G. Scotti

White matter damage in Alzheimer's disease assessed in vivo using diffusion tensor magnetic resonance imaging

Objective: To investigate the extent and the nature of white matter tissue damage of patients with Alzheimers disease using diffusion tensor magnetic resonance imaging (DT-MRI). Background: Although Alzheimers disease pathology mainly affects cortical grey matter, previous pathological and MRI studies showed that also the brain white matter of patients is damaged. However, the nature of Alzheimers disease associated white matter damage is still unclear. Methods: Conventional and DT-MRI scans were obtained from16 patients with Alzheimers disease and 10 sex and age matched healthy volunteers. The mean diffusivity (D̅), fractional anisotropy (FA), and inter-voxel coherence (C) of several white matter regions were measured. Results: D̅ was higher and FA lower in the corpus callosum, as well as in the white matter of the frontal, temporal, and parietal lobes from patients with Alzheimers disease than in the corresponding regions from healthy controls. D̅ and FA of the white matter of the occipital lobe and internal capsule were not different between patients and controls. C values were also not different between patients and controls for any of the regions studied. Strong correlations were found between the mini mental state examination score and the average overall white matter D̅ (r=0.92, p<0.001) and FA (r=0.78; p<0.001). Conclusions: White matter changes in patients with Alzheimers disease are likely to be secondary to wallerian degeneration of fibre tracts due to neuronal loss in cortical associative areas.

Functional Magnetic Resonance Imaging Correlates of Fatigue in Multiple Sclerosis

Although fatigue is a common and troublesome symptom of multiple sclerosis (MS), its pathogenesis is poorly understood. In this study, we used functional magnetic resonance imaging (fMRI) to test whether a different pattern of movement-associated cortical and subcortical activations might contribute to the development of fatigue in patients with MS. We obtained fMRI during the execution of a simple motor task with completely normally functioning hands from 15 MS patients with fatigue (F), 14 MS patients without fatigue (NF), and 15 sex- and age-matched healthy volunteers. F and NF MS patients were also matched for major clinical and MRI variables. FMRI data were analyzed using statistical parametric mapping. In all patients, severity of fatigue was rated using the Fatigue Severity Scale (FSS). Compared to healthy subjects, MS patients showed more significant activations of the contralateral primary somatomotor cortex, the contralateral ascending limb of the Sylvian fissure, the contralateral intraparietal sulcus (IPS), the contralateral supplementary motor area, and the ipsilateral and contralateral cingulate motor area (CMA). Compared to F MS patients, NF patients showed more significant activations of the ipsilateral cerebellar hemisphere, the ipsilateral rolandic operculum, the ipsilateral precuneus, the contralateral thalamus, and the contralateral middle frontal gyrus. In contrast, F MS patients had a more significant activation of the contralateral CMA. Significant inverse correlations were found between FSS scores and relative activations of the contralateral IPS (r = -0.63), ipsilateral rolandic operculum (r = -0.61), and thalamus (r = -0.62). This study provides additional evidence that fatigue in MS is related to impaired interactions between functionally related cortical and subcortical areas. It also suggests that fMRI might be a valuable tool to monitor the efficacy of treatment aimed at reducing MS-related fatigue.

Motor and language DTI Fiber Tracking combined with intraoperative subcortical mapping for surgical removal of gliomas

Preoperative DTI Fiber Tracking (DTI-FT) reconstruction of functional tracts combined with intraoperative subcortical mapping (ISM) is potentially useful to improve surgical procedures in gliomas located in eloquent areas. Aims of the study are: (1) to evaluate the modifications of fiber trajectory induced by the tumor; (2) to validate preoperative DTI-FT results with intraoperative identification of functional subcortical sites through direct subcortical stimulation; (3) to evaluate the impact of preoperative DTI-FT reconstructions in a neuronavigational setup combined with ISM technique on duration and modalities of surgical procedures, and on functional outcome of the patients. Data are available on 64 patients (52 low-grade and 12 high-grade gliomas). DTI-FT was acquired by a 3-T MR scanner with a single-shot EPI sequence (TR/TE 8986/80 ms, b=1000 s/mm) with gradients applied along 32 non-collinear directions. 3D Fast Field Echo (FFE) T1-weighted imaging (TR/TE 8/4 ms) was performed for anatomic guidance. The corticospinal tract (CST), superior longitudinal, inferior fronto-occipital and uncinatus fasciculi were reconstructed. Data were transferred to the neuronavigational system. Functional subcortical sites identified during ISM were correlated with fiber tracts depicted by DTI-FT. In high-grade gliomas, DTI-FT depicted tracts mostly at the tumor periphery; in low-grade gliomas, fibers were frequently located inside the tumor mass. There was a high correlation between DTI-FT and ISM (sensitivity for CST=95%, language tracts=97%). For a proper reconstruction of the tracts, it was necessary to use a low FA threshold of fiber tracking algorithm and to position additional regions of interest (ROIs). The combination of DTI-FT and ISM decreased the duration of surgery, patient fatigue, and intraoperative seizures. Combination of DTI-FT and ISM allows accurate identification of eloquent fiber tracts and enhances surgical performance and safety maintaining a high rate of functional preservation.

