A dual-tuned transceive resonator for (13) C{(1) H} MRS: two open coils in one.

Proton-decoupled, (13) C nuclear MRS experiments require a RF coil that operates at the Larmor frequencies of both (13) C and (1) H. In this work, we designed, built and tested a single-unit, dual-tuned coil based on a half-birdcage open coil design. It was constructed as a low-pass network with a resonant trap in series with each leg. Traps are tuned in alternate legs such that the two resonant modes arise from currents on alternate legs. The coil performance was compared with that of a dual-tuned coil consisting of two proton surface coils operating in quadrature and a single surface coil for (13) C transmission and reception. The half-birdcage coil was shown to produce a more homogeneous RF field at each frequency and was more sensitive to a (13) C signal arising from regions further from the coil surface. The applicability of the coil in vivo was demonstrated by acquiring a proton decoupled, natural abundance (13) C glycogen signal from the calf of a normal volunteer.

Enhancement of spectral editing efficacy of multiple quantum filters in in vivo proton magnetic resonance spectroscopy.

The performance of multiple quantum filters (MQFs) can be disappointing when the background signal also arises from coupled spins. Moreover, at 3.0 T and even higher fields the majority of the spin systems of key brain metabolites fall into the strong-coupling regime. In this manuscript we address comprehensively, the importance of the phase of the multiple quantum coherence-generating pulse (MQ-pulse) in the design of MQFs, using both product operator and numerical analysis, in both zero and double quantum filter designs. The theoretical analyses were experimentally validated with the examples of myo-inositol editing and the separation of glutamate from glutamine. The results demonstrate that the phase of the MQ-pulse per se provides an additional spectral discrimination mechanism based on the degree of coupling beyond the conventional level-of-coherence approach of MQFs. To obtain the best spectral discrimination of strongly-coupled spin systems, therefore, the phase of the MQ-pulse must be included in the portfolio of the sequence parameters to be optimized.

Increased glutamate levels in the medial prefrontal cortex in patients with postpartum depression.

The medial prefrontal cortex (MPFC) is a key brain area in depressive symptomatology; specifically, glutamate (Glu) has been reported to play a significant role in major depression (MD) in this area. MPFC Glu levels are sensitive to ovarian hormone fluctuations and pregnancy and the postpartum period are associated with the most substantial physiological alterations of female hormones. It is therefore logical to measure MPFC Glu levels in women with postpartum depression (PPD). Using in vivo magnetic resonance spectroscopy (MRS) at a field strength of 3 T, we acquired single-voxel spectra from the MPFC of 12 women with PPD and 12 healthy controls (HCs) matched for postpartum scan timing. Water-referenced MPFC Glu levels were measured using a MRS technique that allowed us to be specific for Glu with very little glutamine contamination. The concentrations of other water-quantified brain metabolites such as glycerophosphorylcholine plus phosphorylcholine, N-acetylaspartate (NAA), and creatine plus phosphocreatine were measured in the same MR spectra. MPFC Glu levels were higher in women with PPD (7.21±1.20) compared to matched HCs (6.04±1.21). There were no differences between groups for other brain metabolites measured. These findings suggest an association between Glu dysregulation in the MPFC and PPD. Whether the pathophysiology of PPD differs from the pathophysiology of MD remains to be determined. Further investigations are needed to determine the chronological associations between the occurrence of symptoms of PPD and the onset of changes in MPFC Glu levels.

Contamination of single-voxel multiple quantum filters by external water signals arising from intermolecular multiple quantum coherences.

Multiple-quantum filtered pulse sequences simplify overlapping metabolite spectra by the elimination of peaks from uncoupled spin species, most notably from methyl groups and water, and the minimization of unwanted coupled-spin peaks. However, it is shown in this study that a significant contaminant water signal can pass through this family of filters in the form of intermolecular multiple-quantum coherences. An imaging evaluation of a single-voxel multiple quantum filter experiment confirms that the water contamination is excited from outside of the voxel of interest, thus having an increased potential for broad spectral contamination. Phantom and in vivo experiments at 3.0 T are used to illustrate, first, significant water contamination of a single-voxel double quantum filter experiment optimized for the observation of glutamate, and second, the elimination of the unwanted water signal with conventional phase cycling and optimized filter gradient orientations.

