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P S Allen

Publications and source records attributed to P S Allen.

At least 19 recordsLinked to original sources

Response of metabolites with coupled spins to the STEAM sequence.

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.

Aspartic Acid↗

Relaxation times and microstructures.

A discussion is presented of the evaluation of multiple relaxation components from water protons in biological tissue. The principal focus is to draw attention to the way in which limitations in the raw NMR data, such as signal-to-noise ratio, data sampling density and acquisition window width, affect the precision and resolution in the processed multiple component solution of the return to thermal equilibrium. The second issue discussed is the interpretation of these multiple components in terms of microstructural compartments of the biological sample and, thirdly, we outline some of the successes in determining regional and pathological variations in microstructure in the human body in-vivo, using the technique of multiple relaxation components.

Animals↗

An (1)H-MRS evaluation of the phosphocreatine/creatine pool (tCr) in human muscle.

The human gastrocnemius was examined with and without creatine supplementation under the conditions of rest, ischemic fatigue (IF), and recovery to perturb the pool sizes and equilibrium between phosphocreatine (PCr) and creatine (Cr). (1)H- and (31)P-magnetic resonance spectroscopy (MRS) were used to examine the total creatine (tCr) pool in each of the metabolic states. (31)P-MRS monitored the depletion of the PCr peak during IF to <5% of that at rest. (1)H-MRS focused on the tCr methyl peak at 3.02 ppm (dipolar coupled triplet), at which point it was expected that the triplet peak intensity would be similar both in IF and rest. Initial (1)H-MRS data showed the peak intensity during IF decreased, suggesting a change in tCr pool size. Subsequent studies of transverse relaxation time (T(2)) revealed that this decline was primarily due to a more rapid T(2) decay of the tCr peak in IF (T(2) approximately 40 ms) compared with at rest (T(2) approximately 162 ms). Because Cr is the major contributor to tCr in IF, it is possible that there is a pool of Cr displaying reduced mobility in vivo. Moreover, the residual dipolar coupled triplet observed at rest collapsed into a broad singlet during IF, suggestive of significant changes in the ordered environment experienced at rest for PCr compared with when it is converted to Cr during IF. In addition, these data suggest that in (1)H-MRS studies whose goals include quantitative estimates of tCr pool sizes, standardized metabolic conditions or careful T(2) evaluations will be required.

Creatine↗

Proton magnetic resonance spectroscopy (1H-MRS) of the cerebellum in men with schizophrenia.

OBJECTIVE: To investigate whether there are cerebellar vermis abnormalities in schizophrenia. DESIGN: Prospective imaging study with proton magnetic resonance spectroscopy (1H-MRS). SETTING: Schizophrenia clinic at a large urban hospital. PATIENTS AND CONTROLS: Twelve right-handed male patients with schizophrenia, and 12 control subjects with no psychiatric history. INTERVENTIONS: MRS data were acquired from a 2.0 x 2.0 x 2.0 cm volume of interest that included the entire cerebellar vermis. OUTCOME MEASURES: Spectral peak arising from N-acetylaspartate (NAA), phosphocreatine/creatine (Cr) and choline (Cho). RESULTS: There were no significant differences between the patients with schizophrenia and the controls in cerebellar vermis ratios of NAA to Cr (p = 0.71) or Cho to Cr (p = 0.50). CONCLUSIONS: This study does not support earlier structural studies that found abnormalities of the cerebellar vermis in schizophrenia, although it does support reported neurochemical studies. It does not rule out cerebellar involvement in schizophrenia through mechanisms such as aberrant circuitry. Larger in vivo structural/neurochemical and functional imaging studies in other parts of the cerebellum are needed.

Adult↗

Sources of variability in the response of coupled spins to the PRESS sequence and their potential impact on metabolite quantification.

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.

Brain↗

A numerical approach to non-circular birdcage RF coil optimization: verification with a fourth-order coil.

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.

Algorithms↗

Residual dipolar coupling of the Cr/PCr methyl resonance in resting human medial gastrocnemius muscle.

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.

Algorithms↗

Increasing striatal iron content associated with normal aging.

