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Biomedical subjects

D G Cory

Publications and source records attributed to D G Cory.

12 recordsLinked to original sources

Gradient, high-resolution, magic angle spinning 1H nuclear magnetic resonance spectroscopy of intact cells.

The application of new gradient, high-resolution, magic angle spinning (MAS) 1H nuclear magnetic resonance (NMR) spectroscopy to the study of intact undifferentiated and differentiated NIH 3T3 F442A cells demonstrated improved spectral resolution and sensitivity compared with static studies. MAS of cells permits the detection and quantitation of many cellular metabolites that are not clearly resolved in nonspinning measurements and provides an improved visibility of phospholipids. Gradient, MAS enables the use of diffusion weighting for compartment assignment and the determination of mobility for many metabolites which are incompletely resolved using static techniques. The smaller, undifferentiated preadipocytes show no microscopic evidence of cell lysis after 2 h of MAS at 3.5 kHz and 82% of these cells remain viable by trypan blue exclusion. In contrast, 15-19% of the larger, lipid-laden differentiated adipocytes were found to suffer some degree of cell lysis with MAS. This new method is an attractive alternative to either nonspinning perfusion or extraction techniques for NMR studies of cells.

3T3 Cells

Pulsed gradient NMR probes for solid state studies.

Recently introduced studies of the spatial characteristics of spin dynamics in dipolarly coupled solids rely upon NMR probes with strong magnetic field gradients to create spatial magnetization gratings with periods of from 1 micron to 1 nm. The measurements are carried out as scattering experiments where the spatial displacement of spin coherence is recorded as a phase shift or attenuation of the magnetization grating. Recently we have employed these techniques to make a direct measurement of the spin diffusion rate in single crystal CaF2. Here we discuss designs for strong pulsed gradient NMR probes. Three gradient coil sets were designed and constructed, with coil constants of 0.32, 0.67, and 4.15 T/m/A. When driven by a pulsed current source that provides up to 300 A, pulsed gradients of 100, 200, and 600 T/m, respectively, were generated. These designs are fully described, along with practical issues of coil heating and probe stability.

Algorithms

Pulsed-field-gradient measurements of time-dependent gas diffusion.

Pulsed-field-gradient NMR techniques are demonstrated for measurements of time-dependent gas diffusion. The standard PGSE technique and variants, applied to a free gas mixture of thermally polarized xenon and O2, are found to provide a reproducible measure of the xenon diffusion coefficient (5.71 x 10(-6) m2 s-1 for 1 atm of pure xenon), in excellent agreement with previous, non-NMR measurements. The utility of pulsed-field-gradient NMR techniques is demonstrated by the first measurement of time-dependent (i.e., restricted) gas diffusion inside a porous medium (a random pack of glass beads), with results that agree well with theory. Two modified NMR pulse sequences derived from the PGSE technique (named the Pulsed Gradient Echo, or PGE, and the Pulsed Gradient Multiple Spin Echo, or PGMSE) are also applied to measurements of time dependent diffusion of laser polarized xenon gas, with results in good agreement with previous measurements on thermally polarized gas. The PGMSE technique is found to be superior to the PGE method, and to standard PGSE techniques and variants, for efficiently measuring laser polarized noble gas diffusion over a wide range of diffusion times.

Magnetic Resonance Spectroscopy

Ensemble quantum computing by NMR spectroscopy.

A quantum computer (QC) can operate in parallel on all its possible inputs at once, but the amount of information that can be extracted from the result is limited by the phenomenon of wave function collapse. We present a new computational model, which differs from a QC only in that the result of a measurement is the expectation value of the observable, rather than a random eigenvalue thereof. Such an expectation value QC can solve nondeterministic polynomial-time complete problems in polynomial time. This observation is significant precisely because the computational model can be realized, to a certain extent, by NMR spectroscopy on macroscopic ensembles of quantum spins, namely molecules in a test tube. This is made possible by identifying a manifold of statistical spin states, called pseudo-pure states, the mathematical description of which is isomorphic to that of an isolated spin system. The result is a novel NMR computer that can be programmed much like a QC, but in other respects more closely resembles a DNA computer. Most notably, when applied to intractable combinatorial problems, an NMR computer can use an amount of sample, rather than time, which grows exponentially with the size of the problem. Although NMR computers will be limited by current technology to exhaustive searches over only 15 to 20 bits, searches over as much as 50 bits are in principle possible, and more advanced algorithms could greatly extend the range of applicability of such machines.

Chemical Phenomena

Gradient, high-resolution, magic-angle spinning nuclear magnetic resonance spectroscopy of human adipocyte tissue.

