Susceptibility induced gray–white matter MRI contrast in the human brain

AbstractMR phase images have shown significantly improved contrast between cortical gray and white matter regions compared to magnitude images obtained with gradient echo sequences. A variety of underlying biophysical mechanisms (including iron, blood, myelin content, macromolecular chemical exchange, and fiber orientation) have been suggested to account for this observation but assessing the individual contribution of these factors is limited in vivo.For a closer investigation of iron and myelin induced susceptibility changes, postmortem MRI of six human corpses (age range at death: 56–80years) was acquired in situ. Following autopsy, the iron concentrations in the frontal and occipital cortex as well as in white matter regions were chemically determined. The magnetization transfer ratio (MTR) was used as an indirect measure for myelin content. Susceptibility effects were assessed separately by determining R2* relaxation rates and quantitative phase shifts. Contributions of myelin and iron to local variations of the susceptibility were assessed by univariate and multivariate linear regression analysis.Mean iron concentration was lower in the frontal cortex than in frontal white matter (26±6 vs. 45±6mg/kg wet tissue) while an inverse relation was found in the occipital lobe (cortical gray matter: 41±10 vs. white matter: 34±10mg/kg wet tissue). Multiple regression analysis revealed iron and MTR as independent predictors of the effective transverse relaxation rate R2* but solely MTR was identified as source of MR phase contrast. R2* was correlated with iron concentrations in cortical gray matter only (r=0.42, p<0.05).In conclusion, MR phase contrast between cortical gray and white matter can be mainly attributed to variations in myelin content, but not to iron concentration. Both, myelin and iron impact the effective transverse relaxation rate R2* significantly. Magnitude contrast is limited because it only reflects the extent but not the direction of the susceptibility shift

On Nature of the Gradient Echo MR Signal and Its Application to Monitoring Multiple Sclerosis

Multiple Sclerosis is a common disease, affecting 2.5 million people world-wide. The clinical course is heterogeneous, ranging from benign disease in which patients live an almost normal life to severe and devastating disease that may shorten life. Despite much research, a fully effective treatment for MS is still unavailable and diagnostic techniques for monitoring MS disease evolution are much needed. As a non-invasive tool, Magnetic resonance imaging: MRI) plays a key role in MS diagnosis. Numerous MRI techniques have been proposed over the years. Among most widely used are conventional T1-weighted: T1W), T2-weighted: T2W) and FLuid Attenuated Inversion Recovery: FLAIR) imaging techniques. However their results do not correlate well with neurological findings. Several advanced MRI techniques are also used as research tools to study MS. Among them are magnetization transfer contrast imaging: MT), MR spectroscopy: MRS), and Diffusion Tensor Imaging: DTI) but they have not penetrated to clinical arena yet. Gradient Echo Plural Contrast Imaging: GEPCI) developed in our laboratory is a post processing technique based on multi-echo gradient echo sequence. It offers basic contrasts such as T1W images and T2* maps obtained from magnitude of GEPCI signal, and frequency maps obtained from GEPCI signal phase. Phase information of Gradient Echo MR signal has recently attracted much attention of the MR community since it manifests superior gray matter/ white matter contrast and sub-cortical contrast, especially at high field: 7 T) MRI. However the nature of this contrast is under intense debates. Our group proposed a theoretical framework - Generalized Lorentzian Approach - which emphasizes that, contrary to a common-sense intuition, phase contrast in brain tissue is not directly proportional to the tissue bulk magnetic susceptibility but is rather determined by the geometrical arrangement of brain tissue components: lipids, proteins, iron, etc.) at the cellular and sub-cellular levels - brain tissue magnetic architecture . In this thesis we have provide first direct prove of this hypothesis by measurement of phase contrast in isolated optic nerve. We have also provided first quantitative measurements of the contribution to phase contrast from the water-macromolecule exchange effect. Based on our measurement in protein solutions, we demonstrated that the magnitude of exchange effect is 1/2 of susceptibility effect and to the opposite sign. GEPCI technique also offers a scoring method for monitoring Multiple Sclerosis based on the quantitative T2* maps generated from magnitude information of gradient echo signal. Herein we demonstrated a strong agreement between GEPCI quantitative scores and traditional lesion load assessment. We also established a correlation between GEPCI scores and clinical tests for MS patients. We showed that this correlation is stronger than that found between traditional lesion load and clinical tests. Such studies will be carried out for longer period and on MS subjects with broader range of disease severity in the future. We have also demonstrated that the magnitude and phase information available from GEPCI experiment can be combined in multiple ways to generate novel contrasts that can help with visualization of neurological brain abnormalities beyond Multiple Sclerosis. In summary, in this study, we 1) propose novel contrasts for GEPCI from its basic images; 2) investigate the biophysical mechanisms behind phase contrast; 3) evaluate the benefits of quantitative T2* map offered by GEPCI in monitoring disease of Multiple Sclerosis by comparing GEPCI results to clinical standard techniques; 4) apply our theoretical framework - Generalized Lorentzian Approach - to better understand phase contrast in MS lesions

Isolation and characterisation of imipenem-resistant bacteria from natural environments and clinical settings

