Quantification of metabolites from single-voxelin vivo 1H NMR data of normal human brain by means of time-domain data analysis

We present here a combination of time-domain signal analysis procedures for quantification of human brainin vivo ¹H NMR spectroscopy (MRS) data. The method is based on a separate removal of a residual water resonance followed by a frequency-selective time-domain line-shape fitting analysis of metabolite signals. Calculation of absolute metabolite concentrations was based on the internal water concentration as a reference. The estimated average metabolite concentrations acquired from six regions of normal human brain with a single-voxel spin-echo technique for theN-acetylaspartate, creatine, and choline-containing compounds were 11.4±1.0,6.5±0.5, and 1.7±0.2 mmol kg^–1 wet weight, respectively. The time-domain analyses ofin vivo ¹H MRS data from different brain regions with their specific characteristics demonstrate a case in which the use of frequency-domain methods pose serious difficulties.     

Comparison of in vivo1H MRS of human brain tumours with1H HR-MAS spectroscopy of intact biopsy samples in vitro

High resolution magic angle spinning (MAS)¹H nuclear magnetic resonance (NMR) spectroscopy has been employed to study intact human brain tumour tissue and comparison with the corresponding in vivo spectrum has been made. Two dimensional¹H MAS-NMR measurements, including J-resolved and homonuclear shift correlation spectra, were obtained to aid metabolite signal assignment. MAS gave greatly improved line-shape and reduced line-width in comparison to conventional high resolution in vivo¹H MRS of intact tissue, permitting the simultaneous detection of cellular lipids and metabolites. The technique provides the most direct method for comparison of in vivo spectra with high resolution spectra in vitro and hence allows more reliable peak assignment of in vivo¹H MRS spectra.     

Valproic acid intoxication identified by1H and1H-13C correlated NMR spectroscopy of urine samples

Analysis of biological fluids by proton and carbon nuclear magnetic resonance spectroscopy (¹H and¹³C NMR) is a promising tool in clinical biology. We used this method for rapid toxicological screening in the case of two suicide attempts. For each case, a urine sample was analysed at 300 MHz by 1D and 2D sequences (TOCSY and HMBC) in a short experimental time. Quantification was performed by peak integration on the 1D¹H NMR spectrum. For the two patients, results showed the same resonances of the major metabolite, valproyl-O-glucuronide at concentrations of 121 and 44 mmol/l.     

In vivo localized1 H spectroscopy of the rat eye at 7 T: preliminary studies

Preliminaryin vivo proton spectroscopic studies of the posterior chamber of the rat eye have been undertaken at 7 T. The Spatial and Chemical shift encoded Excitation (SPACE) localization sequence was used to acquire signals from 10-µl voxels and demonstrate the presence of metabolites associated with the vitreous humor, lens, retina, and the optic nerve. LocalizedT ₂ andT ₁ measurements of water in the vitreous humor indicate a relatively fluid environment. Susceptibility maps are used to demonstrate the difficulties ofin vivo spectroscopic investigations in the anterior regions of the eye. Comments are made concerning the implications for spectral resolution in these regions.     

In vivo1H MR spectra analysis by means of second derivative method

Short echo time (TE) in vivo PRESS¹H MR spectra (2 T. TE = 35 ms) of normal brain were fitted in the frequency domain using the second derivative method. In this approach, local maxima and hidden peaks are found as local minima of spectrum second derivative. The Lorentzian robust minimisation procedure (referred to as maximum likelihood or m-estimate fitting) using Levenburg -Marquardt non-linear fitting engine was applied. Spectral lines were approximated under the assumption of the mixed Lorentzian/Gaussian lineshapes. The same procedure was applied to 18 proton spectra. The number of peaks found within the range of 0.74/4.2 parts per million (ppm) was 52 ± 3 and their positions were almost the same. The fitted lines were assigned on the basis of the J-pattern recalculated for the field strength of 2 T and by comparing the chemical shifts with the shifts in the single compound spectra. The ratios of main metabolites, such as NAA/Cr, Cho/Cr, Cho/NAA and ml/Cr, are in accord with those obtained earlier using the software supplied with the MR imager and the absolute concentrations ofN-acetylaspartate (NAA). choline containing compounds (Cho),myo Inositol (ml), glucose (Gle) and glutamate (Glu) obtained from the fit agree with those reported in literature, which confirms the usefulness of the second derivative method in routine analyses of¹H MR brain spectra.     

Application of LCModel for quality control and quantitative in vivo1H MR spectroscopy by short echo time STEAM sequence

The linear combination of model spectra (LCModel) calculation of a parameter for long-term quality control,k _T, was introduced, representing the ratio of the temporal and nominal intensities of CH₃ groups of lactate and acetate in a quality control phantom. This procedure is a part of the quality assurance of the scanner using fully automatic measurement and calculation ofk _T parameters, and utilizing Shewhart regulation control charts for continuous evaluation of the magnetic resonance (MR) scanner setting. The application of thek _T parameter for the correction of in vivo data increases the precision of molar concentration determination by about 4%. This was tested by the quantitative in vivo MR determination of the molar concentrations of 13 prominent metabolites (N-acetylaspartate (NAA),N-acetylaspartylgutamate, creatine and phosphocreatine (Cr), choline-containing compounds (Cho), myo-inositol, scyllo-inositol., γ-aminobutyric acid, glutamine, glutamate, glucose, lactate, alanine, taurine) in the white matter and hippocampus of the brain in groups of volunteers, using a short echo time stimulated echo acquisition mode sequence (echo time =10 ms) and the LCModel technique. The repeatability of the measurement of prominent metabolites such as NAA, Cr and Cho was found to be around 10% (relative standard deviation,n=6); precision in a group of volunteers (n=20 and 28, respectively) was in the range of approximately 13–20%. For other metabolites, which are measured with a lower signal-to-noise ratio, the precision can be much lower.     

The role of relaxation time corrections for the evaluation of long and short echo time <Superscript>1</Superscript>H MR spectra of the hippocampus by NUMARIS and LCModel techniques

1H MR spectroscopy is routinely used for lateralization of epileptogenic lesions. The present study deals with the role of relaxation time corrections for the quantitative evaluation of long (TE=135 ms) and short echo time (TE=10 ms) 1H MR spectra of the hippocampus using two methods (operator-guided NUMARIS and LCModel programs). Spectra of left and right hippocampi of 14 volunteers and 14 patients with epilepsy were obtained by PRESS (TR/TE=5000/135 ms) and STEAM (TR/TE=5000/10 ms) sequences with a 1.5-T imager. Evaluation was carried out using Siemens NUMARIS software and the results were compared with data from LCModel processing software. No significant differences between the two methods of processing spectra with TE=135 ms were found. The range of relaxation corrections was determined. Metabolite concentrations in hippocampi calculated from spectra with TE=135 ms and 10 ms after application of correction coefficients did not differ in the range of errors and agreed with published data (135 ms/10 ms: NAA=10.2±0.6/10.4±1.3 mM, Cho=2.4±0.1/2.7±0.3 mM, Cr=12.2±1.3/11.3±1.3 mM). When relaxation time corrections were applied, quantitative results from short and long echo time evaluation with LCModel were in agreement. Signal intensity ratios obtained from long echo time spectra by NUMARIS operator-guided processing also agreed with the LCModel results.