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1.
Acute phencyclidine (PCP) administration mimics some aspects of schizophrenia in rats, such as behavioral alterations, increased dopaminergic activity and prefrontal cortex dysfunction. In this study, we used single‐voxel 1H‐MRS to investigate neurochemical changes in rat prefrontal cortex in vivo before and after an acute injection of PCP. A short‐echo time sequence (STEAM) was used to acquire spectra in a 32‐µL voxel positioned in the prefrontal cortex area of 12 rats anesthetized with isoflurane. Data were acquired for 30 min before and for 140 min after a bolus of PCP (10 mg/kg, n = 6) or saline (n = 6). Metabolites were quantified with the LCModel. Time courses for 14 metabolites were obtained with a temporal resolution of 10 min. The glutamine/glutamate ratio was significantly increased after PCP injection (p < 0.0001, pre‐ vs. post‐injection), while the total concentration of these two metabolites remained constant. Glucose was transiently increased (+70%) while lactate decreased after the injection (both p < 0.0001). Lactate, but not glucose and glutamine, returned to baseline levels after 140 min. These results show that an acute injection of PCP leads to changes in glutamate and glutamine concentrations, similar to what has been observed in schizophrenic patients, and after ketamine administration in humans. MRS studies of this pharmacological rat model may be useful for assessing the effects of potential anti‐psychotic drugs in vivo. Copyright © 2009 John Wiley & Sons, Ltd.  相似文献   

2.
Ascorbate (Asc, vitamin C) was quantified in the human brain noninvasively using two different 1H NMR spectroscopy methods: short‐echo time STEAM and MEGA‐PRESS homonuclear editing. Taking advantage of increased sensitivity and chemical shift dispersion at 7 T, Asc was quantified with increased reliability relative to our previous study accomplished at 4 T. Asc concentration quantified from short‐echo time spectra measured from the occipital lobe of eight healthy subjects ([Asc] = 1.1 ± 0.3 µmol/g, mean ± SD) was in excellent agreement with Asc concentration quantified from the same volume of interest using homonuclear editing ([Asc] = 1.2 ± 0.2 µmol/g). This agreement indicates that at 7 T, Asc can be reliably quantified in the human brain simultaneously with 15 other metabolites. Additional advantages of the short‐echo time approach were: shorter measurement time than homonuclear editing and minimal effect of T2 relaxation on Asc quantification. High magnetic field was also beneficial for Asc quantification with MEGA‐PRESS because increased chemical shift dispersion enabled editing with full efficiency, which resulted in a supra‐linear gain in signal‐to‐noise ratio relative to 4 T. Copyright © 2009 John Wiley & Sons, Ltd.  相似文献   

3.
The 1H resonances of γ‐aminobutyric acid (GABA) in the human brain in vivo are extensively overlapped with the neighboring abundant resonances of other metabolites and remain indiscernible in short‐TE MRS at 7 T. Here we report that the GABA resonance at 2.28 ppm can be fully resolved by means of echo time optimization of a point‐resolved spectroscopy (PRESS) scheme. Following numerical simulations and phantom validation, the subecho times of PRESS were optimized at (TE, TE2) = (31, 61) ms for detection of GABA, glutamate (Glu), glutamine (Gln), and glutathione (GSH). The in vivo feasibility of the method was tested in several brain regions in nine healthy subjects. Spectra were acquired from the medial prefrontal, left frontal, medial occipital, and left occipital brain and analyzed with LCModel. Following the gray and white matter (GM and WM) segmentation of T1‐weighted images, linear regression of metabolite estimates was performed against the fractional GM contents. The GABA concentration was estimated to be about seven times higher in GM than in WM. GABA was overall higher in frontal than in occipital brain. Glu was about twice as high in GM as in WM in both frontal and occipital brain. Gln was significantly different between frontal GM and WM while being similar between occipital GM and WM. GSH did not show significant dependence on tissue content. The signals from N‐acetylaspartylglutamate were clearly resolved, giving the concentration more than 10 times higher in WM than in GM. Our data indicate that the PRESS TE = 92 ms method provides an effective means for measuring GABA and several challenging J‐coupled spin metabolites in human brain at 7 T. Copyright © 2014 John Wiley & Sons, Ltd.  相似文献   

