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This article demonstrates that a numerical solution of the full quantum mechanical equations for all metabolites with coupled spins is an efficient and accurate means, first, of predicting the optimum STEAM sequence design for quantifying any target metabolite in brain, and, second, for providing the basis lineshapes and yields of these metabolites to facilitate their accurate quantification. Using as illustrations the weakly coupled AX3 system of lactate, the ABX aspartyl group of N-acetylaspartate, which has only two strongly coupled spins, and the much larger strongly coupled AMNPQ glutamyl group of glutamate, the numerical solutions for the response to STEAM highlight the principal source of response variability, namely, the evolution of and transfer between zero quantum terms during the mixing time, TM. These highlights include the rapid oscillations of zero quantum terms due to the chemical shift difference of the coupled spins, the proliferation of oscillating zero order terms due to strong coupling, and the serendipitous smoothing of the response as the number of strongly coupled spins increases. The numerical solutions also demonstrate that the design of the selective 90 degrees pulses is a far less critical factor in determining the response than was the case for the selective 180 degrees pulses of the PRESS sequence (Thompson and Allen, Magn Reson Med 1999;41:1162-1169). The veracity of the method is demonstrated both in phantom solutions and in the parietal lobe of a normal human brain., (Copyright 2001 Wiley-Liss, Inc.)

This paper presents a detailed analysis of the TE dependence of the creatine methyl proton signal at 3.02 ppm, resulting from a symmetric PRESS sequence applied to the resting human gastrocnemius muscle. The analysis shows that a two-component decay of the central peak of the dipolar-coupled-methyl triplet should be interpreted as the superposition of a rapid ( approximately 34 msec) dipolar dephasing and a less rapid ( approximately 162 msec) transverse relaxation. These data do not support a two-pool hypothesis for TE dependence of this signal. Magn Reson Med 42:421-424, 1999., (Copyright 1999 Wiley-Liss, Inc.)

Using a numerical method of solving the equation of motion of the density matrix, an evaluation is presented of the sources of the marked variability in the response to the point resolved spectroscopy (PRESS) pulse sequence of coupled proton spin systems. The consequences of an inappropriate 180 degrees pulse design and of the limitations on radiofrequency power are demonstrated for a weakly coupled example, lactate. The dominating role of strong coupling, which is present in most brain metabolites, is demonstrated for glutamate, in which 160 terms in the density operator were tracked to monitor the gross changes in lineshape and signal intensity as a function of the two echo times. The predictions of the numerical solutions were confirmed by experiments on phantoms of aqueous metabolite solutions.

It is demonstrated that birdcage resonators, satisfying conditions of quadrature operation and radiofrequency field homogeneity, can be realized in practice on formers of non-circular cross section described by an equation of the form (x/a)n + (y/b)n = 1 where a and b are constants and n > or = 2 is an integer. Using a ladder network analogous to that of a conventional circular birdcage, optimization algorithms were employed to determine the elemental current distribution on the non-circular cylindrical surfaces. A comparison of circular, elliptical, symmetric and asymmetric fourth-order (n = 4) section birdcage current distributions is presented. A short, asymmetric fourth-order cage was constructed and tested experimentally at 3 T and compared with a conventional circular-section head coil.

A numerical procedure is outlined that is appropriate for the design of multiple quantum filter sequences targeted for the strongly coupled, multiple spin systems that occur in metabolites present in brain. The procedure uses numerical methods of solution of the density matrix equations, first, to establish the most appropriate resonance to target with the filter; second, to provide contour plots of a performance index of the filter in terms of critical sequence parameters; and third, to produce the response signals of the target and the background metabolites to the optimized filter. The procedure is exemplified for the AMNPQ spin system of the amino acid glutamate at a field strength of 3 T. The 2.3 ppm peak of the PQ multiplet of glutamate was identified as the target resonance, and the performance of the filter so derived was evaluated experimentally on phantom solutions and in human brain. These experiments clearly demonstrate that a linewidth of

An outline is presented of metabolite-specific in vivo NMR spectroscopy (particularly in brain). It reviews from a physical spectroscopist's perspective, the need for and the methods of observation of, individual metabolite resonances.

