Proton T2 relaxation time of J-coupled cerebral metabolites in rat brain at 9.4 T

Knowledge of proton T2 relaxation time of metabolites is essential for proper quantitation of metabolite concentrations in localized proton spectroscopy, especially at moderate to long TEs. Although the T2 relaxation time of singlets, such as that of creatine and N-acetylaspartate, has been characterized in several studies, similar information is lacking from coupled spin resonances of cerebral metabolites. In this study, the T2 relaxation time of coupled spin resonances and singlet resonances of cerebral metabolites was measured in rat brain in vivo at 9.4 T. Spectra were acquired at 11 TEs using the SPin ECho, full Intensity Acquired Localized (SPECIAL) spectroscopy method. Data analysis was performed in the frequency domain with the LCModel software using simulated TE-specific basis sets. The T2 relaxation times in compounds showing singlet resonances were 113 +/- 3 ms (total creatine), 178 +/- 29 ms (total choline) and 202 +/- 12 ms (N-acetylaspartate). The T2 values of J-coupled metabolites ranged from 89 +/- 8 ms (glutamate) to 148 +/- 14 ms (myo-inositol).     

Increased membrane turnover in the brain in cutaneous anthrax without central nervous system disorder: a magnetic resonance spectroscopy study

Cutaneous anthrax, caused by Bacillus anthracis contacting the skin, is the most common form of human anthrax. Recent studies implicate the presence of additional, possibly toxin-related subtle changes, even in patients without neurological or radiological findings. In this study, the presence of subtle changes in cutaneous anthrax was investigated at the metabolite level using magnetic resonance spectroscopy. Study subjects were consisted of 10 patients with cutaneous anthrax without co-morbid disease and/or neurological findings, and 13 healthy controls. There were no statistical differences in age and gender between two groups. The diagnosis of cutaneous anthrax was based on medical history, presence of a typical cutaneous lesion, large gram positive bacilli on gram staining and/or positive culture for B. anthracis from cutaneous samples. Brain magnetic resonance imaging examination consisted of conventional imaging and single-voxel magnetic resonance spectroscopy. Magnetic resonance spectroscopy was performed by using point-resolved spectroscopy sequence (TR: 2000ms, TE: 136ms, 128 averages). Voxels of 20mm×20mm×20mm were placed in normal-appearing parietal white matter to detect metabolite levels. Cerebral metabolite peaks were measured in normal appearing parietal white matter. N-acetyl aspartate/creatine and choline/creatine ratios were calculated using standard analytical procedures. Patients and controls were not statistically different regarding parietal white matter N-acetyl aspartate/creatine ratios (p=0.902), a finding that implicates the conservation of neuronal and axonal integrity and neuronal functions. However, choline/creatine ratios were significantly higher in patient groups (p=0.001), a finding implicating an increased membrane turnover. In conclusion, these two findings point to a possibly anthrax toxins-related subtle inflammatory reaction of the central nervous system at the cellular level.     

Conversion of MCI to dementia: Role of proton magnetic resonance spectroscopy

Mild cognitive impairment (MCI) represents a heterogeneous group of cognitive disturbances at high risk of dementia. The amnestic subtype (aMCI) might be a prodromal state of Alzheimer's disease (AD). The aim of this study is the identification, by proton magnetic resonance spectroscopy (1H MRS), of modifications in brain metabolites able to detect subjects with aMCI at risk of conversion towards AD. Twenty-five subjects with aMCI and 29 normal elderly were enrolled; they underwent a comprehensive clinical and instrumental assessment, a cerebral 1H MRS scan to measure N-acetyl aspartate (NAA), choline (Cho), myo-inositol (mI) and creatine (Cr) in the paratrigonal white matter, bilaterally. After 1 year, 5 MCI subjects became demented (progressive MCI, pMCI). Their baseline levels of metabolites were compared with those evaluated in stable MCI (sMCI) and in controls. We observed a significant difference of the NAA/Cr ratio between pMCI (1.48+/-0.08) and sMCI (1.65+/-0.12) and between pMCI and controls (1.63+/-0.16) in the left hemisphere, suggesting that this metabolic alteration can be detected before the clinical appearance of dementia.     

