Jean-François Le Bas

Macrophage imaging in central nervous system and in carotid atherosclerotic plaque using ultrasmall superparamagnetic iron oxide in magnetic resonance imaging

The long blood circulating time and the progressive macrophage uptake in inflammatory tissues of ultrasmall superparamagnetic iron oxide (USPIO) particles are 2 properties of major importance for magnetic resonance imaging (MRI) pathologic tissue characterization. This article reviews the proof of principle of applications such as imaging of carotid atherosclerotic plaque, stroke, brain tumor characterization, or multiple sclerosis. In the human carotid artery, USPIO accumulation in activated macrophages induced a focal drop in signal intensity compared with preinfusion MRI. The USPIO signal alterations observed in ischemic areas of stroke patients is probably related to the visualization of inflammatory macrophage recruitment into human brain infarction since animal experiments in such models demonstrated the internalization of USPIO into the macrophages localized in these areas. In brain tumors, USPIO particles which do not pass the ruptured blood-brain barrier at early times postinjection can be used to assess tumoral microvascular heterogeneity. Twenty-four hours after injection, when the cellular phase of USPIO takes place, the USPIO tumoral contrast enhancement was higher in high-grade than in low-grade tumors. Several experimental studies and a pilot multiple sclerosis clinical trial in 10 patients have shown that USPIO contrast agents can reveal the presence of inflammatory multiple sclerosis lesions. The enhancement with USPIO does not completely overlap with the gadolinium chelate enhancement. While the proof of concept that USPIO can visualize macrophage infiltrations has been confirmed in animals and patients in several applications (carotid atherosclerotic lesions, stroke, brain tumors and multiple sclerosis), larger prospective clinical studies are needed to demonstrate the clinical benefit of using USPIO as an MRI in vivo surrogate marker for brain inflammatory diseases.

A new approach for analyzing proton magnetic resonance spectroscopic images of brain tumors: nosologic images

A new approach for analyzing proton magnetic resonance spectroscopic images of brain tumors: nosologic images

Functional MRI of the human brain: Predominance of signals from extracerebral veins

This study demonstrates the predominance of extracerebral vascular signals in gradient-echo functional magnetic resonance imaging of motor activity at 1.5 Tesla. The demonstration is based upon a novel experimental approach. Maximum intensity projection images are derived from a large set of contiguous 2D functional MR images, and compared with MR angiograms obtained from the volume covered by the set of functional MR images. The comparison shows that the hyperintensities in the functional MR images cover extensive areas, which can be superimposed with a number of veins in the MR angiograms. These results should trigger a general caution in interpretation of the observations in 1.5 Tesla functional MRI.

Transient metabolic changes observed with proton MR spectroscopy in normal human brain after radiation therapy.

PURPOSE To observe the time course of the proton magnetic resonance spectroscopy (1H-MRS) variations due to radiation therapy on normal human brain. METHODS AND MATERIALS We followed 11 patients receiving an exclusive external radiation therapy for brain tumor for 8 months. They underwent proton MRS scans before any radiation exposure and 1, 4, and 8 months after they began the radiation therapy. The patients received 60 Gy in tumoral area fractionated over 6 weeks. The contralateral normal brain hemisphere received a radiation dose from 20 to 50 Gy. The main metabolite concentrations (N-acetylaspartate (NAA), choline compounds (Cho), creatine (Cr), and lactate (Lac) were evaluated by the areas of the peaks after peak fitting. Normalized values (NV) were obtained by processing the ratio of the peak area of a given metabolite to the sum of all the spectrum peak areas; ratios (NAA/Cho, NAA/Cr, and Cho/Cr) were processed. One patient, who received panencephalic radiotherapy (30 Gy) after metastasectomy from a primary kidney adenocarcinoma, has been monitored with 1H-MRS eight times for 6 months to observe the onset of the metabolic changes. RESULTS Changes were observed in irradiated normal brain tissue 4 months after radiation therapy began: the NAA/Cho and NAA/Cr ratios and the NAA (NV) decreased while the Choline (NV) increased. Four months later, normal values were recovered. CONCLUSION 1H-MRS has the potentiality to detect and to evaluate in vivo early adverse metabolic effects of radiation therapy in the normal human brain. These changes are significant 4 months after the radiation therapy began and appear to resolve over time.

