Showing papers by "David C. Reutens published in 2019"

Probing entanglement in Compton interactions

Abstract: This theoretical research aims to examine areas of the Compton cross section of entangled annihilation photons for the purpose of testing for possible break down of theory, which could have consequences for predicted optimal capabilities of Compton PET systems. We provide maps of the cross section for entangled annihilation photons for experimental verification. We introduce a strategy to derive cross sections in a relatively straight forward manner for the Compton scattering of a hypothetical separable, mixed and entangled states. To understand the effect that entanglement has on the cross section for annihilation photons, we derive the cross section so that it is expressed in terms of the cross section of a hypothetical separable state and of a hypothetical forbidden maximally entangled state. We find lobe-like structures in the cross section which are regions where entanglement has the greatest effect. We also find that mixed states do not reproduce the cross section for annihilation photons, contrary to a recent investigation which reported otherwise. We review the motivation and method of the most precise Compton scattering experiment for annihilation photons, in order to resolve conflicting reports regarding the extent to which the cross section itself has been experimentally verified.

Small changes in synaptic gain lead to seizure-like activity in neuronal network at criticality.

Abstract: Epilepsy is a neurological disorder characterised by spontaneous recurrent seizures. The mechanisms by which multiple molecular and cellular changes lead to seizures is not well understood. Here, we study cortical seizure generation by simulating the activity of neuron groups in a network using the laminar cortex model. We identified a clear boundary between low-amplitude, asynchronous activity and high-amplitude, rhythmic activity, around which small changes in excitatory synaptic gain led to strong oscillatory activity. Neuron groups only responded significantly to stimulation around the boundary. The consequences of biophysical changes induced by epilepsy-related SCN1A mutations were also examined. Marked reduction in neuronal inhibition, as caused by mutations underlying Dravet syndrome, invariably led to strong neuronal firing, whereas small reductions in inhibition could cause significant changes when the network was poised close to the boundary. The study highlights the critical role of network dynamics in seizure genesis.

3D-Spatial encoding with permanent magnets for ultra-low field magnetic resonance imaging.

Abstract: We describe with a theoretical and numerical analysis the use of small permanent magnets moving along prescribed helical paths for 3D spatial encoding and imaging without sample adjustment in ultra-low field magnetic resonance imaging (ULF-MRI). With our developed method the optimal magnet path and orientation for a given encoding magnet number and instrument architecture can be determined. As a proof-of-concept, we studied simple helical magnet paths and lengths for one and two encoding magnets to evaluate the imaging efficiency for a mechanically operated ULF-MRI instrument with permanent magnets. We demonstrate that a single encoding magnet moving around the sample in a single revolution suffices for the generation of a 3D image by back projection.

Optimal-Margin Evolutionary Classifier

Abstract: We introduce a novel approach for discriminative classification using evolutionary algorithms. We first propose an algorithm to optimize the total loss value using a modified 0–1 loss function in a 1-D space for classification. We then extend this algorithm for multidimensional classification using an evolutionary algorithm. The proposed evolutionary algorithm aims to find a hyperplane that best classifies instances while minimizing the classification risk. We test particle swarm optimization, evolutionary strategy (ES), and covariance matrix adaptation ES for optimization purposes. After parameter selection, we compare our results with well-established and state-of-the-art classification algorithms, for both binary and multiclass classification, on 23 benchmark classification problems, with and without noise and outliers. We also compare these methods on a seizure detection task for 12 epileptic patients. Results show that the performance of the proposed algorithm is significantly (Wilcoxon test) better than all other methods in almost all problems tested. We also show that the proposed algorithm is significantly more robust against noise and outliers comparing to other methods. The running time of the algorithm is within a reasonable range for the solution of real-world classification problems.

Efficient Distribution of a Novel Zirconium-89 Labeled Anti-cd20 Antibody Following Subcutaneous and Intravenous Administration in Control and Experimental Autoimmune Encephalomyelitis-Variant Mice.

