Localized singlet‐filtered MRS in vivo

MR is a prominent technology to investigate diseases, with millions of clinical procedures performed every year. Metabolic dysfunction is one common aspect associated with many diseases. Thus, understanding and monitoring metabolic changes is essential to develop cures for many illnesses, including for example cancer and neurodegeneration. MR methodologies are especially suited to study endogenous metabolites and processes within an organism in vivo, which has led to many insights about physiological functions. Advancing metabolic MR techniques is therefore key to further understand physiological processes. Here, we introduce an approach based on nuclear spin singlet states to specifically filter metabolic signals and particularly show that singlet‐filtered glutamate can be observed distinctly in the hippocampus of a living mouse in vivo. This development opens opportunities to make use of the singlet spin phenomenon in vivo and besides its use as a filter to provide scope for new contrast agents.     

Errors in 1H‐MRS estimates of brain metabolite concentrations caused by failing to take into account tissue‐specific signal relaxation

Accurate measurement of brain metabolite concentrations with proton magnetic resonance spectroscopy (¹H‐MRS) can be problematic because of large voxels with mixed tissue composition, requiring adjustment for differing relaxation rates in each tissue if absolute concentration estimates are desired. Adjusting for tissue‐specific metabolite signal relaxation, however, also requires a knowledge of the relative concentrations of the metabolite in gray (GM) and white (WM) matter, which are not known a priori. Expressions for the estimation of the molality and molarity of brain metabolites with ¹H‐MRS are extended to account for tissue‐specific relaxation of the metabolite signals and examined under different assumptions with simulated and real data. Although the modified equations have two unknowns, and hence are unsolvable explicitly, they are nonetheless useful for the estimation of the effect of tissue‐specific metabolite relaxation rates on concentration estimates under a range of assumptions and experimental parameters using simulated and real data. In simulated data using reported GM and WM T₁ and T₂ times for N‐acetylaspartate (NAA) at 3 T and a hypothetical GM/WM NAA ratio, errors of 6.5–7.8% in concentrations resulted when TR = 1.5 s and TE = 0.144 s, but were reduced to less than 0.5% when TR = 6 s and TE = 0.006 s. In real data obtained at TR/TE = 1.5 s/0.04 s, the difference in the results (4%) was similar to that obtained with simulated data when assuming tissue‐specific relaxation times rather than GM–WM‐averaged times. Using the expressions introduced in this article, these results can be extrapolated to any metabolite or set of assumptions regarding tissue‐specific relaxation. Furthermore, although serving to bound the problem, this work underscores the challenge of correcting for relaxation effects, given that relaxation times are generally not known and impractical to measure in most studies. To minimize such effects, the data should be acquired with pulse sequence parameters that minimize the effect of signal relaxation.     

Diffusion‐weighted MRI measurements on stroke patients reveal water‐exchange mechanisms in sub‐acute ischaemic lesions

The aim of this study was to investigate the diffusion time dependence of signal‐versus‐b curves obtained from diffusion‐weighted magnetic resonance imaging (DW‐MRI) of sub‐acute ischaemic lesions in stroke patients. In this case series study, 16 patients with sub‐acute ischaemic stroke were examined with DW‐MRI using two different diffusion times (60 and 260 ms). Nine of these patients showed sufficiently large lesions without artefacts to merit further analysis. The signal‐versus‐b curves from the lesions were plotted and analysed using a two‐compartment model including compartmental exchange. To validate the model and to aid the interpretation of the estimated model parameters, Monte Carlo simulations were performed. In eight cases, the plotted signal‐versus‐b curves, obtained from the lesions, showed a signal–curve split‐up when data for the two diffusion times were compared, revealing effects of compartmental water exchange. For one of the patients, parametric maps were generated based on the extracted model parameters. These novel observations suggest that water exchange between different water pools is measurable and thus potentially useful for clinical assessment. The information can improve the understanding of the relationship between the DW‐MRI signal intensity and the microstructural properties of the lesions. Copyright © 2009 John Wiley & Sons, Ltd.     

