Measurement of the T2 relaxation time of ethanol and cerebral metabolites, in vivo.

The SPACE volume selection technique was combined with a spin-echo sequence to measure the transverse relaxation time of the resonances of ethanol and cerebral metabolites in the dog brain, in vivo. The method was extended to measure brain metabolite T2 values in the rat using 1H NMR microspectroscopy. The T2 decays for the resonances of the metabolites N-acetylaspartate, creatine/phosphocreatine, and choline/phosphorylcholine were found to be biexponential with long T2 components of 490, 260, and 350 ms for the dog and 490, 220, and 355 ms for the rat brain, respectively. The existence of a second T2 component may originate from J-coupled nonresolved metabolite resonances. The relaxation decay for the ethanol triplet could be fitted to a single exponential giving a T2 relaxation time of 335 ms. However, given the large errors in the measurement of ethanol peak intensities at short echo times because of overlapping lipid signal and the effects of J-modulation, a biexponential decay with a long T2 component of 335 ms cannot be ruled out. Ambiguities regarding the reported partial detection of the 1H NMR signal of ethanol in the brain are discussed.     

Magnetic resonance imaging of brain tumors: measurement of T1. Work in progress

Longitudinal relaxation times (T1) of 20 brain tumors were calculated in vivo using a whole-body magnetic resonance unit with a 0.15-T resistive magnet. Images employing standard inversion recovery pulse sequences with different intervals between the 180 degrees pulse and selective excitation pulses were compared on every point of the 256 X 256 pixel matrix. Tumor, white matter, and gray matter were sampled from each patient from the computed T1 image for T1 measurement. Astrocytomas, neurinomas, and metastatic tumors showed longer T1 values than did meningiomas. Lipomas had the shortest T1s. It is concluded that it is difficult to predict histological types of brain tumors by the measurement of T1 alone because of the wide variation in relaxation times, but measurement of T1 can be helpful in differentiating brain tumors when additional information about the patient's condition is known.     

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.     

Compartmental study of T(1) and T(2) in rat brain and trigeminal nerve in vivo.

The integrated T(1)-T(2) characteristics of rat brain and trigeminal nerve water were studied in vivo using a rapid method for acquiring a series of images that depend on T(1) and T(2) relaxation times. Gray matter regions showed only one signal component in both the T(1) and T(2) domains. Trigeminal nerve, however, which has been shown previously to exhibit three T(2) components, was found to also exhibit three T(1) components. The correlations between these T(1) and T(2) components were demonstrated by uniquely filtering out each of the three T(2) components using an inversion-recovery preparation, as determined by the component T(1) values. Based on previous works, it is postulated that each of these three signal components is derived from a unique microanatomical region of the nerve. Knowledge of these T(1) components may thus prove valuable in devising novel methods of identifying the presence and quantifying the volume of tissue subtypes such as myelin.     

Changes in the proton T2 relaxation times of cerebral water and metabolites during forebrain ischemia in rat at 9.4 T.

Proton T(2) relaxation times of cerebral water and metabolites were measured before, during, and after transient forebrain ischemia in rat at 9.4 T using localized proton magnetic resonance spectroscopy ((1)H-MRS) with Hahn echoes formed at different echo times (TEs). It was found that the T(2) values of water and N-acetyl aspartate (NAA) methyl, but not total creatine (tCr) methyl, decrease significantly (approximately 10%) during ischemia, and this T(2) reduction is reversed by reperfusion. The T(2) reduction observed for NAA was most likely caused by the extravascular component of the blood oxygenation level-dependent (BOLD) effect induced by a drastically increased deoxyhemoglobin content during ischemia. The absence of T(2) changes for tCr can probably be explained by the fact that the BOLD-related T(2) decrease was counterbalanced by the conversion of phosphocreatine (PCr) to creatine (Cr), which has a longer T(2) than PCr, during ischemia. The changes in T(2) should be taken into account for the quantification of metabolite concentrations during ischemia.     

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.     

Measurement of spin-lattice relaxation times and chemical exchange rates in multiple-site systems using progressive saturation.

A new method for measuring spin-lattice relaxation times and chemical exchange (CE) rate constants in multiple-site exchanging systems is described. The method, chemical exchange and T(1) measurement using progressive saturation (CUPS), was applied to determine T(1)s and analyze phosphorus exchange among phosphocreatine (PCr), ATP, and inorganic phosphate (Pi), mediated by creatine kinase (CK) and ATP synthase, using (31)P-MRS. Two-site exchange was analyzed in vitro and in the rat leg, and three-site exchange was analyzed in the rat heart. Data were fitted to a model of progressive saturation incorporating T(1) relaxation and CE. For the in vitro system at 8.45 T, we found T(1)(PCr)=2.86 s and T(1)(gamma-ATP)=1.72 s. For the rat gastrocnemius at 1.9T, we found T(1)(PCr) = 6.60 s and T(1)(gamma-ATP) = 2.06 s. For the rat heart at 9.4 T, we found T(1)(PCr)=3.35 s, T(1)(gamma-ATP)=0.69 s, and T(1)(Pi=1.83 s. All of these values were within 20% of literature values. Similarly, the determined exchange rates were in the same range as published values. Using simulations, we compared CUPS with transient saturation transfer as a method for measuring T(1)s and rates. The two methods showed similar sensitivity to noise. We conclude that CUPS is a viable alternative for measuring T(1)s and CE rates in exchanging systems.     

