Biomedical subjects

P G Carlier

Publications and source records attributed to P G Carlier.

At least 19 recordsLinked to original sources

PubMed2006

Influence of vascular filling and perfusion on BOLD contrast during reactive hyperemia in human skeletal muscle.

Mechanisms generating BOLD contrast are complex and depend on parameters that are prone to large variations, in particular in skeletal muscle. Here, we simultaneously measured perfusion by ASL, and BOLD response in the calf muscle of 6 healthy volunteers during post-ischemic reactive hyperemia. We tested whether the relation between the two was altered for varying degrees of leg vascular replenishment induced by prior positioning of the leg at different heights relative to the heart. We found that the BOLD response depended on perfusion, but also on the degree of repletion of leg blood vessels. We conclude that simultaneous determination of perfusion by ASL is important to identify the mechanisms underlying BOLD contrast in the skeletal muscle.

Analysis of Variance↗

PubMed2006

Muscle blood flow and oxygenation measured by NMR imaging and spectroscopy.

Tissue perfusion and oxygenation in many organs can be evaluated by various NMR techniques. This review focuses on the specificities, limitations and adaptations of the NMR tools available to investigate perfusion and oxygenation in the skeletal muscle of humans and animal models. A description of how they may be used simultaneously is provided as well. 1H NMR spectroscopy of myoglobin (Mb) monitors intramyocytic oxygenation. It measures the level of deoxy-Mb, from which Mb concentration, Mb desaturation/resaturation rates, muscle oxygenation changes and intracellular partial oxygen pressure (pO2) can be calculated. Positive and negative blood oxygen level-dependent (BOLD) contrasts exist in skeletal muscle. BOLD contrasts primarily reflect changes in capillary-venous oxygenation, but are also directly or indirectly dependent on muscle blood volume, perfusion, vascular network architecture and angulation, relative to the main magnetic field. Arterial spin labelling (ASL) techniques, having high spatial and temporal resolution, are the methods of choice to quantify and map skeletal muscle perfusion non-invasively. Limitations of ASL are poor contrast-to-noise ratio and sensitivity to movement; however, with the introduction of specific adaptations, it has been proven possible to measure skeletal muscle perfusion at both rest and during exercise. The possibility of combining these NMR measurements with others into a single dynamic protocol is most interesting. The 'multiparametric functional (mpf) NMR' concept can be extended to include the evaluation of muscle energy metabolism simultaneously with 31P NMR or with lactate double quantum filtered 1H NMR spectroscopy, an approach which would make NMR an exceptional tool for non-invasive investigations of integrative physiology and biochemistry in skeletal muscle in vivo.

Animals↗

PubMed2005

How to investigate oxygen supply, uptake, and utilization simultaneously by interleaved NMR imaging and spectroscopy of the skeletal muscle.

Human skeletal muscle perfusion, oxygenation, and high-energy phosphate distribution were measured simultaneously by interleaved (1)H and (31)P NMR spectroscopy and (1)H NMR imaging in vivo. From these parameters, arterial oxygen supply (DO(2)), muscle reoxygenation rate, mitochondrial ATP production, and O(2) consumption (VO(2)) were deduced at the recovery phase of a short ischemic exercise bout. In addition, by using a reformulation of the mass conservation law, muscle maximum O(2) extraction was calculated from these parameters.

Adult↗

PubMed2005

In vivo NMR imaging evaluation of efficiency and toxicity of gene electrotransfer in rat muscle.

In vivo gene electrotransfer (ET) is a simple method of gene delivery in various tissues relying on the injection of plasmid DNA followed by application of electric pulses. Noninvasive tools are needed to evaluate the ET efficiency and the resulting tissue damages. In this study, we performed ET of rat tibialis muscle after injection of either a plasmid coding for luciferase or a contrast agent (CA) detected by using magnetic resonance imaging (MRI). Plasmid expression and CA intracellular trapped quantity were compared throughout the electric field intensity range 0-300 V/cm. Although the CA trapped quantity reflects only the electropermeabilization step, both measurements were correlated. MRI measurements gave easy access to tridimensional visualization of the labelled zones where the CA has been injected and the applied electric field had a value allowing permeabilization. We also performed MRI measurements of the water transverse relaxation time T2 as an indicator of tissue modification, and tested whether another CA specific for necrosis could be used to detect muscle necrosis at high electric field intensity. In conclusion, MRI measurements may bring multiparametric information upon the efficiency and tissue toxicity of an ET protocol by using a simple and safe CA.