Diffusion‐weighted MRI monitoring of pancreatic cancer response to radiofrequency heat‐enhanced intratumor chemotherapy

The aim of this study was to evaluate the feasibility of using diffusion‐weighted MRI to monitor the early response of pancreatic cancers to radiofrequency heat (RFH)‐enhanced chemotherapy. Human pancreatic carcinoma cells (PANC‐1) in different groups and 24 mice with pancreatic cancer xenografts in four groups were treated with phosphate‐buffered saline (PBS) as a control, RFH at 42 °C, gemcitabine and gemcitabine plus RFH at 42 °C. One day before and 1, 7 and 14 days after treatment, diffusion‐weighted MRI and T₂‐weighted imaging were applied to monitor the apparent diffusion coefficients (ADCs) of tumors and tumor growth. MRI findings were correlated with the results of tumor apoptosis analysis. In the in vitro experiments, the quantitative viability assay showed lower relative cell viabilities for treatment with gemcitabine plus RFH at 42 °C relative to treatment with RFH only and gemcitabine only (37 ± 5% versus 65 ± 4% and 58 ± 8%, respectively, p < 0.05). In the in vivo experiments, the combination therapy resulted in smaller relative tumor volumes than RFH only and chemotherapy only (0.82 ± 0.17 versus 2.23 ± 0.90 and 1.64 ± 0.44, respectively, p = 0.003). In vivo, 14‐T MRI demonstrated a remarkable decrease in ADCs at day 1 and increased ADCs at days 7 and 14 in the combination therapy group. The apoptosis index in the combination therapy group was significantly higher than those in the chemotherapy‐only, RFH‐only and PBS treatment groups (37 ± 6% versus 20 ± 5%, 8 ± 2% and 3 ± 1%, respectively, p < 0.05). This study confirms that it is feasible to use MRI to monitor RFH‐enhanced chemotherapy in pancreatic cancers, which may present new options for the efficient treatment of pancreatic malignancies using MRI/RFH‐integrated local chemotherapy. Copyright © 2013 John Wiley & Sons, Ltd.     

Reproducibility of whole‐brain temperature mapping and metabolite quantification using proton magnetic resonance spectroscopy

Assessing brain temperature can provide important information about disease processes (e.g., stroke, trauma) and therapeutic effects (e.g., cerebral hypothermia treatment). Whole‐brain magnetic resonance spectroscopic imaging (WB‐MRSI) is increasingly used to quantify brain metabolites across the entire brain. However, its feasibility and reliability for estimating brain temperature needs further validation. Therefore, the present study evaluates the reproducibility of WB‐MRSI for temperature mapping as well as metabolite quantification across the whole brain in healthy volunteers. Ten healthy adults were scanned on three occasions 1 week apart. Brain temperature, along with four commonly assessed brain metabolites—total N‐acetyl‐aspartate (tNAA), total creatine (tCr), total choline (tCho) and myo‐inositol (mI)—were measured from WB‐MRSI data. Reproducibility was evaluated using the coefficient of variation (CV). The measured mean (range) of the intra‐subject CVs was 0.9% (0.6%‐1.6%) for brain temperature mapping, and 4.7% (2.5%‐15.7%), 6.4% (2.4%‐18.9%) and 14.2% (4.4%‐52.6%) for tNAA, tCho and mI, respectively, with reference to tCr. Consistently larger variability was found when using H₂O as the reference for metabolite quantifications: 7.8% (3.3%‐17.8%), 7.8% (3.1%‐18.0%), 9.8% (3.7%‐31.0%) and 17.0% (5.9%‐54.0%) for tNAA, tCr, tCho and mI, respectively. Further, the larger the brain region (indicated by a greater number of voxels within that region), the better the reproducibility for both temperature and metabolite estimates. Our results demonstrate good reproducibility of whole‐brain temperature and metabolite measurements using the WB‐MRSI technique.     

