Regional Cerebral Disease Progression in Friedreich's Ataxia: A Longitudinal Diffusion Tensor Imaging Study.

BACKGROUND AND PURPOSE: Imaging biomarkers of disease progression are desirable in inherited ataxias. MRI has demonstrated brain damage in Friedreich ataxia (FRDA) in form of regional atrophy of the medulla, peridentate cerebellar white matter (WM) and superior cerebellar peduncles (visible in T1-weighted images) and of change of microstructural characteristics of WM tracts of the brainstem, cerebellar peduncles, cerebellum, and supratentorial structures (visible through diffusion-weighted imaging). We explored the potential of brain MR morphometry and diffusion tensor imaging (DTI) to track the progression of neurodegeneration in FRDA. METHODS: Eight patients (5F, 3M; age 13.4-41.2 years) and 8 healthy controls (2F, 6M; age 26.2-48.3 years) underwent 2 MRI examinations (mean 3.9 and 4.1 years apart, respectively) on the same 1.5T scanner. The protocol included 3D T1-weighted images and axial diffusion-weighted images (b-value 1,000 s/mm(2)) for calculating maps of fractional anisotropy, mean, axial and radial diffusivity, and mode of anisotropy. Tensor-based morphometry was used to investigate regional volume changes and tract-based spatial statistics was used to investigate microstructural changes in WM tracts. RESULTS: Longitudinal analyses showed no differences in regional volume changes but a significant difference in axial diffusivity changes in cerebral and corpus callosum WM of patients as compared to controls (mean longitudinal rate of change for axial diffusivity: -.02 × 10(-3) mm(2)/s/year in patients vs. .01 × 10(-3) mm(2)/s/year in controls). No correlation with number of triplets, disease duration, and worsening of the clinical deficit was observed. CONCLUSION: DTI can track brain microstructural changes in FRDA and can be considered a potential biomarker of disease progression.

Cerebellar hyperperfusion in semantic dementia.

Despite evidence of a cerebellar contribution to language, possible functional changes of the cerebellum in patients with language impairment secondary to cerebral neurodegeneration has not been investigated so far. We examined with resting perfusion single photon emission tomography one patient with semantic dementia and the data were compared with a normal subject database. Region of interest and Statistical Parametric Mapping 2 analysis showed in the patient hypoperfusion of the left temporal and parietal lobe and hyperperfusion in the superior vermis and cerebellar hemispheres (lobules IV, V, and VI). The cerebellum shows increased flow of possible compensatory significance in patients with language disturbance associated to cerebral degenerative changes.

Neurodegeneration in friedreich's ataxia is associated with a mixed activation pattern of the brain. A fMRI study.

Friedreich's ataxia (FRDA) is associated with a distributed pattern of neurodegeneration in the spinal cord and the brain secondary to selective neuronal loss. We used functional MR Imaging (fMRI) to explore brain activation in FRDA patients during two motor-sensory tasks of different complexity, i.e. continuous hand tapping and writing of "8" figure, with the right dominant hand and without visual feedback. Seventeen FRDA patients and two groups of age-matched healthy controls were recruited. Task execution was monitored and recorded using MR-compatible devices. Hand tapping was correctly performed by 11 (65%) patients and writing of the "8" by 7 (41%) patients. After correction for behavioral variables, FRDA patients showed in both tasks areas of significantly lower activation in the left primary sensory-motor cortex and right cerebellum. Also left thalamus and right dorsolateral prefrontal cortex showed hypo-activation during hand tapping. During writing of the "8" task FRDA patients showed areas of higher activation in the right parietal and precentral cortex, globus pallidus, and putamen. Activation of right parietal cortex, anterior cingulum, globus pallidus, and putamen during writing of the "8" increased with severity of the neurological deficit. In conclusion fMRI demonstrates in FRDA a mixed pattern constituted by areas of decreased activation and areas of increased activation. The decreased activation in the primary motor cortex and cerebellum presumably reflects a regional neuronal damage, the decreased activation of the left thalamus and primary sensory cortex could be secondary to deafferentation phenomena, and the increased activation of right parietal cortex and striatum might have a possible compensatory significance.

