Guillaume Duhamel

Imaging Experimental Cerebral Malaria In Vivo: Significant Role of Ischemic Brain Edema

The first in vivo magnetic resonance study of experimental cerebral malaria is presented. Cerebral involvement is a lethal complication of malaria. To explore the brain of susceptible mice infected with Plasmodium berghei ANKA, multimodal magnetic resonance techniques were applied (imaging, diffusion, perfusion, angiography, spectroscopy). They reveal vascular damage including blood-brain barrier disruption and hemorrhages attributable to inflammatory processes. We provide the first in vivo demonstration for blood-brain barrier breakdown in cerebral malaria. Major edema formation as well as reduced brain perfusion was detected and is accompanied by an ischemic metabolic profile with reduction of high-energy phosphates and elevated brain lactate. In addition, angiography supplies compelling evidence for major hemodynamics dysfunction. Actually, edema further worsens ischemia by compressing cerebral arteries, which subsequently leads to a collapse of the blood flow that ultimately represents the cause of death. These findings demonstrate the coexistence of inflammatory and ischemic lesions and prove the preponderant role of edema in the fatal outcome of experimental cerebral malaria. They improve our understanding of the pathogenesis of cerebral malaria and may provide the necessary noninvasive surrogate markers for quantitative monitoring of treatment.

Xenon-129 MR imaging and spectroscopy of rat brain using arterial delivery of hyperpolarized xenon in a lipid emulsion.

Hyperpolarized 129Xe dissolved in a lipid emulsion constitutes an NMR tracer that can be injected into the blood stream, enabling blood‐flow measurement and perfusion imaging. A small volume (0.15 ml) of this tracer was injected in 1.5 s in rat carotid and 129Xe MR spectra and images were acquired at 2.35 T to evaluate the potential of this approach for cerebral studies. Xenon spectra consistently showed two resonances, at 194.5 ppm and 199.0 ppm relative to the gas peak. The signal‐to‐noise ratio (SNR) obtained for the two peaks was sufficient (ranging from 12 to 90) to follow their time courses. 2D transverse‐projection xenon images were obtained with an in‐plane resolution of 900 μm per pixel (SNR range 8–15). Histological analysis revealed no brain damage except in two rats that had received three injections. Magn Reson Med 46:208–212, 2001.

Evaluation of systematic quantification errors in velocity‐selective arterial spin labeling of the brain

Velocity‐selective (VS) sequences potentially permit arterial spin labeling (ASL) perfusion imaging with labeling applied very close to the tissue. In this study the effects of cerebrospinal fluid (CSF) motion, radiofrequency (RF) field imperfections, and sequence timing parameters on the appearance and quantitative perfusion values obtained with VS‐ASL were evaluated. Large artifacts related to CSF motion were observed with moderate velocity weighting, which were removed by inversion recovery preparation at the cost of increased imaging time. Imperfect refocusing and excitation pulses resulting from nonuniform RF fields produced systematic errors in the ASL subtraction images. A phase cycling scheme was introduced to eliminate these errors. Quantitative perfusion images were obtained with CSF suppression and phase cycling. Gray matter blood flow of 27.7 ml 100 g–1 min–1, approximately half the value reported in studies using spatially‐selective ASL, was measured. Potential sources for this underestimation are discussed. Magn Reson Med 50:145–153, 2003.

Measurement of arterial input functions for dynamic susceptibility contrast magnetic resonance imaging using echoplanar images: Comparison of physical simulations with in vivo results

Measurement of the arterial input bolus shape is essential to the quantification of mean transit time and blood flow with dynamic susceptibility contrast (DSC) MRI. Input functions derived from the echoplanar signal intensity within or near arteries are highly nonlinear, yet such input functions are widely used. We employed a physical model for the echoplanar signal intensity from an artery as a function of contrast agent concentration, artery size, and angle to the magnetic field to test approaches for the measurement of the arterial input function. The simulated results confirmed the strong nonlinearity of signal in the neighborhood of vessels. Of the input function measurement methods considered, the simulations suggested that measurement of signal near but not within a large vessel is most accurate, but mean transit times (MTT) calculated with these input functions are highly sensitive to peak bolus concentration. Input functions determined from voxels demonstrating the shortest first moment overestimated the MTT but the measured MTTs were more robust to changes in peak concentration. Characteristics of the measured in vivo input functions were consistent with the simulations. Our results emphasize the important contribution of input function errors to the uncertainty in MTT and blood flow imaging with DSC MRI. Magn Reson Med, 2006.

Magnetization transfer from inhomogeneously broadened lines: A potential marker for myelin

To characterize a new approach to magnetization transfer (MT) imaging with improved specificity for myelinated tissues relative to conventional MT.