The authors report NMR measurements of the changes in water diffusion brought about by in vivo Wallerian degeneration due to either crush- or tie-injuries in the sciatic nerve of the frog. Using a pulsed-gradient spin-echo sequence with a diffusion measurement time of 28 ms, the degree of diffusion coefficient anisotropy ¿D(longitudinal)/D(transverse)¿ 4 weeks after injury in both crush- and tie-injured nerves (2.3 +/- 0.4 and 1.7 +/- 0.1, respectively) is significantly less than in normal frog sciatic nerve (3.9 +/- 0.4). The decrease of anisotropy in the degenerated nerves is due to both a decrease in longitudinal diffusion and an increase in transverse diffusion. The changes in diffusion coefficients are compared with the degree of axonal and myelin breakdown observed in light and electron micrographs of the nerves.

An imaging protocol for a quantitative estimation of disease-induced variations in brain iron is proposed and then validated, first, on a phantom and second, on a group of 11 healthy volunteers. The relative estimate of brain iron is achieved from a rate difference image that measures the enhancement, delta R2app, of the transverse relaxation rate of water protons brought about by the heterogeneous accumulation of iron in the glial cells. At 1.5 T, the phantom study demonstrates, over the range 0-6 A/m, a linear dependence of delta R2app on the magnetization difference between microspheres and a paramagnetic gel, with a sensitivity of approximately 2 s-1 A-1 m. In the group of healthy volunteers (mean age 33 +/- 7 years) devoid of disease-related or appreciable age-related accumulations of iron, the precision of delta R2app was still sufficient to distinguish the globus pallidus and the putamen from all of the other iron-containing brain structures in a manner that was significant at the 99% confidence level.

It has been suggested that the anistropy of the water-diffusion coefficient measured in nerve and in white matter could arise from locally anisotropic background gradients induced by the static field, B0. By utilizing 1) pulse sequences, which minimize the effects of background gradients, and 2) changes in sample orientation, which would maximize the change in the magnitude of these gradients if present, it is shown that in four excised nerves the background gradients do not play a measurable role in the anisotropy of the water-diffusion coefficient at a field strength of 2.35 T. The excised nerves evaluated were the olfactory, trigeminal, and optic nerves of the garfish and the sciatic nerve of the frog.

To validate their correlation with tissue iron concentration, proton transverse relaxation measurements have been made at 2.35 T (100 MHz) in 25 samples of excised, frozen, but unfixed human gray matter tissue obtained from the globus pallidus, putamen, caudate, thalamus, and cortex of five postmortem brains free of neurological disease. The iron concentration was independently measured, using atomic absorption spectroscopy. The proton transverse relaxation measurements exploited the interecho time dependence of the apparent transverse relaxation rate, R2app, obtained from a Carr-Purcell-Meiboom-Gill (CPMG) sequence. An empirical semilogarithmic relationship between R2app and the interecho time provided a measure of the relaxation enhancement due to iron, namely, a slope p, which demonstrated a significant correlation (r = 0.78, P < 0.001) with tissue iron concentration. Moreover, a simple rate difference, delta R2app, determined between interecho time values of 6 and 60 ms, was also found to correlate significantly with iron concentration (r = 0.81, P < 0.001). Both of the foregoing correlations were better than that of R2app itself. When the tissue samples were subdivided into brain structure groups, the intergroup differences in rho reflected their known differences in iron accumulation and correlated with those of the mean group iron content, determined by atomic absorption spectrometry.

The enhancement of the water proton transverse relaxation, delta R2, brought about by a difference between intra and extracellular paramagnetic susceptibilities in a suspension of red blood cells (RBC) has been evaluated both experimentally and theoretically in terms of (i) the refocusing interval, delta 180, of a CPMG pulse sequence, (ii) the difference in paramagnetic susceptibility, and (iii) the shape of the cell surface. At a hematocrit of 45, the increase in the relaxation enhancement, delta R2, with increasing delta 180, was a factor of two greater for the naturally biconcave RBC, than for the quasi-spherical RBC in hypotonic suspensions. This difference could be modeled in terms of a transmembrane correlation time, tau = 5.5 ms, across an RBC surface characterized by a demagnetizing factor which differs by 0.13 from that of a sphere. The increase in delta R2 with increasing magnetization difference between the RBC and its surroundings was found to be marginally less than quadratic, both experimentally and from the model.

