Andrea Falini

Università Vita-Salute San Raffaele, Milano, Lombardy, Italy

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Publications (270)1383.01 Total impact

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    ABSTRACT: Background: Longitudinal MRI studies in Alzheimer's disease (AD) are one of the most reliable way to track brain changes along the course of the disease. Objective: To investigate the evolution of grey matter (GM) atrophy and white matter (WM) damage in AD patients, and to assess the relationships of MRI changes with baseline clinical and cognitive variables and their evolution over time. Methods: Clinical, neuropsychological, and MRI assessments (T1-weighted and diffusion tensor [DT]-MRI) were obtained from 14 patients with AD at baseline and after a 16 ± 3 month period. Lumbar puncture was obtained at study entry. At baseline, AD patients were compared to 37 controls. GM atrophy progression was assessed with tensor-based morphometry and GM volumes of interest, and WM damage progression using tract-based spatial statistics and tractography. Results: At baseline, patients showed cortical atrophy in the medial temporal and parietal regions and a widespread pattern of WM damage involving the corpus callosum, cingulum, and temporo-occipital, parietal, and frontal WM tracts. During follow up, AD patients showed total GM atrophy, while total WM volume did not change. GM tissue loss was found in frontal, temporal, and parietal regions. In addition, AD patients showed a progression of WM microstructural damage to the corpus callosum, cingulum, fronto-parietal and temporo-occipital connections bilaterally. Patients with higher baseline cerebrospinal fluid total tau showed greater WM integrity loss at follow up. GM and WM changes over time did not correlate with each other nor with cognitive evolution. Conclusion: In AD, GM atrophy and WM tract damage are likely to progress, at least partially, independently. This study suggests that a multimodal imaging approach, which includes both T1-weighted and DT MR imaging, may provide additional markers to monitor disease progression.
    Journal of Alzheimer's disease: JAD 09/2015; 47(4):995-1007. DOI:10.3233/JAD-150196 · 4.15 Impact Factor
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    ABSTRACT: The hippocampus is part of the default-mode network (DMN) and is functionally hit early in multiple sclerosis (MS). Hippocampal and DMN dysfunctions have been associated with depression, both in patients with MS and in major depressive disorders. We hypothesized that white matter lesions may contribute, through a disconnection mechanism, to hippocampal dysfunction. To test this, we assessed the relationship between hippocampal resting-state (RS) functional connectivity (FC) abnormalities with brain T2 lesion volumes and the presence and severity of depression. Structural and RS fMRI images were acquired from 69 patients with cognitively intact MS and 42 matched healthy controls (HC). Depression was quantified using the Montgomery-Asberg Depression Rating Scale. Seed-voxel hippocampal RS FC was assessed. SPM8 was used for between-group comparisons and correlation analysis between RS FC abnormalities with clinical and structural MRI variables. Compared to HC, patients with MS showed a significant atrophy of the whole brain and left hippocampus (P < 0.001), and a distributed pattern of decreased RS FC between the hippocampi and several cortical-subcortical regions, which were mostly located within the DMN. Reduced hippocampal RS FC with regions of the DMN was strongly correlated with higher T2 lesion volume, longer disease duration, and the severity of depression and disability. In patients with cognitively preserved MS, brain focal WM lesions are related to the functional integration of the hippocampus to other brain regions of the DMN, suggesting a disconnection syndrome. Such a disruption of hippocampal RS FC is likely to contribute to the occurrence of depression and to clinical disability. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc.
    Human Brain Mapping 09/2015; DOI:10.1002/hbm.22992 · 5.97 Impact Factor
