Cyril Poupon

Diffusion tensor imaging: Concepts and applications

The success of diffusion magnetic resonance imaging (MRI) is deeply rooted in the powerful concept that during their random, diffusion‐driven displacements molecules probe tissue structure at a microscopic scale well beyond the usual image resolution. As diffusion is truly a three‐dimensional process, molecular mobility in tissues may be anisotropic, as in brain white matter. With diffusion tensor imaging (DTI), diffusion anisotropy effects can be fully extracted, characterized, and exploited, providing even more exquisite details on tissue microstructure. The most advanced application is certainly that of fiber tracking in the brain, which, in combination with functional MRI, might open a window on the important issue of connectivity. DTI has also been used to demonstrate subtle abnormalities in a variety of diseases (including stroke, multiple sclerosis, dyslexia, and schizophrenia) and is currently becoming part of many routine clinical protocols. The aim of this article is to review the concepts behind DTI and to present potential applications. J. Magn. Reson. Imaging 2001;13:534–546.

Regularization of diffusion-based direction maps for the tracking of brain white matter fascicles.

Magnetic resonance diffusion tensor imaging (DTI) provides information about fiber local directions in brain white matter. This paper addresses inference of the connectivity induced by fascicles made up of numerous fibers from such diffusion data. The usual fascicle tracking idea, which consists of following locally the direction of highest diffusion, is prone to erroneous forks because of problems induced by fiber crossing. In this paper, this difficulty is partly overcomed by the use of a priori knowledge of the low curvature of most of the fascicles. This knowledge is embedded in a model of the bending energy of a spaghetti plate representation of the white matter used to compute a regularized fascicle direction map. A new tracking algorithm is then proposed to highlight putative fascicle trajectories from this direction map. This algorithm takes into account potential fan shaped junctions between fascicles. A study of the tracking behavior according to the influence given to the a priori knowledge is proposed and concrete tracking results obtained with in vivo human brain data are illustrated. These results include putative trajectories of some pyramidal, commissural, and various association fibers.

The early development of brain white matter: a review of imaging studies in fetuses, newborns and infants

Studying how the healthy human brain develops is important to understand early pathological mechanisms and to assess the influence of fetal or perinatal events on later life. Brain development relies on complex and intermingled mechanisms especially during gestation and first post-natal months, with intense interactions between genetic, epigenetic and environmental factors. Although the babys brain is organized early on, it is not a miniature adult brain: regional brain changes are asynchronous and protracted, i.e. sensory-motor regions develop early and quickly, whereas associative regions develop later and slowly over decades. Concurrently, the infant/child gradually achieves new performances, but how brain maturation relates to changes in behavior is poorly understood, requiring non-invasive in vivo imaging studies such as magnetic resonance imaging (MRI). Two main processes of early white matter development are reviewed: (1) establishment of connections between brain regions within functional networks, leading to adult-like organization during the last trimester of gestation, (2) maturation (myelination) of these connections during infancy to provide efficient transfers of information. Current knowledge from post-mortem descriptions and in vivo MRI studies is summed up, focusing on T1- and T2-weighted imaging, diffusion tensor imaging, and quantitative mapping of T1/T2 relaxation times, myelin water fraction and magnetization transfer ratio.

Distortion Correction and Robust Tensor Estimation for MR Diffusion Imaging

This paper presents a new procedure to estimate the diffusion tensor from a sequence of diffusion-weighted images. The first step of this procedure consists of the correction of the distortions usually induced by eddy-current related to the large diffusion-sensitizing gradients. This correction algorithm relies on the maximization of mutual information to estimate the three parameters of a geometric distortion model inferred from the acquisition principle. The second step of the procedure amounts to replacing the standard least squares-based approach by the Geman-McLure M-estimator, in order to reduce outlier-related artefacts. Several experiments prove that the whole procedure highly improves the quality of the final diffusion maps.

Clinical severity in CADASIL related to ultrastructural damage in white matter: in vivo study with diffusion tensor MRI.