Brain Gray Matter Changes in Migraine Patients With T2-Visible Lesions A 3-T MRI Study

Background and Purpose— In migraine patients, functional imaging studies have shown changes in several brain gray matter (GM) regions. However, 1.5-T MRI has failed to detect any structural abnormality of these regions. We used a 3-T MRI scanner and voxel-based morphometry (VBM) to assess whether GM density abnormalities can be seen in patients with migraine with T2-visible abnormalities and to grade their extent. Methods— In 16 migraine patients with T2-visible abnormalities and 15 matched controls, we acquired a T2-weighted and a high-resolution T1-weighted sequence. Lesion loads were measured on T2-weighted images. An optimized version of VBM analysis was used to assess regional differences in GM densities on T1-weighted scans of patients versus controls. Statistical parametric maps were thresholded at P<0.001, uncorrected for multiple comparisons. Results— Compared with controls, migraine patients had areas of reduced GM density, mainly located in the frontal and temporal lobes. Conversely, patients showed increased periacqueductal GM (PAG) density. Compared with patients without aura, migraine patients with aura had increased density of the PAG and of the dorsolateral pons. In migraine patients, reduced GM density was strongly related to age, disease duration, and T2-visible lesion load (r ranging from −0.84 to −0.73). Conclusions— Structural GM abnormalities can be detected in migraine patients with brain T2-visible lesions using VBM and a high-field MRI scanner. Such GM changes comprise areas with reduced and increased density and are likely related to the pathological substrates associated with this disease.

Increased right caudate nucleus size in obsessive-compulsive disorder: detection with magnetic resonance imaging.

Magnetic resonance images were used to measure the volume of the head of the caudate nucleus in 20 patients with obsessive-compulsive disorder and 16 normal control subjects. The obsessive-compulsive patients showed a significant increase in the volume of the right side of the head of the caudate nucleus compared with that of control subjects. This finding was not correlated with demographic, psychopathological, or clinical characteristics.

Cortical adaptation in patients with MS: a cross-sectional functional MRI study of disease phenotypes

BACKGROUND Movement-associated cortical reorganisation is known to occur in multiple sclerosis (MS). We aimed to define the development of such cortical reorganisation by comparing data from patients with different disease phenotypes. METHODS We studied patients with different phenotypes of MS: 16 patients with a clinically isolated syndrome (CIS), 14 patients with relapsing-remitting MS (RRMS) and no disability, 15 patients with RRMS and mild clinical disability, and 12 patients with secondary progressive MS (SPMS). Patients did a simple motor task with their unimpaired dominant hand during MRI, which was compared across the phenotype groups. FINDINGS Patients with a CIS activated more of the contralateral primary sensorimotor cortex than those with RRMS and no disability, whereas patients with RRMS and no disability activated more of the supplementary motor area than those with a CIS. Patients with RRMS and no disability activated more of the primary sensorimotor cortex, bilaterally, and more of the ipsilateral supplementary motor area than patients with RRMS and mild clinical disability. Conversely, patients with RRMS and mild clinical disability activated more of the contralateral secondary somatosensory cortex and inferior frontal gyrus, and the ipsilateral precuneus. Patients with RRMS and mild clinical disability activated more of the contralateral thalamus and of the ipsilateral secondary somatosensory cortex than those with SPMS. However, patients with SPMS activated more of the inferior frontal gyrus, bilaterally, the middle frontal gyrus, bilaterally, the contralateral precuneus, and the ipsilateral cingulate motor area and inferior parietal lobule. INTERPRETATION Movement-associated cortical reorganisation in patients with MS seems to vary across individuals at different stages of disease. Our study suggests that early in the disease course more areas typically devoted to motor tasks are recruited. Then bilateral activation of these regions is seen, and late in the disease course, areas that healthy people recruit to do novel or complex tasks are activated.

