In Vivo Measurements of Ethanol Concentration in Rabbit Brain by 1H Magnetic Resonance Spectroscopy

In vivo 1H magnetic resonance spectroscopy was used to measure the cerebral ethanol concentration in the rabbit after both intraarterial and intragastric administration. There was good agreement between cerebral and blood ethanol concentrations at all times after administration by either route. Cerebral ethanol levels, measured using in vivo 1H spectroscopy, agreed well with those measured in perchloric acid extracts of brain, analyzed by both high-resolution 1H spectroscopy and gas chromatography. Ethanol may be useful as an indicator to measure cerebral blood flow by 1H spectroscopy and chemical shift-selective magnetic resonance imaging.     

Noninvasive skeletal muscle lactate detection between periods of intense exercise in humans

We investigated whether localized ¹H nuclear magnetic resonance spectroscopy (NMRS) using stimulated echoes (STEAM) with a long mixing time (t _m) allowed the suppression of the fat signal and detection of lactate in skeletal muscle. The ¹H NMRS sequence was first validated in three isolated and perfused rabbit biceps brachii muscles. Spectra were obtained on a wide-bore spectrometer using a dual-tuned probe (¹H and ³¹P). Death was simulated by ceasing the muscle perfusion, which allowed post-mortem changes to be followed. During and after the simulated death, changes in levels of pH and in content of energy-rich compounds were observed with ³¹P NMRS. Our results showed an inverse linear relationship between pH and lactate in each of the three rabbits (r = 0.93, P < 0.001; r = 0.92, P < 0.01; r = 0.89, P < 0.01) and a decrease in phosphocreatine and concomitant increase in lactate. We then investigated whether this sequence allowed repeated detection of lactate in human soleus muscle during the recovery between periods of intense exercise (force-velocity test, F-v test). Seven subjects mean age 25.1 (SEM 0.8) years participated in this study. Soleus muscle lactate was detected at rest and for 3 min 30 s of the 5-min recovery between periods using a 2.35-T 40-cm bore magnet spectrometer. Arm venous plasma lactate concentration was measured at rest, during the F-v test when the subject stopped pedalling (S₁), and at the end of each 5-min recovery between periods (S₂). Results showed that the venous plasma lactate concentration at S₁ and S₂ increased significantly from the beginning of the F-v test to peak anaerobic power (W _an,peak) (P < 0.001). The spectra showed that muscle lactate resonance intensity rose markedly when W _an,peak was achieved. The muscle lactate resonance intensity plotted as a percentage of the resting value increased significantly at W _an,peak compared with submaximal braking forces (P < 0.05). We concluded from these results that localized ¹H NMRS using STEAM with a long t _m allows suppression of the fat signal and repeated detection of lactate on isolated perfused skeletal muscle in animals and between periods of intense exercise in humans. Accepted: 19 January 1998     

Determination of melarsoprol in biological fluids by high-performance liquid chromatography and characterisation of two stereoisomers by nuclear magnetic resonance spectroscopy

The analysis of melarsoprol in whole blood, plasma, urine and cerebrospinal fluid is described. Extraction was made with a mixture of chloroform and acetonitrile followed by back-extraction into phosphoric acid. A reversed-phase liquid chromatography system with ultraviolet detection was used. The relative standard deviation was 1% at concentrations around 10 μmol/l and 3–6% at the lower limit of determination (9 nmol/l in plasma, 93 nmol/l in whole blood, 45 nmol/l in urine and 10 nmol/l in cerebrospinal fluid). Melarsoprol is not a stable compound and samples to be stored for longer periods of time should be kept at −70°C. Plasma samples can be stored at −20°C for upt to 2 months. Chromatography showed that melarsoprol contains two components. Using nuclear magnetic resonance spectroscopy the two components were shown to be diastereomers which slowly equilibrate by inversion of the configuration at the As atom.     

NMR-based metabolomics approach to target biomarkers for human prostate cancer

In the era of genomics and proteomics, metabolomics offers a unique way to probe the underlying biochemistry of malignant transformations. In the context of oncological metabolomics, the study of the global variation of metabolites involved in the development and progression of cancers, few existing techniques offer as much potential to discover biomarkers as nuclear magnetic resonance techniques. The most fundamental magnetic resonance methodologies with regard to human prostate cancer are magnetic resonance spectroscopy and magnetic resonance spectroscopic imaging. Recent in vivo explorations have examined crucial metabolites that may indicate cancerous lesions and have the potential to direct treatment; while ex vivo studies of prostatic fluids and tissues have defined novel diagnostic parameters and indicated that magnetic resonance methodologies will be paramount in future prostate cancer management.     

