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Biomedical subjects

A Leroy-Willig

Publications and source records attributed to A Leroy-Willig.

At least 19 recordsLinked to original sources
PubMed2001

Use of magnetic resonance imaging for noninvasive characterization and follow-up of an experimental injury to normal mouse muscles.

A magnetic resonance imaging protocol was tested in a cardiotoxin-induced myonecrosis of hindlimb muscles of three normal mice to assess the usefulness of data provided by longitudinal follow-up of a few individuals. Magnetic resonance imaging examinations were performed sequentially at 4 T between days 1 and 11 post-injury. Axial T1-weighted images after injection of a paramagnetic contrast agent were used to determine the volume of lesions from regions of increased signal intensity. T2 measurements were performed from a single-slice ten-echo acquisition centered upon the largest section of lesion. Early after injury, a very large T2 increase was observed. As recovery proceeded, T2 values progressively decreased toward normal values. Similarly, the volumes of lesions decreased to virtually zero by days 10-11. The evolution of these indices followed the same time scheme observed in histological studies. The use of a volume probe allowed accurate measurement of T2 values, and the acquisition of volumetric data. Such magnetic resonance imaging follow-up should help gather valuable information using few animals.

Animals↗
PubMed2000

Muscular transverse relaxation time measurement by magnetic resonance imaging at 4 Tesla in normal and dystrophic dy/dy and dy(2j)/dy(2j) mice.

Muscular transverse relaxation times values were measured in vivo in normal mice (strain C57BL6/J, n=14) and in murine models of human congenital muscular dystrophy (dy/dy, n=9; dy(2j)/dy(2j), n=8). A single-slice multi-echo sequence was used. Gastrocnemius/soleus complex, thigh and buttock muscles were studied. Muscular transverse relaxation times values were compared between different muscle groups in each type of animal and between animal groups. Differences were observed between normal and dy(2j)/dy(2j) mice from 3 to 12 weeks of age, and between normal and dy/dy mice at 6 weeks. In specific age ranges, the values of muscular transverse relaxation times in two dystrophic models are different from those in normal mice, and could thus be used as an index of modifications in dystrophic muscle to evaluate therapies.

Animals↗
PubMed1999

Cortical areas activated by bilateral galvanic vestibular stimulation.

The brain areas activated by bilateral galvanic vestibular stimulation (GVS) were studied using functional magnetic resonance imaging. In six human volunteers, GVS led to activation in the region of the temporoparietal junction, the central sulcus, and the anterior interior intraparietal sulcus, which may correspond to macaque areas PIVC, 3aV, and 2v, respectively. In addition, activation was found in premotor regions of the frontal lobe, presumably analogous to areas 6pa and 8a in the monkey. Since these areas were not detected in previous studies using caloric vestibular stimulation, they could be related to the modulation of otolith afferent activity by GVS. However, the simple paradigm used did not allow separation of the otolithic and semicircular canal effects of GVS. Further studies must be performed to clarify the question of cortical representation of the otolithic information in the human and monkey brain.

Adult↗
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

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

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↗
PubMed1998

Fat suppression techniques in MRI: an update.

Due to short relaxation times, fat has a high signal on magnetic resonance images (MRI). This high signal, easily recognized on MRI, may be useful to characterize a lesion. However, small amounts of lipids are more difficult to detect on conventional MRI. In addition, the high signal due to fat may be responsible for artifacts such as ghosting and chemical shift. Lastly, a contrast enhancing tumor may be hidden by the surrounding fat. These problems have prompted development of fat suppression techniques in MRI. Fat may be suppressed on the basis of its difference in resonance frequency with water by means of frequency selective pulses or phase contrast techniques, or on the basis of its short T1 relaxation time by means of inversion recovery sequences. Lastly, hybrid techniques combining several of these fat suppression techniques are also possible. The aim of this paper is to review the basic principles of all these fat suppression techniques and to exemplify their clinical use.

Adipose Tissue↗
PubMed1998

Functional MRI of galvanic vestibular stimulation.

