The Corticospinal Tract in Huntington's Disease.

Huntington's disease (HD) is characterized by progressive motor impairment. Therefore, the connectivity of the corticospinal tract (CST), which is the main white matter (WM) pathway that conducts motor impulses from the primary motor cortex to the spinal cord, merits particular attention. WM abnormalities have already been shown in presymptomatic (Pre-HD) and symptomatic HD subjects using magnetic resonance imaging (MRI). In the present study, we examined CST microstructure using diffusion tensor imaging (DTI)-based tractography in 30-direction DTI data collected from 100 subjects: Pre-HD subjects (n = 25), HD patients (n = 25) and control subjects (n = 50), and T2*-weighted (iron sensitive) imaging. Results show decreased fractional anisotropy (FA) and increased axial (AD), and radial diffusivity (RD) in the bilateral CST of HD patients. Pre-HD subjects had elevated iron in the left CST, regionally localized between the brainstem and thalamus. CAG repeat length in conjunction with age, as well as motor (UHDRS) assessment were correlated with CST FA, AD, and RD both in Pre-HD and HD. In the presymptomatic phase, increased iron in the inferior portion supports the "dying back" hypothesis that axonal damage advances in a retrograde fashion. Furthermore, early iron alteration may cause a high level of toxicity, which may contribute to further damage.

MRI measures of corpus callosum iron and myelin in early Huntington's disease.

Increased iron in subcortical gray matter (GM) structures of patients with Huntington's disease (HD) has been suggested as a causal factor in neuronal degeneration. But how iron content is related to white matter (WM) changes in HD is still unknown. For example, it is not clear whether WM changes share the same physiopathology (i.e. iron accumulation) with GM or whether there is a different mechanism. The present study used MRI to examine iron content in premanifest gene carriers (PreHD, n = 25) and in early HD patients (n = 25) compared with healthy controls (n = 50). 3T MRI acquisitions included high resolution 3D T1, EPI sequences for diffusion tensor imaging (DTI) as an indirect measure of tissue integrity, and T2*-weighted gradient echo-planar imaging for MR-based relaxometry (R2*), which provides an indirect measure of ferritin/iron deposition in the brain. Myelin breakdown starts in the PreHD stage, but there is no difference in iron content values. Iron content reduction manifests later, in the early HD stage, in which we found a lower R2* parameter value in the isthmus. The WM iron reduction in HD is temporally well-defined (no iron differences in PreHD subjects and iron differences only in early HD patients). Iron level in callosal WM may be regarded as a marker of disease state, as iron does not differentiate PreHD subjects from controls but distinguishes between PreHD and HD.

Peculiar CADASIL phenotype in monozygotic twins carrying a novel NOTCH3 pathogenetic variant.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominantly inherited cerebral small vessel disease caused by Neurogenic locus notch homolog protein 3 (NOTCH3) gene mutations. The main clinical features include migraine with aura, recurrent ischemic strokes and dementia. Brain MRI typically shows multiple small lacunar infarcts and severe, diffuse, symmetrical white matter hyperintensities (WMHs), with characteristic involvement of the anterior temporal pole, external capsule, and superior frontal gyrus. Reports of twins with CADASIL are scarce. Herein we describe a pair of monozygotic twins with peculiar CADASIL phenotype, carrying a new NOTCH3 variant. CASE PRESENTATION: Twin A was a 45-year-old male suffering from migraine, obesity, arterial hypertension, and polycythemia (with negative genetic analysis), who complained of a transient, short-lasting (~ 5 minutes) episode of speech difficulties. Brain MRI showed diffuse, symmetrical, confluent periventricular WMHs involving frontal, parietal, and temporal lobes and external capsules, with sparing of anterior temporal poles. Genetic analysis of NOTCH3 gene demonstrated the presence of missense c.3329G>A, p.(Cys1110Tyr) variant, confirming CADASIL diagnosis. Twin B, affected by migraine and polycythemia, as well as his monozygotic twin, presented with a 2-month history of trigeminal neuralgia. Brain MRI demonstrated diffuse WMHs with a pattern of distribution like his twin. Genetic analysis revealed the same NOTCH3 pathogenic variant. CONCLUSIONS: Our monozygotic twins have a strikingly similar neuroimaging picture with sparing of anterior temporal poles. They also have a peculiar phenotype, both presenting polycythemia without genetically confirmed cause. Twin B had trigeminal neuralgia, that is unusual in CADASIL. The possible association of the peculiar findings with the newly reported NOTCH3 variant needs to be confirmed with further observations.

