Biomedical subjects

Peter S Allen

Publications and source records attributed to Peter S Allen.

14 recordsLinked to original sources

PubMed2006

Detection of cerebral degeneration in amyotrophic lateral sclerosis using high-field magnetic resonance spectroscopy.

BACKGROUND: Clinical assessment is insensitive to the degree of cerebral involvement in amyotrophic lateral sclerosis (ALS). Regional brain concentrations N-acetylaspartylglutamate (NAA) plus myo-inositol (Ins), as measured by magnetic resonance spectroscopy, are respectively decreased and increased, suggesting that these compounds may provide a biomarker of the degree of cerebral involvement in ALS. OBJECTIVE: To test the hypothesis that the NAA/Ins ratio may provide an index of cerebral involvement in patients with ALS. DESIGN: High-field (3.0-T) magnetic resonance spectroscopy was performed to determine the NAA/creatine plus phosphocreatine (NAA/Cr), NAA/choline (NAA/Cho), Ins/Cr, and NAA/Ins ratios in the motor cortex. PARTICIPANTS: Seventeen patients with ALS and 15 healthy control subjects were studied. RESULTS: In patients with ALS, the greatest abnormality was a 22% decrease in NAA/Ins (71% sensitivity and 93% specificity, P = .001); Ins/Cr was increased 18% (88% sensitivity and 53% specificity, P = .04), NAA/Cr was decreased 10% (88% sensitivity and 47% specificity, P = .04), and NAA/Cho was decreased 14% (53% sensitivity and 87% specificity, P = .047). Correlation of the ALS Functional Rating Scale with NAA/Ins approached statistical significance (R = 0.43, P = .07). CONCLUSION: The NAA/Ins ratio may provide a meaningful biomarker in ALS given its optimal sensitivity and specificity profile.

Adult↗

PubMed2006

Measurement of brain glutamate and glutamine by spectrally-selective refocusing at 3 Tesla.

A new single-voxel proton NMR spectrally-selective refocusing method for measuring glutamate (Glu) and glutamine (Gln) in the human brain in vivo at 3T is reported. Triple-resonance selective 180 degrees RF pulses with a bandwidth of 12 Hz were implemented within point-resolved spectroscopy (PRESS) for selective detection of Glu or Gln, and simultaneous acquisition of creatine singlets for use as a reference in phase correction. The carriers of the spectrally-selective 180 degrees pulses and the echo times (TEs) were optimized with both numerical and experimental analyses of the filtering performance, which enabled measurements of the target metabolites with negligible contamination from N-acetylaspartate and glutathione. The concentrations of Glu and Gln in the prefrontal cortex were estimated to be 9.7+/-0.5 and 3.0+/-0.7 mM (mean+/-SD, N=7), with reference to Cr at 8 mM.

Adult↗

PubMed2006

Proton spectral editing for discrimination of lactate and threonine 1.31 ppm resonances in human brain in vivo.

A single-voxel proton NMR J-difference editing method for discriminating between the 1.31 ppm resonances of lactate (Lac) and threonine (Thr) in human brain in vivo at 3 T is reported. One double-band and two triple-band Gaussian 180 degrees RF pulses, all with a bandwidth of 15 Hz, were employed within an adiabatic-refocused double-echo localization sequence to induce the target signals of Lac and Thr and simultaneously acquire a creatine singlet in each subscan. The optimum echo time and the editing efficiency were obtained by numerical analysis of the filtering performance. The Lac and Thr signals were extracted, without lipid contamination, from three subspectra. Using the calculated yields, the concentrations of Lac and Thr in the human occipital cortex were estimated to be 0.47+/-0.07 and 0.56+/-0.06 mM (mean+/-SD, N=7), respectively, with reference to Cr at 8 mM.

Algorithms↗

PubMed2006

T2 measurement and quantification of glutamate in human brain in vivo.

