Proton Spin Relaxation Research Articles

Multivariate Analysis of Magnetic Resonance Imaging Signals of the Human Brain.

Magnetic resonance imaging (MRI) of the human brain plays an important role in the field of medical imaging as well as basic neuroscience. It measures proton spin relaxation, the time constant of which depends on tissue type, and allows us to visualize anatomical structures in the brain. It can also measure functional signals that depend on the local ratio of oxyhemoglobin to deoxyhemoglobin in the blood, which is believed to reflect the degree of neural activity in the corresponding area. MRI thus provides anatomical and functional information about the human brain with high spatial resolution. Conventionally, MRI signals are measured and analyzed for each individual voxel. However, these signals are essentially multivariate because they are measured from multiple voxels simultaneously, and the pattern of activity might carry more useful information than each individual voxel does. This paper reviews recent trends in multivariate analysis of MRI signals in the human brain, and discusses applications of this technique in the fields of medical imaging and neuroscience.

Nuclear magnetic relaxation by the dipolar EMOR mechanism: Three-spin systems.

In aqueous systems with immobilized macromolecules, including biological tissue, the longitudinal spin relaxation of water protons is primarily induced by exchange-mediated orientational randomization (EMOR) of intra- and intermolecular magnetic dipole-dipole couplings. Starting from the stochastic Liouville equation, we have developed a non-perturbative theory that can describe relaxation by the dipolar EMOR mechanism over the full range of exchange rates, dipole couplings, and Larmor frequencies. Here, we implement the general dipolar EMOR theory for a macromolecule-bound three-spin system, where one, two, or all three spins exchange with the bulk solution phase. In contrast to the previously studied two-spin system with a single dipole coupling, there are now three dipole couplings, so relaxation is affected by distinct correlations as well as by self-correlations. Moreover, relaxation can now couple the magnetizations with three-spin modes and, in the presence of a static dipole coupling, with two-spin modes. As a result of this complexity, three secondary dispersion steps with different physical origins can appear in the longitudinal relaxation dispersion profile, in addition to the primary dispersion step at the Larmor frequency matching the exchange rate. Furthermore, and in contrast to the two-spin system, longitudinal relaxation can be significantly affected by chemical shifts and by the odd-valued ("imaginary") part of the spectral density function. We anticipate that the detailed studies of two-spin and three-spin systems that have now been completed will provide the foundation for developing an approximate multi-spin dipolar EMOR theory sufficiently accurate and computationally efficient to allow quantitative molecular-level interpretation of frequency-dependent water-proton longitudinal relaxation data from biophysical model systems and soft biological tissue.

Nuclear magnetic relaxation by the dipolar EMOR mechanism: General theory with applications to two-spin systems.

In aqueous systems with immobilized macromolecules, including biological tissue, the longitudinal spin relaxation of water protons is primarily induced by exchange-mediated orientational randomization (EMOR) of intra- and intermolecular magnetic dipole-dipole couplings. We have embarked on a systematic program to develop, from the stochastic Liouville equation, a general and rigorous theory that can describe relaxation by the dipolar EMOR mechanism over the full range of exchange rates, dipole coupling strengths, and Larmor frequencies. Here, we present a general theoretical framework applicable to spin systems of arbitrary size with symmetric or asymmetric exchange. So far, the dipolar EMOR theory is only available for a two-spin system with symmetric exchange. Asymmetric exchange, when the spin system is fragmented by the exchange, introduces new and unexpected phenomena. Notably, the anisotropic dipole couplings of non-exchanging spins break the axial symmetry in spin Liouville space, thereby opening up new relaxation channels in the locally anisotropic sites, including longitudinal-transverse cross relaxation. Such cross-mode relaxation operates only at low fields; at higher fields it becomes nonsecular, leading to an unusual inverted relaxation dispersion that splits the extreme-narrowing regime into two sub-regimes. The general dipolar EMOR theory is illustrated here by a detailed analysis of the asymmetric two-spin case, for which we present relaxation dispersion profiles over a wide range of conditions as well as analytical results for integral relaxation rates and time-dependent spin modes in the zero-field and motional-narrowing regimes. The general theoretical framework presented here will enable a quantitative analysis of frequency-dependent water-proton longitudinal relaxation in model systems with immobilized macromolecules and, ultimately, will provide a rigorous link between relaxation-based magnetic resonance image contrast and molecular parameters.

Molecular Level Insights on Collagen-Polyphenols Interaction Using Spin-Relaxation and Saturation Transfer Difference NMR.

