Vincent Dousset

Comparative Overview of Brain Perfusion Imaging Techniques

Background and Purpose— Numerous imaging techniques have been developed and applied to evaluate brain hemodynamics. Among these are positron emission tomography, single photon emission computed tomography, Xenon-enhanced computed tomography, dynamic perfusion computed tomography, MRI dynamic susceptibility contrast, arterial spin labeling, and Doppler ultrasound. These techniques give similar information about brain hemodynamics in the form of parameters such as cerebral blood flow or cerebral blood volume. All of them are used to characterize the same types of pathological conditions. However, each technique has its own advantages and drawbacks. Summary of Review— 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. Conclusions— For clinicians, this article should offer a clearer picture of the pros and cons of currently available brain perfusion imaging techniques and assist them in choosing the proper method for every specific clinical setting.

MRI in multiple sclerosis: current status and future prospects

Many promising MRI approaches for research or clinical management of multiple sclerosis (MS) have recently emerged, or are under development or refinement. Advanced MRI methods need to be assessed to determine whether they allow earlier diagnosis or better identification of phenotypes. Improved post-processing should allow more efficient and complete extraction of information from images. Magnetic resonance spectroscopy should improve in sensitivity and specificity with higher field strengths and should enable the detection of a wider array of metabolites. Diffusion imaging is moving closer to the goal of defining structural connectivity and, thereby, determining the functional significance of lesions at specific locations. Cell-specific imaging now seems feasible with new magnetic resonance contrast agents. The imaging of myelin water fraction brings the hope of providing a specific measure of myelin content. Ultra-high-field MRI increases sensitivity, but also presents new technical challenges. Here, we review these recent developments in MRI for MS, and also look forward to refinements in spinal-cord imaging, optic-nerve imaging, perfusion MRI, and functional MRI. Advances in MRI should improve our ability to diagnose, monitor, and understand the pathophysiology of MS.

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.

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.

Cognitive impairment as marker of diffuse brain abnormalities in early relapsing remitting multiple sclerosis

Objectives: To establish the frequency of cognitive impairment in a population based sample of patients with recently diagnosed relapsing-remitting multiple sclerosis (RRMS), and to determine the relation between cognitive abnormalities and the extent of macroscopic and microscopic tissue damage revealed by magnetic resonance imaging (MRI) and magnetisation transfer (MT) imaging. Methods: 58 patients with RRMS consecutively diagnosed in the previous six months in Aquitaine and 70 healthy controls underwent a battery of neuropsychological tests. Lesion load and atrophy indices (brain parenchymal fraction and ventricular fraction) were measured on brain MRI. MT ratio (MTR) histograms were obtained from lesions, normal appearing white matter (NAWM), and normal appearing grey matter (NAGM). Gadolinium enhanced lesions were counted. Results: 44 RRMS patients could be individually matched with healthy controls for age, sex, and education. Patients performed worse in tests of verbal and spatial memory, attention, information processing speed, inhibition, and conceptualisation. Measures of attention and information processing speed were correlated with lesion load, mean NAWM MTR, and the peak location of the NAGM MTR histogram in the patients. Multivariate regression analysis showed that lesion load and mean NAWM MTR were among the MR indices that were most significantly associated with impairment of attention and information processing speed in these early RRMS cases. Conclusions: Cognitive impairment appears to be common in the early stages of RRMS, mainly affecting attention, information processing speed, memory, inhibition, and conceptualisation. The severity of these deficits reflects the extent of the lesions and the severity of tissue disorganisation outside lesions.

Psychiatric comorbidity in the evolution from migraine to medication overuse headache

We set out to study the role of psychiatric comorbidity in the evolution of migraine to medication overuse headache (MOH) by a comparative study of 41 migraineurs (MIG) and 41 patients suffering from MOH deriving from migraine. There was an excess risk of suffering from mood disorders [odds ratio (OR) = 4.5, 95% confidence interval (CI) 1.5, 13.5], anxiety (OR = 5, 95% CI 1.2, 10.7) and disorders associated with the use of psychoactive substances other than analgesics (OR = 7.6, 95% CI 2.2, 26.0) in MOH compared with MIG. Retrospective study of the order of occurrence of disorders showed that in the MOH group, psychiatric disorders occurred significantly more often before the transformation from migraine into MOH than after. There was no crossed-family transmission between MOH and psychiatric disorders, except for substance-related disorders. MOH patients have a greater risk of suffering from anxiety and depression, and these disorders may be a risk factor for the evolution of migraine into MOH. Moreover, MOH patients have a greater risk of suffering from substance-related disorders than MIG sufferers. This could be due to the fact that MOH is part of the spectrum of addictive disorders.

