Brain metabolite composition during early human brain development as measured by quantitative in vivo 1H magnetic resonance spectroscopy.

Biochemical maturation of the brain can be studied noninvasively by (1)H magnetic resonance spectroscopy (MRS) in human infants. Detailed time courses of cerebral tissue contents are known for the most abundant metabolites only, and whether or not premature birth affects biochemical maturation of the brain is disputed. Hence, the last trimester of gestation was observed in infants born prematurely, and their cerebral metabolite contents at birth and at expected term were compared with those of fullterm infants. Successful quantitative short-TE (1)H MRS was performed in three cerebral locations in 21 infants in 28 sessions (gestational age 32-43 weeks). The spectra were analyzed with linear combination model fitting, considerably extending the range of observable metabolites to include acetate, alanine, aspartate, cholines, creatines, gamma-aminobutyrate, glucose, glutamine, glutamate, glutathione, glycine, lactate, myo-inositol, macromolecular contributions, N-acetylaspartate, N-acetylaspartylglutamate, o-phosphoethanolamine, scyllo-inositol, taurine, and threonine. Significant effects of age and location were found for many metabolites, including the previously observed neuronal maturation reflected by an increase in N-acetylaspartate. Absolute brain metabolite content in premature infants at term was not considerably different from that in fullterm infants, indicating that prematurity did not affect biochemical brain maturation substantially in the studied population, which did not include infants of extremely low birthweight.     

New method for the simultaneous detection of metabolites and water in localized in vivo 1H nuclear magnetic resonance spectroscopy.

A new two-scan method for localized 1H in vivo NMR spectroscopy (MRS) without water suppression (WS) is described. In one of the scans, two chemical shift selective 180 degrees pulses are applied prior to a standard localization sequence to invert all metabolite signals upfield and downfield from water, which remains unaffected. The difference spectrum records the metabolites whereas water and accompanying gradient induced artifacts are widely suppressed. The method was implemented on a 4.7-T system using point resolved spectroscopy with a short echo time of 18 ms. Phantom measurements proved the feasibility of absolute quantification using water as an internal reference. Measurements on healthy rat brain yielded comparable spectrum quality as measurements with water presaturation. The method does not require additional adjustments or sophisticated data postprocessing and scales favorably with increasing B(0) field. Therefore, the method should be useful for 1H MRS without WS. Although the two-step method doubles the minimum total measurement time, it may also be of interest for spectroscopic imaging (SI) without WS, in particular if fast SI techniques are applied.     

A constrained least‐squares approach to the automated quantitation of in vivo 1H magnetic resonance spectroscopy data

Totally Automatic Robust Quantitation in NMR (TARQUIN), a new method for the fully automatic analysis of short echo time in vivo ¹H Magnetic resonance spectroscopy is presented. Analysis is performed in the time domain using non‐negative least squares, and a new method for applying soft constraints to signal amplitudes is used to improve fitting stability. Initial point truncation and Hankel singular value decomposition water removal are used to reduce baseline interference. Three methods were used to test performance. First, metabolite concentrations from six healthy volunteers at 3 T were compared with LCModel?. Second, a Monte‐Carlo simulation was performed and results were compared with LCModel? to test the accuracy of the new method. Finally, the new algorithm was applied to 1956 spectra, acquired clinically at 1.5 T, to test robustness to noisy, abnormal, artifactual, and poorly shimmed spectra. Discrepancies of less than approximately 20% were found between the main metabolite concentrations determined by TARQUIN and LCModel? from healthy volunteer data. The Monte‐Carlo simulation revealed that errors in metabolite concentration estimates were comparable with LCModel?. TARQUIN analyses were also found to be robust to clinical data of variable quality. In conclusion, TARQUIN has been shown to be an accurate and robust algorithm for the analysis of magnetic resonance spectroscopy data making it suitable for use in a clinical setting. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

In vivo 1H NMR spectroscopy of the human brain at 7 T.

In vivo 1H NMR spectra from the human brain were measured at 7 T. Ultrashort echo-time STEAM was used to minimize J-modulation and signal attenuation caused by the shorter T2 of metabolites. Precise adjustment of higher-order shims, which was achieved with FASTMAP, was crucial to benefit from this high magnetic field. Sensitivity improvements were evident from single-shot spectra and from the direct detection of glucose at 5.23 ppm in 8-ml volumes. The linewidth of the creatine methyl resonance was at best 9 Hz. In spite of the increased linewidth of singlet resonances at 7 T, the ability to resolve overlapping multiplets of J-coupled spin systems, such as glutamine and glutamate, was substantially increased. Characteristic spectral patterns of metabolites, e.g., myo-inositol and taurine, were discernible in the in vivo spectra, which facilitated an unambiguous signal assignment.     

