Application of synthetic data in the training of artificial intelligence for automated quality assurance in magnetic resonance imaging.

BACKGROUND: Magnetic resonance imaging scanner faults can be missed during routine quality assurance (QA) if they are subtle, intermittent, or the test being performed is insensitive to the type of fault. Coil element malfunction is a common fault within MRI scanners, which may go undetected for quite some time. Consequently, this may lead to poor image quality and the potential for misdiagnoses. PURPOSE: Daily QA typically consists of an automated signal to noise ratio test and in some instances this test is insensitive to coil element malfunction. Instead of relying on daily QA testing, it was proposed to utilize patient images in conjunction with a trained neural network to detect coil element malfunction, even when it presents as a very subtle defect. The advantage to using patient images over phantom testing is real-time monitoring can be achieved. This allows clinical staff to focus more on patient throughput without being burdened by daily testing. METHODS: A neural network was trained using simulated coil failure in 3958 abdominal or pelvic images from 497 patients. The accuracy of the trained network was then tested on an unseen dataset of 109 images from which 44 patients which had coil element malfunction present. Five MRI radiographers were shown 249 images with and without real coil malfunction to assess their accuracy compared to the neural network in identifying the scanner fault. RESULTS: The neural network achieved an accuracy of 91.74% in identifying coil element malfunction in the unseen data. Radiographers tasked with identifying coil element malfunction had an average accuracy of 59.99%. In the same test case, the neural network outperformed all radiographers with an accuracy of 91.56%. CONCLUSION: This work demonstrates that neural networks trained with artificial data can successfully identify MRI scanner coil element malfunction in clinical images. The method provided better accuracy than MRI radiographers (technologists) at identifying coil element malfunction and highlights the potential utility of AI methods as an alternative to support traditional QA. Further, our methodology of training neural networks with simulated data could potentially identify other faults, allowing centers to produce robust fault detection systems with minimal data.

The Remarkable Outer Hair Cell: Proceedings of a Symposium in Honour of W. E. Brownell.

In 1985, Bill Brownell and colleagues published the remarkable observation that cochlear outer hair cells (OHCs) express voltage-driven mechanical motion: electromotility. They proposed OHC electromotility as the mechanism for the elusive "cochlear amplifier" required to explain the sensitivity of mammalian hearing. The finding and hypothesis stimulated an explosion of experiments that have transformed our understanding of cochlear mechanics and physiology, the evolution of hair cell structure and function, and audiology. Here, we bring together examples of current research that illustrate the continuing impact of the discovery of OHC electromotility.

Joint British Society consensus recommendations for magnetic resonance imaging for patients with cardiac implantable electronic devices.

Magnetic Resonance Imaging (MRI) is increasingly a fundamental component of the diagnostic pathway across a range of conditions. Historically, the presence of a cardiac implantable electronic device (CIED) has been a contraindication for MRI, however, development of MR Conditional devices that can be scanned under strict protocols has facilitated the provision of MRI for patients. Additionally, there is growing safety data to support MR scanning in patients with CIEDs that do not have MR safety labelling or with MR Conditional CIEDs where certain conditions are not met, where the clinical justification is robust. This means that almost all patients with cardiac devices should now have the same access to MRI scanning in the National Health Service as the general population. Provision of MRI to patients with CIED, however, remains limited in the UK, with only half of units accepting scan requests even for patients with MR Conditional CIEDs. Service delivery requires specialist equipment and robust protocols to ensure patient safety and facilitate workflows, meanwhile demanding collaboration between healthcare professionals across many disciplines. This document provides consensus recommendations from across the relevant stakeholder professional bodies and patient groups to encourage provision of safe MRI for patients with CIEDs.

Origin of eukaryotes: What can be learned from the first successfully isolated Asgard archaeon.

The origin of cellular complexity characterizing eukaryotic cells remains a central unresolved issue in the study of diversification of cellular life on Earth. The isolation by Imachi et al.1 of a member of the Asgard archaea2 - a contemporary relative of organisms thought to have given rise to eukaryotic cells about 2 billion years ago - now promises new insight. The complete genome sequence of the isolated Lokiarchaeum strain confirms that the eukaryotic signature proteins (ESPs) previously identified in the Lokiarchaeota3 and other Asgard archaea2 are indeed encoded by these archaeal genomes and do not represent contamination from eukaryotes. These ESPs encode homologs of eukaryotic actins, small GTPases and the ESCRT complex proteins and are required for the functioning of complex eukaryotic cells. The new, slowly growing, anaerobic laboratory strain allows a first direct look at these organisms and provides key insights into the morphology and metabolism of an Asgard archaeal organism. The work has provided valuable information for other laboratories that aim to isolate and characterize related organisms from other environments.