Interaction of small molecules with collagen has far reaching consequences in biological and industrial processes. The interaction between collagen and selected polyphenols, viz., gallic acid (GA), pyrogallol (PG), catechin (CA), and epigallocatechin gallate (EGCG), has been investigated by various solution NMR measurements, viz., (1)H and (13)C chemical shifts (δH and δC), (1)H nonselective spin-lattice relaxation times (T1NS) and selective spin-lattice relaxation times (T1SEL), as well as spin-spin relaxation times (T2). Furthermore, we have employed saturation transfer difference (STD) NMR method to monitor the site of GA, CA, PG, and EGCG which are in close proximity to collagen. It is found that -COOH group of GA provides an important contribution for the interaction of GA with collagen, as evidenced from (13)C analysis, while PG, which is devoid of -COOH group in comparison to GA, does not show any significant interaction with collagen. STD NMR data indicates that the resonances of A-ring (H2', H5' and H6') and C-ring (H6 and H8) protons of CA, and A-ring (H2' and H6'), C-ring (H6 and H8), and D-ring (H2″and H6″) protons of EGCG persist in the spectra, demonstrating that these protons are in spatial proximity to collagen, which is further validated by independent proton spin-relaxation measurement and analysis. The selective (1)H T1 measurements of polyphenols in the presence of protein at various concentrations have enabled us to determine their binding affinities with collagen. EGCG exhibits high binding affinity with collagen followed by CA, GA, and PG. Further, NMR results propose that presence of gallic acid moiety in a small molecule increases its affinity with collagen. Our experimental findings provide molecular insights on the binding of collagen and plant polyphenols.

TU-EF-BRA-01: NMR and Proton Density MRI of the 1D Patient

TU-EF-BRA-01: NMR and Proton Density MRI of the 1D Patient

TU‐EF‐BRA‐04: Into 2, 3, and 4 Dimensions

TU‐EF‐BRA‐04: Into 2, 3, and 4 Dimensions

TU-EF-BRA-02: Longitudinal Proton Spin Relaxation and T1-Imaging

TU-EF-BRA-02: Longitudinal Proton Spin Relaxation and T1-Imaging

TU-EF-BRA-00: MR Basics I

TU-EF-BRA-00: MR Basics I

TU-EF-BRA-03: Free Induction Decay (without the Decay) and Spin-Echo Imaging

TU-EF-BRA-03: Free Induction Decay (without the Decay) and Spin-Echo Imaging

Rotation-induced recovery and bleaching in magnetic resonance.

Thurber and Tycko recently described a 'bleaching effect' that occurs in magnetic resonance when solid samples that are doped with paramagnetic agents are subjected to rotation by magic angle spinning (MAS) in a static magnetic field with a rotation period comparable to the longitudinal relaxation time T1e of the electron spins. The bleaching effect has been investigated by Thurber and Tycko in samples spinning at temperatures near 20 K in a field of 9.4 T and by Corzilius et al. near 80 K in a field of 4.9 T. In our experience, the bleaching effect is not very severe at temperatures near 100 K in a field of 9.4 T at spinning frequencies up to 12 kHz. Bleaching can partly cancel DNP enhancements that are normally evaluated by comparing signal intensities with and without microwave irradiation. The signal attenuation due to doping and sample rotation is usually not taken into consideration when defining enhancement factors. In this paper, we describe a novel observation that the rotation of glassy samples doped with lanthanides spinning at frequencies as low as 0.1 kHz can lead to a significant reduction of the spin-lattice relaxation times T1((1)H) of protons. This effect, which bears similarities with the so-called spin refrigerators, may contribute to the success of 'brute force polarization' at sample temperatures in the mK range. The acceleration of longitudinal proton relaxation also allows one to improve the signal-to-noise ratio per unit time.

Effect of partial H2O-D2O replacement on the anisotropy of transverse proton spin relaxation in bovine articular cartilage.

Anisotropy of transverse proton spin relaxation in collagen-rich tissues like cartilage and tendon is a well-known phenomenon that manifests itself as the “magic-angle” effect in magnetic resonance images of these tissues. It is usually attributed to the non-zero averaging of intra-molecular dipolar interactions in water molecules bound to oriented collagen fibers. One way to manipulate the contributions of these interactions to spin relaxation is by partially replacing the water in the cartilage sample with deuterium oxide. It is known that dipolar interactions in deuterated solutions are weaker, resulting in a decrease in proton relaxation rates. In this work, we investigate the effects of deuteration on the longitudinal and the isotropic and anisotropic contributions to transverse relaxation of water protons in bovine articular cartilage. We demonstrate that the anisotropy of transverse proton spin relaxation in articular cartilage is independent of the degree of deuteration, bringing into question some of the assumptions currently held over the origins of relaxation anisotropy in oriented tissues.