Imaging of Subthalamic Nucleus and Ventralis Intermedius of the Thalamus

The techniques of targeting the subthalamic nucleus (STN) and the ventralis intermedius nucleus (Vim) are similar, only the coordinates are different. Targeting ideally consists of gathering all data about a target and positioning the electrode correctly within that target. The electrode should be positioned within a statistical range of coordinates, where the neuronal firing fits a given pattern and responds to external stimuli, particularly to proprioceptive inputs, in a somatotopically organized manner. Moreover, final placement should provide the best clinical improvement of symptoms under the stimulation parameters expected to be used in the long term. This latter criterion is by far the most important, because intraoperative findings indicate the functional benefit for the patient, which is the ultimate purpose of this surgery. A variety of radiological modalities are available to provide data for electrode placement, but each type has its drawbacks. Ventriculography, although safe when performed accordingly to strict technical procedure, is the most precise method but provides more indirect targeting and is more invasive than magnetic resonance imaging (MRI). MRI is the best method for visualizing the STN and, to some extent, for discerning the Vim, but it is plagued with unpredictable and nonreproducible deformations that induce a systematic distortion. These shortcomings no doubt will be corrected in the near future, and the technologies will better assist us in the proper placement of electrodes, which will provide the patient with the highest possible benefit.

Pyramidal tract side effects induced by deep brain stimulation of the subthalamic nucleus

Objective: To study the pyramidal tract side effects (PTSEs) induced by the spread of current from the subthalamic nucleus (STN) to the pyramidal tract (PT), in patients with parkinsonism undergoing STN stimulation. Methods: 14 patients bilaterally implanted with tetrapolar electrodes were assessed. For each side separately, the threshold of adverse effects induced by monopolar stimulation delivered by the chronically used contact was detected. The voltage was progressively increased until the patient experienced discomfort. All the PTSEs induced at 130 Hz (high-frequency stimulation (HFS)) and 2 or 3 Hz (low-frequency stimulation (LFS)) were videotaped. By superimposing the preoperative and postoperative MR images, the minimum distance (R) from the centre of the used contact to the medial border of the PT were measured. Results: The progressive increase in voltage at HFS induced tonic motor contractions, mainly located in the face, in 27/28 electrodes. LFS induced synchronous rhythmic myoclonus in the same territory. PTSEs induced at threshold voltage by HFS were observed in the upper face at 13/28 electrodes (bilaterally in six cases) and in the contralateral lower face at five electrodes. A positive correlation was found between the stimulus intensity capable of eliciting motor contractions at HFS and R. Conclusions: HFS of the STN preferentially activates the corticobulbar tract over the corticospinal tract. Therefore, cranial motor contractions need to be looked for during electrical parameter setting. The positive correlation between the electrical intensity threshold for PTSEs and R reflects the need for millimetre accuracy in electrode positioning.

Impaired fMRI Activation in Patients with Primary Brain Tumors

To characterize peritumoral BOLD contrast disorders, 25 patients referred for resection of primary frontal or parietal neoplasms (low-grade glioma (LGG) (n=8); high-grade glioma (HGG) (n=7); meningioma (n=10)) without macroscopic tumoral infiltration of the primary sensorimotor cortex (SM1) were examined preoperatively using BOLD fMRI during simple motor tasks. Overall cerebral BOLD signal was estimated using vasoreactivity to carbogen inhalation. Using bolus of gadolinium, cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) were estimated. In a 1cm(3) region-of-interest centered on maximal T-value in SM1 contralateral to movements, interhemispheric asymmetry was evaluated using interhemispheric ratios for BOLD and perfusion parameters. During motor tasks contralateral to the tumor, ipsitumoral sensorimotor activations were decreased in HGG and meningiomas, correlated to the distance between the tumor and SM1. Whereas CBV was decreased in ipsitumoral SM1 for HGG, it remained normal in meningiomas. Changes in basal perfusion could not explain motor activation impairment in SM1. Decreased interhemispheric ratio of the BOLD response to carbogen was the best predictor to model the asymmetry of motor activation (R=0.51). Moreover, 94.9+/-4.9% of all motor activations overlapped significant BOLD response to carbogen inhalation.