In vivo single-shot, proton-localized 13C MRS of rhesus monkey brain

A single-shot, proton-localized, polarization transfer (13)C spectroscopic method was proposed and implemented on a 4.7 T scanner for studying rhesus monkey brains. The polarization transfer sequence was mostly adiabatic, minimizing signal loss due to B(1) inhomogeneity. RF pulses in polarization transfer were also used for voxel selection of protons with gradient fields. The transferred (13)C magnetization was refocused by additional refocusing adiabatic pulses. With the intravenous infusion of D-[1-(13)C]glucose solution, (13)C NMR spectra from a 30 mL voxel were acquired for the resonances of C1 of glucose, C2,3,4 of glutamate and glutamine. The time-resolved turnover of glutamate, glutamine and aspartate from intravenously infused D-[1-(13)C]glucose at a temporal resolution of 12 min was demonstrated with excellent spectral resolution and signal-to-noise ratio. Typically, the half-height linewidth of the decoupled (13)C peaks was approximately 4 Hz. Data obtained with infusion of sodium [2-(13)C]acetate using the proposed polarization transfer method and data from the carboxylic carbon region using non-localized acquisition are also presented.     

Neurometabolic and structural alterations in rat brain due to acute hypobaric hypoxia: in vivo 1H MRS at 7 T

In response to hypobaric hypoxia (HH), which occurs at high altitude, the brain undergoes deleterious changes at the structural and metabolite level. In vivo T₂ weighted imaging (T2WI) and ¹H‐MRS was performed to understand the structural and metabolic changes in the hippocampus region of rat brain. Data were acquired pre‐exposure (baseline controls), immediately after exposure and subsequently at the first, fourth, seventh and 14th days post exposure at normoxia. T₂ weighted images of rat brain showed hyperintensity in the CA2/CA3 region of the hippocampus 7 d after acute HH, which persisted till 14 d, probably indicating structural changes in the hippocampus. ¹H‐MRS results showed no change in metabolite level immediately after acute HH exposure, but on the first day of normoxia the myo‐inositol level was significantly decreased, possibly due to altered astrocyte metabolism. Metabolic alterations showing an increase in choline and decrease in glutamate on the fourth day of normoxia may be seen as a process of demyelination and loss of glutamate pool respectively. On the seventh and 14th days of normoxia, decreases in N‐acetylaspartate, creatine and glutamine + glutamate were observed, which might be due to decreased viability of glutamatergic neurons. In vivo ¹H‐MRS demonstrated early neurometabolic changes prior to probable structural changes post acute HH exposure. The extension of these studies will help in early risk assessment, developing intervention and strategies for combating HH related changes. Copyright © 2014 John Wiley & Sons, Ltd.     

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).     

Proton magnetic resonance spectroscopy of brain metabolic shifts induced by acute administration of 2‐deoxy‐d‐glucose and lipopolysaccharides

In vivo proton magnetic resonance spectroscopy (¹H MRS) of outbred stock ICR male mice (originating from the Institute of Cancer Research) was used to study the brain (hippocampus) metabolic response to the pro‐inflammatory stimulus and to the acute deficiency of the available energy, which was confirmed by measuring the maximum oxygen consumption. Inhibition of glycolysis by means of an injection with 2‐deoxy‐d ‐glucose (2DG) reduced the levels of gamma‐aminobutyric acid (GABA, p < 0.05, in comparison with control, least significant difference (LSD) test), N‐acetylaspartate (NAA, p < 0.05, LSD test) and choline compounds, and at the same time increased the levels of glutamate and glutamine. An opposite effect was found after injection with bacterial lipopolysaccharide (LPS) – a very common pro‐inflammatory inducer. An increase in the amounts of GABA, NAA and choline compounds in the brain occurred in mice treated with LPS. Different metabolic responses to the energy deficiency and the pro‐inflammatory stimuli can explain the contradictory results of the brain ¹H MRS studies under neurodegenerative pathology, which is accompanied by both mitochondrial dysfunction and inflammation. The prevalence of the excitatory metabolites such as glutamate and glutamine in 2DG treated mice is in good agreement with excitation observed during temporary reduction of the available energy under acute hypoxia or starvation. In turn, LPS, as an inducer of the sickness behavior, which was manifested as depression, sleepiness, loss of appetite etc., shifts the brain metabolic pattern toward the prevalence of the inhibitory neurotransmitter GABA. Copyright © 2014 John Wiley & Sons, Ltd.     

