%0 Journal Article %J Magnetic Resonance Imaging %D 2007 %T Dispersion measurements using time-of-flight remote detection MRI %A Granwehr, J. %A Harel, E. %A Hilty, C. %A Garcia, S. %A Chavez, L. %A Pines, A. %A Sen, P. N. %A Song, Y. Q. %K flow %X

Remote detection nuclear magnetic resonance and magnetic resonance imaging can be used to study fluid flow and dispersion in a porous medium from a purely Eulerian point of view (i.e., in a laboratory frame of reference). Information about fluid displacement is obtained on a macroscopic scale in a long-time regime, while local velocity distributions are averaged out. It is shown how these experiments can be described using the common flow propagator formalism and how experimental data can be analyzed to obtain effective porosity, flow velocity inside the porous medium, fluid dispersion and flow tracing of fluid. (C) 2007 Elsevier Inc. All rights reserved.

%B Magnetic Resonance Imaging %V 25 %P 449-452 %8 May %@ 0730-725X %G English %U ://WOS:000246425100004 %N 4 %M WOS:000246425100004 %! Dispersion measurements using time-of-flight remote detection MRI %R Doi 10.1016/J.Mri.2006.11.011 %0 Journal Article %J Journal of Physical Chemistry B %D 2007 %T Quantifying the diffusion of a fluid through membranes by double phase encoded remote detection magnetic resonance imaging %A Telkki, V. V. %A Hilty, C. %A Garcia, S. %A Harel, E. %A Pines, A. %K mri %X

We demonstrate that a position correlation magnetic resonance imaging (MRI) experiment based on two phase encoding steps separated by a delay can be used for quantifying diffusion across a membrane. This method is noninvasive, and no tracer substance or concentration gradient across the membrane is required. Because, in typical membranes, the T-1 relaxation time of the fluid spins is usually much longer than the T-2 time, we developed and implemented a new position correlation experiment based on a stimulated spin-echo, in which the relaxation attenuation of the signal is dominated by T-1 instead of T-2. This enables using relatively long delays needed in the diffusion measurements. The sensitivity of the double encoded experiment detected in a conventional way is still low because of the low filling factor of the fluid inside the NMR coil around the sample. We circumvent this problem by using the remote detection technique, which significantly increases the sensitivity, making it possible to do the measurements with gaseous fluids that have a low spin-density compared to liquids. We derive a model that enables us to extract a diffusion constant characterizing the diffusion rate through the membrane from the obtained correlation images. The double phase encoded MRI method is advantageous in any kind of diffusion studies, because the propagator of fluid molecules can directly be seen from the correlation image.

%B Journal of Physical Chemistry B %V 111 %P 13929-13936 %8 Dec 20 %@ 1520-6106 %G English %U ://WOS:000251615400011 %N 50 %M WOS:000251615400011 %! Quantifying the diffusion of a fluid through membranes by double phase encoded remote detection magnetic resonance imaging %R Doi 10.1021/Jp076760e %0 Journal Article %J Journal of Magnetic Resonance %D 2007 %T Sensitivity enhancement by exchange mediated magnetization transfer of the xenon biosensor signal %A Garcia, S. %A Chavez, L. %A Lowery, T. J. %A Han, S. I. %A Wemmer, D. E. %A Pines, A. %K resonance %X

Hyperpolarized xenon associated with ligand derivatized cryptophane-A cages has been developed as a NMR based biosensor. To optimize the detection sensitivity we describe use of xenon exchange between the caged and bulk dissolved xenon as an effective signal amplifier. This approach, somewhat analogous to 'remote detection' described recently, uses the chemical exchange to repeatedly transfer spectroscopic information from caged to bulk xenon, effectively integrating the caged signal. After an optimized integration period, the signal is read out by observation of the bulk magnetization. The spectrum of the caged xenon is reconstructed through use of a variable evolution period before transfer and Fourier analysis of the bulk signal as a function of the evolution time. (c) 2006 Elsevier Inc. All rights reserved.

%B Journal of Magnetic Resonance %V 184 %P 72-77 %8 Jan %@ 1090-7807 %G English %U ://WOS:000243568900009 %N 1 %M WOS:000243568900009 %! Sensitivity enhancement by exchange mediated magnetization transfer of the xenon biosensor signal %R Doi 10.1016/J.Jmr.2006.09.010 %0 Journal Article %J Journal of Magnetic Resonance %D 2006 %T Auxiliary probe design adaptable to existing probes for remote detection NMR, MRI, and time-of-flight tracing %A Han, S. I. %A Granwehr, J. %A Garcia, S. %A McDonnell, E. E. %A Pines, A. %K flow %X

A versatile, detection-only probe design is presented that can be adapted to any existing NMR or MRI probe with the purpose of making the remote detection concept generally applicable. Remote detection suggests freeing the NMR experiment from the confinement of using the same radio frequency (RF) coil and magnetic field for both information encoding and signal detection. Information is stored during the encoding step onto a fluid sensor medium whose magnetization is later measured in a different location. The choice of an RF probe and magnetic field for encoding can be made based solely on the size and characteristics of the sample and the desired information quality without considering detection sensitivity, as this aspect is dealt with by a separate detector. While early experiments required building probes that included two resonant circuits, one for encoding and one for detection, a modular approach with a detection-only probe as presented here can be used along with any existing NMR probe of choice for encoding. The design of two different detection-only probes is presented, one with a saddle coil for milliliter-sized detection volumes, and the other one with a microsolenoid coil for sub-microliter fluid quantities. As example applications, we present time-of-flight (TOF) tracing of hyperpolarized Xe-129 spins in a gas mixture through coiled tubing using the microsolenoid coil detector and TOF flow imaging through a nested glass container where the gas flow changes its direction twice between inlet and outlet using the saddle coil detector. (c) 2006 Elsevier Inc. All rights reserved.

