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Chemical exchange saturation transfer (CEST) at about 2.8 ppm downfield from water is characterized besides other compounds by exchanging amine protons of relatively high concentration amino acids and is determined by several physiological (pH, T) and experimental (B0 , B1 , tsat ) parameters. Although the weighting of the CEST effect observed in vivo can be attributed mainly to one compound depending on the organism and organ, there are still several other amino acids, proteins and molecules that also contribute. These contributions in turn exhibit dependences and thus can lead to possible misinterpretation of the measured changes in the CEST effect. With this in mind, this work aimed to determine the exchange rates of six important amino acids as a function of pH and temperature, and thus to create multi-pool models that allow the accurate analysis of the CEST effect concerning different physiological and experimental parameters for a wide variety of organisms. The results show that small changes in the above parameters have a significant impact on the CEST effect at about 2.8 ppm for the chosen organisms, i.e. the human brain (37 °C) and the brain of polar cod (1.5 °C), furthermore, the specificity of the CEST effect observed in vivo can be significantly affected. Based on the exchange rates ksw (pH, T) determined for six metabolites in this study, it is possible to optimize the intensity and the specificity for the CEST effect of amino acids at about 2.8 ppm for different organisms with their specific physiological characteristics. By adjusting experimental parameters accordingly, this optimization will help to avoid possible misinterpretations of CEST measurements. Furthermore, the multi-pool models can be utilized to further optimize the saturation.
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Aminoácidos/química , Imageamento por Ressonância Magnética/métodos , Aminas/química , Animais , Peixes , Humanos , Concentração de Íons de Hidrogênio , Prótons , TemperaturaRESUMO
The neurochemical information provided by proton magnetic resonance spectroscopy (MRS) or MR spectroscopic imaging (MRSI) can be severely compromised if strong signals originating from brain water and extracranial lipids are not properly suppressed. The authors of this paper present an overview of advanced water/lipid-suppression techniques and describe their advantages and disadvantages. Moreover, they provide recommendations for choosing the most appropriate techniques for proper use. Methods of water signal handling are primarily focused on the VAPOR technique and on MRS without water suppression (metabolite cycling). The section on lipid-suppression methods in MRSI is divided into three parts. First, lipid-suppression techniques that can be implemented on most clinical MR scanners (volume preselection, outer-volume suppression, selective lipid suppression) are described. Second, lipid-suppression techniques utilizing the combination of k-space filtering, high spatial resolutions and lipid regularization are presented. Finally, three promising new lipid-suppression techniques, which require special hardware (a multi-channel transmit system for dynamic B1+ shimming, a dedicated second-order gradient system or an outer volume crusher coil) are introduced.
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Encéfalo/diagnóstico por imagem , Consenso , Lipídeos/química , Imageamento por Ressonância Magnética , Espectroscopia de Prótons por Ressonância Magnética , Água/química , Prova Pericial , Humanos , Metaboloma , Ondas de Rádio , Processamento de Sinais Assistido por ComputadorRESUMO
Chemical exchange saturation transfer (CEST) from taurine to water (TauCEST) can be used for in vivo mapping of taurine concentrations as well as for measurements of relative changes in intracellular pH (pHi ) at temperatures below 37°C. Therefore, TauCEST offers the opportunity to investigate acid-base regulation and neurological disturbances of ectothermic animals living at low temperatures, and in particular to study the impact of ocean acidification (OA) on neurophysiological changes of fish. Here, we report the first in vivo application of TauCEST imaging. Thus, the study aimed to investigate the TauCEST effect in a broad range of temperatures (1-37°C) and pH (5.5-8.0), motivated by the high taurine concentration measured in the brains of polar fish. The in vitro data show that the TauCEST effect is especially detectable in the low temperature range and strictly monotonic for the relevant pH range (6.8-7.5). To investigate the specificity of TauCEST imaging for the brain of polar cod (Boreogadus saida) at 1.5°C simulations were carried out, indicating a taurine contribution of about 65% to the in vivo expected CEST effect, if experimental parameters are optimized. B. saida was acutely exposed to three different CO2 concentrations in the sea water (control normocapnia; comparatively moderate hypercapnia OAm = 3300 µatm; high hypercapnia OAh = 4900 µatm). TauCEST imaging of the brain showed a significant increase in the TauCEST effect under the different CO2 concentrations of about 1.5-3% in comparison with control measurements, indicative of changes in pHi or metabolite concentration. Consecutive recordings of 1 H MR spectra gave no support for a concentration induced change of the in vivo observed TauCEST effect. Thus, the in vivo application of TauCEST offers the possibility of mapping relative changes in pHi in the brain of polar cod during exposure to CO2 .