Proton and deuterium nuclear spin relaxation study of the SmA and SmC* phases of BP8Cl-d17 : a self-consistent analysis.

A self-consistent analysis of proton and deuterium nuclear spin relaxation times in the smectic phases of a partially deuterated smectogen is presented here. Proton spin-lattice relaxation times T(1Z) were measured as a function of Larmor frequency over a range of 1 kHz to 300 MHz at selected temperatures. Deuterium spin relaxation times T(1Z) and T(1Q) were measured as a function of temperature at two different magnetic fields in the smectic A phase. The deuterium data provide dynamic parameters such as rotational diffusion constants and internal jump rates as well as the nematic order parameter S. The proton data are analyzed using a number of relaxation mechanisms, one of which is the molecular reorientation. It is found helpful in these latter analyses to use the nematic order parameter and to fix the contribution from molecular reorientations determined by the deuterium spin relaxation. The fits to the proton T(1) frequency and temperature dispersions by the remaining relaxation mechanisms such as layer undulations and translational self-diffusion will be discussed for the smectic A and chiral smectic C phases.

¹H-²H cross-relaxation study in a partially deuterated nematic liquid crystal.

A detailed study of the cross-relaxation effects between the ¹H and ²H spins systems is presented in the nematic phase of a 5-cyanobiphenyl (5CB) liquid crystal, partially deuterated at α position (5CB-αd₂). The proton spin-lattice relaxation time was measured at a frequency range from 5 kHz to 100 MHz at a temperature 5 K below the nematic-isotropic phase transition. In the low frequency domain, the spin-lattice relaxation rate (T₁⁻¹) dispersion clearly differs from that of the fully protonated 5CB homologue. At two distinct frequencies, T₁⁻¹ presents two distinct local maxima and for low frequencies T₁⁻¹ presents a stronger frequency dependence when compared with what is observed for 5CB. The T₁⁻¹ dispersion obtained for 5CB-αd₂ for frequencies above 60 kHz was interpreted in terms of the relaxation mechanisms usually accepted to interpret the spin-lattice relaxation in nematic phases in general and 5CB in particular. For lower frequencies it was necessary to consider cross-relaxation contributions between the proton and deuterium reservoirs. A detailed model interpretation of the deuterium quadrupolar dips with respect to the proton-spin relaxation is presented. The analysis of the quadrupolar relaxation independently confirms that the order director fluctuations is the dominant mechanism of proton relaxation in the low frequency domain.

Mechanisms of Gadographene-Mediated Proton Spin Relaxation.

Gd(III) associated with carbon nanomaterials relaxes water proton spins at an effectiveness that approaches or exceeds the theoretical limit for a single bound water molecule. These Gd(III)-labeled materials represent a potential breakthrough in sensitivity for Gd(III)-based contrast agents used for magnetic resonance imaging (MRI). However, their mechanism of action remains unclear. A gadographene library encompassing GdCl3, two different Gd(III)-complexes, graphene oxide (GO), and graphene suspended by two different surfactants and subjected to varying degrees of sonication was prepared and characterized for their relaxometric properties. Gadographene was found to perform comparably to other Gd(III)-carbon nanomaterials; its longitudinal (r1) and transverse (r2) relaxivity is modulated between 12-85 mM-1s-1 and 24-115 mM-1s-1, respectively, depending on the Gd(III)-carbon backbone combination. The unusually large relaxivity and its variance can be understood under the modified Florence model incorporating the Lipari-Szabo approach. Changes in hydration number (q), water residence time (τM), molecular tumbling rate (τR), and local motion (τfast) sufficiently explain most of the measured relaxivities. Furthermore, results implicated the coupling between graphene and Gd(III) as a minor contributor to proton spin relaxation.