Axial diffusivity is increased in the degenerating superior cerebellar peduncles of Friedreich's ataxia.

INTRODUCTION: Decreased fractional anisotropy (FA) demonstrated by diffusion tensor MR imaging (DTI) in areas of white matter (WM) damage is generally associated with increase of radial diffusivity, while axial diffusivity is reported to be decreased, unchanged, or increased. Aiming to better define the type of axial diffusivity change occurring in a typical human neurodegenerative disease, we investigated axial and radial diffusivity in Friedreich's ataxia (FRDA) which is characterized by selective neuronal loss of the dentate nuclei and atrophy and decreased FA of the superior cerebellar peduncles (SCPs). METHODS: Axial and radial diffusivity of the whole-brain WM were evaluated in 14 patients with FRDA and 14 healthy volunteers using DTI at 1.5 T and the tract-based spatial statistics (TBSS) method, part of FSL software. RESULTS: TBSS analysis showed a single area in the central midbrain corresponding to the decussation of the SCPs which exhibited lower FA in patients than in controls. In this area, a significant increase of both axial and radial diffusivity was observed. No clusters of significantly decreased axial diffusivity were observed, while additional clusters of increase of radial diffusivity were present throughout the brain. CONCLUSIONS: The selective decrease of FA in SCPs of FRDA patients reflecting chronic WM tract damage is associated with increase of both the axial and radial diffusivity, the latter more pronounced than the former. The ultrastructural and biophysical bases of the increased axial diffusivity in chronically degenerating WM tracts deserve further studies.

Assessment of brain white matter fiber bundle atrophy in patients with Friedreich ataxia.

PURPOSE: To investigate in vivo severity and topographic distribution of brain white matter (WM) fiber bundle atrophy in patients with Friedreich ataxia, a condition characterized by an uneven involvement of brain WM, and to correlate such findings with the clinical status of the patients. MATERIALS AND METHODS: The study was conducted with institutional review board approval. Written informed consent was obtained from each participant. Sixteen patients with Friedreich ataxia and 15 healthy control subjects were studied by using a 1.5-T magnetic resonance (MR) imager and 3-mm-thick diffusion-tensor images with 15 noncollinear directions. The size of WM fiber bundles was examined at a voxel level by using a recently developed method, which relies on production of anisotropy maps and nonlinear registration. Data were analyzed by using statistical parametric mapping software and an analysis of covariance model adjusted for age and sex. RESULTS: Compared with control subjects, patients with Friedreich ataxia had WM atrophy in (a) the central portion of the medulla oblongata, (b) the dorsal upper pons, (c) the superior cerebellar peduncles, (d) the central portion of the midbrain, (e) the medial portion of the right cerebral peduncle, (f) the peridentate region, bilaterally, and (g) the optic chiasm. The severity of the neurologic deficits correlated significantly with atrophy of the peridentate WM, bilaterally, and that of the superior cerebellar peduncle decussation. CONCLUSION: Findings of this study show that it is feasible to obtain in vivo atrophy estimates of specific brain WM fiber bundles in patients with Friedreich ataxia and that such estimates correlate with patients' clinical status. This approach has the potential to provide new information that is likely to improve the understanding of the pathophysiology of inherited ataxias.

Peduncular hallucinosis: a polysomnographic and spect study of a patient and efficacy of serotonergic therapy.

