Interindividual,repositioning, and time‐of‐day effects on single voxel proton MR spectroscopy of the anterior cingulate cortex

Purpose:

To measure interindividual, repositioning, and time‐of‐day effects of single voxel PRESS (P oint RES olved S pectroscopy) proton magnetic resonance spectroscopy (¹H‐MRS) acquisition of the anterior cingulate cortex (AC) in healthy human subjects.

Materials and Methods:

AC ¹H‐MRS measurements were performed in 15 healthy adult volunteers using a short echo PRESS sequence (GE Healthcare 3 Tesla, TE/TR = 30/2500 ms, 192 acquisitions, 6 cm³ voxels). For each individual, a total of eight spectra were obtained during two identical scanning sessions separated by 3.5 h. In each, two consecutive AC spectra were acquired. After the first two scans, the subject left the scanner, then immediately returned for repositioning and acquisition of two more consecutive spectra. The subject then left the imaging centre to return 3.5 h later for a repeated procedure. Spectroscopic postprocessing was done using LCmodel. Interindividual, repositioning and time‐of‐day effects were measured using restricted maximum likelihood (REML) models of variance components analysis, where response variables were levels of creatine/phosphocreatine (Cr), N‐acetyl‐aspartate (NAA), myo‐inositol (mI), choline (Cho), and the glutamate‐glutamine complex (Glx).

Results:

Interindividual effects were markedly higher than time‐of‐day and repositioning effects for all metabolites.

Conclusion:

Our findings show that ¹H‐MRS measurements of the AC are sensitive to interindividual differences, while time of day and repositioning are markedly less important. J. Magn. Reson. Imaging 2010;32:276–282. © 2010 Wiley‐Liss, Inc.     

Determination of regional brain temperature using proton magnetic resonance spectroscopy to assess brain-body temperature differences in healthy human subjects.

Proton magnetic resonance spectroscopy ((1)H MRS) was used to determine brain temperature in healthy volunteers. Partially water-suppressed (1)H MRS data sets were acquired at 3T from four different gray matter (GM)/white matter (WM) volumes. Brain temperatures were determined from the chemical-shift difference between the CH(3) of N-acetyl aspartate (NAA) at 2.01 ppm and water. Brain temperatures in (1)H MRS voxels of 2 x 2 x 2 cm(3) showed no substantial heterogeneity. The volume-averaged temperature from single-voxel spectroscopy was compared with body temperatures obtained from the oral cavity, tympanum, and temporal artery regions. The mean brain parenchyma temperature was 0.5 degrees C cooler than readings obtained from three extra-brain sites (P < 0.01). (1)H MRS imaging (MRSI) data were acquired from a slice encompassing the single-voxel volumes to assess the ability of spectroscopic imaging to determine regional brain temperature within the imaging slice. Brain temperature away from the center of the brain determined by MRSI differed from that obtained by single-voxel MRS in the same brain region, possibly due to a poor line width (LW) in MRSI. The data are discussed in the light of proposed brain-body temperature gradients and the use of (1)H MRSI to monitor brain temperature in pathologies, such as brain trauma.     

Metabolic alterations: A biomarker for radiation‐induced normal brain injury—an MR spectroscopy study

Purpose

To assess if interval changes in metabolic status in normal cerebral tissue after radiation therapy (RT) can be detected by 2D CSI (chemical shift imaging) proton spectroscopy.

Materials and Methods

Eleven patients with primary brain tumors undergoing cranial radiation therapy (RT) were included. 2D‐CSI MRS was performed before, during, and after the course of RT with the following parameters: TE/TR 144/1500 ms, field of view (FOV) 24, thickness 10 mm, matrix 16 × 16. The metabolic ratios choline/creatine (Cho/Cr), N‐acetylaspartate (NAA)/Cr, and NAA/Cho in normal brain tissue were calculated.

Results

NAA/Cr and Cho/Cr were significantly decreased at week 3 during RT and at 1 month and 6 months after RT compared to values prior to RT (P < 0.01). The NAA/Cr ratio decreased by ?0.19 ± 0.05 (mean ± standard error [SE]) at week 3 of RT, ?0.14 ± 0.06 at the last week of RT, ?0.14 ± 0.05 at 1 month after RT, and ?0.30 ± 0.08 at 6 months after RT compared to the pre‐RT value of 1.43 ± 0.04. The Cho/Cr ratio decreased by ?0.27 ± 0.05 at week 3 of RT, ?0.11 ± 0.05 at the last week of RT, ?0.26 ± 0.05 at 1 month after RT and ?0.25 ± 0.07 at 6 months after RT from the pre‐RT value of 1.29 ± 0.03. Changes in Cho/Cr were correlated with the interaction of the radiation dose and dose‐volume at week 3 of RT, during the last week of RT (P < 0.005), and at 1 month after RT (P = 0.017).