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.     

Detection of metabolite changes in response to a varying visual stimulation paradigm using short‐TE 1H MRS at 7 T

The two‐fold benefit of ¹H magnetic resonance spectroscopy (MRS) at high B₀ fields – enhanced sensitivity and increased spectral dispersion – has been used previously to study dynamic changes in metabolite concentrations in the human brain in response to visual stimulation. In these studies, a strong visual on/off stimulus was combined with MRS data acquisition in a voxel location in the occipital cortex determined by an initial functional magnetic resonance imaging experiment. However, 1) to exclude the possibility of systemic effects (heartbeat, blood flow, etc.), which tend to be different for on/off conditions, a modified stimulation condition not affecting the target voxel needs to be employed, and 2) to assess important neurotransmitters of low concentration, in particular γ‐aminobutyric acid (GABA), it may be advantageous to analyze steady‐state, rather than dynamic, conditions. Thus, the aim of this study was to use short‐TE ¹H MRS methodology at 7 T to detect differences in steady‐state metabolite levels in response to a varying stimulation paradigm in the human visual cortex. The two different stimulation conditions were termed voxel and control activation. Localized MR spectra were acquired using the SPECIAL (spin‐echo full‐intensity acquired localized) sequence. Data were analyzed using LCModel. Fifteen individual metabolites were reliably quantified. On comparison of steady‐state concentrations for voxel versus control activation, a decrease in GABA of 0.05 mmol/L (5%) and an increase in lactate of 0.04 mmol/L (7%) were found to be the only significant effects. The observed reduction in GABA can be interpreted as reduced neuronal inhibition during voxel activation, whereas the increase in lactate hints at an intensification of anaerobic glycolysis. Differences from previous studies, notably the absence of any changes in glutamate, are attributed to the modified experimental conditions. This study demonstrates that the use of advanced ¹H MRS methodology at 7 T allows the detection of subtle changes in metabolite concentrations involved in neuronal activation and inhibition.     

Probing metabolite diffusion at ultra‐short time scales in the mouse brain using optimized oscillating gradients and “short”‐echo‐time diffusion‐weighted MRS

Measuring diffusion at ultra‐short time scales may yield information about short‐range intracellular structure and cytosol viscosity. However, reaching such time scales usually requires oscillating gradients, which in turn imply long echo times T_E. Here we propose a new kind of stretched oscillating gradient that allows us to increase diffusion‐weighting b while preserving spectral and temporal properties of the gradient modulation. We used these optimized gradients to measure metabolite diffusion in the mouse brain down to effective diffusion times of 1 ms while keeping T_E relatively short (60 ms). At such T_E, a significant macromolecule signal could still be observed and used as an internal reference of approximately null diffusivity, which proved critical to discard datasets corrupted by some motion artifact. The methods introduced here may be useful to improve the accuracy and precision of metabolite apparent diffusion coefficient measurements with oscillating gradients.     

Neurological and brain MRS findings in patients with Gaucher disease type 1

Gaucher disease type 1 (GD1) is an autosomal recessive lysosomal storage disorder, characterised by accumulation of glycosphingolipids in visceral organs. Although considered non-neuronopathic neurological involvement has been reported in single cases. The aim of our study was to investigate central and peripheral nervous system involvement in patients with GD1. We investigated nine unrelated patients with GD1 by three-dimensional cerebral 1H-magnetic resonance spectroscopic imaging and clinical and neurophysiological tests. We found an increased choline level on MRS in four patients. One of these patients had mixed axonal neuropathy and subclinical involvement of the central somatosensory tract as well as monoclonal gammopathy. One patient with normal cerebral choline levels had evidence of bilateral carpal tunnel syndrome upon neurophysiological exam. The N370S mutation was found in 11 out of 18 alleles. Three patients were compound heterozygous for the L444P mutation. There was no correlation between increased cerebral choline levels and type of mutations. MRS findings suggest that in patients with classical non-neuronopathic GD1, the brain is involved at a subclinical level in some patients.     

