The influence of skeletal muscle anisotropy on electroporation: in vivo study and numerical modeling

The aim of this study was to theoretically and experimentally investigate electroporation of mouse tibialis cranialis and to determine the reversible electroporation threshold values needed for parallel and perpendicular orientation of the applied electric field with respect to the muscle fibers. Our study was based on local electric field calculated with three-dimensional realistic numerical models, that we built, and in vivo visualization of electroporated muscle tissue. We established that electroporation of muscle cells in tissue depends on the orientation of the applied electric field; the local electric field threshold values were determined (pulse parameters: 8 × 100 μs, 1 Hz) to be 80 V/cm and 200 V/cm for parallel and perpendicular orientation, respectively. Our results could be useful electric field parameters in the control of skeletal muscle electroporation, which can be used in treatment planning of electroporation based therapies such as gene therapy, genetic vaccination, and electrochemotherapy

Les bases physico-chimiques du contraste en imagerie par résonance magnétique

L’Imagerie par Résonance Magnétique (IRM) a atteint au cours de la dernière décennie un niveau de développement technologique qui en fait une technique de mesure fiable et non destructrice. Cet article rappelle, dans une première partie, le principe de la localisation spatiale et de la mesure du signal en IRM. Dans une seconde partie, il examine différentes informations apportées par l’IRM, principalement dans le domaine biomédical, sur la relaxivité, le mouvement des spins et l’information chimique

Functional MRI of galvanic vestibular stimulation.

International audienceThe 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

Muscle energetics in fibromyalgia patients explored by magnetic resonance imaging and 31P-spectroscopy

Objectives: The aim of this study was to use magnetic resonance imaging and 31P spectroscopy in order to explore muscle metabolism during exercise in fibromyalgia patients. Methods: Eight women with fibromyalgia (FM) and 30 healthy volunteers were included in this study. Magnetic resonance imaging of the dominant leg was acquired in order to determine the maximal transverse section (MTS) of calf muscles and thus to calculate the different loads of exercise (dynamic plantar flexions). Subjects performed 3-6 bouts of 2 minutes with workload increments until exhaustion. Spectra were acquired continuously at rest, during the exercise and recovery periods. The analysis concerned the -, - and - ATP, Pi, PCr peaks, and intracellular pH. At the end of the exercise, a muscular efficacy index and the PCr re-phosphorylation time constant were calculated. Results: The MTS of the ankle plantar flexors reached respectively 43 7 cm² and 36.7 5 cm² in control and FM groups (p > 0.05). No significant difference (p > 0.05) was observed between both groups in spectroscopic data registered at rest [10.7 (control) vs 9.1 (FM) for PCr/Pirest ; 7.01 (control) vs 6.99 (FM) for pHrest] and at the end of exercise [1.18 (control) vs 0.68 (FM) for PCr/Piend ; 6.89 (control) vs 6.81 (FM) for pHend]. The muscular efficacy index was significantly reduced in FM patients (1.25) in comparison with control group (2.46) (p 0.05). Conclusions: This study did not indicate any abnormalities in glycolytic and oxydative pathways in FM patients. We demonstrated a low efficiency of chemical to mechanical energy shift in FM patients. These results suggested a deconditioning syndrome without primitive muscular abnormalities in FM patients and displayed the importance of aerobic muscular rehabilitation

Cortical areas activated by bilateral galvanic vestibular stimulation.

International audienceThe 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

Cortical areas activated by bilateral galvanic vestibular stimulation.

International audienceThe 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

Use of magnetic resonance imaging and 31p-spectroscopy to explore muscle energetics in fibromyalgia patients

Background: Fibromyalgia (FM) is defined as a chronic syndrome characterized by diffuse pain. FM patients generally complain of muscle fatigue during physical activities and symptoms worsening after exercise. Some studies have explored muscle performances in FM patients. Similarly, we reported that all variables of muscle performances were decreased in FM patients as compared to the controls [1]. We found that muscle impairment predominated over aerobic processes. The 31P nuclear magnetic resonance spectroscopy (NMRS) appears especially useful to study muscle energy metabolism because it is non-invasive and allows the exploration during exercise. Objectives: The purposes were: (1) to determine the maximal transverse section (MTS) of calf muscles by Magnetic Resonance Imaging (MRI) in order to calculate the individual mechanical loads of exercise without requiring the measurement of the maximal voluntary torque; (2) to monitor, by 31P-NMRS, high-energy phosphate metabolism and intracellular pH at rest, during exercise and recovery periods by means of continuous spectra acquisitions with an adequate temporal resolution; (3) to determine an original efficacy muscular index with the help of the ergometric and spectroscopic parameters; (4) to explore the oxidative pathway by means of determination of the PCr rephosphorylation time constant. Methods: Eight women with fibromyalgia (FM) and 30 healthy volunteers were included in this study. MRI of the dominant leg was acquired in order to determine the MTS of calf muscles and thus to calculate the different loads of exercise (dynamic plantar flexions). Subjects performed 3-6 bouts of 2 minutes with workload increments until exhaustion. Spectra were acquired continuously at rest, during the exercise and recovery periods. The analysis concerned the gamma-, alpha- and beta- ATP, Pi, PCr peaks, and intracellular pH. At the end of the exercise, the muscular efficacy index and the PCr re-phosphorylation time constant were calculated. Results: The MTS of the ankle plantar flexors reached respectively 43 cm² and 36.7 cm² in the control and FM groups (p > 0.05). No significant difference (p > 0.05) was observed between both groups in spectroscopic data registered at rest [10.7 (control) vs 9.1 (FM) for PCr/Pi rest ; 7.01 (control) vs 6.99 (FM) for pHrest] and at the end of exercise [1.18 (control) vs 0.68 (FM) for PCr/Pi end ; 6.89 (control) vs 6.81 (FM) for pHend]. However, the muscular efficacy index was significantly reduced in FM patients (1.25) in comparison with control group (2.46) (p 0.05). Conclusion: Our original protocol, not based on maximum voluntary contraction assessment, did not indicate any abnormalities in glycolytic and oxydative pathways in FM patients. We demonstrated a low efficiency of chemical to mechanical energy shift in FM patients. These results suggested a deconditioning syndrome without primitive muscular abnormalities in FM patients and displayed the importance of aerobic muscular rehabilitation. References: [1]Maquet D, Croisier JL, Renard C, Crielaard JM. Muscle performance in patients with fibromyalgia. J Bone Spine. 2002;69:293-9