Conclusion

The results of this study suggest that MRS can detect early metabolic changes in normal irradiated brain tissue. J. Magn. Reson. Imaging 2009;29:291–297. © 2009 Wiley‐Liss, Inc.

     

High resolution localized two‐dimensional MR spectroscopy in mouse brain in vivo

Localized two‐dimensional MR spectroscopy (2D MRS) is impacting the in vivo studies of brain metabolites due to improved spectral resolution and unambiguous assignment opportunities. Despite the large number of transgenic mouse models available for neurological disorders, localized 2D MRS has not yet been implemented in the mouse brain due to size constraints. In this study we optimized a localized 2D proton chemical shift correlated spectroscopic sequence at field strength of 9.4T to obtain highly resolved 2D spectra from localized regions in mouse brains in vivo. The combination of the optimized 2D sequence, high field strength, strong gradient system, efficient water suppression, and the use of a short echo time allowed clear detection of cross‐peaks of up to 16 brain metabolites, allowing their direct chemical shift assignments in vivo. To our knowledge this is the first in vivo 2D MRS study of the mouse brain, demonstrating its feasibility to resolve and simultaneously assign several metabolite resonances in the mouse brain in vivo. Implementation of 2D MRS will be invaluable in the identification of new biomarkers during disease progression and treatment using the various available mouse models. Magn Reson Med 60:449–456, 2008. © 2008 Wiley‐Liss, Inc.     

Regional apparent metabolite concentrations in young adult brain measured by (1)H MR spectroscopy at 3 Tesla

PURPOSE: To quantify and examine the distribution of brain metabolites in normal young adults using single voxel MR spectroscopy at 3 Tesla (T). MATERIALS AND METHODS: Short-echo time single-voxel PRESS technique was used to measure the apparent concentration of five metabolites at nine locations in the brains of young adults. Concentrations were estimated by means of an automated fitting method (LCModel) with reference to an unsuppressed water signal and were corrected for T(1) relaxation, T(2) relaxation, and cerebrospinal fluid partial volume. Analysis of variance with Tukey post hoc test was used to evaluate regional variations. RESULTS: Statistically significant differences in regional concentrations were detected for each of the metabolites. The number of significant differences was greatest for total choline, whereas myo-inositol and the sum of glutamine and glutamate had the fewest. Magnitude of variation was greatest for total choline and least for the sum of N-acetyl aspartate and N-acetylaspartylglutamate. CONCLUSION: In agreement with previous studies at other field strengths, we found heterogeneous distribution of the major spectroscopically measurable brain metabolites. Although the most distinct differences are between tissue types, there is appreciable variation within a tissue type at different locations. The spectra and metabolite concentrations presented should provide a useful reference for both clinical and research MR spectroscopy studies performed at 3T.     

Assessment of metabolite quantitation reproducibility in serial 3D-(1)H-MR spectroscopic imaging of human brain using stereotactic repositioning.

Intrasubject reproducibility of metabolite quantitation in three-dimensional proton magnetic resonance spectroscopic imaging (3D-MRSI) was investigated in 10 healthy volunteers over five separate sessions using two echo times (TEs): 144 and 30 ms. The use of a Gill-Thomas-Cosman (GTC) stereotactic head frame enabled precise subject repositioning and immobilization. Metabolite levels from each voxel in the volume of interest (VOI) were quantified using the Linear Combination of Model spectra (LCModel) analysis algorithm, and coefficients of variation (CVs) were calculated. Standard error estimates (%SD or Cramer-Rao lower bounds) generated by LCModel were used as a confidence filter. The 95% confidence interval (CI) was found for each metabolite, providing an indication of the normal fluctuation expected for 3D-MRSI. In vivo, median CVs at the %SD < or = 20 level were found to be (%CV for TE = 144 and 30 ms, respectively): N-acetyl-aspartate plus N-acetyl-aspartyl-glutamate (NAA): 10.2% and 13.5%; creatine plus phosphocreatine (Cr), 14.4% and 21.7%; and choline-containing compounds (Cho), 15.2% and 18.4%. Relaxing the statistical filtering criteria to %SD < or = 30 increased median CVs by less than 5% and permitted in vivo quantitation reproducibility to be evaluated for glutamine plus glutamate (Glx) and myoinositol (Ins) for TE = 30 ms, yielding CVs of 24.0% and 21.0%, respectively.     