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Encéfalo/metabolismo , Dióxido de Carbono/farmacologia , Peixes/metabolismo , Imageamento por Ressonância Magnética , Taurina/metabolismo , Animais , Encéfalo/diagnóstico por imagem , Concentração de Íons de Hidrogênio , Espectroscopia de Ressonância Magnética , Imagens de Fantasmas , TemperaturaRESUMO
OBJECTIVES: Temperature dependent chemical shifts of important brain metabolites measured by localised 1H MRS were investigated to test how the use of incorrect prior knowledge on chemical shifts impairs the quantification of metabolite concentrations. MATERIALS AND METHODS: Phantom measurements on solutions containing 11 metabolites were performed on a 7 T scanner between 1 and 43 °C. The temperature dependence of the chemical shift differences was fitted by a linear model. Spectra were simulated for different temperatures and analysed by the AQSES program (jMRUI 5.2) using model functions with chemical shift values for 37 °C. RESULTS: Large differences in the temperature dependence of the chemical shift differences were determined with a maximum slope of about ±7.5 × 10-4 ppm/K. For 32-40 °C, only minor quantification errors resulted from using incorrect chemical shifts, with the exception of Cr and PCr. For 1-10 °C considerable quantification errors occurred if the temperature dependence of the chemical shifts was neglected. CONCLUSION: If 1H MRS measurements are not performed at 37 °C, for which the published chemical shift values have been determined, the temperature dependence of chemical shifts should be considered to avoid systematic quantification errors, particularly for measurements on animal models at lower temperatures.
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Encéfalo/metabolismo , Espectroscopia de Prótons por Ressonância Magnética/métodos , Algoritmos , Animais , Simulação por Computador , Creatina/metabolismo , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Humanos , Imagens de Fantasmas , Fosfocreatina/metabolismo , Espectroscopia de Prótons por Ressonância Magnética/estatística & dados numéricos , Software , TemperaturaRESUMO
3D imaging has a significant impact on many challenges in life sciences, because biology is a 3-dimensional phenomenon. Current 3D imaging-technologies (various types MRI, PET, SPECT) are labeled, i.e. they trace the localization of a specific compound in the body. In contrast, 3D MALDI mass spectrometry-imaging (MALDI-MSI) is a label-free method imaging the spatial distribution of molecular compounds. It complements 3D imaging labeled methods, immunohistochemistry, and genetics-based methods. However, 3D MALDI-MSI cannot tap its full potential due to the lack of statistical methods for analysis and interpretation of large and complex 3D datasets. To overcome this, we established a complete and robust 3D MALDI-MSI pipeline combined with efficient computational data analysis methods for 3D edge preserving image denoising, 3D spatial segmentation as well as finding colocalized m/z values, which will be reviewed here in detail. Furthermore, we explain, why the integration and correlation of the MALDI imaging data with other imaging modalities allows to enhance the interpretation of the molecular data and provides visualization of molecular patterns that may otherwise not be apparent. Therefore, a 3D data acquisition workflow is described generating a set of 3 different dimensional images representing the same anatomies. First, an in-vitro MRI measurement is performed which results in a three-dimensional image modality representing the 3D structure of the measured object. After sectioning the 3D object into N consecutive slices, all N slices are scanned using an optical digital scanner, enabling for performing the MS measurements. Scanning the individual sections results into low-resolution images, which define the base coordinate system for the whole pipeline. The scanned images conclude the information from the spatial (MRI) and the mass spectrometric (MALDI-MSI) dimension and are used for the spatial three-dimensional reconstruction of the object performed by image registration techniques. Different strategies for automatic serial image registration applied to MS datasets are outlined in detail. The third image modality is histology driven, i.e. a digital scan of the histological stained slices in high-resolution. After fusion of reconstructed scan images and MRI the slice-related coordinates of the mass spectra can be propagated into 3D-space. After image registration of scan images and histological stained images, the anatomical information from histology is fused with the mass spectra from MALDI-MSI. As a result of the described pipeline we have a set of 3 dimensional images representing the same anatomies, i.e. the reconstructed slice scans, the spectral images as well as corresponding clustering results, and the acquired MRI. Great emphasis is put on the fact that the co-registered MRI providing anatomical details improves the interpretation of 3D MALDI images. The ability to relate mass spectrometry derived molecular information with in vivo and in vitro imaging has potentially important implications. This article is part of a Special Issue entitled: Computational Proteomics in the Post-Identification Era. Guest Editors: Martin Eisenacher and Christian Stephan.