An in vivo ultrahigh field 14.1 T 1H‐MRS study on 6‐OHDA and α‐synuclein‐based rat models of Parkinson's disease: GABA as an early disease marker

The detection of Parkinson's disease (PD) in its preclinical stages prior to outright neurodegeneration is essential to the development of neuroprotective therapies and could reduce the number of misdiagnosed patients. However, early diagnosis is currently hampered by lack of reliable biomarkers. ¹H magnetic resonance spectroscopy (MRS) offers a noninvasive measure of brain metabolite levels that allows the identification of such potential biomarkers. This study aimed at using MRS on an ultrahigh field 14.1 T magnet to explore the striatal metabolic changes occurring in two different rat models of the disease. Rats lesioned by the injection of 6‐hydroxydopamine (6‐OHDA) in the medial‐forebrain bundle were used to model a complete nigrostriatal lesion while a genetic model based on the nigral injection of an adeno‐associated viral (AAV) vector coding for the human α‐synuclein was used to model a progressive neurodegeneration and dopaminergic neuron dysfunction, thereby replicating conditions closer to early pathological stages of PD. MRS measurements in the striatum of the 6‐OHDA rats revealed significant decreases in glutamate and N‐acetyl‐aspartate levels and a significant increase in GABA level in the ipsilateral hemisphere compared with the contralateral one, while the αSyn overexpressing rats showed a significant increase in the GABA striatal level only. Therefore, we conclude that MRS measurements of striatal GABA levels could allow for the detection of early nigrostriatal defects prior to outright neurodegeneration and, as such, offers great potential as a sensitive biomarker of presymptomatic PD. Copyright © 2012 John Wiley & Sons, Ltd.     

Absolute metabolite concentrations calibrated using the total water signal in brain 1H MRS

Magnetic resonance spectroscopy (MRS) has been coupled with a multi‐echo imaging sequence to determine the relaxation corrected signal areas of the metabolites and the tissue water. Stimulated echo acquisition mode (STEAM) spectra (TE/TM/TR 30/13.7/5000 ms) acquired from gray and white matter voxels in 43 healthy volunteers were fit using LCModel. Corresponding water signals, measured using a multi‐echo T₂ imaging sequence, were fit with a Non‐Negative Least Squares algorithm. Using this approach the water area could be T₁ and T₂ corrected for all three water compartments: cerebrospinal fluid (CSF), intra‐ and extra‐cellular water, and myelin water. The image‐based water measurement is an improvement over spectroscopy methods because it can be more sensitive to water changes in diseased tissue. Metabolite areas were also corrected for relaxation losses. In occipital gray matter, the concentrations of Cho, Cr, and N‐acetyl aspartate (NAA) were 1.27 (0.06), 8.9 (0.3), and 9.3 (0.3) mmol/L tissue, respectively and in parietal white matter they were 1.90 (0.05), 7.9 (0.2), and 9.8 (0.2) mmol/L tissue. The Cho and Cr concentrations were different in occipital gray compared to parietal white matter (p < 0.0001 and <0.005, respectively). Copyright © 2008 John Wiley & Sons, Ltd.     

Diffusion‐weighted imaging of the abdomen: Impact of b‐values on texture analysis features

