Revisiting Panda 100, the first archaeological chimpanzee nut-cracking site.

Archaeological recovery of chimpanzee Panda oleosa nut cracking tools at the Panda 100 (P100) and Noulo sites in the Taï Forest, Côte d'Ivoire, showed that this behavior is over 4000 years old, making it the oldest known evidence of non-human tool use. In 2002, the first report on the lithic material from P100 was directly compared to early hominin stone tools, highlighting their similarities and proposing the name 'Pandan' for the chimpanzee material. Here we present an expanded and comprehensive technological, microscopic, and refit analysis of the late twentieth century lithic assemblage from P100. Our re-analysis provides new data and perspectives on the applicability of chimpanzee nut cracking tools to our understanding of the percussive behaviors of early hominins. We identify several new refit sets, including the longest (>17 m) hammerstone transport seen in the chimpanzee archaeological record. We provide detailed evidence of the fragmentation sequences of Panda nut hammerstones, and characterize the percussive damage on fragmented material from P100. Finally, we emphasize that the chimpanzee lithic archaeological record is dynamic, with the preservation of actual hammerstones being rare, and the preservation of small broken pieces more common. P100 - the first archaeological chimpanzee nut cracking lithic assemblage - provides a valuable comparative sample by which to identify past chimpanzee behavior elsewhere, as well as similar hominin percussive behavior in the Early Stone Age.

Visibility of lipid resonances in HR-MAS spectra of brain biopsies subject to spinning rate variation.

Lipid resonances from mobile lipids can be observed by ¹H NMR spectroscopy in multiple tissues and have also been associated with malignancy. In order to use lipid resonances as a marker for disease, a reference standard from a healthy tissue has to be established taking the influence of variable factors like the spinning rate into account. The purpose of our study was to investigate the effect of spinning rate variation on the HR-MAS pattern of lipid resonances in non-neoplastic brain biopsies from different regions and visualize polar and non-polar lipids by fluorescence microscopy using Nile Red staining. ¹H HR-MAS NMR spectroscopy demonstrated higher lipid peak intensities in normal sheep brain pure white matter biopsies compared to mixed white and gray matter biopsies and pure gray matter biopsies. High spinning rates increased the visibility particularly of the methyl resonances at 1.3 and the methylene resonance at 0.89 ppm in white matter biopsies stronger compared to thalamus and brainstem biopsies, and gray matter biopsies. The absence of lipid droplets and presence of a large number of myelin sheaths observed in white matter by Nile Red fluorescence microscopy suggest that the observed lipid resonances originate from the macromolecular pool of lipid protons of the myelin sheath's plasma membranes. When using lipid contents as a marker for disease, the variable behavior of lipid resonances in different neuroanatomical regions of the brain and at variable spinning rates should be considered. The findings may open up interesting possibilities for investigating lipids in myelin sheaths.

Separation of small metabolites and lipids in spectra from biopsies by diffusion-weighted HR-MAS NMR: a feasibility study.

High Resolution Magic Angle Spinning (HR-MAS) NMR allows metabolic characterization of biopsies. HR-MAS spectra from tissues of most organs show strong lipid contributions that are overlapping metabolite regions, which hamper metabolite estimation. Metabolite quantification and analysis would benefit from a separation of lipids and small metabolites. Generally, a relaxation filter is used to reduce lipid contributions. However, the strong relaxation filter required to eliminate most of the lipids also reduces the signals for small metabolites. The aim of our study was therefore to investigate different diffusion editing techniques in order to employ diffusion differences for separating lipid and small metabolite contributions in the spectra from different organs for unbiased metabonomic analysis. Thus, 1D and 2D diffusion measurements were performed, and pure lipid spectra that were obtained at strong diffusion weighting (DW) were subtracted from those obtained at low DW, which include both small metabolites and lipids. This subtraction yielded almost lipid free small metabolite spectra from muscle tissue. Further improved separation was obtained by combining a 1D diffusion sequence with a T2-filter, with the subtraction method eliminating residual lipids from the spectra. Similar results obtained for biopsies of different organs suggest that this method is applicable in various tissue types. The elimination of lipids from HR-MAS spectra and the resulting less biased assessment of small metabolites have potential to remove ambiguities in the interpretation of metabonomic results. This is demonstrated in a reproducibility study on biopsies from human muscle.