To clarify the result that marked diffusional anisotropy had been found in nomyelinated nerve, and in completion of an evaluation of the role of all longitudinal axonal structures, we report NMR measurements of water diffusion in the giant axon of the squid, where diffusional anisotropy is determined by the neurofilamentary structure. The diffusion coefficients of water parallel and perpendicular to the long axis of the squid giant axon at 20 degrees C are (1.61 +/- 0.06) x 10(-5) cm2 s-1 and (1.33 +/- 0.09) x 10(-5) cm2 s-1, respectively, which yield an anisotropic diffusion ratio of 1.2 +/- 0.1. Water diffusion in the squid giant axon is therefore quite rapid and nearly isotropic, thus eliminating the possibility of a significant role for the longitudinally oriented neurofilaments in producing diffusional anisotropy within the axoplasm. In conjunction with our work on garfish nerves therefore, only membranes, either as numerous axonal membranes or as myelin (if present), remain to fulfill the role of the primary determinant of anisotropic water diffusion in nerve and in white matter.

We report NMR diffusion measurements of water in three central nervous system models, namely the nonmyelinated olfactory, and the myelinated trigeminal and optic nerves of the spotted and long-nosed garfish. A similar degree of anisotropy of the average diffusion coefficients (DNMR) is observed for all three freshly excised nerve types (DNMR(parallel)/DNMR-(perpendicular) is 3.6 +/- 1.2, 3.2 +/- 0.9, and 2.6 +/- 0.4 for the olfactory, trigeminal, and optic nerves, respectively). The anisotropy of DNMR for the nonmyelinated olfactory nerve argues strongly that myelin is not a necessary determinant of diffusional anisotropy in ordered axonal systems (even though it may contribute when present). Garfish nerves treated with vinblastine, in order to depolymerize microtubules and inhibit fast axonal transport, also exhibit diffusional anisotropy (DNMR(parallel)/DNMR(perpendicular) is 2.6 +/- 0.4, 2.8 +/- 0.8, and 2.2 +/- 0.7 for the olfactory, trigeminal, and optic nerves, respectively) thus excluding a significant role for microtubules and fast axonal transport in that observed anisotropy.

This study reports on the development of a model for studying skeletal muscle metabolism in humans using NMR spectroscopy. Graded exercise was simulated using electrical stimulation in 10 healthy, fit subjects (mean VO2max = 53 +/- 4 ml.kg-1.min-1). The effects of varying the stimulation parameters, namely, the stimulation frequency, the stimulation intensity, and the duty cycle, as well as the spectral interrogation volume, were compared using data acquired from the rectus femoris muscle. With stimulation, the inorganic phosphate to phosphocreatine concentration ratio ([P(i)]/[PCr]) and the intracellular pH both follow curvilinear relationships over the stimulation frequencies from 3 to 30 Hz, with the magnitude of the observed change related closely to stimulation intensity and duty cycle. Oxidative phosphorylation predominates at stimulation frequencies below 12 Hz, while anaerobic metabolism increases sharply above 12 Hz. Our findings show clearly the interdependence of the effects of the various stimulation parameters and emphasize the care that must be exercised in interpreting the physiological significance of the biochemical data obtained from electrical stimulation models used to study skeletal muscle metabolism.

A 19F magnetic resonance spectroscopy (MRS) approach to measuring hypoxia in experimental tumors in rats at a field strength of 2.35 T has been investigated in a combined study of in situ and excised tumors. The detection of tumor hypoxia is based on the hypoxia marker approach which depends on the selective, covalent binding of a fluorinated 2-nitroimidazole to hypoxic cells. The 19F MRS measurement of in vivo hypoxia marker binding was made at a fixed postinjection time when unbound, circulating marker molecule concentrations had dropped below detectable levels. A correlation between 19F MRS and scintillation counting measures of tumor-bound, tritium-labeled hypoxia marker was observed. There was no correlation between integrated 19F MRS hypoxia marker signals and the in vivo 31P MRS parameters of hypoxia which have been developed to measure normal tissue ischemia. Radiolabeling studies and previous immunohistochemical studies with the fluorinated hypoxia marker support the conclusion that the 19F MRS approach has promise as a physically noninvasive guide to the use of hypoxia-dependent therapies at clinically usable MRS field strengths.

The suppression of water signals in in vivo proton spectra by means of multiple-quantum filtering can be brought about in several ways. This communication exposes the shortcomings of using purely subtractive filtering techniques to observe signals from metabolites that contain proton couplings of the form AX3.