Marie Poirier-Quinot

In vivo single cell detection of tumor-infiltrating lymphocytes with a clinical 1.5 Tesla MRI system

We demonstrate the feasibility of detecting individual tumor‐infiltrating cells in vivo, by means of cellular magnetic labeling and a 1.5 Tesla clinical MRI device equipped with a high‐resolution surface coil. Using a recently developed high‐temperature superconducting (HTS) surface coil, single cells were detected in vitro in voxels of (60 μm)3 at magnetic loads as low as 0.2 pg of iron per cell. The same imaging protocol was used in vivo to monitor infiltration of ovalbumin‐expressing tumors by transferred OVA antigen‐specific cytotoxic lymphocytes with low iron load. Magn Reson Med 60:1292–1297, 2008.

Active Trans-Plasma Membrane Water Cycling in Yeast Is Revealed by NMR

Plasma membrane water transport is a crucial cellular phenomenon. Net water movement in response to an osmotic gradient changes cell volume. Steady-state exchange of water molecules, with no net flux or volume change, occurs by passive diffusion through the phospholipid bilayer and passage through membrane proteins. The hypothesis is tested that plasma membrane water exchange also correlates with ATP-driven membrane transport activity in yeast (Saccharomyces cerevisiae). Longitudinal (1)H(2)O NMR relaxation time constant (T(1)) values were measured in yeast suspensions containing extracellular relaxation reagent. Two-site-exchange analysis quantified the reversible exchange kinetics as the mean intracellular water lifetime (τ(i)), where τ(i)(-1) is the pseudo-first-order rate constant for water efflux. To modulate cellular ATP, yeast suspensions were bubbled with 95%O(2)/5%CO(2) (O(2)) or 95%N(2)/5%CO(2) (N(2)). ATP was high during O(2), and τ(i)(-1) was 3.1 s(-1) at 25°C. After changing to N(2), ATP decreased and τ(i)(-1) was 1.8 s(-1). The principal active yeast ion transport protein is the plasma membrane H(+)-ATPase. Studies using the H(+)-ATPase inhibitor ebselen or a yeast genetic strain with reduced H(+)-ATPase found reduced τ(i)(-1), notwithstanding high ATP. Steady-state water exchange correlates with H(+)-ATPase activity. At volume steady state, water is cycling across the plasma membrane in response to metabolic transport activity.

Adipose Tissue Macrophages: MR Tracking to Monitor Obesity-associated Inflammation

PURPOSE To investigate whether cellular imaging by using ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance (MR) imaging can allow detection and quantification of adipose tissue macrophage-related inflammation within adipose tissue in a mouse model. MATERIALS AND METHODS Experimental protocols were conducted in accordance with French government policies. Adipose tissue macrophages were detected and quantified with a 4.7-T MR imager in ob/ob obese mice on the basis of the signal variance of adipose tissue triggered by injection of P904 iron oxide nanoparticles (USPIO). Mice were either intravenously injected with 1000 μmol of iron per kilogram of body weight of P904 (10 ob/ob and 11 ob/+) or used as noninjected control animals (seven ob/ob and six ob/+). Three-dimensional T2*-weighted gradient-echo MR images were acquired 10 days after intravenous injection. MR imaging signal variance in mice was correlated to adipose tissue macrophage quantification by using monoclonal antibody to F4/80 immunostaining, to proinflammatory marker quantification by using reverse transcription polymerase chain reaction (CCl2, Tnfα, Emr1), and to P904 quantification by using electron paramagnetic resonance imaging. Quantitative data were compared by using the Mann-Whitney or Student t test, and correlations were performed by using the Pearson correlation test. RESULTS MR imaging measurements showed a significant increase in adipose tissue signal variance in ob/ob mice compared with ob/+ controls or noninjected animals (P < .0001), which was consistent with increased P904 uptake by adipose tissue in ob/ob mice. There was a significant and positive correlation between adipose tissue macrophage quantification at MR imaging and P904 iron oxide content (r = 0.87, P < .0001), adipose tissue macrophage-related inflammation at immunohistochemistry (r = 0.60, P < .01), and adipose tissue proinflammatory marker expression (r = 0.55, 0.56, and 0.58 for CCl2, Tnfα, and Emr1, respectively; P < .01). CONCLUSION P904 USPIO-enhanced MR imaging is potentially a tool for noninvasive assessment of adipose tissue inflammation during experimental obesity. These results provide the basis for translation of MR imaging into clinical practice as a marker of patients at risk for metabolic syndrome.