Long-term research sites as refugia for threatened and over-harvested species.

The presence of researchers, ecotourists or rangers inside protected areas is generally assumed to provide a protective effect for wildlife populations, mainly by reducing poaching pressure. However, this assumption has rarely been empirically tested. Here, we evaluate and quantify the conservation benefits of the presence of a long-term research area in Taï National Park, Côte d'Ivoire. A wildlife survey following 225 km of line transects revealed considerably higher primate and duiker encounter rates within the research area when compared with adjacent areas. This positive effect was particularly pronounced for threatened and over-harvested species, such as the endangered red colobus monkey (Procolobus badius). This pattern was clearly mirrored by a reversed gradient in signs of poaching, which decreased towards and inside the research area, a trend that was also supported with park-wide data. This study demonstrates that even relatively simple evidence-based analytical approaches can bridge the gap between conservation theory and practice. In addition, it emphasizes the value of establishing long-term research sites as an integral part of protected area management.

Dental development of the Taï Forest chimpanzees revisited.

Developmental studies consistently suggest that teeth are more buffered from the environment than other skeletal elements. The surprising finding of late tooth eruption in wild chimpanzees (Zihlman et al., 2004) warrants reassessment in a broader study of crown and root formation. Here we re-examine the skeletal collection of Taï Forest juvenile chimpanzees using radiography and physical examination. Several new individuals are included, along with genetic and histological assessments of questionable identities. Only half of the Taï juveniles employed by Zihlman et al. (2004) have age of death known with accuracy sufficient for precise comparisons with captive chimpanzees. One key individual in the former study, misidentified during field recovery as Xindra (age 8.3), is re-identified as Goshu (age 6.4). For crown formation we find that onset and duration greatly overlap captive chimpanzees, whereas root development may be more susceptible to acceleration in captive individuals. Kuykendall's (1996) equation relating captive tooth formation stage to age gives reasonable estimates of young wild subjects' true ages. Direct comparisons of tooth eruption ages are limited. A key 3.76 year-old individual likely possessed an emerging mandibular M1 at death (previously estimated from the maxillary molar as occurring at 4.1 years). Wild individuals appear to fall near the middle or latter half of captive eruption ranges. While minor developmental differences are apparent in some comparisons, our reanalysis does not show an "unambiguous pattern" of slower tooth formation in this wild environment. These data do not undermine recent developmental studies of the comparative life histories of fossil hominins.

BOLD correlates of EEG alpha phase-locking and the fMRI default mode network.

Phase locking or synchronization of brain areas is a key concept of information processing in the brain. Synchronous oscillations have been observed and investigated extensively in EEG during the past decades. EEG oscillations occur over a wide frequency range. In EEG, a prominent type of oscillations is alpha-band activity, present typically when a subject is awake, but at rest with closed eyes. The spectral power of alpha rhythms has recently been investigated in simultaneous EEG/fMRI recordings, establishing a wide-range cortico-thalamic network. However, spectral power and synchronization are different measures and little is known about the correlations between BOLD effects and EEG synchronization. Interestingly, the fMRI BOLD signal also displays synchronous oscillations across different brain regions. These oscillations delineate so-called resting state networks (RSNs) that resemble the correlation patterns of simultaneous EEG/fMRI recordings. However, the nature of these BOLD oscillations and their relations to EEG activity is still poorly understood. One hypothesis is that the subunits constituting a specific RSN may be coordinated by different EEG rhythms. In this study we report on evidence for this hypothesis. The BOLD correlates of global EEG synchronization (GFS) in the alpha frequency band are located in brain areas involved in specific RSNs, e.g. the 'default mode network'. Furthermore, our results confirm the hypothesis that specific RSNs are organized by long-range synchronization at least in the alpha frequency band. Finally, we could localize specific areas where the GFS BOLD correlates and the associated RSN overlap. Thus, we claim that not only the spectral dynamics of EEG are important, but also their spatio-temporal organization.

