Observation of rat hind limb skeletal muscle during arterial occlusion and reperfusion by 31P MRS and 1H MRI

31P NMR spectra and 1H MR T1- and T2-weighted spin-echo images were concurrently observed in rat hind limb during arterial occlusion and following reperfusion. With arterial occlusion, phosphocreatine level decreased and inorganic phosphate (Pi) level increased in 31P NMR spectra. Intracellular pH's dropped as a function of time. Beta-ATP started to decrease in three hours. In six hours after the occlusion, any peaks other than Pi were scarcely detected. The signal intensities in the 1H MR images increased homogeneously in both T1- and T2-weighted conditions, but the changes were more profound with T2-weighted images. After the release of the arterial occlusion, the 31P NMR spectra recovered to the preischemic state in several hours. The 1H MR images during reperfusion showed characteristic heterogenous pattern. The signal intensities in the anterior tibial muscle and the gastrocnemius muscle remained high in T1-weighted condition and the intensities further increased in T2-weighted condition, while those in other parts returned to the preischemic level. These changes were found to be irreversible even 12 hr after the release. The high signal intensities suggested the increase of water in the extracellular compartment induced by so-called reperfusion injury. Multinuclear analysis using in vivo NMR was valuable to consecutively detect time-dependent and location-specific response in skeletal muscle during ischemia and reperfusion.     

Effect of creatine monohydrate in improving cellular energetics and muscle strength in ambulatory Duchenne muscular dystrophy patients: a randomized,placebo-controlled P MRS study

Randomized, placebo-controlled single blinded study was carried out to evaluate the effect of oral creatine supplementation on cellular energetics, manual muscle test (MMT) score and functional status in steroid-naive, ambulatory boys suffering with Duchenne muscular dystrophy (DMD; n=33). Eighteen patients received creatine monohydrate (Cr; 5 g/day for 8 weeks), while 15 received placebo (500 mg of vitamin C). Phosphorus metabolite ratios were determined from the right calf muscle of patients using phosphorus magnetic resonance spectroscopy (³¹P MRS) both prior to (baseline) and after supplementation of Cr or placebo. In addition, metabolite ratios were determined in normal calf muscle of age and sex matched controls (n=8). Significant differences in several metabolite ratios were observed between controls and DMD patients indicating a lower energy state in these patients. Analysis using analysis of covariance adjusted for age and stature showed that the mean phosphocreatine (PCr)/inorganic phosphate (Pi) ratio in patients treated with Cr (4.7; 95% CI; 3.9–5.6) was significantly higher (P=.03) compared to the placebo group (3.3; 95% CI; 2.5–4.2). The mean percentage increase in PCr/Pi ratio was also more in patients <7 years of age compared to older patients after Cr supplementation indicating variation in therapeutic effect with the age. In the placebo group, significant reduction in PCr/Pi (P=.0009), PCr/t-ATP (P=.05) and an increase in phosphodiester (PDE)/PCr ratios was observed after supplementation. Further, in the placebo group, patients <7 years showed reduction of PCr/t-ATP and Pi/t-ATP compared to older patients (>7 years), after supplementation. These results imply that the significant difference observed in PCr/Pi ratio between the Cr and the placebo groups after supplementation may be attributed to a decrease of PCr in the placebo group and an increase in PCr in the Cr group. Changes in MMT score between the two groups was significant (P=.04); however, no change in functional scale (P=.19) was observed. Parents reported subjective improvement on Cr supplementation versus worsening in placebo (P=.02). Our results indicated that Cr was well tolerated and oral Cr significantly improved the muscle PCr/Pi ratio and preserved the muscle strength in short term. However, this study provides no evidence that creatine will prove beneficial after long-term treatment, or have any positive effect on patient lifespan.     

Radio-frequency probe for 1H decoupled 31P MRS of the head and neck region.

For optimal performance of 31P MRS at 1.5 Tesla, the use of a double resonant probe is essential to enable the application of 1H decoupling and Nuclear Overhauser Enhancement. This note describes the design, evaluation and safety validation of a versatile and compact probe optimized for 1H decoupled 31P MRS studies of tumors close to the surface of the body, in particular the head and neck region.     