Multimodal MRI analysis of the corpus callosum reveals white matter differences in presymptomatic and early Huntington's disease.

Recent magnetic resonance imaging (MRI) studies suggest that abnormalities in Huntington's disease (HD) extend to white matter (WM) tracts in early HD and even in presymptomatic stages. Thus, changes of the corpus callosum (CC) may reflect various aspects of HD pathogenesis. We recruited 17 HD patients, 17 pre-HD subjects, and 34 healthy age-matched controls. Three-dimensional anatomical MRI and diffusion tensor images of the brain were acquired on a 3T scanner. Combining region-of-interest analyses, voxel-based morphometry, and tract-based spatial statistics, we investigated callosal thickness, WM density, fractional anisotropy, and radial and axial diffusivities. Compared with controls, pre-HD subjects showed reductions of the isthmus, likely due to myelin damage. Compared with pre-HD subjects, HD patients showed reductions of isthmus and body, with axonal damage confined to the body. Compared with controls, HD patients had significantly decreased callosal measures in extended regions across almost the entire CC. At this disease stage, both myelin and axonal damage are detectable. Supplementary multiple regression analyses revealed that WM reduction density in the isthmus as well as Disease Burden scores allowed to predict the "HD development" index. While callosal changes seem to proceed in a posterior-to-anterior direction as the diseases progresses, this observation requires validation in future longitudinal investigations.

Infratentorial lesion volume correlates with sensory functional system in multiple sclerosis patients: a 3.0-Tesla MRI study.

PURPOSE: This study sought to correlate lesion volume in infratentorial areas using 3.0-T proton-density (PD)-weighted images with disability scales and appropriate functional system scores in patients with multiple sclerosis (MS). MATERIALS AND METHODS: We examined 20 consecutive patients (13 women and 7 men) with a median age of 47 years (range 26-70). Neurological examination included the Expanded Disability Status Scale and its functional systems, the Barthel Index (BI) and the Rivermead Mobility Index (RMI). MRI scans were performed on a system operating at 3.0 T using a quadrature birdcage head coil. Acquired images imported as Digital Imaging and Communication in Medicine (DICOM) files, and the region of interest (ROI) files were converted to Neuroimaging Informatics Technology Initiative (NIfTI) format and normalised to the Montreal Neurological Institute (MNI) standard template. An automated segmentation algorithm was used to distinguish between supratentorial and infratentorial areas. Normalisation to the magnetisation-prepared rapid acquisition with gradient echo (MPRAGE) T1-weighted sequence allowed lesion volume estimation in the different anatomical areas. RESULTS: A significant correlation was found between infratentorial lesion volume and the sensory functional system score (rho=0.76, p=0.002). No significant correlation was found between supratentorial lesion volume and Expanded Disability Status Scale (EDSS), RMI and BI scores. CONCLUSIONS: The described method, by means of anatomical assignment of MS lesions, allows detection of significant correlation coefficients between clinical and MRI lesion burden in MS patients at the infratentorial level.

User interface of a teleradiology system for the MR assessment of multiple sclerosis.

The aim of this study was to assess the image display of a web-based teleradiology system that uses a common web browser and has no need of proprietary applets, plug-ins, or dedicated software for DICOM display. The teleradiology system (TS) is connected to the Internet by ADSL and to radiological modalities using the DICOM standard with TCP/IP. Images were displayed on a PC through Internet connection with the remote TS using a common web browser. MS lesion number and volume in T1- and T2-weighted images (T1w and T2w, respectively) of 30 brain MR studies were quantified using both the TS and a conventional software. Wilcoxon signed ranks test and intraclass correlation coefficient (ICC) were used to assess the variability and concordance between intra- and inter-observer and TS and conventional DICOM viewer, setting significance at p < 0.05. No significant differences in T1w and T2w volumes between the TS and the conventional software were found by either operator. The ICC results showed a high level of inter-operator agreement in volume estimation in T1w and T2w images using the two systems. Quantitative assessment of MS lesion volumes in T1w and T2w images with a user interface of a teleradiology system that allows the consultation by means of a common web browser, without the need for proprietary plug-ins, applets, or dedicated software for DICOM display showed no significant differences from, and almost complete agreement with, conventional DICOM viewers.