Reproducibility of cerebral phenylalanine levels in patients with phenylketonuria determined by 1H-MR spectroscopy.

The reproducibility of metabolite content determined by MR spectroscopy (MRS) is usually at best a few percent for the prominent singlets. When studying low-concentration metabolites, like phenylalanine (Phe), where tissue content can be <100 micromol/kg, better reproducibility is paramount-particularly in view of using MRS results for potential individual treatment advice. An optimized, targeted spectroscopy method was established at 1.5T and reproducibility was established in 21 patients with phenylketonuria (PKU) where three spectra were recorded in each of three independent sessions, two of which were in immediate succession to minimize physiologic variation. Intersession variation was found to be only 7 micromol/kg Phe for back-to-back repetition of sessions, in close agreement with the variation of 16 micromol/kg observed for single spectra within a session. Analysis of variance proved the individuality of the blood/brain Phe ratio-though this ratio seems to be influenced by physiologic factors that are not stable in time. The excellent reproducibility was achieved through optimization of various factors, including signal-to-noise ratio, repositioning, and prescan calibrations, but also by enforcing as much prior information as possible (e.g., lineshape and phase from reference scans, constant prior-knowledge-locked baseline). While the application of maximum general prior knowledge is a general method to reduce fluctuations, one should remember that it may introduce systematic errors.

Ability of dGEMRIC and T2 mapping to evaluate cartilage repair after microfracture: a goat study.

OBJECTIVE: To investigate the ability of delayed gadolinium-enhanced magnetic resonance (MR) imaging of cartilage (dGEMRIC) and T2 mapping to evaluate the quality of repair tissue after microfracture. DESIGN: Twelve knees from 12 goats were studied. An osteochondral defect (diameter, 6mm; depth, 3mm) with microfracture was created in the weight-bearing aspect of both the medial and lateral femoral condyles. Goats were euthanized at 24 weeks (n=6) and 48 weeks (n=6) postsurgery. Pre-contrast R1 (R1pre) and post-contrast R1 (R1post) measurements for dGEMRIC and a pre-contrast T2 measurement for T2 mapping were performed with a 3T MR imaging system. MR imaging findings were compared with histological and biochemical assessments. RESULTS: In native cartilage, significant correlations were observed between the R1post and the glycosaminoglycan (GAG) concentration, as well as DeltaR1 (difference between the R1pre and R1post) and the GAG concentration (P<0.05). In repair tissue, a significant correlation was observed between DeltaR1 and the GAG concentration (P<0.05), but not between the R1post and the GAG concentration. In both repair tissue and native cartilage, no correlation was observed between T2 and the water concentration or between T2 and the hydroxyproline (HP) concentration. A zonal variation of T2 and a clear dependence of T2 on the angles relative to B0 were observed in native cartilage, but not in repair tissue. CONCLUSION: dGEMRIC with DeltaR1 measurement might be useful for the evaluation of the GAG concentration in repair tissue after microfracture. T2 mapping might be useful for the differentiation of repair tissue after microfracture from native cartilage; however, its potential to assess the specific biochemical markers in native cartilage as well as repair tissue may be limited.

The role of bioactives in energy metabolism and metabolic syndrome.

