MR imaging of relapsing multiple sclerosis patients using ultra-small-particle iron oxide and compared with gadolinium.

BACKGROUND AND PURPOSE: Inflammatory multiple sclerosis (MS) lesions are characterized by microglia activation and infiltration of T cells, B cells, and macrophages across the blood-brain barrier (BBB). In the experimental autoimmune encephalomyelitis (EAE) rat model of MS, previous MR imaging investigations with a new contrast agent ultra-small-particle iron oxide (USPIO) that accumulates in phagocytic cells revealed in vivo the presence of macrophage brain infiltration. The goal of this study was to characterize MS lesions with the use of this contrast agent. METHODS: A prospective MR imaging study of 10 patients with MS in acute relapses was achieved by using USPIO and gadolinium. RESULTS: Twenty-four hours after USPIO injection, 33 acute MS lesions in 9 patients showed USPIO uptake. Lesions were seen as high signal intensities on T1-weighted images and low signal intensities on T2-weighted images. Gadolinium enhancement was seen in 31 of these lesions in 7 patients. These 7 patients presented 24 gadolinium-enhanced lesions that did not enhance with USPIO. Two patients showed USPIO-enhanced lesions but no gadolinium-enhanced lesions. CONCLUSION: Taken together with earlier findings obtained in experimental models or in human stroke, the visualization of macrophage activity in vivo with USPIO characterize a distinct cellular and inflammatory event of the dynamic process of MS lesion formation. The macrophage activity information obtained with USPIO is distinct and complementary to the increased BBB permeability seen with gadolinium.

Early macrophage MRI of inflammatory lesions predicts lesion severity and disease development in relapsing EAE.

Magnetic resonance imaging (MRI) is of great utility in diagnosis and monitoring of multiple sclerosis (MS). Axonal loss is considered the main cause of accumulating irreversible disability. MRI using ultrasmall-super-paramagnetic-iron-oxide (USPIO) nanoparticles is a new technique to disclose in vivo central nervous system (CNS) inflammatory lesions infiltrated by macrophages in experimental autoimmune encephalomyelitis (EAE). Here, we raised the question of whether USPIO-enhanced MRI could serve as a tool to predict disease severity. We investigated, in a relapsing EAE model with various degrees of disease severity, the interindividual differences at the beginning of CNS inflammation as revealed in vivo by MRI with USPIO in correlation to the severity of both acute and chronic tissue damage including axonal loss. At the onset of the disease, observation of MRI alterations with USPIO allowed assignment of animals into USPIO+ and USPIO- groups. In 54.5% of diseased rats, MRI with USPIO+ at first attack revealed signal abnormalities mainly localized in the brainstem and cerebellum. Although animals did not present any clinically significant differences during the first attack, USPIO+ rats presented significantly more important tissue alterations at the first attack (onset and initiated recovery phase) and, at the second attack, more severe clinical disease with axonal loss compared to USPIO- rats. MRI lesion load and volume at the first attack correlate significantly with inflammation, macrophage recruitment, demyelination, acute axonal damage and, at the second attack, extent of axonal loss. This new MRI application of in vivo monitoring of macrophage infiltration provides a new platform to investigate the severity of inflammatory demyelinating CNS diseases.

Comparative overview of brain perfusion imaging techniques.

Numerous imaging techniques have been developed and applied to evaluate brain hemodynamics. Among these are: Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT), Xenon-enhanced Computed Tomography (XeCT), Dynamic Perfusion-computed Tomography (PCT), Magnetic Resonance Imaging Dynamic Susceptibility Contrast (DSC), Arterial Spin-Labeling (ASL), and Doppler Ultrasound. These techniques give similar information about brain hemodynamics in the form of parameters such as cerebral blood flow (CBF) or volume (CBV). All of them are used to characterize the same types of pathological conditions. However, each technique has its own advantages and drawbacks. This article addresses the main imaging techniques dedicated to brain hemodynamics. It represents a comparative overview, established by consensus among specialists of the various techniques. For clinicians, this paper should offers a clearer picture of the pros and cons of currently available brain perfusion imaging techniques, and assist them in choosing the proper method in every specific clinical setting.

Functional MR imaging analysis of pain-related brain activation after acute mechanical stimulation.

BACKGROUND AND PURPOSE: Most studies concerning imaging of pain processing have used thermal, chemical, or electrical nociceptive stimulation. The aim of the present study was to determine the cortical representation of mechanical pain. For this, using functional MR (fMR) imaging at 1.5 T, we compared activation patterns during painful and nonpainful tonic mechanical stimulation in healthy volunteers. METHODS: Eleven right-handed subjects ranging in age from 21 to 46 years underwent gradient-echo echo-planar fMR imaging while quantified tonic pressure was applied to the first metacarpophalangeal joint. Imaging parameters were 3,000/60 (TR/TE) with a 5-mm section thickness in a 7.30-minute sequence with 2 x 90 seconds of painful stimulation interleaved with 3 x 90 seconds of nonpainful stimulation. Functional images were processed using dedicated IDL software. RESULTS: Mechanical tonic nociceptive pressure was associated with activation of the primary somatosensory cortex contralateral to the hand stimulated and variable, often bilateral activation of the secondary somatosensory, temporal, anterior and posterior cingulate, insular, and prefrontal cortexes. Thalamic activation was inconsistent and always contralateral to stimulation. CONCLUSION: The interindividual variability found in this fMR imaging study calls for repetitive single-subject analysis or more extensive studies of large groups of patients. Either may be based on fMR imaging analysis of brain activation after tonic mechanically induced pain, which leads to deep pain sensation similar to patients' painful sensations most commonly encountered in clinical practice.