弥散加权成像及1H磁共振波谱在新生儿缺氧缺血性脑病中的诊断价值

目的:探讨弥散加权成像、1H磁共振波谱诊断新生儿缺氧缺血性脑病的应用价值。方法:以本院收治的缺氧缺血性脑病新生儿37例为研究组,另选择健康新生儿40例作为对照组,两组新生儿均接受弥散加权成像及1H磁共振波谱检查,观察研究组新生儿普通MRI与弥散加权成像检查结果,对比研究组和对照组新生儿的脑代谢化合物相对浓度。结果:与普通MRI检出率相比,研究组患儿的弥散加权成像信号明显升高,差异存在统计学意义(P0.05)。研究组NAA/Cr比值低于对照组,Cho/Cr、MI/Cr、Glu-Gln/Cr、Lac/Cr比值高于对照组,差异存在统计学意义(P0.05)。结论:临床上诊断新生儿缺氧缺血性脑病时,弥散加权成像与1H磁共振波谱的联合应用可提升诊断准确率,通过对代谢物浓度的分析有利于评价缺氧缺血导致脑组织损害的严重程度。     

Human metabolic profiles are stably controlled by genetic and environmental variation

¹H Nuclear Magnetic Resonance spectroscopy (¹H NMR) is increasingly used to measure metabolite concentrations in sets of biological samples for top‐down systems biology and molecular epidemiology. For such purposes, knowledge of the sources of human variation in metabolite concentrations is valuable, but currently sparse. We conducted and analysed a study to create such a resource. In our unique design, identical and non‐identical twin pairs donated plasma and urine samples longitudinally. We acquired ¹H NMR spectra on the samples, and statistically decomposed variation in metabolite concentration into familial (genetic and common‐environmental), individual‐environmental, and longitudinally unstable components. We estimate that stable variation, comprising familial and individual‐environmental factors, accounts on average for 60% (plasma) and 47% (urine) of biological variation in ¹H NMR‐detectable metabolite concentrations. Clinically predictive metabolic variation is likely nested within this stable component, so our results have implications for the effective design of biomarker‐discovery studies. We provide a power‐calculation method which reveals that sample sizes of a few thousand should offer sufficient statistical precision to detect ¹H NMR‐based biomarkers quantifying predisposition to disease.     

Nondestructive Detection of Glutamate by 1H Nuclear Magnetic Resonance Spectroscopy in Cortical Brain Slices from the Guinea Pig: Evidence for Changes in Detectability During Severe Anoxic Insults

31P and 1H nuclear magnetic resonance spectroscopy (NMR) was used to study the metabolism of intact superfused cortical brain slices during normoxia and anoxia. Attention was focused on quantification of 1H NMR-detected glutamate by a water-suppressed spin-echo method, using N-acetyl aspartate as an internal concentration reference. To quantify the 1H NMR signals, the spin-spin relaxation times and saturation effects were estimated for given metabolites. In addition, absolute concentrations of metabolites were determined by biochemical methods from acid extracts of the preparations after NMR experiments. Under aerobic conditions, 1H NMR detected 79% of the glutamate determined biochemically from the brain slice extracts. During anoxia in the absence of glucose when a severe energetic failure was evident, both 1H NMR and biochemical assays gave closely matching levels for glutamate. We conclude that in the brain cortex 21% of glutamate is located in an intracellular compartment in which this amino acid does not contribute to the 1H NMR signal. However, during severe anoxia an intracellular reorganisation occurs increasing the detectability of this amino acid neurotransmitter by NMR.     

Order and fluidity in the terminal methyl region of dipalmitoyl phosphatidylcholine multibilayers: A comparison of raman and H-NMR spectroscopy

Deuterium magnetic resonance (²H-NMR) and Raman spectroscopy are used to investigate order and fluidity at the terminal methyl position in 16-d₃, 16′-d₃ dipalmitoylphosphatidylcholine (16-d₆ DPPC) multibilayers. These methods reveal substantial motion and disorder in the gel phase, 5–10°C below the gel-liquid crystal phase transition temperature (T_m). The phase transition is sensed in the ²H-NMR spectrum as a reduction in the quadrupole splitting from 14 kHz to 3 kHz. In contrast, the Raman parameter used to characterize the CD₃ vibrations is quite insensitive to the melting process, although an analogous parameter does sense disordering at T_m at the 10 and 10′ position in 10-d₂, 10′-d₂ DPPC. The difference in the response of the NMR and Raman parameters may arise because the vibrational spectrum of the CD₃ group is inhomogenously broadened and is therefore quite sensitive to alterations in the local environment around the methyl group. In contrast, the NMR quadrupole splitting is sensitive to both local motion of the methyl group and, near Tm, to motions of the CD₂ group induced by transgauche isomerizations further up the chain. The difficulties that arise when results from different spectroscopic techniques are compared are demonstrated.     