Some food bioactives potentially exert anti-obesity effects. Anthocyanins (ACN), catechins, ß-glucan (BG) and n-3 long chain PUFA (LCPUFA) are among the most promising candidates and have been considered as a strategy for the development of functional foods counteracting body weight gain. At present, clinical trials, reviews and meta-analyses addressing anti-obesity effects of various bioactives or bioactive-rich foods show contradictory results. Abdominal obesity is an important criterion for metabolic syndrome (MetS) diagnosis along with glucose intolerance, dyslipidaemia and hypertension. Food bioactives are supposed to exert beneficial effects on these parameters, therefore representing alternative therapy approaches for the treatment of MetS. This review summarises outcomes on MetS biomarkers in recent clinical trials supplementing ACN, catechins, BG and n-3 LCPUFA, focusing mainly on anti-obesity effects. Overall, it is clear that the level of evidence for the effectiveness varies not only among the different bioactives but also among the different putative health benefits suggested for the same bioactive. Limited evidence may be due to the low number of controlled intervention trials or to inconsistencies in trial design, i.e. duration, dose and/or the method of bioactive supplementation (extracts, supplements, rich or enriched food). At present, the question 'Are bioactives effective in weight management and prevention of metabolic syndrome?' remains inconclusive. Thus, a common effort to harmonise the study design of intervention trials focusing on the most promising bioactive molecules is urgently needed to strengthen the evidence of their potential in the treatment of obesity, MetS and related diseases.

Effects of four-week high-fructose diet on gene expression in skeletal muscle of healthy men.

AIMS: A high-fructose diet (HFrD) may play a role in the obesity and metabolic disorders epidemic. In rodents, HFrD leads to insulin resistance and ectopic lipid deposition. In healthy humans, a four-week HFrD alters lipid homoeostasis, but does not affect insulin sensitivity or intramyocellular lipids (IMCL). The aim of this study was to investigate whether fructose may induce early molecular changes in skeletal muscle prior to the development of whole-body insulin resistance. METHODS: Muscle biopsies were taken from five healthy men who had participated in a previous four-week HFrD study, during which insulin sensitivity (hyperinsulinaemic euglycaemic clamp), and intrahepatocellular lipids and IMCL were assessed before and after HFrD. The mRNA concentrations of 16 genes involved in lipid and carbohydrate metabolism were quantified before and after HFrD by real-time quantitative PCR. RESULTS: HFrD significantly (P<0.05) increased stearoyl-CoA desaturase-1 (SCD-1) (+50%). Glucose transporter-4 (GLUT-4) decreased by 27% and acetyl-CoA carboxylase-2 decreased by 48%. A trend toward decreased peroxisomal proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) was observed (-26%, P=0.06). All other genes showed no significant changes. CONCLUSION: HFrD led to alterations of SCD-1, GLUT-4 and PGC-1alpha, which may be early markers of insulin resistance.

Patient-rated long-term results after complete denervation of the wrist.

The aim of this study was to examine the long-term results after the denervation of the wrist. Between 1977 and 2001, we treated 375 patients in our clinic. The mean age was 43.5 years; 81% were male and 19% female. The long-term results were assessed by a questionnaire assessing pain on a visual analog scale and patient satisfaction and by the DASH questionnaire. After a mean follow-up of 12.23 years, we found an overall pain reduction of 52.1%. In 67.7% of the patients, we found a relief of pain: of these, 44% are free of pain until today and 56% were temporarily asymptomatic. Patients with a painful osteoarthritic condition without dynamic instability and good range of motion are ideal candidates to benefit from the denervation. The complete denervation of the wrist is an effective treatment option in patients with painful wrist conditions to reduce pain and improve the overall function.

Large neutral amino acids block phenylalanine transport into brain tissue in patients with phenylketonuria.