Investigating nonlinear dynamics from time series: The influence of symmetries and the choice of observables

When a dynamical system is investigated from a time series, one of the most challenging problems is to obtain a model that reproduces the underlying dynamics. Many papers have been devoted to this problem but very few have considered the influence of symmetries in the original system and the choice of the observable. Indeed, it is well known that there are usually some variables that provide a better representation of the underlying dynamics and, consequently, a global model can be obtained with less difficulties starting from such variables. This is connected to the problem of observing the dynamical system from a single time series. The roots of the nonequivalence between the dynamical variables will be investigated in a more systematic way using previously defined observability indices. It turns out that there are two important ingredients which are the complexity of the coupling between the dynamical variables and the symmetry properties of the original system. As will be mentioned, symmetries and the choice of observables also has important consequences in other problems such as synchronization of nonlinear oscillators. (c) 2002 American Institute of Physics.     

ESR and31P NMR study of metabolic changes in mouse tumor and liver after combined misonidazole and irradiation treatment

A combination of ESR and³¹P NMR techniques was used to study the mechanism of the radiosensitizing influence of misonidazole (MISO) on mouse tumors and liver. The MISO injection (1 g/kg) was shown to cause significant metabolic changes in tumors, such as an increase in the content of nitrosyl complexes, increases in adenosine diphosphate and inorganic phosphate levels, and decreases in phosphomonoesters, phosphodiesters, adenosine triphosphate and phosphocreatine in the initial period of observation. These alterations were accompanied by slight cytosol alkalinization (pH shift ca 0.15). A decrease in the ESR signal intensity of Mo⁵⁺-containing enzymes, an increase in the cytochrome P-450 signal and a significant increase in the free radical signal were observed in liver after MISO treatment. Local irradiation of tumors (30 Gy) 30 min after MISO injection led to the enhancement and prolongation of nearly all the effects induced by MISO treatment. The combined effect of MISO and irradiation was not simply the sum of their separate effects. It is suggested that radiation enhances cytotoxic effects of nitrocompounds on hypoxic tumor cells, inhibiting glycolysis and inducing greater production of toxic and highly reactive intermediates resulting from incomplete nitro group reduction. The latter appears to be considered as the major factor involved in the radiosensitizing action of nitrocompounds.     

The linear and nonlinear intersubband optical absorption coefficients and refractive index changes in a V-shaped quantum well under the applied electric and magnetic fields

In this study, the changes in the optical absorption coefficients and the refractive index in a V-shaped quantum well have investigated theoretically. Within the effective mass approximation, the electronic structure of the V-shaped quantum well is calculated by numerical methods from the Schrödinger equation. Optical properties are obtained using the compact density-matrix approach. In the present work, the linear, third-order nonlinear and total absorption and refractive index changes investigated as a function of the quantum well width, the incident optical intensity, strengths of the magnetic and electric fields. Our results show that the magnetic and electric fields strengths, the quantum well width and incident optical intensity have a great effect on the optical characteristics of these structures.     

The effects of external applied voltage on the nonlinear refractive index and the birefringence of a dye-doped nematic mixture

The nonlinear refractive index, n₂, and the birefringence, Δn, of a nematic liquid crystal mixture (denoted as 1294-1b) doped with a anthraquinone derivative (denoted as AQ) dye were measured as a function of an external ac applied voltage. The self-phased modulation effect was used to measure the nonlinear refractive index of homeotropical-aligned samples. The change of the dyed liquid crystal nonlinearity, which is the direct impact of the applied voltage on the dye molecules orientation, was not observed for the nonlinear response of the pure liquid crystal. Planar (homogeneous) aligned samples were used for birefringence measurements by taking into account the absorption coefficients of the dye. The birefringence decreased to a limiting value in the high voltage region for both pure and dye-doped samples, although in the presence of the absorbing dye the birefringence of the liquid crystal was not approximately changed.The polarized absorption spectra of the dye in nematic mixture were recorded in parallel-aligned liquid crystal cell and its dichroic ratio R and the order parameter S_d were obtained. The electro-optical effect of the guest-host system was also using polarized spectroscopic method.     

The effects of hydrostatic pressure on the nonlinear intersubband transitions and refractive index changes of different QW shapes

In this study, the effects of hydrostatic pressure on the linear and nonlinear intersubband transitions and the refractive index changes in the conduction band of different quantum well shapes are theoretically calculated within framework of the effective mass approximation. Results obtained show that intersubband properties and the energy levels in different QWs can be modified and controlled by the hydrostatic pressure. The modulation of the absorption coefficients and the refractive index changes which can be suitable for good performance optical modulators and various infrared optical device applications can be easily obtained by tuning the hydrostatic pressure strength.     