Reproducibility of MRI-based white matter tract estimation using multi-fiber probabilistic tractography: effect of user-defined parameters and regions.

OBJECTIVE: There is a pressing need to assess user-dependent reproducibility of multi-fibre probabilistic tractography in order to encourage clinical implementation of these advanced and relevant approaches. The goal of this study was to evaluate both intrinsic and inter-user reproducibility of corticospinal tract estimation. MATERIALS AND METHODS: Six clinical datasets including motor functional and diffusion MRI were used. Three users performed an independent tractography analysis following identical instructions. Dice indices were calculated to quantify the reproducibility of seed region, fMRI-based end region, and streamline maps. RESULTS: The inter-user reproducibility ranged 41-93%, 29-94%, and 50-92%, for seed regions, end regions, and streamline maps, respectively. Differences in streamline maps correlated with differences in seed and end regions. Good inter-user agreement in seed and end regions, yielded inter-user reproducibility close to the intrinsic reproducibility (92-97%) and in most cases higher than 80%. DISCUSSION: Uncertainties related to user-dependent decisions and the probabilistic nature of the analysis should be considered when interpreting probabilistic tractography data. The standardization of the methods used to define seed and end regions is a necessary step to improve the accuracy and robustness of multi-fiber probabilistic tractography in a clinical setting. Clinical users should choose a feasible compromise between reproducibility and analysis duration.

A resolution record for cryoEM.

Cryo electron microscopy (cryoEM) is a fast-growing technique for structure determination. Two recent papers report the first atomic resolution structure of a protein obtained by averaging images of frozen-hydrated biomolecules. They both describe maps of symmetric apoferritin assemblies, a common test specimen, in unprecedented detail. New instrument improvements, different in the two studies, have contributed better images, and image analysis can extract structural information sufficient to resolve individual atomic positions. While true atomic resolution maps will not be routine for most proteins, the studies suggest structures determined by cryoEM will continue to improve, increasing their impact on biology and medicine.

Macromolecular and electrical coupling between inner hair cells in the rodent cochlea.

Inner hair cells (IHCs) are the primary receptors for hearing. They are housed in the cochlea and convey sound information to the brain via synapses with the auditory nerve. IHCs have been thought to be electrically and metabolically independent from each other. We report that, upon developmental maturation, in mice 30% of the IHCs are electrochemically coupled in 'mini-syncytia'. This coupling permits transfer of fluorescently-labeled metabolites and macromolecular tracers. The membrane capacitance, Ca2+-current, and resting current increase with the number of dye-coupled IHCs. Dual voltage-clamp experiments substantiate low resistance electrical coupling. Pharmacology and tracer permeability rule out coupling by gap junctions and purinoceptors. 3D electron microscopy indicates instead that IHCs are coupled by membrane fusion sites. Consequently, depolarization of one IHC triggers presynaptic Ca2+-influx at active zones in the entire mini-syncytium. Based on our findings and modeling, we propose that IHC-mini-syncytia enhance sensitivity and reliability of cochlear sound encoding.

Implementation of clinical tractography for pre-surgical planning of space occupying lesions: An investigation of common acquisition and post-processing methods compared to dissection studies.