Quantitative T1rho NMR spectroscopy of rat cerebral metabolites in vivo: effects of global ischemia.

The NMR relaxation times (T(1rho), T(2), and T(1)) of water, N-acetylaspartate (NAA), creatine (Cr), choline-containing compounds (Cho), and lactate (Lac) were quantified in rat brain at 4.7 T. In control animals, the cerebral T(1rho) figures, as determined with a spin-lock field of 1.0 G, were 575 +/- 30 ms, 380 +/- 19 ms, 705 +/- 53 ms, and 90 +/- 1 ms for NAA, Cr, Cho, and water, respectively. The T(1rho) figures were 62-103% longer than their respective T(2) values determined by a multiecho method. In global (ischemic) ischemia, T(1rho) of NAA declined by 34%, that of Cr and Cho did not change, and that of water increased by 10%. The T(1rho) of lactate in ischemic brain was 367 +/- 44 ms. Similar patterns of changes were observed in the multiecho T(2) of these cerebral metabolites. The T(1) of water and NAA changed in a fashion similar to that of T(1rho) and T(2). These results show differential responses in metabolite and water T(1rho) relaxation times following ischemia, and indicate that metabolite T(1rho) and T(2) relaxation times behave similarly in the ischemic brain. The contributions of dipolar and nondipolar effects on T(1rho) relaxation in vivo are discussed in this work.     

Comparison of T(1) and T(2) metabolite relaxation times in glioma and normal brain at 3T

PURPOSE: To measure T(1) and T(2) relaxation times of metabolites in glioma patients at 3T and to investigate how these values influence the observed metabolite levels. MATERIALS AND METHODS: A total of 23 patients with gliomas and 10 volunteers were studied with single-voxel two-dimensional (2D) J-resolved point-resolved spectral selection (PRESS) using a 3T MR scanner. Voxels were chosen in normal appearing white matter (WM) and in regions of tumor. The T(1) and T(2) of choline containing compounds (Cho), creatine (Cr), and N-acetyl aspartate (NAA) were estimated. RESULTS: Metabolite T(1) relaxation values in gliomas were not significantly different from values in normal WM. The T(2) of Cho and Cr were statistically significantly longer for grade 4 gliomas than for normal WM but the T(2) of NAA was similar. These differences were large enough to impact the corrections of metabolite levels for relaxation times with tumor grade in terms of metabolite ratios (P < 0.001). CONCLUSION: The differential increase in T(2) for Cho and Cr relative to NAA means that the ratios of Cho/NAA and Cr/NAA are higher in tumor at longer echo times (TEs) relative to values in normal appearing brain. Having this information may be useful in defining the acquisition parameters for optimizing contrast between tumor and normal tissue in MR spectroscopic imaging (MRSI) data, in which limited time is available and only one TE can be used.     

Localized 7Li MR spectroscopy and spin relaxation in rat brain in vivo.

Localized 7Li MR point-resolved spectroscopy (PRESS) was developed as a technique to measure lithium (Li) concentration in rat brain in vivo. Localized 7Li spectra could be obtained at 4.7 T in a 0.7-ml voxel in rat brain over the entire therapeutic range of serum Li for humans. Localized 7Li spin-lattice (T1) and spin-spin (T2) relaxation times were measured. Measured intensities were corrected for spin relaxation effects and 7Li MR visibility in vivo. The average T1 was 3.3 +/- 0.9 sec, and the average T2 was 82 +/- 20 ms. Neither T1 nor T2 correlated with brain concentration. No statistically significant change was found in either T1 or T2 from approximately 7-17 days of Li dosing.     

