A closer look into DESIRE for NMR microscopy

The major challenge of nuclear magnetic resonance (NMR) microscopy at a spatial resolution of a few micrometers is to obtain a sufficiently high signal-to-noise-ratio (SNR) within a reasonable measurement time. As a particular difficulty, molecular self-diffusion poses a serious limitation to true spatial resolution and SNR if conventional Fourier encoding techniques are used. Opposed to that, the alternative DESIRE (Diffusion Enhancement of SIgnal and REsolution) approach to NMR microscopy utilises diffusion to increase the SNR. Being a real-space imaging method, spatial localisation is accomplished by saturation pulses while diffusion continuously replaces the saturated by unsaturated spins. For this technique a signal enhancement of up to three orders of magnitude has been predicted and initial experimental data have provided a proof of principle. In the present work, a detailed investigation of one-dimensional (1D) DESIRE is presented including simulations of a real implementation of the method, a quantitative experimental analysis, and basic 1D imaging. The simulations reveal the importance and provide the means of ensuring the true spatial resolution for this particular way of localisation, enable the selection of useful experimental parameters, and predict the specific image contrast to be expected around barriers restricting diffusion. Experimental data are presented with resolutions down to 3 microm and DESIRE enhancement up to 25 that are in good agreement with the simulation results. In particular, 1D DESIRE imaging in a phantom confirms the expected signal drop close to barriers due to spatially restricted diffusion.     

Time-independent point-spread function for NMR microscopy.

The resolution of NMR microscopy is analyzed in terms of the point-spread function, PSF(r), and the equivalent k space modulation transfer function, MTF(k). The analysis is developed for NMR spin warp and projection reconstruction imaging experiments; however, the framework provided is quite general. Incoherent spin motion is analyzed to predict what limits, if any, on spatial resolution are imposed by diffusion. Previous estimates of diffusion limits at 1-5 microns were developed for specific imaging techniques, typically using a mean displacement argument. Although qualitatively correct, the quantitative predictions represent practical rather than fundamental limits. It is shown that diffusion-dependent "blurring" can be made arbitrarily small and that the practical limits are less stringent than previously thought. A major point illustrated by the PSF-MTF formulation is that the irreversible loss of coherence by randomly diffusing spins occurs faster than the physical displacement, thereby reducing their effect considerably on the frequency or phase of the net detected signal. The irreversible loss of signal due to diffusive motion will contribute to and possibly dominate the signal-to-noise limit of resolution. The resolution as measured by the width of the PSF and MTF for diffusion is shown to be independent of the signal acquisition time, and their functional forms allow selection of microscopic imaging parameters. An example of a three-dimensional spin-warp image of a green algae cell is shown with resolution of approximately 16 microns x 13 microns x 10 microns.     

One micrometer resolution NMR microscopy

We obtained a magnetic resonance image of 1 microm resolution and 75 microm(3) voxel volume for a phantom filled with hydrocarbon oil within an hour at 14.1 T. For this work, a specially designed probe with a high sensitivity RF coil and gradient coils generating over 1000 G/cm was built. The optimal pulse sequence was analyzed in consideration of the bandwidth, diffusion coefficients, and T(1) and T(2) relaxations of the medium. The system was applied to the in vivo imaging of a geranium leaf stem to get the images of 2 microm resolution and 200 microm(3) voxel volume.     

NMR microscopy of polyurethane foams

NMR microimaging has been applied to the characterization of foam materials, in order to understand their properties and gain deeper insight into their structures. The structure of "open cell" foams can be visualized with sufficient resolution to obtain the size and shape of cells, as well as their spatial distribution within specimens. Statistics of cell sizes have been calculated from NMR microscopy and are in good agreement with results obtained from electron microscopy. We demonstrate that the local density of foams, which are parameters largely inaccessible by other analytical methods, readily can be determined by NMR microscopy.     

A new general-purpose fully automatic baseline-correction procedure for 1D and 2D NMR data

A new procedure for automatic baseline correction of NMR data sets is presented. It is based on an improved automatic recognition of signal-free regions that uses a Continuous Wavelet transform derivative calculation, followed by a baseline modelling procedure based on the Whittaker smoother algorithm. The method has been proven to automatically flatten 1D and 2D NMR spectra with large baseline distortions arising from different sources, is tolerant to low signal-to-noise ratio spectra, and to signals of varying widths in a single spectrum. Even though this procedure has so far only been applied to NMR spectra, we believe it to also be applicable to other spectroscopies having relatively narrow peaks (e.g., mass spectrometry), and potentially to those with broad peaks (e.g., near infrared or ultraviolet).     

Partially and fully cured thin film photoresist waveguides for integrated optics

A systematic and detailed study of waveguide fabrication and characterization of a commercially available (from Shipley) photoresist is reported. Various waveguide properties such as refractive index, optical losses, waveguide thickness, dispersion and birefringence are reported. Effect of temperature of guide formation, curing (partial and full) and UV exposure on these parameters is also presented.     