Proton T (1) and T (2) relaxation times of human brain metabolites at 3 Tesla

Longitudinal and transverse relaxation times were measured for proton MRS signals from human brain metabolites at 3 T using a short-echo STEAM protocol and a surface coil as a transmitter/receiver. Volumes of interest containing mostly grey or mostly white matter were selected in occipital lobes of healthy subjects and relaxation times for the following resonances were obtained: N-acetylaspartate at 2.01 ppm (T(1) and T(2)), glutamate at 2.35 ppm (T(1)), creatine at 3.03 and 3.92 ppm (T(1) and T(2)), choline-containing substances at 3.22 ppm (T(1) and T(2)), myo-inositol at 3.57 and 3.65 ppm (T(1)) and the overlapping signals of glutamate and glutamine at 3.75 ppm (T(1)). The T(1) relaxation times obtained range from 0.97 to 1.47 s for grey matter and from 0.87 to 1.35 s for white matter. On the other hand, T(2) relaxation times range from 116 to 247 ms and from 141 to 295 ms in grey and white matter, respectively. Generally, the T(1) values measured at 3 T are close to the previously published data found at 1.5, 2 and 4.1 T. Also, the T(2) values confirm the previously observed decrease in transverse relaxation times with increasing static magnetic field. The proton relaxation times obtained will allow improved sequence design and spectra quantitation at 3 T, currently tested for enhanced clinical applications.     

Scyllo-inositol in normal aging human brain: 1H magnetic resonance spectroscopy study at 4 Tesla

The scyllo-inositol and myo-inositol concentrations of 24 normal human subjects were measured in vivo using 1H magnetic resonance spectroscopy at 4 T. Single-voxel short-echo (TE = 15 ms) metabolite spectra were collected from the white matter region of the corona radiata. Test-retest studies performed on 10 normal subjects demonstrated coefficient of variation for scyllo-inositol measurement of 37%, compared with 6% for N-acetyl aspartate. Comparisons between old and young subjects showed higher concentration of scyllo-inositol and myo-inositol in older subjects and a trend for a correlation between scyllo-inositol and myo-inositol levels across subjects.     

Proton T2 relaxation of cerebral metabolites of normal human brain over large TE range

T2 of NAA, creatine and choline-containing compounds were measured in posterior frontal white matter and occipital grey matter in 10 healthy human volunteers. Decay curves comprised signals from eight TE times ranging from 30 to 800 ms with TR 2000 ms acquired with a PRESS sequence on a 1.5 T clinical scanner. Simulations were conducted to assess the precision of T2 estimates from decay curves comprising varying numbers and ranges of TE points. Mean and standard errors for T2s of NAA, creatine and choline-containing compounds were 300(8), 169(3) and 239(4) ms in posterior frontal white matter and 256(6), 159(8) and 249(8) ms in occipital grey matter. In vivo T2s found for choline and NAA were shorter than the T2s in the literature. The elevation of literature T2s is accounted for by the simulation results, which demonstrated that there is a bias towards lengthened T2s when T2 is measured with a maximum TE approximately T2. Concentration estimates are at risk of being underestimated if previously reported T2 corrections are used.     

Sensitive and fast T1 mapping based on two inversion recovery images and a reference image

We developed a fast method to obtain T1 relaxation maps in magnetic resonance imaging (MRI) based on two inversion recovery acquisitions and a reference acquisition, while maintaining high sensitivity by utilizing the full dynamic range of the MRI signal. Optimal inversion times for estimating T1 in the human brain were predicted using standard error propagation theory. In vivo measurements on nine healthy volunteers yielded T1 values of 1094+/-18 ms in gray matter and 746+/-40 ms in white matter, in reasonable agreement with literature values using conventional approaches. The proposed method should be useful for clinical studies because the T1 maps can be obtained within a few seconds.     