Hippocampal atrophy is the critical brain change in patients with hypoxic amnesia.

Anoxia is considered a good model for studying amnesia. However, not all individuals who experience anoxic events develop memory problems. Moreover, the question still remains about whether, after anoxia, damage is limited to the hippocampus in patients with amnesia and without other significant cognitive deficits. Here we investigated brain damage in a selected sample of adults affected exclusively by an amnesic syndrome after an anoxic episode. The cerebral MR images of these patients were submitted to visual inspection, volumetric measurements of the mesial temporal structures following manual segmentation, and to Voxel-Based Morphometry of the whole brain. We studied five anoxic patients and thirty-three well-matched healthy subjects. Our aim was to: (a) quantify regional atrophic changes associated with chronic anoxic damage compared to control subjects (Group Comparison Analysis); (b) identify regions of common abnormality across all patients (Conjunction Analysis in the VBM); (c) investigate whether measures of regional volume reduction correlated with neuropsychological memory scores; (d) compare the results obtained with visual inspection and ROI analyses with those obtained with VBM. We found that anoxic patients presented a significant reduction of gray matter volume in the hippocampus bilaterally compared to healthy subjects. The only common atrophic region across all patients was the hippocampus bilaterally. Correlation analysis showed only a trend between the Prose immediate free recall test and the left hippocampus. Our findings confirm that the hippocampus is very sensitive to damage stemming from anoxia. Patients with hypoxic amnesia may present damage in other brain regions, but only hippocampal atrophy is common in all of them.

Reduced oxygen due to high-altitude exposure relates to atrophy in motor-function brain areas.

BACKGROUND AND PURPOSE: At high altitudes barometric pressure is reduced and, thus, less oxygen is inhaled. Reduced oxygen concentration in brain tissue can lead to cerebral damage and neurological and cognitive deficits. The present study was designed to explore the effects of high-altitude exposure using a quantitative MRI technique, voxel-based morphometry. METHODS: We studied nine world-class mountain climbers before (baseline) and after (follow-up) an extremely high-altitude ascent of Everest and K2. We investigated the effects of repeated extremely high-altitude exposures by comparing mountain climbers' scans at baseline with scans of 19 controls. In addition, we measured the effects of a single extremely high-altitude expedition by comparing mountain climbers' scans at baseline and follow-up. RESULTS: A region of reduced white matter density/volume was found in the left pyramidal tract near the primary (BA 4) and supplementary (BA 6) motor cortex when mountain climbers at baseline were compared with controls. Further, when mountain climbers' scans before and after the expedition were compared, a region of reduced grey matter density/volume was found in the left angular gyrus (BA 39). CONCLUSION: These findings suggest that extremely high-altitude exposures may cause subtle white and grey matter changes that mainly affect brain regions involved in motor activity.

Navigating toward a novel environment from a route or survey perspective: neural correlates and context-dependent connectivity.

When we move toward a novel environment we may learn it in different ways, i.e., by walking around or studying a map. Both types of learning seem to be very effective in daily life navigation and correspond to two different types of mental representation of space: route and survey representation. In the present study, we investigated the neural basis of route and survey perspectives during learning and retrieval of novel environments. The study was carried out over 5 days, during which participants learned two paths from a different perspective (i.e., route learning and survey learning). Then participants had to retrieve these paths using a survey or route perspective during fMRI scans, on the first and fifth day. We found that the left inferior temporal lobe and right angular gyrus (AG) were activated more during recall of paths learned in a survey perspective than in a route perspective. We also found a session by perspective interaction effect on neural activity in brain areas classically involved in navigation such as the parahippocampal place area (PPA) and the retrosplenial cortex (RSC). A set of frontal, parietal and temporal areas showed different patterns of activity according to the type of retrieval perspective. We tested the context-dependent connectivity of right PPA, RSC and AG, finding that these areas showed different patterns of connectivity in relation to the learning and recalling perspective. Our results shed more light on the segregation of neural circuits involved in the acquisition of a novel environment and navigational strategies.

