Diffusely elevated cerebral choline and creatine in relapsing-remitting multiple sclerosis.

It is well known that multiple sclerosis (MS) pathogenesis continues even during periods of clinical silence. To quantify the metabolic characteristics of this activity we compared the absolute levels of N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) in the normal-appearing white matter (NAWM) between relapsing-remitting (RR) MS patients and controls. Metabolite concentrations were obtained with 3D proton MR spectroscopy at 1.5 T in a 480 cm(3) volume-of-interest (VOI), centered on the corpus callosum of 11 MS patients and 9 matched controls. Gray/white-matter/cerebral-spinal-fluid (CSF) volumes were obtained from MRI segmentation. Patients' average VOI tissue volume (V(T)), 410.8 +/- 24.0 cm(3), and metabolite levels, NAA = 6.33 +/- 0.70, Cr = 4.67 +/- 0.52, Cho = 1.40 +/- 0.17 mM, were different from the controls by -8%, -9%, +22% and +32%. The Cho level was the only single metric differentiating patients from controls at 100% specificity and >90% sensitivity. Diffusely elevated Cho and Cr probably reflect widespread microscopic inflammation, gliosis, or de- and remyelination in the NAWM. Both metabolites are potential prognostic indicators of current disease activity, preceding NAA decline and atrophy.     

Comparison of longitudinal metabolite relaxation times in different regions of the human brain at 1.5 and 3 Tesla.

In vivo longitudinal relaxation times of N-acetyl compounds (NA), choline-containing substances (Cho), creatine (Cr), myo-inositol (mI), and tissue water were measured at 1.5 and 3 T using a point-resolved spectroscopy (PRESS) sequence with short echo time (TE). T(1) values were determined in six different brain regions: the occipital gray matter (GM), occipital white matter (WM), motor cortex, frontoparietal WM, thalamus, and cerebellum. The T(1) relaxation times of water protons were 26-38% longer at 3 T than at 1.5 T. Significantly longer metabolite T(1) values at 3 T (11-36%) were found for NA, Cho, and Cr in the motor cortex, frontoparietal WM, and thalamus. The amounts of GM, WM, and cerebrospinal fluid (CSF) within the voxel were determined by segmentation of a 3D image data set. No influence of tissue composition on metabolite T(1) values was found, while the longitudinal relaxation times of water protons were strongly correlated with the relative GM content.     

Lactate imaging of the human brain at 1.5 T using a double-quantum filter

The use of a double-quantum filtered ¹H NMR spectroscopic imaging technique is described to detect the spatial distribution of lactate in the human brain. In two patients the feasibility of this technique is shown and compared with existing single-quantum spectroscopic imaging and single voxel techniques. Singles lice double-quantum fitered lactate images were obtained showing the lactate distribution over the entire slice in the brain. The lipid signal suppression was sufficient for the unambiguous detection of lactate. The signal loss of the lactate signal due to the incorporation of the double-quantum filter was 50–70% relative to the single-quantum signal.     

Proton T2 relaxation study of water, N-acetylaspartate, and creatine in human brain using Hahn and Carr-Purcell spin echoes at 4T and 7T.

Carr-Purcell and Hahn spin-echo (SE) measurements were used to estimate the apparent transverse relaxation time constant (T2) of water and metabolites in human brain at 4T and 7T. A significant reduction in the T2 values of proton resonances (water, N-acetylaspartate, and creatine/phosphocreatine) was observed with increasing magnetic field strength and was attributed mainly to increased dynamic dephasing due to increased local susceptibility gradients. At high field, signal loss resulting from T2 decay can be substantially reduced using a Carr-Purcell-type SE sequence.     

Assessment of absolute metabolite concentrations in human tissue by 31P MRS in vivo. Part I: Cerebrum,cerebellum, cerebral gray and white matter

Absolute metabolite concentrations were determined in four different brain regions using phosphorus magnetic resonance spectroscopy (³¹P MRS) on 10 healthy adult volunteers. Localized spectra were collected simultaneously from the cerebellum and the cerebrum and, later, from deep white matter and cortical gray matter by means of a two-volume lSlS pulse sequence and a Helmholtz-type RF-coil. Each brain spectrum was quantified with a calibration spectrum from a head-shaped simulation phantom. A time-domain fitting routine was used to process the fully relaxed data. Several metabolite concentrations (mmolAiter) differed significantly between the cerebrum and the cerebellum (PME = 3.2 f 0.3 and 4.0 & 0.6, PC:r = 2.9 & 0.3 and 3.9 f 0.4, NTP = 2.9 f 0.2 and 2.6 & 0.2, respectively) and between cortical gray matter and deep white matter (PME = 3.1 f 0.4 and 4.3 ± 0.8, PDE = 10.1 f 2.5 and 14.2 & 2.6, respectively). The concentration of free magnesium ion was found to be similar in all four brain regions (0.53 ± 0.21 mmol/liter) but the intracellular pH was significantly higher in the cerebellum (7.04 ± 0.03) than in the cerebrum (6.99 ± 0.02).     

