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Biomedical subjects

Laurent Lemaire

Publications and source records attributed to Laurent Lemaire.

9 recordsLinked to original sources

Dynamics of cerebral edema and the apparent diffusion coefficient of water changes in patients with severe traumatic brain injury. A prospective MRI study.

The distinction between intracellular (ICE) and extracellular edema (ECE) has a crucial prognostic and therapeutic importance in patients with severe traumatic brain injury (STBI). Indeed, ICE usually leads to cellular death, and maintenance of a cerebral perfusion pressure (CPP) above 70 mmHg is still under debate since this practice may increase ECE. The purpose of this study was to describe the ECE and ICE kinetics associated with STBI using quantitative diffusion MRI. Twelve patients were prospectively studied. The initial ADC in ICE measured on day 1.3+/-0.7 is significantly reduced compared to normal-appearing parenchyma (0.51+/-0.12 * 10(-3) mm2/s vs. 0.76+/-0.03 * 10(-3) mm2/s, n=12, P<0.0001) and reaches normality on MRI 3 performed on day 14.2+/-3.3. In patients presenting an extension of ICE on MRI 2 performed on day 6.7+/-1.4 (ADC(MRI2)=0.40+/-0.11 * 10(-3) mm2/s), ADC values in the extension area at the first MRI were slightly, but not significantly reduced compared to normal parenchyma (0.69+/-0.05 * 10(-3) mm2/s, P=0.29). Normalization occurred equally by day 14. ADC in ECE (1.34+/-0.22 * 10(-3) mm2/s) was elevated and stable with time under CPP therapy. Therefore, ECE is not worsened by CCP therapy, and ICE appears more relevant than ECE in STBI.

Adolescent↗

Single-scan quantitative T2* methods with susceptibility artifact reduction.

Two imaging methods, MSSAVE (Multiple echo SubSlice AVEraging imaging), based on sub-slice averaging and MGESEPI (Multiple echo Gradient-Echo Slice-Excitation Profile Imaging), based on over-sampling in the slice direction, are proposed for single-scan quantitative T(2)* evaluation with susceptibility artifact compensation. Their potentials in terms of sensitivity, minimum performance time, susceptibility artifact reduction and T(2)* quantitation quality, were compared with existing single-scan methods such as classical FLASH two- or three-dimensional or z-shimmed methods both in vitro and in vivo in normal rat brain. MGESEPI offered good quality T(2)* maps nearly free of artifacts but required a long acquisition time. MSSAVE was faster, but at the expense of reduced artifact compensation and the achievable T(2)* quantitation quality.

Animals↗

Texture analysis of magnetic resonance images of rat muscles during atrophy and regeneration.

OBJECTIVES: The goals of the current study were (i) to introduce texture analysis on magnetic resonance imaging (MRI-TA) as a noninvasive method of muscle investigation that can discriminate three muscle conditions in rats; these are normal, atrophy and regeneration; and (ii) to show consistency between MRI-TA results and histological results of muscle type 2 fibers' cross-sectional area. METHOD: Twenty-three adult female Wistar rats were randomized into (i) control (C), (ii) immobilized (I) and (iii) recovering (R) groups. For the last two groups, the right hind limb calf muscles were immobilized against the abdomen for 14 days; then, the hind limb was remobilized only for the R group for 40 days. At the end of each experimental period, MRI was performed using 7-T magnet Bruker Avance DRX 300 (Bruker, Wissembourg); T1-weighted MRI acquisition parameters were applied to show predominantly muscle fibers. Rats were sacrificed, and the gastrocnemius muscle (GM) was excised immediately after imaging. (A) Histology: GM type 2 fibers (fast twitch) were selectively stained using the adenosine triphosphatase (ATPase) technique. The mean cross-sectional areas were compared between the three groups. (B) Image analysis: regions of interest (ROIs) were selected on GM MR images where statistical methods of texture analysis were applied followed by linear discriminant analysis (LDA) and classification. RESULTS: Histological analysis showed that the fibers' mean cross-sectional areas on GM transversal sections represented a significant statistical difference between I and C rats (ANOVA, P<.001) as well as between R and I rats (ANOVA, P<.01), but not between C and R rats. Similarly, MRI-TA on GM transversal images detected different texture for each group with the highest discrimination values (Fisher F coefficient) between the C and I groups, as well as between I and R groups. The lowest discrimination values were found between C and R groups. LDA showed three texture classes schematically separated. CONCLUSION: Quantitative results of MRI-TA were statistically consistent with histology. MRI-TA can be considered as a potentially interesting, reproducible and nondestructive method for muscle examination during atrophy and regeneration.