Effects of premedication with oral hydroxyzine on patient motion during inhalation of 32% xenon for regional cerebral blood flow mapping.

Because of its anesthetic properties, inhalation of 30-35% Xenon is associated with uncontrolled patient motion in 3-15% of the cases. This constitutes a major setback to regional cerebral blood flow studies with Xenon-enhanced computed tomography (Xe-CT CBF). The present study attempted to determine the effects of oral premedication with hydroxyzine (H) in the control of motion. Patients scheduled for Xe-CT CBF, aged 20-55 years, were randomly allocated to 3 groups: H 50 mg (n = 41), H 100 mg (n = 36) or Placebo (n = 43). The drugs were administered orally 90 minutes before Xenon inhalation. This consisted a gas mixture of 32% Xe and 25% oxygen. Motion was classified as controlled or uncontrolled depending on whether CBF data acquisition was possible or not. Anxiolysis and sedation were evaluated by a visual analogue scale. Motion was significantly reduced in the H 50 mg (0.8% vs 2.5% in the H 100 mg and 6.7% in the Placebo group). An anxiolytic effect of hydroxyzine was suggested.

Experimental allergic encephalomyelitis animal models for analyzing features of multiple sclerosis.

Various animal models with experimental allergic encephalomyelitis (EAE) have been developed applying immunologic, virologic, toxic and traumatic parameters in order to understand features of multiple sclerosis (MS). The main simulating aspects of the EAE models and the precautions for their interpretation in determining differences and common features between EAE and MS are presented. In view of an early diagnosis of CNS lesions in human, we present with particular interest the application of human-related technologies, such as MR imaging techniques, and the development of new markers to follow the dynamic of CNS lesions in vivo in EAE animal models.

Metastases from a pituitary adenoma: MRI.

Few cases of pituitary adenoma with metastases have been reported. We report a case with histologically benign intracranial and cauda equina metastases. We compare it to the others in the literature.

A functional magnetic resonance imaging study of mental subtraction in human subjects.

The neuronal network involved in a precise type of calculation procedure, mental subtraction, was investigated by means of functional magnetic resonance imaging. Two tasks were used requiring covert production of numbers: (1) with calculation; (2) without calculation. During the first task, activation was observed in the left dorsolateral prefrontal and premotor cortices, in Broca's area and bilaterally in the inferior parietal cortex. During the second task, activation was mainly observed in Broca's area and to a less extent in the left prefrontal and premotor cortices. Statistical comparison of data in the two situations revealed that the procedure of mental subtraction is mediated by a distributed system which includes predominantly the left dorsolateral prefrontal cortex and the inferior parietal cortex bilaterally.

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 micromol/kg Fe. The objective was to test the feasibility at the human recommended dose of 45 micromol/kg Fe. METHODS: Two groups of EAE rats were tested with AMI-227 using 45 and 300 micromol/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.

Age-related changes in the cervical spines of front-line rugby players.

Cervical spine trauma occurs frequently in front-line rugby players. To evaluate the accumulative effects of this trauma, magnetic resonance imaging scans of the cervical spine were performed on 47 rugby players and 40 age-matched control subjects. The aim of this study was to compare the changes in the cervical spine of players at different points in their careers. A study of cervical spine changes, including spinal curve, spinal constituents, posttraumatic deformities, and degenerative modifications, was completed by a study of cervical measurements. Front-line rugby players showed more early degenerative alterations on magnetic resonance imaging scans than did the control subjects of the same age. These changes correlated with age and were probably linked with repetitive cervical trauma throughout the players' careers. Particular attention should be paid to the data confirming cervical spine canal stenosis in front-line players, which may place these athletes at risk for acute neurapraxia while playing this collision sport.

[Influence of individual strategies on brain activation patterns during cognitive tasks]. / Influence des stratégies individuelles sur le patron d'activation cérébrale au cours de tâches cognitives.

Functional magnetic resonance imaging (fMRI) at 1.5 T was used to investigate the influence of cognitive strategies on cortical activation during mental calculation. Twenty-nine right-handed subjects performed a serial subtraction of prime numbers. Data were analyzed taking into account whether the spontaneous strategy of subjects was verbal (n = 15) or visual (n = 14). Even thought a common corpus of brain areas was activated during this mental calculation task, i.e. the dorsolateral prefrontal, premotor and parietal cortices, and Broca's area, differences appeared between the two groups of subjects. In subjects using a verbal strategy, the main activation was located in the whole left dorsolateral frontal cortex with a little activation of the inferior parietal cortices. In subjects using a visual strategy, a bilateral activation in the prefrontal cortex and a high activation in the left inferior parietal cortex were observed. These results demonstrate that numbers are processed through a distributed network of cortical areas, the lateralization of which is clearly influenced by subject strategy. Taken together this data reveals a functional interaction between the left inferior parietal cortex and the right prefrontal cortex in the visuo-spatial sketchpad for number processing. This network could be involved in sustained selective attention to mental numerical images generated in the left inferior parietal cortex.