In vivo 31P MRS of human brain at high/ultrahigh fields: a quantitative comparison of NMR detection sensitivity and spectral resolution between 4 T and 7 T

The primary goal of this study was to establish a rigorous approach for determining and comparing the NMR detection sensitivity of in vivo ³¹P MRS at different field strengths (B₀). This was done by calculating the signal-to-noise ratio (SNR) achieved within a unit sampling time at a given field strength. In vivo ³¹P spectra of human occipital lobe were acquired at 4 and 7 T under similar experimental conditions. They were used to measure the improvement of the human brain ³¹P MRS when the field strength increases from 4 to 7 T. The relaxation times and line widths of the phosphocreatine (PCr) resonance peak and the RF coil quality factors (Q) were also measured at these two field strengths. Their relative contributions to SNR at a given field strength were analyzed and discussed. The results show that in vivo ³¹P sensitivity was significantly improved at 7 T as compared with 4 T. Moreover, the line-width of the PCr resonance peak showed less than a linear increase with increased B₀, which leads to a significant improvement in ³¹P spectral resolution. These findings indicate the advantage of high-field strength to improve in vivo ³¹P MRS quality in both sensitivity and spectral resolution. This advantage should improve the reliability and applicability of in vivo ³¹P MRS in studying high-energy phosphate metabolism, phospholipid metabolism and cerebral biogenetics in the human at both normal and diseased states noninvasively. Finally, the approach used in this study for calculating in vivo ³¹P MRS sensitivity provides a general tool in estimating the relative NMR detection sensitivity for any nuclear spin at a given field strength.     

One-dimensional Ising-like systems: an analytical investigation of the static and dynamic properties, applied to spin-crossover relaxation

We investigate the dynamical properties of the 1-D Ising-like Hamiltonian taking into account short and long range interactions, in order to predict the static and dynamic behavior of spin crossover systems. The stochastic treatment is carried out within the frame of the local equilibrium method [1]. The calculations yield, at thermodynamic equilibrium, the exact analytic expression previously obtained by the transfer matrix technique [2]. We mainly discuss the shape of the relaxation curves: (i) for large (positive) values of the short range interaction parameter, a saturation of the relaxation curves is observed, reminiscent of the behavior of the width of the static hysteresis loop [3]; (ii) a sigmoidal (self-accelerated) behavior is obtained for large enough interactions of any type; (iii) the relaxation curves exhibit a sizeable tail (with respect to the mean-field curves) which is clearly associated with the transient onset of first-neighbor correlations in the system, due to the effect of short-range interactions. The case of negative short-range interaction is briefly discussed in terms of two-step properties. Received 29 October 1999 and Received in final form 30 December 1999     

The time course and magnitude of perceptual acclimatization to frequency responses: evidence from monaural fitting of hearing aids.

At high presentation levels, normally aided ears yield better performance for speech identification than normally unaided ears, while at low presentation levels the converse is true [S. Gatehouse, J. Acoust. Soc. Am. 86, 2103-2106 (1989)]. To explain this process further, the speech identification abilities of four subjects with bilateral symmetric sensorineural hearing impairment were investigated following provision of a single hearing aid. Results showed significant increases in the benefit from amplifying speech in the aided ear, but not in the control ear. In addition, a headphone simulation of the unaided condition for the fitted ear shows a decrease in speech identification. The benefits from providing a particular frequency spectrum do not emerge immediately, but over a time course of at least 6-12 weeks. The findings support the existence of perceptual acclimatization effects, and call into question short-term methods of hearing aid evaluation and selection by comparative speech identification tests.     

Effect of magnetic fields on the linear and nonlinear intersubband optical absorption coefficients and refractive index changes in square and graded quantum wells

In this study, both the intersubband optical absorption coefficients and the refractive index changes as dependent on the magnetic field are calculated in square and graded quantum wells. Our results show that the position and the magnitude of the linear and total absorption coefficients and refractive index changes depend on the magnetic field strength and the shape of potential. The incident optical intensity has a great effect on the total absorption and refractive index changes.     

On neglecting chemical exchange when correcting in vivo (31)P MRS data for partial saturation: commentary on: "Pitfalls in the measurement of metabolite concentrations using the one-pulse experiment in in Vivo NMR"

This article replies to Spencer et al. (J. Magn. Reson. 149, 251--257, 2001) concerning the degree to which chemical exchange affects partial saturation corrections using saturation factors. Considering the important case of in vivo (31)P NMR, we employ differential analysis to demonstrate a broad range of experimental conditions over which chemical exchange minimally affects saturation factors, and near-optimum signal-to-noise ratio is preserved. The analysis contradicts Spencer et al.'s broad claim that chemical exchange results in a strong dependence of saturation factors upon M(0)'s and T(1) and exchange parameters. For Spencer et al.'s example of a dynamic (31)P NMR experiment in which phosphocreatine varies 20-fold, we show that our strategy of measuring saturation factors at the start and end of the study reduces errors in saturation corrections to 2% for the high-energy phosphates.     