Clinical NOE 13C MRS for neuropsychiatric disorders of the frontal lobe.

In this communication, a scheme is described whereby in vivo (13)C MRS can safely be performed in the frontal lobe, a human brain region hitherto precluded on grounds of SAR, but important in being the seat of impaired cognitive function in many neuropsychiatric and developmental disorders. By combining two well known features of (13)C NMR-the use of low power NOE and the focus on (13)C carbon atoms which are only minimally coupled to protons, we are able to overcome the obstacle of SAR and develop means of monitoring the (13)C fluxes of critically important metabolic pathways in frontal brain structures of normal volunteers and patients. Using a combination of low-power WALTZ decoupling, variants of random noise for nuclear overhauser effect enhancement it was possible to reduce power deposition to 20% of the advised maximum specific absorption rate (SAR). In model solutions (13)C signal enhancement achieved with this scheme were comparable to that obtained with WALTZ-4. In human brain, the low power procedure effectively determined glutamine, glutamate and bicarbonate in the posterior parietal brain after [1-(13)C] glucose infusion. The same (13)C enriched metabolites were defined in frontal brain of human volunteers after administration of [1-(13)C] acetate, a recognized probe of glial metabolism. Time courses of incorporation of (13)C into cerebral glutamate, glutamine and bicarbonate were constructed. The results suggest efficacy for measurement of in vivo cerebral metabolic rates of the glutamate-glutamine and tricarboxylic acid cycles in 20 min MR scans in previously inaccessible brain regions in humans at 1.5 T. We predict these will be clinically useful biomarkers in many human neuropsychiatric and genetic conditions.

Spatial profiling of the corticospinal tract in amyotrophic lateral sclerosis using diffusion tensor imaging.

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) was used as a noninvasive method to evaluate the anatomy of the corticospinal tract (CST) and the pattern of its degeneration in amyotrophic lateral sclerosis (ALS). METHODS: Fourteen patients with ALS and 15 healthy controls underwent DTI. Parameters reflecting coherence of diffusion (fractional anisotropy, FA), bulk diffusion (apparent diffusion coefficient, ADC), and directionality of diffusion (eigenvalues) parallel to (lambda( parallel)) or perpendicular to (lambda( perpendicular)) fiber tracts were measured along the intracranial course of the CST. RESULTS: FA and lambda( parallel) increased, and ADC and lambda( perpendicular) decreased progressively from the corona radiata to the cerebral peduncle in all subjects. The most abnormal finding in patients with ALS was reduced FA in the cerebral peduncle contralateral to the side of the body with the most severe upper motor neuron signs. lambda( parallel) was increased in the corona radiata. Internal capsule FA correlated positively with symptom duration, and cerebral peduncle ADC positively with the Ashworth spasticity score. CONCLUSION: There is a spatial dependency of diffusion parameters along the CST in healthy individuals. Evidence of intracranial CST degeneration in ALS was found with distinct diffusion changes in the rostral and caudal regions.

Measurement of GABA and contaminants in gray and white matter in human brain in vivo.

A preliminary study of discrimination between GABA and macromolecules (MMs) in human brain by proton double quantum filtering (DQF) at 3.0 T in vivo is presented. GABA-tuned and MM-tuned DQ filters were designed with dual-band 180 degrees radiofrequency (RF) pulses that were tuned for selective refocusing of GABA (3.0 and 1.9 ppm) and putative MM resonances (3.0 and 1.7 ppm), respectively. GABA and putative MM signals were extracted from a combined analysis of the filtered mixture signals and the calculated editing yields. Unexpectedly, the GABA and putative MM signals exhibited a similar doublet linewidth at the optimized TE = 82 ms. Furthermore, substantial MM-tuned DQF signal remained at TE = 148 ms, indicating the presence of a component other than MM. With water segmentation data, the GABA-tuned and MM-tuned DQF measures from the medial prefrontal and left frontal lobes were combined to give the concentrations of GABA and the additional component as 1.1 +/- 0.1 and 0.8 +/- 0.1 mM (mean +/- SD, N=3) for gray matter (GM) and 0.4 +/- 0.1 and 0.7+/-0.1 mM (N=3) for white matter (WM), respectively.

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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.