Abstract: Objective: To investigate the imaging and biodistribution of a novel zirconium-89 (89Zr)-labeled mouse anti-cd20 monoclonal antibody (mAb) in control and experimental autoimmune encephalomyelitis (EAE) mice following subcutaneous (s. c.) and intravenous (i.v.) administration. Background: Anti-cd20-mediated B-cell depletion using mAbs is a promising therapy for multiple sclerosis. Recombinant human myelin oligodendrocyte glycoprotein (rhMOG)-induced EAE involves B-cell-mediated inflammation and demyelination in mice. Design/Methods: C57BL/6J mice (n = 39) were EAE-induced using rhMOG. On Day 14 post EAE induction, 89Zr-labeled-anti-cd20 mAb was injected in control and EAE mice in the right lower flank (s.c.) or tail vein (i.v.). Positron emission tomography/computed tomography (PET/CT) imaging and gamma counting (ex vivo) were performed on Days 1, 3, and 7 to quantify tracer accumulation in the major organs, lymphatics, and central nervous system (CNS). A preliminary study was conducted in healthy mice to elucidate full and early kinetics of the tracer that were subsequently applied in the EAE and control mice study. Results: 89Zr-labeled anti-cd20 mAb was effectively absorbed from s.c. and i.v. injection sites and distributed to all major organs in the EAE and control mice. There was a good correlation between in vivo PET/CT data and ex vivo quantification of biodistribution of the tracer. From gamma counting studies, initial tracer uptake within the lymphatic system was found to be higher in the draining lymph nodes (inguinal or subiliac and sciatic) following s.c. vs. i.v. administration; within the CNS a significantly higher tracer uptake was observed at 24 h in the cerebellum, cerebrum, and thoracic spinal cord (p < 0.05 for all) following s.c. vs. i.v. administration. Conclusions: The preclinical data suggest that initial tracer uptake was significantly higher in the draining lymph nodes (subiliac and sciatic) and parts of CNS (the cerebellum and cerebrum) when administered s.c. compared with i.v in EAE mice.

Age-related differences in structural and functional prefrontal networks during a logical reasoning task

Abstract: In logical reasoning, difficulties in inhibition of currently-held beliefs may lead to unwarranted conclusions, known as belief bias. Aging is associated with difficulties in inhibitory control, which may lead to deficits in inhibition of currently-held beliefs. But, no study, to date, has investigated the underlying neural substrates of age-related differences in logical reasoning and the impact of belief loads. The aim of the present study was to delineate age differences in brain activity during a syllogistic logical reasoning task while the believability load of the logical inferences was manipulated. Twenty-nine, healthy, younger and thirty, healthy, older adults (males and females) completed a functional magnetic resonance imaging experiment in which they were asked to determine the logical validity of conclusions. Unlike younger adults, older adults engaged a large-scale network including anterior cingulate cortex (ACC) and inferior frontal gyrus (IFG) during conclusion stage. Our functional connectivity results suggest that while older adults engaged the ACC network to overcome their intuitive responses for believable inferences, the IFG network contributed to higher control over responses during both believable and unbelievable conditions. This result was further supported by mediation analysis indicating the role of Uncinate Fasciculus tract as a mediator for a relationship between age and rejection of believable statements. These novel findings lend evidence for age-related differences in belief bias, with potentially important implications for socially-relevant decision making where currently-held beliefs and given assumptions are in conflict.

Optimization of Distributions Differences for Classification

Abstract: In this paper, we introduce a new classification algorithm called the optimization of distribution differences (ODD). The algorithm aims to find a transformation from the feature space to a new space where the instances in the same class are as close as possible to one another, whereas the gravity centers of these classes are as far as possible from one another. This aim is formulated as a multiobjective optimization problem that is solved by a hybrid of an evolutionary strategy and the quasi-Newton method. The choice of the transformation function is flexible and could be any continuous space function. We experiment with a linear and a nonlinear transformation in this paper. We show that the algorithm can outperform eight other classification methods, namely naive Bayes, support vector machines, linear discriminant analysis, multilayer perceptrons, decision trees, and $k$ -nearest neighbors, and two recently proposed classification methods, in 12 standard classification data sets. Our results show that the method is less sensitive to the imbalanced number of instances compared with these methods. We also show that ODD maintains its performance better than other classification methods in these data sets and hence offers a better generalization ability.

Monopole antenna array design for 3 T and 7 T magnetic resonance imaging.