Peduncular hallucinosis (PH) consists of formed and coloured visual images, which the patient knows are unreal; it is often associated with lesions of the pons, midbrain and diencephalon. A 72-year-old man had noted the sudden onset of visual hallucinations one year before, specifying the time and body position in a 4-week, 24-h diary. Thereafter, he underwent video-polysomnography (VPSG), brain magnetic resonance imaging (MRI), angiography (MRA), proton spectroscopy ((1)H MRS), and single photon emission tomography (SPECT). Patient's diaries and VPSG showed a strong clustering of hallucinatory experiences during the evening/night time while lying in supine position, similar to hypnagogic hallucination and sleep paralysis in supine position. Repeated episodes of REM sleep behaviour disorder (RBD) occurred during the night. MRI and MRA showed an elongated and dilated left internal carotid artery displacing the left subthalamus upwards, and (1)H MRS relatively decreased N-acetyl-aspartate in the left subthalamus. Brain SPECT during PH revealed hypoperfusion in the right temporal region and hyperperfusion in the left occipital and right opercular regions (the latter possibly related to the patient's awareness of unreality). PH resolved with serotonergic (citalopram) therapy.

Impact of cerebrospinal fluid contamination on brain metabolites evaluation with 1H-MR spectroscopy: a single voxel study of the cerebellar vermis in patients with degenerative ataxias.

PURPOSE: To investigate the impact of cerebrospinal fluid (CSF) contamination on metabolite evaluation in the superior cerebellar vermis with single-voxel (1)H-MRS in normal subjects and patients with degenerative ataxias. MATERIALS AND METHODS: Twenty-nine healthy volunteers and 38 patients with degenerative ataxias and cerebellar atrophy were examined on a 1.5 Tesla scanner. Proton spectra of a volume of interest placed in the superior vermis were acquired using a four TE PRESS technique. We calculated N-acetyl aspartate (NAA)/creatine (Cr), choline (Cho)/Cr, and NAA/Cho ratios, T(2) relaxation times and concentrations of the same metabolites using the external phantom method. Finally, concentrations were corrected taking into account the proportion of nervous tissue and CSF, that was determined as Volume Fraction (VF). RESULTS: In healthy subjects, a significant difference was observed between metabolite concentrations with and without correction for VF. As compared to controls, patients with ataxias showed significantly reduced NAA/Cr and NAA concentrations, while only corrected Cr concentration was significantly increased. The latter showed an inverse correlation with VF. CONCLUSION: CSF contamination has a not negligible effect on the estimation of brain metabolites. The increase of Cr concentration in patients with cerebellar atrophy presumably reflects the substitutive gliosis which takes place along with loss of neurons.

Brain white matter damage in SCA1 and SCA2. An in vivo study using voxel-based morphometry, histogram analysis of mean diffusivity and tract-based spatial statistics.

BACKGROUND AND PURPOSE: Neurodegeneration in spinocerebellar ataxia type 1(SCA1) and 2(SCA2) is associated with white matter(WM) damage. Voxel-Based Morphometry(VBM), histogram analysis of mean diffusivity(MD) and Tract-Based Spatial Statistics(TBSS) enable an in vivo quantitative analysis of WM volume and structure. We assessed with these 3 techniques the whole brain WM damage in SCA1 and SCA2. PATIENTS AND METHODS: Ten patients with SCA1, 10 patients with SCA2 and 10 controls underwent MRI with acquisition of T1-weighted and diffusion tensor images. The results were correlated with severity of clinical deficit. RESULTS: VBM showed atrophy of the brainstem and cerebellar WM without significant differences between SCA1 and SCA2. Focal atrophy of the cerebral subcortical WM was also present. Histogram analysis revealed increased MD in the brainstem and cerebellum in patients with SCA1 and SCA2 which in SCA2 was more pronounced and combined with mild increase of the MD in the cerebral hemispheres in SCA2. In SCA1 and SCA2 TBSS revealed decreased fractional anisotropy(FA) in the inferior, middle and superior cerebellar peduncles, pontine transverse fibres, medial and lateral lemnisci, spinothalamic tracts, corticospinal tracts and corpus callosum. The extent of tract changes was greater in SCA2 patients who also showed decreased FA in the short intracerebellar tracts. In both diseases VBM, histogram and TBSS results correlated with clinical severity. CONCLUSIONS: Brain WM damage featuring a pontocerebeellar atrophy is similar in SCA1 and SCA2 but more pronounced in SCA2. In both diseases it correlates with severity of the clinical deficit.