OPENCORE NMR: open-source core modules for implementing an integrated FPGA-based NMR spectrometer

A tool kit for implementing an integrated FPGA-based NMR spectrometer [K. Takeda, A highly integrated FPGA-based nuclear magnetic resonance spectrometer, Rev. Sci. Instrum. 78 (2007) 033103], referred to as the OPENCORE NMR spectrometer, is open to public. The system is composed of an FPGA chip and several peripheral boards for USB communication, direct-digital synthesis (DDS), RF transmission, signal acquisition, etc. Inside the FPGA chip have been implemented a number of digital modules including three pulse programmers, the digital part of DDS, a digital quadrature demodulator, dual digital low-pass filters, and a PC interface. These FPGA core modules are written in VHDL, and their source codes are available on our website. This work aims at providing sufficient information with which one can, given some facility in circuit board manufacturing, reproduce the OPENCORE NMR spectrometer presented here. Also, the users are encouraged to modify the design of spectrometer according to their own specific needs. A home-built NMR spectrometer can serve complementary roles to a sophisticated commercial spectrometer, should one comes across such new ideas that require heavy modification to hardware inside the spectrometer. This work can lower the barrier of building a handmade NMR spectrometer in the laboratory, and promote novel and exciting NMR experiments.     

Quantitative NMR microscopy on intact plants

Quantitative high resolution images on intact young maize plants were acquired by using magnetization-prepared NMR microscopy. Although the spatial resolution is low compared with that of light microscopy, the calculated spin density and T₁ maps exhibit contrasts that are in excellent agreement with photomicrographic images. The T₂ map gives image contrasts that are not visible in a usual light microscopic image. The diffusion images show an anisotropic behavior of the water self-diffusion coefficient in the vascular bundles, which can be understood by the cell morphology in this plant section. This work demonstrates that quantitative imaging on intact plant systems is possible and that long total acquisition times are no obstacle. Furthermore, the different single parameter maps give a better insight into the morphology of plants under in vivo conditions.     

NMR Q-space microscopy of concentrated oil-in-water emulsions

The pulsed field gradient stimulated echo technique with selective excitation is used to probe the diffusion of water in the continuous phase of concentrated oil-in-water emulsions. The dependence of the echo amplitude, S(q,Delta), on wavevector, q, and diffusion time, Delta, shows that the water diffusion propagator is sensitive to emulsion microstructure. This is analyzed using a multiple exponential time series expansion of S(q,Delta) in Delta, with wavevector dependent expansion coefficients. These coefficients are compared with predictions from several theoretical models for three types of stable emulsion, each differing in microstructure. The relationship between the nuclear magnetic resonance q-space measurements and bulk rheology for all three types of emulsion is also explored.     

A procedure for obtaining pure absorption 2D J-spectra: application to quantitative fully J-decoupled homonuclear NMR spectra

The phase-twisted lines, resulting from a double complex Fourier transform, can greatly alter the quality of two-dimensional spectra. This problem, which is generally overcome by experimental procedures (requiring twice as much time as a standard measurement), is inevitable in the two-dimensional J-resolved experiment. This experiment is revisited theoretically and a postprocessing treatment, leading to pure 2D J-spectra, is deduced. Quantitative fully J-decoupled homonuclear spectra are accordingly obtained by means of a projection onto the F2 axis after a 45 degrees tilt.     

TopSpin核磁共振软件中集成的DOSY采集／处理模块DOSYmTM

Bruker TopSpinTM核磁共振软件中集成的DOSY数据采集和处理模块DOSYm^TM,可以方便简单地进行DOSY实验的在线数据采集与处理,并已很好地应用于复杂混合物的定性和定量分析,如天然混合物、石油产品、医药产品、食品工业及质量控制等领域．本文介绍了DOSY实验的原理,数据采集和处理的方法及DOSYm^TM模块的应用．     

Velocity and diffusion imaging in dynamic NMR microscopy

The imposition of resolution gradients in a pulsed-gradient spin-echo (PGSE) NMR sequence induces motionally dependent phase and amplitude modulation in the image, a technique which we have termed dynamic NMR microscopy. Fourier analysis of this modulation gives a dynamic displacement profile for each pixel which can then be analyzed to obtain velocity and diffusion maps. The application of this method at high spatial resolution is motivated by a desire to measure vascular flow in living plants and variations in molecular self-diffusion under the influence of velocity shear in narrow capillaries. The theory of dynamic NMR microscopy is presented and potential artifacts discussed, including the effect of slice selection gradients, PGSE gradient nonuniformity, and specific problems associated with the measurement of self-diffusion in the presence of velocity gradients. It is demonstrated that a double-echo PGSE pulse sequence can be used to restore coherent phase shifts associated with steady-state flow, and examples of self-diffusion maps and signed velocity maps from sequences of phase-encoded images obtained by projection reconstruction are given. This method has been applied at 20,um transverse resolution in laminar capillary flow.     