4.
To date, the majority of MRS reproducibility studies have been conducted in healthy younger adults, with only a few conducted in older adults at 3 T. With the growing interest in applying MRS methods to study the longitudinal course and effects of treatments in neurodegenerative disease, it is important to establish reproducibility in age‐matched controls, especially in older individuals. In this study, spectroscopic data were acquired using a stimulated echo acquisition mode (STEAM) localization technique in two regions (anterior and posterior cingulate cortices—ACC, PCC, respectively) in 10 healthy, cognitively normal older adults (64 ± 8.1 years). Reproducibility was assessed via mean coefficients of variation (CVs) and relative differences (RDs) calculated across two visits performed 2–3 months apart. Metabolites with high signal‐to‐noise ratio (SNR) such as NAA, tCho, and Glu had mean CVs of 10% or less and mean RDs of 15% or less across both regions. Metabolites with lower SNR such as GABA and Gln had slightly higher mean CVs of 22% or less and mean RDs of 27% or less across both regions. These results demonstrate the feasibility of acquiring MRS data at 7 T in older subjects, and establish that the spectroscopic data are reproducible in both the ACC and PCC in older, healthy subjects to the same extent as in previous studies in young subjects.  相似文献   

5.
1H MRS investigations have reported altered glutamatergic neurotransmission in a variety of psychiatric disorders. The unraveling of glutamate from glutamine resonances is crucial for the interpretation of these observations, although this remains a challenge at clinical static magnetic field strengths. Glutamate resolution can be improved through an approach known as echo time (TE) averaging, which involves the acquisition and subsequent averaging of multiple TE steps. The process of TE averaging retains the central component of the glutamate methylene multiplet at 2.35 ppm, with the simultaneous attenuation of overlapping phase‐modulated coupled resonances of glutamine and N‐acetylaspartate. We have developed a novel post‐processing approach, termed phase‐adjusted echo time (PATE) averaging, for the retrieval of glutamine signals from a TE‐averaged 1H MRS dataset. The method works by the application of an optimal TE‐specific phase term, which is derived from spectral simulation, prior to averaging over TE space. The simulation procedures and preliminary in vivo spectra acquired from the human frontal lobe at 2.89 T are presented. Three metabolite normalization schemes were developed to evaluate the frontal lobe test–retest reliability for glutamine measurement in six subjects, and the resulting values were comparable with previous reports for within‐subject (9–14%) and inter‐subject (14–20%) measures. Using the acquisition parameters and TE range described, glutamine quantification is possible in approximately 10 min. The post‐processing methods described can also be applied retrospectively to extract glutamine and glutamate levels from previously acquired TE‐averaged 1H MRS datasets. Copyright © 2012 John Wiley & Sons, Ltd.  相似文献   

6.
Therapeutic hypothermia is standard care for infants with moderate to severe encephalopathy. 1H MRS thermometry (MRSt) measures regional brain absolute temperature using the temperature‐dependent water chemical shift. This study evaluates the clinical feasibility of MRSt in human neonates, and correlates white matter (WM) and thalamus (Thal) MRSt with conventional rectal temperature (Trectal) measurement. Fifty‐six infants born at term underwent perinatal MRSt for suspected hypoxic–ischaemic brain injury and 33 infants born preterm had MRSt at a term‐equivalent age; 56 of the 89 had Trectal measured after MRSt of either a Thal or posterior WM voxel, or both. MRSt used point‐resolved spectroscopy (no water suppression; TR = 1370 ms; TE = 288 ms; 1.5 × 1.5 × 1.5 cm3 Thal and 1.1 × 1.3 × 1.4 cm3 WM voxels). Time domain data were phase and frequency corrected before summation and motion‐corrupted data were excluded from further analysis using simple criteria [preprocessing + quality assurance (QA)]. Two published water temperature‐dependence calibrations [both using cerebral creatine (Cr), choline (Cho) and N‐acetylaspartate (Naa) as independent reference peaks] were compared. The temperature measurements derived from Cr, Cho and Naa were combined to give a single amplitude‐weighted combination temperature (TAWC). WM and Thal TAWC correlated linearly with Trectal (Thal slope, 0.82 ± 0.04, R2 = 0.85, p < 0.05; WM slope, 0.95 ± 0.04, R2 = 0.78, p < 0.05). Preprocessing + QA improved the correlation between WM TAWC and Trectal (R2 increased from 0.27 to 0.78, p < 0.001). Both calibration datasets showed specific inconsistencies between the temperatures calculated using Cr, Cho and Naa reference peaks when applied to this neonatal dataset. Neonatal MRSt is clinically feasible. Preprocessing + QA improved MRSt reliability in WM. The consideration of MRSt calibration internal biases is necessary before combining MRSt temperatures from multiple reference peaks to obtain TAWC. Copyright © 2012 John Wiley & Sons, Ltd.  相似文献   