Abstract: Ultra-high field magnetic resonance imaging poses a number of challenges for robust radio frequency coil designs. A monopole antenna array can potentially overcome key limitations of birdcage coil designs and may provide a useful radio frequency coil for brain imaging. Four, 8 and 12 element monopole antenna arrays were simulated using 3 T and 7T magnetic resonance imaging frequencies. For comparison, 4, 8 and 12 element birdcage coils were also simulated. Coil performance was evaluated and compared and the impact of shielding was assessed. A 4 element monopole antenna array was fabricated and bench tested. Comparison of the 4, 8 and 12 element designs suggest that the monopole antenna array leads to better field properties than the birdcage coil in all configurations studied: unloaded, loaded with saline and loaded using a head phantom. Improvements in field properties and homogeneity were evident at both field strengths, implying that the monopole antenna array has potential for head imaging. The monopole antenna array also appears to be more efficient than the comparable birdcage coil design. Additionally, the former is scalable via the addition of more elements whereas our results suggest that this is not the case for the latter. Bench testing results show that the monopole antenna array is well matched with the transmission line, and mutual coupling between elements is sufficiently low. We found the monopole antenna array generated a larger field intensity than the birdcage coil design, whilst also producing a more useful magnetic resonance imaging field as measured by radio frequency field homogeneity. Our study suggests that magnetic resonance imaging of the brain can likely benefit from the use of radio frequency monopole antenna arrays.

Synthesis and Characterisation of Indium(iii) Bis-Thiosemicarbazone Complexes: 18F Incorporation for PET Imaging

Abstract: Several structurally related indium chlorido complexes of bis-thiosemicarbazones were prepared, starting from the appropriately substituted bis-thiosemicarbazones, using sodium methoxide in methanol. Detailed NMR studies were conducted to assign the structure including COSY, HSQC, and HMBC techniques. The structures of all indium complexes were solved using single crystal X-ray diffraction. The chlorido ligand was present at the apex of the square pyramidal coordination sphere in all indium complexes. In some complexes, an intermolecular hydrogen bond was present between the chlorine atom and an NH group. Three different indium chlorido complexes were converted into the corresponding fluorido-derivative by a simple halide exchange method using K18F. These novel complexes, containing the positron emitting isotope 18F, may have potential applications in positron emission tomography (PET).

NMR, X-Ray Crystal Structure Studies and Mechanism for Formation of a Novel Di-gallium Complex and 5-Methoxy-4,5,6-triphenyl-4,5-dihydro-1,2,4-triazene-3(2H)-thione

Abstract: Gallium complexes of bis-thiosemicarbazones were prepared and characterized using NMR and X-ray crystallography. Formation of a gallium nitrate complex was proven by NMR spectroscopy. Surprisingly, this complex was found to convert on standing to a new hydroxido-bridged di-gallium complex. The X-ray crystal structure of the digallium complex is described. Similarly, a triazene compound was formed during the preparation of the gallium complex comprising a tetraphenyl unit in the bis-thiosemicarbazone structure. We propose a mechanism for the formation of both the di-gallium species as well as triazene compound in solution. The lattice parameters for the digallium complex is as follows: a: 17.6854(13) A, b:16.6492(7) A, c: 21.4659(14) A, β = 112.383(8)°.

Investigation on the impact of three different quaternary methyl ammonium cartridges on the radiosynthetic yields of [18F]fluoromethyl tosylate

Abstract: Our recent investigations for the radiosynthesis of [18 F]fluoromethyl tosylate have highlighted that choice of quaternary methyl ammonium (QMA) cartridge used during the radiosynthesis can significantly impact the radiochemical yields. Often the details of the QMA cartridge used in fluourine-18 syntheses are not fully described. However, our studies demonstrate that the type, the size, and nature (method by which it has been conditioned) of the QMA cartridge used during the radiosynthesis can make a significant impact in the labelling efficiency. This paper investigates the use of three QMA cartridges and demonstrates that radiochemical yield (decay corrected) of [18 F]fluoromethyl tosylate can increase from 46% to 60% by simply changing the QMA cartridge (and leaving all other reagents and labelling conditions exactly the same). These learnings may be applied to improve the radiochemical yields of a number of [18 F]-fluorinated tracers (and synthons), where the labelling step is base-sensitive to increase the radiochemical yield, thereby significantly benefiting the radiochemistry and nuclear medicine community. This paper also highlights the necessity of the radiochemistry community to ensure the details of QMA cartridges used in fluorine-18 chemistry are fully and accurately described, since this will improve the translation of radiochemical methods from one laboratory to another.