Analysis of Variance↗

Assessment of myocardial viability in rats: Evaluation of a new method using superparamagnetic iron oxide nanoparticles and Gd-DOTA at high magnetic field.

The aim of this study was to detect salvageable peri-infarction myocardium by MRI in rats after infarction, using with a double contrast agent (CA) protocol at 7 Tesla. Intravascular superparamagnetic iron oxide (SPIO) nanoparticles and an extracellular paramagnetic CA (Gd-DOTA) were used to characterize the peri-infarction zone, which may recover function after reperfusion occurs. Infarcted areas measured from T1-weighted (T1-w) images post Gd-DOTA administration were overestimated compared to histological TTC staining (52% +/- 3% of LV surface area vs. 40% +/- 3%, P=0.03) or to T2-w images post SPIO administration (41% +/- 4%, P=0.04), whereas areas measured from T2-w images post SPIO administration were not significantly different from those measured histologically (P=0.7). Viable and nonviable myocardium portions of ischemically injured myocardium were enhanced after diffusive Gd-DOTA injection. The subsequent injection of vascular SPIO nanoparticles enables the discrimination of viable peri-infarction regions by specifically altering the signal of the still-vascularized myocardium.

Analysis of Variance↗

Influence of 5-fluorouracil-loaded microsphere formulation on efficient rat glioma radiosensitization.

PURPOSE: To determine (i) the efficiency of radiosensitizing 5-FU-loaded microspheres and (ii) the impact of microparticle formulation on response to treatment. METHODS: C6 tumor-bearing rats were stereotactically implanted with microspheres and/or allocated to: control groups (untreated) or treatment (only radiotherapy; fast-release 5-FU microspheres + radiotherapy; slow-release 5-FU microspheres + radiotherapy). The next day, fractionated radiotherapy, limited to the hemibrain, was initiated in all treated animals. The irradiation cycle included 36 Gy, given in 9 sessions for 3 consecutive weeks. Tumor development was assessed by T2-weighted MRI. RESULTS: 5-FU microspheres associated with radiotherapy caused a 47% complete remission rate (9/19) as opposed to the 8% rate (1/12) when radiotherapy alone or 0% in control animals. Drug delivery for 3 weeks produced better survival results (57%) compared to one-week sustained release (41%). MR images showed exponentially increasing tumor volumes during the first half of the radiotherapy cycle, followed by a decrease, and the disappearance of the tumor if survival exceeded 120 days. CONCLUSIONS: 5-FU controlled delivery is a promising strategy for radiosensitizing gliomas. Drug delivery system formulation is unambiguously implicated in both the response to treatment and the limitation of toxic side effects.

Animals↗

Anti-cancer drug diffusion within living rat brain tissue: an experimental study using [3H](6)-5-fluorouracil-loaded PLGA microspheres.

This study was performed (i) to monitor the diffusion of the anti-cancer drug 5-fluorouracil (5-FU) and (ii) to elucidate the fate of poly(lactide-co-glycolide) (PLGA) based microspheres within living rat brain tissue upon intracranial implantation. Drug-loaded microparticles were prepared using a solvent emulsion/extraction process and administered into healthy and C6 glioma-bearing Sprague-Dawley rats. The same surgical procedure was carried out with magnetite-loaded microspheres. To monitor 5-FU diffusion from the implantation site, tissue combustion was performed on animals implanted with tritiated drug microspheres. T2-weighted nuclear magnetic resonance imaging was undertaken on animals implanted with magnetite-loaded microspheres to determine microsphere localization after deposit. Results show that an important microparticle backflow occurs in healthy rats, whereas the microspheres remain at the site of administration in C6 glioma-bearing rats. Drug diffusion is limited to the vicinity of the implantation site.