7.
Manganese cations (Mn(2+)) can be used as an intracellular contrast agent for structural, functional and neural pathway imaging applications. However, at high concentrations, Mn(2+) is neurotoxic and may influence the concentration of (1)H MR-detectable metabolites. Furthermore, the paramagnetic Mn(2+) cations may also influence the relaxation of the metabolites under investigation. Consequently, the purpose of this study was to investigate the effect of paramagnetic Mn(2+) cations on (1)H-MR spectra of the brain using in vivo and phantom models at 4.7 T. To investigate the direct paramagnetic effects of Mn(2+) cations on the relaxation of N-acetylaspartate (NAA), creatine and choline, T(1) relaxation times of metabolite solutions, with and without 5% albumin, and containing different Mn(2+) concentrations were determined. Relaxivity values with/without 5% albumin for NAA (4.8/28.1 s(-1) mM(-1)), creatine (2.8/2.8 s(-1) mM(-1)) and choline (1.8/1.1 s(-1) mM(-1)) showed NAA to be the most sensitive metabolite to the relaxation effects of the cations. Using an in vivo optic tract tracing imaging model, we obtained two adjacent regions of interest in the superior colliculi with different water T(1) values (Mn(2+)-enhanced = 1.01 s; unenhanced = 1.14 s) 24 h after intravitreal injection of 3 microL 50 mM MnCl(2). Using phantom and in vivo water relaxation time data, we estimated the in vivo Mn(2+) concentration to be 2-8 microM. The phantom data suggest that limited metabolite relaxation effects would be expected at this concentration. Consequently, this study indicates that, in this model, the presence of Mn(2+) cations does not significantly affect (1)H-MR spectra despite possible toxic and paramagnetic effects.  相似文献   

8.
9.
The aims of this study were to observe the behavior of carnosine peaks in human soleus (SOL) and gastrocnemius (GM) muscles following acute exercise, to determine the relaxation times and to assess the repeatability of carnosine quantification by 1H MRS at 7 T. Relaxation constants in GM and SOL were measured by a stimulated echo acquisition mode (STEAM) localization sequence. For T1 measurement, an inversion recovery sequence was used. The repeatability of the measurement and the absolute quantification of carnosine were determined in both muscles in five healthy volunteers. For absolute quantification, an internal water reference signal was used. The effect of acute exercise on carnosine levels and resonance lines was tested in eight recreational runners/cyclists. The defined carnosine measurement protocol was applied three times – before and twice after (approximately 20 and 40 min) a 1‐h submaximal street run and additional toe‐hopping. The measured T1 relaxation times for the C2‐H carnosine peak at 7 T were 2002 ± 94 and 1997 ± 259 ms for GM and SOL, respectively, and the T2 times were 95.8 ± 9.4 and 81.0 ± 21.8 ms for GM and SOL, respectively. The coefficient of variation of the carnosine quantification measurement was 9.1% for GM and 6.3% for SOL, showing high repeatability, and the intraclass correlation coefficients (ICCs) of 0.93 for GM and 0.98 for SOL indicate the high reliability of the measurement. Acute exercise did not change the concentration of carnosine in the muscle, but affected the shape of the resonance lines, in terms of the shifting and splitting into doublets. Carnosine measurement by 1H MRS at 7 T in skeletal muscle exhibits high repeatability and reliability. The observed effects of acute exercise were more prominent in GM, probably as a result of the larger portion of glycolytic fibers in this muscle and the more pronounced exercise‐induced change in pH. Our results support the application of the MRS‐based assessment of carnosine for pH measurement in muscle compartments. © 2015 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.  相似文献   