The proton NMR transverse relaxation time T(2) of glutamate (Glu) in human brain was measured by means of spectrally selective refocusing at 3.0 T in vivo. An 81.4-ms-long dual-band Gaussian 180 degrees RF pulse, designed for refocusing at 2.35 and 3.03 ppm, was employed within point-resolved spectroscopy (PRESS) to generate the Glu C4-proton target multiplet and the total creatine (tCr) singlet. Six optimal echo times (TEs) between 128 and 380 ms were selected from numerical analysis of the filtering performance for effective detection of the Glu signal with minimal contamination from glutamine (Gln), N-acetylaspartate (NAA), and glutathione (GSH). The magnetization of Glu and tCr was extracted from spectral fitting of experimental and calculated spectra. Apparent T(2) values of Glu and tCr were estimated as 201 +/- 18 and 164 +/- 12 ms for the medial prefrontal (PF) cortex, and 198 +/- 22 and 169 +/- 15 ms (mean +/- SD, N = 5) for the left frontal (LF) cortex, respectively. With water segmentation data, the magnetization values of Glu and tCr of the two adjacent voxels, calculated from the T(2) values and spectra following the thermal equilibrium magnetization, were combined to give the Glu and tCr concentrations as 10.37 +/- 1.06 and 8.87 +/- 0.56 mM for gray matter (GM), and 5.06 +/- 0.57 and 5.16 +/- 0.45 mM (mean +/- SD, N = 5) for white matter (WM), respectively.

Adult↗

PubMed2005

Decreased prefrontal Myo-inositol in major depressive disorder.

BACKGROUND: Postmortem studies have shown robust prefrontal cortex glial losses and more subtle neuronal changes in major depressive disorder (MDD). Earlier proton magnetic resonance spectroscopy (1H-MRS) studies of the glial marker myo-inositol in MDD were subject to potential confounds. The primary hypothesis of this study was that MDD patients would show reduced prefrontal/anterior cingulate cortex levels of myo-inositol. METHODS: Thirteen nonmedicated moderate-severe MDD patients and 13 matched control subjects were studied (six male, seven female per group). Proton magnetic resonance spectroscopy stimulated echo acquisition mode spectra (3.0 T; echo time=168 msec; mixing time=28 msec; repetition time=3000 msec) were obtained from prefrontal/anterior cingulate cortex. Metabolite data were adjusted for tissue composition. RESULTS: Patients with MDD showed significantly lower myo-inositol/creatine ratios (.94+/-.23) than control subjects (1.32+/-.37) [F(1,23)=6.9; p=.016]. CONCLUSIONS: These data suggest a reduction of myo-inositol in prefrontal/anterior cingulate cortex in MDD, which could be a consequence of glial loss or altered glial metabolism. Additional in vivo studies of glial markers could add to the understanding of the pathophysiology of MDD.

Adult↗

PubMed2005

Analytical approach to noncircular section birdcage coil design: verification with a Cassinian oval coil.

A general analytical framework is presented for the design of birdcage radiofrequency resonators on cylindrical formers having arbitrary cross-sectional shape. The primary objective of such shapes would be to improve the sensitivity of the NMR experiment to noncircular regions of the human anatomy while maintaining field homogeneity and quadrature polarization comparable to those of standard circular birdcage coils. The shape of the corresponding radiofrequency screen, which is required to decouple the coil from the rest of the NMR system and which is key to the performance, is also provided by this methodology. The theory was tested by constructing a 3-T, quadrature, proton coil on a shape conforming to the anthropomorphic mean of the human head, namely, the oval of Cassini. Both bench tests (Q) and in vivo spectral and imaging comparisons of the Cassinian coil with an equivalently dimensioned and constructed circular birdcage coil, respectively, predicted and demonstrated in vivo an improvement in SNR of approximately 24% over the circular section coil. The experimental RF field homogeneity and quadrature performance were comparable for both coil geometries, with the circular coil being marginally superior.

Equipment Design↗

PubMed2005

Variability of metabolite yield using STEAM or PRESS sequences in vivo at 3.0 T, illustrated with myo-inositol.