Large neutral amino acids (LNAAs), including phenylalanine (Phe), compete for transport across the blood-brain barrier (BBB) via the L-type amino acid carrier. Accordingly, elevated plasma Phe impairs brain uptake of other LNAAs in patients with phenylketonuria (PKU). Direct effects of elevated brain Phe and depleted LNAAs are probably major causes for disturbed brain development and function in PKU. Competition for the carrier might conversely be put to use to lower Phe influx when the plasma concentrations of all other LNAAs are increased. This hypothesis was tested by measuring brain Phe in patients with PKU by quantitative 1H magnetic resonance spectroscopy during an oral Phe challenge with and without additional supplementation with all other LNAAs. Baseline plasma Phe was approximately 1,000 micromol/l and brain Phe was approximately 250 micromol/l in both series. Without LNAA supplementation, brain Phe increased to approximately 400 micromol/l after the oral Phe load. Electroencephalogram (EEG) spectral analysis revealed acutely disturbed brain activity. With concurrent LNAA supplementation, Phe influx was completely blocked and there was no slowing of EEG activity. These results are relevant for further characterization of the LNAA carrier and of the pathophysiology underlying brain dysfunction in PKU and for treatment of patients with PKU, as brain function might be improved by continued LNAA supplementation.

Line-scan diffusion tensor imaging of the posttraumatic brain stem: changes with neuropathologic correlation.

Following trauma, imaging of brain stem lesions is often inconclusive. In a man who suffered a lethal accident, postmortem MR diffusion tensor (DT) imaging of the brain and neuropathologic examination were performed. DT imaging showed a disorganization of fibers in the brain stem that was not found in 2 controls and corresponded to changes on neuropathologic correlation. Diffusion tensor imaging provides an insight into the organization of myelinated structures of the CNS, potentially allowing diagnosis of traumatic fiber tract rupture.

Early assessment of brain maturation by MR imaging segmentation in neonates and premature infants.

PURPOSE: We evaluated the impact of premature extrauterine life on brain maturation. PATIENTS AND METHODS: Twelve neonates underwent MR imaging at 40 (39.64 +/- 0.98) weeks (full term). Fifteen premature infants underwent 2 MR imaging examinations, after birth (preterm at birth) and at 40 weeks (41.03 +/- 1.33) (preterm at term). A 3D MR imaging technique was used to measure brain volumes compared with intracranial volume: total brain volume, cortical gray matter, myelinated white matter, unmyelinated white matter, basal ganglia (BG), and CSF. RESULTS: The average absolute volume of intracranial volume (269.8 mL +/- 36.5), total brain volume (246.5 +/- 32.3), cortical gray matter (85.53 mL +/- 22.23), unmyelinated white matter (142.4 mL +/-14.98), and myelinated white matter (6.099 mL +/-1.82) for preterm at birth was significantly lower compared with that for the preterm at term: the average global volume of intracranial volume (431.7 +/- 69.98), total brain volume (391 +/- 66,1), cortical gray matter (179 mL +/- 41.54), unmyelinated white matter (185.3 mL +/- 30.8), and myelinated white matter (10.66 mL +/- 3.05). It was also lower compared with that of full-term infants: intracranial volume (427.4 mL +/- 53.84), total brain volume (394 +/- 49.22), cortical gray matter (181.4 +/- 29.27), unmyelinated white matter (183.4 +/- 27.37), and myelinated white matter (10.72 +/- 4.63). The relative volume of cortical gray matter (30.62 +/- 5.13) and of unmyelinated white matter (53.15 +/- 4.8) for preterm at birth was significantly different compared with the relative volume of cortical gray matter (41.05 +/- 5.44) and of unmyelinated white matter (43.22 +/- 5.11) for the preterm at term. Premature infants had similar brain tissue volumes at 40 weeks to full-term infants. CONCLUSION: MR segmentation techniques demonstrate that cortical neonatal maturation in moderately premature infants at term and term-born infants was similar.

Tools for opening new chapters in the book of Treponema pallidum evolutionary history.

