Signal Improvement and Contrast Enhancement in Magnetic Resonance Imaging

This thesis reports advances in magnetic resonance imaging (MRI), with the ultimate goal of improving signal and contrast in biomedical applications. More specifically, novel MRI pulse sequences have been designed to characterize microstructure, enhance signal and contrast in tissue, and image functional processes. In this thesis, rat brain and red bone marrow images are acquired using iMQCs (intermolecular multiple quantum coherences) between spins that are 10 μm to 500 μm apart. As an important application, iMQCs images in different directions can be used for anisotropy mapping. We investigate tissue microstructure by analyzing anisotropy mapping. At the same time, we simulated images expected from rat brain without microstructure. We compare those with experimental results to prove that the dipolar field from the overall shape only has small contributions to the experimental iMQC signal. Besides magnitude of iMQCs, phase of iMQCs should be studied as well. The phase anisotropy maps built by our method can clearly show susceptibility information in kidneys. It may provide meaningful diagnostic information. To deeply study susceptibility, the modified-crazed sequence is developed. Combining phase data of modified-crazed images and phase data of iMQCs images is very promising to construct microstructure maps. Obviously, the phase image in all above techniques needs to be highly-contrasted and clear. To achieve the goal, algorithm tools from Susceptibility-Weighted Imaging (SWI) and Susceptibility Tensor Imaging (STI) stands out superb useful and creative in our system.

Electrostatic Energetics of Bacillus subtilis Ribonuclease P Protein Determined by Nuclear Magnetic Resonance-Based Histidine pKa Measurements.

The pKa values of ionizable groups in proteins report the free energy of site-specific proton binding and provide a direct means of studying pH-dependent stability. We measured histidine pKa values (H3, H22, and H105) in the unfolded (U), intermediate (I), and sulfate-bound folded (F) states of RNase P protein, using an efficient and accurate nuclear magnetic resonance-monitored titration approach that utilizes internal reference compounds and a parametric fitting method. The three histidines in the sulfate-bound folded protein have pKa values depressed by 0.21 ± 0.01, 0.49 ± 0.01, and 1.00 ± 0.01 units, respectively, relative to that of the model compound N-acetyl-l-histidine methylamide. In the unliganded and unfolded protein, the pKa values are depressed relative to that of the model compound by 0.73 ± 0.02, 0.45 ± 0.02, and 0.68 ± 0.02 units, respectively. Above pH 5.5, H22 displays a separate resonance, which we have assigned to I, whose apparent pKa value is depressed by 1.03 ± 0.25 units, which is ∼0.5 units more than in either U or F. The depressed pKa values we observe are consistent with repulsive interactions between protonated histidine side chains and the net positive charge of the protein. However, the pKa differences between F and U are small for all three histidines, and they have little ionic strength dependence in F. Taken together, these observations suggest that unfavorable electrostatics alone do not account for the fact that RNase P protein is intrinsically unfolded in the absence of ligand. Multiple factors encoded in the P protein sequence account for its IUP property, which may play an important role in its function.

An introduction to biological nuclear magnetic resonance spectroscopy

ABSTRACT Nuclear magnetic resonance (NMR) spectroscopy is one of the most powerful analytical techniques available to biology. This review is an introduction to the potential of this method and is aimed at readers who have little or no experience in acquiring or analyzing NMR spectra. We focus on spectroscopic applications of the magnetic resonance effect, rather than imaging ones, and explain how various aspects of the NMR phenomenon make it a versatile tool with which to address a number of biological problems. Using detailed examples, we discuss the use of 1H NMR spectroscopy in mixture analysis and metabolomics, the use of 13C NMR spectroscopy in tracking isotopomers and determining the flux through metabolic pathways (‘fluxomics’) and the use of 31P NMR spectroscopy in monitoring ATP generation and intracellular pH homeotasis in vivo. Further examples demonstrate how NMR spectroscopy can be used to probe the physical environment of a cell by measuring diffusion and the tumbling rates of individual metabolites and how it can determine macromolecular structures by measuring the bonds and distances which separate individual atoms. We finish by outlining some of the key challenges which remain in NMR spectroscopy and we highlight how recent advances— such as increased magnet field strengths, cryogenic cooling, microprobes and hyperpolarisation—are opening new avenues for today’s biological NMR spectroscopists.

Degradation of 4-fluorobiphenyl by mycorrhizal fungi as determined by (19)F nuclear magnetic resonance spectroscopy and (14)C radiolabelling analysis

The pathways of biotransformation of 4-fluorobiphenyl (4FBP) by the ectomycorrhizal fungus Tylospora fibrilosa and several other mycorrhizal fungi were investigated by using (19)F nuclear magnetic resonance (NMR) spectroscopy in combination with (14)C radioisotope-detected high-performance liquid chromatography ((14)C-HPLC). Under the conditions used in this study T. fibrillosa and some other species degraded 4FBP. (14)C-HPLC profiles indicated that there were four major biotransformation products, whereas (19)F NMR showed that there were six major fluorine-containing products. We confirmed that 4-fluorobiphen-4'-ol and 4-fluorobiphen-3'-ol were two of the major products formed, but no other products were conclusively identified. There was no evidence for the expected biotransformation pathway (namely, meta cleavage of the less halogenated ring), as none of the expected products of this route were found. To the best of our knowledge, this is the first report describing intermediates formed during mycorrhizal degradation of halogenated biphenyls.