Assessment of glutamate and glutamine contribution to in vivo N-acetylaspartate quantification in human brain by (1)H-magnetic resonance spectroscopy.

N-Acetylaspartate (NAA) is one of the most important metabolites detectable by brain (1)H-MRS being considered an index of neuronal integrity. At the low magnetic field used in most clinical settings beta,gamma-glutamate/glutamine (Glx) resonances are very close and partially overlap the methyl-NAA resonance interfering with NAA quantification especially at low TE and in the presence of increased Glx signals. NAA overestimation due to Glx on a set of model solutions containing NAA, glutamate, and glutamine in variable amounts was evaluated and the result tested in vivo in six healthy controls and five age- and sex-matched patients with hepatic encephalopathy (HE), the latter having an increased Glx content. A method to assess in vivo the NAA overestimation caused by Glx is proposed. A perfect match was obtained between the assessment of Glx contamination on the NAA of healthy controls and that obtained on the model solutions. However, a substantial difference in NAA overestimation was found between controls and HE patients that cannot be explained by our model. An interpretative hypothesis is provided.     

Regional metabolite concentrations in human brain as determined by quantitative localized proton MRS

The regional distribution of brain metabolites was studied in several cortical white and gray matter areas, cerebellum, and thalamus of young adults with use of quantitative single-voxel proton MRS at 2.0 T. Whereas the neuronal compound N-acetylaspartate is distributed homogeneously throughout the brain, N-acetylaspartylglutamate increases caudally and exhibits higher concentrations in white matter than in gray matter. Creatine, myo-inositol, glutamate, and glutamine are less concentrated in cortical white matter than in gray matter. The highest creatine levels are found in cerebellum, parallel to the distribution of creatine kinase and energy-requiring processes in the brain. Also myo-inositol has highest concentrations in the cerebellum. Choline-containing compounds exhibit a marked regional variability with again highest concentrations in cerebellum and lowest levels and a strong caudally decreasing gradient in gray matter. The present findings neither support a metabolic gender difference (except for a 1.3-fold higher myo-inositol level in parietal white matter of female subjects) nor a metabolic hemispheric asymmetry.     

Lactate, choline, and creatine levels measured by vitro 1H-MRS as prognostic parameters in patients with non-small-cell lung cancer

PURPOSE: To determine the biochemical characteristics of lung cancer tissue using in vitro (1)H-MRS, and investigate the correlation between survival probabilities and lactate (Lac), creatine (Cr), and choline (Cho) concentrations measured by in vitro (1)H-MRS. MATERIALS AND METHODS: A total of 21 patients with lung cancer were included in this retrospective study. (1)H-MRS spectra measurements were performed at 6.35T using a JNM-EX270, high-resolution FT-NMR spectrometer. RESULTS: When normal lung tissue was compared with lung cancer tissue, significant differences were noted most consistently in the levels of Lac and Cho, with lung cancer tissue showing higher values than normal lung tissue. Lac concentrations of lung cancer tissue were significantly higher in patients with recurrence compared to patients without recurrence (0.285 +/- 0.096 mumol/g). The mean overall survival of patients in the low-Lac group was 50.28 +/- 6.47 months, which is significantly higher compared to the high-Lac group, which had a mean survival time of only 30.49 +/- 5.41 months. CONCLUSION: Kaplan-Meier analysis of the data showed that the overall and disease-free survival probabilities were significantly higher in patients with low tumor Lac values than in those with high tumor Lac concentrations.     

Toward understanding transverse relaxation in human brain through its field dependence

Apparent transverse‐relaxation rate constants (R = 1/T) were measured in various regions of the healthy human brain using a multiecho adiabatic spin‐echo sequence at five different magnetic fields, 1.5, 1.9, 3, 4.7, and 7 T. The R values showed a clear dependence on magnetic field strength (B₀). The regional distribution of the R was well explained by the sum of three components: (1) regional nonhemin iron concentration ([Fe]), (2) regional macromolecular mass fraction (f_M), and (3) a region‐independent factor. Accordingly, R = α[Fe] + βf_M + γ, where coefficients α, β, and γ were experimentally determined at each magnetic field by a least square fitting method using multiple regression analysis. Although the coefficient α linearly increased with B₀, β showed a quadratic dependence on top of a field‐independent component. The coefficient γ also increased slightly with B₀ on top of a field‐independent component. The linear dependence of α on B₀ was consistent with that observed for the transverse‐relaxation rate of water protons in ferritin solutions as found previously by others. The quadratic dependence of β on B₀ was accounted for by isochronous and anisochronous exchange mechanisms using intrinsic‐relaxation parameters obtained from the literature. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.     

Magnetic field and tissue dependencies of human brain longitudinal 1H2O relaxation in vivo.