BACKGROUND AND PURPOSE: There is limited standardization of acquisition and processing methods in diffusion tractography for pre-surgical planning, leading to a range of approaches. In this study, a number of representative acquisition variants and post processing methods are considered, to assess their importance when implementing a clinical tractography program. METHODS: Diffusion MRI was undertaken in ten healthy volunteers, using protocols typical of clinical and research scanning: a 32-direction diffusion acquisition with and without peripheral gating, and a non-gated 64 diffusion direction acquisition. All datasets were post-processed using diffusion tensor reconstruction with streamline tractography, and with constrained spherical deconvolution (CSD) with both streamline and probabilistic tractography, to delineate the cortico-spinal tract (CST) and optic radiation (OR). The accuracy of tractography results was assessed against a histological atlas using a novel probabilistic Dice overlap technique, together with direct comparison to tract volumes and distance of Meyer's loop to temporal pole (ML-TP) from dissections studies. Three clinical case studies of patients with space occupying lesions were also investigated. RESULTS: Tracts produced by CSD with probabilistic tractography provided the greatest overlap with the histological atlas (overlap scores of 44% and 52% for the CST and OR, respectively) and best matched tract volume and ML-TP distance from dissection studies. The acquisition protocols investigated had limited impact on the accuracy of the tractography. In all patients, the CSD based probabilistic tractography created tracts with greatest anatomical plausibility, although in one case anatomically plausible pathways could not be reconstructed without reducing the probabilistic threshold, leading to an increase in false positive tracts. CONCLUSIONS: Advanced post processing techniques such as CSD with probabilistic tractography are vital for pre-surgical planning. However, overall accuracy relative to dissection studies remains limited.

Implementation of clinically relevant and robust fMRI-based language lateralization: Choosing the laterality index calculation method.

The assessment of language lateralization has become widely used when planning neurosurgery close to language areas, due to individual specificities and potential influence of brain pathology. Functional magnetic resonance imaging (fMRI) allows non-invasive and quantitative assessment of language lateralization for presurgical planning using a laterality index (LI). However, the conventional method is limited by the dependence of the LI on the chosen activation threshold. To overcome this limitation, different threshold-independent LI calculations have been reported. The purpose of this study was to propose a simplified approach to threshold-independent LI calculation and compare it with three previously reported methods on the same cohort of subjects. Fifteen healthy subjects, who performed picture naming, verb generation, and word fluency tasks, were scanned. LI values were calculated for all subjects using four methods, and considering either the whole hemisphere or an atlas-defined language area. For each method, the subjects were ranked according to the calculated LI values, and the obtained rankings were compared. All LI calculation methods agreed in differentiating strong from weak lateralization on both hemispheric and regional scales (Spearman's correlation coefficients 0.59-1.00). In general, a more lateralized activation was found in the language area than in the whole hemisphere. The new method is well suited for application in the clinical practice as it is simple to implement, fast, and robust. The good agreement between LI calculation methods suggests that the choice of method is not key. Nevertheless, it should be consistent to allow a relative comparison of language lateralization between subjects.

Wnts control membrane potential in mammalian cancer cells.

KEY POINTS: Wnt ligands belonging to both canonical and non-canonical Wnt pathways regulate membrane potential signifying a very early event in the signal transduction. Wnts activate K+ currents by elevating intracellular Ca2+ and trigger Ca2+ release from intracellular stores. Control of potential by Wnt ligands has significant implications for gene transcription and opens up a novel avenue to interfere with this critical pathway. ABSTRACT: The Wnt signalling network determines gene transcription with free intracellular Ca2+ ( Cai2+ ) and ß-catenin as major intracellular signal transducers. Despite its critical importance during development and disease, many of the basic mechanisms of Wnt signal activation remain unclear. Here we show by single cell recording and simultaneous Cai2+ imaging in mammalian prostate cancer cells that an early step in the signal cascade is direct action on the cell membrane potential. We show that Wnt ligands 5A, 9B and 10B rapidly hyperpolarized the cells by activating K+ current by Ca2+ release from intracellular stores. Medium-throughput multi-well recordings showed responses to Wnts at concentrations of 2 nm. We identify a putative target for early events as a TRPM channel. Wnts thus act as ligands for ion channel activation in mammalian cells and membrane potential is an early indicator of control of transcription.

A Free Virtual Reality Experience to Prepare Pediatric Patients for Magnetic Resonance Imaging: Cross-Sectional Questionnaire Study.