1H-MRS定量测定脑代谢物的研究

磁共振频谱(magnetic resonance spectroscopy,MRS)是利用核磁共振基本成像原理及其化学位移和自旋耦合现象,在活体上无创伤地测定能量代谢和体内化学物的一种检测技术,为疾病诊断和治疗提供有价值的信息.长期以来,MRS分析的脑代谢物检测结果以代谢物之间的比率来表达,但不可靠,近年来应用内标准和装有标准脑代谢物的外标准来获得脑代谢物的绝对浓度.在临床MRS应用中,代谢物绝对浓度的分析较比率分析有更多优点.本文就MRS的基本原理及1H-MRS定量测定脑代谢物浓度的方法作一综述.     

Proton magnetic resonance spectroscopy of brain tumors correlated with pathology

RATIONALE AND OBJECTIVES: Evaluate proton magnetic resonance spectroscopy ((1)H-MRS) for assessing and grading brain tumors. MATERIALS AND METHODS: The research was done at Detroit Medical Center in a 1.5-T Siemens MR magnet using single-voxel or multivoxel MRS. This study consisted of 27 patients: 10 females and 17 males ages 22-83 years (average age 43.8). The data were recorded for three peaks-N-acetyl aspartate (NAA), choline (Cho), creatine (Cr)-which were used to calculate the ratios Cho/NAA and Cho/Cr. RESULTS: Abnormal spectra were seen in 25 patients and normal spectra in 2. In 16 patients with brain astrocytoma of various grades, the pathology grading was correlated with Cho/NAA and Cho/Cr. These values were 6.53 and 3.35 for nine patients with Grade 4 astrocytoma; 1.85 and 1.62 for three patients with Grade 3 astrocytoma; 2.21 and 1.50 for three patients with Grade 2 astrocytoma; and 1.45 and 1.49 for one patient with Grade 1 astrocytoma. The remaining nine patients with abnormal spectra were also correlated with pathology. CONCLUSION: MRS ratios can be used to differentiate malignant and nonmalignant lesions from normal brain tissue. In general, high-grade astrocytoma have higher Cho/NAA and Cho/Cr ratios compared with low-grade astrocytoma.     

Edited 1H magnetic resonance spectroscopy in vivo: Methods and metabolites

The Proton magnetic resonance (¹H-MRS) spectrum contains information about the concentration of tissue metabolites within a predefined region of interest (a voxel). The conventional spectrum in some cases obscures information about less abundant metabolites due to limited separation and complex splitting of the metabolite peaks. One method to detect these metabolites is to reduce the complexity of the spectrum using editing. This review provides an overview of the one-dimensional editing methods available to interrogate these obscured metabolite peaks. These methods include sequence optimizations, echo-time averaging, J-difference editing methods (single BASING, dual BASING, and MEGA-PRESS), constant-time PRESS, and multiple quantum filtering. It then provides an overview of the brain metabolites whose detection can benefit from one or more of these editing approaches, including ascorbic acid, γ-aminobutyric acid, lactate, aspartate, N-acetyl aspartyl glutamate, 2-hydroxyglutarate, glutathione, glutamate, glycine, and serine. Magn Reson Med 77:1377–1389, 2017. © 2017 International Society for Magnetic Resonance in Medicine.     

Detection of elevated glutathione in meningiomas by quantitative in vivo 1H MRS.

Glutathione has major roles in removing free radicals and toxins from normal tissues, but its presence in tumor cells hinders the effectiveness of many anticancer therapies. Analysis of short echo time brain tumor (1)H spectra at 1.5 T using a linear combination of metabolite spectra (LCModel) suggested a significant contribution of glutathione to meningioma spectra. By in vivo MRS (TE = 30 ms, TR = 2020 ms), reduced glutathione was found to be significantly elevated in meningiomas (3.3 +/- 1.5 mM, Mann Whitney, P < 0.005) compared to normal white matter (1.2 +/- 0.15 mM) and low-grade gliomas (1.0 +/- 0.26 mM), in agreement with published histofluorescence studies of tumor biopsies. Glx concentrations were also found to be elevated in meningiomas compared to astrocytomas or normal white matter, indicative of metabolic differences. The ability to noninvasively quantify reduced glutathione in vivo may aid selection of treatment therapies and also provide an indication of tumor aggressiveness.     