Using as an example the myo-inositol (mI) band at approximately 3.6 ppm in the proton spectrum from brain, an evaluation is presented that highlights the difficulties of quantifying metabolites with strongly coupled spins with either STEAM or PRESS and demonstrates some advantages of prospective sequence analysis when measuring their concentrations. The analysis emphasizes the variation in coupled-spin signal yield and lineshape, compared with that of uncoupled singlets such as N-acetylaspartate, a variation that differs from one metabolite spin system to another. This difference in variation between a target metabolite (e.g., mI) and its contaminating background metabolites (e.g., glutamate and taurine, etc.) is shown to provide in certain circumstances a substantial reduction in background contamination (both metabolite and macromolecule) while maintaining sufficient signal-to-noise ratio for precise quantification. For example, sequence times are demonstrated, both for STEAM and for PRESS, that, relative to the short echo-time sequences typical in the literature, enhance the signal to metabolite background of the 3.6-ppm band of mI by factors of 1.7 and 1.3, respectively, essentially eliminate the macromolecular baseline, and yet in vivo retain an S/N approximately 10 in both cases.

Brain↗

PubMed2005

Brain gamma-aminobutyric acid measurement by proton double-quantum filtering with selective J rewinding.

An optimized single-shot proton double-quantum (DQ) filter for the quantification of gamma-aminobutyric acid (GABA) levels in human brain is reported. It is demonstrated that creation of DQ coherences following dual-resonance-selective refocusing gives a theoretical editing efficiency of 50% for the detection of the GABA resonance at 3.01 ppm. The sequence times are optimized with both numerical and experimental analyses of the editing performance, giving an experimental editing efficiency of 42%. It is acknowledged that homocarnosine is partially coedited, leading to a 20% contribution to the edited signal; however, macromolecule contamination is negligible in vivo under these experimental conditions. The GABA concentration in human prefrontal cortex is estimated to be 0.8 +/- 0.1 micromol/g (mean +/- SD, n = 6), with reference to the internal standard creatine at 9 micromol/g.

Adult↗

PubMed2005

Effect of strong homonuclear proton coupling on localized (13)C detection using PRESS.

The effect of strong homonuclear proton coupling on (13)C incorporation measurements by either indirect or direct means was investigated (and illustrated with glutamate) both numerically and experimentally at 3.0 T. In particular, two sequences were considered, each using a proton PRESS sequence for localization. The indirect (13)C detection method incorporated the POCE (proton observe carbon edited) technique onto PRESS, and for direct (13)C detection a DEPT (distortionless enhancement by polarization transfer) sequence was appended to the PRESS localization. Both analysis and experiment demonstrate that when strong homonuclear coupling of protons is additional to heteronuclear coupling with (13)C spins, the (13)C measures derived from either the indirect PRESS-POCE sequence or the direct-but-enhanced PRESS-DEPT sequence are significantly modified. Specifically, the MR lineshapes of both (13)C-bonded and nonbonded protons are changed during (13)C incorporation, giving rise, for example, to a potential cross-contamination of < or =30% between glutamate (13)C(3) and (13)C(4) measures from the PRESS-POCE indirect method. During direct-but-enhanced detection, the DEPT enhancement is reduced for glutamate (13)C(2), (13)C(3), and (13)C(4) but not equally, and the reduction is further exacerbated by proton PRESS localization, which gives rise to enhancements that are strong functions of PRESS TE(1) and TE(2).

Algorithms↗

PubMed2004

Strategy for the spectral filtering of myo-inositol and other strongly coupled spins.