Primary and transitional progressive MS A clinical and MRI cross-sectional study

Background: Ten percent of patients with MS have a progressive course from onset with no history of relapses or remissions. A smaller subgroup follow a similar progressive course but have a single relapse at some point (transitional progressive [TP] MS). To date these patients have been excluded from receiving licensed treatments for MS and from most therapeutic trials. Objective: To document the clinical and MRI characteristics of a large cohort of progressive patients, including 158 with primary progressive (PP) MS and 33 with TPMS. Data from a small reference group of 20 patients with secondary progressive (SP) MS are also presented for reference. Methods: Patients were recruited from six European centers. All underwent a clinical assessment including scoring on the Expanded Disability Status Scale (EDSS) and MRI of the brain and spinal cord. Results: The men-to-women ratio was 81:77 (51% men) in the PP group, 14:19 (42% men) in the TP group, and 5:15 (25% men) in the SP group. The mean age at disease onset was significantly higher in the PP group than it was in the other two groups (PP 40.2 years, TP 34.9 years, SP 28.7 years). On MRI the PP group had lower mean brain T2 and T1 hypointensity lesion loads than the SP group (T2 12.02 versus 27.74 cm3, p = 0.001; T1 4.34 versus 7.04 cm3, p = 0.015). The SP and TP cohorts had significantly more T2-weighted lesions in the spinal cord than the PP patients, and the SP cohort had the greatest degree of atrophy. There was a correlation in the PP and TP patients between EDSS score and brain and spinal cord atrophy (r = 0.3, 0.2, p ≤ 0.006) but not with brain lesion load. The PP and TP patients who presented with spinal cord pathology had significantly lower brain T2 and T1 lesion loads than those with non-spinal cord presentations (p = 0.002). Conclusions: The monitoring of disease progression in PPMS is difficult, although measures of atrophy correlate with the EDSS and appear most promising. This study increases our understanding of this unique patient group, which will be further expanded with the acquisition of serial data.

Diffusion tensor MRI of the spinal cord

Apparent diffusion tensor (ADT) measurements on the spinal cord using a pulsed‐field‐gradient (PFG) multi‐shot echo‐planar imaging (EPI) sequence are presented. In a study of 10 healthy volunteers, the obtained rotationally invariant anisotropy information is compared to the results obtained by the rotationally dependent methods. The water diffusivity in the direction parallel to the fibers was found to be almost 2.5 times higher than the average diffusivity in directions perpendicular to the fibers and showed cylindrically symmetric anisotropy characteristics. The influence of partial volume effects and the point spread function on the measured results was evaluated, and it was the concluded that a resolution of 1 mm in the read and phase directions is required to obtain unbiased values. Possible clinical implications were demonstrated by investigating the diffusion characteristics of 10 patients suffering from narrowing of the cervical canal. The changes in the diffusion characteristics were found to be large enough to allow a robust detection of diffusion changes in the spine, even in cases in which conventional T2 and T1 weighted images were unable to detect any lesion. Magn Reson Med 44:884–892, 2000.

Early structural changes in acute MS lesions assessed by serial magnetization transfer studies

Background: Whether acute MS lesions are primarily inflammatory or demyelinative is unresolved. Our study examined acute MS lesions longitudinally by quantitative magnetization transfer (MT), an MRI technique that identifies tissue integrity and destruction. Methods: Four MS patients were studied by serial MRI including MT, conventional T2-weighted images, and postgadolinium T1-weighted images for 9 to 12 months. In 15 new lesions, the MT ratio (MTR) was calculated retrospectively. Results: In 13 lesions, a marked decrease in the MTR was present early during the first 2 months after the onset of the lesion and was followed by a variable increase. In two other lesions, the MTR progressively declined. Conclusions: These results suggest that major early structural changes compatible with demyelination and followed by remyelination and gliosis, or by continuous demyelination, occur in new MS lesions. The various MTR profiles provide in vivo confirmation of the current knowledge of the progression in MS lesions. Furthermore, MTR may be used to monitor in vivo drug efficacy in new MS lesions.

A multicenter measurement of magnetization transfer ratio in normal white matter

To assess the importance of intercenter variations when measuring magnetization transfer ratio (MTR) in the brain, six European centers measured MTR in normal white matter. MTR ranged from 9 to 51 percent units (25 sequences). The effective flip angle of the saturating pulse divided by the pulse repetition time (ENRsat degrees/msec) was a good predictor of MTR (MTR = 3.25 ENRsat).J. Magn. Reson. Imaging 1999; 9:441–446.