Automatic quantification of multi-modal rigid registration accuracy using feature detectors.

In radiotherapy, the use of multi-modal images can improve tumor and target volume delineation. Images acquired at different times by different modalities need to be aligned into a single coordinate system by 3D/3D registration. State of the art methods for validation of registration are visual inspection by experts and fiducial-based evaluation. Visual inspection is a qualitative, subjective measure, while fiducial markers sometimes suffer from limited clinical acceptance. In this paper we present an automatic, non-invasive method for assessing the quality of intensity-based multi-modal rigid registration using feature detectors. After registration, interest points are identified on both image data sets using either speeded-up robust features or Harris feature detectors. The quality of the registration is defined by the mean Euclidean distance between matching interest point pairs. The method was evaluated on three multi-modal datasets: an ex vivo porcine skull (CT, CBCT, MR), seven in vivo brain cases (CT, MR) and 25 in vivo lung cases (CT, CBCT). Both a qualitative (visual inspection by radiation oncologist) and a quantitative (mean target registration error-mTRE-based on selected markers) method were employed. In the porcine skull dataset, the manual and Harris detectors give comparable results but both overestimated the gold standard mTRE based on fiducial markers. For instance, for CT-MR-T1 registration, the mTREman (based on manually annotated landmarks) was 2.2 mm whereas mTREHarris (based on landmarks found by the Harris detector) was 4.1 mm, and mTRESURF (based on landmarks found by the SURF detector) was 8 mm. In lung cases, the difference between mTREman and mTREHarris was less than 1 mm, while the difference between mTREman and mTRESURF was up to 3 mm. The Harris detector performed better than the SURF detector with a resulting estimated registration error close to the gold standard. Therefore the Harris detector was shown to be the more suitable method to automatically quantify the geometric accuracy of multimodal rigid registration.

Abnormal motor preparation in severe traumatic brain injury with good recovery.

Movement-related cortical potentials (MRCPs) were examined in seven patients with severe traumatic brain injury (TBI) and 12 matched control subjects. All patients had clinically established good recovery by the time of testing. Flexion movements of the index finger of the left or right hand were recorded in two (alternating and repetitive) self-paced conditions and in one externally triggered condition. In control subjects, the bereitschaftspotential (BP) component of MRCP was detected approximately 2000 msec prior to movement onset in the self-paced conditions and was larger and earlier in the alternating compared to the repetitive condition. The BP component was absent in the externally triggered condition. In TBI patients, the BP was greatly reduced and no difference between the alternating-repetitive conditions was detected; in contrast, only small differences were present in the controls for the negative slope (NS) and MP components and no difference for the reafferent positivity (RAP) component. A dipole analysis indicated the supplementary motor area and the premotor area as the likely generators of BP and NS' components, respectively. Gradientrecalled echo magnetic resonance imaging allowed the detection of a number of small hypointense lesions primarily located in the frontal lobes, as in diffuse axonal injury. This pattern of results indicates a selective deficit in motor preparation and a relatively spared pattern of activation during and following movement in these patients. Imaging data appear generally consistent with the pattern of MRCPs observed in the patient group. Implications of these results for the problem of slowness in TBI patients are discussed.

Involvement of the limbic system in multiple sclerosis patients with depressive disorders.

