Biomedical engineering degrees at Lyon 1 University.

Biomedical diploma degrees have a long tradition at Lyon 1, Claude Bernard University. Since 2004, the transition towards the LMD system leaded to a unified Bachelor and Master Degree in Biomedical Engineering. A next evolution plans the creation of a Biomedical Engineering Department in the future Polytechnic School of Claude Bernard University. This department will form professionals in Biomedical Engineering, Medical Physics and for academic employment in Universities and research structures.

Investigation of NMR limits of detection for implantable microcoils.

Although NMR has the ability to investigate biological systems non-destructively, its low sensitivity primarily has hampered their investigation compared to other analytical techniques. Therefore, optimi zing radio frequency (RF) coils to improve sensitivity do offer benefits in MR spectroscopy (MRS). Sensitivity may be improved for mass- and volume-limited samples if the size of the detection RF coils matches the sample size. In this paper, the mass- and concentration-limit of detection (LOD(m), LOD(c)) for an implantable microcoil will be estimated by MRS measurements and then compared with their analytical values. For a sample containing a solution of several cerebral metabolites, for the Choline case, the LODm is 5.7 . 10(-9)mol and LODc of 3.8 mM. These preliminary results enable to open largely the biomedical applications based on cerebral metabolism investigation on small animal experiments.

NMR planar micro coils for micro spectroscopy: design and characterisation.

The goal of this study is to determine the concentration sensitivity and the limit of detection of a SNMR receiver planar micro coil with ellipsoidal geometry 1000x500 microm, fabricated using an electroplating technique and used as SNMR receiver coil at 200 MHz. The maximum signal intensity on the NMR images and simulation of RF field distribution allows defining an active volume of 0.8 microL. The localised spectroscopy based on a PRESS sequence shows that the concentration sensitivity is closed to S(C)=2.33 M(-1) and the limit of detection LOD=0.8 M. This micro-system offers the possibility of new investigation techniques based on implantable micro coils used for in vivo study of local cerebral metabolites occupying a small volume (microL to nL order).

Metabolite concentrations of healthy mouse brain by Magnetic Resonance Spectroscopy at 7 Tesla.

In vivo1H short echo-time Magnetic Resonance spectra are made up of overlapping spectral components from many metabolites. Typically, they exibit low signal-to-noise ratio. Metabolite concentrations are obtained by quantitating such spectra. Quantitation is difficult due to the superposition of metabolite resonances, macromolecules, lipids and water residue contributions. A fitting algorithm invoking extensive prior knowledge is needed. We quantitated1H in vivo mouse brain spectra obtained at 7 Tesla using the time-domain QUEST method combined with in vitro metabolite basis set signals. Brain metabolite concentrations estimated from eight mouse brain signals are compared to previously reported results.

Evaluation of adipose tissue distribution in obese fa/fa Zucker rats by in vivo MR imaging: effects of peroxisome proliferator-activated receptor agonists.

High-resolution MRI of obese (fa/fa) Zucker rats was investigated to characterize and assess in vivo adipose tissue distribution. Thirty animals were gavaged with a placebo, a PPARgamma activator (pioglitazone), or a dual PPARalphagamma activator (LM 4156). At day 15, T1-weighted images were acquired in vivo using a 2TMRI system with a high in-plane spatial resolution (254 microm). Fat volumes of selected territories were measured by image segmentation, and the retroperitoneal fat was weighed post-mortem. Body-weight gain was significant with pioglitazone (101.8+/-5.9 g, p<0.01 vs. placebo). The good quality of MR images allowed the delimitation and quantification of different fat territories. In response to pioglitazone, the retroperitoneal fat was more important compared to placebo (+23%, p<0.01) while subcutaneous fat was not different. No significant effects were observed with LM 4156. In vivo measurements of fat volumes were strongly correlated with ex vivo tissue weights (r=0.91). High-resolution MRI provides an in vivo measurement of adipose tissue distribution in obese Zucker rats. Specific fat depots of regions that were particularly involved in drug response were determined in vivo. Fat remodeling was observed with pioglitazone but not with a dual PPARalphagamma activator (LM 4156).