Ultrastructure of cellulose crystallites in flax textile fibres

Seven varieties of flax (Linum usitatissimum) fibres were analyzed in order to gain a deeper insight into the morphological features of the crystalline assembly. Different spectroscopic techniques and a chemical bleaching process were used to provide an accurate description of the lateral arrangement of the polysaccharide chains within the fibre cell wall. The flax fibres were analyzed in their natural state and after an extraction treatment of the non-crystalline components such as hemicelluloses, pectins and phenolics. The chemical bleaching process consisted of a Soxhlet extraction in toluene, a sodium chlorite treatment and an alkaline extraction of the residual hemicelluloses. Solid-state 13C nuclear magnetic resonance (NMR) confirmed the sequential removal of the non-cellulosic components from the flax cell wall. Both wide-angle X-ray diffraction (WAXD) and solid-state 13C NMR provided measures of the crystallite thicknesses and overall crystallinities before and after treatment. The existence of non-cellulosic highly ordered paracrystalline domains was also evidenced by proton spin relaxation time calculation. Whereas the overall crystallinity determined by WAXD decreased after treatment, the cellulose crystallinity calculated with the help of the solid-state 13C NMR slightly increased. This is explained by the difference in chemical selectivity between these two techniques and by the paracrystalline state of both hemicelluloses and pectins. Strong adhesion between cellulose crystallites, hemicelluloses and pectins in the fibres was evidenced by low spin–spin relaxation times and by an increase in crystallite thickness after bleaching. A simple model is proposed that describes the rearrangement of the macromolecules during the bleaching process.

1H relaxation dispersion in solutions of nitroxide radicals: Effects of hyperfine interactions with 14N and 15N nuclei

(1)H relaxation dispersion of decalin and glycerol solutions of nitroxide radicals, 4-oxo-TEMPO-d(16)-(15)N and 4-oxo-TEMPO-d(16)-(14)N was measured in the frequency range of 10 kHz-20 MHz (for (1)H) using STELAR Field Cycling spectrometer. The purpose of the studies is to reveal how the spin dynamics of the free electron of the nitroxide radical affects the proton spin relaxation of the solvent molecules, depending on dynamical properties of the solvent. Combining the results for both solvents, the range of translational diffusion coefficients, 10(-9)-10(-11) m(2)/s, was covered (these values refer to the relative diffusion of the solvent and solute molecules). The data were analyzed in terms of relaxation formulas including the isotropic part of the electron spin - nitrogen spin hyperfine coupling (for the case of (14)N and (15)N) and therefore valid for an arbitrary magnetic field. The influence of the hyperfine coupling on (1)H relaxation of solvent molecules depending on frequency and time-scale of the translational dynamics was discussed in detail. Special attention was given to the effect of isotope substitution ((14)N/(15)N). In parallel, the influence of rotational dynamics on the inter-molecular (radical - solvent) electron spin - proton spin dipole-dipole coupling (which is the relaxation mechanism of solvent protons) was investigated. The rotational dynamics is of importance as the interacting spins are not placed in the molecular centers. It was demonstrated that the role of the isotropic hyperfine coupling increases for slower dynamics, but it is of importance already in the fast motion range (10(-9)m(2)/s). The isotope effects is small, however clearly visible; the (1)H relaxation rate for the case of (15)N is larger (in the range of lower frequencies) than for (14)N. It was shown that when the diffusion coefficient decreases below 5 × 10(-11) m(2)/s electron spin relaxation becomes of importance and its role becomes progressively more significant when the dynamics slows done. As far as the influence of the rotational dynamics is concerned, it was show that this process is of importance not only in the range of higher frequencies (like for diamagnetic solutions) but also at low and intermediate frequencies.

A Nano-Combinatorial Approach to Developing Cancer Diagnostics: Nano-Combinatorial Diagnostics Discovery

Challenges in imaging modalities to detect microscopic tumors Current clinical management in oncology relies heavily on both anatomic imaging and functional imaging with computed tomography (CT), PET and MRI. These imaging modalities have been clinically tested and validated for upfront staging and serial assessment in various subsets of all human malignancies. However, each modality suffers from various limitations in the detection of microscopic (tumors formed in early tumorigenesis or early metastasis and found in the residual tumor bed immediately after surgical extirpation) tumors. CT imaging employs x-rays to construct 3D spatial relationships between normal tissue and the tumor. The signal-to-noise ratio of CT is usually enhanced by increasing tube voltage, current or scan time. However, this results in excess ionizing radiation on the patient [1]. CT imaging forms a fundamental dataset in the assessment of cancer and is critical for dose calculations in radiation therapy. While this technology continues to be very useful, it has become limited by an inherent inability to contrast the large variety of soft tissues within the body and by the inability to resolve microscopic tumors below a few millimeters in size. PET produces a 3D image of metabolic processes in the body by detecting pairs of g-rays emitted indirectly by a positron-emitting radionuclide that is introduced into the body on a biologically active molecule. When the molecule chosen for PET is [F]-fluorodeoxyglucose, an analog of glucose, the concentration of tracer reflects tissue metabolic activity in terms of regional glucose uptake. The physics of this detection process limits most commercial [F]-fluorodeoxyglucose-PET detection systems to a resolution of no better than 5 mm under optimal circumstances [1]. However, MRI–PET fusion scanners can now optimize the morphologic and spatial definition of MRI combined with the functional data of PET [2]. MRI has a good signal-to-noise ratio due to the differences in proton spin relaxation properties of the various tissues found in the body. These differences enhance the contrast between tissues of varying proton density. MRI obviates ionizing radiation during image acquisition in addition to enhancing contrast-related morphologic imaging quality advantages. However, the spatial resolution associated with MRI is based on the field of view and data collection matrix size and is not inherently superior to CT [1]. With most commercially available units, image resolution is limited to a few millimeters.