Le diagnostic et le suivi thérapeutique des tumeurs cérébrales intra-parenchymateuses par l’imagerie par résonance magnétique multimodale

The multimodal magnetic resonance imaging (MMRI) has an important role in cancer care. This non-invasive and non-ionizing technique provides vital information for the diagnosis and answers to various questions of clinicians before, during and after treatment. The MMRI can specify the localization expanding process; it allows establishing the differential diagnosis of a brain tumor and a circumscribed lesion of another type, to approach the diagnosis of the tumor lesion nature as well as establishing the histological grade of glial tumor in view of lesion monitoring after treatment. The multimodal magnetic resonance imaging has a major contribution to the management progress of the brain tumors. Thus, this paper reviews the value of these MRI modalities in the diagnosis, management and therapy of brain tumors.     

Neurochemical Changes in Brain Induced by Chronic Morphine Treatment: NMR Studies in Thalamus and Somatosensory Cortex of Rats

To investigate the effects of chronic morphine treatment and its cessation on thalamus and the somatosensory cortex, an ex vivo high resolution (500 MHz) ¹H nuclear magnetic resonance spectroscopy (NMRS), in the present study, was applied to detect multiple alterations of neurochemicals and/or neurometabolites in the rats. Ten days of chronic morphine administration was observed to markedly increase the total amount of lactate (Lac), myo-inositol (my-Ins) (each P < 0.01) and aspartate (Asp) (P < 0.05), and significantly decrease that of glutamate (Glu) and glutamine (Gln) in the rats thalamus (each P < 0.05). In the somatosensory cortex, chronic morphine was shown to increase the level of Lac and my-Ins, and decrease that of Glu (each P < 0.05). Interestingly, the ratio of Glu/GABA was found to decrease in these two brain areas after chronic morphine treatment, and among the detectable neurochemicals in those two cerebral areas, only taurine (Tau) showed to result in a significant increment in thalamus during the process of morphine discontinuation (P < 0.05). Moreover, the alterations of multiple neurochemicals due to chronic morphine exhibited a tendency of recovery to the normal level over the course of morphine withdrawal. The results suggested that, in thalamus and the somatosensory cortex, chronic morphine administration and its cessation could induce multiple neurochemical changes, which may involve in the brain energy metabolism, activity and transition of neurotransmitters.     

磁共振波谱分析在颅脑胶质瘤分级中的应用研究

目的 分析脑胶质瘤的氢质子磁共振波谱（proton magnetic resonance spectroscopy,1H-MRS）表现及其临床意义;探讨脑胶质瘤的1H-MRS特点与其病理级别相关性.方法 搜集经临床手术、病理证实的脑胶质瘤病例49例,按照WHO诊断标准分成两组：低级别脑胶质瘤组、高级别脑胶质瘤组.所有患者在术前行1H-MRs检查,均在MR非增强成像的基础上获得.使用Philips Achieva 1.5T超导磁共振扫描仪,单体素或多体素扫描,点分辨法,检测不同区域代谢物变化.结果 脑胶质瘤的1H-MRS表现：肌酸（Cr）轻度下降,N-乙酰天门冬氨酸（NAA）显著下降,胆碱（Cho）显著增高.低、高级别脑胶质瘤的肿瘤组织与对侧止常脑组织的NAA、Cho、NAA/Cr、NAA/Cho值存在显著性差异（P〈0.05）;低级别和高级别脑胶质瘤的肿瘤组织的NAA/Cr、NAA/Cho值存在显著性差异（P〈0.05）.脑胶质瘤的NAA/Cho、Cho/Cr、NAA/Cr值与病理级别相关,其中NAA/Cho和NAA/Cr值反映肿瘤级别较稳定;NAA/Cr、NAA/Cho值呈负相关关系,Cho/Cr值呈正相关关系.结论 ：1H-MRS结合MKI能提高脑胶质瘤术前诊断的准确性.1H-MRS能对胶质瘤进行分级,反映胶质瘤代谢特性以及肿瘤生长潜能.     

Towards structure determination of neurotoxin II bound to nicotinic acetylcholine receptor: a solid-state NMR approach

Solid-state magic-angle spinning nuclear magnetic resonance (NMR) has sufficient resolving power for full assignment of resonances and structure determination of immobilised biological samples as was recently shown for a small microcrystalline protein. In this work, we show that highly resolved spectra may be obtained from a system composed of a receptor-toxin complex. The NMR sample used for our studies consists of a membrane preparation of the nicotinic acetylcholine receptor from the electric organ of Torpedo californica which was incubated with uniformly 13C-,15N-labelled neurotoxin II. Despite the large size of the ligand-receptor complex ( > 290 kDa) and the high lipid content of the sample, we were able to detect and identify residues from the ligand. The comparison with solution NMR data of the free toxin indicates that its overall structure is very similar when bound to the receptor, but significant changes were observed for one isoleucine.