Multicomponent Relaxation Research Articles

Rapid three‐dimensional multicomponent relaxation imaging of the cervical spinal cord

Currently, little is known about the pathology of myelin in spinal cord disease due to the technical challenges of specifically measuring myelin content noninvasively. Multicomponent relaxometry allows estimation of the myelin water fraction, which is related to myelin content. However, conventional multiple-echo spin-echo-based multicomponent relaxometry techniques require prohibitively long acquisition times, lack spatial coverage, and are sensitive to artifacts common in spinal cord imaging. Multicomponent driven equilibrium single pulse observation of T(1) and T(2) (mcDESPOT) offers a promising alternative to conventional multicomponent relaxometry techniques. The goal of this pilot study was to assess the efficacy of mcDESPOT for obtaining high spatial resolution spinal cord myelin water fraction data covering the entire cervical spinal cord. Myelin water fraction values were found to be highly reproducible between subjects and over time but varied considerably along the length of the cord. Other relaxation characteristics that relate to tissue structure and health were also reliably measured.

Large-scale human metabolic phenotyping and molecular epidemiological studies via 1H NMR spectroscopy of urine: investigation of borate preservation.

Borate is an antibacterial preservative widely used in clinical and large-scale epidemiological studies involving urine sample analysis. Since it readily forms covalent adducts and reversible complexes with hydroxyl and carboxylate groups, the effects of borate preservation in (1)H NMR-spectroscopy-based metabolic profiling of human urine samples have been assessed. Effects of various concentrations of borate (range 0-30 mM) on (1)H NMR spectra of urine were observed at sequential time points over a 12 month period. Consistent with known borate chemistry, the principal alterations in the (1)H resonance metabolite patterns were observed for compounds such as mannitol, citrate, and alpha-hydroxyisobutyrate and confirmed by ESI-MS analysis. These included line-broadening, T(1) and T(2) relaxation, and chemical shift changes consistent with complex formation and chemical exchange processes. To further investigate complexation behavior in the urinary metabolite profiles, a new tool for visualization of multicomponent relaxation variations in which the spectra were color-coded according to the T(1) and T(2) proton relaxation times respectively (T(1) or T(2) ordered projection spectroscopy, TOPSY) was also developed and applied. Addition of borate caused a general decrease in (1)H T(1) values, consistent with nonspecific effects such as solution viscosity changes. Minor changes in proton T(2) relaxation rates were observed for the most strongly complexing metabolites. From a molecular phenotyping and epidemiologic viewpoint, typical interpersonal biological variation was shown to be vastly greater than any variation introduced by the borate complexation, which had a negligible effect on the metabolic mapping and classification of samples. While caution is indicated in the assignment of biomarker signals where metabolites have diol groupings or where there are adjacent hydroxyl and carboxylate functions, it is concluded that borate preservation is "fit-for-purpose" for (1)H NMR-based epidemiological studies, since the essential biochemical classification features of the samples are robustly maintained.

Investigations of Energy Migration in an Organic Dendrimer Macromolecule for Sensory Signal Amplification

The issue of macromolecular exciton delocalization length and fluorescence sensing of energetic materials is investigated and modeled from results of nonlinear optical and time-resolved spectroscopy. By using two- and three-photon absorption techniques the fluorescence quenching effects of an organic dendrimer for sensing TNT were carried out. The Stern-Volmer plots for the set of dendrimers were examined and a large quenching constant for the dendrimer G4 was obtained (1400 M(-1)). The quenching constant was found to increase with the dendrimer generation number. The mechanism for the enhanced sensitivity of the dendrimer system was examined by probing the exciton dynamics with femtosecond fluorescence up-conversion. Fluorescence lifetime measurements revealed a multicomponent relaxation that varied with dendrimer generation. Fluorescence anisotropy decay measurements were used to probe the exciton migration length in these dendrimer systems and for the large structure the excitation migration area covers approximately 20 units. All of these results were used in a model that describes the exciton localization length with the fluorescence quenching strength. The use of time-resolved techniques allows for a closer and more detailed description of the mechanism of sensory amplification in organic macromolecules.