Animals↗

PubMed2005

In vivo functional NMR imaging of resistance artery control.

Arterial spin labeling (ASL) in combination with NMR imaging is an in vivo technique that quantifies tissue perfusion in absolute values (ml blood x min(-1) x g tissue(-1)) with high temporal (1-10 s) and spatial (0.1-3 mm) resolution. It uses the arterial water spins as endogenous freely diffusible markers of perfusion and, hence, is a totally noninvasive method. The technique has been successfully applied to quantify baseline perfusion in many organs, including the heart, in humans and animals, and results were validated by comparison with gold standards, PET and microspheres, respectively. Because of the high sampling rate of perfusion with ASL and the possibility that measurements could be obtained without harm over indefinite periods of time, the technique has the potential for use in functional investigations of microcirculation regulation and resistance artery control in vivo. We describe examples of the use of ASL to this end. With use of specific technological developments, ASL determination of perfusion can be coupled with simultaneous acquisitions of (1)H and (31)P NMR spectroscopy data. These protocols offer new possibilities whereby the microcirculatory control of cell oxygenation and high-energy phosphate metabolism can be explored.

Animals↗

PubMed2004

Metabolic and vascular support for the role of myoglobin in humans: a multiparametric NMR study.

In human muscle the role of myoglobin (Mb) and its relationship to factors such as muscle perfusion and metabolic capacity are not well understood. We utilized nuclear magnetic resonance (NMR) to simultaneously study the Mb concentration ([Mb]), perfusion, and metabolic characteristics in calf muscles of athletes trained long term for either sprint or endurance running after plantar flexion exercise and cuff ischemia. The acquisitions for (1)H assessment of Mb desaturation and concentration, arterial spin labeling measurement of muscle perfusion, and (31)P spectroscopy to monitor high-energy phosphate metabolites were interleaved in a 4-T magnet. The endurance-trained runners had a significantly elevated [Mb] (0.28 +/- 0.06 vs. 0.20 +/- 0.03 mmol/kg). The time constant of creatine rephosphorylation (tauPCr), an indicator of oxidative capacity, was both shorter in the endurance-trained group (34 +/- 6 vs. 64 +/- 20 s) and negatively correlated with [Mb] across all subjects (r = 0.58). The time to reach maximal perfusion after cuff release was also both shorter in the endurance-trained group (306 +/- 74 vs. 560 +/- 240 s) and negatively correlated with [Mb] (r = 0.56). Finally, Mb reoxygenation rate tended to be higher in the endurance-trained group and was positively correlated with tauPCr (r = 0.75). In summary, these NMR data reveal that [Mb] is increased in human muscle with a high oxidative capacity and a highly responsive vasculature, and the rate at which Mb resaturates is well correlated with the rephosphorylation rate of Cr, each of which support a teleological role for Mb in O(2) transport within highly oxidative human skeletal muscle.

Exercise↗

PubMed2003

[Exploration of exercise intolerance by 31P NMR spectroscopy of calf muscles coupled with MRI and ergometry].

One hundred patients presenting with exercise intolerance or rhabdomyolysis episodes have been examined successively by 31P Nuclear Magnetic Resonance Spectroscopy (MRS) of leg plantar flexor muscles with exercise test. In all cases a muscle biopsy was performed. At the end of investigations, diagnosis of a metabolic myopathy was made in 33 patients: glycogenolysis or glycolysis deficiency in 8 cases, mitochondrial myopathy in 24 cases and CPT II deficiency in one case. Muscular dystrophy or congenital myopathy were diagnosed in 6 cases. No precise etiology could be found in 30 patients with either high CK levels or muscle biopsy abnormalities. Seven patients had rhabdomyolysis related to excessive physical activities. Twenty-four patients had functional symptoms. The principal MRS parameters used for diagnosis were the values of intracellular pH at the end of exercise and the time constant of phosphocreatine resynthesis during recovery. Lack of acidosis after exercise was observed in all patients with blockade of glycogenolysis or glycolysis. A slowing in phosphocreatine resynthesis was found in 66 p.cent of patients with definite mitochondrial myopathy. The specificity of these parameters were respectively 92.4 p.cent and 85.5 p.cent for the two groups. In conclusion (31)P MRS allows the detection of muscular glycogenoses with a sensitivity close to 100 p.cent. However, its sensitivity was lower for the detection of mitochondrial myopathies, as is also known for the other in vivo metabolic investigations, reflecting the heterogeneity of expression of mitochondrial abnormalities in a given muscle. The integration of imaging in the examination protocol may help to orientate towards the diagnostic of a dystrophy in some patients.