This study investigates the relationship between depression and both anatomic and cerebral blood flow abnormalities in multiple sclerosis (MS) patients. Ten nondepressed MS patients were compared with 10 depressed MS patients matched for age, sex, and functional disability. Both groups were evaluated by means of neuropsychological tests, magnetic resonance imaging, and single-photon emission tomography imaging. There was no difference between the two groups with regard to the global cognitive score. Magnetic resonance imaging data showed no significant differences in the number, side, location, and area of the demyelinating lesions between the two groups; however, regional cerebral blood flow asymmetries in the limbic cortex did distinguish the two groups. Analysis of variance showed a significant effect of depression on the perfusion asymmetries in the limbic cortex. Finally, perfusion asymmetries in limbic cortex significantly correlated with depression test scores. Our findings suggest that depression in MS patients could be induced by a disconnection between subcortical and cortical areas involved in the function of the limbic system.

Effect of side and rate of stimulation on cerebral blood flow changes in motor areas during finger movements in humans.

We measured, using single photon emission computed tomography, the regional CBF (rCBF) changes in the motor areas of 24 right-handed normal volunteers during the performance of a motor task consisting of sequential finger-to-thumb opposition. Twelve of them performed the task with their right and their left hands consecutively with a fast frequency and large amplitude. The other 12 subjects performed the task with their right hand only at a slow frequency and small amplitude. The contralateral primary sensorimotor areas (S1/M1), supplementary motor area (SMA), and ipsilateral cerebellum were significantly activated during right and left finger movements performed at fast frequency and large amplitude. No significant difference was found between the rCBF changes induced by the right dominant and left nondominant hands. When the task was performed with a slow rate and small amplitude, the SMA was significantly activated while no significant changes were observed in the contralateral S1/M1 or in the ipsilateral cerebellum. These results demonstrate (a) that hand dominance evokes no differences in the activation of the main motor areas and (b) that the frequency and amplitude of the movement have a major effect on the quantitative and qualitative aspect of activation of motor areas in humans.

Supplementary and primary sensory motor area activity in Parkinson's disease. Regional cerebral blood flow changes during finger movements and effects of apomorphine.

We have measured with single-photon emission tomography the regional cerebral blood flow changes that occurred in the supplementary motor areas and in the primary sensory motor areas during sequential finger-to-thumb opposition movements of the right hand in seven akinetic patients with Parkinson's disease and in nine normal volunteers. Parkinsonian patients were studied before ("off" condition) and after a subcutaneous injection of apomorphine hydrochloride which was able to switch them "on" (on condition). In normal volunteers and parkinsonian patients in the on condition, regional cerebral blood flow significantly increased in the supplementary motor areas and in the contralateral primary sensory motor cortex but not in the ipsilateral primary sensory motor cortex. On the contrary, no significant regional cerebral blood flow change was observed in these areas in parkinsonian patients in the off condition. These results support the hypothesis that a functional cortical motor area deafferentation is involved in the pathophysiological makeup of akinesia and that this abnormality is reversed by dopaminergic drugs.

Use of Bacille Calmette-Guèrin (BCG) in multiple sclerosis.

We studied the effect of Bacille Calmette-Guerin (BCG) vaccine as an immunomodulator in MS. According to the guidelines for clinical trials in MS, a single crossover, MRI-monitored trial was performed in 14 patients with relapsing-remitting MS. After treatment, MRI activity was significantly reduced. No major adverse effects were reported. Adjuvant therapy with BCG vaccine was safe and merits study in MS.

Diazepam effects on the cerebral responses to tonic pain: a SPET study.

RATIONALE: Pain is a complex phenomenon with a strong affective-emotional component in addition to a sensory-discriminative one. This causes the activation of multiple brain areas, which process different aspects of pain simultaneously. OBJECTIVES: We investigated the effects of diazepam (DZ) on a well-known pattern of brain regions activated by cold, tonic pain stimuli. METHODS: Quantitative cerebral blood flow (CBF) was assessed by single photon emission tomography (SPET) and the Xe-133 inhalatory method, at rest and during tonic pain activation in eight normal, right-handed, male volunteers. The cold pressor test (CPT) was performed by immersion of the left hand in cold water twice, first during CPT alone, and again 30 min after intravenous administration of diazepam (CPT+DZ). RESULTS: During CPT we observed a significant CBF increase in the right thalamus, primary sensory-motor cortex (S1/M1), frontal and temporal regions, and in the left temporal region and anterior cingulate cortex (ACC). During CPT+DZ, the average CBF was significantly lower than during the CPT state (-11%, P<0.05). After normalisation, during CPT+DZ we again observed a significant CBF increase in the right thalamus, S1/M1 and frontal regions, and in the left ACC, though not in the temporal regions. DZ administration first causes a global reduction in CBF, then modifies the pattern of brain activation. CONCLUSIONS: During CPT, activation of the temporal regions has been interpreted as part of the affective-emotional component of pain response. DZ seems to affect the "pain-related" pattern of activation by abolishing the CBF increase in the temporal regions, without, however, modifying the pain perception or determining a sedating effect.