Mini-MRI scanner and some possibilities for its use for studying living tissues

We show that a laboratory table-top MRI scanner can be used to obtain images of living tissues in the hand of a patient and to record spin–spin relaxation of protons in water and protons in lipid compounds. We have identified variations in the spin–spin relaxation rate as high as 24% due to the individual biochemical characteristics of the patients. We present the results of using the instrument for diagnosis of age-related changes in bone tissues density and estimating the variation in the spin–spin relaxation constants.

The decomposition of windrowed, chipped logging slash and tree seedling response: A plant growth and nuclear magnetic resonance spectroscopy study

Forest management practices historically have reduced the mass of logging slash to facilitate planting and reduce fire risk. However, coarse woody debris (CWD) is considered an important component of unmanaged forests of western and coastal North America. An experiment was established in northern California using chipped logging slash concentrated in windrows to emulate large fallen logs to determine the effects of alternative logging residue treatments on soil fertility and the performance of planted ponderosa pine. Chip piles warmed faster than mineral soil, but upper regions dried quickly during the dry summers. Fourteen years after planting, growth response was positive, as seedling volume declined with distance from the windrows. After 6 and 10 years, chip samples showed little variation in total C, but total N was higher for 10-year samples, with slightly higher values at the base and for N-fertilized sections. Analysis by solid state 13C CPMAS NMR, verified by spin-counting and triplicate analysis showed only subtle differences among 10-year samples, with non-carbohydrate C slightly more abundant at the base of the piles and for windrows originally fertilized with N. However, proton spin relaxation editing (PSRE), based on differences in T 1H relaxation rates, was able to distinguish between C in relatively undecomposed lignocellulose (slowly relaxing) and more decomposed material and microbial residues (rapidly relaxing). The small differences between top and base, and between fertilized and control samples were concentrated in the rapidly relaxing component. Bulk composition of 10-year chip windrows was similar to CWD naturally decomposed by white-rot fungi, but PSRE offers a new approach to monitor spatially heterogeneous development of microsites more characteristic of brown rot.

ChemInform Abstract: Solid State Proton Spin Relaxation in Ethylbenzenes: Methyl Reorientation Barriers and Molecular Structure

We have investigated the dynamics of the ethyl groups and their constituent methyl groups in polycrystalline ethylbenzene (EB), 1,2‐diethylbenzene (1,2‐DEB), 1,3‐DEB, and 1,4‐DEB using the solid state proton spin relaxation (SSPSR) technique. The temperature and Larmor frequency dependence of the Zeeman spin‐lattice relaxation rate is reported and interpreted in terms of the molecular dynamics. We determine that only the methyl groups are reorienting on the nuclear magnetic resonance time scale. The observed barrier of about 12 kJ/mol for methyl group reorientation in the solid samples of EB, 1,2‐DEB, and 1,3‐DEB is consistent with that of the isolated molecule, implying that in the solid state, intermolecular electrostatic interactions play a minor role in determining the barrier. The lower barrier of 9.3±0.2 kJ/mol for the more symmetric 1,4‐DEB suggests that the crystal structure is such that the minimum in the anisotropic part of the intramolecular potential is raised by the intermolecular interactions leading to a 3 kJ/mol decrease in the total barrier. We are able to conclude that the methyl group is well away from the plane of the benzene ring (most likely orthogonal to it) in all four molecules, and that in 1,2‐DEB, the two ethyl groups are in the anticonfiguration. Our SSPSR results are compared with the results obtained by microwave spectroscopy and supersonic molecular jet laser spectroscopy, both of which determine molecular geometry better than SSPSR, but neither of which can determine ground electronic state barriers for these molecules.