皮质下缺血性脑血管病的磁共振波谱研究

目的:检测皮质下缺血性脑血管病(SIVD)患者和正常对照组不同脑区脑组织的代谢水平,探讨其与认知功能损害的关系。方法:采用多体素磁共振波谱(1 H-MRS)技术评测SIVD患者(SIVD组,n=32例)和体检健康人(对照组,n=21)额叶及顶叶皮质、白质的代谢物N-乙酰天门冬氨酸(NAA)、胆碱(Cho)、肌酸(Cr);计算有关比值NAA/Cr、Cho/Cr,分析有无认知功能损害SIVD患者上述比值的变化。结果:(1)SIVD组额叶皮质、白质及顶叶皮质、白质各体素NAA/Cr比值明显低于对照组(P0.01);(2)SIVD组顶叶皮质及白质的Cho/Cr比值明显高于对照组(P0.01);(3)SIVD组有认知功能损害患者的额叶皮质和顶叶皮质、白质NAA/Cr比值显著低于无认知功能损害者(P值分别0.01、0.01、0.05),Cho/Cr比值的两者间差异无统计学意义(P0.05)。结论:SIVD患者脑组织存在NAA/Cr、Cho/Cr比值改变,且额叶皮质和顶叶皮质、白质NAA/Cr的下降与认知损害有关。     

An account of the discrepancy between MRI and PET cerebral blood flow measures. A high-field MRI investigation

There is controversy concerning the discrepancy between absolute cerebral blood flow (CBF) values measured using positron emission tomography (PET) and magnetic resonance imaging (MRI). To gain insight into this problem, the increased signal-to-noise ratio (SNR) and extended T(1) relaxation times of blood and tissue at 3.0 T were exploited to perform pulsed arterial spin labeling (PASL) MRI measurements as a function of spatial resolution and post-labeling delay. The results indicate that, when using post-labeling delays shorter than 1500 ms, MRI gray matter flow values may become as high as several times the correct CBF values owing to tissue signal contamination by remaining arterial blood water label. For delays above 1500 ms, regional PASL-based CBF values (n = 5; frontal gray matter: 48.8 +/- 3.3(SD) ml/100 g/min; occipital gray matter: 49.3 +/- 4.5 ml/100 g/min) comparable with PET-based measurements can be obtained by using spatial resolutions comparable with PET (5-7.5 mm in-plane). At very high resolution (2.5 x 2.5 x 3 mm(3)), gray matter CBF values were found to increase by 10-20%, a consequence attributed to reduction in partial volume effects with cerebrospinal fluid and white matter. The recent availability of MRI field strengths of 3.0 T and higher will facilitate the use of MRI-based CBF measurements in the clinic.     

Optimized diffusion-weighted spectroscopy for measuring brain glutamate apparent diffusion coefficient on a whole-body MR system

A diffusion-weighted stimulated echo acquisition mode sequence was implemented in order to measure the glutamate apparent diffusion coefficient (ADC) in the monkey brain on a whole-body 3 T system. TE and TM were adjusted for maximizing glutamate signal intensity. Glutamate ADC was measured in a 5.8 mL voxel made of gray and white matter in macaque monkeys. The effect of post-processing on the estimated ADC was carefully assessed and appeared to be critical. Individual scan phasing and macromolecule subtraction corrected for approximately 25% and approximately 15% biases in glutamate ADC, respectively. Proper data processing yielded ADC values of 0.21 +/- 0.03 microm(2)/ms for glutamate, 0.15 +/- 0.04 microm(2)/ms for N-acetylaspartate + N-acetylaspartylglutamate, 0.12 +/- 0.03 microm(2)/ms for creatine, 0.11 +/- 0.05 microm(2)/ms for choline and 0.18 +/- 0.04 microm(2)/ms for myo-inositol.     

Two-dimensional 1H spectroscopic imaging for evaluating the local metabolic response to focal ischemia in the conscious rat.

