34 research outputs found

    Studies Of Proton Nuclear Magnetic Resonance Relaxation In Human Cortical Bone: From Ex Vivo Spectroscopy To Clinical Imaging Methods

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    Current clinical bone diagnostic measures rely predominantly on X-ray-based contrast and are primarily sensitive to bone mineral content. Since bone also contains collagen and water components, which are heavily implicated in fracture resistance, these X-ray measures are micro-anatomically incomplete and do not identify individuals who will fracture. This dissertation aims to improve clinical bone fracture risk assessment through the use of novel magnetic resonance imaging (MRI) methods, which provide quantitative measures of the non-mineral bone components. The overall goal is to advance our understanding of 1H nuclear magnetic resonance (NMR) relaxation in human cortical bone to the point that diagnostically-relevant parameters may be extracted from in vivo bone MRI measurements. To accomplish this, custom NMR hardware was first developed for a rigorous, NMR relaxation-based characterization of ex vivo cortical bone. Such characterization was used to identify the micro-anatomical origins of cortical bone NMR signal components, which included collagen, bound water, and pore water protons. These signal components correlated well with various bone mechanical properties, indicating diagnostic relevance. Using the well-characterized cortical bone relaxation characteristics, novel and clinically practical methods for quantitative, diagnostic bone MRI were developed and validated. Collectively, this work represents a biophysical basis for cortical bone MRI, which stands ready for translation to clinical and research studies

    Quantitative Characterization of Biological Tissues by NMR Relaxation in the Rotating Frame

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    Measurements of the spin-lattice relaxation rate in the rotating frame, R1rho, using spin-locking techniques have long been exploited to investigate relatively slow molecular motions and, more recently, to analyze chemical exchange. The variation of R1rho with spin-lock amplitude, or R1rho dispersion, provides the means to examine dynamic processes occurring on the time scale of the applied effective field, but corresponding techniques have been somewhat overlooked by the MRI community. Chemical exchange contributions to R1rho of protons in tissues are shown to dominate conventional dipole-dipole interactions at high fields, and R1rho dispersion depends on the exchange rate and chemical shift of the labile species. In addition, proton diffusion in the presence of intrinsic susceptibility gradients also contributes significantly to R1rho dispersion at low spin-lock amplitudes. Simulations and experiments performed in this work reveal these effects to largely be the dominant mechanisms influencing spin-locked relaxation at high static magnetic fields, and demonstrate the potential for using R1rho to characterize tissues across a variety of pathologies. Exchange-based R1rho methods are used to quantify exchange rates in solutions containing one or two solute pools and to produce images in which the contrast emphasizes the presence of metabolites exchanging at specific rates rather than with specific chemical shifts. A novel theory is derived that quantifies diffusion-based R1rho dispersion, which is subsequently applied to create parametric maps that reflect average sub-voxel microstructure and to calculate intrinsic gradient strengths in model systems of polystyrene microspheres and Red Blood Cells (RBC’s). This approach may further be used to estimate cell sizes and to emphasize vasculature of specific sizes in fMRI studies. Exchange and diffusion effects are also verified to be independent processes that may be analyzed simultaneously in biologically relevant applications. Collectively, R1rho dispersion methods provide a powerful alternative to traditional MRI methods and produce novel complementary information for quantitative tissue characterize

    Correlations of measured peak stress and T<sub>2</sub> spectral component amplitudes (NMR, left) and avBMD measured by μCT (right).

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    <p>Blue, red, and green data show integrated amplitudes (<i>S<sub>A</sub></i>, <i>S<sub>B</sub></i>, and <i>S<sub>C</sub></i>) of the T<sub>2</sub>-discriminated signals from pools A, B, and C, respectively. The black data show the total <sup>1</sup>H NMR signal (<i>S<sub>A</sub></i>+<i>S<sub>B</sub></i>+<i>S<sub>C</sub></i>), and the purple data are derived from μCT-based measures of avBMD. Each of the NMR signals amplitudes shows a significant linear correlation with peak stress and both <i>S<sub>B</sub></i> and <i>S<sub>C</sub></i> correlate more strongly with peak stress than does avBMD. Note that the total <sup>1</sup>H NMR signal does not correlate well with peak stress.</p

    Solid line shows a the T<sub>2</sub> spectrum from a typical bone sample, and the dotted line shows the spectrum that results following the complex average of two signals, with and without an adiabatic full passage magnetization preparation.

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    <p>The total integrated signal from this long-T<sub>2</sub> suppressed spectrum is 95% from signals with T<sub>2</sub><1 ms, thereby demonstrating in principle a simple and practical method for generating a MRI contrast dominated by <i>S<sub>A</sub></i>+<i>S<sub>B</sub></i>.</p

    Summary of T<sub>2</sub> spectra measured from 40 human cortical bone samples.

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    <p>All spectra exhibited a short-T<sub>2</sub> component (T<sub>2</sub>≈60 µs), derived primarily from collagen protons, an intermediate T<sub>2</sub> components (T<sub>2</sub>≈400 µs), derived primarily from collagen-bound water protons, and a broad distribution of long-T<sub>2</sub> components (1 ms2<1 s), derived from a combination of pore water and lipid protons.</p

    Non-invasive predictors of human cortical bone mechanical properties: T(2)-discriminated H NMR compared with high resolution X-ray.

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    Recent advancements in magnetic resonance imaging (MRI) have enabled clinical imaging of human cortical bone, providing a potentially powerful new means for assessing bone health with molecular-scale sensitivities unavailable to conventional X-ray-based diagnostics. To this end, (1)H nuclear magnetic resonance (NMR) and high-resolution X-ray signals from human cortical bone samples were correlated with mechanical properties of bone. Results showed that (1)H NMR signals were better predictors of yield stress, peak stress, and pre-yield toughness than were the X-ray derived signals. These (1)H NMR signals can, in principle, be extracted from clinical MRI, thus offering the potential for improved clinical assessment of fracture risk

    Theory of Chemical Exchange Saturation Transfer MRI in the context of different magnetic fields

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    Chemical Exchange Saturation Transfer (CEST) MRI is a versatile MRI method that provides contrast based on the level of molecular and metabolic activity. This contrast arises from indirect measurement of protons in low concentration molecules that are exchanging with the abundant water proton pool. The indirect measurement is based on magnetization transfer of rf-prepared magnetization from the small pool to the water pool. The signal can be modeled by the Bloch-McConnell equations combining standard magnetization dynamics and chemical exchange processes. In this article, we will review analytical solutions of the Bloch-McConnell equations and especially the derived CEST signal equations and their implications. The analytical solutions give direct insight on the dependency of measurable CEST effects on underlying parameters such as the exchange rate and concentration of the solute pools, but also on the system parameters such as the rf irradiation field B1 as well as the static magnetic field B0. These theoretical field strength dependencies and their influence on sequence design are highlighted herein. In vivo results of different groups making use of these field strength benefits/dependencies are reviewed and discussed
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