Animals↗

Magnetic resonance imaging of the neuroprotective effect of xaliproden in rats.

RATIONALE AND OBJECTIVES: The neurotrophic effect of Xaliproden has been followed using sequential cerebral magnetic resonance imaging (MRI) in rats with vincristine-induced brain lesion as a model of Alzheimer disease. METHODS: Nineteen rats received an intraseptal injection of vincristine on day 0, followed by a daily gavage with either the vehicle (Tween-20 1%) (n = 10) or Xaliproden (10 mg/kg) (n = 9). Eight sham-operated controls received a daily gavage with either the vehicle (n = 4) or Xaliproden (n = 4). Brain MR imaging was performed at 4.7 T on a Biospec 47/30 MR system before surgery then 3, 7, 10, and 14 days after surgery. RESULTS: At day 3 following vincristine injection, an increase in MR signal intensity in the septum was observed on T2-weighted images. This increase was maximal at day 10, and remained stable until day 14. Daily treatment with Xaliproden delayed the appearance of hypersignals until day 7 and reduced by Ca. 50% the magnitude of the increase in signal intensity from day 10. No changes were observed in the hippocampus. CONCLUSION: Quantitative MRI objectifies noninvasively the neuroprotective effect of Xaliproden on rat brain anatomy.

Alzheimer Disease↗

Adoptive immunotherapy monitored by micro-MRI in experimental colorectal liver metastasis.

In this study we used the colon carcinoma DHDK12 cell line and generated single metastasis after subcapsular injection in BDIX rats as an experimental tumor model. The aim of the work was to set up in vitro experimental conditions to prepare immune effector cells and in vivo conditions for monitoring the effects of such cells injected as adoptive immunotherapy. Dendritic cells can process tumor cell antigens, induce a T-cell response and be used ex vivo to prepare activated lymphocytes. Lymphocytes were harvested from mesenteric lymph nodes and cocultured with bone marrow-derived autologous dendritic cells previously loaded with irradiated tumor cells. In vitro, the coculture: 1) induced the proliferation of lymphocytes, 2) expanded a preferential subpopulation of T CD8 lymphocytes, and 3) was in favor of lymphocyte cytotoxic activity against the DHDK12 tumor cell line. Activated lymphocytes were injected in the tumor-bearing rat portal vein. Parameters could be set to monitor tumor volume by micro MRI. This monitoring before and after treatment and immunohistochemical examinations revealed that: 1) micro MRI is an appropriate tool to survey metastasis growth in rat, 2) injected lymphocytes increase lesional infiltration with T CD8 cells even 15 days after treatment, 3) a dose of 50 millions lymphocytes is not sufficient to act on the course of the tumor.

Animals↗

Release kinetics of 5-fluorouracil-loaded microspheres on an experimental rat glioma.

BACKGROUND: Biodegradable loaded systems are promising devices for controlled and sustained release of anticancer drugs to brain tumours. We investigated the influence of drug-release profiles of 5-fluorouracil-loaded microspheres designed for the treatment of malignant gliomas. MATERIALS AND METHODS: 2.5 mg 5-FU delivered by either fast. (1 formulation) or slow-(2 formulations) 5-FU release microspheres (MS) were tested in C6-glioma rat brains. Tumor response was assessed by T2-weighted MRI. RESULTS: All treated animals, whatever the release profile considered, displayed a comparable 50% increase in life span versus controls. Delays in C6-glioma development appeared to correspond to the in vitro release periods of MS. In terms of curative prospect, complete remission was only observed in 11% of 5-FU-treated animals (4 out of 38). CONCLUSION: Formulation was unambiguously implicated in the response observed after local delivery of 5-FU to glioma.

Animals↗