Treponema pallidum infections causing yaws disease and venereal syphilis are globally widespread in human populations, infecting hundreds of thousands and millions annually respectively; endemic syphilis is much less common, and pinta has not been observed in decades. We discuss controversy surrounding the origin, evolution and history of these pathogens in light of available molecular and anthropological evidence. These bacteria (or close relatives) seem to affect many wild African nonhuman primate (NHP) species, though to date only a single NHP Treponema pallidum genome has been published, hindering detection of spillover events and our understanding of potential wildlife reservoirs. Similarly, only ten genomes of Treponema pallidum infecting humans have been published, impeding a full understanding of their diversity and evolutionary history. Research efforts have been hampered by the difficulty of culturing and propagating Treponema pallidum. Here we highlight avenues of research recently opened by the coupling of hybridization capture and next-generation sequencing. We present data generated with such an approach suggesting that asymptomatic bones from NHP occasionally contain enough treponemal DNA to recover large fractions of their genomes. We expect that these methods, which naturally can be applied to modern biopsy samples and ancient human bones, will soon considerably improve our understanding of these enigmatic pathogens and lay rest to old yet unresolved controversies.

Hepatic and intramyocellular glycogen stores in adults with type 1 diabetes and healthy controls.

Glycogen levels in liver and skeletal muscle assessed non-invasively using magnetic resonance spectroscopy after a 48-h pre-study period including a standardized diet and withdrawal from exercise did not differ between individuals with well-controlled Type 1 DM and matched healthy controls.

Variability of blood-brain ratios of phenylalanine in typical patients with phenylketonuria.

Blood-brain ratios (BBR) of phenylalanine (Phe) were determined by quantitative in vivo 1H magnetic resonance spectroscopy (1H-MRS) in 17 adult patients with early-treated phenylketonuria who were randomly selected from a sample of 75 adults. Measurements were performed in all patients during steady-state conditions. The BBR showed a unimodal distribution with a mean of 4.0 (range 3.3 to 4.5). Blood-brain ratios were comparable for subgroups of patients with genotypes classified as severe, moderate, or mild and for patients on different types of diets. Brain Phe concentrations showed a strong linear correlation with blood Phe values (r = 0.93, P < 0.001). There were no saturation effects for blood Phe values up to 1.8 mmol/L, and a local regression analysis did not confirm increasing BBR for increasing blood Phe values. The intellectual outcome (Wechsler Adult Intelligence Scale) was correlated with long-term dietary control (r = -0.65, P < 0.05), fluctuation of blood Phe values during treatment (r = -0.60, P < 0.05), and concurrent blood and brain Phe concentration. The severity of white matter changes visible on magnetic resonance images (MRI) was increased with high blood and brain Phe concentrations but failed to reach statistical significance. No correlation was found between BBR values, intelligence quotient, and MRI grade. Based on the assumption that BBR show intraindividual stability, the current data do not support the hypothesis that blood-brain barrier transport of Phe is a key explanatory factor for outcome variability in the vast majority of "typical" patients with phenylketonuria.

Molecular aspects of magnetic resonance imaging and spectroscopy.

Magnetic resonance imaging (MRI) is a well known diagnostic tool in radiology that produces unsurpassed images of the human body, in particular of soft tissue. However, the medical community is often not aware that MRI is an important yet limited segment of magnetic resonance (MR) or nuclear magnetic resonance (NMR) as this method is called in basic science. The tremendous morphological information of MR images sometimes conceal the fact that MR signals in general contain much more information, especially on processes on the molecular level. NMR is successfully used in physics, chemistry, and biology to explore and characterize chemical reactions, molecular conformations, biochemical pathways, solid state material, and many other applications that elucidate invisible characteristics of matter and tissue. In medical applications, knowledge of the molecular background of MRI and in particular MR spectroscopy (MRS) is an inevitable basis to understand molecular phenomenon leading to macroscopic effects visible in diagnostic images or spectra. This review shall provide the necessary background to comprehend molecular aspects of magnetic resonance applications in medicine. An introduction into the physical basics aims at an understanding of some of the molecular mechanisms without extended mathematical treatment. The MR typical terminology is explained such that reading of original MR publications could be facilitated for non-MR experts. Applications in MRI and MRS are intended to illustrate the consequences of molecular effects on images and spectra.