Cerebral abnormalities: use of calculated T1 and T2 magnetic resonance images for diagnosis

The potential clinical importance of T1 and T2 relaxation times in distinguishing normal and pathologic tissue with magnetic resonance (MR) is discussed and clinical examples of cerebral abnormalities are given. T1 and T2 values may be used in three ways: (a) Relative values, obtained by an analysis of intensity images with varying dependence on T1 and T2, may be used if absolute values for T1 and T2 are not required for diagnosis. (b) If an absolute value is desired, the numerical values for the relaxation times may be generated using a region of interest on the intensity images. (c) In cases in which both T1 and T2 change may require a calculated image to indicate the contribution of each to the signal intensity, the numerical value may be used to generate analogue images of T1 or T2 calculations. Five patients with cerebral infarction, 15 with multiple sclerosis, two with Wilson disease, and four with tumors were imaged. Hemorrhagic and ischemic cerebrovascular accidents were distinguished using the spin echo technique. In the patients with multiple sclerosis, lesions had prolonged T1 and T2 times, but the definition of plaque was limited by spatial resolution. No abnormalities in signal intensity were seen in the patient with Wilson disease who was no longer severely disabled; abnormal increased signal intensity in the basal ganglia was found in the second patient with Wilson disease. Four tumors produced abnormal T1 and T2 relaxation times but these values alone were not sufficient for tumor characterization.     

T1, T2, and concentrations of brain metabolites in neonates and adolescents estimated with H-1 MR spectroscopy

The protein and lipid content of the human brain increases dramatically from infancy to adolescence. The authors investigated whether this change influences the relaxation behavior of metabolites measurable with hydrogen-1 magnetic resonance (MR) spectroscopy. H-1 MR spectroscopy was performed in eight neonates and eight adolescents at 1.5 T with STEAM (stimulated-echo acquisition mode) sequences. Five spectra were obtained in each volume of interest with different TE and TR values. T1 and T2 were subsequently calculated. T1 and T2 for inositols, choline-containing compounds (Cho), phosphocreatine plus creatine (PCr + Cr), and N-acetylaspartate (NAA) did not differ significantly between the two subject groups. Metabolite concentrations were estimated by using the fully relaxed water signal as an internal standard. Mean estimated concentrations of NAA and PCr + Cr were higher in the adolescent group, whereas the concentration of Cho was lower. The concentration of inositols was similar in the two groups.     

Proton T2 relaxation of cerebral metabolites during transient global ischemia in rat brain

Putative changes of metabolite T₂ relaxation times were investigated before and after a 20-min period of global ischemia in rat brain in vivo (n= 10) using localized proton MRS at different echo times (2.35 T). Neither absolute T₂ relaxation times (TE = 20-270 ms) nor time courses of T₂-weighted metabolite signals (TE = 135 ms) revealed statistically significant changes during the occlusion or early reperfusion relative to pre-ischemic baseline. These findings are in line with reports of relaxation changes at much later stages and further demonstrate that altered T₂ relaxation is not a confounding factor in diffusion-weighted long-TE proton MRS during early ischemic events.     

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.     

In vivo 31P magnetic resonance spectroscopy of human brain at 7 T: an initial experience.

In vivo (31)P spectra were acquired from the human primary visual cortex at 7 T. The relaxation times of the cerebral metabolites, intracellular pH, rate constant (k(f)) of the creatine kinase (CK) reaction, and nuclear Overhauser enhancement (NOE) on the detected phosphorus moieties from irradiation of the water spins were measured from normal subjects. With a 5-cm-diameter surface coil, 3D (31)P chemical shift imaging was performed with a spatial resolution of 7.5 ml and an acquisition resolution of 8 min, resulting in a signal-to-noise ratio (SNR) for phosphocreatine (PCr) resonance of 32. The apparent T(1) and T(2) of PCr measured at 7 T were 3.37 +/- 0.29 s and 132.0 +/- 12.8 ms, respectively, which were considerably longer than those of adenosine triphosphate (ATP) (T(1): 1.02-1.27 s; T(2): 25-26 ms). The NOE measured in this study was 24.3% +/- 1.6% for PCr, and 10% for ATP. The k(f) measured in the human primary visual cortex was 0.24 +/- 0.03 s(-1). The results from this study suggest that ultra-high-field strength is advantageous for performing in vivo (31)P magnetic resonance spectroscopy (MRS) in the human brain.     

Calculated T1 and T2 MR images and 31P MR spectra in rabbit thigh V2 carcinoma to monitor the effect of steroid administration

T1 and T2 proton relaxation times in six rabbit thigh V2 carcinomas were obtained from regions of interest on calculated MR images at 2.35 tesla before and after steroid administration. Mean T1 and T2 values of viable tumor tissue decreased after steroid administration, consistent with decreased tissue water content. After steroid withdrawal, T1 and T2 values returned toward baseline. Relaxation times of peritumoral muscle tissue and normal contralateral thigh muscle essentially remained unchanged. In a separate experiment, six rabbit thigh V2 carcinomas were monitored before and after steroids by 31P spectroscopy using a surface coil. No substantial steroid-related changes were recognizable. A fall of the ratio of phosphocreatine to inorganic phosphate and a signal increase from phosphomonoester and phosphodiester compounds were observed during various stages of tumor growth. Analysis of 31P spectra changes and sequential measurements of relaxation times may prove valuable for assessment of tumor growth and therapeutic response in diagnostic oncology.     

