Diffusion tensor imaging can be used in vivo to assess the longitudinal and regional microstructural changes occurring after middle cerebral artery (MCA) infarcts in humans. Nine patients were investigated 1 week (D7), 1 (M1), 3 (M3), and 6 months (M6) after the occurrence of an isolated MCA infarction. First, an overall analysis was performed using histograms of mean diffusivity (MD) and fractional anisotropy (FA) in each hemisphere. Thereafter, the regional pattern of diffusion changes was investigated voxel by voxel with statistical parametric mapping 99. In the hemisphere ipsilateral to the infarction, histogram analysis revealed a significant decrease in FA between D7 and M6 associated with a progressive increase in MD from D7 to M3. Remote from the MCA territory, the voxel by voxel analyses detected a significant increase in MD within the thalamus at M3 and M6 and a reduction in FA along the pyramidal tract at M6. In the contralateral hemisphere, between D7 and M6, a significant hemispheric atrophy was observed in association with a global reduction in anisotropy, in the absence of distinctive regional diffusion changes. These results suggest that micro- and macrostructural tissue modifications can be detected with diffusion tensor imaging in regions remote from the ischemic area in both hemispheres.

Background: Cerebral infarcts are responsible for functional alterations and microscopic tissue damage at distance from the ischaemic area. Such remote effects have been involved in stroke recovery. Thalamic hypometabolism is related to motor recovery in middle cerebral artery ( MCA) infarcts but little is known concerning the tissue changes underlying these metabolic changes. Diffusion tensor imaging ( DTI) is highly sensitive to microstructural tissue alterations and can be used to quantify in vivo the longitudinal microscopic tissue changes occurring in the thalamus after MCA infarcts in humans.Methods: Nine patients underwent DTI after an isolated MCA infarct. Mean diffusivity ( MD), fractional anisotropy ( FA), and thalamic region volume were measured from the first week to the sixth month after stroke onset in these patients and in 10 age matched controls.Results: MD significantly increased in the ipsilateral thalamus between the first and the sixth month ( 0.766 x 10(-3) mm(2)/ s first month; 0.792 x 10(-3) mm(2)/ s third month; 0.806 x 10(-3) mm(2)/ s sixth month). No significant modification of FA was detected. In six patients, the ipsilateral/ contralateral index of MD was higher than the upper limit of the 95% CI calculated in 10 age matched controls. An early decrease of MD preceded the increase of ipsilateral thalamic diffusion in one patient at the first week and in two other patients at the first month.Conclusion: After MCA infarcts, an increase in diffusion is observed with DTI in the ipsilateral thalamus later than 1 month after the stroke onset. This is presumably because of the progressive loss of neurons and/ or glial cells. In some patients, this increase is preceded by a transient decrease in diffusion possibly related to an early swelling of these cells or to microglial activation. Further studies in larger series are needed to assess the clinical correlates of these findings.

Background and Purpose - The shape and exact size of lacunar infarcts have been investigated only postmortem. Recent imaging techniques based on triangulation and connectivity can now be used for 3D segmentation of cerebral lesions. The shape and size of lacunar infarcts was investigated using these techniques in 10 cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients.Methods - We segmented 102 lacunar infarcts on T1-weighted images. The surface of the corresponding set of voxels was computed as a mesh of triangles. Thereafter, the shape of each lesion in 3D was visually analyzed by 2 investigators.Results - The volume of lesions ranged from 10.5 to 1146 mm, with 93% of them having a volume <500 mm; 83% lacunar infarcts had a spheroid or ovoid shape, but 17% presented as sticks, slabs, or with a complex shape. Lesions with multiple components appeared larger than the others, and a tail extension was noticed in 13 of 102 lesions.Conclusions - These results suggest the following: (1) most lacunar infarcts in CADASIL have a volume far below one third of that of a sphere of 15 mm in diameter, the upper limit currently used for their identification on 2D imaging; (2) a significant proportion of lacunar infarcts have a shape distinct from the spheroid-ovoid morphology; and (3) lesions with a complex shape may result from the involvement of the largest small arteries, confluence of ischemic lesions, or secondary tissue degeneration. The segmentation of lacunar infarcts appears promising to better understand the pathophysiology of tissue lesions secondary to small vessel diseases.

