Nuclear magnetic resonance spectroscopy and ultrasound

The work described in this thesis is directed to the examination of the hypothesis that ultrasound may be used to perturb molecular motion in the liquid phase. These changes can then be detected by nuclear magnetic resonance (NMR) in spin-lattice and spin-spin relaxation times. The objective being to develop a method capable of reducing the pulsed NMR acquisition times of slowly relaxing nuclei. The thesis describes the theoretical principles underlying both NMR spectroscopy and ultrasonics with particular attention being paid to factors that impinge on testing the above hypothesis. Apparatus has been constructed to enable ultrasound at frequencies between 1 and 10 mega-hertz with a variable power up to 100W/cm-2 to be introduced in the NMR sample. A broadband high frequency generator is used to drive PZT piezo-electric transducer via various transducer to liquid coupling arrangements. A commercial instrument of 20 kilo-hertz has also been employed to test the above hypothesis and also to demonstrate the usefulness of ultrasound in sonochemistry. The latter objective being, detection of radical formation in monomer and polymer ultrasonic degradation. The principle features of the results obtained are: Ultrasonic perturbation of T1 is far smaller for pure liquids than is for mixtures. The effects appear to be greater on protons (1H) than on carbon-13 nuclei (13C) relaxation times. The observed effect of ultrasonics is not due to temperature changes in the sample. As the power applied to the transducer is progressively increased T1 decreases to a minimum and then increases. The T1's of the same nuclei in different functional groups are influenced to different extents by ultrasound. Studies of the 14N resonances from an equimolar mixture of N, N-dimethylformamide and deuterated chloroform with ultrasonic frequencies at 1.115, 6, 6.42 and 10 MHz show that as the frequency is increased the NMR signal to noise ratio decreases to zero at the Larmor frequency of 6.42 MHz and then again rises. This reveals the surprising indication that an effect corresponding to nuclear acoustic saturation in the liquid may be observable. Ultrasonic irradiation of acidified ammonium chloride solution at and around 6.42 MHz appears to cause distinctive changes in the proton-nitrogen J coupling resonance at 89.56 MHz. Ultrasonic irradiation of N, N-dimethylacetamide at 2 KHz using the lowest stable power revealed the onset of coalescence in the proton spectrum. The corresponding effect achieved by direct heating required a temperature rise of approximately 30oC. The effects of low frequency (20 KHz) on relaxation times appear to be nil. Detection of radical formation proved difficult but is still regarded as the principle route for monomer and polymer degradation. The initial hypothesis is considered proven with the results showing significant changes in the mega-hertz region and none at 20 KHz.

Nuclear magnetic resonance studies of molecular interactions and structures

This thesis is concerned with the investigation, by nuclear magnetic resonance spectroscopy, of the molecular interactions occurring in mixtures of benzene and cyclohexane to which either chloroform or deutero-chloroform has been added. The effect of the added polar molecule on the liquid structure has been studied using spin-lattice relaxation time, 1H chemical shift, and nuclear Overhauser effect measurements. The main purpose of the work has been to validate a model for molecular interaction involving local ordering of benzene around chloroform. A chemical method for removing dissolved oxygen from samples has been developed to encompass a number of types of sample, including quantitative mixtures, and its supremacy over conventional deoxygenation technique is shown. A set of spectrometer conditions, the use of which produces the minimal variation in peak height in the steady state, is presented. To separate the general diluting effects of deutero-chloroform from its effects due to the production of local order a series of mixtures involving carbon tetrachloride, instead of deutero-chloroform, have been used as non-interacting references. The effect of molecular interaction is shown to be explainable using a solvation model, whilst an approach involving 1:1 complex formation is shown not to account for the observations. It is calculated that each solvation shell, based on deutero-chloroform, contains about twelve molecules of benzene or cyclohexane. The equations produced to account for the T1 variations have been adapted to account for the 1H chemical shift variations in the same system. The shift measurements are shown to substantiate the solvent cage model with a cage capacity of twelve molecules around each chloroform molecule. Nuclear Overhauser effect data have been analysed quantitatively in a manner consistent with the solvation model. The results show that discrete shells only exist when the mole fraction of deutero-chloroform is below about 0.08.