The cortical processing of vestibular information is not hierarchically organized as the processing of signals in the visual and auditory modalities. Anatomic and electrophysiological studies in the monkey revealed the existence of multiple interconnected areas in which vestibular signals converge with visual and/or somatosensory inputs. Although recent functional imaging studies using caloric vestibular stimulation (CVS) suggest that vestibular signals in the human cerebral cortex may be similarly distributed, some areas that apparently form essential constituents of the monkey cortical vestibular system have not yet been identified in humans. Galvanic vestibular stimulation (GVS) has been used for almost 200 years for the exploration of the vestibular system. By contrast with CVS, which mediates its effects mainly via the semicircular canals (SCC), GVS has been shown to act equally on SCC and otolith afferents. Because galvanic stimuli can be controlled precisely, GVS is suited ideally for the investigation of the vestibular cortex by means of functional imaging techniques. We studied the brain areas activated by sinusoidal GVS using functional magnetic resonance imaging (fMRI). An adapted set-up including LC filters tuned for resonance at the Larmor frequency protected the volunteers against burns through radio-frequency pickup by the stimulation electrodes. Control experiments ensured that potentially harmful effects or degradation of the functional images did not occur. Six male, right-handed volunteers participated in the study. In all of them, GVS induced clear perceptions of body movement and moderate cutaneous sensations at the electrode sites. Comparison with anatomic data on the primate cortical vestibular system and with imaging studies using somatosensory stimulation indicated that most activation foci could be related to the vestibular component of the stimulus. Activation appeared in the region of the temporo-parietal junction, the central sulcus, and the intraparietal sulcus. These areas may be analogous to areas PIVC, 3aV, and 2v, respectively, which form in the monkey brain, the "inner vestibular circle". Activation also occurred in premotor regions of the frontal lobe. Although undetected in previous imaging-studies using CVS, involvement of these areas could be predicted from anatomic data showing projections from the anterior ventral part of area 6 to the inner vestibular circle and the vestibular nuclei. Using a simple paradigm, we showed that GVS can be implemented safely in the fMRI environment. Manipulating stimulus waveforms and thus the GVS-induced subjective vestibular sensations in future imaging studies may yield further insights into the cortical processing of vestibular signals.

Adult↗
PubMed1998

[Functional imaging of human muscle].

Medical imaging is now giving access not only to anatomy but also to functions of organs in the human body. Functional imaging may yield a direct appreciation of the function of a given organ, as is the case when measuring ejection fraction of heart with SPECT. Alternately the approach is indirect. This is the case of cerebral functional imaging, either with PET or NMR, where the perfusion increase induced by neuronal activity is detected. Recent developments of NMR, combining imaging and spectroscopy, allow now to detect modification of physiological parameters induced by muscular activity. Indirect detection of muscle activity is very rich in information alternately requiring invasive techniques. Water shifts resulting from intense exercise are detected either from muscle volume increase or water signal modifications, using simple NMR sequences. Then it is easy to identify which muscle is involved in a given protocol. These water shifts, studied in various muscles and several types of exercise protocols, reflect the perfusion increase induced by exercise, and the contribution of metabolic products such as lactate. In some patients with metabolic myopathies a decreased adaptation of perfusion has been detected. Perfusion measurements, previously performed by using venous occlusion plethysmography or radioactive tracers, now benefit from recently developed MR techniques. Oxygenation of muscle may be measured either by spectroscopy of myoglobin, allowing a time resolution of 1 second, or by spectroscopic imaging allowing a spatial resolution of 1-2 cm in a few minutes. Muscle temperature may be non invasively monitored by diffusion-weighted MR. Direct detection of muscle activity is useful only in those muscles that cannot be directly observed. Ultrafast MR imaging may be used to study vocal cords or oculomotor muscles. More interesting is the measurement of contractility, either in myocardium or skeletal muscle, allowed by MR with spin-tagging. Another contribution of MR to muscle studies is the possibility to quantify muscle cross section and muscle volume, in order to normalize strength or metabolism measurements. Sequences using T1 or T2 differences between muscular and adipose tissue allow to quantify the true muscular volume in patients with neuromuscular disorders. Protocols combining several of these parameters by interleaved NMR measurements of perfusion, phosphorylated metabolites, lactate, myoglobin, now open the way to many comprehensive non-invasive pathophysiological studies.

Body Water↗
PubMed1997

Body composition determined with MR in patients with Duchenne muscular dystrophy, spinal muscular atrophy, and normal subjects.