Assuntos
Mineração de Dados , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Cromatografia Líquida , Imageamento TridimensionalRESUMO
Chemical exchange saturation transfer (CEST) from glutamate to water (GluCEST) is a powerful tool for mapping glutamate concentration and intracellular pH. GluCEST could also be helpful to understand the physiology of lower aquatic vertebrates and invertebrates. Therefore, this study aimed to investigate the GluCEST effect and the exchange rate ksw from amine protons of glutamate to water in a broad range of temperatures (1-37°C) and pH (5.5-8.0). Z-spectra were measured from glutamate solutions at different pH values and temperatures and analysed by numerically solving the Bloch-McConnell equation. As expected, a strong dependence of the GluCEST effect and the determined ksw values on pH and temperature was observed. In addition, a strong dependence of the GluCEST effect on phosphate buffer concentration was confirmed. The in vitro data show that GluCEST is detectable in the whole temperature range, even at 1°C. An interpolation function for the exchange rate ksw was determined for the considered range of temperatures and pH values, showing a bijective relation between the exchange rate and pH at a given temperature. To investigate the specificity of GluCEST imaging at low temperatures, the CEST effect was investigated for several metabolites relevant for CEST imaging of the brain. As an example, the contribution of GluCEST to the total CEST effect at 3 ppm was estimated for zebrafish (Danio rerio). It is shown that also at lower temperatures glutamate is the major contributor to the total CEST effect, particularly if the experimental parameters are optimized.
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Água Corporal/química , Química Encefálica , Temperatura Baixa , Ácido Glutâmico/análise , Concentração de Íons de Hidrogênio , Espectroscopia de Ressonância Magnética/métodos , Algoritmos , Animais , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Peixe-ZebraRESUMO
Synthetic, ecofriendly fuels and chemicals can be produced through Power-To-X (PtX) processes. To study such catalytic processes operando and spatially resolved, magnetic resonance imaging (MRI) is a versatile tool. A main issue in the application of MRI in reactive studies is a lack of knowledge about how the gathered signals can be interpreted into reaction data like temperature or species concentration. In this work, the interaction of methane and gaseous water is studied regarding their longitudinal relaxation time T 1 and the chemical shift. To this end, defined quantities of methane-water mixtures were sealed in glass tubes and probed at temperatures between 130 and 360 °C and pressures from 6 to 20 bar. From the obtained T 1 relaxation times, the collision cross section of methane with water σ j,CH4-H2O is derived, which can be used to estimate the temperature and molar concentration of methane during the methanation reaction. The obtained T 1 relaxation times can additionally be used to improve the timing of MRI sequences involving water vapor or methane. Further, details about the measurement workflow and tube preparation are shared.
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Catalytic hydrogenation reactions are important in a modern hydrogen-based society. To optimize these gas-phase reactions, a deep understanding of heat, mass, and momentum transfer inside chemical reactors is required. Nuclear magnetic resonance (NMR) measurements can be used to obtain spatially resolved values of temperature, gas composition, and velocity in the usually opaque catalytic macrostructures. For this, the desired values are calculated from measured NMR parameters like signal amplitude, T 1, or T 2. However, information on how to calculate target values from these NMR parameters in gases is scarce, especially for mixtures of gases. To enable detailed NMR studies of hydrogenation reactions, we investigated the T 1 relaxation of methane and hydrogen, which are two gases commonly present in hydrogenation reactions. To achieve industrially relevant conditions, the temperatures are varied from 290 to 600 K and the pressure from 1 bara to 5 bara, using different mixtures of methane and hydrogen. The results show that hydrogen, which is usually considered to be nondetectable in standard MRI sequences, can be measured at high concentrations, starting at a pressure of 3 bara even at temperatures above 400 K. In the investigated parameter range, the absolute T 1 values of hydrogen show only small dependence on temperature, pressure, and composition, while T 1 of methane is highly dependent on all three parameters. At a pressure of 5 bara, the measured values of T 1 for methane agree very well with theoretical predictions, so that they can also be used for temperature calculations. Further, it can be shown that the same measurement technique can be used to accurately calculate gas ratios inside each voxel. In conclusion, this study covers important aspects of spatially resolved operando NMR measurements of gas-phase properties during hydrogenation reactions at industrially relevant conditions to help improve chemical processes in the gas phase.