Purpose: To investigate the diffusion tensor properties of the human optic nerve in vivo using a non-Carr-Purcell-Meiboom-Gill (CPMG) fast spin echo (FSE) sequence.Materials and Methods: This non-CPMG FSE sequence, which is based on a quadratic phase modulation of the refocusing pulses, allows diffusion measures to be acquired with full signal and without artifacts from geometric distortions due to magnetic field inhomogeneities, which are among the main problems encountered in the orbital area.Results: Good-quality images were obtained at a resolution of 0.94 x 0.94 x 3 mm. The mean diffusivity (MD) and fractional anisotropy (FA) were respectively 1.1 +/- 0.2 x 10(-3) mm(2) /second and 0.49 +/- 0.06, reflecting the optic nerve anisotropy.Conclusion: This non-CPMG-FSE sequence provides reliable diffusion-weighted images of the human optic nerve. This approach could potentially improve the diagnosis and management of optic nerve diseases or compression, such as optic neuritis, orbit tumors, and muscle hypertrophy.

Recent studies in human neuroimaging, primate neurophysiology, and developmental neuropsychology indicate that the human ability for arithmetic has a tangible cerebral substrate. The human intraparietal sulcus is systematically activated in all number tasks and could host a central amodal representation of quantity. Areas of the precentral and inferior prefrontal cortex also activate when subjects engage in mental calculation. A monkey analogue of these parieto-frontal regions has recently been identified, and a neuronal population code for number has been characterized. Finally, pathologies of this system, leading to acalculia in adults or to developmental dyscalculia in children, are beginning to be understood, thus paving the way for brain-oriented intervention studies.

Diffusion tensor imaging (DTI) can provide quantitative information of brain abnormalities in patients with temporal lobe epilepsy (TLE) that are not detectable with conventional magnetic resonance imaging (MRI).Seventeen patients with medically TLE were selected for the study. The patients and ten healthy subjects underwent 25 directions DTI acquisition. The patients were separated into two groups based on the MRI findings: eight TLE MRI-negative patients with no signal abnormalities on conventional MRI and nine TLE patients with hippocampal sclerosis (HS). Fractional anisotropy (FA), mean diffusivity (MD), and the three diffusivities (λ1, λ2 and λ3) were measured in bilateral hippocampi of controls, MRI-negative, and HS patients. Comparisons between the three groups were performed for hippocampi ipsi- and contralateral to epileptogenic zone.The ipsilateral hippocampus of MRI-negative patients presented statistical increased anisotropy and no significant difference in diffusivities versus controls. Significant differences in anisotropy and diffusivities were detected between the ipsilateral hippocampus of HS when compared with controls.DTI depicted hippocampal abnormalities in TLE patients with a normal conventional MRI different from those found in patients with HS. Diffusivity and anisotropy indices provide significant differences inside hippocampus and should be jointly considered to improve the DTI measurements specificity in TLE patients.L'imagerie en tenseur de diffusion (DTI) peut fournir des informations quantitatives sur les anomalies cérébrales chez les patients ayant une épilepsie du lobe temporal (TLE) qui ne sont pas détectables avec les techniques d'imagerie par résonance magnétique (IRM) conventionnelles.Dix-sept patients ayant une épilepsie temporale clinique ont été sélectionnés pour l'étude. Les patients et dix sujets sains ont été étudiés par tenseur de diffusion en 25 directions. Les patients ont été séparés en deux groupes sur la base des résultats de l'IRM conventionnelle : huit patients ayant une IRM normale (MRI-négative) et neuf patients ayant sclérose hippocampique (HS). La fraction d'anisotropie (FA), la diffusivité moyenne (MD) et les trois diffusivités (λ1, λ2 and λ3) ont été mesurées dans les hippocampes bilatéraux chez les témoins, les patients MRI-negative et les patients HS. Les comparaisons entre les trois groupes ont été effectuées dans les hippocampes ipsilatéraux et controlatéraux à la zone épileptogène.L'hippocampe ipsilatéral chez les patients MRI-négative présente une anisotropie statistiquement différente et aucune différence significative pour les diffusivités par rapport aux témoins. Des différences significatives de l'anisotropie et des diffusivités ont été détectées dans l'hippocampe ipsilatéral du group HS par rapport aux témoins.Le tenseur de diffusion a détecté des anomalies hippocampiques chez des patients ayant une épilepsie temporale et une IRM conventionnelle normale différentes des celles trouvées chez les patients ayant une sclérose hippocamique. L'anisotropie et la diffusivité présentent des différences significatives dans l'hippocampe et devraient être considérées conjointement pour améliorer la spécificité des mesures DTI chez les patients ayant une épilepsie temporale.