Contrast enhancement in atherosclerosis development in a mouse model: in vivo results at 2 Tesla.

To develop an MRI method for the evaluation of contrast enhancement in early atherosclerotic plaque development in the abdominal aorta of a mouse model. Male apoE-/- mice from three groups, respectively 4 (n = 6), 8 (n = 11) and 16 (n = 4) weeks were included. Axial T1 spin echo images of the abdominal aorta were obtained above and below the renal arteries (90 microm spatial resolution) before and over 1 h after the injection of a macromolecular contrast agent. Signal enhancement was measured in the vessel wall and compared to histological features. Maximal arterial wall signal enhancement was obtained from 16 to 32 min post injection. During this time, the signal-to-noise ratio increased by a factor up to 1.7 in 16 week mice and 2.7 and 2.4 in 8 and 4 weeks mice, respectively. The enhancement of the arterial wall appeared less pronounced in the oldest mice, 16 weeks old, exhibiting more advanced lesions. Using a macromolecular gadolinium agent, contrast uptake in atherogenesis varies with lesion stage and may be related to vessel-wall permeability. Dynamic contrast-enhanced MRI may be useful to evaluate the atherosclerotic plaque activity in mice.

Trabecular alveolar bone microarchitecture in the human mandible using high resolution magnetic resonance imaging.

OBJECTIVES: Cancellous bone microarchitecture in the mandible can influence the success of dental implant osseointegration. The aims of this study were to explore the feasibility of two-dimensional (2D) high resolution magnetic resonance imaging (MRI) for the evaluation of trabecular bone architecture and to compare architecture parameters derived from MR images between different areas in the mandible, and between sex and dental status. METHODS: 45 mandibular bone specimens (8 mm thickness) were cut from 15 fresh cadavers. MR images were obtained at 2 T using a multislice 2D spin-echo sequence. After MR image binarization, histomorphometry parameters, i.e. bone area fraction (BAF), specific perimeter (La), trabecular bone width (Tb.Wi), trabecular bone separation (Tb.Sp) and trabecular network anisotropy (R), were computed from the mean intercept length. The angle between trabeculae and tooth axis and the Euler-Poincaré characteristics (EPCs) were also computed. RESULTS: BAF, Tb.Wi and R were significantly higher in male specimens compared with female specimens, whereas Tb.Sp was significantly lower. The apparent Tb.Wi was found to be significantly higher in dentate specimens compared with edentulous ones. The highest anisotropy, corresponding to the smallest R value, was seen in the incisal specimens. The preferential orientation of the trabeculae was close to perpendicular to the tooth axis, especially in the molar specimens. CONCLUSION: BAF, La, Tb.Wi, Tb.Sp and R, the most variable parameters, may potentially have a relationship with the biomechanical competence of trabecular bone and play a role both in primary stabilization of dental implant and the time needed before loading.

MR perfusion imaging using encapsulated laser-polarized 3He.

In this work, the use of a new carrier agent for intravascular laser-polarized 3He imaging is reported. Lipid-based helium microbubbles were investigated. Their average diameter of 3 microm, which is smaller than that of the capillaries, makes it possible to conduct in vivo studies. The NMR relaxation parameters T1, T2, and T2* of a microbubble suspension were measured as 90 s, 300 ms, and 4.5 ms, respectively, and in vivo images of encapsulated 3He with signal-to-noise ratios (SNRs) larger than 30 were acquired. Dynamic cardiac images and vascular images of encapsulated 3He were obtained in rats using intravenous injections of microbubble suspensions. Excellent preservation of 3He polarization through the lung capillaries and heart cavities was observed. The first images of 3He microbubble distributions in the lungs were obtained. Additionally, the potential of this technique for lung perfusion assessment was validated through an experimental embolism model with the visualization of perfusion defects.

Atherosclerotic plaques: classification and characterization with T2-weighted high-spatial-resolution MR imaging-- an in vitro study.