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Identifying the limiting processes of electroactive biofilms is key to improve the performance of bioelectrochemical systems (BES). For modelling and developing BES, spatial information of transport phenomena and biofilm distribution are required and can be determined by Magnetic Resonance Imaging (MRI) in vivo, in situ and in operando even inside opaque porous electrodes. A custom bioelectrochemical cell was designed that allows MRI measurements with a spatial resolution of 50 µm inside a 500 µm thick porous carbon electrode. The MRI data showed that only a fraction of the electrode pore space is colonized by the Shewanella oneidensis MR-1 biofilm. The maximum biofilm density was observed inside the porous electrode close to the electrode-medium interface. Inside the biofilm, mass transport by diffusion is lowered down to 45% compared to the bulk growth medium. The presented data and the methods can be used for detailed models of bioelectrochemical systems and for the design of improved electrode structures.
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The combination of the principles of two fast spectroscopic imaging (SI) methods, spectroscopic missing pulse steady-state free precession and echo planar SI (EPSI) is described as an approach toward fast 3D SI. This method, termed missing pulse steady-state free precession echo planar SI, exhibits a considerably reduced minimum total measurement time T(min), allowing a higher temporal resolution, a larger spatial matrix size, and the use of k-space weighted averaging and phase cycling, while maintaining all advantages of the original spectroscopic missing pulse steady-state free precession sequence. The minor signal-to-noise ratio loss caused by using oscillating read gradients can be compensated by applying k-space weighted averaging. The missing pulse steady-state free precession echo planar SI sequence was implemented on a 3 T head scanner, tested on phantoms and applied to healthy volunteers.
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Encéfalo/metabolismo , Imagem Ecoplanar/métodos , Imageamento Tridimensional/métodos , Espectroscopia de Ressonância Magnética/métodos , Humanos , Aumento da Imagem/métodos , PrótonsRESUMO
The use of water suppression for in vivo proton MR spectroscopy diminishes the signal intensities from resonances that undergo magnetization exchange with water, particularly those downfield of water. To investigate these exchangeable resonances, an inversion transfer experiment was performed using the metabolite cycling technique for non-water-suppressed MR spectroscopy from a large brain voxel in 11 healthy volunteers at 3.0 T. The exchange rates of the most prominent peaks downfield of water were found to range from 0.5 to 8.9 s(-1), while the T(1) relaxation times in absence of exchange were found to range from 175 to 525 ms. These findings may help toward the assignments of the downfield resonances and a better understanding of the sources of contrast in chemical exchange saturation transfer imaging.
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Água Corporal/metabolismo , Encéfalo/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Adulto , Distribuição de Qui-Quadrado , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , PrótonsRESUMO
Recently, in situ studies using nuclear magnetic resonance (NMR) have shown the possibility to monitor local transport phenomena of gas-phase reactions inside opaque structures. Their application to heterogeneously catalyzed reactions remains challenging due to inherent temperature and pressure constraints. In this work, an NMR-compatible reactor was designed, manufactured, and tested, which can endure high temperatures and increased pressure. In temperature and pressure tests, the reactor withstood pressures up to 28 bars at room temperature and temperatures over 400 °C and exhibited only little magnetic shielding. Its applicability was demonstrated by performing the CO2 methanation reaction, which was measured operando for the first time by using a 3D magnetic resonance spectroscopic imaging sequence. The reactor design is described in detail, allowing its easy adaptation for different chemical reactions and other NMR measurements under challenging conditions.
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The use of spectroscopic Missing Pulse--SSFP (spMP-SSFP) for fast three-dimensional (3D) proton MR spectroscopic imaging (MRSI) at 7 Tesla (T) is demonstrated. Sequence modifications were required regarding the limits of the specific absorption rate as well as hardware limitations with respect to maximum B(1) field strength and B(0) gradient slew rate, as compared to previous studies performed at 3T. The combination of two spatially selective radiofrequency (RF) pulses (with orthogonal slice orientation) and a dual-band chemical shift selective RF pulse for simultaneous water and lipid suppression proved to enable fast 3D MRSI measurements of the brain of healthy volunteers. Using a total measurement time of approximately 8.5 minutes and a nominal and real voxel size of 0.62 cm(3) and 2.6 cm(3), respectively, signals of N-acetyl aspartate, total creatine, choline containing compounds, myo-inositol, and glutamate+glutamine could be detected.
