Danielle Ibarrola

Rapid-Clearance Iron Nanoparticles for Inflammation Imaging of Atherosclerotic Plaque: Initial Experience in Animal Model

PURPOSE To evaluate the use of a recently developed fast-clearing ultrasmall superparamagnetic iron oxide (USPIO) for detection of vascular inflammation in atherosclerotic plaque. MATERIALS AND METHODS The study protocol was approved by the animal experimentation ethics committee. A recently introduced USPIO, P904, and a reference-standard USPIO, ferumoxtran-10, were tested in a rabbit model of induced aortic atherosclerosis. In vivo magnetic resonance (MR) angiography and T2*-weighted plaque MR imaging were performed at baseline and after administration of P904 and ferumoxtran-10 (administered dose for both, 1000 micromol of iron per kilogram of body weight) in 26 hyperlipidemic New Zealand white rabbits. The variation in vessel wall area over time was evaluated with nonparametric testing. Ex vivo MR imaging findings were compared with iron content at linear regression analysis. RESULTS With in vivo MR imaging, plaque analysis was possible as early as 24 hours after P904 injection. The authors observed a 27.75% increase in vessel wall area due to susceptibility artifacts on day 2 (P = .04) and a 38.81% increase on day 3 (P = .04) after P904 administration compared with a 44.5% increase in vessel wall area on day 7 (P = .04) and a 34.8% increase on day 10 (P = .22) after ferumoxtran-10 administration. These susceptibility artifacts were correlated with intraplaque iron uptake in the corresponding histologic slices. The number of pixels with signal loss on the ex vivo MR images was linearly correlated with the logarithm of the iron concentration (P = .0001; R(2) = 0.93). CONCLUSION Plaque inflammation in rabbits can be detected earlier with P904 than with ferumoxtran-10 owing to the faster blood pharmacokinetics and the early uptake of P904 in the reticuloendothelial system. SUPPLEMENTAL MATERIAL http://radiology.rsnajnls.org/cgi/content/full/252/2/401/DC1.

Correlation of Diffusion and Metabolic Alterations in Different Clinical Forms of Multiple Sclerosis

Diffusion tensor imaging (DTI) and MR spectroscopic imaging (MRSI) provide greater sensitivity than conventional MRI to detect diffuse alterations in normal appearing white matter (NAWM) of Multiple Sclerosis (MS) patients with different clinical forms. Therefore, the goal of this study is to combine DTI and MRSI measurements to analyze the relation between diffusion and metabolic markers, T2-weighted lesion load (T2-LL) and the patients clinical status. The sensitivity and specificity of both methods were then compared in terms of MS clinical forms differentiation. MR examination was performed on 71 MS patients (27 relapsing remitting (RR), 26 secondary progressive (SP) and 18 primary progressive (PP)) and 24 control subjects. DTI and MRSI measurements were obtained from two identical regions of interest selected in left and right centrum semioval (CSO) WM. DTI metrics and metabolic contents were significantly altered in MS patients with the exception of N-acetyl-aspartate (NAA) and NAA/Choline (Cho) ratio in RR patients. Significant correlations were observed between diffusion and metabolic measures to various degrees in every MS patients group. Most DTI metrics were significantly correlated with the T2-LL while only NAA/Cr ratio was correlated in RR patients. A comparison analysis of MR methods efficiency demonstrated a better sensitivity/specificity of DTI over MRSI. Nevertheless, NAA/Cr ratio could distinguish all MS and SP patients groups from controls, while NAA/Cho ratio differentiated PP patients from controls. This study demonstrated that diffusivity changes related to microstructural alterations were correlated with metabolic changes and provided a better sensitivity to detect early changes, particularly in RR patients who are more subject to inflammatory processes. In contrast, the better specificity of metabolic ratios to detect axonal damage and demyelination may provide a better index for identification of PP patients.

Thalamus abnormalities during working memory in schizophrenia. An fMRI study

We aimed to identify and compare cerebral activations in schizophrenia patients and controls during a working memory (WM) task at the same performance level for both a verbal and a spatial task. Whereas the performances of the patients (n=22) and controls (n=15) were similar, cerebral activations were significantly increased in the patients, particularly in the thalamus/basal ganglia for the two tasks and in regions of the prefrontal cortex and the cerebellum for the spatial task only. Our results suggest that stronger activations of deep brain structures in patients may be the result from a compensating mechanism for WM difficulties.

Implementation of an Absolute Brain

Magnetic resonance spectroscopy has emerged as a sensitive modality to detect early and diffuse alterations in multiple sclerosis. Recently, the hypothesis of neurodegenerative pathogenesis has highlightened the interest for measurement of metabolites concentrations, to gain specificity, in a large brain volume encompassing different tissue alterations. Therefore, we proposed in this paper the implementation of an absolute quantification method based on localized spectroscopy at short (30 ms) and long (135 ms) echo time of a volume including normal appearing white matter, cortical gray matter, and lesions. First, methodological developments were implemented including external calibration, and corrections of phased-array coil sensitivity and cerebrospinal fluid volume contribution. Second, these improvements were validated and optimized using an original methodology based on simulations of brain images with lesions. Finally, metabolic alterations were assessed in 65 patients including 26 relapsing-remitting, 17 primary-progressive (PP), 22 secondary-progressive (SP) patients, and in 23 normal subjects. Results showed increases of choline, creatine, and myo-inositol concentrations in PP and SP patients compared to controls, whereas the concentration of N-acetyl compounds remained constant. The major finding of this study was the identification of Cho concentration and Cho/tNA ratio as putative markers of progressive onset, suggesting interesting perspectives in detection and followup of neurodegenerative processes.