Proton magnetic resonance spectroscopy of choroid plexus tumors in children.

A variety of lesions may present as intraventricular masses in children. We report quantitative proton magnetic resonance spectroscopy (MRS) of two intraventricular tumors of the choroid plexus: choroid plexus carcinoma (CPC) and choroid plexus papilloma (CPP). Both lesions were characterized by high levels of choline-containing compounds and a complete absence of creatine and the neuronal/axonal marker N-acetyl aspartate. The CPC showed higher levels of choline compared to the CPP, and it also had elevated lactate. These preliminary results, if confirmed in a larger cohort of patients, indicate that proton MRS may have a role in the presurgical diagnosis of choroid plexus tumors in children, which may also have important implications for therapy and prognosis.     

Noninvasive temperature measurement in Vivo using a temperature-sensitive lanthanide complex and 1H magnetic resonance spectroscopy

A new lanthanide complex, praseodymium-2-methoxyethyl-DO3A, was tested as a temperature indicator for ¹H magnetic resonance spectroscopy under in vivo conditions, using a 2-T imaging system. The chemical shift of the methoxy group of the compound is strongly temperature dependent. In vitro, a shift change of ?0.131 ppm/°C was found. The signal was shifted by about ?24 ppm relative to the water signal, allowing easy water suppression and signal identification in vivo. The body temperatures of eight anesthetized rats were measured in the liver after intravenous administration of 1 mmol/kg of the praseodymium complex under different heating conditions of the animal. The temperatures calculated from the spectra were in good agreement (deviation < ± 1°C) with values obtained simultaneously with a thermocouple placed in the rectum of the animals.     

Differentiation of metabolic concentrations between gray matter and white matter of human brain by in vivo 1H magnetic resonance spectroscopy

Differentiation of absolute metabolite concentrations between gray and white matter in the occipital region of normal human brain was performed by in vivo localized single-voxel ¹H magnetic resonance spectroscopy at 1.5 Testa with long echo time (136 ms). With the combination of image segmentation between white and gray matter and cerebrospinal fluid, signal compensation of T, and T₂ effects, tissue water signal as the internal concentration reference, as well as compensation by different water contents in gray and white matters, it was determined that the levels of N-acetylaspartate (NAA), creatine and/or phosphocreatine (Cr), and choline-containing compounds (Cho) in gray matter were significantly higher than in white matter. The averaged NAA, Cr, and Cho concentrations in gray matter were 11.0, 9.7, and 1.9 mM/liter, respectively, in comparison with 7.5, 5.2, and 1.6 mM/liter in white matter. These results suggest that precise composition of white and gray matter and cerebrospinal fluid is necessary to avoid partial voluming effect in a single voxel and to accurately quantify the metabolite concentrations.     

1H magnetic resonance spectroscopy in human hydrocephalus

PURPOSE: To evaluate cerebral metabolism in clinical hydrocephalus with (1)H magnetic resonance spectroscopy (MRS). MATERIALS AND METHODS: In 24 children and adults with progressive, arrested, or normal pressure hydrocephalus, long-echo time (1)H MR spectra were acquired from periventricular white matter and intraventricular cerebrospinal fluid (CSF). Metabolite ratios, and the presence of lactate, were compared with 38 age-matched controls. RESULTS: Metabolite ratios of patients were within the 95% confidence interval (CI) of controls. A small lactate resonance was detected in 20% of control and hydrocephalic subjects. Lactate was consistently visible in CSF spectra, though lactate concentrations were normal. The CSF lactate T(2) was long in comparison with the known intracellular metabolite T(2) relaxation times. In three neonates with hydrocephalus and spina bifida, 3-hydroxybutyrate was detected in CSF in vivo. CONCLUSION: Within the limits of the present methods, (1)H MRS could not detect cerebral metabolic abnormalities in human hydrocephalus and provided no additional diagnostic information. The long T(2) of lactate in CSF explains its high visibility. Hence, the detection of lactate in spectra acquired from voxels that contain CSF does not necessarily imply cerebral ischemia.     