The purpose of this work was to systematically assess the impact of the b‐value on texture analysis in MR diffusion‐weighted imaging (DWI) of the abdomen. In eight healthy male volunteers, echo‐planar DWI sequences at 16 b‐values ranging between 0 and 1000 s/mm² were acquired at 3 T. Three different apparent diffusion coefficient (ADC) maps were computed (0, 750/100, 390, 750 s/mm²/all b‐values). Texture analysis of rectangular regions of interest in the liver, kidney, spleen, pancreas, paraspinal muscle and subcutaneous fat was performed on DW images and the ADC maps, applying 19 features computed from the histogram, grey‐level co‐occurrence matrix (GLCM) and grey‐level run‐length matrix (GLRLM). Correlations between b‐values and texture features were tested with a linear and an exponential model; the best fit was determined by the smallest sum of squared residuals. Differences between the ADC maps were assessed with an analysis of variance. A Bonferroni‐corrected p‐value less than 0.008 (=0.05/6) was considered statistically significant. Most GLCM and GLRLM‐derived texture features (12–18 per organ) showed significant correlations with the b‐value. Four texture features correlated significantly with changing b‐values in all organs (p < 0.008). Correlation coefficients varied between 0.7 and 1.0. The best fit varied across different structures, with fat exhibiting mostly exponential (17 features), muscle mostly linear (12 features) and the parenchymatous organs mixed feature alterations. Two GLCM features showed significant variability in the different ADC maps. Several texture features vary systematically in healthy tissues at different b‐values, which needs to be taken into account if DWI data with different b‐values are analyzed. Histogram and GLRLM‐derived texture features are stable on ADC maps computed from different b‐values.     

Noise correlations and SNR in phased‐array MRS

The acquisition of magnetic resonance spectroscopy (MRS) signals by multiple receiver coils can improve the signal‐to‐noise ratio (SNR) or alternatively can reduce the scan time maintaining a reliable SNR. However, using phased array coils in MRS studies requires efficient data processing and data combination techniques in order to exploit the sensitivity improvement of the phased array coil acquisition method. This paper describes a novel method for the combination of MRS signals acquired by phased array coils, even in presence of correlated noise between the acquisition channels. In fact, although it has been shown that electric and magnetic coupling mechanisms produce correlated noise in the coils, previous algorithms developed for MRS data combination have ignored this effect. The proposed approach takes advantage of a noise decorrelation stage to maximize the SNR of the combined spectra. In particular Principal Component Analysis (PCA) was exploited to project the acquired spectra in a subspace where the noise vectors are orthogonal. In this subspace the SNR weighting method will provide the optimal overall SNR. Performance evaluation of the proposed method is carried out on simulated ¹H‐MRS signals and experimental results are obtained on phantom ¹H‐MR spectra using a commercially available 8‐element phased array coil. Noise correlations between elements were generally low due to the optimal coil design, leading to a fair SNR gain (about 0.5%) in the center of the field of view (FOV). A greater SNR improvement was found in the peripheral FOV regions. Copyright © 2009 John Wiley & Sons, Ltd.     

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.     

Combined spiroergometry and 31P–MRS of human calf muscle during high‐intensity exercise

Simultaneous measurements of pulmonary oxygen consumption (VO₂), carbon dioxide exhalation (VCO₂) and phosphorus magnetic resonance spectroscopy (³¹P–MRS) are valuable in physiological studies to evaluate muscle metabolism during specific loads. Therefore, the aim of this study was to adapt a commercially available spirometric device to enable measurements of VO₂ and VCO₂ whilst simultaneously performing ³¹P–MRS at 3 T. Volunteers performed intense plantar flexion of their right calf muscle inside the MR scanner against a pneumatic MR‐compatible pedal ergometer. The use of a non‐magnetic pneumotachograph and extension of the sampling line from 3 m to 5 m to place the spirometric device outside the MR scanner room did not affect adversely the measurements of VO₂ and VCO₂. Response and delay times increased, on average, by at most 0.05 s and 0.79 s, respectively. Overall, we were able to demonstrate a feasible ventilation response (VO₂ = 1.05 ± 0.31 L/min; VCO₂ = 1.11 ± 0.33 L/min) during the exercise of a single calf muscle, as well as a good correlation between local energy metabolism and muscular acidification (τ_{PCr fast} and pH; R² = 0.73, p < 0.005) and global respiration (τ_{PCr fast} and VO₂; R² = 0.55, p = 0.01). This provides improved insights into aerobic and anaerobic energy supply during strong muscular performances.