Adaptive functional changes in the cerebral cortex of patients with nondisabling multiple sclerosis correlate with the extent of brain structural damage

In multiple sclerosis, the mechanisms underlying the accumulation of disability are poorly understood. Recently, it has been suggested that adaptive cortical changes may limit the clinical impact of multiple sclerosis injury. In this study, functional magnetic resonance imaging and a general search method were used to assess patterns of brain activation associated with a simple motor task in 14 right‐handed, nondisabled relapsing‐remitting multiple sclerosis patients that were compared to those from 15 right‐handed, sex‐ and age‐matched healthy volunteers. Also investigated were the extent to which the functional magnetic resonance imaging changes correlated with T2 lesion volume and severity of multiple sclerosis pathology in lesions and normal‐appearing brain tissue, measured using magnetisation transfer and diffusion tensor magnetic resonance imaging. Compared to controls, multiple sclerosis patients showed increased activation in the contralateral primary sensorimotor cortex, bilaterally in the supplementary motor area, bilaterally in the cingulate motor area, in the contralateral ascending bank of the sylvian fissure, and in the contralateral intraparietal sulcus. T2 lesion volume was correlated with relative activation in the ipsilateral supplementary motor area, and in the ipsilateral and contralateral cingulate motor area. Average lesion magnetisaiton transfer ratio and average lesion water diffusivity were correlated with relative activation in the contralateral sensorimotor cortex. Average lesion magnetisation transfer ratio was also correlated with relative activation in the ipsilateral cingulate motor area. Average water diffusivity and peak height of the normal‐appearing brain tissue diffusivity histogram were both correlated with relative activation in the contralateral intraparietal sulcus. This study shows that cortical activation occurs over a rather distributed sensorimotor network in nondisabled relapsing‐remitting multiple sclerosis patients. It also suggests that increased recruitment of this cortical network contributes to the limitation of the functional impact of white matter multiple sclerosis injury.

Perceptual and associative disorders of visual recognition Relationship to the side of the cerebral lesion

IN 1890, Lissauerl described the first welldocumented case of visual agnosia and proposed a subdivision of this disorder into an apperceptive and an associative form, according to which stage of the process of visual recognition was primarily af€ected. By apperception he meavt the higher level of processing of sense data (the lower level being designated as perception) which enables the subject to identify and discriminate complex patterns. In Lissauers opinion, this impairment can be evaluated by requiring the patient to [I] describe the formal features of the pattern, [2] reproduce it by drawing, and [3] recognize it among similar alternatives. The associative stage, on the other hand, consists of the linkage of the processed visual data with memory images laid down in the brain through other sensory modalities and with names, which Lissauer considered as the most simple and basic representation ( Vorstellung ) aroused by objects. Only through these linkages does apperception acquire a meaning. Lissauer assumed that his patient was affected by associative agnosia since he did not recognize objects, although he performed fairly well on purely apperceptive tasks such as discriminating arabesques. In the subsequent history of visual agnosia, the dichotomy between associative and apperceptive disorders has been somewhat neglected and attention has been concentrated on the content of the patterns the patient fails to recognize, distinguishing object agnosia, color agnosia, face agnosia, and others. This classifi-

Hemispheric Contribution to Exploration of Space Through the Visual and Tactile Modality

Summary Control and unilaterally brain-damaged patients were given two tests requiring the exploration of space through the visual and the tactile modalities. In the visual test, the patient was required to identify a number on a display board among alternatives, while in the tactile test he had to find a marble in a maze. The score was the time spent in searching for the item. On the visual test, controls performed better when the item was on the left side than when it was on the right. This “normal” left-right gradient (probably due to reading habits) was found to be significantly increased in left brain-damaged patients and reversed in right brain-damaged patients, a finding which supports the assumption that injury to one hemisphere mainly impairs the exploration of contralateral field. On the tactile test, each hemispheric group performed worse in the contralateral field. This lengthening of the searching time cannot be explained by disruption of the sensorimotor mechanism subserving space exploration and points to the impairment of a higher level ability, identifiable as the representation of contralateral space. When performance was scored in terms of failure in finding the marble within the 90 sec time limit, right hemisphere patients with visual field defects turned out to be significantly more impaired than any other brain-damaged subgroup. This finding is suggestive for the occurrence of unilateral neglect also in the tactile modality and it lends support to the hypothesis that hemi-inattention does not depend so much on perceptual and motor factors as on a mutilated representation of space.

A modified damped Richardson-Lucy algorithm to reduce isotropic background effects in spherical deconvolution

Spherical deconvolution methods have been applied to diffusion MRI to improve diffusion tensor tractography results in brain regions with multiple fibre crossing. Recent developments, such as the introduction of non-negative constraints on the solution, allow a more accurate estimation of fibre orientations by reducing instability effects due to noise robustness. Standard convolution methods do not, however, adequately model the effects of partial volume from isotropic tissue, such as gray matter, or cerebrospinal fluid, which may degrade spherical deconvolution results. Here we use a newly developed spherical deconvolution algorithm based on an adaptive regularization (damped version of the Richardson-Lucy algorithm) to reduce isotropic partial volume effects. Results from both simulated and in vivo datasets show that, compared to a standard non-negative constrained algorithm, the damped Richardson-Lucy algorithm reduces spurious fibre orientations and preserves angular resolution of the main fibre orientations. These findings suggest that, in some brain regions, non-negative constraints alone may not be sufficient to reduce spurious fibre orientations. Considering both the speed of processing and the scan time required, this new method has the potential for better characterizing white matter anatomy and the integrity of pathological tissue.