Absolute Cerebral Blood Volume and Blood Flow Measurements Based on Synchrotron Radiation Quantitative Computed Tomography

Synchrotron radiation computed tomography opens new fields by using monochromatic x-ray beams. This technique allows one to measure in vivo absolute contrast-agent concentrations with high accuracy and precision, and absolute cerebral blood volume or flow can be derived from these measurements using tracer kinetic methods. The authors injected an intravenous bolus of an iodinated contrast agent in healthy rats, and acquired computed tomography images to follow the temporal evolution of the contrast material in the blood circulation. The first image acquired before iodine infusion was subtracted from the others to obtain computed tomography slices expressed in absolute iodine concentrations. Cerebral blood volume and cerebral blood flow maps were obtained after correction for partial volume effects. Mean cerebral blood volume and flow values (n = 7) were 2.1 ± 0.38 mL/100 g and 129 ± 18 mL · 100 g–1 · min–1 in the parietal cortex; and 1.92 ± 0.32 mL/100 g and 125 ± 17 mL · 100 g–1 · min–1 in the caudate putamen, respectively. Synchrotron radiation computed tomography has the potential to assess these two brain-perfusion parameters.

Pre-orthographic character string processing and parietal cortex: A role for visual attention in reading?

The visual front-end of reading is most often associated with orthographic processing. The left ventral occipito-temporal cortex seems to be preferentially tuned for letter string and word processing. In contrast, little is known of the mechanisms responsible for pre-orthographic processing: the processing of character strings regardless of character type. While the superior parietal lobule has been shown to be involved in multiple letter processing, further data is necessary to extend these results to non-letter characters. The purpose of this study is to identify the neural correlates of pre-orthographic character string processing independently of character type. Fourteen skilled adult readers carried out multiple and single element visual categorization tasks with alphanumeric (AN) and non-alphanumeric (nAN) characters under fMRI. The role of parietal cortex in multiple element processing was further probed with a priori defined anatomical regions of interest (ROIs). Participants activated posterior parietal cortex more strongly for multiple than single element processing. ROI analyses showed that bilateral SPL/BA7 was more strongly activated for multiple than single element processing, regardless of character type. In contrast, no multiple element specific activity was found in inferior parietal lobules. These results suggests that parietal mechanisms are involved in pre-orthographic character string processing. We argue that in general, attentional mechanisms are involved in visual word recognition, as an early step of word visual analysis.

Functional MRI evidence for language plasticity in adult epileptic patients: Preliminary results

The present fMRI study explores the cerebral reorganisation of language in patients with temporal lobe epilepsy, according to the age of seizures onset (early or late) and the hippocampal sclerosis (associated or not). Seven right-handed control volunteers and seven preoperative adult epileptic patients performed a rhyme decision (language condition) and a visual detection (control condition) tasks in visually presented words and unreadable characters, respectively. All patients were left hemisphere dominant for language. Appropriate statistical analyses provided the following preliminary results: (1) patients compared with healthy subjects showed lower degree of hemispheric lateralization with supplementary involvement of the right hemisphere; (2) the degree of hemispheric specialization depends on the considered region; (3) patients with early seizures show signs of temporal and parietal reorganization more frequently than patients with late onset of seizures; (4) patients with early seizures show a tendency for intra-hemispheric frontal reorganisation; (5) associated hippocampal sclerosis facilitates the inter-hemispheric shift of temporal activation. Although our patients were left hemisphere predominant for language, the statistical analyses indicated that the degree of lateralization was significantly lower than in healthy subjects. This result has been considered as the indication of atypical lateralization of language.