Gleaning multicomponent T1 and T2 information from steady‐state imaging data

The driven-equilibrium single-pulse observation of T(1) (DESPOT1) and T(2) (DESPOT2) are rapid, accurate, and precise methods for voxelwise determination of the longitudinal and transverse relaxation times. A limitation of the methods, however, is the inherent assumption of single-component relaxation. In a variety of biological tissues, in particular human white matter (WM) and gray matter (GM), the relaxation has been shown to be more completely characterized by a summation of two or more relaxation components, or species, each believed to be associated with unique microanatomical domains or water pools. Unfortunately, characterization of these components on a voxelwise, whole-brain basis has traditionally been hindered by impractical acquisition times. In this work we extend the conventional DESPOT1 and DESPOT2 approaches to include multicomponent relaxation analysis. Following numerical analysis of the new technique, renamed multicomponent driven equilibrium single pulse observation of T(1)/T(2) (mcDESPOT), whole-brain multicomponent T(1) and T(2) quantification is demonstrated in vivo with clinically realistic times of between 16 and 30 min. Results obtained from four healthy individuals and two primary progressive multiple sclerosis (MS) patients demonstrate the future potential of the approach for identifying and assessing tissue changes associated with several neurodegenerative conditions, in particular those associated with WM.

Investigating exchange and multicomponent relaxation in fully‐balanced steady‐state free precession imaging

To investigate the effect of chemical exchange and multicomponent relaxation on the rapid T(2) mapping method, DESPOT2 (driven equilibrium single pulse observation of T(2)) and the steady-state free precession (SSFP) sequence upon which it is based. Although capable of rapid T(2) determination, an assumption implicit of the method is single-component relaxation. In many biological tissues (such as white and gray matter), it is well established that the T(2) decay curve is more accurately described by the summation of more than one relaxation species. The effects of exchange were first incorporated into the general SSFP magnetization expressions and its effect on the measured SSFP signal investigated using Bloch-McConnell simulations. Corresponding imaging experiments were performed to support the presented theory. Simulations show the measured multicomponent SSFP signal may be expressed as a linear summation of signal from each species under usual imaging conditions where the repetition time is much less than T(2). Imaging experiments performed using dairy cream demonstrate strong agreement with the presented theory. Finally, using a dairy cream model, we demonstrate quantification of multicomponent relaxation from multiangle SSFP data for the first time, showing good agreement with reference spin-echo values. SSFP and DESPOT2 may provide a new method for investigating multicomponent systems, such as human brain, and disease processes, such as multiple sclerosis.

Organic nanocrystals: an NMR study of cyclohexane in porous silica

The formation of cyclohexane nanocrystals in porous silica (60 Å, 200 Å and 500 Å nominal pore sizes) of well characterized geometry has been studied using T 2 and T1ρ nuclear magnetic resonance (NMR) measurements over a temperature range from 295K to 77K. The confined solid was found to behave in a substantially different way from the bulk material, and exhibited pore size dependency. Below the melting point, multi-component relaxation times indicated a mixed phase system, with evidence for the coexistence of an ordered nanocrystal and a highly disordered region. The disordered region is of considerable interest since it is highly mobile and preliminary measurements have indicated anomalously fast diffusion. Measurements also demonstrated enhanced anisotropic reorientational motion, the suppression of the formation of the rigid lattice and the loss of the solid–solid phase transition for smaller pores.