Adolescent↗

PubMed2002

A comparison of voluntary and electrically induced contractions by interleaved 1H- and 31P-NMRS in humans.

Skeletal muscle voluntary contractions (VC) and electrical stimulations (ES) were compared in eight healthy men. High-energy phosphates and myoglobin oxygenation were simultaneously monitored in the quadriceps by interleaved (1)H- and (31)P-NMR spectroscopy. For the VC protocol, subjects performed five or six bouts of 5 min with a workload increment of 10% of maximal voluntary torque (MVT) at each step. The ES protocol consisted of a 13-min exercise with a load corresponding to 10% MVT. For both protocols, exercise consisted of 6-s isometric contractions and 6-s rest cycles. For an identical mechanical level (10% MVT), ES induced larger changes than VC in the P(i)-to-phosphocreatine ratio [1.38 +/- 1.14 (ES) vs. 0.13 +/- 0.04 (VC)], pH [6.69 +/- 0.11 (ES) vs. 7.04 +/- 0.07 (VC)] and myoglobin desaturation [43 +/- 15.9 (ES) vs. 6.1 +/- 4.6% (VC)]. ES activated the muscle facing the NMR coil to a greater extent than did VCs when evaluated under identical technical conditions. This metabolic pattern can be interpreted in terms of specific temporal and spatial muscle cell recruitment. Furthermore, at identical levels of energy charge, the muscle was more acidotic and cytoplasm appeared more oxygenated during ES than during VC. These results are in accordance with a preferential recruitment of type II fibers and a relative muscle hyperperfusion during ES.

Adenosine Diphosphate↗

PubMed2001

Determination of skeletal muscle perfusion using arterial spin labeling NMRI: validation by comparison with venous occlusion plethysmography.

T(1)-based determination of perfusion was performed with the high temporal and spatial resolution that monitoring of exercise physiology requires. As no data were available on the validation of this approach in human muscles, T(1)-based NMRI of perfusion was compared to standard strain-gauge venous occlusion plethysmography performed simultaneously within a 4 T magnet. Two different situations were investigated in 21 healthy young volunteers: 1) a 5-min ischemia of the leg, or 2) a 2-3 min ischemic exercise consisting of a plantar flexion on an amagnetic ergometer. Leg perfusion was monitored over 5-15 min of the recovery phase, after the air-cuff arterial occlusion had been released. The interesting features of the sequence were the use of a saturation-recovery module for the introduction of a T(1) modulation and of single-shot spin echo for imaging. Spatial resolution was 1.7 x 2.0 mm and temporal resolution was 2 s. For data analysis, ROIs were traced on different muscles and perfusion was calculated from the differences in muscle signal intensity in successive images. To allow comparison with the global measurement of perfusion by plethysmography, the T(1)-based NMR measurements in exercising muscles were rescaled to the leg cross-section. The perfusion measurements obtained by plethysmography and NMRI were in close agreement with a correlation coefficient between 0.87 and 0.92. This indicates that pulsed arterial techniques provide determination of muscle perfusion not only with superior spatial and temporal resolution but also with exactitude.

Adult↗

PubMed2001

Comparison of single-shot fast spin-echo and conventional spin-echo sequences for MR imaging of the heart: initial experience.

A conventional T1-weighted spin-echo (SE) magnetic resonance (MR) imaging sequence was compared with breath-hold and non-breath-hold half- Fourier single-shot fast SE MR sequences with black-blood preparation and high spatial resolution for imaging of various cardiac diseases. The optimized single-shot fast SE sequence provided better or equal image quality in less time. Breath-hold and non-breath-hold single-shot fast SE sequences may replace the conventional T1-weighted SE sequence for first-line cardiac MR imaging.

Adult↗

PubMed1999

Evidence for bi-exponential transverse relaxation of lactate in excised rat muscle.

To elucidate the low proton nuclear magnetic resonance (NMR) visibility of muscle lactate previously demonstrated in excised rat muscle, lactate transverse relaxation was investigated in the same model using double quantum editing sequences with effective echo times ranging from 55 to 475 msec. On this time scale, muscle lactate clearly exhibits a bi-exponential transverse relaxation with a short T2 of 33+/-5 msec (mean +/- SE, n = 3) and a long T2 of 230+/-10 msec. The relative populations (84+/-4% vs. 16+/-4%, respectively) of these two lactate pools are compatible with compartmentation between intra- and extracellular muscle lactate.