Free-radical-mediated mechanisms may contribute to neuronal damage in Parkinson's disease (PD), other neurodegenerative conditions also associated with aging, and the aging process itself. Cytotoxic free radicals are generated in the brain by oxidation/reduction reactions that are catalyzed by transition metals such as iron. Any regional increase in brain iron concentration may increase the potential for local free-radical formation. The purpose of this study was to determine the relationship between age and basal ganglia iron content in 20 normal individuals ranging from 24 to 79 years of age. We used an in vivo magnetic resonance method to quantify the effects of paramagnetic centers sequestered inside cellular membranes, thereby enabling the determination of a quantitative index of local brain iron content. We observed a strong direct relationship between age and regional iron content in the putamen (r = 0.76, p < 0.0001) and caudate (r = 0.69, p < 0.001), but not in the globus pallidus (r = 0.32, p = 0.17) or thalamus (r = 0.13, p = 0.58). In conclusion, striatal iron content increases with advancing age. This increase may increase the probability of free-radical formation in the striatum, therefore representing a risk factor for the development of neurodegenerative disorders such as PD in which nigrostriatal neurons may be affected by increased oxidant stress.

Adult↗

A new multiple quantum filter design procedure for use on strongly coupled spin systems found in vivo: its application to glutamate.

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 <or=4 Hz is required for full resolution of glutamate from glutamine at 3 T using this double quantum filter. Nevertheless, even at a linewidth of approximately 7 Hz in vivo, the 2.3 ppm peak of glutamate dominates the filter response and thereby removes a significant cause of uncertainty in measuring changes in glutamate by eliminating most of the background observed in unedited spectra obtained using PRESS or STEAM.

Brain↗

Multi-component T1 relaxation and magnetisation transfer in peripheral nerve.

We report here a study of longitudinal relaxation (T1) and magnetisation transfer (MT) in peripheral nerve. Amphibian sciatic nerve was maintained in vitro and studied at a magnetic field strength of 3 T. A CPMG pulse sequence was modified to include either a saturation pulse to measure T1 relaxation or an off-resonance RF irradiation pulse to measure MT. The resulting transverse relaxation (T2) spectra yielded four components corresponding to three nerve compartments, taken to result from myelinic, axonal, and inter-axonal water, and a fourth corresponding to the buffer solution water in which the nerve sample was bathed. Each nerve component was analysed for T1 relaxation and MT. All three nerve T2 components exhibited unique T1 relaxation and MT characteristics, providing further support for the assignment of the components to unique physical compartments of water. Numerical investigation of T1sat measurements of each of the three nerve T2 components indicates that while the two shorter-lived exhibit similar steady-state magnetisation transfer ratios (MTRs), their respective MT properties are quite different. Simulations demonstrate that mobile water exchange between these two components is not necessary to explain their similar steady-state MTR. In the context of the assignment of these two components to signal from myelinic and axonal water, this is to say that these two microanatomical regions of nerve may exhibit similar steady-state MTR characteristics despite possessing widely different MT exchange rates. Therefore, interpreting changes in MTR solely to reflect a change in degree of myelination could lead to erroneous conclusions.

Animals↗

Multicomponent water proton transverse relaxation and T2-discriminated water diffusion in myelinated and nonmyelinated nerve.

The influence of compartmental boundaries on water proton transverse relaxation and diffusion measurements was investigated in three distinct excised nerves, namely, the non-myelinated olfactory nerve, the Schwann cell myelinated trigeminal nerve, and the oligodendrocyte myelinated optic nerve of the garfish. The transverse relaxation decay curves were multiexponential and their decomposition yielded three primary components with T2 values approximately 30-50, 150, and 500 ms, which were subsequently assigned to water protons in the myelin, axoplasm, and interaxonal compartments. The short T2 component was absent in the non-myelinated olfactory nerve, but present in both myelinated nerves and thus provides supporting evidence for the use of quantitative T2 measurements to measure the degree of myelination. The signal contribution of each T2 component to the apparent diffusion coefficient measurements was varied by incrementing the spin-echo time with a preparatory CPMG train of radiofrequency pulses. The apparent diffusion coefficient and its anisotropy were shown to be independent of the spin-echo time over the range of 70 to 450 ms.

Algorithms↗

Increased basal ganglia iron in striatonigral degeneration: in vivo estimation with magnetic resonance.

BACKGROUND: As many as 20% of individuals with the clinical diagnosis of Parkinson's disease (PD) do not have the characteristic neuropathologic features of PD at post mortem. The striatonigral degeneration (SND) subtype of multiple system atrophy is one of the categories of pathology which may be incorrectly diagnosed as PD on the basis of clinical presentation. SND may be associated with increased iron deposition in the putamen which can be detected with magnetic resonance imaging. METHODS: We have estimated regional brain iron content in a patient with probable SND, using a novel imaging method developed in our laboratory, and have compared the results in this patient to those which we have previously reported in patients with PD and in age-matched controls. RESULTS: We observed that putamenal iron content was increased in our SND patient, beyond the 95% confidence limit for inclusion in the PD group, even when considering clinical severity. In contrast, pallidal and thalamic iron were within the PD range. CONCLUSIONS: The demonstration of increased putamenal iron content may be a useful adjunctive investigative procedure in patients with suspected SND.