MR IMAGING OF THE BREAST: Imaging and Tissue Characterization Without Intravenous Contrast

The development of noninvasive techniques should always be an important goal of diagnostic radiology. Despite the recent excitement regarding intravenous MR imaging contrast agents (e.g., Gd-DTPA), the role of noncontrast MR imaging for the breast should not be overlooked. First, it must be kept in mind that administration of an intravenous contrast material is an invasive procedure that poses some health concern and may not be acceptable to certain patients. Second, injection of intravenous contrast media is an expensive procedure that incurs costs related to the contrast media itself as well as from the personnel required to administer the media and monitor any adverse reactions. Third, there may be specific imaging situations in which a lesion must be located prior to administration of contrast media, for example, when dynamic contrast enhanced imaging is to be performed and temporal resolution limits the volume of coverage to only a few slices. Finally, noncontrast MR imaging techniques also may be useful in their own right for obtaining information not otherwise available from a contrast-enhanced study, particularly quantitative relaxometric and spectroscopic measurements that may be useful for tissue characterization. It should also be noted that optimized noncontrast MR methods also might be used in conjunction with contrast agents to improve overall clinical utility. The heterogeneous nature of the breast and the overlap in T1 and T2 between different normal and abnormal breast tissue types frequently renders conventional noncontrast breast MR images confusing and ambiguous. Hybrid imaging approaches combining T1 weighting, T2 weighting, and fat suppression techniques as well as multivariate image analysis may be helpful for improving the sensitivity of MR imaging to breast disease; however, specificity remains a problem. Recent advances in clinical MR imaging have provided the opportunity to explore other approaches which may shed new light on the characterization of breast disease including NMRD, spin locking, magnetization transfer, and multicomponent relaxation analysis. MR imaging derived morphologic factors (i.e., lesion spiculation, parenchymal patterns) also may have a role to play in breast disease diagnosis and risk assessment. Several avenues of future development of noncontrast breast MR imaging would seem fruitful. NMRD and spin locking results suggest the potential contrast benefit of low field imaging of the breast, particularly, with the probable development of open concept low field MR imaging devices, which will provide improved access and low cost. In vivo relaxation time measurements, particularly multi-component T2 analysis and incorporation of MTC and chemical shift imaging techniques, may improve breast MR image specificity.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of discreteT2 components of NMR relaxation for aqueous solutions in hollow fiber capillaries

An analysis is presented of proton NMR T2 relaxation times measured for aqueous solutions in simple bundles of hollow fibers. The relaxation times are calculated with a two-compartment diffusive exchange model using the known relaxation times of the aqueous solutions and the fiber geometry. When the relaxation time outside the fibers is short (approximately 1 ms), three or more relaxation components are observed from this two compartment system, in agreement with the calculation. The amplitude and relaxation times of the third component are consistent with those of a diffusion-mediated mode, as suggested theoretically by Brownstein and Tarr (Phys. Rev. A 19, 2446 (1979)). The possible contribution of such modes to the multicomponent relaxation observed in tissues is discussed.

Clinical Effectiveness of Non-Drug Treatment for Hypertension: a Meta-Analysis

Abstract We conducted a meta-analysis of the clinical effectiveness of treatments for essential hypertension using 166 studies that evaluated the effects of diuretics, beta-blockers, and calcium-channel blockers, weight reduction, sodium and alcohol restriction, physical exercise, calcium and potassium supplements, single-component and multi-component relaxation therapy, and individualized cognitive-behavioral therapies. The findings were consistent with previous reviews that weight reduction, physical exercise, reduced sodium and alcohol intake, potassium supplements, and standardized relaxation treatments led to pressure reductions which mostly fell below effect size magnitudes observed with drug therapies. Of the non-drug approaches, weight reduction/physical exercise, and individualized cognitive-behavioral psychological therapy were particularly effective and did not differ from drug treatments in observed raw effect sizes for systolic blood pressure reductions. Calcium supplements were the least effective intervention. Drug therapies were initiated at higher initial levels of blood pressure than non-drug therapies with average pressures of 154.1 mmHg vs. 145.4 mmHg systolic and 101.5 mmHg vs. 94.3 mmHg diastolic pressure for drug/non-drug treatments respectively. After adjustment for differences in initial pressure levels, the effects for non-drug therapies increased, and the effect size of individualized psychological therapy matched the effect sizes of drug treatments for systolic and diastolic pressure reduction. These findings suggest that some non-drug therapies are more effective than commonly believed especially when differences in pre-treatment blood pressure levels are accounted for.