10.
Saturation recovery spectra (STEAM) were acquired at 1.5 T with 7 TRs ranging from 530 to 5000 ms and a constant TE of 30 ms in voxels (7.2 ml) located in occipital grey, parietal white and frontal white matter (10 subjects each location). Spectra were also acquired at 7, 21 and 37 degrees C from separate 100 mm solutions of inositol (Ins), choline-containing compounds (Cho), N-acetyl-aspartate (NAA) and creatine. Simulations of T(1) fits with 2, 3 and 7 TRs demonstrated that at typical SNR there is potential for both inaccurate and biased results. In vivo, different metabolites had significantly different T(1)s within the same brain volume. The same order from shortest to longest T(1) (Ins, Cho, NAA, creatine) was found for all three brain regions. The order (Ins, NAA, creatine, Cho) was found in the metabolite solutions and was consistent with a simple model in which T(1) is inversely proportional to molecular weight. For all individual metabolites, T(1) increased from occipital grey to parietal white to frontal white matter. This study demonstrates that, in spectra acquired with TR near 1 s, T(1) weightings are substantially different for metabolites within a single tissue and also for the same metabolites in different tissues.  相似文献   

11.
Glioblastoma (GBM), the most common primary brain tumor, is resistant to currently available treatments. The development of mouse models of human GBM has provided a tool for studying mechanisms involved in tumor initiation and growth as well as a platform for preclinical investigation of new drugs. In this study we used 1H MR spectroscopy to study the neurochemical profile of a human orthotopic tumor (HOT) mouse model of human GBM. The goal of this study was to evaluate differences in metabolite concentrations in the GBM HOT mice when compared with normal mouse brain in order to determine if MRS could reliably differentiate tumor from normal brain. A TE =19 ms PRESS sequence at 9.4 T was used for measuring metabolite levels in 12 GBM mice and 8 healthy mice. Levels for 12 metabolites and for lipids/macromolecules at 0.9 ppm and at 1.3 ppm were reliably detected in all mouse spectra. The tumors had significantly lower concentrations of total creatine, GABA, glutamate, total N‐acetylaspartate, aspartate, lipids/macromolecules at 0.9 ppm, and lipids/macromolecules at 1.3 ppm than did the brains of normal mice. The concentrations of glycine and lactate, however, were significantly higher in tumors than in normal brain. Copyright © 2014 John Wiley & Sons, Ltd.  相似文献   

12.
T2 measurement of J-coupled metabolites in the human brain at 3T   总被引:1,自引:0,他引:1  
Proton T2 relaxation times of metabolites in the human brain were measured using point resolved spectroscopy at 3T in vivo. Four echo times (54, 112, 246 and 374 ms) were selected from numerical and phantom analyses for effective detection of the glutamate multiplet at ~ 2.35 ppm. In vivo data were obtained from medial and left occipital cortices of five healthy volunteers. The cortices contained predominantly gray and white matter, respectively. Spectra were analyzed with LCModel software using volume‐localized calculated spectra of brain metabolites. The estimate of the signal strength vs. TE was fitted to a monoexponential function for estimation of apparent T2 (T2?). T2? was estimated to be similar between the brain regions for creatine, choline, glutamate and myo‐inositol, but significantly different for N‐acetylaspartate singlet and multiplet. T2?s of glutamate and myo‐inositol were measured as 181 ± 16 and 197 ± 14 ms (mean ± SD, N = 5) for medial occipital cortices, and 180 ± 12 and 196 ± 17 ms for left occipital cortices, respectively. Copyright © 2011 John Wiley & Sons, Ltd.  相似文献   