Performance of a miniature high‐temperature superconducting (HTS) surface coil for in vivo microimaging of the mouse in a standard 1.5T clinical whole‐body scanner

The performance of a 12‐mm high‐temperature superconducting (HTS) surface coil for in vivo microimaging of mice in a standard 1.5T clinical whole‐body scanner was investigated. Systematic evaluation of MR image quality was conducted on saline phantoms with various conductivities to derive the sensitivity improvement brought by the HTS coil compared with a similar room‐temperature copper coil. The observed signal‐to‐noise ratio (SNR) was correlated to the loaded quality factor of the radio frequency (RF) coils and is theoretically validated with respect to the noise contribution of the MR acquisition channel. The expected in vivo SNR gain was then extrapolated for different anatomical sites by monitoring the quality factor in situ during animal imaging experiments. Typical SNR gains of 9.8, 9.8, 5.4, and 11.6 were found for brain, knee, back, and subcutaneous implanted tumors, respectively, over a series of mice. Excellent in vivo image quality was demonstrated in 16 min with native voxels down to (59 μm)3 with an SNR of 20. The HTS coil technology opens the way, for the first time at the current field strength of clinical MR scanners, to spatial resolutions below 10–3 mm3 in living mice, which until now were only accessible to specialized high‐field MR microscopes. Magn Reson Med 60:917–927, 2008.

Magnetic tagging of cell-derived microparticles: new prospects for imaging and manipulation of these mediators of biological information

AIMS Submicron membrane fragments termed microparticles (MPs), which are released by apoptotic or activated cells, are newly considered as vectors of biological information and actors of pathology development. We propose the tagging of MPs with magnetic nanoparticles as a new approach allowing imaging, manipulation and targeting of cell-derived MPs. MATERIALS & METHODS MPs generated in vitro from human endothelial cells or isolated from atherosclerotic plaques were labeled using citrate-coated 8 nm iron-oxide nanoparticles. MPs were tagged with magnetic nanoparticles on their surface and detected as Annexin-V positive by flow cytometry. RESULTS Labeled MPs could be mobilized, isolated and manipulated at a distance in a magnetic field gradient. Magnetic mobility of labeled MPs was quantified by micromagnetophoresis. Interactions of labeled MPs with endothelial cells could be triggered and modulated by magnetic guidance. Nanoparticles served as tracers at different scales: at the subcellular level by electron microscopy, at the cellular level by histology and at the macroscopic level by MRI. CONCLUSION Magnetic labeling of biogenic MPs opens new prospects for noninvasive monitoring and distal manipulations of these biological effectors.

Novel inductive decoupling technique for flexible transceiver arrays of monolithic transmission line resonators.

This article presents a novel inductive decoupling technique for form‐fitting coil arrays of monolithic transmission line resonators, which target biomedical applications requiring high signal‐to‐noise ratio over a large field of view to image anatomical structures varying in size and shape from patient to patient.

Implanted, inductively-coupled, radiofrequency coils fabricated on flexible polymeric material: application to in vivo rat brain MRI at 7 T.

Combined with high-field MRI scanners, small implanted coils allow for high resolution imaging with locally improved SNR, as compared to external coils. Small flexible implantable coils dedicated to in vivo MRI of the rat brain at 7 T were developed. Based on the Multi-turn Transmission Line Resonator design, they were fabricated with a Teflon substrate using copper micromolding process and a specific metal-polymer adhesion treatment. The implanted coils were made biocompatible by PolyDimethylSiloxane (PDMS) encapsulation. The use of low loss tangent material achieves low dielectric losses within the substrate and the use of the PDMS layer reduces the parasitic coupling with the surrounding media. An implanted coil was implemented in a 7 T MRI system using inductive coupling and a dedicated external pick-up coil for signal transmission. In vivo images of the rat brain acquired with in plane resolution of (150 μm)(2) thanks to the implanted coil revealed high SNR near the coil, allowing for the visualization of fine cerebral structures.