Co-registration of magnetoencephalography with magnetic resonance imaging using bite-bar-based fiducials and surface-matching

Objective: To introduce a new technique for co-registration of Magnetoencephalography (MEG) with magnetic resonance imaging (MRI). We compare the accuracy of a new bite-bar with fixed fiducials to a previous technique whereby fiducial coils were attached proximal to landmarks on the skull. Methods: A bite-bar with fixed fiducial coils is used to determine the position of the head in the MEG co-ordinate system. Co-registration is performed by a surface-matching technique. The advantage of fixing the coils is that the co-ordinate system is not based upon arbitrary and operator dependent fiducial points that are attached to landmarks (e.g. nasion and the preauricular points), but rather on those that are permanently fixed in relation to the skull. Results: As a consequence of minimizing coil movement during digitization, errors in localization of the coils are significantly reduced, as shown by a randomization test. Displacement of the bite-bar caused by removal and repositioning between MEG recordings is minimal (∼0.5 mm), and dipole localization accuracy of a somatosensory mapping paradigm shows a repeatability of ∼5 mm. The overall accuracy of the new procedure is greatly improved compared to the previous technique. Conclusions: The test-retest reliability and accuracy of target localization with the new design is superior to techniques that incorporate anatomical-based fiducial points or coils placed on the circumference of the head. © 2003 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Three-dimensional modeling of the human eye based on magnetic resonance imaging

PURPOSE. A methodology for noninvasively characterizing the three-dimensional (3-D) shape of the complete human eye is not currently available for research into ocular diseases that have a structural substrate, such as myopia. A novel application of a magnetic resonance imaging (MRI) acquisition and analysis technique is presented that, for the first time, allows the 3-D shape of the eye to be investigated fully. METHODS. The technique involves the acquisition of a T2-weighted MRI, which is optimized to reveal the fluid-filled chambers of the eye. Automatic segmentation and meshing algorithms generate a 3-D surface model, which can be shaded with morphologic parameters such as distance from the posterior corneal pole and deviation from sphericity. Full details of the method are illustrated with data from 14 eyes of seven individuals. The spatial accuracy of the calculated models is demonstrated by comparing the MRI-derived axial lengths with values measured in the same eyes using interferometry. RESULTS. The color-coded eye models showed substantial variation in the absolute size of the 14 eyes. Variations in the sphericity of the eyes were also evident, with some appearing approximately spherical whereas others were clearly oblate and one was slightly prolate. Nasal-temporal asymmetries were noted in some subjects. CONCLUSIONS. The MRI acquisition and analysis technique allows a novel way of examining 3-D ocular shape. The ability to stratify and analyze eye shape, ocular volume, and sphericity will further extend the understanding of which specific biometric parameters predispose emmetropic children subsequently to develop myopia. Copyright © Association for Research in Vision and Ophthalmology.

Development of a novel magnetic resonance imaging contrast agent for pressure measurements using lipid-coated microbubbles

The aim of this study was to prepare gas-filled lipid-coated microbubbles as potential MRI contrast agents for imaging of fluid pressure. Air-filled microbubbles were produced with phospholipid 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) in the presence or absence of cholesterol and/or polyethylene-glycol distearate (PEG-distearate). Microbubbles were also prepared containing a fluorinated phospholipid, perfluoroalkylated glycerol-phosphatidylcholine, F-GPC shells encompassing perfluorohexane-saturated nitrogen gas. These microbubbles were evaluated in terms of physico-chemical characteristics such as size and stability. In parallel to these studies, DSPC microbubbles were also formulated containing nitrogen (N2) gas and compared to air-filled microbubbles. By preventing advection, signal drifts were used to assess their stability. DSPC microbubbles were found to have a drift of 20% signal change per bar of applied pressure in contrast to the F-GPC microbubbles which are considerably more stable with a lower drift of 5% signal change per bar of applied pressure. By increasing the pressure of the system and monitoring the MR signal intensity, the point at which the majority of the microbubbles have been damaged was determined. For the DSPC microbubbles this occurs at 1.3 bar whilst the F-GPC microbubbles withstand pressures up to 2.6 bar. For the comparison between air-filled and N2-filled microbubbles, the MRI sensitivity is assessed by cycling the pressure of the system and monitoring the MR signal intensity. It was found that the sensitivity exhibited by the N2-filled microbubbles remained constant, whilst the air-filled microbubbles demonstrated a continuous drop in sensitivity due to continuous bubble damage.

