Christophe Delalande

In vivo macrophage activity imaging in the central nervous system detected by magnetic resonance

Cell‐specific imaging has been proposed to increase the potential of magnetic resonance imaging (MRI) for tissue analysis. The hypothezis of the present work was that following intravenous injection of ultra‐small particle iron oxide, a contrast agent that accumulates in mononuclear phagocyte cells, macrophages with iron burden would be detectable by MRI within the central nervous system at sites of inflammatory cellular activity. In experimental autoimmune encephalomyelitis in Lewis rats (in which intense macrophage activity results from both hematogenous macrophages and activated microglia), lesions have been seen by MRI as low signal intensities related to magnetic susceptibility effects induced by iron particles. Electron microscopy has revealed the presence of such particles within the cytoplasm of cells that had the morphological aspect of macrophages. Macrophage activity imaging might increase MRI capability with regard to the in vivo pathophysiological aspects of central nervous system (CNS) diseases and might help in therapeutic trials in the numerous CNS diseases in which macrophages are involved. Magn Reson Med 41:329–333, 1999.

In vivo evaluation of remyelination in rat brain by magnetization transfer imaging

The aim of this work was to assess quantitatively and qualitatively the ability of magnetization transfer imaging to follow in vivo remyelination. Demyelination lesions were induced in rats by the injection of L-alpha-lysophosphatidylcholine stearoyl into the corpus callosum and imaging was performed in vivo on a 4.7-Tesla system at different time points. The percentage of magnetization transfer ratio (MTR) decrease was calculated for each animal. To evaluate the MTR findings for remyelination, myelin was quantitated by histological analysis of the lesion size and counting the number of remyelinating axons. An MTR decrease was observed when demyelination was present at 7 days after injection. During the remyelinating phase between day 30 and 40 after injection, contralateral values almost complete returned to normal, thus indicating remyelination. Histologically, at days 30 and 40 after injection, the lesion area was reduced in size and the axons were surrounded by a thin myelin sheath, indicating the remyelination process. Statistical analysis showed that the profile of MTR values was significantly correlated with the course of remyelination. All the MTR changes show a correlation with both myelin damage and repair. In conclusion, the study of the MTR profile in this myelin lesion model demonstrates in vivo the loss of myelin and the presence of spontaneous remyelination. This methodological approach which can also be applied to multiple sclerosis patients to show demyelination, should prove helpful to determine the degree of spontaneous and therapeutically induced remyelination in multiple sclerosis lesions, and thus to validate therapeutic treatments for myelin repair.

Fast lipid-suppressed MR temperature mapping with echo-shifted gradient-echo imaging and spectral-spatial excitation

The water proton resonance frequency (PRF) is temperature dependent and can thus be used for magnetic resonance (MR) thermometry. Since lipid proton resonance frequencies do not depend on temperature, fat suppression is essential for PRF‐based temperature mapping. The efficacy of echo‐shifted (TE > TR) gradient‐echo imaging with spectral‐spatial excitation is demonstrated, resulting in accurate and rapid, lipid‐suppressed, MR thermometry. The method was validated on phantoms, fatty duck liver, and rat thigh, demonstrating improvements in both the speed and precision of temperature mapping. Heating of a rat thigh with focused ultrasound was monitored in vivo with an accuracy of 0.37°C and a time resolution of 438 msec. Magn Reson Med 42:53–59, 1999.

On-line correction and visualization of motion during MRI-controlled hyperthermia.

Displacement of tissue during MRI‐controlled hyperthermia therapy can cause significant problems. Errors in calculated temperature may result from motion‐related image artifacts and inter‐image object displacement, leading to incorrect spatial temperature reference. Here, cyclic navigator echoes were incorporated in rapid gradient‐echo MRI sequences, used for temperature mapping based on the proton resonance frequency. On‐line evaluation of navigator information was used in three ways. First, motion artifacts were minimized in echo‐shifted (TE > TR) gradient‐echo images using the phase information of the navigator echo. Second, navigator profiles were matched for a quantitative evaluation of displacement. Together with a novel processing method, this information was employed to correct the reference temperature maps, thereby avoiding persistence of motion‐related temperature errors throughout the hyperthermic period. Third, on‐line visualization of displacement, together with temperature maps and thermal dose images, was developed, allowing physician intervention at all times. Examples are given of on‐line corrections during hyperthermia procedures with focused ultrasound and radiofrequency heat sources. Magn Reson Med 45:128–137, 2001.

Dose and scanning delay using USPIO for central nervous system macrophage imaging.

Rationale and objectives: In experimental allergic encephalomyelitis (EAE), central nervous system (CNS) macrophage imaging is achievable by MRI using AMI-227 an ultra-small particle iron oxide contrast agent at a dose of 300 μmol/kg Fe. The objective was to test the feasibility at the human recommended dose of 45 μmol/kg Fe.Methods: Two groups of EAE rats were tested with AMI-227 using 45 and 300 μmol/kg Fe respectively. Following i.v. injection of AMI-227, they were scanned after a delay of 4–6 and 20–24 h.Results: With a high dose of AMI-227, all animals showed low signal intensity related to iron-loaded macrophages in the CNS. At low dose no abnormalities were found in the CNS. Furthermore, a delay of 4–6 h failed to demonstrate abnormalities even at high dose.Conclusions: Dose, scanning delay after administration and blood half-life are major parameters for T2* CNS macrophage imaging.

MR imaging of intrarenal macrophage infiltration in an experimental model of nephrotic syndrome.