Animals↗

PubMed1999

Effect of chronic magnesium supplementation on magnesium distribution in healthy volunteers evaluated by 31P-NMRS and ion selective electrodes.

AIMS: The role of magnesium (Mg) intake in the prevention and treatment of diseases is greatly debated. Mg biodistribution after chronic Mg supplementation was investigated, using state-of-the-art technology to detect changes in free ionized Mg, both at extra- and intracellular levels. METHODS: Thirty young healthy male volunteers participated in a randomised, placebo (P)-controlled, double-blind trial. The treated group (MgS) took 12 mmol magnesium lactate daily for 1 month. Subjects underwent in vivo 31P-NMR spectroscopy and complete clinical and biological examinations, on the first and last day of the trial. Total Mg was measured in plasma, red blood cells and 24 h urine ([Mg]U ). Plasma ionized Mg was measured by ion-selective electrodes. Intracellular free Mg concentrations of skeletal muscle and brain tissues were determined noninvasively by in vivo 31P-NMR at 3T. NMR data were automatically processed with the dedicated software MAGAN. RESULTS: Only [Mg]U changed significantly after treatment (in mmol/24 h, for P, from 4.2+/-1.4 before to 4.1+/-1.3 after and, for MgS, from 3.9+/-1.1 before to 5. 1+/-1.1 after, t=2.15, P=0.04). The two groups did not differ, either before or after the trial, in any other parameter, whether clinical, biological or in relation with the Mg status. CONCLUSIONS: Chronic oral administration of Mg tablets to young healthy male volunteers at usual pharmaceutical doses does not alter Mg biodistribution. This study shows that an adequate and very complete noninvasive methodology is now available and compatible with the organization of clinical protocols which aim at a thorough evaluation of Mg biodistribution.

Adult↗

PubMed1998

13C/31P NMR studies of glucose transport in human skeletal muscle.

The muscle intracellular (IC) free glucose concentration and the rate of muscle glycogen synthesis were measured by using in vivo 13C and 31P NMR spectroscopy in normal volunteers under hyperinsulinemic ( approximately 300 pM) clamp conditions at the following three plasma glucose levels: euglycemia ( approximately 6 mM), mild ( approximately 10 mM), and high ( approximately 16 mM) hyperglycemia. In keeping with biopsy studies, muscle IC free glucose concentration at euglycemia (-0.03 +/- 0.03 mmol/kg of muscle, mean +/- SEM, n = 10) was not statistically different from zero. A small but statistically significant amount of IC free glucose was observed during mild and high hyperglycemia: 0.15 +/- 0.08 (n = 5) and 0.43 +/- 0.20 mmol/kg of muscle (n = 5), respectively. Muscle glycogen synthesis rate, in mmol per kg of muscle per min, was 111 +/- 11 at euglycemia (n = 10), 263 +/- 29 during mild hyperglycemia (n = 5), and 338 +/- 42 during high hyperglycemia (n = 5), these three rates being significantly different from each other. As previous in vitro and in vivo studies, these rates suggest a Km (concentration at which unidirectional glucose transport reaches half-maximal rate) of the muscle glucose transport system in the 15-25 mM range under hyperinsulinemic conditions. The low concentrations of muscle IC free glucose observed under hyperinsulinemic conditions were interpreted, with this estimate and in the framework of metabolic control theory, as glucose transport being the predominant step controlling muscle glucose flux not only at euglycemia but also during hyperglycemia.

Biological Transport↗

PubMed1998

Evidence of muscle BOLD effect revealed by simultaneous interleaved gradient-echo NMRI and myoglobin NMRS during leg ischemia.

The purpose of this work was to investigate the temporal relationship between intensity changes in T2*-weighted NMR images and tissue oxygen content, measured by myoglobin proton NMR spectroscopy, in the skeletal muscle. During an ischemic stress test, the calf muscles of five healthy volunteers were studied at 3 Tesla. An interleaved NMRI-NMRS sequence was used, which made it possible to record T2*-weighted images and myoglobin spectra simultaneously. During ischemia, rapid changes in muscle signal intensity were observed on T2*-weighted images, which immediately preceded myoglobin desaturation. Bearing in mind the respective P50 of hemoglobin and myoglobin, this observation clearly favored the hypothesis that hemoglobin desaturation was responsible for the changes in T2*. This interpretation was further supported by the temporal coincidence between the experimental NMR data and a model of hemoglobin desaturation solely derived from physiological considerations.