BACKGROUND: A magnetic resonance image (MRI) is a diagnostic test that requires patients to lie still for prolonged periods within a claustrophobic and noisy environment. This can be difficult for children to tolerate, and often general anesthetic (GA) is required at considerable cost and detriment to patient safety. Virtual reality (VR) is a newly emerging technology that can be implemented at low cost within a health care setting. It has been shown to reduce fear associated with a number of high-anxiety situations and medical procedures. OBJECTIVE: The goal of the research was to develop a VR resource to prepare pediatric patients for MRI, helping to reduce anxieties in children undergoing the procedure. METHODS: A freely accessible VR preparation resource was developed to prepare pediatric patients for their upcoming MRI. The resource consists of an app and supporting preparation book and used a series of panoramic 360 degree videos of the entire MRI journey, including footage from within the bore of the scanner. The app, deployed via the Android Play Store and iOS App Store, can be viewed on most mobile phones, allowing a child to experience an MRI in VR using an inexpensive Google Cardboard headset. The app contains 360 degree videos within an animated, interactive VR interface designed for 4 to 12-year-olds. The resource was evaluated as part of a clinical audit on 23 patients (aged 4 to 12 years), and feedback was obtained from 10 staff members. In 5 patients, the resource was evaluated as a tool to prepare patients for an awake MRI who otherwise were booked to have an MRI under GA. RESULTS: The VR preparation resource has been successfully implemented at 3 UK institutions. Of the 23 patients surveyed, on a scale of 1 to 10, the VR resource was rated with a median score of 8.5 for enjoyment, 8 for helpfulness, and 10 for ease of use. All patients agreed that it made them feel more positive about their MRI, and all suggested they would recommend the resource to other children. When considering their experiences using the resource with pediatric patients, on a scale of 1 to 10, the staff members rated the VR resource a median score of 8.5 for enjoyment, 9 for helpfulness, and 9 for ease of use. All staff believed it could help prepare children for an awake MRI, thus avoiding GA. A successful awake MRI was achieved in 4 of the 5 children for whom routine care would have resulted in an MRI under GA. CONCLUSIONS: Our VR resource has the potential to relieve anxieties and better prepare patients for an awake MRI. The resource has potential to avoid GA through educating the child about the MRI process.

Differential Free Intracellular Calcium Release by Class II Antiarrhythmics in Cancer Cell Lines.

Class II antiarrhythmics or ß-blockers are antisympathetic nervous system agents that act by blocking ß-adrenoceptors. Despite their common clinical use, little is known about the effects of ß-blockers on free intracellular calcium (Ca2+ i), an important cytosolic second messenger and a key regulator of cell function. We investigated the role of four chemical analogs, commonly prescribed ß-blockers (atenolol, metoprolol, propranolol, and sotalol), on Ca2+ i release and whole-cell currents in mammalian cancer cells (PC3 prostate cancer and MCF7 breast cancer cell lines). We discovered that only propranolol activated free Ca2+ i release with distinct kinetics, whereas atenolol, metoprolol, and sotalol did not. The propranolol-induced Ca2+ i release was significantly inhibited by the chelation of extracellular calcium with ethylene glycol tetraacetic acid (EGTA) and by dantrolene, an inhibitor of the endoplasmic reticulum (ER) ryanodine receptor channels, and it was completely abolished by 2-aminoethoxydiphenyl borate, an inhibitor of the ER inositol-1,4,5-trisphosphate (IP3) receptor channels. Exhaustion of ER stores with 4-chloro-m-cresol, a ryanodine receptor activator, or thapsigargin, a sarco/ER Ca2+ ATPase inhibitor, precluded the propranolol-induced Ca2+ i release. Finally, preincubation of cells with sotalol or timolol, nonselective blockers of ß-adrenoceptors, also reduced the Ca2+ i release activated by propranolol. Our results show that different ß-blockers have differential effects on whole-cell currents and free Ca2+ i release and that propranolol activates store-operated Ca2+ i release via a mechanism that involves calcium-induced calcium release and putative downstream transducers such as IP3 The differential action of class II antiarrhythmics on Ca2+ i release may have implications on the pharmacology of these drugs.

Intercellular Ca2+ signalling in the adult mouse cochlea.