Magnetic resonance imaging was used to determine total fat mass of patients with neuromuscular disorders, accounting for intramuscular fat. Nineteen boys aged 9 to 12 (eight with Duchenne muscular dystrophy, three with type II spinal muscular atrophy and eight control subjects) underwent whole-body magnetic resonance imaging examination and anthropometric measurements. Whole-body fat mass was deduced from automated analysis of images normalized by a reference signal. Intramuscular and subcutaneous fat masses were deduced from manual analysis of twelve reference slices. Affected children significantly differed from control subjects for higher total fat mass, mostly related to intramuscular fat mass. Shorter protocols validated from whole-body data were shown to be more accurate than fat mass estimation derived from anthropometric measurements.

Adipose Tissue↗
PubMed1996

MR quantification of muscle fatty replacement in McArdle's disease.

McArdle's disease is an energy-dependent disorder of skeletal muscle caused by the inability to break down glycogen. The aim of this study was to quantify fatty replacement in patients with McArdle's disease. Calf and thigh axial spin echo T1-weighted magnetic resonance (MR) images (repetition time 500 ms, echo time 25 ms) were obtained at 0.5 T in nine patients with McArdle's disease (age 51 +/- 16 years, range 26-74) and nine sex- and age-matched healthy subjects (age 52 +/- 16 years, range 29-78) to quantify intramuscular fat. Regions of interest were drawn manually, encompassing the largest cross section of muscle. A fatty replacement index (IF) was determined from histograms of signal in the regions of interest in calf and thigh muscles. In normal subjects, IF = 3.6 +/- 2.8% in calf and 4.9 +/- 2.3% in thigh. In patients, IF = 11 +/- 9.3% in calf and 13.5 +/- 10.4% in thigh, significantly different from IF values in normal subjects (p = .03). IF correlated well with age in patients (p = .03). In older patients, up to 25% of the muscle volume was replaced by fat. Patients with McArdle's disease, usually weakly disabled, exhibit significant muscle fatty replacement on MR images. These findings suggest a progressive muscle loss over time related to the disease process.

Adipose Tissue↗
PubMed1995

Chronic mitochondrial energy impairment produces selective striatal degeneration and abnormal choreiform movements in primates.

Although the gene defect responsible for Huntington disease (HD) has recently been identified, the pathogenesis of the disease remains obscure. One potential mechanism is that the gene defect may lead to an impairment of energy metabolism followed by slow excitotoxic neuronal injury. In the present study we examined whether chronic administration of 3-nitropropionic acid (3-NP), an irreversible inhibitor of succinate dehydrogenase, can replicate the neuropathologic and clinical features of HD in nonhuman primates. After 3-6 weeks of 3-NP administration, apomorphine treatment induced a significant increase in motor activity as compared with saline-treated controls. Animals showed both choreiform movements, as well as foot and limb dystonia, which are characteristic of HD. More prolonged 3-NP treatment in two additional primates resulted in spontaneous dystonia and dyskinesia accompanied by lesions in the caudate and putamen seen by magnetic resonance imaging. Histologic evaluation showed that there was a depletion of calbindin neurons, astrogliosis, sparing of NADPH-diaphorase neurons, and growth-related proliferative changes in dendrites of spiny neurons similar to changes in HD. The striosomal organization of the striatum and the nucleus accumbens were spared. These findings show that chronic administration of 3-NP to nonhuman primates can replicate many of the characteristic motor and histologic features of HD, further strengthening the possibility that a subtle impairment of energy metabolism may play a role in its pathogenesis.

Animals↗
PubMed1995

Phospholipid abnormalities in early Alzheimer's disease. In vivo phosphorus 31 magnetic resonance spectroscopy.

OBJECTIVE: To determine whether changes in phosphomonoester and phosphodiester levels could be detected in vivo with phosphorus magnetic resonance spectroscopy in the early stage of Alzheimer's disease (AD). DESIGN: Survey-type of case-control study using neuropsychological testing as criterion standard with blinded data analysis. SETTING: Patients were from a neurology clinic in Paris, France. The controls were from the community. Magnetic resonance measurements were performed in the prefrontal region of the brain with a clinical 1.5-T scanner. Blinded data analysis. PARTICIPANTS: Twenty-four patients with mild AD and 15 age-matched healthy volunteers. Subjects were separated into two groups, both composed of patients with AD and healthy volunteers. Two successive acquisition protocols were used in the two groups. RESULTS: A significant increase in the phosphomonoester-total phosphorus ratio was found in patients with AD compared with controls. In this series, use of a ratio above 11% as a threshold to test our sample yielded an 83.3% sensitivity and a 73.3% specificity test for AD. Other metabolite ratios (inorganic phosphate, phosphodiesters, phosphocreatine, and nucleotide phosphates to total phosphorus) were not significantly different between patients and controls. No metabolite ratio correlated with the neuropsychological status as assessed by the Mini-Mental State Examination. CONCLUSION: Changes in phospholipid metabolism can be detected in vivo in the early stage of AD. Discrepancies in the literature may be due to differences in technical setting or in subject population types.