13.
Magnetization transfer (MT) was measured in the parotid gland in vivo by (1)H MR spectroscopy in 10 adult volunteers. A comparison was made of stimulated (excess saliva) and resting parotid gland (SPG and RPG, respectively). Following irradiation at an MT pulse of 150 Hz downfield from the water proton signal, signal reductions in SPG and RPG were 83.8 +/- 4.7 and 91.4 +/- 5.7%, respectively. The larger reduction for SPG indicates that an increase in the amount of water in gland cells for the production of more parotid saliva may lead to greater affinity between the protons adjacent to macromolecules and free water which contributes to the MT effect. Activity in the parotid gland correlates with the effect. This method is useful for diagnosing disorders of parotid gland secretion.  相似文献   

14.
2‐Hydroxyglutarate (2HG) is produced in gliomas with mutations of isocitrate dehydrogenase (IDH) 1 and 2. The 1H resonances of the J‐coupled spins of 2HG are extensively overlapped with signals from other metabolites. Here, we report a comparative study at 3 T of the utility of the point‐resolved spectroscopy sequence with a standard short TE (35 ms) and a long TE (97 ms), which had been theoretically designed for the detection of the 2HG 2.25‐ppm resonance. The performance of the methods is evaluated using data from phantoms, seven healthy volunteers and 22 subjects with IDH‐mutated gliomas. The results indicate that TE = 97 ms provides higher detectability of 2HG than TE = 35 ms, and that this improved capability is gained when data are analyzed with basis spectra that include the effects of the volume localizing radiofrequency and gradient pulses. Copyright © 2013 John Wiley & Sons, Ltd.  相似文献   

15.
In vivo MRS of the human brain at 7 tesla allows identification of a large number of metabolites at higher spatial resolutions than currently possible at lower field strengths. However, several challenges complicate in vivo localization and artifact suppression in MRS at high spatial resolution within a clinically feasible scan time at 7 tesla. Published MRS sequences at 7 tesla suffer from long echo times, inherent signal‐to‐noise ratio (SNR) loss, large chemical shift displacement artifacts or long repetition times because of excessive radiofrequency (RF) power deposition. In the present study a pulse‐acquire sequence was used that does not suffer from these high field drawbacks. A slice selective excitation combined with high resolution chemical shift imaging for in‐plane localization was used to limit chemical shift displacement artifacts. The pulse‐acquire approach resulted in a very short echo time of 1.4 ms. A cost function guided shimming algorithm was developed to constrain frequency offsets in the excited slice, therefore adiabatic frequency selective suppression could be employed to minimize artifacts from high intensity lipids and water signals in the excited slice. The high sensitivity at a TR of 1 s was demonstrated both on a supraventricular slice as well as in an area very close to the skull in the frontal cortex at a nominal spatial resolution of 0.25 cc within a feasible scan time. Copyright © 2011 John Wiley & Sons, Ltd.  相似文献   

16.
The T1 values of metabolites were measured in eight subjects with clinically definite multiple sclerosis (MS) having at least one large brain lesion (2.6 ± 0.7 mL) and in eight age‐ and sex‐matched healthy controls. MRS examinations were conducted at 1.5 T using point‐resolved spectroscopy (PRESS) (TE = 30 ms, TR = 530, 750, 1200, 1500, 3500, 5000 ms). Spectra were acquired from a voxel placed in the largest lesion in the subject with MS, and in a corresponding voxel (same size and region) in normal white matter (NWM) in the matched control, and were fitted using LCModel. As there are regional variations in metabolite and water T1 and metabolite signal areas, careful placement of the control voxel was necessary to measure subtle differences between the lesions and NWM. The T1 and T1‐corrected signal areas of creatine were the same in MS lesions as in controls. The T1 values of choline were significantly shorter in MS lesions located in occipital and parietal, but not in frontal, white matter. N‐Acetylaspartate (NAA) and myoinositol T1 values in MS lesions were similar to those in NWM; however, the area of myoinositol correlated directly with lesion water T1, and the area of NAA correlated inversely with lesion water T1. MR spectra acquired at short TR require T1 correction of choline for accurate quantification. Careful voxel placement in controls to match lesion location in subjects with MS enables a clearer view of the subtle changes in lesions. Copyright © 2010 John Wiley & Sons, Ltd.  相似文献   