PURPOSE: To evaluate if T2-weighted high-spatial-resolution magnetic resonance (MR) imaging (117 microm per pixel) can help accurate classification of atherosclerotic plaques. MATERIALS AND METHODS: Thirty human arteries and 11 carotid endarterectomy specimens from 31 patients underwent T2-weighted MR imaging (2-T magnet; repetition time, 2,000 msec; echo time, 50 msec) at room temperature. After imaging, Bouin fixative was used to fix 26 arteries, and the other 15 arteries were fixed by means of freezing. Specimens were stained with hematoxylin-eosin and safranin or Sudan lipid stain. MR images and histologic slices were classified independently by two radiologists and a pathologist, respectively, on the basis of the American Heart Association classification. RESULTS: Results with MR imaging were the following: type I-II plaques, sensitivity of 67% and specificity of 100%; type IV-Va plaques, sensitivity of 74% and specificity of 85%; type Vb plaques, sensitivity of 90% and specificity of 100%; type Vc plaques, sensitivity of 80% and specificity of 90%. No type III plaque was diagnosed in the study. The overall kappa value was 0.68. CONCLUSION: High-spatial-resolution MR imaging with T2 weighting alone can help accurate classification of fibrocalcic plaques (type Vb), but it is subject to limitations for the classification and analysis of other types of atherosclerotic plaques.

Vascular and perfusion imaging using encapsulated laser-polarized helium.

In this work, the use of hyperpolarized (HP) 3He for in vivo intravascular imaging on animal is reported. To overcome the problem of the low solubility of helium in blood, we propose an approach based on helium encapsulation in lipid-based carrier agents. The mean diameter of the 3He microbubbles, measured equal to 3.0+/-0.2 microm, makes it possible to conduct in vivo studies. In vitro spectroscopy yielded a longitudinal relaxation time T(1) equal to 90 s and an apparent transverse relaxation time T(2)(*) of 4.5 ms. Angiographic imaging (venous and cardiac cavity visualization), as well as lung perfusion imaging, were demonstrated in rats using intravenous injections of microbubble suspensions. Suitable signal and spatial resolution were achieved. The potential of this technique for lung perfusion assessment was assessed using an experimental animal embolism model. Lung perfusion defects and recovery towards a normal perfusion state were visualized. This study was completed with the demonstration of a new ventilation-perfusion lung exploration method based entirely on HP 3He.

Dipolar contrast for dense tissues imaging.

A new type of contrast called dipolar contrast is obtained by a decrease in the dipolar line broadening of protons. This contrast is usable for dense tissue NMR imaging and more generally for the study of dipolar linked protons in biological tissues. The sequence used is based on a variant of the Magic Sandwich Echoes (MSE) technique. In vitro experiments on a tendon sample are used to reinforce the image intensity of regions where the direct proton dipolar interaction exists.

The Ets transcription factor GABP is required for postsynaptic differentiation in vivo.

At chemical synapses, neurotransmitter receptors are concentrated in the postsynaptic membrane. During the development of the neuromuscular junction, motor neurons induce aggregation of acetylcholine receptors (AChRs) underneath the nerve terminal by the redistribution of existing AChRs and preferential transcription of the AChR subunit genes in subsynaptic myonuclei. Neural agrin, when expressed in nonsynaptic regions of muscle fibers in vivo, activates both mechanisms resulting in the assembly of a fully functional postsynaptic apparatus. Several lines of evidence indicate that synaptic transcription of AChR genes is primarily dependent on a promoter element called N-box. The Ets-related transcription factor growth-associated binding protein (GABP) binds to this motif and has thus been suggested to regulate synaptic gene expression. Here, we assessed the role of GABP in synaptic gene expression and in the formation of postsynaptic specializations in vivo by perturbing its function during postsynaptic differentiation induced by neural agrin. We find that neural agrin-mediated activation of the AChR epsilon subunit promoter is abolished by the inhibition of GABP function. Importantly, the number of AChR aggregates formed in response to neural agrin was strongly reduced. Moreover, aggregates of acetylcholine esterase and utrophin, two additional components of the postsynaptic apparatus, were also reduced. Together, these results are the first direct in vivo evidence that GABP regulates synapse-specific gene expression at the neuromuscular junction and that GABP is required for the formation of a functional postsynaptic apparatus.

Laser-polarized (3)He as a probe for dynamic regional measurements of lung perfusion and ventilation using magnetic resonance imaging.