Current theories of number processing postulate that the human abilities for arithmetic are based on cerebral circuits that are partially laid down under genetic control and later modified by schooling and education. This view predicts the existence of genetic diseases that interfere specifically with components of the number system. Here, we investigate whether Turner syndrome (TS) corresponds to this definition. TS is a genetic disorder which affects one woman in 2500 and is characterized by partial or complete absence of one X chromosome. In addition to well-characterized physical and hormonal dysfunction, TS patients exhibit cognitive deficits including dyscalculia. We tested 12 women with Turner syndrome and 13 control subjects on a cognitive battery including arithmetical tests (addition, subtraction, multiplication, division) as well as tests of the understanding of numerosity and quantity (cognitive estimation, estimation, comparison, bisection, subitizing/counting). Impairments were observed in cognitive estimation, subitizing, and calculation. We examine whether these deficits can be attributed to a single source, and discuss the possible implications of hormonal and genetic factors in the neuropsychological profile of TS patients.

Analysis of brain structure in Turner syndrome (TS) provides the opportunity to identify the consequences of the loss of one X chromosome on brain anatomy and to characterize the neural bases underlying the specific cognitive profile of TS subjects which includes deficits in spatial-numerical processing and social cognition. Fourteen subjects with TS and fourteen controls were investigated using voxel-based analysis of high resolution anatomical and diffusion tensor images and using sulcal morphometry. The analysis of anatomical images provided evidence for macroscopical changes in cortical regions involved in social cognition such as the left superior temporal sulcus and orbito-frontal cortex and in a region involved in spatial and numerical cognition such as the right intraparietal sulcus. Diffusion tensor images showed a displacement of the grey-white matter interface of the left and right superior temporal sulcus and revealed bilateral microstructural anomalies in the temporal white matter. The analysis of fiber orientation suggests specific alterations of fiber tracts connecting posterior to anterior temporal regions. Last, sulcal morphometry confirmed the anomalies of the left and right superior temporal sulci and of the right intraparietal sulcus. Our results thus provide converging evidence of regionally specific structural changes in TS that are highly consistent with the hallmark symptoms associated with TS.

Cognitive theories of numerical representation suggest that understanding of numerical quantities is driven by a magnitude representation associated with the intraparietal sulcus and possibly under genetic control. The aim of this study was to investigate, using fMRI and structural imaging, the interaction between the abnormal development of numerical representation in an X-linked condition, Turner syndrome (TS), and the development of the intraparietal sulcus. fMRI during exact and approximate calculation in TS showed an abnormal modulation of intraparietal activations as a function of number size. Morphological analysis revealed an abnormal length, depth, and sulcal geometry of the right intraparietal sulcus, suggesting an important disorganization of this region in TS. Thus, a genetic form of developmental dyscalculia can be related to both functional and structural anomalies of the right intraparietal sulcus, suggesting a crucial role of this region in the development of arithmetic abilities.

Disconnection syndromes are often conceptualized exclusively within cognitive box-and-arrow diagrams unrelated to brain anatomy. In a patient with alexia in his left visual field resulting from a posterior callosal lesion, we illustrate how diffusion tensor imaging can reveal the anatomical bases of a disconnection syndrome by tracking the degeneration of neural pathways and relating it to impaired fMRI activations and behavior. Compared to controls, an abnormal pattern of brain activity was observed in the patient during word reading, with a lack of activation of the left visual word form area (VWFA) by left-hemifield words. Statistical analyses of diffusion images revealed a damaged fiber tract linking the left ventral occipito-temporal region to its right homolog across the lesioned area of corpus callosum and stopping close to the areas found active in fMRI. The behavioral disconnection syndrome could, thus, be related functionally to abnormal fMRI activations and anatomically to the absence of a connection between those activations. The present approach, based on the “negative tracking” of degenerated bundles, provides new perspectives on the understanding of human brain connections and disconnections.