Brain structural damage in spinocerebellar ataxia type 1 : a VBM study.

BACKGROUND AND OBJECTIVE: Neuropathological description of the brain in spinocerebellar ataxia type 1(SCA1) is limited to a few cases. Voxel-based morphometry (VBM) enables an unbiased in vivo whole-brain quantitative analysis of regional differences in gray matter (GM) and white matter (WM) volume. We assessed with VBM the structural damage in patients with genetically confirmed SCA1. METHOD: Fifteen SCA1 patients and 15 age-matched healthy controls underwent MR examination with acquisition of high-resolution T1-weighted images. The results were correlated with the disease duration and severity of the clinical deficit assessed with the International Cerebellar Ataxia Rating Scale (ICARS) and Inherited Ataxia Clinical Rating Scale (IACRS). RESULTS: As compared to controls, patients with SCA1 showed a significant (p < 0.05 corrected for multiple comparison) symmetric loss of volume of the GM in the rostral cerebellar vermis and paramedian portions of the anterior cerebellar lobes. WM was decreased in the peridentate region and middle cerebellar peduncles but not in the pons. No GM or WM volume loss was found in the cerebral hemispheres. The cerebellar and brainstem GM and WM volume loss correlated with disease duration and the ICARS and IACRS scores. CONCLUSIONS: VBM confirms that atrophy predominantly involves the brainstem and cerebellum in SCA1. The correlation with the clinical features indicates that VBM might be useful to monitor disease progression.

Brain structural damage in spinocerebellar ataxia type 2. A voxel-based morphometry study.

Voxel-based morphometry (VBM) enables an unbiased in-vivo whole-brain quantitative analysis of differences in gray matter (GM), white matter (WM) and cerebro-spinal fluid (CSF) volumes. We assessed with VBM 20 spinocerebellar ataxia Type 2 (SCA2) patients with mild or moderate cerebellar deficit and 20 age and sex-matched healthy controls. SCA2 patients showed a significant (P < 0.05 corrected for multiple comparison) symmetric loss of GM in the cerebellar vermis and hemispheres sparing lobules I,II, Crus II,VII, and X, and of the WM in the peridentate region, middle cerebellar peduncles, dorsal pons, and cerebral peduncles. The CSF volume was increased in the posterior cranial fossa. No GM, WM or CSF volume changes were observed in the supratentorial compartment. A mild (P < 0.05, >0.01) correlation was observed between the GM and WM loss and severity of the neurological deficit. In SCA2 patients with mild to moderate cerebellar deficit, GM and WM volume loss and CSF volume increase are confined to the posterior cranial fossa.

Brain white matter tracts degeneration in Friedreich ataxia. An in vivo MRI study using tract-based spatial statistics and voxel-based morphometry.

BACKGROUND AND PURPOSE: Neuropathological examination in Friedreich ataxia (FRDA) reveals neuronal loss in the gray matter (GM) nuclei and degeneration of the white matter (WM) tracts in the spinal cord, brainstem and cerebellum, while the cerebral hemispheres are substantially spared. Tract-based spatial statistics (TBSS) enables an unbiased whole-brain quantitative analysis of the fractional anisotropy (FA) and mean diffusivity (MD) of the brain WM tracts in vivo. PATIENTS AND METHODS: We assessed with TBSS 14 patients with genetically confirmed FRDA and 14 age- and sex-matched healthy controls who were also examined with voxel-based morphometry (VBM) to assess regional atrophy of the GM and WM. RESULTS: TBSS revealed decreased FA in the inferior and superior cerebellar peduncles and the corticospinal tracts in the medullary pyramis, in WM tracts of the right cerebellar hemisphere and in the right occipito-frontal and inferior longitudinal fasciculi. Increased MD was observed in the superior cerebellar peduncles, deep cerebellar WM, posterior limbs of the internal capsule and retrolenticular area, bilaterally, and in the WM underlying the left central sulcus. Decreased FA in the left superior cerebellar peduncle correlated with clinical severity. VBM showed small symmetric areas of loss of bulk of the peridentate WM which also correlated with clinical severity. CONCLUSIONS: TBSS enables in vivo demonstration of degeneration of the brainstem and cerebellar WM tracts which neuropathological examination indicates to be specifically affected in FRDA. TBSS complements VBM and might be a more sensitive tool to detect WM structural changes in degenerative diseases of the CNS.