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Algoritmos , Encéfalo/anatomia & histologia , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos , Processamento de Sinais Assistido por Computador , Encéfalo/metabolismo , Humanos , Imageamento por Ressonância Magnética/instrumentação , Imagens de Fantasmas , PrótonsRESUMO
MR velocimetry of liquid flow in opaque porous filters may play an important role in better understanding the mechanisms of deep bed filtration. With this knowledge, the efficiency of separating the suspended solid particles from the vertically flowing liquid can be improved, and thus a wide range of industrial applications such as wastewater treatment and desalination can be optimized. However, MR velocimetry is challenging for such studies due to the low velocities, the severe B0 inhomogeneity in porous structures, and the demand for high spatial resolution and an appropriate total measurement time during which the particle deposition will change velocities only marginally. In this work, a modified RARE-based MR velocimetry method is proposed to address these issues for velocity mapping on a deep bed filtration cell. A dedicated RF coil with a high filling factor is constructed considering the limited space available for the vertical cell in a horizontal MR magnet. Several means are applied to optimize the phase contrast RARE MRI pulse sequence for accurately measuring the phase contrast in a long echo train, even in the case of a low B1 homogeneity. Two means are of particular importance. One uses data acquired with zero flow to correct the phase contrast offsets from gradient imperfections, and the other combines the phase contrast from signals of both odd and even echoes. Results obtained on a 7T preclinical MR scanner indicate that the low velocities in the heterogeneous system can be correctly quantified with high spatial resolution and an adequate total measurement time, enabling future studies on flow during the filtration process.
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The influence of noise on the standard deviation of spectral integrals is examined. Calculations assuming discrete Fourier-transform data are compared with Monte-Carlo simulations. The effects of zero-filling and apodization are examined for free-induction-decay (FID) signals and for symmetric spin-echo signals in one and two dimensions, with particular attention to features not previously presented in the literature. Findings suggest that for mild apodization, the known sensitivity enhancement due to zero-filling in either the real or the imaginary part signal [E. Bartholdi, R.R. Ernst, Fourier spectroscopy and the causality principle, J. Magn. Reson., 11 (1973) 9-19] is maintained; however, for stronger apodization filters, this enhancement can be obliterated completely. It is shown that results obtained by analysis of one-dimensional signals can be readily applied to multi-dimensional data. Furthermore, zero-filling has a negligible effect for symmetric spin-echo signals with implications for signal averaging in magnetic resonance imaging and spectroscopic imaging.
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A fast proton spectroscopic imaging pulse sequence based on the condition of steady-state free precession is presented. High 3D spatial and temporal resolution is achieved using simultaneous detection of both one spatial and one spectral dimension, with a time-dependent gradient cycle known from echo planar imaging. Additionally, in order to increase the spectral width of the measurement, an interleaved acquisition scheme is shown either for systems with limited gradient switching capabilities or applications with a wide chemical shift range. The pulse sequence is implemented on a standard 4.7-T nuclear magnetic resonance animal imaging system. Measurements with a total measurement time of less than 2.5 min and a nominal voxel size of 6.75 microl using a total of 64 x 32 x 16 voxels are performed on phantoms and healthy rat brain in vivo allowing the rapid detection of signals from both uncoupled and J-coupled spin systems with high signal-to-noise ratio.
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Mapeamento Encefálico/métodos , Encéfalo/metabolismo , Imagem Ecoplanar/métodos , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos , Neurotransmissores/análise , Animais , Encéfalo/anatomia & histologia , Imagem Ecoplanar/instrumentação , Estudos de Viabilidade , Feminino , Imageamento por Ressonância Magnética/instrumentação , Espectroscopia de Ressonância Magnética/instrumentação , Imagens de Fantasmas , Prótons , Ratos , Ratos Wistar , Processamento de Sinais Assistido por ComputadorRESUMO
Modern NMR imaging systems used for biomedical research are equipped with B0 gradient systems with strong maximum gradient strength and short switching time enabling (1)H NMR measurements of samples with very short transverse relaxation times. However, background signal originating from non-optimized RF coils may hamper experiments with ultrashort delays between RF excitation and signal reception. We demonstrate that two simple means, outer volume suppression and the use of shaped B0 fields produced by higher-order shim coils, allow a considerable suppression of disturbing background signals. Thus, the quality of NMR images acquired at ultrashort or zero echo time is improved and systematic errors in quantitative data evaluation are avoided. Fields of application comprise MRI with ultrashort echo time or relaxation time analysis, for both biomedical research and characterizing porous media filled with liquids or gases.