Brain water proton (1H2O) longitudinal relaxation time constants (T1) were obtained from three healthy individuals at magnetic field strengths (B0) of 0.2 Tesla (T), 1.0T, 1.5T, 4.0T, and 7.0T. A 5-mm midventricular axial slice was sampled using a modified Look-Locker technique with 1.5 mm in-plane resolution, and 32 time points post-adiabatic inversion. The results confirmed that for most brain tissues, T1 values increased by more than a factor of 3 between 0.2T and 7T, and over this range were well fitted by T1 (s)=0.583(B0)0.382, T1(s)=0.857(B0)0.376, and T1(s)=1.35(B0)0.340 for white matter (WM), internal GM, and blood 1H2O, respectively. The ventricular cerebrospinal fluid (CSF) 1H2O T1 value did not change with B0, and its average value (standard deviation (SD)) across subjects and magnetic fields was 4.3 (+/-0.2) s. The tissue 1/T1 values at each field were well correlated with the macromolecular mass fraction, and to a lesser extent tissue iron content. The field-dependent increases in 1H2O T1 values more than offset the well-known decrease in typical MRI contrast reagent (CR) relaxivity, and simulations predict that this leads to lower CR concentration detection thresholds with increased magnetic field.     

1H metabolite relaxation times at 3.0 tesla: Measurements of T1 and T2 values in normal brain and determination of regional differences in transverse relaxation

PURPOSE: To measure 1H relaxation times of cerebral metabolites at 3 T and to investigate regional variations within the brain. MATERIALS AND METHODS: Investigations were performed on a 3.0-T clinical whole-body magnetic resonance (MR) system. T2 relaxation times of N-acetyl aspartate (NAA), total creatine (tCr), and choline compounds (Cho) were measured in six brain regions of 42 healthy subjects. T1 relaxation times of these metabolites and of myo-inositol (Ins) were determined in occipital white matter (WM), the frontal lobe, and the motor cortex of 10 subjects. RESULTS: T2 values of all metabolites were markedly reduced with respect to 1.5 T in all investigated regions. T2 of NAA was significantly (P < 0.001) shorter in the motor cortex (247 +/- 13 msec) than in occipital WM (301 +/- 18 msec). T2 of the tCr methyl resonance showed a corresponding yet less pronounced decrease (162 +/- 16 msec vs. 178 +/- 9 msec, P = 0.021). Even lower T2 values for all metabolites were measured in the basal ganglia. Metabolite T1 relaxation times at 3.0 T were not significantly different from the values at 1.5 T. CONCLUSION: Transverse relaxation times of the investigated cerebral metabolites exhibit an inverse proportionality to magnetic field strength, and especially T2 of NAA shows distinct regional variations at 3 T. These can be attributed to differences in relative WM/gray matter (GM) contents and to local paramagnetism.     

High magnetic field water and metabolite proton T1 and T2 relaxation in rat brain in vivo.

Comprehensive and quantitative measurements of T1 and T2 relaxation times of water, metabolites, and macromolecules in rat brain under similar experimental conditions at three high magnetic field strengths (4.0 T, 9.4 T, and 11.7 T) are presented. Water relaxation showed a highly significant increase (T1) and decrease (T2) with increasing field strength for all nine analyzed brain structures. Similar but less pronounced effects were observed for all metabolites. Macromolecules displayed field-independent T2 relaxation and a strong increase of T1 with field strength. Among other features, these data show that while spectral resolution continues to increase with field strength, the absolute signal-to-noise ratio (SNR) in T1/T2-based anatomical MRI quickly levels off beyond approximately 7 T and may actually decrease at higher magnetic fields.     

Apparent transverse relaxation rate in human brain varies linearly with tissue iron concentration at 4.7 T.

Multiple pairs of adiabatic passage pulses were implemented in a spin-echo sequence to achieve accurate measurements of the apparent transverse relaxation time (T(2)(dagger)) in a short scan time. In experiments on agarose gel phantoms with T(2) values ranging from 30 to 105 ms, the measured T(2)(dagger) values were in good agreement with transverse relaxation times measured with a nonselective Carr-Purcell-Meiboom-Gill sequence. In experiments on normal human brain at 4.7 T, T(2) (dagger) values in five different gray matter regions were found to range from 38 +/- 2 ms (globus pallidus) to 64 +/- 2 ms (frontal cortex). The apparent relaxation rate (1/T(2)(dagger)) in these five regions showed strong correlation (r = 0.97) with published levels of iron (Fe) in those regions. The linear coefficient relating 1/T(2)(dagger) and [Fe] at 4.7 T was measured to be 0.551 (s x mg Fe/100 g f.w.)(-1). When compared with the values obtained in a previous report for six different static fields (B(0)) up to 1.5 T, the current measurement confirms the linear dependence of the linear coefficient on B(0) up to 4.7 T (r = 0.99). These results suggest that the T(2)(dagger) value in the human brain is predominantly affected by the nonhemin iron distribution. The strong correlation between the obtained T(2)(dagger) values and the regional iron concentrations suggests a role for this pulse sequence in quantifying in vivo brain iron at high magnetic field.