Basal Ganglia↗

The role of the N-acetylaspartate multiplet in the quantification of brain metabolites.

N-Acetylaspartate, whose methyl singlet is the primary magnetic resonance marker of neuronal dysfunction, also gives rise to a sequence-dependent, strongly coupled multiplet that overlaps the resonances of several other metabolites. Results are presented in this paper of a full numerical calculation of the response of the strongly coupled aspartate multiplet of N-acetylaspartate to a PRESS pulse sequence employing practical slice-selective pulses. These calculations, confirmed by experiments on phantoms, demonstrate the ability to predict the dependence of the response of strongly coupled spins on pulse design, as well as on interpulse evolutions, thereby facilitating a more rigorous comparison of the use of spectral fitting routines employed to extract metabolite concentrations on different instruments.

Aspartic Acid↗

Estimation of brainstem neuronal loss in amyotrophic lateral sclerosis with in vivo proton magnetic resonance spectroscopy.

In vivo proton magnetic resonance spectroscopy (MRS) may be used to quantify brainstem neuronal degeneration in ALS because of the neuronal localization of N-acetylaspartate and N-acetylaspartylglutamate, together termed NA, which are estimated with this technique. We measured the ratio of NA to creatine/phosphocreatine (NA/Cr) with proton MRS at 3.0 tesla (T) in a 4.3-cm3 volume in the pons and upper medulla of 12 ALS patients and 17 age-matched control subjects. Brainstem NA/Cr was reduced in ALS versus control subjects (mean +/- SD: 1.57 +/- 0.20 versus 1.95 +/- 0.14; p < 0.0001). Patients with severe spasticity or prominent bulbar weakness had the lowest NA/Cr ratios; those with predominantly lower motor neuron limb weakness had near-normal ratios. We conclude that proton MRS may quantify region-specific neuronal dysfunction in ALS.

Adult↗

Metabolite-specific NMR spectroscopy in vivo.

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.

Animals↗

Simultaneous 31P MRS of the soleus and gastrocnemius in Sherpas during graded calf muscle exercise.

The observation that the amount of lactate formed during hypobaric hypoxia decreases with the severity of hypoxia has become known as the "lactate paradox." We used noninvasive 31P magnetic resonance spectroscopy (MRS) to further probe this problem and explore the nature of muscle metabolism during rest-exercise-recovery transitions in Sherpas indigenous to the high Himalayas of Nepal. MRS data were obtained using a whole body 1-m bore, 1.5-T Phillips Gyroscan spectrometer. Muscle-specific localization of MRS data acquisition was achieved by means of a modified image-selected in vivo spectroscopy sequence (ISIS). The spectra acquired from the medial and lateral gastrocnemius muscle, rich in fast-twitch fibers, were well constrained by selective excitation and by the boundary of the leg. The spectra from a third region contained signals predominantly from the soleus, a muscle formed mainly of slow-twitch fibers. We quantified relative concentration changes in phosphocreatine (PCr), Pi, and ATP during a series of calf muscle work bouts; free ADP concentrations were calculated on the assumption that the creatine phosphokinase reaction was always essentially at equilibrium. Hydrogen ion concentrations were calculated from the chemical shift of Pi, which represents the equilibrium between mono- and diprotonated phosphate. Plantar flexion was quantified using a calf muscle ergometer designed for operation within a 1-m whole body magnet. We found that the concentration of ATP was rigorously regulated and thus did not change despite large changes in ATP turnover rates required through exercise. The relative concentrations of PCr and Pi were linear functions of the percent maximum work rate of the lateral and medial gastrocnemius, but on transition to exercise the fractional concentration changes in these metabolites were much less than the fractional change in muscle ATP turnover rates. The relationship between muscle ATP turnover rate and free ADP concentration was complex; again, a kinetic order of 1 was not observed. In contrast to the gastrocnemius, the soleus muscle sustained much smaller changes in the concentrations of these crucial metabolites during rest-work-recovery transitions. Unlike the situation in most other muscles rich in fast-twitch fibers characterized by lactate-associated acidosis during muscle work, the intracellular pH in gastrocnemius of Sherpas was stable through these protocols, which is consistent with the low lactate production (i.e., with the lactate paradox) observed in indigenous highlanders.

Adenosine Diphosphate↗