Two-dimensional 1H spectroscopic imaging and magnetic resonance imaging were used to study focal ischemia induced by middle cerebral artery occlusion in rats. A water suppressing spin-echo sequence was used at 4.7 T. Phase encoding during the spin-echo delay (TE = 272 ms) yielded an 8 x 8 array of 35 microL voxels. The injured area of the brain had a higher lactate level and markedly lower N-acetyl aspartate, creatine and choline levels than did the non-ischemic regions. The spectroscopic imaging data clearly showed the localization of the infarct, which agreed well with both magnetic resonance imaging and the histological data obtained post-mortem. This study demonstrates the potential usefulness of combining magnetic resonance imaging and 1H spectroscopic imaging for studying animal models of stroke, and indicates the suitability of the technique for further pharmacological approaches.     

T2 measurement of J-coupled metabolites in the human brain at 3T

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.     

T1 relaxation times for viability evaluation of the engrafted and the native liver in a rat model of heterotopic auxiliary liver transplantation: a pilot study

Following a heterotopic auxiliary liver transplantation, commonly used measurements are either invasive or non-indicative of individual viability of the coexisting engrafted and native livers. Magnetic resonance imaging (MRI) was therefore tested for its potential to monitor the post-transplant hepatic viability in a rat model. Thirteen Wistar rats were systematically evaluated with MRI and serum biochemical liver parameters. Post-transplant complications and the causes of animal death were identified by autopsy and histo-pathological examinations. The data of the healthy survivors were compared with those of the rats that developed complications. On MRI, the hepatic complications could be depicted in the individual livers. A specific pattern of signal evolution was found in the livers of the healthy survivors: the mean T1 relaxation times of the engrafted livers increased immediately after transplantation (476 +/- 64 ms, mean +/- standard deviation, pre-operative; 730 +/- 48 ms, week 1) and then declined steadily to a 3 month value of 489 +/- 246 ms, while, following a transient first rise (476 +/- 64 ms, pre-operative; 589 +/- 28 ms, week 1), the mean T1 value of the native livers increased again 4 weeks after surgery and reached a 3 month value of 859 +/- 43 ms. However, in the rats with various complications, the mean T1 relaxation times of the engrafted livers continued to increase throughout the first post-operative month (760 +/- 48 ms, week 1; 922 +/- 76 ms, week 4), while that of the native liver only varied mildly (546 +/- 25 ms, week 1; 473 +/- 25 ms, week 4). After the first post-transplant week, the healthy engrafted livers could already be distinguished from those with complications by a significant decrease in T1 relaxation times. These data suggest that, besides demonstrating major complications, MRI may allow one to monitor the viability of each liver by analysing the relative signal intensity and T1 relaxation times after a heterotopic auxiliary liver transplantation.     

定量质子磁共振波谱对鉴别良性与恶性脑膜瘤的价值(英文)

本研究致力于探讨定量质子磁共振波谱(MRS)对鉴别良性与恶性脑膜瘤的价值。研究利用1.5T磁共振仪,对23例脑膜瘤(良性组(WHO I级)19例,恶性组(WHOⅡ～Ⅲ级)4例)进行单体素MRS检查(PRESS序列,TR/TE=2000ms/68,136,272ms),通过指数衰减模型估计组织水和胆碱(Choline,Cho)的T2弛豫时间,并以组织水为内参照计算Cho的绝对浓度,然后按MRS体素内坏死或囊变组织的比例对Cho浓度进行校正。研究发现,良、恶性脑膜瘤的组织水T2弛豫时间分别是(105±41)ms和(151±42)ms,差异有显著性(P=0.033)。良、恶性脑膜瘤的Cho T2弛豫时间分别是(242±73)ms和(316±102)ms,无显著差异(P=0.105)。良、恶性脑膜瘤的Cho浓度在校正前分别是(2.86±0.86)mmol/kg wet weight和(3.53±0.60)mmol/kg wet weight,在校正后分别是(2.98±0.93)mmol/kg wet weight和(4.58±1.22)mmol/kg wet weight,校正后差异具有显著性(P=0.019)。研究...     