BACKGROUND AND PURPOSE CADASIL is a newly recognized cause of subcortical ischemic strokes that progressively leads to dementia associated with pseudobulbar palsy and severe motor disability. This deleterious progression and the severity of clinical presentation are widely variable among affected subjects. The exact role played by MRI white-matter abnormalities, a hallmark of the disease, in the severity of the clinical phenotype remains poorly understood. METHODS To address this issue, we used diffusion tensor imaging (DTI), a new MRI technique highly sensitive to white-matter microstructural changes, in 16 symptomatic patients and 10 age-matched controls. Mean diffusivity and anisotropy of diffusion were measured within hyperintensities identified on T2-weighted images (T2WI) and outside these lesions on 4 slices at the level of centrum semiovale. RESULTS We found a 60% increase of water mean diffusivity and a parallel loss of diffusion anisotropy in hyperintensities identified on T2WI. The same pattern of diffusion changes, but of lesser intensity, was found in the normal-appearing white matter on T2WI. Mean diffusivity in regions with increased signal on T2WI was higher in patients with severe clinical disability compared with those with no or mild deficit (1.33+/-0.11 versus 1.13+/-0.11 10(-3) mm(2)/s, P<0.01). Furthermore, diffusion measured within T2 hyperintensities correlated with both the Mini-Mental State Examination and Rankin scale scores. In patients with a severe clinical status, the increase of water diffusion in these regions exceeded 70% in comparison with values obtained in the normal white matter in control subjects. CONCLUSIONS These results indicate that DTI is able to detect important ultrastructural changes in regions with increased signal on T2WI and within the normal-appearing white matter in CADASIL. The diffusion changes might be related to both neuronal loss and demyelination. The degree of the underlying ultrastructural alterations is related to the severity of the clinical status with a possible threshold level of white-matter damage above which severe neurological impairment may occur in this disease. DTI appears to be a promising technique for monitoring disease progression in CADASIL.

Transient decrease in water diffusion observed in human occipital cortex during visual stimulation

Using MRI, we report the observation of a transient decrease of the apparent diffusion coefficient (ADC) of water in the human brain visual cortex during activation by a black and white 8-Hz-flickering checkerboard. The ADC decrease was small (<1%), but significant and reproducible, and closely followed the time course of the activation paradigm. Based on the known sensitivity of diffusion MRI to cell size in tissues and on optical imaging studies that have revealed changes in the shape of neurons and glial cells during activation, the observed ADC findings have been tentatively ascribed to a transient swelling of cortical cells. These preliminary results suggest a new approach to produce images of brain activation with MRI from signals directly associated with neuronal activation, and not through changes in local blood flow.

New diffusion phantoms dedicated to the study and validation of high-angular-resolution diffusion imaging (HARDI) models.

We present new diffusion phantoms dedicated to the study and validation of high‐angular‐resolution diffusion imaging (HARDI) models. The phantom design permits the application of imaging parameters that are typically employed in studies of the human brain. The phantoms were made of small‐diameter acrylic fibers, chosen for their high hydrophobicity and flexibility that ensured good control of the phantom geometry. The polyurethane medium was filled under vacuum with an aqueous solution that was previously degassed, doped with gadolinium‐tetraazacyclododecanetetraacetic acid (Gd‐DOTA), and treated by ultrasonic waves. Two versions of such phantoms were manufactured and tested. The phantoms applicability was demonstrated on an analytical Q‐ball model. Numerical simulations were performed to assess the accuracy of the phantom. The phantom data will be made accessible to the community with the objective of analyzing various HARDI models. Magn Reson Med 60:1276–1283, 2008.

In vivo evidence for the selective subcortical degeneration in Huntington's disease.