Prehospital use of APSAC: results of a placebo-controlled study.

Thrombolytic treatment efficacy is greater when the delay between onset of pain and treatment is short. To give treatment before admission to a coronary care unit, responsibility needs to be transferred from cardiologists to other physicians working in mobile care units. We conducted a 2-part feasibility study to investigate this strategy. Part 1 evaluated the diagnostic accuracy of mobile care unit physicians. Results from this study indicate that with regard to the diagnosis of acute myocardial infarction, the risk of a wrong diagnosis is low. Part 2 was a placebo-controlled trial involving 100 patients in which 57 received anisoylated plasminogen streptokinase activator complex (APSAC) (30 U) at home and 43 received placebo at home. Patients receiving placebo at home were reevaluated on arrival in a coronary care unit and received APSAC (30 U) if indicated. The main results were that (1) diagnostic accuracy was good--all patients had an acute coronary syndrome and 97 of 100 patients had myocardial infarction; (2) time gain was approximately 60 minutes; (3) coronary patency rate was 72%; (4) ejection fraction was higher in the prehospital group (56.7%) than in the control group (53.4%), but the difference was not significant; (5) there was no rhythmic or bleeding complication related to the prehospital treatment; (6) 5 patients died from cardiogenic shock--2 between home and hospital and 3 in the hospital (3 received thrombolytic treatment at home and 2 received placebo at home and APSAC in the hospital); and (7) prehospital administration of APSAC did not induce a delay in arrival to the coronary care unit.(ABSTRACT TRUNCATED AT 250 WORDS)

Observation of intramyocellular lipids by 1H-magnetic resonance spectroscopy.

Magnetic resonance (MR) methods are increasingly being used to investigate the physiology of human muscle. Although MR imaging (MRI) reveals the morphology of muscles in great detail, for example, for determining their volume and fiber orientation, MR spectroscopy (MRS) provides information on the chemical composition of the tissue. Depending on the observed nucleus, MRS allows the observation of high-energy phosphates (31P-MRS), glycogen (13C-MRS), or intramyocellular lipids (1H-MRS), to give only a few examples. 1H-MRS of human skeletal muscle requires special techniques because 1H nuclei in water or adipose tissue are far more concentrated than in any other metabolite of human tissue. The strong signal from water can be suppressed by special prepulses, whereas large signals from fat in adipose tissue can be reduced by carefully selecting the region of interest. Until recently, it was presumed that only a few metabolites would be visible underneath the large resonances of water and subcutaneous fat. Meanwhile, it was clear that 1H-MR spectra of human muscle reveal much metabolic and structural information. The determination of intramyocellular lipids (IMCL) by 1H-MRS was initiated by the observation of two compartments of triacylglycerols with a resonance-frequency shift of approximately 0.2 ppm. The two resonances can be attributed to CH2 protons of lipids in fat cells, and to lipids inside muscle cells (IMCL). 1H-MRS examinations are noninvasive and, therefore, can be repeated many times and with a high temporal resolution. MRS has the potential to replace biopsy to follow-up IMCL levels; however, biopsy still has the advantage that other methods, such as molecular biology, can be applied to the sample. It can be shown that IMCL levels (expressed in mMol/kg wet weight and volume %) are muscle specific and vary with diet and physical activity. In addition, it has been reported that IMCL levels are correlated with insulin sensitivity. A comparison of different methods for assessing IMCL levels, including MRS, chemical analysis, and morphometry, revealed a satisfactory correlation among them and a superior correlation of MRS with the average of the three methods. The observation of IMCL levels by means of 1H-MRS is extremely promising, but several methodological limitations and pitfalls need to be considered.