Pitfalls and advantages of different strategies for the absolute quantification of N‐acetyl aspartate,creatine and choline in white and grey matter by 1H‐MRS

This study extensively investigates different strategies for the absolute quantitation of N‐acetyl aspartate, creatine and choline in white and grey matter by ¹H‐MRS at 1.5 T. The main focus of this study was to reliably estimate metabolite concentrations while reducing the scan time, which remains as one of the main problems in clinical MRS. Absolute quantitation was based on the water‐unsuppressed concentration as the internal standard. We compared strategies based on various experimental protocols and post‐processing strategies. Data were obtained from 30 control subjects using a PRESS sequence at several TE to estimate the transverse relaxation time, T₂, of the metabolites. Quantitation was performed with the algorithm QUEST using two different metabolite signal basis sets: a whole‐metabolite basis set (WhoM) and a basis set in which the singlet signals were split from the coupled signals (MSM). The basis sets were simulated in vivo for each TE used. Metabolites' T₂s were then determined by fitting the estimated signal amplitudes of the metabolites obtained at different TEs. Then the absolute concentrations (mM) of the metabolites were assessed for each subject using the estimated signal amplitudes and either the mean estimated relaxation times of all subjects (mean protocol, MP) or the T₂ estimated from the spectra derived from the same subject (individual protocol, IP). Results showed that MP represents a less time‐consuming alternative to IP in the quantitation of brain metabolites by ¹H‐MRS in both grey and white matter, with a comparable accuracy when performed by MSM. It was also shown that the acquisition time might be further reduced by using a variant of MP, although with reduced accuracy. In this variant, only one water‐suppressed and one water‐unsuppressed spectra were acquired, drastically reducing the duration of the entire MRS examination. However, statistical analysis highlights the reduced accuracy of MP when performed using WhoM, particularly at longer echo times. Copyright © 2009 John Wiley & Sons, Ltd.     

Magnetization transfer attenuation of creatine resonances in localized proton MRS of human brain in vivo

To assess putative magnetization transfer effects on the proton resonances of cerebral metabolites in human brain, we performed quantitative proton magnetic resonance spectroscopy (2.0 T, STEAM, TR/TE/TM = 6000/40/10 ms, LCModel data evaluation) of white matter (7.68 mL, 10 healthy young subjects) in the absence and presence of fast repetitive off-resonance irradiation (2.1 kHz from the water resonance) using a train of 100 Gaussian-shaped RF pulses (12.8 ms duration, 120 Hz nominal bandwidth, 40 ms repetition period, 1080 degrees nominal flip angle). A comparison of pertinent metabolite concentrations revealed a magnetization transfer attenuation factor of the methyl and methylene resonances of creatine and phosphocreatine of 0.87 +/- 0.05 (p < 0.01). No attenuation was observed for the resonances of N-acetylaspartate and N-acetylaspartylglutamate, glutamate and glutamine, choline-containing compounds, and myo-inositol. The finding for total creatine is in excellent agreement with data reported for rat brain. The results are consistent with the hypothesis of a chemical exchange of mobile creatine or phosphocreatine molecules with a small immobilized or 'bound' pool.     

Magnetic resonance imaging demonstrates incomplete myelination in 18q- syndrome

Magnetic resonance imaging (MRI) and MRI relaxometry were used to investigate disturbed brain myelination in 18q- syndrome, a disorder characterized by mental retardation, dysmorphic features, and growth failure. T1-weighted and dual spin-echo T2-weighted MR images were obtained, and T1 and T2 parametric image maps were created for 20 patients and 12 controls. MRI demonstrated abnormal brain white matter in all patients. White matter T1 and T2 relaxation times were significantly prolonged in patients compared to controls at all ages studied, suggesting incomplete myelination. Chromosome analysis using fluorescence in situ hybridization techniques showed that all patients with abnormal MRI scans and prolonged white matter T1 and T2 relaxation times were missing one copy of the myelin basic protein (MBP) gene. The one patient with normal-appearing white matter and normal white matter T1 and T2 relaxation times possessed two copies of the MBP gene. MRI and molecular genetic data suggest that incomplete cerebral myelination in 18q- is associated with haploinsufficiency of the gene for MBP. Am. J. Med. Genet. 74:422–431, 1997. © 1997 Wiley-Liss, Inc.     