Although Huntingtons disease is largely considered to be a subcortical disease, there is no clear consensus on whether all deep grey matter loss is a direct downstream consequence of the massive degeneration of the medium-size spiny neurons in the striatum. Our aim was to characterise in vivo such preferential degeneration by analysing various distinct diffusion imaging measures including mean diffusivity, anisotropy, fibre orientation (using the information of the principal diffusion direction) and white matter tractography. All results converged to demonstrate the selective degeneration of connections in subcortical grey and white matter, degeneration which was likely to originate with the death of the striatal medium-size spiny neurons. Indeed, we found a significant increase of MD and FA in all the subcortical grey matter structures involved in the cortico-striato-thalamo-cortical loops. The atypical striatal and pallidal increase of FA was concurrent to a decrease of the dispersion of the fibre orientation, unambiguously characterising a preferential loss of connections along specific radiating directions from these structures while some others are comparatively spared. Analysis of striatal and pallidal white matter tracts revealed that striato-pallidal projections were the most affected. The ability of DTI to uncover the impact of such neurodegenerative disease on some specific neuronal/axonal populations is a further step towards the future definition of a surrogate marker of this disease. Beyond Huntingtons disease, we prove here that diffusion imaging technique, associated to adequate methodological analyses, can provide insight into any neurodegenerative disorder for which some neuronal populations or connections are selectively targeted over others.

Validation of q-ball imaging with a diffusion fibre-crossing phantom on a clinical scanner

Magnetic resonance (MR) diffusion imaging provides a valuable tool used for inferring structural anisotropy of brain white matter connectivity from diffusion tensor imaging. Recently, several high angular resolution diffusion models were introduced in order to overcome the inadequacy of the tensor model for describing fibre crossing within a single voxel. Among them, q-ball imaging (QBI), inherited from the q-space method, relies on a spherical Radon transform providing a direct relationship between the diffusion-weighted MR signal and the orientation distribution function (ODF). Experimental validation of these methods in a model system is necessary to determine the accuracy of the methods and to optimize them. A diffusion phantom made up of two textile rayon fibre (comparable in diameter to axons) bundles, crossing at 90°, was designed and dedicated to ex vivo q-ball validation on a clinical scanner. Normalized ODFs were calculated inside regions of interest corresponding to monomodal and bimodal configurations of underlying structures. Three-dimensional renderings of ODFs revealed monomodal shapes for voxels containing single-fibre population and bimodal patterns for voxels located within the crossing area. Principal orientations were estimated from ODFs and were compared with a priori structural fibre directions, validating efficiency of QBI for depicting fibre crossing. In the homogeneous regions, QBI detected the fibre angle with an accuracy of 19° and in the fibre-crossing region with an accuracy of 30°.

The coeruleus/subcoeruleus complex in rapid eye movement sleep behaviour disorders in Parkinson’s disease

In Parkinson’s disease, rapid eye movement sleep behaviour disorder is an early non-dopaminergic syndrome with nocturnal violence and increased muscle tone during rapid eye movement sleep that can precede Parkinsonism by several years. The neuronal origin of rapid eye movement sleep behaviour disorder in Parkinson’s disease is not precisely known; however, the locus subcoeruleus in the brainstem has been implicated as this structure blocks muscle tone during normal rapid eye movement sleep in animal models and can be damaged in Parkinson’s disease. Here, we studied the integrity of the locus coeruleus/subcoeruleus complex in patients with Parkinson’s disease using combined neuromelanin-sensitive, structural and diffusion magnetic resonance imaging approaches. We compared 24 patients with Parkinson’s disease and rapid eye movement sleep behaviour disorder, 12 patients without rapid eye movement sleep behaviour disorder and 19 age- and gender-matched healthy volunteers. All subjects underwent clinical examination and characterization of rapid eye movement sleep using video-polysomnography and multimodal imaging at 3 T. Using neuromelanin-sensitive imaging, reduced signal intensity was evident in the locus coeruleus/subcoeruleus area in patients with Parkinson’s disease that was more marked in patients with than those without rapid eye movement sleep behaviour disorder. Reduced signal intensity correlated with the percentage of abnormally increased muscle tone during rapid eye movement sleep. The results confirmed that this complex is affected in Parkinson’s disease and showed a gradual relationship between damage to this structure, presumably the locus subcoeruleus, and abnormal muscle tone during rapid eye movement sleep, which is the cardinal marker of rapid eye movement sleep behaviour disorder. In longitudinal studies, the technique may also provide early markers of non-dopaminergic Parkinson’s disease pathology to predict the occurrence of Parkinson’s disease.