Self-paced frequency of a simple motor task and brain activation. An fMRI study in healthy subjects using an on-line monitor device.

Application of fMRI to clinical neurology implies the selection of a simple task and control of the task performance. The capability to objectively monitor variables related to task execution is, therefore, important and could improve accuracy of clinical fMRI studies. We assessed the influence of different self-paced frequencies of a simple motor task on brain activation in healthy subjects. A device was developed to measure the force exerted by a subject in pressing an air-filled rubber bulb with the last four fingers of the dominant hand. The task frequency was determined by analysis of the force signal. Nine healthy subjects performed twice the task with self-paced slow (0.35+/-0.09 Hz), intermediate (0.58+/-0.21 Hz) or fast (0.98+/-0.32 Hz) frequency. The device revealed impaired task execution in 1 subject. The coefficient of variation of frequency was 8.7% for slow, 12.2% for intermediate and 15.8% for fast paced task. No significant differences were found comparing the activation maps obtained at slow, intermediate and fast frequencies in the contralateral sensorimotor cortex and ipsilateral cerebellum. Cluster reproducibility was good for location (standard deviation

Pontine hyperperfusion in sporadic hyperekplexia.

OBJECTIVE: To explore with neuroimaging techniques the anatomical and functional correlates of sporadic hyperekplexia. METHODS: Two elderly women with sporadic hyperekplexia underwent neurophysiological assessment, MRI of the brain and proton magnetic resonance spectroscopy (1H-MRS) of the brainstem and frontal lobes. Regional cerebral blood flow was investigated with single photon emission tomography (SPECT) during evoked startles and at rest. RESULTS: Both patients showed excessively large and non-habituating startle responses. In both patients, MRI showed impingement of the brainstem by the vertebrobasilar artery, lack of frontal or brainstem abnormalities on 1H-MRS and hyperperfusion in the dorsal pons and cingulate cortex, and superior frontal gyrus at SPECT during evoked startles. CONCLUSIONS: In our patients with hyperekplexia, the vertebrobasilar arteries were found to impinge on the brainstem. Neurophysiological findings and neurofunctional imaging of evoked startles indicated a pontine origin of the movement disorder modulated by activation in cortical, especially frontal, areas. The neurofunctional correlates of evoked startles in human sporadic hyperekplexia are similar to those observed for the startle circuit in animals.

Subcortical damage and cortical functional changes in men and women with Fabry disease: a multifaceted MR study.

PURPOSE: To prospectively compare brain magnetic resonance (MR) imaging and hydrogen 1 (1H) MR spectroscopy findings and to use functional MR imaging to explore the patterns of brain activation in men and women with Fabry disease (FD). MATERIALS AND METHODS: Eight men and eight women with FD (mean age, 38.8 years +/- 13.9 [standard deviation]) with absent or mild neurologic deficit and 16 healthy control subjects (eight men and eight women; mean age, 42.7 years +/- 15.3) gave informed consent to participate in the study, which was approved by the local ethical committee. Patients and control subjects underwent MR imaging, 1H MR spectroscopy of the frontal cortex and subcortical white matter, and functional MR imaging during repetitive flexion-extension of the last four fingers of the right hand. Extent of cerebral white matter damage was rated on fluid-attenuated inversion recovery MR images by using a visual score. Areas of activation were identified by using statistical parametric mapping software and the adoption of a height threshold of P < .001 (uncorrected) and an extent threshold of P < .05 (corrected). RESULTS: Men and women with FD showed a similar distribution of cerebral white matter changes, lacunar and cortical infarcts, small hemorrhages, and vertebrobasilar dolichoectasia. No significant (P > .05) difference was observed between patients with FD and control subjects for concentration of N-acetylaspartate, creatine, and choline. During the motor task, patients showed recruitment of additional cortical areas in comparison with control subjects. Increased activation of the contralateral sensorimotor area correlated (P = .002) with extent of white matter damage. CONCLUSION: Subcortical ischemic changes in men and women with FD are similar and are associated with increased recruitment of the sensorimotor network during a simple motor task, which might limit the functional effect of the white matter small-vessel disease.