MR thermometry

Minimally invasive thermal therapy as local treatment of benign and malignant diseases has received increasing interest in recent years. Safety and efficacy of the treatment require accurate temperature measurement throughout the thermal procedure. Noninvasive temperature monitoring is feasible with magnetic resonance (MR) imaging based on temperature-sensitive MR parameters such as the proton resonance frequency (PRF), the diffusion coefficient (D), T1 and T2 relaxation times, magnetization transfer, the proton density, as well as temperature-sensitive contrast agents. In this article the principles of temperature measurements with these methods are reviewed and their usefulness for monitoring in vivo procedures is discussed. Whereas most measurements give a temperature change relative to a baseline condition, temperature-sensitive contrast agents and spectroscopic imaging can provide absolute temperature measurements. The excellent linearity and temperature dependence of the PRF and its near independence of tissue type have made PRF-based phase mapping methods the preferred choice for many in vivo applications. Accelerated MRI imaging techniques for real-time monitoring with the PRF method are discussed. Special attention is paid to acquisition and reconstruction methods for reducing temperature measurement artifacts introduced by tissue motion, which is often unavoidable during in vivo applications.     

MRS定量测量急性缺氧缺血脑损伤猪脑代谢物研究

目的 评价外标准法MRS结合LCModel软件绝对定量测量急性缺氧缺血脑损伤猪脑N-乙酰天冬氨酸(NAA)、肌酸(Cr)和乳酸(Lac)浓度变化的价值.方法 8头7日龄健康猪麻醉后未作任何处理(正常组),麻醉清醒后1 d制成缺氧缺血性脑病(HIE)模型(HIE组),先后与内含已知浓度物质的外标准模型一起行1H-MRS检查,数据采集完毕后用LCModel软件定量分析测量NAA、Cr、Lac浓度,HIE前、后猪脑代谢物NAA、Cr、Lac间比较采用多元方差分析,并对2头HIE猪缺氧缺血0、2 h脑代谢物动态变化情况作初步观察.结果 l头猪因麻醉过深死亡而剔除,最后统计数据为7头.小猪急性缺氧缺血前脑NAA、Cr、Lac分别为(6.86±0.49)、(4.65±0.73)、0.00 mmol/kg,缺氧缺血后即刻脑NAA、Cr、Lac分别为(5.73±0.88)、(4.40±0.80)、(0.43±0.39)mmol/kg.急性缺氧缺血后即刻猪脑NAA浓度下降,差异有统计学意义(F=8.608,P=0.013);Cr浓度有所下降,但差异无统计学意义(F=0.379,P=0.550);Lac浓度升高,差异有统计学意义(F=8.600,P=0.013).初步观察脑代谢物动态变化见HIE后即刻出现Lac峰,2 h Lac峰下降.结论 外标准法MRS结合LCModel定量分析软件能方便准确地定量测量脑内代谢物,NAA与Lac浓度的改变均能敏感地反映急性缺氧缺血脑损伤早期改变,且以NAA浓度的改变稍敏感.     

Test‐retest reliability and reproducibility of short‐echo‐time spectroscopic imaging of human brain at 3T

A ¹H magnetic resonance spectroscopic imaging study at 3T and short echo time was conducted to evaluate both the reproducibility, as measured by the interscan coefficient of variation (CV), and test‐retest reliability, as measured by the intraclass correlation coefficient (ICC), of measurements of glutamate (Glu), combined glutamate and glutamine (Glx), myo‐inositol (mI), N‐acetylaspartate, creatine, and choline in 21 healthy subjects. The effect of partial volume correction on these measures and the relationship of reproducibility and reliability to data quality were also examined. A ¹H magnetic resonance spectroscopic imaging slice was prescribed above the lateral ventricles and single repeat scans were performed within 30 min to minimize physiologic variability. Interscan CVs based on all the voxels varied from 0.05 to 0.07 for N‐acetylaspartate, creatine, and choline to 0.10–0.13 for mI, Glu, and Glx. Findings on the reproducibility of gray and white matter estimates of N‐acetylaspartate, creatine, and choline are consistent with previous studies using longer echo times, with CVs in the range of 0.02–0.04 and ICC in the range of 0.65–0.90. CVs for Glu, Glx, and mI are much lower than reported in previous studies at 1.5T, while white matter mI (CV = 0.04, ICC = 0.93) and gray matter Glx (CV = 0.04, ICC = 0.68) demonstrated both high reproducibility and test‐retest reliability. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Diagnostic value of proton MR spectroscopy and diffusion-weighted MR imaging in childhood inherited neurometabolic brain diseases and review of the literature