Analysis of Betaine and Choline Contents of Aleurone, Bran, and Flour Fractions of Wheat (Triticum aestivum L.) Using 1H Nuclear Magnetic Resonance (NMR) Spectroscopy

In conventional milling, the aleurone layer is combined with the bran fraction. Studies indicate that the bran fraction of wheat contains the majority of the phytonutrients betaine and choline, with relatively minor concentrations in the refined flour. This present study suggests that the wheat aleurone layer (Triticum aestivum L. cv. Tiger) contains the greatest concentration of both betaine and choline (1553.44 and 209.80 mg/100 g of sample, respectively). The bran fraction contained 866.94 and 101.95 mg/100 g of sample of betaine and choline, respectively, while the flour fraction contained 23.30 mg/100 g of sample (betaine) and 28.0 mg/100 g of sample (choline). The betaine content for
the bran was lower, and the choline content was higher compared to previous studies, although it is known that there is large variation in betaine and choline contents between wheat cultivars. The ratio of betaine/choline in the aleurone fraction was approximately 7:1; in the bran, the ratio was approximately 8:1; and in the flour fraction, the ratio was approximately 1:1. The study further
emphasizes the superior phytonutrient composition of the aleurone layer.
INTRODUCTION
Wheat is a valuable source of betaine, choline (1, 2), B
vitamins, vitamin E, and a number of minerals, including iron,
zinc, magnesium, and phosphorus (3). Epidemiological studies
indicate that whole-grain consumption is protective against
several chronic diseases (4-12). It has not been fully elucidated
how whole-grain cereals or specific fractions (13) exert their
protective effect, but it is thought to be due to their content of
several nutrients associated with the reduced risk of disease.
Conventionally, whole grain is separated during milling into
bran, germ, and flour (14). The nutrient composition of these
fractions differ markedly; refined wheat flour contains approximately
50% less vitamins and minerals than whole-grain
flour (

Nuclear magnetic resonance-determined lipoprotein subclass profile in the DCCT/EDIC cohort:associations with carotid intima-media thickness

To relate nuclear magnetic resonance lipoprotein subclass profiles (NMR-LSP) and other lipoprotein-related factors with carotid intima-media thickness (IMT) in Type 1 diabetes.

Lipoprotein subclass profiles of hyperlipidemic diabetic mice measured by nuclear magnetic resonance spectroscopy

Dyslipidemia accelerates vascular complications of diabetes. Nuclear magnetic resonance (NMR) analysis of lipoprotein subclasses is used to evaluate a mouse model of human familial hypercholesterolemia +/- streptozotocin (STZ)-induced diabetes. A double knockout (DKO) mouse (low-density lipoprotein receptor [LDLr] -/-; apolipoprotein B [apoB] mRNA editing catalytic polypeptide-1 [Apobec1] -/-) was studied. Wild-type (WT) and DKO mice received sham or STZ injections at age 7 weeks, yielding control (WT-C, DKO-C) and diabetic (WT-D, DKO-D) groups. Fasting serum was collected when the mice were killed (age 40 weeks) for Cholestech analysis (Cholestech Corp, Hayward, CA) and NMR lipoprotein subclass profile. By Cholestech, fasting triglyceride and total cholesterol increased in DKO-C versus WT-C. Diabetes further increased total cholesterol in DKO. High-density lipoprotein cholesterol (HDL-C) was similar among all groups. NMR revealed that LDL in all groups was present in a subclass the size of large human LDL and was increased 48-fold in DKO-C versus WT-C animals, but was unaffected by diabetes. HDL was found in a subclass equivalent to large human HDL, and was similar among groups. In conclusion, NMR analysis reveals lipoprotein subclass distributions and the effects of genetic modification and diabetes in mice, but lack of particles the size of human small LDL and small HDL may limit the relevance of the present animal model to human disease.

Determination of 3,4-methylenedioxyamphetamine analogues (''ecstasy'') by proton nuclear magnetic resonance spectrometry

A procedure for the determination of three commonly encountered ecstasy type drugs has been demonstrated using proton nuclear magnetic resonance spectrometry (H-1-NMR).