%B Journal of Magnetic Resonance %V 182 %P 260-272 %8 Oct %@ 1090-7807 %G English %U ://WOS:000241203900010 %N 2 %M WOS:000241203900010 %! Auxiliary probe design adaptable to existing probes for remote detection NMR, MRI, and time-of-flight tracing %R Doi 10.1016/J.Jmr.2006.06.024 %0 Journal Article %J Chembiochem %D 2006 %T Optimization of xenon biosensors for detection of protein interactions %A Lowery, T. J. %A Garcia, S. %A Chavez, L. %A Ruiz, E. J. %A Wu, T. %A Brotin, T. %A Dutasta, J. P. %A King, D. S. %A Schultz, P. G. %A Pines, A. %A Wemmer, D. E. %K complexes %X

Hyperpolarized Xe-129 NMR spectroscopy can detect the presence of specific low-concentration biomolecular analytes by means of a xenon biosensor that consists of a water-soluble, targeted cryptophane-A cage that encapsulates the xenon. In this work, we use the prototypical biotinylated xenon biosensor to determine the relationship between the molecular composition of the xenon biosensor and the characteristics of protein-bound resonances. The effects of diastereomer overlap, dipole-dipole coupling, chemical-shift anisotropy, xenon exchange, and biosensor conformotional exchange on the protein-bound biosensor signal were assessed. It was found that an optimal protein-bound biosensor signal can be obtained by minimizing the number of biosensor diastereomers and using a flexible linker of appropriate length. Both the line width and sensitivity of chemical shift to protein binding of the xenon biosensor were found to be inversely proportional to linker length.

%B Chembiochem %V 7 %P 65-73 %8 Jan %@ 1439-4227 %G English %U ://WOS:000234701000012 %N 1 %M WOS:000234701000012 %! Optimization of xenon biosensors for detection of protein interactions %R Doi 10.1002/Cbic.200500327 %0 Journal Article %J Analytical Chemistry %D 2005 %T NMR-based biosensing with optimized delivery of polarized Xe-129 to solutions %A Han, S. I. %A Garcia, S. %A Lowery, T. J. %A Ruiz, E. J. %A Seeley, J. A. %A Chavez, L. %A King, D. S. %A Wemmer, D. E. %A Pines, A. %K blood %X

Laser-enhanced (LE) Xe-129 nuclear magnetic resonance (NMR) is an exceptional tool for sensing extremely small physical and chemical changes; however, the difficult mechanics of bringing polarized xenon and samples of interest together have limited applications, particularly to biological molecules. Here we present a method for accomplishing solution Xe-129 biosensing based on flow (bubbling) of LE Xe-129 gas through a solution in situ in the NMR probe, with pauses for data acquisition. This overcomes fundamental limitations of conventional solution-state LE Xe-129 NMR, e.g., the difficulty in transferring hydrophobic xenon into aqueous environments, and the need to handle the sample to refresh LE Xe-129 after an observation pulse depletes polarization. With this new method, we gained a factor of > 100 in sensitivity due to improved xenon transfer to the solution and the ability to signal average by renewing the polarized xenon. Polarized xenon in biosensors was detected at very low concentrations, <= 250 nanomolar, while retaining all the usual information from NMR. This approach can be used to simultaneously detect multiple sensors with different chemical shifts and is also capable of detecting signals from opaque, heterogeneous samples, which is a unique advantage over optical methods. This general approach is adaptable for sensing minute quantities of xenon in heterogeneous in vitro samples, in miniaturized devices and should be applicable to certain in-vivo environments.

%B Analytical Chemistry %V 77 %P 4008-4012 %8 Jul 1 %@ 0003-2700 %G English %U ://WOS:000230270800035 %N 13 %M WOS:000230270800035 %! NMR-based biosensing with optimized delivery of polarized Xe-129 to solutions %R Doi 10.1021/Ac0500479 %0 Journal Article %J Physical Review Letters %D 2005 %T Time-of-flight flow imaging using NMR remote detection %A Granwehr, J. %A Harel, E. %A Han, S. %A Garcia, S. %A Pines, A. %A Sen, P. N. %A Song, Y. Q. %K mri %X

A time-of-flight imaging technique is introduced to visualize fluid flow and dispersion through porous media using NMR. As the fluid flows through a sample, the nuclear spin magnetization is modulated by rf pulses and magnetic field gradients to encode the spatial coordinates of the fluid. When the fluid leaves the sample, its magnetization is recorded by a second rf coil. This scheme not only facilitates a time-dependent imaging of fluid flow, it also allows a separate optimization of encoding and detection subsystems to enhance overall sensitivity. The technique is demonstrated by imaging gas flow through a porous rock.

%B Physical Review Letters %V 95 %8 Aug 12 %@ 0031-9007 %G English %U ://WOS:000231247300028 %N 7 %M WOS:000231247300028 %! Time-of-flight flow imaging using NMR remote detection %R Doi 10.1103/Physrevlett.95.075503