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Of the 600-700 mg inorganic phosphate (Pi) removed during a 4-hour hemodialysis session, a maximum of 10% may be extracted from the extracellular space. The origin of the other 90% of removed phosphate is unknown. This study tested the hypothesis that the main source of phosphate removed during hemodialysis is the intracellular compartment. Six binephrectomized pigs each underwent one 3-hour hemodialysis session, during which the extracorporeal circulation blood flow was maintained between 100 and 150 ml/min. To determine in vivo phosphate metabolism, we performed phosphorous ((31)P) magnetic resonance spectroscopy using a 1.5-Tesla system and a surface coil placed over the gluteal muscle region. (31)P magnetic resonance spectra (repetition time =10 s; echo time =0.35 ms) were acquired every 160 seconds before, during, and after dialysis. During the dialysis sessions, plasma phosphate concentrations decreased rapidly (-30.4 %; P=0.003) and then, plateaued before increasing approximately 30 minutes before the end of the sessions; 16 mmol phosphate was removed in each session. When extracellular phosphate levels plateaued, intracellular Pi content increased significantly (11%; P<0.001). Moreover, βATP decreased significantly (P<0.001); however, calcium levels remained balanced. Results of this study show that intracellular Pi is the source of Pi removed during dialysis. The intracellular Pi increase may reflect cellular stress induced by hemodialysis and/or strong intracellular phosphate regulation.

H-MRS Quantification Method to Assess Different Tissue Alterations in Multiple Sclerosis

The purpose of the present study was to evaluate in vivo the effect of a non competitive antagonist of the NMDA receptor, eliprodil, on the size of a focal ischaemic insult and on its temporal evolution in a rat model, using a spin-echo diffusion magnetic resonance imaging multislice technique. Rats were either injected with 1 mg/kg i.v. of eliprodil or with the vehicle only (placebo) 5 min after middle cerebral artery occlusion, or not injected (controls). Ten coronal slices were acquired every hour, up to 7 h after occlusion of the artery, and the volume of hyperintense signals was measured at each time point and for each animal. Diffusion magnetic resonance images revealed that the administration of eliprodil reduced significantly (by 50% or more) the volume of ischaemia, up to 7 h after occlusion, particularly in the cortex of the ipsilateral hemisphere. The results show the potential efficacy of eliprodil to reduce the cerebral ischaemic volume after arterial occlusion, thus confirming the interest of glutamate receptor antagonists in the treatment of ischaemia.

Intracellular Phosphate Dynamics in Muscle Measured by Magnetic Resonance Spectroscopy during Hemodialysis

BACKGROUND MRI is routinely used in patients undergoing intracerebral electroencephalography (icEEG) in order to precisely locate the position of intracerebral electrodes. In contrast, fMRI has been considered unsafe due to suspected greater risk of radiofrequency-induced (RF) tissue heating at the vicinity of intracerebral electrodes. We determined the possible temperature change at the tip of such electrodes during fMRI sessions in phantom and animals. METHODS A human-shaped torso phantom and MRI-compatible intracerebral electrodes approved for icEEG in humans were used to mimic a patient with four intracerebral electrodes (one parasagittal and three coronal). Six rabbits were implanted with one or two coronal electrodes. MRI-induced temperature changes at the tip of electrodes were measured using a fibre-optic thermometer. All experiments were performed on Siemens Sonata 1.5T scanner. RESULTS For coronally implanted electrodes with wires pulled posteriorly to the magnetic bore, temperature increase recorded during EPI sequences reached a maximum of 0.6°C and 0.9°C in phantom and animals, respectively. These maximal figures were decreased to 0.2°C and 0.5°C, when electrode wires were connected to cables and amplifier. When electrode wires were pulled anteriorly to the magnetic bore, temperature increased up to 1.3°C in both phantom and animals. Greater temperature increases were recorded for the single electrode implanted parasagitally in the phantom. CONCLUSION Variation of the temperature depends on the electrode and wire position relative to the transmit body coil and orientation of the constant magnetic field (B0). EPI sequence with intracerebral electrodes appears as safe as standard T1 and T2 sequence for implanted electrodes placed perpendicular to the z-axis of the magnetic bore, using a 1.5T MRI system, with the free-end wires moving posteriorly, in phantom and animals.

The effect of eliprodil on the evolution of a focal cerebral ischaemia in vivo.

We hypothesized that children with benign childhood epilepsy with centrotemporal spikes (BCECTS) might have altered social cognitive skills and underlying neural networks.