The development and spread of bacterial resistance to antimicrobials is now recognised as a key threat to public health and society. A small number of antimicrobials, including imipenem and vancomycin, are now considered to be the drugs of ‘last resort’ for treating antibiotic resistant bacteria. This study investigates and characterises antibiotic (imipenem) resistant bacteria in environmental and clinical samples from the U.K. Imipenem resistant (ImR) bacteria were isolated and characterised from river water samples from East Yorkshire and soil samples from Lincolnshire. ImR clinical isolates from different hospitals (York, Sheffield and Hull) were also characterised. Phenotypic resistance to imipenem was observed in 11.2% (75/670 CFU ml⁻¹), 13.3% (145.35 x 10⁵/ 109.1 x 10⁶ CFU g⁻¹) and 38.5% (42/109) of water, soil and clinical bacterial isolates, respectively.The minimum inhibitory concentrations (MICs) of the clinical isolates were generally higher (> 32 mg L⁻¹ in 71.4% of isolates) than those of the environmental isolates, which were around 4 mg L⁻¹ in 63.4% of water isolates and in 42.7% of soil isolates. β-lactamase activity studies showed that the most common β-lactamases among the environmental isolates were class B metallo β-lactamases (MBLs) (84.2%), while class A Klebsiella pneumoniae carbapenemases (KPCs) (40.5%) were the most common β-lactamases observed in the clinical isolates. Higher frequencies of multi-drug resistant (MDR) patterns were detected among the environmental isolates than among the clinical strains. Sequencing of 16S rRNA genes identified 30 (17 species), 96 (27 species), and 42 (11 species) ImR bacteria in water, soil and clinical samples, respectively. The most abundant genera identified were Caulobacter (36.7%), Stenotrophomonas (44.8%) and Stenotrophomonas (40.5%) from water, soil and clinical environments, respectively. PCR products were generated from ImR clinical isolates and some of the environmental isolates using primers targeting β-lactamase genes. Sequence analysis of these products from clinical isolates showed that they were specific and related to β-lactamase genes. However, the products from environmental isolates were not related to known genes characterised from antibiotic resistant clinically important bacteria. This suggests that there is a potentially large and divergent gene pool encoding for imipenem ressitance within natural environments, and that river water and agricultural soil are important as reservoirs of novel antibiotic resistance. Genome sequencing was used to characterise 8 MDR Stenotrophomonas spp. isolates from water, soil and clinical samples. This analysis showed the detection of β-lactamases genes (between 8 and 15 genes per isolate) including class A (L2), B (L1) and C (AmpC), fluoroquinolones resistance genes (between 4-8 genes per isolate), and genes encoding MDR efflux pumps (between 23-32 genes per isolate). Antibiotic resistance genes for other antimicrobials were also observed in small numbers; these represented aminoglycoside, sulphonamide and tetracycline resistance. Genes encoding resistance to heavy metal resistance (between 13-27 genes per isolate) were also observed. Overall, this research has demonstrated the widespread presence of imipenem resistant bacteria in environmental and clinical settings, carrying multiple resistances to other antibiotics. In particular, imipenem resistant Stenotrophomonas spp. were present in all of the environments studied and these bacteria were found to harbour multiple and diverse antibiotic resistance genes, that differed between isolates from environmental and clinical origins

Technical developments for clinical MR applications at 7 T

The aim of this thesis was to develop methods to enable the use of 7 Tesla MRI in clinical practice. A number of technical developments have been performed to facilitate clinical studies and to achieve the full potential of high field. Studies have been performed for imaging of different anatomies of the human body, including visualization of the right coronary artery and high resolution imaging of the brain in patients with neurodegenerative diseasesPhilips HealthcareUBL - phd migration 201

Susceptibility mapping in high field MRI

Phase images of the human brain acquired using gradient echo based Magnetic Resonance Imaging techniques show excellent contrast at 7T. This contrast is attributed to small variations in magnetic susceptibility that perturb the main magnetic field and thus yield a spatial variation of the NMR frequency. The work described in this thesis is primarily concerned with mapping the distribution of magnetic susceptibility within the human brain using these phase images. The main technical challenges of the project were first to extract accurate field maps based on phase data, and then to solve the ill-posed problem of inverting these field maps to reconstruct susceptibility (ϰ) maps. In initial work, simulations of field shifts based on known ϰ -distributions are compared to field maps acquired in vivo to highlight the non-local relationship between measured field offsets and the underlying susceptibility. These simulations were carried out using a recently derived Fourier method. The bulk of the thesis is then devoted to a detailed study of the process of inverting field maps generated from phase data using the Fourier relationship to yield quantitative 3D ϰ -maps. Unfortunately, the inversion problem is ill-posed and requires careful conditioning, either through rotation of the sample being imaged or through regularisation. A simple k-space threshold is introduced to condition the inversion and the preliminary results of applying this method to brain data from healthy subjects and patients with Parkinson's disease and multiple sclerosis are presented. The results suggest that susceptibility mapping is sensitive to iron deposition and could be a useful tool in investigating the progression of neurodegeneratived diseases. Iterative inversion algorithms, which deal with noise more robustly and allow more sophisticated filtering techniques to be employed, are then presented. These powerful regularisation methods are compared to previously described techniques, and are shown to yield high quality whole-brain ϰ -maps