Localized proton NMR spectroscopy in different regions of the human brain in vivo. Relaxation times and concentrations of cerebral metabolites

High-resolution proton NMR spectra of normal human brain in vivo have been obtained from selected 27- and 64-ml volumes-of-interest (VOI) localized in the insular area, the occipital area, the thalamus, and the cerebellum of normal volunteers. Localization was achieved by stimulated echo (STEAM) sequences using a conventional 1.5-T whole-body MRI system (Siemens Magnetom). The proton NMR spectra show resonances from lipids, lactate, acetate, N-acetylaspartate (NAA), gamma-aminobutyrate, glutamine, glutamate, aspartate, creatine and phosphocreatine, choline-containing compounds, taurine, and inositols. While T1 relaxation times of most of these metabolites were about 1100-1700 ms without significant regional differences, their T2 relaxation times varied between 100 and 500 ms. The longest T2 values of about (500 +/- 50) ms were observed for the methyl protons of NAA in the white matter of the occipital lobe compared to (320 +/- 30) ms in the other parts of the brain. No significant regional T2 differences were found for choline and creatine methyl resonances. The relative concentrations of NAA in gray and white matter were found to be 35% higher than those in the thalamus and cerebellum. Assuming a concentration of 10 mM for total creatine the resulting NAA concentrations of 13-18 mM are by a factor of 2-3 higher than previously reported using analytical techniques. Cerebral lactate reached a maximum concentration of about 1.0 mM.     

Multiexponential proton spin-spin relaxation in MR imaging of human brain tumors

In vivo measurements of proton relaxation processes in human brain tumors have been performed by magnetic resonance (MR) imaging using a whole-body superconductive MR scanner, operating at 1.5 T. The T1 and T2 relaxation time measurements were based on a combined Carr-Purcell/Carr-Purcell-Meiboom-Gill sequence with two interleaved repetition times and 32 echoes. First, comparative measurements in the imager and with the spectrometer of relaxation times were performed on phantoms containing fluids of different T1 and T2 to evaluate accuracy. A maximum deviation of approximately 10% was found. Multislicing with a gap width of one slice thickness influenced the accuracy of T1 relaxation measurement. A gap width of at least two times the slice thickness was necessary for reliable determination of T1. No influence on T2 values was observed by multislicing. Second, in human head imaging the multiexponential behavior of the T2 decay curves has been analyzed in each pixel, where the mean square deviation has been used as a criterion to discriminate between mono- and biexponential behavior. Mean values of monoexponential T1 and multiexponential T2 relaxation data for white matter, gray matter, CSF, edema, and tumor were sampled in 12 patients with brain tumors. T2 showed monoexponential behavior in white and gray matter, whereas CSF, edema, and tumor showed distinct biexponentiality. The biexponential analysis generally yields "fast" and "slow" components with T2f = 80 +/- 17 ms and T2s = 2,030 +/- 210 ms for CSF (partial volume effect), T2f = 104 +/- 25 ms and T2s = 677 +/- 152 ms for edematous tissues, T2f = 97 +/- 19 ms and T2s = 756 +/- 99 ms for tumor tissues, respectively. Using a stepwise discriminant analysis by forward selection, the two best discriminating parameters of the multiexponential relaxation analysis for each pair of classification groups have been selected. For the discrimination of edematous and tumor tissues a retrospective overall accuracy of 94% has been found.     

Measurement of solute proton spin-lattice relaxation times in water using the 1,3,3,1 sequence

1H NMR spin-lattice relaxation times (T1) of the N-CH3 proton resonances of phosphocreatine (PCr) and creatine (Cr) in water solutions were obtained using the 1,3,3,1 pulse sequence. These T1 values were equivalent to those obtained in D2O and water using either the conventional inversion-recovery experiment or the 1,3,3,1 pulse sequence. Thus, the 1,3,3,1 sequence of proton NMR can provide an independent means along with phosphorous NMR for assess PCr and for the study of the creatine kinase reaction (PCr + ADP in equilibrium ATP + Cr) in aqueous solutions and perhaps in biological preparations.     

Musculoskeletal tumors: T1 and T2 relaxation times

The T1 and T2 relaxation times of primary tumors of the musculoskeletal system were calculated in 54 patients. No correlation was found between the relaxation values and the histopathologic type of the tumors. Lipoma had the same relaxation characteristics as normal fat. Otherwise tumors could be differentiated from normal tissue, but there was no significant difference between malignant and benign tumors, and the mean values for the different histopathologic types differed significantly only in a few instances. Hence T1 and T2 measurements are of limited value for histologic characterization of musculoskeletal tumors.