Risk-benefit analysis of X-ray exposure associated with lung cancer screening in the Italung-CT trial.

OBJECTIVE: Prior analyses of X-ray exposures in lung cancer screening with CT considered the basic acquisition technique in single-detector scanners and the effects of a lifetime screening regimen, whereas the potential benefit in terms of lives saved was not addressed. MATERIALS AND METHODS: We determined the total-body effective dose of different acquisition techniques for one single-detector and one MDCT scanner and made projections about the cumulative radiation exposure to smokers undergoing four annual CT examinations on the same scanners in the Italung-CT Trial. Combining these data with estimates of radiation-induced fatal cancer and of the benefit of screening, we calculated the risk-benefit ratio for participants in the trial, ex-smokers, and never-smokers. RESULTS: The cumulative effective doses per 1,000 subjects were 3.3 Sv using an MDCT scanner and 5.8 or 7.1 Sv using a single-detector scanner. Potential fatal cancers associated with radiation exposure were 0.11 per 1,000 subjects for MDCT scanners and 0.20 or 0.24 for single-detector scanners, which is about 10-100 times lower than the number of expected lives saved by screening assuming a 20-30% lung cancer-specific mortality reduction in current smokers. They were, however, of similar magnitude to the lives saved by screening in never-smokers and former smokers assuming a 10% efficacy of screening. CONCLUSION: MDCT is associated with lower radiation doses than single-detector CT technology. The risk of radiation dose in the Italung-CT Trial is compensated for by the expected benefit. CT screening for lung cancer should not be offered to never-smokers, whereas its recommendation in former smokers is debatable.

Huntington disease: volumetric, diffusion-weighted, and magnetization transfer MR imaging of brain.

PURPOSE: To investigate whether diffusion-weighted and magnetization transfer (MT) magnetic resonance (MR) imaging depict regional and/or global brain abnormalities in patients with Huntington disease (HD). MATERIALS AND METHODS: Twenty-one carriers of the HD mutation (mean age, 58 years +/- 11 [SD]) and 21 healthy control subjects (mean age, 54 years +/- 13) underwent conventional, diffusion-weighted, and MT MR imaging. Volumes, mean apparent diffusion coefficients (ADCs), and MT ratios (MTRs) for left and right caudate nucleus, putamen, and cerebral periventricular white matter-as well as an index of normalized brain volume and whole-brain ADC and MT histograms-were computed. Asymmetry in volume, ADC, and MTR measurements in caudate nucleus, putamen, and periventricular white matter in control subjects and HD carriers were evaluated with Wilcoxon testing for paired samples. Differences in MR imaging variables between HD carriers and control subjects were evaluated with Mann-Whitney U testing; correlations between stages of clinical severity and MR imaging data were investigated with Spearman rank correlation testing. RESULTS: No significant asymmetry was observed for any of the MR imaging variables. Caudate nucleus, putamen, and whole-brain volumes were smaller (P <.001 for all) in HD carriers than in control subjects. HD carriers also had increased ADC in the caudate nucleus (P =.002), putamen (P <. 001), cerebral periventricular white matter (P <.001), and whole brain (P <.001). MTR was not significantly different between HD carriers and control subjects. Correlation was observed between stages of increasing clinical disease severity and both decrease in volume of caudate nucleus (Spearman rho = -0.63), putamen (rho = -0.64), and whole brain (rho = -0.46) and increase in ADC in caudate nucleus (rho = 0.52), periventricular white matter (rho = 0.45), and whole brain (rho = 0.44). CONCLUSION: Regional and global volume loss in HD is accompanied by an increase in ADC; this correlates with disease severity.