Determining adsorbate configuration on alumina surfaces with 13C nuclear magnetic resonance relaxation time analysis

Relative strengths of surface interaction for individual carbon atoms in acyclic and cyclic hydrocarbons adsorbed on alumina surfaces are determined using chemically resolved 13C nuclear magnetic resonance (NMR) T1 relaxation times. The ratio of relaxation times for the adsorbed atoms T1,ads to the bulk liquid relaxation time T1,bulk provides an indication of the mobility of the atom. Hence a low T1,ads/T1,bulk ratio indicates a stronger surface interaction. The carbon atoms associated with unsaturated bonds in the molecules are seen to exhibit a larger reduction in T1 on adsorption relative to the aliphatic carbons, consistent with adsorption occurring through the carbon-carbon multiple bonds. The relaxation data are interpreted in terms of proximity of individual carbon atoms to the alumina surface and adsorption conformations are inferred. Furthermore, variations of interaction strength and molecular configuration have been explored as a function of adsorbate coverage, temperature, surface pre-treatment, and in the presence of co-adsorbates. This relaxation time analysis is appropriate for studying the behaviour of hydrocarbons adsorbed on a wide range of catalyst support and supported-metal catalyst surfaces, and offers the potential to explore such systems under realistic operating conditions when multiple chemical components are present at the surface.

Degradation of 4-fluorobiphenyl by mycorrhizal fungi as determined by 19F nuclear magnetic resonance spectroscopy and 14C radiolabelling analysis

The pathways of biotransformation of 4-fluorobiphenyl (4FBP) by the ectomycorrhizal fungus Tylospora fibrilosa and several other mycorrhizal fungi were investigated by using ¹⁹F nuclear magnetic resonance (NMR) spectroscopy in combination with ¹⁴C radioisotope-detected high-performance liquid chromatography (¹⁴C- HPLC). Under the conditions used in this study T. fibrillosa and some other species degraded 4FBP. ¹⁴C-HPLC profiles indicated that there were four major biotransformation products, whereas ¹⁹F NMR showed that there were six major fluorine-containing products. We confirmed that 4-fluorobiphen-4'-ol and 4-fluorobiphen-3'-ol were two of the major products formed, but no other products were conclusively identified. There was no evidence for the expected biotransformation pathway (namely, meta cleavage of the less halogenated ring), as none of the expected products of this route were found. To the best of our knowledge, this is the first report describing intermediates formed during mycorrhizal degradation of halogenated biphenyls.

Nuclear magnetic resonance-determined lipoprotein subclasses and carotid intima-media thickness in type 1 diabetes

BACKGROUND: Dyslipidemia has been linked to vascular complications of Type 1 diabetes (T1DM). We investigated the prospective associations of nuclear magnetic resonance-determined lipoprotein subclass profiles (NMR-LSP) and conventional lipid profiles with carotid intima-media thickness (IMT) in T1DM.

METHODS: NMR-LSP and conventional lipids were measured in a subset of Diabetes Control and Complications Trial (DCCT) participants (n = 455) at study entry ('baseline', 1983-89), and were related to carotid IMT determined by ultrasonography during the observational follow-up of the DCCT, the Epidemiology of Diabetes Interventions and Complications (EDIC) study, at EDIC Year 12 (2004-2006). Associations were defined using multiple linear regression stratified by gender, and following adjustment for HbA1c, diabetes duration, body mass index, albuminuria, DCCT randomization group, smoking status, statin use, and ultrasound devices.

RESULTS: In men, significant positive associations were observed between some baseline NMR-subclasses of LDL (total IDL/LDL and large LDL) and common and/or internal carotid IMT, and between conventional total- and LDL-cholesterol and non-HDL-cholesterol and common carotid IMT, at EDIC Year 12; these persisted in adjusted analyses (p < 0.05). Large LDL particles and conventional triglycerides were positively associated with common carotid IMT changes over 12 years (p < 0.05). Inverse associations of mean HDL diameter and large HDL concentrations, and positive associations of small LDL with common and/or internal carotid IMT (all p < 0.05) were found, but did not persist in adjusted analyses. No significant associations were observed in women.

CONCLUSION: NMR-LSP-derived LDL particles, in addition to conventional lipid profiles, may help in identifying men with T1DM at highest risk for vascular disease.

Radiographers perceptions of magnetic resonance imaging: a study of the causes that lead to the exams repetition

Purpose: To know how often occur the repetitions of MRI exams and sequences in radiology departments. Methods and Materials: A self applied-questionnaire was used as instrument and assigned to 57 radiographers who performed MRI exams to determine which were the causes that lead to the repetition. The questionnaires were interpreted and statistically analyzed through descriptive statistics and Spearman’s rho correlations. Results: At a 95% confidence interval, the major results suggest that the patient’s movement during de MRI exams is the main cause to repeat this exams (mean of 3.88 on a 5 points likert scale). However, there are causes related to the radiographer’s and the results showed that the introduction of wrong imaging parameters by the performer are a major cause too (N=26). Spearman rho correlations between radiographer’s time of experience and frequency of MRI exams repetitions were poor and not significant (r=0.141; p=0.297). The correlations between radiographer’s tiredness and frequency of MRI exams repetitions were negative, weak and not significant (r= -0.151; p=0.263). Conclusion: The patients’ movement may disrupt the examination or degrade the images with artifacts. The level of experience doesn’t influence the repetitions of MRI exams, it seems that seniors radiographers don’t have improvements in performance as it should be expected. It’s recommendable to do training courses regularly to improve the performance and systematically evaluate. Several features will need to be identified which would decrease the MRI exams repetitions.