(1)H magnetic resonance spectroscopy of preinvasive and invasive cervical cancer: in vivo-ex vivo profiles and effect of tumor load

PURPOSE: To compare in vivo (1)H magnetic resonance (MR) spectra of preinvasive and invasive cervical lesions with ex vivo magic angle spinning (MAS) spectra of intact biopsies from the same subjects and to establish the effects of tumor load in the tissue sampled on the findings. MATERIALS AND METHODS: A total of 51 subjects (nine with normal cervix, 10 with cervical intraepithelial neoplasia [CIN], and 32 with cervical cancer) underwent endovaginal MR at 1.5 T. Single-voxel (3.4 cm(3)) (1)H MR spectra were acquired and voxel tumor load was calculated (tumor volume within voxel as a percentage of voxel volume). Resonances from triglycerides -CH(2) and -CH(3) and choline-containing compounds (Cho) were correlated with voxel tumor load. Biopsies analyzed by (1)H MAS-MR spectroscopy (MRS) had metabolite levels correlated with tumor load in the sample at histology. RESULTS: In vivo studies detected Cho in normal, CIN, and cancer patients with no significant differences in levels (P = 0.93); levels were independent of voxel tumor load. Triglyceride -CH(2) and -CH(3) signals in-phase with Cho were present in 77% and 29%, respectively, of cancer subjects (but not in normal women or those with CIN), but did not correlate with voxel tumor load. Ex vivo cancer biopsies showed levels of triglycerides -CH(2) and -CH(3) and of Cho that were significantly greater than in normal or CIN biopsies (P < 0.05); levels were independent of the tumor load in the sample. The presence of -CH(2) in vivo predicted the presence of cancer with a sensitivity and specificity of 77.4% and 93.8% respectively, positive (PPV) and negative (NPV) predictive values were 96% and 68.2%; for -CH(2) ex vivo, sensitivity was 100%; specificity, 69%; PPV, 82%; and NPV, 100%. CONCLUSION: Elevated lipid levels are detected by MRS in vivo and ex vivo in cervical cancer and are independent of tumor load in the volume of tissue sampled.     

1H mrs of human brain abscesses in vivo and in vitro

Five patients, each with a brain abscess, were examined by means of ¹H MR spectroscopic imaging in vivo. The aspirated pus was analyzed in vitro by means of 1D and 2D COSY ¹H MRS. In addition to resonance lines from compounds (lactate, alanine and lipids) often found in the spectra from intracranial tumors, resonance lines were detected from a number of markers of infectious involvement (acetate, succinate, and various amino acids). These results suggest that ¹H MRS in vivo might contribute in establishing noninvasively a differential diagnosis between brain abscess and tumor.     

Dynamically shimmed multivoxel 1H magnetic resonance spectroscopy and multislice magnetic resonance spectroscopic imaging of the human brain

In vivo multivoxel Magnetic Resonance Spectroscopy (MRS) and multislice Magnetic Resonance Spectroscopic Imaging (MRSI) are extremely susceptible to poor homogeneity of the static magnetic field. Existing room-temperature (RT) shim technology can adequately optimize the B(0) homogeneity of local volumes, such as single voxels. However, the widespread global homogeneity required for in vivo spectral acquisitions from multiple volumes in the human brain cannot be attained with a single RT shim setting. Dynamic shim updating (DSU) allows for use of local RT shim B(0) homogeneity compensation capabilities in a global fashion. Here, by updating first- and second-order shims on a voxel- and slice-specific basis using a pre-emphasized DSU system, we present multivoxel MRS and multislice MRSI of the human brain. These results demonstrate that DSU can increase multivoxel MRS acquisition capabilities and significantly improve the quality of multislice MRSI data.     

Quantitative 1H spectroscopic imaging of human brain at 4.1 T using image segmentation

Metabolic differences in the content of N-acetylaspartate (NAA), creatine (CR), and choline (CH) in cerebral gray and white matter can complicate the interpretation of ¹H spectroscopic images. To account for these variations, the gray-and white-matter content of each voxel must be known. To provide these data, a T₁-based image segmentation scheme was implemented at 4.1 T. The tissue composition of each voxel was determined using the point-spread function of the spectroscopic imaging acquisition and the segmented anatomical image. Pure gray- and white-matter values for CR/NAA and CH/NAA, and the content of CR, CH, and NAA, were determined using a linear-regression analysis of 984 voxels acquired from 10 subjects using white-matter CR as an internal standard. This information was used to establish means and confidence intervals for CR/NAA and CH/NAA from a voxel of arbitrary tissue composition. Using a single-tailed t test, the extent and locations of the metabolic abnormalities (P < 0.05) in a patient with multiple sclerosis were identified.