A multi-modal approach to functional neuroimaging

The work undertaken involves the use of functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) as separate but complementary non-invasive functional brain imaging modalities. The aim in combining fMRI and MEG is centred around exploitation of the high temporal resolution available in MEG, and the high spatial resolution available in fMRI. However, whilst MEG represents a direct measure of neuronal activity, BOLD fMRI is an indirect measure and this makes the two modalities truly complementary. In both cases, the imaging signals measured are relatively poorly understood and so the fundamental question asked here is: How are the neuromagnetic effects detectable using MEG related to the metabolic effects reflected in the fMRI BOLD response? Initially, a novel technique is introduced for the detection and spatial localisation of neuromagnetic effects in MEG. This technique, based on a beamforming approach to the MEG inverse problem, is shown to yield accurate results both in simulation and using experimental data. The technique introduced is applied to MEG data from a simple experiment involving stimulation of the visual cortex. A number of heterogeneous neuromagnetic effects are shown to be detectable, and furthermore, these effects are shown to be spatially and temporally correlated with the fMRI BOLD response. The limitations to comparing only two measures of brain activity are discussed, and the use of arterial spin labelling (ASL) to make quantitative measurements of physiological parameters supplementing these two initial metrics is introduced. Finally, a novel technique for accurate quantification of arterial cerebral blood volume using ASL is described and shown to produce accurate results. A concluding chapter then speculates on how these aCBV measurements might be combined with those from MEG in order to better understand the fMRI BOLD response

A multi-modal approach to functional neuroimaging

The work undertaken involves the use of functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) as separate but complementary non-invasive functional brain imaging modalities. The aim in combining fMRI and MEG is centred around exploitation of the high temporal resolution available in MEG, and the high spatial resolution available in fMRI. However, whilst MEG represents a direct measure of neuronal activity, BOLD fMRI is an indirect measure and this makes the two modalities truly complementary. In both cases, the imaging signals measured are relatively poorly understood and so the fundamental question asked here is: How are the neuromagnetic effects detectable using MEG related to the metabolic effects reflected in the fMRI BOLD response? Initially, a novel technique is introduced for the detection and spatial localisation of neuromagnetic effects in MEG. This technique, based on a beamforming approach to the MEG inverse problem, is shown to yield accurate results both in simulation and using experimental data. The technique introduced is applied to MEG data from a simple experiment involving stimulation of the visual cortex. A number of heterogeneous neuromagnetic effects are shown to be detectable, and furthermore, these effects are shown to be spatially and temporally correlated with the fMRI BOLD response. The limitations to comparing only two measures of brain activity are discussed, and the use of arterial spin labelling (ASL) to make quantitative measurements of physiological parameters supplementing these two initial metrics is introduced. Finally, a novel technique for accurate quantification of arterial cerebral blood volume using ASL is described and shown to produce accurate results. A concluding chapter then speculates on how these aCBV measurements might be combined with those from MEG in order to better understand the fMRI BOLD response

Robust laser-free entanglement with trapped ions

Trapped ions with microwave radiation are a promising platform for universal quantum computing. However, a major obstacle in the way of scalability is the coupling of the qubits to their noisy environment. This thesis offers means to improve the fidelity of two-qubit entangling gates. To this end, we investigate noise from classical control hardware and study quantum control methods that increase the gate’s robustness. The noise spectrums of classical control hardware typically exhibit non-Markovian behaviour. Therefore, a transfer function in frequency space is derived for each source, transforming hardware noise to qubit-frame noise. It is found that voltage noise on the electrodes is a significant contribution to decoherence as it displaces the ions within the static magnetic field gradient. We propose and demonstrate a voltage noise cancellation scheme that is compatible with microfabricated surface traps. We then identify a library of quantum control methods that increase the robustness of a bichromatic interaction to both spin and motional decoherence. We also propose a novel σz ⊗ σz entangling gate which makes use of the intrinsic J-coupling interaction of ions in a static magnetic gradient. The resulting interaction is virtually insensitive to motional decoherence, which alleviates stringent experimental requirements. We finally demonstrate a bichromatic interaction that is simultaneously robust to spin and motional decoherence, by means of continuous dynamical decoupling and phase modulation on the sidebands. Recalling that noise in the ion’s position couples into magnetic field noise due to the static magnetic field gradient, we use this noise mechanism as the basis of a promising electric field sensor. We experimentally demonstrate AC electrometry with a sensitivity of S = 7.0(5)mVm−1Hz−1/2. Noise spectroscopy was also demonstrated and was limited by the noise floor, where the minimum sensitivity was 545 nVm−1Hz−1/2.Open Acces

Development of reflectance imaging methodologies to investigate super-paramagnetic iron oxide nanoparticles

Engineered nanoparticles, such as super paramagnetic iron oxide nanoparticles (SPIONs) offer significant benefits for the development of various diagnostic and therapeutic strategies. Limitations of existing imaging methodologies in the study of NPs, such as the effects of fluorescent labelling and diffraction limited resolution, and the advantages that visualization of spatial localization can offer in studies, increases the demand for new and optimized imaging routines. Reflectance Confocal Microscopy (RCM) methods were optimized and Reflectance Structured Illumination Microscopy (R-SIM) was introduced, offering a two fold increase in resolution - particularly advantageous for NP quantification and localization studies. Analysis routines were developed to enable the automated quantification of NP presence within cells via the different methodologies. Correlative procedures were also established for imaging the same sample with different reflectance methods and TEM, maximizing the information attainable from a single sample and allowing comparisons between the techniques for specific applications. These aforementioned optimized techniques were then applied to the determination of NP uptake and trafficking in cancer cell lines, and, in combination with siRNA, to ascertain proteins that are involved in the uptake process. Studies were also performed to model the degradative process of SPIONs within cellular compartments. This thesis thus provided several important tools for the future assessment of the efficacy and safety of NPs for clinical use, enabling quantitative analysis of uptake route, sub-cellular localization and NP intracellular fate