Aged↗
PubMed1995

Impairment of the exercise-induced increase in muscle perfusion in McArdle's disease.

In McArdle's disease (myophosphorylase deficiency) exercise intolerance is generally attributed to a lack of glycogenolysis, which decreases energy production during exercise. Magnetic resonance imaging data have recently suggested an impairment of the increase in muscle perfusion during exercise in these patients. We have tested this hypothesis by direct measurement of local muscle perfusion increase. Increase in muscle perfusion was assessed by positron emission tomography with oxygen-15 labelled water in five patients with McArdle's disease and five age- and sex-matched healthy volunteers. Radioactivity was measured in both forearms before and after exercise of the right forearm. The exercise intensity was biochemically assessed by in vivo phosphorus-31 magnetic resonance spectroscopy. The estimated increase in muscle perfusion with exercise was 5.7+/-5.5-fold in the patients (range 1.5-12.8) and 22.3+/-12.0-fold in the healthy subjects (range 10.1-37) (P=0.022). The results show a significant impairment of increase in muscle perfusion with exercise in McArdle's disease. Thus patients may suffer not only from a direct lack of glycogenolysis but also from indirectly impaired vasodilation.

Adult↗
PubMed1995

Simultaneous measurements of diffusion and transverse relaxation in exercising skeletal muscle.

The aim of this study was to compare proton T2 and apparent diffusion coefficient (ADC) variations induced by exercise in skeletal muscle, to provide some more information on the source of their variations. T2 and ADC were measured in the forearm flexor digitorum muscles in 12 healthy volunteers at rest and after an exercise, using a sequence allowing simultaneous measurements of both parameters. At rest, T2 was 30.6 +/- 1.8 ms (mean +/- 1 SD) and ADC was 1.82 +/- 0.11 x 10(-9) m2/s. With exercise, T2 varied by +2.8 +/- 12% (p < .001 vs. rest) and ADC varied by +12 +/- 3% (p < .001). The recovery of T2 after exercise was faster than that of ADC, with half-times of 7 +/- 2 min and of 15 +/- 8 min (p < .01), respectively. It is concluded that both T2 and ADC with exercise are probably different, T2 mostly reflecting changes in water content and ADC reflecting temperature variations.

Adult↗
PubMed1995

Is interictal temporal hypometabolism related to mesial temporal sclerosis? A positron emission tomography/magnetic resonance imaging confrontation.

The mechanism of interictal glucose hypometabolism remains unclear, but this abnormality occurs more frequently in temporal lobe epilepsy (TLE) than in other types of partial epilepsy. Therefore temporal hypometabolism has been suggested to reflect mesial temporal sclerosis (MTS). To investigate this, we selected 22 patients with refractory partial epilepsy of mesial temporal lobe origin (MTLE) who had hippocampal atrophy based on magnetic resonance imaging (MRI) volumetric analysis. We then analyzed the metabolic correlates of unilateral hippocampal atrophy. Thirteen temporal regions of interest (ROI) were defined on MRI scans for each individual and then applied to high-resolution FDG-positron emission tomography (PET) images obtained parallel to the long axis of the hippocampus. The most hypometabolic regions were the temporal pole and the hippocampal region. When we analyzed ensembles of temporal regions grouped into related networks, the temporolimbic network, which included the hippocampal region and the temporal pole, was abnormal in 95% of the patients at a 3-SD threshold. PET hypometabolism was highly correlated with the degree of hippocampal atrophy in this network, but not in other parts of the temporal lobe, which were less frequently hypometabolic. These data indicate that hypometabolism is a consequence of MTS in the temporolimbic region but not necessarily in the other parts of the temporal lobe. Our results also suggest that the combination of PET and MRI may facilitate the noninvasive diagnosis of MTLE.

Adult↗