Franck Lethimonnier

Artifacts and pitfalls in diffusion MRI

Although over the last 20 years diffusion MRI has become an established technique with a great impact on health care and neurosciences, like any other MRI technique it remains subject to artifacts and pitfalls. In addition to common MRI artifacts, there are specific problems that one may encounter when using MRI scanner gradient hardware for diffusion MRI, especially in terms of eddy currents and sensitivity to motion. In this article we review those artifacts and pitfalls on a qualitative basis, and introduce possible strategies that have been developed to mitigate or overcome them. J. Magn. Reson. Imaging 2006.

Dynamic Study of Blood–Brain Barrier Closure after its Disruption using Ultrasound: A Quantitative Analysis

Delivery of therapeutic or diagnostic agents to the brain is majorly hindered by the blood–brain barrier (BBB). Recently, many studies have demonstrated local and transient disruption of the BBB using low power ultrasound sonication combined with intravascular microbubbles. However, BBB opening and closure mechanisms are poorly understood, especially the maximum gap that may be safely generated between endothelial cells and the duration of opening of the BBB. Here, we studied BBB opening and closure under magnetic resonance (MR) guidance in a rat model. First, MR contrast agents (CA) of different hydrodynamic diameters (1 to 65 nm) were employed to estimate the largest molecular size permissible across the cerebral tissues. Second, to estimate the duration of the BBB opening, the CA were injected at various times post-BBB disruption (12 minutes to 24 hours). A T1 mapping strategy was developed to assess CA concentration at the ultrasound (US) focal point. Based on our experimental data and BBB closure modeling, a calibration curve was obtained to compute the half closure time as a function of CA hydrodynamic diameter. These findings and the model provide an invaluable basis for optimal design and delivery of nanoparticles to the brain.

Optimized diffusion gradient orientation schemes for corrupted clinical DTI data sets

AbstractObject:A method is proposed for generating schemes of diffusion gradient orientations which allow the diffusion tensor to be reconstructed from partial data sets in clinical DT-MRI, should the acquisition be corrupted or terminated before completion because of patient motion. Materials and methods: A general energy-minimization electrostatic model was developed in which the interactions between orientations are weighted according to their temporal order during acquisition. In this report, two corruption scenarios were specifically considered for generating relatively uniform schemes of 18 and 60 orientations, with useful subsets of 6 and 15 orientations. The sets and subsets were compared to conventional sets through their energy, condition number and rotational invariance. Schemes of 18 orientations were tested on a volunteer. Results: The optimized sets were similar to uniform sets in terms of energy, condition number and rotational invariance, whether the complete set or only a subset was considered. Diffusion maps obtained in vivo were close to those for uniform sets whatever the acquisition time was. This was not the case with conventional schemes, whose subset uniformity was insufficient. Conclusion: With the proposed approach, sets of orientations responding to several corruption scenarios can be generated, which is potentially useful for imaging uncooperative patients or infants.

Regional assessment of wall curvature and wall stress in left ventricle with magnetic resonance imaging

Left ventricular functional abnormalities are associated with regional increases of wall stress and modifications of wall curvature. This study describes the integration of the short-axis and long-axis wall curvatures for determining peak systolic wall stress. Quantification was realized with cine magnetic resonance imaging (MRI) from the location of the endocardial and epicardial borders of the left ventricle on pairs of consecutive short-axis sections. Fifteen normal volunteers were subjected to cine MRI, and different methods of calculating peak systolic wall stress were compared. A short-axis analysis showed a 55 +/- 13% increase of the circumferential mean of the peak systolic wall stress between apical and basal sections. Regarding the curvature, no significant increase of wall stress was observed except on the septal wall (31 +/- 18%). Short-axis studies proved to be insufficient for determining the regional variations of left ventricular wall stress and for providing normal reference values for the location of abnormal regions in patients.

Three-dimensional coronary artery mr imaging using prospective real-time respiratory navigator and linear phase shift processing : Comparison with conventional coronary angiography

Respiratory gating with navigator echo is a recent technique to detect diaphragm position in 3D magnetic resonance (MR) coronary angiography. The purpose of our study was to image proximal coronary arteries and to detect significant stenoses in patients with coronary artery diseases and to compare with contrast enhanced angiography results. Twenty patients with coronary artery diseases who were referred for conventional angiography underwent magnetic resonance angiography (MRA). Three-dimensional gradient echo volumes were acquired using cardiac and respiratory gating and fat suppression. Using reformatted oblique planes and maximum intensity projection technique, visualization coronary segments and detection of significant coronary stenoses were made. Eighty-three coronary segments were analyzed. The sensitivity and specificity were 65% and 93%, respectively. The corresponding positive and negative predictive values were 69% and 91%. This study shows the ability to image correctly coronary arteries and to identify proximal stenoses, but image quality need to be improved for an efficiency detection of coronary artery stenoses in clinical practice.

A new paradigm for high-sensitivity 19F magnetic resonance imaging of perfluorooctylbromide

In the present work, the NMR properties of perfluorooctylbromide are revisited to derive a high‐sensitivity fluorine MRI strategy. It is shown that the harmful effects of J‐coupling can be eliminated by carefully choosing the bandwidth of the 180° pulses in a spin‐echo sequence. The T2 of the CF3 resonance of the molecule is measured using a multispin‐echo sequence and shown to dramatically depend on the interpulse delay. Following these observations, an optimized multispin‐echo imaging sequence is derived and compared with short TE/pulse repetition time gradient echo and chemical shift imaging sequences. The unparalleled sensitivity yielded by the multispin‐echo sequence is promising for future applications, in particular for targeted contrast agents such as perfluorooctylbromide nanoparticles. Magn Reson Med 63:1119–1124, 2010.