Phase behaviour of blend systems containing nitrile copolymers examined by solid-state nuclear magnetic resonance and differential scanning calorimetry

Solid-state cross-polarization magic angle spinning (CP-MAS) nuclear magnetic resonance (n.m.r.) and differential scanning calorimetry (d.s.c.) methods have been applied to examine the phase behaviour of binary blends of acrylonitrile/methyl acrylate/butadiene terpolymer (B210) with poly(ethylene- co-maleic anhydride) (PEMA) and poly(oxycarbonyloxy-1,4-phenyleneisopropylylidene-1,4-phenylene) (PC). Spinlattice relaxation times of the protons in the rotating frame for blends and pure components have been measured by monitoring the CP-MAS generated carbon signal intensities as a function of variable proton spin-lock time. Since single component n.m.r. relaxation behaviour was observed over the entire range of compositions, phase homogeneity was demonstrated for the B210/PEMA system. These monophase blends exhibit single-component rotating frame spin-lattice relaxation times, intermediate in value as compared to the pure components. The d.s.c. examinations also showed that B210/PEMA blends have a single composition-dependent glass transition temperature ( T g). By contrast, the solid state CP-MAS n.m.r. study of B210/PC blends revealed that they display multicomponent relaxation behaviour indicating the presence of a mixed phase along with pure phases of each individual polymer. Additionally, based on the d.s.c. measurements, the T g behaviour of B210/PC blends appears to have a three-component character consistent with a multiphase system.

Compatibility in polymer blends of poly(vinyl acetate) and poly(methyl methacrylate) studied by nuclear magnetic relaxation

The nuclear magnetic relaxation times T 1 and T 1 ϱ were measured as a function of temperature and composition in blends of poly(methyl methacrylate) (PMMA) and poly(vinyl acetate) (PVAc) prepared from benzene solutions. For temperatures in the solid state at which the reorientations of the α-methyl groups in PMMA cause minima in T 1 and T 1 ϱ , the multicomponent relaxation behaviour was discussed in terms of spin diffusion. The diffusion lengths were estimated using a simple multiphase model and correspond to dimensions of domains of the order of 20 nm. After annealing, an irreversible phase separation was observed. The results discussed are supported by additional studies.

Changes in the electric dipole vector of human serum albumin due to complexing with fatty acids

The magnitude of the electric dipole vector of human serum albumin, as measured by the dielectric increment of the isoionic solution, is found to be a sensitive, monotonic indicator of the number of moles (up to at least 5) of long chain fatty acid complexed. The sensitivity is about three times as great as it is in bovine albumin. New methods of analysis of the frequency dispersion of the dielectric constant were developed to ascertain if molecular shape changes also accompany the complexing with fatty acid. Direct two-component rotary diffusion constant analysis is found to be too strongly affected by cross modulation between small systematic errors and physically significant data components to be a reliable measure of structural modification. Multicomponent relaxation profiles are more useful as recognition patterns for structural comparisons, but the equations involved are ill-conditioned and solutions based on standard least-squares regression contain mathematical artifacts which mask the physically significant spectrum. By constraining the solution to non-negative coefficients, the magnitude of the artifacts is reduced to well below the magnitudes of the spectral components. Profiles calculated in this way show no evidence of significant dipole direction or molecular shape change as the albumin is complexed with 1 mol of fatty acid. In these experiments albumin was defatted by incubation with adipose tissue at physiological pH, which avoids passing the protein through the pH of the N-F transition usually required in defatting. Addition of fatty acid from soluion in small amounts of ethanol appears to form a complex indistinguishable from the "native" complex.