Magnetic resonance imaging (MRI) using laser-polarized noble gases, such as (129)Xe and (3)He, allows unparalleled noninvasive information on gas distribution in lung airways and distal spaces. In addition to pulmonary ventilation, lung perfusion assessment is crucial for proper diagnosis of pathological conditions, such as pulmonary embolism. Magnetic resonance perfusion imaging usually can be performed using techniques based on the detection of water protons in tissues. However, lung proton imaging is extremely difficult due to the low proton density and the magnetically inhomogeneous structure of the lung parenchyma. Here we show that laser-polarized (3)He can be used as a noninvasive probe to image, in a single MRI experiment, not only the ventilation but also the perfusion state of the lungs. Blood volume maps of the lungs were generated based on the (3)He signal depletion during the first pass of a superparamagnetic contrast agent bolus. The combined and simultaneous lung ventilation and perfusion assessments are demonstrated in normal rat lungs and are applied to an experimental animal model of pulmonary embolism. Magn Reson Med 44:1-4, 2000.

Dynamic imaging of hyperpolarized (3)He distribution in rat lungs using interleaved-spiral scans.

The use of spiral scan techniques is investigated for (3)He lung imaging on small animals. Dynamic series of up to 40 high temporal resolution (3)He ventilation images are obtained using a single bolus of gas. General properties of the spiral technique are discussed and compared to those of standard imaging techniques in relation to the specific case of rare gas imaging. To improve temporal resolution of the image series, the efficiency of a sliding window technique, combining data from two consecutive spiral images, is demonstrated. An example of the typical global (3)He signal variation during the (3)He breathing of the animal is shown. Pixel-by-pixel measurements of the (3)He signal derivative during the gas inspiration are performed. A corresponding lung map of the magnetization per time unit entering the lung during gas inflow is presented.

Magnetic resonance imaging of rodent teeth.

In this paper, the anatomical structures of rat jaws are studied using magnetic resonance imaging (MRI) with high spatial resolution. In vivo microimages of teeth from 3- and 12-week-old (young and adult) rats have been performed. A 2 T nuclear magnetic resonance microscope was used to collect, with multiple orientations, non-invasive 2D data images using the spin-echo technique. MRI appears well suited to give images of the oral area and may represent a useful tool for diagnosis of dental diseases and more particularly of pulp pathologies.

A combined 1H perfusion/3He ventilation NMR study in rat lungs.

The assessment of both pulmonary perfusion and ventilation is of crucial importance for a proper diagnosis of some lung diseases such as pulmonary embolism. In this study, we demonstrate the feasibility of combined magnetic resonance imaging lung ventilation and perfusion performed serially in rat lungs. Lung ventilation function was assessed using hyperpolarized 3He, and lung perfusion proton imaging was demonstrated using contrast agent injection. Both imaging techniques have been implemented using projection-reconstruction sequences with free induction decay signal acquisitions. The study focused on fast three-dimensional (3D) data acquisition. The projection-reconstruction sequences used in this study allowed 3D data set acquisition in several minutes without high-performance gradients. 3D proton perfusion/helium ventilation imaging has been demonstrated on an experimental rat model of pulmonary embolism showing normal lung ventilation associated with lung perfusion defect. Assuming the possibility, still under investigation, of showing lung obstruction pathologies using 3He imaging, these combined perfusion/ventilation methods could play a significant clinical role in the future for diagnosis of several pulmonary diseases.

A new approach for on-resonance magnetization transfer parameter optimization.

On-resonance radio frequency pulse sequences for magnetization transfer are optimized using a frequency domain approach. The method presented here was developed using binomial pulses and it is demonstrated that a simple analysis leads to accurate sequence parameters that can be used directly for magnetic resonance imaging. With thus optimized parameters it is possible to produce an efficient saturation of protons having short transverse relaxation time while protons with long transverse relaxation time are kept nearly unaffected by the radio frequency. The method is particularly well suited to the design of new magnetization transfer sequences and to the estimation of the limits of the accuracy of a T2 selection. Additionally in vitro tests have been performed on beef tendon oriented with a zero fiber to field angle.