In vivo 129Xe NMR in rat brain during intra-arterial injection of hyperpolarized 129Xe dissolved in a lipid emulsion

Hyperpolarized 129Xe was dissolved in a lipid emulsion and administered to anaesthetized rats by manual injections into the carotid (approximately 1-1.5 mL in a maximum time of 30 s). During injection, 129Xe NMR brain spectra at 2.35 T were recorded over 51 s, with a repetition time of 253 ms. Two peaks assigned to dissolved 129Xe were observed (the larger at 194 +/- 1 ppm assigned to intravascular xenon and the smaller at 199 +/- 1 ppm to xenon dissolved in the brain tissue). Their kinetics revealed a rapid intensity increase, followed by a plateau (approximately 15 s duration) and then a decrease over 5 s. This behaviour was attributed to combined influences of the T1 relaxation of the tracer, of radiofrequency sampling, and of the tracer perfusion rate in rat brain. Similar kinetics were observed in experiments carried out on a simple micro-vessel phantom. An identical experimental set-up was used to acquire a series of 2D projection 129Xe images on the phantom and the rat brain.

Tract-specific and age-related variations of the spinal cord microstructure: a multi-parametric MRI study using diffusion tensor imaging (DTI) and inhomogeneous magnetization transfer (ihMT).

Being able to finely characterize the spinal cord (SC) microstructure and its alterations is a key point when investigating neural damage mechanisms encountered in different central nervous system (CNS) pathologies, such as multiple sclerosis, amyotrophic lateral sclerosis or myelopathy.

Global and regional cerebral blood flow measurements using NMR of injected hyperpolarized xenon-129

RATIONALE AND OBJECTIVES Xenon is an inert gas characterized by a nuclear halfspin and a high solubility in lipids. It appears to diffuse freely in biological tissues and, in particular, through the blood-brain barrier. Spin-exchange with optically pumped rubidiu mvapo rincrease sth enuclea rpolarizatio no f 129 Xe gas by several orders of magnitude above the polarization at thermal equilibrium, resulting in “hyperpolarized” (HP) xenon. HP xenon can be used as a magnetic resonance (MR) tracer because of its NMR-enhanced sensitivity combined with its high solubility. This HP tracer is a potential exogenous NMR probe for cerebral imaging studies. The purpose of this paper is to describe the preparation of this HP tracer and to demonstrate that it can be used in NMR for absolute cerebral perfusion measurements.

Spinal cord blood flow measurement by arterial spin labeling.

The assessment of spinal cord (SC) hemodynamics, and especially SC blood flow (SCBF), plays a key role in the pathophysiological description and understanding of many SC diseases such as ischemia, or spinal cord injury. SCBF has been previously measured in animals with invasive techniques such as autoradiography or labeled microspheres; no MR technique, however, has been proposed so far. The possibility of quantitatively measuring SCBF in mice using MRI was investigated using a presaturated FAIR (flow‐sensitive alternating inversion recovery) arterial spin labeling (ASL) technique. SCBF measurements were performed at the cervical level of the mouse as well as on the brain so as to use cerebral blood flow (CBF) values as internal references. With a spatial resolution of 133 × 133 μm2 for the SCBF maps, absolute regional perfusion values could be measured within the different structures of the SC (gray matter, white matter, and cerebrospinal fluid area). Similar perfusion values were found in SC gray matter (330 ± 90 mL/100g/min) and in brain (295 ± 22 mL/100g/min for thalamus). This result, in agreement with SCBF/CBF measurements performed with non‐MR techniques, opens new perspectives for noninvasive longitudinal and in vivo animal studies. Application to human experiments may also be possible. Magn Reson Med 59:846–854, 2008.

Experimental comparison of four FAIR arterial spin labeling techniques for quantification of mouse cerebral blood flow at 4.7 T.

Pulsed arterial spin labeling (ASL) is an attractive and robust method for quantification of rodent cerebral blood flow (CBF) in particular, although there is a need for sensitivity optimization. Look–Locker flow‐sensitive alternating inversion recovery (FAIR) echo planar imaging (EPI) (LLFAIREPI) was expected to be a likely candidate for assessing sensitivity, although it has not yet been applied to rodents. In this study, the performance of two FAIR techniques and two Look–Locker FAIR techniques were compared in mouse brain at 4.7 T. FAIR‐EPI (single inversion time, FAIREPI‐1TI), FAIR‐EPI (eight inversion times, FAIREPI‐8TI), LLFAIREPI and Look–Locker FAIR gradient echo (LLFAIRGE) sequences were implemented with equal spatial resolution and equal FAIR preparation modules. Measurements were carried out sequentially on the brain in 10 healthy mice, and quantitative CBF maps were obtained after different acquisition times up to 23 min. All methods gave similar group variability in CBF. Especially at shorter acquisition times, LLFAIREPI gave lower relative variations in CBF within selected brain regions than the other techniques at the same acquisition time. The Look–Locker techniques, however, overestimated CBF compared with classical FAIR‐EPI, which was attributed to bulk flow in arterioles and T2 effects. The image quality with LLFAIREPI was less reproducible within the group. Both FAIREPI‐1TI and LLFAIREPI appear to be good candidates for serial rapid measurement of CBF, but LLFAIREPI has the additional advantage that apparent T1 can be measured simultaneously with CBF. Copyright