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Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética/instrumentação , Carbono/química , Dimetil Sulfóxido/química , Desenho de Equipamento , Gases , Géis , Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional , Reconhecimento Automatizado de Padrão , Porosidade , Processamento de Sinais Assistido por Computador , Água/químicaRESUMO
The present paper provides a summary of the collision-induced dissociation of protonated and deprotonated phase II metabolites of drugs and pesticides. This overview is based on published literature and unpublished data from the authors. In particular, glutathione conjugates and their biotransformation products are discussed in detail. In addition, the fragmentation of the major classes of conjugates, i.e. glucuronides, glucosides, malonylglucosides, sulfates, acetates, methyl and glycine conjugates, is reported. Collision-induced dissociation, as studied by tandem mass spectrometry, allows the rapid identification of the type of conjugate, whereas the exact conjugation site can in general be determined only by additional NMR experiments.
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Espectrometria de Massas/métodos , Praguicidas/metabolismo , Preparações Farmacêuticas/metabolismoRESUMO
Diabetes diagnostic therapy and research would strongly benefit from noninvasive accurate imaging of the functional ß-cells in the pancreas. Here, we developed an analysis of functional ß-cell mass (BCM) by measuring manganese (Mn(2+)) uptake kinetics into glucose-stimulated ß-cells by T1-weighted in vivo Mn(2+)-mediated MRI (MnMRI) in C57Bl/6J mice. Weekly MRI analysis during the diabetes progression in mice fed a high-fat/high-sucrose diet (HFD) showed increased Mn(2+)-signals in the pancreas of the HFD-fed mice during the compensation phase, when glucose tolerance and glucose-stimulated insulin secretion (GSIS) were improved and BCM was increased compared with normal diet-fed mice. The increased signal was only transient; from the 4th week on, MRI signals decreased significantly in the HFD group, and the reduced MRI signal in HFD mice persisted over the whole 12-week experimental period, which again correlated with both impaired glucose tolerance and GSIS, although BCM remained unchanged. Rapid and significantly decreased MRI signals were confirmed in diabetic mice after streptozotocin (STZ) injection. No long-term effects of Mn(2+) on glucose tolerance were observed. Our optimized MnMRI protocol fulfills the requirements of noninvasive MRI analysis and detects already small changes in the functional BCM.
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Diabetes Mellitus Experimental/metabolismo , Células Secretoras de Insulina/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Manganês/metabolismo , Animais , Diabetes Mellitus Experimental/patologia , Células Secretoras de Insulina/patologia , Masculino , CamundongosRESUMO
Proton magnetic resonance spectroscopy (1H-MRS) is a quantitative MR imaging technique often used to complement conventional MR imaging with specific metabolic information. A key metabolite is the amino acid derivative N-Acetylaspartate (NAA) which is an accepted marker to measure the extent of neurodegeneration in multiple sclerosis (MS) patients. NAA is catabolized by the enzyme aspartoacylase (ASPA) which is predominantly expressed in oligodendrocytes. Since the formation of MS lesions is paralleled by oligodendrocyte loss, NAA might accumulate in the brain, and therefore, the extent of neurodegeneration might be underestimated. In the present study, we used the well-characterized cuprizone model. There, the loss of oligodendrocytes is paralleled by a reduction in ASPA expression and activity as demonstrated by genome-wide gene expression analysis and enzymatic activity assays. Notably, brain levels of NAA were not increased as determined by gas chromatography-mass spectrometry and 1H-MRS. These important findings underpin the reliability of NAA quantification as a valid marker for the paraclinical determination of the extent of neurodegeneration, even under conditions of oligodendrocyte loss in which impaired metabolization of NAA is expected. Future studies have to reveal whether other enzymes are able to metabolize NAA or whether an excess of NAA is cleared by other mechanisms rather than enzymatic metabolism.