In vivo CEST MR imaging of U87 mice brain tumor angiogenesis using targeted LipoCEST contrast agent at 7 T

LipoCEST are liposome‐encapsulating paramagnetic contrast agents (CA) based on chemical exchange saturation transfer with applications in biomolecular MRI. Their attractive features include biocompatibility, subnanomolar sensitivity, and amenability to functionalization for targeting biomarkers. We demonstrate MR imaging using a targeted lipoCEST, injected intravenously. A lipoCEST carrying Tm(III)‐complexes was conjugated to RGD tripeptide (RGD‐lipoCEST), to target integrin ανβ3 receptors involved in tumor angiogenesis and was compared with an unconjugated lipoCEST. Brain tumors were induced in athymic nude mice by intracerebral injection of U87MG cells and were imaged at 7 T after intravenous injection of either of the two contrast agents (n = 12 for each group). Chemical exchange saturation transfer‐MSME sequence was applied over 2 h with an average acquisition time interval of 13.5 min. The chemical exchange saturation transfer signal was ∼1% in the tumor and controlateral regions, and decreased to ∼0.3% after 2 h; while RGD‐lipoCEST signal was ∼1.4% in the tumor region and persisted for up to 2 h. Immunohistochemical staining revealed a persistent colocalization of RGD‐lipoCEST with ανβ3 receptors in the tumor region. These results constitute an encouraging step toward in vivo MRI imaging of tumor angiogenesis using intravenously injected lipoCEST. Magn Reson Med, 2013.

High sensitivity 19F MRI of a perfluorooctyl bromide emulsion: application to a dynamic biodistribution study and oxygen tension mapping in the mouse liver and spleen

We have recently developed an optimized multi‐spin echo (MSE) sequence dedicated to perfluorooctyl bromide (PFOB) imaging yielding an excellent sensitivity in vitro. The aim of the present study was to apply this sequence to quantitative measurements in the mouse liver and spleen after intravenous (i.v.) injection of PFOB emulsions. We first performed oxygenation maps 25.5 min after a single infusion of emulsion and, contrary to previous studies, shortly after injection. The signal‐to‐noise ratio (SNR) in the liver and spleen was as high as 45 and 120, respectively, for 3‐min images with 11.7‐μL pixels. Values of oxygen tension tended to be slightly higher in the spleen than in the liver. Dynamic biodistribution experiments were then performed immediately after intravenous (i.v.) injection of PFOB emulsions grafted with different quantities of polyethylene glycol (PEG) for stealth. Images were acquired every 7 min for 84 min and the SNR measured in the liver and spleen was at least four from the first time point. Uptake rates could be assessed for each PEG amount and, in spite of high standard deviations (SDs) owing to interanimal variability, our data confirmed that increasing quantities of PEG allow more gradual uptake of the emulsion particles by the liver and spleen. In conclusion, our method seems to be a powerful tool to non‐invasively perform accurate in vivo quantitative measurements in the liver and spleen using 19 F MRI. Copyright

GLOBAL LEFT VENTRICULAR CARDIAC FUNCTION : COMPARISON BETWEEN MAGNETIC RESONANCE IMAGING, RADIONUCLIDE ANGIOGRAPHY, AND CONTRAST ANGIOGRAPHY

RATIONALE AND OBJECTIVES Cardiac magnetic resonance imaging (MRI) has been shown to be a robust and noninvasive method to assess left ventricular (LV) cardiac function. This study sought to assess volumes and mass calculated with MRI using fast techniques for acquisition and postprocessing, and to compare results in terms of cost-effectiveness with those of radionuclide angiography (RNA) or contrast angiography (CA). METHODS Thirty-five patients and 15 healthy volunteers were studied. All patients underwent an MRI examination during the same period that they underwent ventriculography (26 patients) or radiography (25 patients). From 7 to 11 short-axis slices were acquired with a breath-hold fast-gradient echo-segmented sequence from apex to base. Contours were drawn with an automated border detection software. RESULTS Ejection fraction (EF) correlated well between modalities (r = 0.77, P<0.001, for MRI and RNA; r = 0.72, P< 0.001, for MRI and CA). CONCLUSIONS Cardiac MRI is a fast and accurate technique for estimation of LV volumes, EF, and mass.

A new sequence for single-shot diffusion-weighted NMR spectroscopy by the trace of the diffusion tensor.

Diffusion‐weighted spectroscopy is a unique tool for exploring the intracellular microenvironment in vivo. In living systems, diffusion may be anisotropic, when biological membranes exhibit particular orientation patterns. In this work, a volume selective diffusion‐weighted sequence is proposed, allowing single‐shot measurement of the trace of the diffusion tensor, which does not depend on tissue anisotropy. With this sequence, the minimal echo time is only three times the diffusion time. In addition, cross‐terms between diffusion gradients and other gradients are cancelled out. An adiabatic version, similar to localization by adiabatic selective refocusing sequence, is then derived, providing partial immunity against cross‐terms. Proof of concept is performed ex vivo on chicken skeletal muscle by varying tissue orientation and intra‐voxel shim. In vivo performance of the sequence is finally illustrated in a U87 glioblastoma mouse model, allowing the measurement of the trace apparent diffusion coefficient for six metabolites, including J‐modulated metabolites. Although measurement performed along three separate orthogonal directions would bring similar accuracy on trace apparent diffusion coefficient under ideal conditions, the method described here should be useful for probing intimate properties of the cells with minimal experimental bias. Magn Reson Med, 2012.