Comparison of ultrasmall particles of iron oxide (USPIO)-enhanced T2-weighted, conventional T2-weighted, and gadolinium-enhanced T1-weighted MR images in rats with experimental autoimmune encephalomyelitis.

BACKGROUND AND PURPOSE: Ultrasmall particles of iron oxide (USPIO) constitute a contrast agent that accumulates in cells from the mononuclear phagocytic system. In the CNS they may accumulate in phagocytic cells such as macrophages. The goal of this study was to compare USPIO-enhanced MR images with conventional T2-weighted images and gadolinium-enhanced T1-weighted images in a model of experimental autoimmune encephalomyelitis (EAE). METHODS: Nine rats with EAE and four control rats were imaged at 4.7 T and 1.5 T with conventional T1- and T2-weighted sequences, gadolinium-enhanced T1-weighted sequences, and T2-weighted sequences obtained 24 hours after intravenous injection of a USPIO contrast agent, AMI-227. Histologic examination was performed with hematoxylin-eosin stain, Perls' stain for iron, and ED1 immunohistochemistry for macrophages. RESULTS: USPIO-enhanced images showed a high sensitivity (8/9) for detecting EAE lesions, whereas poor sensitivity was obtained with T2-weighted images (1/9) and gadolinium-enhanced T1-weighted images (0/9). All the MR findings in the control rats were negative. Histologic examination revealed the presence of macrophages at the site where abnormalities were seen on USPIO-enhanced images. CONCLUSION: The high sensitivity of USPIO for macrophage activity relative to other imaging techniques is explained by the histologic findings of numerous perivascular cell infiltrates, including macrophages, in EAE. This work supports the possibility of intracellular USPIO transport to the CNS by monocytes/macrophages, which may have future implications for imaging of human inflammatory diseases.

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.

Bilateral decrease in interictal hippocampal blood flow in unilateral mesiotemporal epilepsy.

OBJECT: The goal of this study was to determine whether regional cerebral blood flow (rCBF) changes that were found contralaterally to a verified unilateral epileptic focus were associated with the spatiotemporal organization of epileptic abnormalities. METHODS: The CBF in both hippocampi was assessed using stable Xe-enhanced computerized tomography in a series of 19 patients with unilateral mesiotemporal epilepsy. Results were compared according to the distribution of interictal spiking and the spatiotemporal organization of the ictal discharges as determined by stereoelectroencephalography. Two groups were defined: in Group 1 (nine patients), the discharge remained unilateral; in Group 2 (10 patients), the discharge spread to contralateral mesiotemporal structures. For Group 1, the rates of ipsi- and contralateral hippocampal blood flow (HBF) were 32.88+/-15.53 and 45.88+/-17.19 ml/100 g/minute, respectively, whereas in Group 2 they were 36.7+/-11.54 and 36.4+/-11.27 ml/100 g/minute (mean+/-standard deviation). A two-way analysis of variance combining type of seizure (Group 1 compared with Group 2) and HBF (ipsi- compared with contralateral absolute values) demonstrated a main effect for HBF (F[1,17] = 5.051; p = 0.0382), a significant interaction between the two factors (F[1,17] = 6.188; p = 0.0235), and no main effect for type of seizure (F[1,17] = 0.258; p = 0.6178). CONCLUSIONS: In unilateral mesiotemporal epilepsy, asymmetrical interictal hippocampal perfusion was correlated with restricted unilateral ictal discharges, whereas bilateral hippocampal hypoperfusion was correlated with ictal discharges spreading to the contralateral mesiotemporal structures. The lack of correlation between the degree of hypoperfusion and the percentage of neuron cell loss indicated that the decrease in rCBF has both functional and lesional origins.

[Evaluation of the efficacy of foraminal infusions of corticosteroids guided by computed tomography in the treatment of radicular pain by foraminal injection]. / Evaluation de l'efficacité des infiltrations foraminales de corticoïdes guidées sous tomodensitométrie, dans le traitement des radiculalgies par conflit foraminal.

PURPOSE: To evaluate the efficacy of foraminal steroid injections performed under CT guidance for the management of radicular pain. METHODS: Periganglionic infiltrations were performed in 160 patients with radicular pain refractory to medical treatment. Imaging showed either degenerative foraminal stenosis, herniated disk or postsurgical fibrosis. RESULTS: 102 patients (63.8%) had significant pain reduction. Pain relief was lasting in 68 (66.6%). CT showed the position of the needle tip, as well as the diffusion of the therapeutic compounds. CONCLUSION: We consider that CT-guided periganglionic steroid injections should be an integral part of the management strategy for radicular pain resistant to medical treatment.