A multiple quantum filter strategy is presented for spectrally discriminating metabolites with strongly coupled spins from those whose spins are either uncoupled or weakly coupled. The strategy also includes a means for selectively suppressing the background multiplets of metabolites that also have strongly coupled spins. As a demonstration of its efficacy at 3.0 T, the strategy is shown to enhance by a factor of approximately 5 the signal-to-background ratio of the myo-inositol band at 3.6 ppm relative to that in response to a PRESS sequence with the same sequence timings. This is done by eliminating the uncoupled resonance of glycine and the weakly coupled multiplets of glutamate and glutamine, and by selectively suppressing the strongly coupled taurine multiplet 3-fold. The macromolecular background was effectively removed through its transverse decay over 105 ms. The associated cost of gaining the signal to background enhancement is a drop in signal yield by a factor of 0.75 relative to PRESS at the same timings. The myo-inositol signal to noise ratio was nevertheless maintained by the filter at approximately 12.

Adult↗

PubMed2002

Sensitivity calculations and comparisons for shielded elliptical and circular birdcage coils.

An analytical framework is presented which justifies the use of a confocal elliptical shield (previously adopted on empirical or numerical grounds) to limit the spatial extent of the radiofrequency (RF) field produced by an elliptical birdcage coil, while concurrently minimizing field inhomogeneities. From this analytical capability it is further shown that the relative linear mode geometric sensitivities depend only on the shield dimensions and can be readily evaluated, thus providing an upper bound to the improvement in signal-to-noise ratio (SNR) of the damped elliptical birdcage over a circular coil of similar dimensions. The mismatch in the linear mode sensitivities can also be evaluated, and a method for the design of an appropriate feed configuration that ensures quadrature operation is given.

Artifacts↗

PubMed2002

GABA X2 multiplet measured pre- and post-administration of vigabatrin in human brain.

This work demonstrates, in solution and in human brain at 3 tesla, that the X(2)-multiplet of the A(2)M(2)X(2) proton spin system of GABA at 2.315 ppm can be readily resolved from that of the overlapping background, particularly the glutamate multiplet, i.e., the PQ multiplet of the glutamate AMNPQ spin system. Prior to experiment, the values of the stimulated echo acquisition mode (STEAM) sequence parameters TE and TM that maximized the GABA-X(2) discrimination from its background (i.e., 168 ms and 28 ms, respectively) were determined numerically. The determination was made by calculating the spectral response of all contributing metabolites to the STEAM sequence throughout TE/TM space. A baseline GABA concentration (mean +/- standard deviation (SD) of the mean) of 0.78 +/- 0.04 mM was estimated from spectra acquired from a 3 x 3 x 3 cm(3) volume in the parieto-occipital cortex of eight normal control subjects. Five of the eight control subjects were also studied 24 hr post-administration of a single dose of 50 mg.kg(-1) vigabatrin. Four of the five showed increases in GABA in the range of 15-120% of their baseline level.

Brain↗

PubMed2002

Multiple gradient echo sequence optimized for rapid, single-scan mapping of R(2)(*) at high B0.

A multiple-gradient-echo sequence is proposed for accurately mapping R(2)(*) in the presence of in-slice macroscopic susceptibility gradients. In-slice signal loss caused by background macroscopic susceptibility gradients is mitigated by combining three successive gradient-echo images whose slice refocus gradients are successively incremented. The optimum incrementation of slice-refocusing gradients was determined by numerical simulation. By repeating further cycles of three images in the same sequence, artifact-compensated data spanning a range of echo times (TEs) was acquired leading to single-scan, R(2) (*) maps that are quantitatively reflective of microscopic field inhomogeneities. The performance of the sequence was demonstrated at 3.0T, first with a doped aqueous phantom, and then on the head of a normal volunteer. That performance is compared quantitatively with previously published work.

Artifacts↗

PubMed2002

Comments on "theoretical model for an MRI radio frequency resonator".

In contrast to a previous report [Baertlein et al. (2000)], the transverse electomagnetic resonator used in magnetic resonance imaging is shown to be similar to the high-pass "birdcage" resonator in having an electric field minimum in correspondence with the maximum of the magnetic field. The noise performance of each resonator will, in consequence, be comparable, since at high frequencies patient conductive losses are predominant.

Electromagnetic Fields↗