Three-dimensional magnetic resonance imaging of the phakic crystalline lens during accommodation

To quantify changes in crystalline lens curvature, thickness, equatorial diameter, surface area, and volume during accommodation using a novel two-dimensional magnetic resonance imaging (MRI) paradigm to generate a complete three-dimensional crystalline lens surface model.

Evaluation of the sonically induced narrowing of nuclear magnetic resonance spectra of solids

The Nuclear Magnetic Resonance (NMR) spectra of liquids contain a wealth of quantitative information that may be derived, for instance, from chemical shifts and spin-spin couplings. The available information depends on the incoherent rapid molecular motion that causes complicating effects present in the solid state to average to zero. Whereas liquid state NMR spectra show narrow lines, the corresponding NMR spectra from the solid state are normally composed of exceedingly broad resonance lines due to highly restricted molecular motion. It is, therefore, difficult to obtain directly as detailed information from the spectra of solids as from those derived from the liquid state. Studies on a new technique (SINNMR, the sonically induced narrowing of the NMR spectra of solids) to remove line broadening effects in the NMR spectra of the solid state are reported within this thesis. SINNMR involves narrowing the NMR absorptions from solid particles by irradiating them with ultrasound when they are suspended in a support liquid. It is proposed that ultrasound induces incoherent motion of the suspended particles, producing motional characteristics of the particles similar to those of rather large molecules. The first report of apparently successful experiments involving SINNMR[1] emphasised both the irreproducibility of the technique and the uncertainty regarding its true origin. If SINNMR can be made reproducible and the effect definitively attributed to the sonically induced incoherent motional averaging of particles, the technique could offer a simple alternative to the now classical magic-angle spinning (MAS) NMR[2] and the recently reported dynamic angle spinning (DAS)[3] and double rotation (DOR)[4] techniques. Evidence is presented in this thesis to support the proposal that ultrasound may be used to narrow the NMR spectral resonances from solids by inducing incoherent motion of particles suspended in support liquids and, additionally, for some solids, by inducing rotational motion of molecular constituents in the lattices of solids. Successful SINNMR line narrowing using 20 kHz ultrasound is reported for a variety of samples: including trisodium orthophosphate, polytetrafluoroethylene and aluminium alloys. Investigations of SINNMR line narrowing in trisodium phosphate have revealed the relationship between ultrasonic power, particle size and support liquid density for the production of optimum SINNMR conditions. It is also proposed that the incoherent motion of particles induced by 20 kHz ultrasound can originate from interactions between acoustically induced cavitation microjets and particles.

Three-dimensional fluid pressure mapping in porous media using magnetic resonance imaging with gas-filled liposomes

This paper presents and demonstrates a method for using magnetic resonance imaging to measure local pressure of a fluid saturating a porous medium. The method is tested both in a static system of packed silica gel and in saturated sintered glass cylinders experiencing fluid flow. The fluid used contains 3% gas in the form of 3-μm average diameter gas filled 1,2-distearoyl-sn-glycero-3-phosphocholine (C18:0, MW: 790.16) liposomes suspended in 5% glycerol and 0.5% Methyl cellulose with water. Preliminary studies at 2.35 T demonstrate relative magnetic resonance signal changes of 20% per bar in bulk fluid for an echo time TE=40 ms, and 6-10% in consolidated porous media for TE=10 ms, over the range 0.8-1.8 bar for a spatial resolution of 0.1 mm3 and a temporal resolution of 30 s. The stability of this solution with relation to applied pressure and methods for improving sensitivity are discussed. © 2007 Elsevier Inc. All rights reserved.