The objective of this study was to use MR imaging to detect macrophage infiltration of the kidney after injection of ultrasmall superparamagnetic iron oxide (USPIO) particles in a rat model of experimental nephropathy. Ninety μmol of USPIO were injected intravenously in 10 rats with nephropathy secondary to intravenous injection of 5 mg of puromycin aminonucleoside (PAN), and in 10 control rats. The signal intensity was measured in each kidney compartment before and 24 h after injection of the contrast agent. FLASH sequences were performed on a spectrometer operating at 4.7 T. MR findings were compared with histological data. Twenty‐four hours after injection of USPIO, a significant decrease (P < 0.0001) was observed in signal intensity in each kidney compartment in the PAN group. There was no variation in the control group. In the diseased kidneys, histological data revealed the presence of macrophages with iron oxide particles within their cytoplasm and lysosomes. Using USPIO, MR imaging can evidence infiltration of the rat kidney by macrophages. Magn Reson Med 41:156‐162, 1999.

An echo-shifted gradient-echo MRI method for efficient diffusion weighting

A segmented magnetic resonance imaging (MRI) method is introduced with time‐efficient diffusion weighting resulting in total imaging times similar to those of single‐shot methods. The approach is based on the principles of echo shifting with a train of observations (PRESTO) MRI sequence. The time efficiency of the sequence is based on the use of diffusion gradient pulses that also serve to shift the echo train to the next TR period, resulting in TE > TR. Each diffusion gradient is therefore used twice, for dephasing one set of spins as well as rephasing a second set of spins. Diffusion weighting and acquisition are thus achieved simultaneously. The sequence is validated in vitro and in vivo on rat kidney. Magn Reson Med 41:1000–1008, 1999.

Correlation between Clinical Status and Macrophage Activity Imaging in the Central Nervous System of Rats

In both multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), macrophages are involved ubiquitously (a) to promote inflammation by interacting with other immune cells, (b) to attack the myelin sheath, and (c) to function as scavengers for myelin debris (1,2). In pathologic conditions, intrinsic central nervous system (CNS) cells called microglia are rapidly and intensively activated, and blood monocytes are recruited (1,2). We described a method to investigate in vivo by magnetic resonance imaging (MRI) the activity of macrophagic cells using ultrasmall superparamagnetic iron oxide (USPIO) (3–6). The USPIO particles accumulate in macrophages due to the affinity of iron for the C3 complement receptor. Their long relaxivities induce a T1 and a T2 shortening (7), detectable by MRI in the CNS of animals with EAE (4,6). Because macrophages are closely related to the activity of inflammatory and demyelinating diseases, we aimed this experimental study at evaluating the relationship between the clinical symptoms of EAE and the abnormalities seen by macrophage activity imaging (MAI). Groups of animals with EAE were clinically followed during the 28 days after inoculation, and MRI using USPIO was performed every day from day 3 to day 15 after inoculation.

31P Magnetic resonance spectroscopy of human liver in elderly patients: Changes according to nutritional status and inflammatory state

Magnetic resonance spectroscopy (MRS) was used to determine the phosphorylated metabolite content in the liver of elderly patients in various nutritional states: normal, with protein deprivation, and with acute inflammatory syndrome. 31P-MRS investigations were performed at 1.5 T, and localized liver spectra were recorded using a two-dimensional chemical shift imaging sequence. Comparison to control spectra recorded on 10 healthy volunteers (age, 30.5 +/- 2.1 years) showed that the aging process does not significantly modify 31P-MRS liver spectra. Patients with protein deprivation exhibited a higher value than controls for the phosphomonoesters/nucleoside triphosphates (PME/NTP) ratio (P < .05). This increase was not due to the decrease of NTP, since the ratio of inorganic phosphate to NTP (Pi/NTP) remained constant. A decrease in the phosphodiesters to NTP (PDE/NTP) ratio (P < .04) contributed to the observed increase in the PME/PDE ratio (P < .01). In contrast, no significant difference in 31P-MRS spectra was found between elderly patients with hypoalbuminemia associated with inflammatory syndrome and the control group. We conclude that elderly patients with protein deprivation displayed changes in the level of phosphorylated metabolites in the liver that were not observed in the case of inflammatory syndrome despite lower serum albumin (Alb) concentrations.

Localised proton magnetic resonance spectroscopy of the brain after perinatal hypoxia : a preliminary report

Objectives. Perinatal hypoxic ischaemic injury is a significant cause of neurodevelopmental impairment. The aim of this study was to evaluate localised proton magnetic resonance spectroscopy (1H-MRS) after birth asphyxia. Materials and methods. Thirty newborn infants suspected of having perinatal asphyxia (Apgar score < 3) were studied. The mean gestational age was 37 weeks, mean age at the MR examination was 18 days and mean weight was 2.9 kg. A 1.5-T unit was used for imaging and spectroscopy. None of the babies had mechanically assisted ventilation. No sedation was used. Axial T1-weighted and T2-weighted images were obtained. 1H-MRS was recorded in a single voxel, localised in white matter, using a STEAM sequence. Results. Image quality was good in 25 of 30 babies. 1H-MRS was performed in 19 of 30 subjects, with adequate quality in 16. Choline, creatine/phosphocreatine and N-acetylaspartate peaks and peak-area ratios were analysed. Lactate was detected in four infants. The N-acetylaspartate/choline ratio was lower in infants with an impaired neurological outcome, but the difference was not statistically significant. Conclusions. This study suggests that 1H-MRS may be useful for assessing cerebral metabolism in the neonate. A raised lactate level and decreased N-acetylaspartate/choline ratio may be predictive of a poor outcome. However, in our experience this method is limited by the difficulty in performing the examination during the first hours after birth in critically ill babies, the problems related to use of a monovoxel sequence, the dispersion of the ratios and the lack of determination of the absolute concentration of the metabolites.