BACKGROUND AND PURPOSE:In cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a large increase in water diffusion has been found both inside and outside the cerebral lesions as detected on conventional MRI. The aim of the present study was to assess the sensitivity of diffusion tensor imaging for monitoring the progression of cerebral tissue damage during the course of CADASIL.METHODS:With the use of diffusion tensor imaging, whole brain trace of the diffusion tensor [Trace(D)] histograms were obtained in 22 CADASIL patients and 12 age-matched controls at baseline, in 14 patients after a mean delay of 21 months, and in 5 controls after a mean delay of 29 months. Parameters derived from these histograms (mean value, peak height, and peak location) were analyzed at baseline and during the follow-up.RESULTS:At baseline, all the histogram parameters differed between patients and controls and were found to be significantly correlated with both the Mini-Mental State Examination score and Rankin Scale score in the patient group. The follow-up study showed a decrease in the peak height associated with an increase in the mean value of whole brain Trace(D) histograms in the 14 CADASIL patients scanned twice. The diffusion changes appeared larger in the patients whose Rankin score increased during the study period.CONCLUSIONS:These results suggest that the measurement of water diffusion over time is a sensitive marker for the progression of tissue damage in the brain. Thus, quantitative diffusion MRI can be used to monitor disease progression in CADASIL and possibly in other types of small-vessel brain disorders.

BACKGROUND AND PURPOSE:In cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), water diffusion changes suggestive of microstructural tissue alterations have been recently reported in abnormal- and normal-appearing white matter as seen on T2-weighted images. In the subcortical gray matter, typical lacunar infarcts are repeatedly observed. Whether microstructural tissue changes are also present outside these lesions within the putamen or thalamus remains unknown.METHODS:We used diffusion tensor imaging, an MRI method highly sensitive to cerebral microstructure, in 20 CADASIL patients and 12 controls. Both the trace of the diffusion tensor [Tr(D)] and an anisotropic diffusion index (volume ratio) of diffusion were measured within the putamen and thalamus outside typical lacunar infarcts as detected on both T1- and T2-weighted images.RESULTS:A significant increase in Tr(D) and a decrease in anisotropy were observed in the putamen and thalamus in patients. The right/left indices of Tr(D) in the thalamus, but not in the putamen, were strongly correlated with the corresponding indices calculated in the white matter of the centrum semiovale. In addition, the diffusion increase in the thalamus was positively correlated with Tr(D) and with the load of small deep infarcts within the white matter and negatively correlated with the Mini-Mental State Examination score.CONCLUSIONS:Our results suggest that microstructural tissue alterations are present in the putamen and thalamus, outside the typical lacunar infarcts in CADASIL. In the thalamus, these microstructural changes appear constant and are even observed in asymptomatic subjects. Some of these thalamic changes appear to result from degeneration of thalamocortical pathways secondary to ischemic white matter damage. The importance of this degenerative phenomenon in the pathophysiology of CADASIL requires further investigation.

P18 Background and Purpose: Variable microstructural changes have been reported within the white-matter in CADASIL. Lacunar infarcts are frequently observed in the subcortical grey matter. However, whether microstructural tissular alterations are also present within the non-infarcted putamen (NIP) or thalamus (NIT), remains unknown. Methods: We used diffusion tensor imaging, a MRI method highly sensitive to the cerebral microstructure, in 20 CADASIL patients and 12 age-matched controls. Both Trace(D) and anisotropy (volume-ratio index) of diffusion were measured within the NIP and NIT. In addition, diffusion parameters and the load of small infarcts were calculated within the white-matter of the centrum semi-ovale. A one way ANOVA was performed to compare the diffusion parameters between patients and controls. Thereafter, correlations between the significant results in our patients and the diffusion parameters in the white-matter or the MMSE scores were tested. Results: A significant increase in Trace(D) and decrease in anisotropy were observed in both the NIP and NIT in our patients. Conversely to the results in the NIP, only significant in the presence of associated putaminal infarcts, the diffusion changes in the NIT were significant both in the presence and absence of associated thalamic infarcts. The asymmetry indices of Trace(D) in the NIT and in the white-matter were strongly correlated. The diffusion increase in the NIT was also positively correlated both to Trace(D) and to the load of small deep infarcts within the centrum semi-ovale. Elsewhere, the diffusion increase in the NIT, but not in the NIP, was negatively correlated to the MMSE score in our patients. Conclusions: These results suggest that microstructural alterations are present in both the NIP and NIT in CADASIL. In the NIT, microstructural alterations appear secondary to remote lesions of thalamo-cortical pathways. Diffusion measured in the NIT mirror both the degree of white-matter tissular damage and the clinical severity in CADASIL. This study highlights the importance of secondary neurodegeneration in a typical model of “pure vascular dementia”.

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.