radiotherapy is novel, and potentially very beneficial. In this work we introduced a workflow to test the reliability of one of these systems, developed in house, to localize an ultrasound transducer for ultrasound guided radiation therapy (USgRT). Accuracy, precision, latency, sensitive volume and sensitivity to light intensity were evaluated. The workflow we proposed allowed us to establish that, while all the clinically relevant parameters of the system are acceptable, accuracy in locating the transducer could be as poor as 7-8 mm, therefore not acceptable for the intended purpose of the system

Constrained peptides mimic a viral suppressor of RNA silencing

Contains fulltext : 244210.pdf (Publisher’s version ) (Open Access