Pitfalls in the measurement of metabolite concentrations using the one-pulse experiment in in Vivo NMR: commentary on "On neglecting chemical exchange effects when correcting in vivo (31)P MRS data for partial saturation"

In an article in a previous issue of the Journal of Magnetic Resonance, Ouwerkerk and Bottomley (J. Magn. Reson. 148, pp. 425--435, 2001) show that even in the presence of chemical exchange, the dependence of saturation factors on repetition time in the one-pulse experiment is approximately monoexponential. They conclude from this fact that the effect of chemical exchange on the use of saturation factors when correcting for partial saturation is negligible. We take issue with this conclusion and demonstrate that because saturation factors in the presence of chemical exchange are strongly dependent upon all of the chemical parameters of the system, that is, upon all T(1)'s and M(0)'s of resonances in the exchange network and upon the reaction rates themselves, it is problematic to apply saturation factor corrections in situations in which any of these parameters may change. The error criterion we establish reflects actual errors in quantitation, rather than departures from monoexponentiality.     

Cumulative "roof effect" in high-resolution in vivo 31P NMR spectra of human calf muscle and the Clebsch-Gordan coefficients of ATP at 1.5 T

NMR spectra of non-weakly coupled spin systems exhibit asymmetries in line intensities known as "roof effect" in 1D spectroscopy. Due to limited spectral resolution, this effect has not been paid much attention so far in in vivo spectroscopy. But when high-quality spectra are obtained, this effect should be taken into account to explain the quantum-mechanical fine structure of the system. Adenosine 5'-triphosphate (ATP) represents a 31P spin system with multiple line splittings which are caused by J-couplings of medium strength at 1.5 T. We analyzed the ATP roof effect in vivo, especially for the beta-ATP multiplet. The intensities of its outer resonances deviate by ca. 12.5% from a symmetrical triplet. As this asymmetry reflects the transition from Paschen-Back to Zeeman effect with total spin that is largely broken up, the Clebsch-Gordan coefficients of the system can be indicated in analogy to the hyperfine structure of hydrogen. Taking the roof effect into account, the chi2 of fitting in vivo ATP resonances is reduced by ca. 9% (p<0.005).     

Simultaneous measurement of perfusion and oxygenation changes using a multiple gradient-echo sequence: application to human muscle study

We have developed a magnetic resonance imaging (MRI) technique based on a multiple gradient-echo sequence designed to probe perfusion and oxygenation simultaneously within skeletal muscle. Processing of the images acquired at successive echo times (TEs) generates two functional maps: one of the signal intensity (SI) extrapolated to zero echo time, which is sensitive to perfusion; and a second one of R21, which reflects oxygenation. An advantage of the processing procedure lies in the selection of tissue of interest through the profile of T₂1 decay, leading to automatic rejection of pixels containing small vessels. This allows a more specific assessment of tissue perfusion and oxygenation. This technique was demonstrated successfully during post-ischemic reactive hyperemia in human calf. A perfusion peak of 123 mL ×100 g⁻¹ × min⁻¹ was measured immediately after ischemia, whereas R21 value showed an 11.5% decrease at the same time, essentially reflecting blood oxygenation changes. Differences in the time courses of reperfusion and re-oxygenation were observed, oxygenation presenting a slower recovery. The mechanisms responsible for such a differential dynamic response are discussed.     

Time resolved observation of resonant and non-resonant contributions to the nonlinear susceptibility χ(3)

The resonant and nonresonant part of χ⁽³⁾ are distinguished by their different time behavior. The medium is coherently excited by two picosecond light pulses of defined frequency difference and the state of the system is monitored by a third properly delayed probe pulse. Results are presented on neat liquids of carbontetrachloride and cyclohexane and on the mixture of CCl₄: C₆H₁₂.     

The loop space representation of 2+1 gravity: Physical observables,variational principles,and the issue of time

We consider the loop space representation of Rovelli and Smolin as the starting point for the analysis of quantum gravity in 2+1 dimensions. To do so, we introduce observables directly within this representation and consider the problem of its Lagrangian formulation. The implications of this framework for the issue of time are discussed and the extension of these results to 3+1 gravity is also considered.