17.
NAD+ and NADH play key roles in cellular respiration. Intracellular redox state defined by the NAD+/NADH ratio (RX) reflects the cellular metabolic and physiopathological status. By taking advantage of high/ultrahigh magnetic field strengths, we have recently established a novel in vivo 31P MRS‐based NAD assay for noninvasive and quantitative measurements of intracellular NAD concentrations and redox state in animal and human brains at 16.4 T, 9.4 T and 7 T. To explore its potential for clinical application, in this study we investigated the feasibility of assessing the NAD metabolism and redox state in human brain at a lower field of 4 T by incorporating the 1H‐decoupling technique with the in vivo 31P NAD assay. The use of 1H decoupling significantly narrowed the linewidths of NAD and α‐ATP resonances, resulting in higher sensitivity and better spectral resolution as compared with the 1H‐coupled 31P spectrum. These improvements made it possible to reliably quantify cerebral NAD concentrations and RX, consistent with previously reported results obtained from similar age human subjects at 7 T. In summary, this work demonstrates the capability and utility of the 1H‐decoupled 31P MRS‐based NAD assay at lower field strength; thus, it opens new opportunities for studying intracellular NAD metabolism and redox state in human brain at clinical settings. This conclusion is supported by the simulation results, indicating that similar performance and reliability as observed at 4T can be achieved at 3 T with the same signal‐to‐noise ratio. Copyright © 2016 John Wiley & Sons, Ltd.  相似文献   

18.
19.
This study demonstrates the feasibility of the noninvasive determination of important biomarkers of human (breast) tumor metabolism using high‐field (7‐T) MRI and MRS. 31P MRSI at this field strength was used to provide a direct method for the in vivo detection and quantification of endogenous biomarkers. These encompass phospholipid metabolism, phosphate energy metabolism and intracellular pH. A double‐tuned, dual‐element transceiver was designed with focused radiofrequency fields for unilateral breast imaging and spectroscopy tuned for optimized sensitivity at 7 T. T1‐weighted three‐dimensional MRI and 1H MRS were applied for the localization and quantification of total choline compounds. 31P MRSI was obtained within 20 min per subject and mapped in three dimensions over the breast with pixel volumes of 10 mL. The feasibility of monitoring in vivo metabolism was demonstrated in two patients with breast cancer during neoadjuvant chemotherapy, validated by ex vivo high‐resolution magic angle spinning NMR and compared with data from an age‐matched healthy volunteer. Concentrations of total choline down to 0.4 mM could be detected in the human breast in vivo. Levels of adenosine and other nucleoside triphosphates, inorganic phosphate, phosphocholine, phosphoethanolamine and their glycerol diesters detected in glandular tissue, as well as in tumor, were mapped over the entire breast. Altered levels of these compounds were observed in patients compared with an age‐matched healthy volunteer; modulation of these levels occurred in breast tumors during neoadjuvant chemotherapy. To our knowledge, this is the first comprehensive MRI and MRS study in patients with breast cancer, which reveals detailed information on the morphology and phospholipid metabolism from volumes as small as 10 mL. This endogenous metabolic information may provide a new method for the noninvasive assessment of prognostic and predictive biomarkers in breast cancer treatment. Copyright © 2011 John Wiley & Sons, Ltd.  相似文献   

20.
In vivo MRS of the human brain at ultrahigh field allows for the identification of a large number of metabolites at higher spatial resolutions than currently possible in clinical practice. However, the in vivo localization of single‐voxel spectroscopy has been shown to be challenging at ultrahigh field because of the low bandwidth of refocusing radiofrequency (RF) pulses. Thus far, the proposed methods for localized MRS at 7 T suffer from long TE, inherent signal loss and/or a large chemical shift displacement artifact that causes a spatial displacement between resonances, and results in a decreased efficiency in editing sequences. In this work, we show that, by driving a standard volume coil with two RF amplifiers, focusing the B field in a certain location and using high‐bandwidth adiabatic refocusing pulses, a semi‐LASER (semi‐localized by adiabatic selective refocusing) localization is feasible at short TE in the human brain with full signal acquisition and a low chemical shift displacement artifact at 7 T. Copyright © 2011 John Wiley & Sons, Ltd.  相似文献   

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