A multimodal investigation of dynamic face perception using functional magnetic resonance imaging and magnetoencephalography

Motion is an important aspect of face perception that has been largely neglected to date. Many of the established findings are based on studies that use static facial images, which do not reflect the unique temporal dynamics available from seeing a moving face. In the present thesis a set of naturalistic dynamic facial emotional expressions was purposely created and used to investigate the neural structures involved in the perception of dynamic facial expressions of emotion, with both functional Magnetic Resonance Imaging (fMRI) and Magnetoencephalography (MEG). Through fMRI and connectivity analysis, a dynamic face perception network was identified, which is demonstrated to extend the distributed neural system for face perception (Haxby et al.,2000). Measures of effective connectivity between these regions revealed that dynamic facial stimuli were associated with specific increases in connectivity between early visual regions, such as inferior occipital gyri and superior temporal sulci, along with coupling between superior temporal sulci and amygdalae, as well as with inferior frontal gyri. MEG and Synthetic Aperture Magnetometry (SAM) were used to examine the spatiotemporal profile of neurophysiological activity within this dynamic face perception network. SAM analysis revealed a number of regions showing differential activation to dynamic versus static faces in the distributed face network, characterised by decreases in cortical oscillatory power in the beta band, which were spatially coincident with those regions that were previously identified with fMRI. These findings support the presence of a distributed network of cortical regions that mediate the perception of dynamic facial expressions, with the fMRI data providing information on the spatial co-ordinates paralleled by the MEG data, which indicate the temporal dynamics within this network. This integrated multimodal approach offers both excellent spatial and temporal resolution, thereby providing an opportunity to explore dynamic brain activity and connectivity during face processing.

Examination of the predictive value of structural magnetic resonance scans in bipolar disorder:a pattern classification approach

Background - Bipolar disorder (BD) is one of the leading causes of disability worldwide. Patients are further disadvantaged by delays in accurate diagnosis ranging between 5 and 10 years. We applied Gaussian process classifiers (GPCs) to structural magnetic resonance imaging (sMRI) data to evaluate the feasibility of using pattern recognition techniques for the diagnostic classification of patients with BD. Method - GPCs were applied to gray (GM) and white matter (WM) sMRI data derived from two independent samples of patients with BD (cohort 1: n = 26; cohort 2: n = 14). Within each cohort patients were matched on age, sex and IQ to an equal number of healthy controls. Results - The diagnostic accuracy of the GPC for GM was 73% in cohort 1 and 72% in cohort 2; the sensitivity and specificity of the GM classification were respectively 69% and 77% in cohort 1 and 64% and 99% in cohort 2. The diagnostic accuracy of the GPC for WM was 69% in cohort 1 and 78% in cohort 2; the sensitivity and specificity of the WM classification were both 69% in cohort 1 and 71% and 86% respectively in cohort 2. In both samples, GM and WM clusters discriminating between patients and controls were localized within cortical and subcortical structures implicated in BD. Conclusions - Our results demonstrate the predictive value of neuroanatomical data in discriminating patients with BD from healthy individuals. The overlap between discriminative networks and regions implicated in the pathophysiology of BD supports the biological plausibility of the classifiers.

Moderate relationships between NAA and cognitive ability in healthy adults:implications for cognitive spectroscopy

Background: Proton Magnetic Resonance Spectroscopy (H-MRS) is a non-invasive imaging technique that enables quantification of neurochemistry in vivo and thereby facilitates investigation of the biochemical underpinnings of human cognitive variability. Studies in the field of cognitive spectroscopy have commonly focused on relationships between measures of N-acetyl aspartate (NAA), a surrogate marker of neuronal health and function, and broad measures of cognitive performance, such as IQ. Methodology/Principal Findings: In this study, we used H-MRS to interrogate single-voxels in occipitoparietal and frontal cortex, in parallel with assessments of psychometric intelligence, in a sample of 40 healthy adult participants. We found correlations between NAA and IQ that were within the range reported in previous studies. However, the magnitude of these effects was significantly modulated by the stringency of data screening and the extent to which outlying values contributed to statistical analyses. Conclusions/Significance: H-MRS offers a sensitive tool for assessing neurochemistry non-invasively, yet the relationships between brain metabolites and broad aspects of human behavior such as IQ are subtle. We highlight the need to develop an increasingly rigorous analytical and interpretive framework for collecting and reporting data obtained from cognitive spectroscopy studies of this kind. © 2014 Patel, Blyth, Griffiths, Kelly and Talcott.