Preliminary ex vivo 3D microscopy of coronary arteries using a standard 1.5 T MRI scanner and a superconducting RF coil

This paper presents the feasibility of three-dimensional (3D) magnetic resonance (MR) histology of atheromatous coronary lesions in the entire human heart ex vivo using a standard 1.5 T scanner and a 12 mm high-temperature superconducting (HTS) surface coil. The HTS coil was a five-turn transmission-line resonator operated at 77 K, affording a signal-to-noise ratio (SNR) gain of about ninefold as compared to a similar, room-temperature copper coil. Local microscopy at the surface of an explanted, entire heart was achieved by a 3D spoiled gradient echo sequence and assessed by comparison with conventional histology. One hundred and twenty four adjacent cross sections of the coronary artery, with voxels of 59×59×100 μm3 and an SNR of about 20, were obtained in 25 min. Consecutive data sets were combined to reconstruct extended views along the artery. Compared to histology, MR microscopy allowed precise nondestructive 3D depiction of the architecture of the atheromatous plaques. This is the first report of microscopic details (less than 10−3 mm3 voxels) of diseased arteries obtained in an entire human heart preserving the arterial integrity and the spatial geometry of atheroma. This noninvasive microscopy approach using a HTS surface coil might be applied in vivo to study the architecture and components of superficial human structures, using routine MR scanners.

Method for nonlinear characterization of radio frequency coils made of high temperature superconducting material in view of magnetic resonance imaging applications

A contactless method based on reflectometry to accurately characterize an inductive radio frequency (rf) resonator even in the occurrence of a strong electrical nonlinearity is presented. Nonlinear extraction of the unloaded quality factor and resonance frequency is possible by combining an initial low-level swept-frequency calibration with high-level single-frequency measurements. The extraction protocol relies on a simple intrinsic R, L, C model and does not involve a fitting procedure according to a particular nonlinearity model. It includes a correction for strong coupling conditions between the probe and the rf coil, which allows extending the analysis over a wide range of transmitted power. Electrical modeling based on the extracted intrinsic data allows predicting the coil behavior when loaded by any kind of matching network. The method will have implications in different domains such as Magnetic Resonance (MR) applications with superconducting probe heads or analysis of rf properties in nonlinear materials. The method is demonstrated here by characterizing a high temperature superconducting (HTS) coil dedicated to MR imaging at 64 MHz. The coil consists in a multiturn spiral design that is self-resonant close to the MR frequency of interest. The Q factor and the resonance frequency are determined as a function of the actual power dissipated in the HTS coil accounting for losses occurring in the measurement system. Further characteristics of the HTS coil are considered in the present paper. The relation between the transmitted power and the magnetic field generated by the coil, which is the most relevant characteristics for MR applications, is directly accessible. The equivalent impedance of the coil under test is also expressed as a function of the total current flowing in the windings. The method could be extended to assess the fundamental properties of the nonlinear material (e.g., the London penetration depth or the critical current density) by including any pertinent model.

Multi-turn multi-gap transmission line resonators – Concept, design and first implementation at 4.7 T and 7 T

A novel design scheme for monolithic transmission line resonators (TLRs) is presented - the multi-turn multi-gap TLR (MTMG-TLR) design. The MTMG-TLR design enables the construction of TLRs with multiple turns and multiple gaps. This presents an additional degree of freedom in tuning self-resonant TLRs, as their resonance frequency is fully determined by the coil geometry (e.g. diameter, number of turns, conductor width, etc.). The novel design is evaluated at 4.7T and 7T by simulations and experiments, where it is demonstrated that MTMG-TLRs can be used for MRI, and that the B1 distribution of MTMG-TLRs strongly depends on the number and distribution of turns. A comparison to conventional loop coils revealed that the B1 performance of MTMG-TLRs is comparable to a loop coil with the same mean diameter; however, lower 10g SAR values were found for MTMG-TLRs. The MTMG-TLR design is expected to bring most benefits at high static field, where it allows for independent size and frequency selection, which cannot be achieved with standard TLR design. However, it also enables more accurate geometric optimization at low static field. Thereby, the MTMG-TLR design preserves the intrinsic advantages of TLRs, i.e. mechanical flexibility, high SAR efficiency, mass production, and coil miniaturization.