The recently developed technique of gradient, high-resolution magic-angle spinning NMR (g-hr-MAS-NMR) spectroscopy was applied to the study of ex vivo human lipoma and liposarcoma tissue. Compared with conventional 1H-NMR, the g-hr-MAS method yielded a large improvement in spectral resolution and permitted the detection of metabolite resonance's in a well-differentiated liposarcoma that was not observed in spectra of similar samples obtained using nonspinning NMR methods. These findings suggest that g-hr-MAS-NMR spectroscopy provides a key improvement in spectral quality for ex vivo lipoma and liposarcoma tissue thereby permitting a more precise determination of tissue metabolite composition than conventional nonspinning NMR methods.

Adipocytes

RF gradient BIRD/TANGO sequence to eliminate uncoupled magnetization.

A modification of the BIRD and TANGO sequences is presented which employs radiofrequency field gradients to eliminate the net magnetization from uncoupled spins, while completely preserving coupled magnetization. The standard BIRD and TANGO sequences cause selective nutation of protons directly bound to a coupling partner, while returning uncoupled magnetization to +z. These sequences lend themselves naturally to modification using RF gradients, which require no increase in pulse-sequence complexity while providing substantial suppression of uncoupled resonances and elimination of typical antiphase and multiple-quantum error terms that arise from improperly set pulse lengths or delays. In the RF-gradient BIRD/TANGO sequence, the uncoupled magnetization is dephased in a plane orthogonal to the RF axis, while the desired signal components are refocused, effectively in a rotary echo. The sequence has applications to solvent suppression and selective isotopomer excitation. It is demonstrated for selective excitation of the satellites in a sample of chloroform, yielding suppression of the uncoupled magnetization by factor of approximately 800.

Chloroform

Shimming a high-resolution MAS probe.

A systematic and efficient approach to shimming a high-resolution, magic angle sample spinning probe is introduced. The method takes into account the different symmetries of the normal shim coils and the MAS experiment.

Computer Graphics

Nuclear magnetic resonance imaging of solid rocket propellants at 14.1 T.

Proton NMR images of solid propellant materials, consisting of a polybutadiene binder material filled with 82% solid particles, have been obtained at a magnetic field strength of 14.1 T and at a resolution of 8.5 x 8.5 micron. The images are the first of elastomeric materials obtained at a proton frequency of 600 MHz and have the highest spatial resolution yet reported. The images display a high contrast and are rich in information content. They reveal the distribution of individual filler particles in the polymer matrix as well as a thin polymer film of about 10-30 micron which is found to surround some of the larger filler particles.

Fossil Fuels

Distortions in multiple-pulse solid state NMR imaging: gradient decoupling, time-sequenced second averaging, and over-sampling.

Three approaches to reducing image artifacts are described that are specific to multiple-pulse line-narrowing methods of NMR imaging. Gradient decoupling avoids excess line broadening from off-resonance gradient phase evolution by restricting the gradient to selected windows in which the gradient Hamilton an commutes with the toggling frame state, and where the averaged Hamiltonian between gradient pulses is either cyclic or anti-cyclic. This forces the residual averaged dipolar Hamiltonian to be independent of the gradient evolution. Time-sequenced second averaging addresses the on-resonance broadening, where residual error terms dominate the spin dynamics (a lack of second averaging), by adding a second coherent averaging that retains part of the modulation associated with off-resonance terms, and thus smoothes out the line-narrowing efficiency with spatial offset. Over-sampling is useful to increase both the resolution and sensitivity of an image, but it introduces a sampling modulation that produces sidebands. These are eliminated by a series of prepulses in a fashion reminiscent of CYCLOPS phase cycling.

Magnetic Resonance Spectroscopy

Multiple pulse NMR imaging of polymers and chemistry.

Multiple pulse line narrowing techniques can be used to improve resolution and sensitivity in solid state NMR imaging. For example, pulse sequences which remove homonuclear dipolar broadening have been used to image proton-containing materials. Further enhancements in resolution and sensitivity are obtained by removing inhomogeneous interactions such as chemical shift, susceptibility, and heteronuclear dipolar broadening. Pulse sequences have been designed which provide efficient line narrowing over large spectral widths by taking into account the experimenter's control over the amplitude and time dependence of the gradient-induced resonance offset. These methods have been applied to centimeter sized samples to obtain images of polymers, composite materials, and gas-solid chemical reactions. T1 and T2 contrast allows differentiation between materials.

Magnetic Resonance Spectroscopy

Measurement of translational displacement probabilities by NMR: an indicator of compartmentation.

We introduce and demonstrate an NMR pulsed gradient stimulated echo method of directly obtaining the molecular translational displacement probability (displacement profile) of a liquid. The temporal development of the displacement profile reflects the presence of diffusion, restrictions to diffusion (e.g., walls, membranes), flow, and spatially dependent relaxation sinks. This approach allows the study of compartments which are too small to be observed by conventional NMR imaging methods. The distribution of spatial properties of compartments can be characterized over a spatial field of about 0.1 to 25 microns, completely independent of the absolute spatial location of the individual compartments.

Dimethyl Sulfoxide