A Multimodality Hybrid Gamma-Optical Camera for Intraoperative Imaging

The development of low profile gamma-ray detectors has encouraged the production of small field of view (SFOV) hand-held imaging devices for use at the patient bedside and in operating theatres. Early development of these SFOV cameras was focussed on a single modality-gamma ray imaging. Recently, a hybrid system-gamma plus optical imaging-has been developed. This combination of optical and gamma cameras enables high spatial resolution multi-modal imaging, giving a superimposed scintigraphic and optical image. Hybrid imaging offers new possibilities for assisting clinicians and surgeons in localising the site of uptake in procedures such as sentinel node detection. The hybrid camera concept can be extended to a multimodal detector design which can offer stereoscopic images, depth estimation of gamma-emitting sources, and simultaneous gamma and fluorescence imaging. Recent improvements to the hybrid camera have been used to produce dual-modality images in both laboratory simulations and in the clinic. Hybrid imaging of a patient who underwent thyroid scintigraphy is reported. In addition, we present data which shows that the hybrid camera concept can be extended to estimate the position and depth of radionuclide distribution within an object and also report the first combined gamma and Near-Infrared (NIR) fluorescence images.Peer-reviewedPublisher Versio

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Design and implementation of a prototype head and neck phantom for the performance evaluation of gamma imaging systems

BACKGROUND: A prototype anthropomorphic head and neck phantom has been designed to simulate the adult head and neck anatomy including some internal organs and tissues of interest, such as thyroid gland and sentinel lymph nodes (SLNs). The design of the head and neck phantom includes an inner jig holding the simulated SLNs and thyroid gland. The thyroid gland structure was manufactured using three-dimensional (3D) printing taking into consideration the morphology and shape of a healthy adult thyroid gland. RESULT: The head and neck phantom was employed to simulate a situation where there are four SLNs distributed at two different vertical levels and at two depths within the neck. Contrast to noise ratio (CNR) calculations were performed for the detected SLNs at an 80 mm distance between both pinhole collimators (0.5 and 1.0 mm diameters) and the surface of the head and neck phantom with a 100 s acquisition time. The recorded CNR values for the simulated SLNs are higher when the hybrid gamma camera (HGC) was fitted with the 1.0 mm diameter pinhole collimator. For instance, the recorded CNR values for the superficially simulated SLN (15 mm depth) containing 0.1 MBq of (99m)Tc using 0.5 and 1.0 mm diameter pinhole collimators are 6.48 and 16.42, respectively (~87% difference). Gamma and hybrid optical images were acquired using the HGC for the simulated thyroid gland. The count profiles through the middle of the simulated thyroid gland images provided by both pinhole collimators were obtained. The HGC could clearly differentiate the individual peaks of both thyroid lobes in the gamma image produced by the 0.5-mm pinhole collimator. In contrast, the recorded count profile for the acquired image using the 1.0-mm-diameter pinhole collimator showed broader peaks for both lobes, reflecting the degradation of the spatial resolution with increasing the diameter of the pinhole collimator. CONCLUSIONS: This anthropomorphic head and neck phantom provides a valuable tool for assessing the imaging ability of gamma cameras used for imaging the head and neck region. The standardisation of test phantoms for SFOV gamma systems will provide an opportunity to collect data across various medical centres. The phantom described is cost effective, reproducible, flexible and anatomically representative

A Multimodality Hybrid Gamma-Optical Camera for Intraoperative Imaging

The development of low profile gamma-ray detectors has encouraged the production of small field of view (SFOV) hand-held imaging devices for use at the patient bedside and in operating theatres. Early development of these SFOV cameras was focussed on a single modality-gamma ray imaging. Recently, a hybrid system-gamma plus optical imaging-has been developed. This combination of optical and gamma cameras enables high spatial resolution multi-modal imaging, giving a superimposed scintigraphic and optical image. Hybrid imaging offers new possibilities for assisting clinicians and surgeons in localising the site of uptake in procedures such as sentinel node detection. The hybrid camera concept can be extended to a multimodal detector design which can offer stereoscopic images, depth estimation of gamma-emitting sources, and simultaneous gamma and fluorescence imaging. Recent improvements to the hybrid camera have been used to produce dual-modality images in both laboratory simulations and in the clinic. Hybrid imaging of a patient who underwent thyroid scintigraphy is reported. In addition, we present data which shows that the hybrid camera concept can be extended to estimate the position and depth of radionuclide distribution within an object and also report the first combined gamma and Near-Infrared (NIR) fluorescence images

Structure-based design of selective fat mass and obesity associated protein (FTO) inhibitors

FTO catalyzes the Fe(II) and 2-oxoglutarate (2OG)-dependent modification of nucleic acids, including the demethylation of N6-methyladenosine (m6A) in mRNA. FTO is a proposed target for anti-cancer therapy. Using information from crystal structures of FTO in complex with 2OG and substrate mimics, we designed and synthesized two series of FTO inhibitors, which were characterized by turnover and binding assays, and by X-ray crystallography with FTO and the related bacterial enzyme AlkB. A potent inhibitor employing binding interactions spanning the FTO 2OG and substrate binding sites was identified. Selectivity over other clinically targeted 2OG oxygenases was demonstrated, including with respect to the hypoxia-inducible factor prolyl and asparaginyl hydroxylases (PHD2 and FIH) and selected JmjC histone demethylases (KDMs). The results illustrate how structure-based design can enable the identification of potent and selective 2OG oxygenase inhibitors and will be useful for the development of FTO inhibitors for use in vivo

Simeprevir potently suppresses SARS-CoV-2 replication and synergizes with remdesivir

202307 bcchVersion of RecordRGCOthersH2020 SC1-PHE-Coronavirus-2020; National Institute of Allergy and Infectious Diseases; Croucher Foundation; Hong Kong Baptist University; Fondation pour la Recherche Médicale; National Research Foundation of Korea; Chinese University of Hong Kong; Faculty of Medicine, Prince of Songkla University; Ministry of Science and ICT, South KoreaPublishe

5-Carboxy-8-hydroxyquinoline is a broad spectrum 2-oxoglutarate oxygenase inhibitor which causes iron translocation

2-Oxoglutarate and iron dependent oxygenases are therapeutic targets for human diseases. Using a representative 2OG oxygenase panel, we compare the inhibitory activities of 5-carboxy-8-hydroxyquinoline (IOX1) and 4-carboxy-8-hydroxyquinoline (4C8HQ) with that of two other commonly used 2OG oxygenase inhibitors, N-oxalylglycine (NOG) and 2,4-pyridinedicarboxylic acid (2,4-PDCA). The results reveal that IOX1 has a broad spectrum of activity, as demonstrated by the inhibition of transcription factor hydroxylases, representatives of all 2OG dependent histone demethylase subfamilies, nucleic acid demethylases and γ-butyrobetaine hydroxylase. Cellular assays show that, unlike NOG and 2,4-PDCA, IOX1 is active against both cytosolic and nuclear 2OG oxygenases without ester derivatisation. Unexpectedly, crystallographic studies on these oxygenases demonstrate that IOX1, but not 4C8HQ, can cause translocation of the active site metal, revealing a rare example of protein ligand-induced metal movement. © 2013 The Royal Society of Chemistry