KEY POINTS: Intercellular Ca2+ waves are increases in cytoplasmic Ca2+ levels that propagate between cells. Periodic Ca2+ waves have been linked to gene regulation and are thought to play a crucial role in the development of our hearing epithelium, the organ of Corti and the acquisition of hearing. We observed regular periodic intercellular Ca2+ waves in supporting cells of an ex vivo preparation of the adult mouse organ of Corti, and these waves were found to propagate independently of extracellular ATP and were inhibited by the gap junction blockers 1-octanol and carbenoxolone. Our results establish that the existence of periodic Ca2+ waves in the organ of Corti is not restricted to the prehearing period. ABSTRACT: We have investigated wave-like cytoplasmic calcium (Ca2+ ) signalling in an ex vivo preparation of the adult mouse organ of Corti. Two types of intercellular Ca2+ waves that differ in propagation distance and speed were observed. One type was observed to travel up to 100 µm with an average velocity of 7 µm/s. Such waves were initiated by local tissue damage in the outer hair cell region. The propagation distance was decreased when the purinergic receptor antagonists pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS; 50 µm) or suramin (150 µm) were added to the extracellular buffer. Immunocytochemical analysis and experiments with calcium indicator dyes showed that both P2X and P2Y receptors were present in supporting cells. A second class of waves identified to travel longitudinally along the organ of Corti propagated at a lower velocity of 1-3 µm/s. These 'slow' Ca2+ waves were particularly evident in the inner sulcus and Deiters' cells. They travelled for distances of up to 500 µm. The slow Ca2+ signalling varied periodically (approximately one wave every 10 min) and was maintained for more than 3 h. The slow waves were not affected by apyrase, or by the P2 receptor agonists suramin (150 µm) or PPADS (50 µm) but were blocked by the connexin channel blockers octanol (1 mm) and carbenoxolone (100 µm). It is proposed that the observed Ca2+ waves might be a physiological response to a change in extracellular environment and may be involved in critical gene regulation activities in the supporting cells of the cochlea.

Outer Hair Cells and Electromotility.

Outer hair cells (OHCs) of the mammalian cochlea behave like actuators: they feed energy into the cochlear partition and determine the overall mechanics of hearing. They do this by generating voltage-dependent axial forces. The resulting change in the cell length, observed by microscopy, has been termed "electromotility." The mechanism of force generation OHCs can be traced to a specific protein, prestin, a member of a superfamily SLC26 of transporters. This short review will identify some of the more recent findings on prestin. Although the tertiary structure of prestin has yet to be determined, results from the presence of its homologs in nonmammalian species suggest a possible conformation in mammalian OHCs, how it can act like a transport protein, and how it may have evolved.

The neuroscience of hearing or how to do a hard job with soft components.

The inner ear is a small and relatively inaccessible structure. The use of multiple biophysical recording techniques from the late 1970s onwards, combined with molecular genetics to identify genes critically involved in cochlear development, has revealed how the cochlea acts as the front end for the central nervous system analysis of the auditory world. Some notable progress has been made in clarifying the mechanisms of frequency coding and cochlear amplification, and of mechano-transduction in hair cells and in establishing molecules necessary for normal (and by implication in abnormal) development of hearing and balance. There has been a parallel growth in understanding some of the neural networks in the brainstem and cortical areas responsible for processing the information derived from the auditory nerve. Informing future technical improvements to hearing aids and cochlear implants (electrically and optogenetically encoded), this chapter concentrates mainly on the neuroscience of peripheral hearing.

Outcome study of the pipeline embolization device for treatment of intracranial aneurysms at a single UK institution.

BACKGROUND: The introduction of flow-diverting stents in the last decade provides an alternative endovascular treatment choice in selected intracranial aneurysms. This retrospective analysis of a UK centre's experience provides insight into clinical and radiographic outcomes. METHODS: Electronic patient records, diagnostic and procedural images and written procedural records for patients treated with the PED between August 2009 and April 2014 were reviewed. Follow-up TOF MRA was performed after treatment. Clinical and radiographic outcomes were analyzed and compared with other PED studies. RESULTS: Twenty-nine patients with 30 attempted PED treatments were reviewed representing 3.5% of the treated aneurysm patient cohort. 63.6% (21/33) of the aneurysms were wide-necked (>4 mm), 60.6% (20/33) were large or giant (≥10 mm). The mean aneurysm sac diameter was 12.0 mm; the mean neck width was 4.5 mm. Mortality and morbidity rates were 3.3% and 10.0%, respectively. The total adequate occlusion rate was 78.1% (25/32) at 18 months. The neck width of aneurysms with residual sac filling and complete occlusion differed significantly (p = 0.04). CONCLUSIONS: Highly selected aneurysms treated with a PED in a UK centre have similar occlusion and complication rates when compared to non-UK studies. Again, it appeared that delayed aneurysm rupture remained a risk for PED treatment in large or giant aneurysms. Follow-up with TOF MRA gave similar occlusion results compared to those obtained with DSA in other studies. The influence of neck size on occlusion rate should be examined in future PED studies.