The purpose of this study is to evaluate parenchymal diffusion properties and metabolite ratios in affected brain tissues of inherited neurometabolic brain diseases with an overview of the current literature about the diagnostic data of both techniques in childhood inherited metabolic brain diseases. The study group was consisting, 19 patients (15 males, 4 females; mean age, 54 months (4.5 years); age range, 1-171 months (14.25 years)) diagnosed with inherited neurometabolic brain disease. Single- and multivoxel proton MRS was carried out and NAA/Cr, Cho/Cr, mI/Cr, Glx/Cr ratios were calculated. Presence of lactate peak and abnormal different peaks were noted. ADC values were calculated from brain lesions. Results are compared with age and sex matched normal subjects. Elevated NAA/Cr ratio (Canavan disease), galactitol peak (galactosemia) at 3.7 ppm, branched chain amino acids (Maple syrup urine disease—MSUD) at 0.9 ppm were seen on different diseases. In Leigh disease and MSUD restricted diffusion was detected. Different diffusion properties were seen only in one Glutaric aciduria lesions. NAA/Cr ratios and calculated ADC values were significantly different from normal subjects (p < 0.05). DWI combined with MRS are complementary methods to routine cranial MRI for evaluating neurometabolic diseases which can give detailed information about neurochemistry of affected brain areas.     

In vivo proton magnetic resonance spectroscopy of large focal hepatic lesions and metabolite change of hepatocellular carcinoma before and after transcatheter arterial chemoembolization using 3.0-T MR scanner

PURPOSE: To investigate the value of in vivo proton magnetic resonance spectroscopy (MRS) in the assessment of large focal hepatic lesions and to measure the metabolite change of hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE) using 3.0-T scanner. MATERIALS AND METHODS: In this prospective study, 43 consecutive patients with large (not less than 3 cm in diameter) hepatic tumors and eight normal volunteer were included. MRS of the lesions in addition to uninvolved liver parenchyma was carried out using a whole-body 3.0-T scanner. Among the patients with proven HCC, eight lesions were evaluated before and two to five days after TACE. The choline-to-lipid (cho/lipid) ratio was measured by dividing the peak area of choline at 3.2 ppm by the peak area of lipid at 1.3 ppm. The sensitivity and specificity profiles of MRS in the diagnosis of malignant hepatic tumors were determined by plotting empirical receiver operating characteristic (ROC) curve. The mean cho/lipid ratios in different groups before and after TACE were also measured. RESULTS: The technical success rate for MRS was 90% (53/59). The ROC curve showed proton MRS has moderate discriminating ability in diagnosing malignant hepatic tumors, although the sensitivity was less than 50% while 1-specificity was less than 20%. The area under the curve was 0.71 (P < 0.05). The mean +/- 1 standard error (SE) of cho/lipid ratios for uninvolved liver (N = 8), benign tumor (N = 8), and malignant tumor (N = 21; 19 HCC, one angiosarcoma, and one lymphoma) were 0.06 +/- 0.02, 0.02 +/- 0.02, and 0.17 +/- 0.05, respectively. A significantly statistical difference (ANOVA planned contrast test, P = 0.01 and Games-Howell procedure, P = 0.03) was achieved in the mean cho/lipid ratio between malignant and benign tumors. The mean cho/lipid ratios were significantly decreased from 0.23 +/- 0.11 before TACE to 0.01 +/- 0.00 after the treatment (t = 2.01, P < 0.05, one-tail paired t-test; z = -2.37, P < 0.05, Wilcoxon Signed Ranks Test). CONCLUSION: In vivo proton MRS is technically feasible for the evaluation of focal hepatic lesions. The technique has potential in the detection of early metabolite change in malignant liver tumors after TACE but limitation still exists in clear differentiation between normal liver and benign and malignant tumor.