Presurgical integrated MRI/SPECT localization of the sensorimotor cortex in a patient with a low-grade astrocytoma in the rolandic area.

We describe the case of a young man who, despite the presence of a tumour in the left sensorimotor cortex, exhibited no motor deficit. Integrated MRI/SPECT-CBF study during motor activation was aimed at determining which cerebral areas were involved in movement execution in this patient and their relationship with the tumour. CBF changes during motor activation were located in two motor areas: anteriorly and medially to the tumour in the left frontal lobe (+29%) and in the right medial frontal cortex (+43%). Integrated MRI/SPECT images provided both an anatomical and functional definition of the motor areas in a patient with a rolandic tumour and could prove useful in determining preoperatively an appropriate surgical strategy.

Demyelinating plaques in relapsing-remitting and secondary-progressive multiple sclerosis: assessment with diffusion MR imaging.

BACKGROUND AND PURPOSE: Conventional MR imaging does not provide specific information that can be reliably associated with the pathologic substrate and clinical status of patients with multiple sclerosis (MS). Our goals were 1) to determine whether the orientationally averaged water diffusion coefficient () can be used to distinguish between plaques of different severity in these patients and 2) to assess possible correlations between values and disease duration, Expanded Disability Status Scale (EDSS) score, and signal intensity on T1-weighted MR images. METHODS: Twenty patients (10 with relapsing-remitting MS and 10 with secondary-progressive MS) and 11 healthy volunteers underwent a combined conventional and diffusion-weighted MR study of the brain. , a parameter that is proportional to the trace of the diffusion tensor, was computed by averaging the apparent diffusion coefficients measured in the x, y, and z directions. measurements were obtained for selected areas of white matter plaques. Differences in among the three groups were tested using analysis of variance. RESULTS: was significantly higher (1.445 +/- 0.129 x 10(-3) mm2/s) in secondary-progressive lesions than in relapsing-remitting lesions (0.951 +/- 0.08), and both values were higher than in normal white matter (0.732 +/- 0.02). There was a significant negative correlation between and the degree of hypointensity on T1-weighted images, and a positive correlation between and both EDSS score and disease duration. CONCLUSION: Our findings suggest that is useful for distinguishing MS lesions of different severities, which are associated with different degrees of clinical disability.

[Cerebral blood volume, endarterectomy and SPECT]. / Volume sanguin cérébral, endartérectomie et SPECT.

Cerebral blood flow and cerebral blood volume were measured and quantified using single photon emission computed tomography before and after unilateral endarterectomy in 3 patients with bilateral severe lesions of the internal carotid artery. These parameters were measured using an intravenous injection of 133 Xenon and 99m Technetium respectively. Before endarterectomy cerebral blood volume was high in all patients suggesting a focal vasodilatation in response to a reduced cerebral perfusion pressure. After endarterectomy a decrease of cerebral blood volume and an increase of cerebral blood flow were observed. These preliminary results confirm that the hemodynamic adaptative mechanisms secondary to carotid occlusion are reversible when the stenosis is removed and demonstrate that these changes can be accurately measured using single photon emission computed tomography. Positron emission tomography was previously considered to be the only method able to quantify cerebral blood volume in man. Single photon emission computed tomography can also be considered a reliable technique to measure both cerebral blood flow and cerebral blood volume. This technique can then be used to assess individual cerebral vascular adaptative states and to evaluate the influence of cerebral hemodynamic changes on stroke occurrence in large longitudinal studies.