ADC mapping of neurodegeneration in the brainstem and cerebellum of patients with progressive ataxias.

Analysis of the apparent diffusion coefficient (ADC) maps derived from diffusion-weighted MR imaging is emerging as a reproducible, sensitive, and quantitative tool to evaluate brain damage in diseases of the white and gray matter. To explore the potentials of ADC maps analysis in degenerative ataxias, we examined 28 patients and 26 age-matched controls with T1, T2, and diffusion (b values 0-1000 along the three main body axes)-weighted MR images. Twenty-four patients had inherited genetically proven diseases including spinocerebellar ataxia type 1 (SCA1) (n = 9), spinocerebellar ataxia type 2 (SCA2) (n = 8), and Friedreich's ataxia (FA) (n = 7), whereas four patients had sporadic adult onset pure cerebellar ataxia (three idiopathic, one gluten intolerance). Area and linear measurements of the CNS structures contained in the posterior cranial fossa (PCF) preliminary enabled classification of the patients in the three morphological categories reflecting the gross pathology findings, namely olivopontocerebellar atrophy (OPCA) (n = 10: six SCA2 and four SCA1), spinal atrophy (SA) (n = 7: all FA), and cortical cerebellar atrophy (CCA) (n = 4: three idiopathic and one gluten intolerance). Seven patients with SCA1 (n = 5) or SCA2 (n = 2) had morphologic changes reminiscent of OPCA, but their values were still in the lower normal range and were classified as undefined. Mean diffusivity (D) maps of the entire brain were generated and D was measured with regions of interest (ROI) in the medulla, pons, middle cerebellar peduncles, and the peridentate white matter. Moreover, after exclusion of the skull with manual segmentation and of the CSF with application of a threshold value, histograms were obtained for D of the brainstem and cerebellum and for D of the cerebral hemispheres. As compared to controls, a (P < 0.001) increase of D was observed in the medulla, middle cerebellar peduncles, and peridentate white matter in OPCA and undefined patients groups who had also significantly increased values of the 25th and 50th percentiles in the brainstem and cerebellum D histogram. In CCA (P = 0.01), an increase of the 25th and 50th percentile of the D value was observed in the brainstem and cerebellum histograms. The SA group showed (P < 0.001) an increased D in the medulla only. A correlation between clinical severity as assessed with the Inherited Ataxias Clinical Rating Scale (IACRS) and the 50th percentile of the D value in the brainstem and cerebellum histogram (r = 0.69) was observed in patients with SCA1 or SCA2. Diffusion MR imaging reveals variable patterns of increase of D in the brainstem, cerebellum, and cerebral hemispheres in degenerative ataxias that match the known distribution of the neuropathological changes.

Whole brain apparent diffusion coefficient histogram: a new tool for evaluation of leukoaraiosis.

PURPOSE: To test whole brain apparent diffusion coefficient histogram analysis as an alternative approach to visual score for the assessment of leukoaraiosis (LA). MATERIALS AND METHODS: T2 and diffusion weighted images were obtained in 15 elderly patients. LA extension was assessed on T2 weighted images by two observers using a semiquantitative visual score. Apparent diffusion coefficient (ADC) maps of the entire brain were generated and, after exclusion of the skull with manual tracing and of the cerebrospinal fluid (CSF) by application of a threshold value, whole brain (WB)-ADC histogram was obtained. Moreover, a brain volume index (BVI) was calculated on ADC maps as (intracranial volume - CSF volume) /intracranial volume. RESULTS: The kappa inter-observer agreement for LA scoring was 0.69. Manual segmentation of the skull showed a mean inter-operator coefficient of variation below 3%. The median value of whole brain ADC histogram directly correlated with LA extension (P = 0.013). Moreover a significant inverse correlation (P = 0.002) was found between WB-ADC median value and BVI. CONCLUSION: WB-ADC histogram is a reproducible alternative tool for assessing LA extension and severity.