Regional age-related effects in the monkey brain measured with H magnetic resonance spectroscopy

The rhesus monkey is a useful model for examining age-related effects on the brain, because of the extensive neuroanatomical homology between the monkey and the human brain, the tight control for neurological diseases as well as the possibility of obtaining relevant behavioral data and post-mortem tissue for histological analyses.Here, proton magnetic resonance spectroscopy (¹H-MRS) was used together with high-resolution anatomical MRI images to carefully assess regional concentrations of brain metabolites in a group of 20 rhesus monkeys.In an anterior volume of interest (VOI) that covered frontal and prefrontal areas, significant positive correlations of myo-inositol and of total creatine concentrations with age were detected, whereas N-acetyl aspartate (NAA) and choline compounds (Cho) were not significantly correlated with age. In an occipito-parietal VOI, all metabolites showed no statistically significant age-dependent trend.Strong correlations were found between NAA concentration and gray matter fraction in the VOIs as well as between choline compounds and white matter fraction.     

Age-related glutamate and glutamine concentration changes in normal human brain: 1H MR spectroscopy study at 4 T

Proton magnetic resonance spectroscopy was performed at 4 T to determine effects of age, region and gender on glutamate and glutamine in the normal human brain. Furthermore, glutamate and glutamine alterations with age were tested for correlations with other cerebral metabolites. Two 8 cm3 volumes were selected in corona radiata and mesial motor cortex in normal subjects (N = 24) between 24 and 68 years old. Older subjects had lower glutamate concentration in the motor cortex compared to younger subjects (p < 0.001). In corona radiata, older subjects demonstrated a trend in higher glutamine compared to younger subjects (p = 0.05). Glutamate in the motor cortex was positively correlated with glutamine, N-acetyl aspartate and creatine. Reduced glutamate and N-acetyl aspartate in the motor cortex is consistent with neuronal loss/shrinkage with age. In conclusion, different patterns in association with normal aging in these brain regions were detected in this study.     

The interaction between apparent diffusion coefficients and transverse relaxation rates of human brain metabolites and water studied by diffusion‐weighted spectroscopy at 7 T

The dependence of apparent diffusion coefficients (ADCs) of molecules in biological tissues on an acquisition‐specific timescale is a powerful mechanism for studying tissue microstructure. Unlike water, metabolites are confined mainly to intracellular compartments, thus providing higher specificity to tissue microstructure. Compartment‐specific structural and chemical properties may also affect molecule transverse relaxation times (T₂). Here, we investigated the correlation between diffusion and relaxation for N‐acetylaspartate, creatine and choline compounds in human brain white matter in vivo at 7 T, and compared them with those of water under the same experimental conditions. Data were acquired in a volume of interest in parietal white matter at two different diffusion times, Δ = 44 and 246 ms, using a matrix of three echo times (T_E) and five diffusion weighting values (up to 4575 s/mm²). Significant differences in the dependence of the ADCs on T_E were found between water and metabolites, as well as among the different metabolites. A significant decrease in water ADC as a function of T_E was observed only at the longest diffusion time (p < 0.001), supporting the hypothesis that at least part of the restricted water pool can be associated with longer T₂, as suggested by previous studies in vitro. Metabolite data showed an increase of creatine (p < 0.05) and N‐acetylaspartate (p < 0.05) ADCs with T_E at Δ = 44 ms, and a decrease of creatine (p < 0.05) and N‐acetylaspartate (p = 0.1) ADCs with T_E at Δ = 246 ms. No dependence of choline ADC on T_E was observed. The metabolite results suggest that diffusion and relaxation properties are dictated not only by metabolite distribution in different cell types, but also by other mechanisms, such as interactions with membranes, exchange between “free” and “bound” states or interactions with microsusceptibility gradients. Copyright © 2014 John Wiley & Sons, Ltd.