Adult↗

PubMed1998

1H NMR spectroscopy study of the dynamic properties of glycogen in solution by steady-state magnetisation measurement with off-resonance irradiation.

The dynamics of size-selected fractions of glycogen in solution have been investigated by proton NMR spectroscopy, using a recently described relaxation study method which relies on strong offresonance irradiation. The dependence of the steady-state magnetisation on angle and intensity of the effective radio-frequency field was measured and compared to theoretical curves derived from different models of motion. Absence or presence of contributions to relaxation from molecular motions on the microsecond time scale can be tested with this method, without having to resort to models. We found that glycogen dipolar relaxation did not result from isotropic Brownian rotation, and despite some contribution from slow motion (> 1 microsecond) to relaxation in glycogen alpha-particles extracted from rat liver, bulk movement of the molecules did not appear to participate in averaging the dipolar term to zero. Whereas hepatic glycogen rat beta-particles and commercial oyster glycogen displayed very similar relaxation properties, alpha-particles showed significantly different behaviour. However, all results were compatible with a diversity of movements within the molecule, ranging from freely rotating pyranoside rings through collective chain motion and possibly to bulk movement of the beta sub-units within the alpha-particle.

Animals↗

PubMed1998

Simultaneous measurement of perfusion and oxygenation changes using a multiple gradient-echo sequence: application to human muscle study.

We have developed a magnetic resonance imaging (MRI) technique based on a multiple gradient-echo sequence designed to probe perfusion and oxygenation simultaneously within skeletal muscle. Processing of the images acquired at successive echo times (TEs) generates two functional maps: one of the signal intensity (SI) extrapolated to zero echo time, which is sensitive to perfusion; and a second one of R2*, which reflects oxygenation. An advantage of the processing procedure lies in the selection of tissue of interest through the profile of T2* decay, leading to automatic rejection of pixels containing small vessels. This allows a more specific assessment of tissue perfusion and oxygenation. This technique was demonstrated successfully during post-ischemic reactive hyperemia in human calf. A perfusion peak of 123 mL x 100 g(-)1 x min(-1) was measured immediately after ischemia, whereas R2* value showed an 11.5% decrease at the same time, essentially reflecting blood oxygenation changes. Differences in the time courses of reperfusion and re-oxygenation were observed, oxygenation presenting a slower recovery. The mechanisms responsible for such a differential dynamic response are discussed.

Adult↗

PubMed1997

Simultaneous determination of muscle perfusion and oxygenation by interleaved NMR plethysmography and deoxymyoglobin spectroscopy.

A novel approach is presented that combines NMR-plethysmography and NMRS of deoxymyoglobin in real-time, using line-by-line interleaved acquisitions of both gradient echo images during venous occlusion and of the N-delta proton signal of myoglobin's proximal F8 histidine. This method allowed simultaneous measurement of peripheral regional perfusion and skeletal muscle oxygen content. During reactive hyperaemia, using our combined NMRI-NMRS protocol, we explored the relationship between muscle reoxygenation (myoglobin resaturation half-time, y in s) and reperfusion (x in ml/100 g tissue/min) and found it to be highly significant (y = 70.83x-0.94; r2 = 0.70; F = 64.40; p = 9.73 x 10(-9). We also demonstrated that at low flow, muscle perfusion was a rate-limiting factor to reoxygenation. Making certain hypotheses, muscle oxygen extraction was derived from perfusion and myoglobin resaturation rate. Muscle oxygen extraction during early post-ischemic recovery (0.78 +/- 0.11, 0.79 +/- 0.09 and 0.72 +/- 0.05 at 0, 60 and 100 Torr counter-pressure, respectively) was shown to be independent of perfusion and maximum at each step of the protocol in most volunteers but also to display significant variability among subjects in this supposedly normal population sample.

Adult↗

PubMed1997

Evidence for 100% 13C NMR visibility of glucose in human skeletal muscle.

The accuracy of the measurement of total muscle glucose by in vivo 13C NMR spectroscopy was tested in five normal volunteers during a euglycemic [1-13C]glucose infusion. The NMR visible concentration calibrated using an external reference was compared with that calculated from plasma glucose concentration, assuming that glucose remained extracellular. The NMR measurement always provided higher values than the calculation from plasma glucose: 0.51 +/- 0.035 (mean +/- SE) versus 0.38 +/- 0.005 mmol/liter of muscle on average. This systematic difference was interpreted as reflecting the presence of muscle glucose-6-phosphate, co-resonating with free glucose. Thus, glucose appeared to be virtually 100% NMR visible in human skeletal muscle.

Adult↗