Purpose-designed probes and their applications for dynamic NMR microscopy in an electromagnet.

The electromagnet provides a favorable environment for certain applications of NMR microscopy. These include plant imaging experiments and measurements of slow molecular diffusion, where high magnetic field gradients for the pulsed gradient spin echo (PGSE) technique are required. In this paper, two probes designed specifically for these two applications are described. In the first case, the open space within the probe has been maximized in order to incorporate environmental support systems for the plant, while in the second the smallest possible PGSE gradient coil former has been used to maximize the gradient strength. Examples are given of Dynamic NMR Microscopy experiments on a castor bean stem and on poly(ethylene oxide)/water solutions under shear thinning conditions.     

Signal-to-noise improvements in three-dimensional NMR microscopy using limited-angle excitation

The 3D FT variant of spin-echo imaging has previously been successfully used to yield images at microscopic resolution. In obtaining such high resolution, optimization of signal to noise for a given acquisition time is crucial. Using a limited-angle (<60) slice-selective pulse one can improve the effective signal to noise or reduce the experimental time. The spin echo is generated through gradient refocusing. A phantom with T₁ of 800 and 1200 ms was used to simulate white and gray matter. Signal intensity was modeled by the expression $\text{M=}\text{M}{}_0\text{sin}\text{θ[1−}\text{exp}\text{(−}\text{T}{}_{\mathrm{R}}\text{T}{}_1\text{)]}\text{1−}\text{exp}\text{(−}\text{T}{}_{\mathrm{R}}\text{T}{}_1\text{)}\text{cos}\text{θ}$ For T_R < 200 ms, limited-angle excitation can yield improvements in signal to noise by greater than a factor of two. These results were experimentally verified on a 1.5 T prototype system (General Electric, Milwaukee, Wis.) configured with gradient and rf coils designed for NMR microscopy. In those cases where signal-to-noise concerns do not require signal averaging beyond that which is inherent in the 3D FT technique, the limited-angle approach can reduce the acquisition time by as much as a factor of four. These results were verified in small animal studies of the brain of a 200 g rat.     

Solvent aided NMR microscopy of γ-irradiatedcis 1,4-polybutadiene

Cross-linked structure of γ-irradiatedcis 1,4-polybutadiene (PBi) was studied by NMR microscopy with the aid of deuterated benzene. After PBi was swollen (PBiS) in C₆D₆, the¹H NMR linewidth of the polymer was reduced from 4 to 2 kHz. The images show that the relaxation times,T ₁ andT ₂, of PBiS are longer than those of PBi. The simultaneous increase ofT ₁ andT ₂ implies that the molecular chains of PBi become more mobile upon swelling. The enhanced mobility of the molecular chains may provide a possibility of the increase in space resolution.     

Short-TE projection reconstruction NMR microscopy of trabecular bone.

The aim of this study was to assess the potential of projection reconstruction (PR) NMR microscopy in the quantitative evaluation of trabecular bone architecture. Short-TE PR spin-echo microimages were acquired at 7.05 T on normal bone explants. The main structural parameters such as bone volume fraction (BVF), trabecular thickness (Tb.Th.) and trabecular separation (Tb.Sp.) were obtained from the 3D microimages using the method of directed secants. Quantitative structural data were then compared with those derived from conventional spin-echo microimages. Our study indicates that projection reconstruction NMR microscopy promises to be more accurate than the conventional FTI method in the analysis of trabecular bone.     

Dielectric interface effects in subsurface microscopy of integrated circuits

We investigate the defocus and image quality affected by a dielectric interface on high numerical aperture focusing of linearly polarized illumination in aplanatic mode. Theoretical and experimental demonstration is performed on subsurface backside microscopy of silicon integrated circuits, showing that the high longitudinal magnification provided by solid immersion lens microscopy allows the observation of significant astigmatism. It is shown that a 50 micron longitudinal displacement of the objective lens with respect to the sample is necessary to achieve maximum resolutions in two directions.     

A novel application of NMR microscopy: measurement of water diffusion inside bioadhesive bonds.

The self-diffusion coefficient of water (D) inside bioadhesive bonds formed by dry and prehydrated hydrophilic matrices has been spatially resolved using nuclear magnetic resonance (NMR) microscopy. One-dimensional profiles showing the variation of D inside bioadhesive bonds were calculated from nine diffusion-weighted profiles obtained immediately after bond formation and every 5 min for 30 min. The resulting data indicated that the hydration state of a hydrophilic matrix can significantly and dramatically influence the dynamics of water movement inside a bioadhesive bond.