Spatiotemporal Feature Selection Improves Prediction Accuracy of Multi-Voxel Pattern Classification

Abstract: The importance of spatiotemporal feature selection in fMRI decoding studies has not been studied exhaustively. Temporal embedding of features allows the incorporation of brain activity dynamics into multivariate pattern classification, and may provide enriched information about stimulus-specific response patterns and potentially improve prediction accuracy. This study investigates the possibility of enhancing the classification performance by exploring spatial and temporal (spatiotemporal) domain, to identify the optimum combination of the spatiotemporal features based on the classification performance. We investigated the importance of spatiotemporal feature selection using a slow event-related design adapted from the classic Haxby et al. (2001) study. Data were collected using a multiband fMRI sequence with temporal resolution of 0.568 seconds. A wide range of spatiotemporal observations was created as various combinations of spatiotemporal features. Using both random forest, and support vector machine, classifiers, prediction accuracies for these combinations were then compared with the single time-point spatial multivariate pattern approach that uses only a single temporal observation. The results showed that on average spatiotemporal feature selection improved prediction accuracy. Moreover, the random forest algorithm outperformed the support vector machine and benefitted from temporal information to a greater extent. As expected, the most influential temporal durations were found to be around the peak of the hemodynamic response function, a few seconds after the stimuli onset until ∼4 seconds after the peak of the hemodynamic response function. The superiority of spatiotemporal feature selection over single time-point spatial approaches invites future work to design systematic and optimal approaches to the incorporation of spatiotemporal dependencies into feature selection for decoding. Highlights Spatiotemporal feature selection effect on MVPC was assessed in slow event-related fMRI Spatiotemporal feature selection improved brain decoding accuracy From ∼2-11 seconds after stimuli onset were the most informative part of each trial Random forest outperformed support vector machines Random forest benefited more from temporal changes compared with support vector machine

A new role of hippocampus during logical reasoning and belief bias in aging

Abstract: Reasoning requires initial encoding of the semantic association between premises or assumptions, retrieval of these semantic associations from memory, and recombination of information to draw a logical conclusion. Currently-held beliefs can interfere with the content of the assumptions if not congruent and inhibited. This study aimed to investigate the role of the hippocampus and hippocampal networks during logical reasoning tasks in which the congruence between currently-held beliefs and assumptions varies. Participants of younger and older age completed a series of syllogistic reasoning tasks in which two premises and one conclusion were presented and they were required to decide if the conclusion logically followed the premises. The belief load of premises was manipulated to be either congruent or incongruent with currently-held beliefs. Our whole-brain results showed that older adults recruited the hippocampus during the premise integration stage more than their younger counterparts. Functional connectivity using a hippocampal seed revealed that older, but not younger, adults recruited a hippocampal network that included anterior cingulate and inferior frontal regions when premises were believable. Importantly, this network contributed to better performance in believable inferences, only in older adults group. Further analyses suggested that, in older adults group, the integrity of the left cingulum bundle was associated with the higher correct rejection of believable premises more than unbelievable ones. Using multimodal imaging, this study highlights the importance of the hippocampus during premise integration and supports the compensatory role of the hippocampal network during a logical reasoning task among older adults.

Synthesis of 18F-radiolabeled diphenyl gallium dithiosemicarbazone using a novel halogen exchange method and in vivo biodistribution

Abstract: 18 F-radiolabeled diphenyl gallium thiosemicarbazone was prepared by [18 F] fluoride exchange of a nitrato anion under mild conditions. The diphenyl gallium thiosemicarbazone chloride is easily prepared in gram quantities and can be used at room temperature in the presence of oxygen. The corresponding nitrate complex is prepared using silver nitrate in methanol solvent and can be stored under nitrogen for weeks before radiolabeling. The biodistribution of this new tracer was studied in mice using positron emission tomography (PET).

Probing entanglement in Compton interactions.

Abstract: This theoretical research aims to examine areas of the Compton cross section of entangled annihilation photons for the purpose of testing for possible break down of theory, which could have consequences for predicted optimal capabilities of Compton PET systems.We provide maps of the cross section for entangled annihilation photons for experimental verification.We introduce a strategy to derive cross sections in a relatively straight forward manner for the Compton scattering of a hypothetical separable, mixed and entangled states. To understand the effect that entanglement has on the cross section for annihilation photons, we derive the cross section so that it is expressed in terms of the cross section of a hypothetical separable state and of a hypothetical forbidden maximally entangled state.We find lobe-like structures in the cross section which are regions where entanglement has the greatest effect.We also find that mixed states do not reproduce the cross section for annihilation photons, contrary to a recent investigation which reported otherwise.We review the motivation and method of the most precise Compton scattering experiment for annihilation photons, in order to resolve conflicting reports regarding the extent to which the cross section itself has been experimentally verified.