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    ABSTRACT: Objective: To use a multimodal approach to assess brain structural pathways and resting state (RS) functional connectivity abnormalities in patients with Parkinson's disease and freezing of gait (PD-FoG). Methods: T1-weighted, diffusion tensor (DT) MRI and RS functional MRI (fMRI) were obtained from 22 PD-FoG patients and 35 controls on a 3.0 T MR scanner. Patients underwent clinical, motor, and neuropsychological evaluations. Gray matter (GM) volumes and white matter (WM) damage were assessed using voxel based morphometry and tract-based spatial statistics, respectively. The pedunculopontine tract (PPT) was studied using tractography. RS fMRI data were analyzed using a model free approach investigating the main sensorimotor and cognitive brain networks. Multiple regression models were performed to assess the relationships between structural, functional, and clinical/cognitive variables. Analysis of GM and WM structural abnormalities was replicated in an independent sample including 28 PD-FoG patients, 25 PD patients without FoG, and 30 healthy controls who performed MRI scans on a 1.5 T scanner. Results: Compared with controls, no GM atrophy was found in PD-FoG cases. PD-FoG patients showed WM damage of the PPT, corpus callosum, corticospinal tract, cingulum, superior longitudinal fasciculus, and WM underneath the primary motor, premotor, prefrontal, orbitofrontal, and inferior parietal cortices, bilaterally. In PD-FoG, right PTT damage was associated with a greater disease severity. Analysis on the independent PD sample showed similar findings in PD-FoG patients relative to controls as well as WM damage of the genu and body of the corpus callosum and right parietal WM in PD-FoG relative to PD no-FoG patients. RS fMRI analysis showed that PD-FoG is associated with a decreased functional connectivity of the primary motor cortex and supplementary motor area bilaterally in the sensorimotor network, frontoparietal regions in the default mode network, and occipital cortex in the visual associative network. Conclusions: This study suggests that FoG in PD can be the result of a poor structural and functional integration between motor and extramotor (cognitive) neural systems. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc.
    Human Brain Mapping 09/2015; DOI:10.1002/hbm.22994 · 5.97 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate the supportive role of molecular and structural biomarkers (CSF protein levels, FDG PET and MRI) in the early differential diagnosis of dementia in a large sample of patients with neurodegenerative dementia, and in determining the risk of disease progression in subjects with mild cognitive impairment (MCI). We evaluated the supportive role of CSF Aβ42, t-Tau, p-Tau levels, conventional brain MRI and visual assessment of FDG PET SPM t-maps in the early diagnosis of dementia and the evaluation of MCI progression. Diagnosis based on molecular biomarkers showed the best fit with the final diagnosis at a long follow-up. FDG PET SPM t-maps had the highest diagnostic accuracy in Alzheimer's disease and in the differential diagnosis of non-Alzheimer's disease dementias. The p-tau/Aβ42 ratio was the only CSF biomarker providing a significant classification rate for Alzheimer's disease. An Alzheimer's disease-positive metabolic pattern as shown by FDG PET SPM in MCI was the best predictor of conversion to Alzheimer's disease. In this clinical setting, FDG PET SPM t-maps and the p-tau/Aβ42 ratio improved clinical diagnostic accuracy, supporting the importance of these biomarkers in the emerging diagnostic criteria for Alzheimer's disease dementia. FDG PET using SPM t-maps had the highest predictive value by identifying hypometabolic patterns in different neurodegenerative dementias and normal brain metabolism in MCI, confirming its additional crucial exclusionary role.
    European Journal of Nuclear Medicine 09/2015; DOI:10.1007/s00259-015-3170-y · 5.38 Impact Factor
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    ABSTRACT: To explore the role of diffusion tensor imaging (DTI)-based histogram analysis and functional diffusion maps (fDMs) in evaluating structural changes of low-grade gliomas (LGGs) receiving temozolomide (TMZ) chemotherapy. Twenty-one LGG patients underwent 3T-MR examinations before and after three and six cycles of dose-dense TMZ, including 3D-fluid-attenuated inversion recovery (FLAIR) sequences and DTI (b = 1000 s/mm(2), 32 directions). Mean diffusivity (MD), fractional anisotropy (FA), and tensor-decomposition DTI maps (p and q) were obtained. Histogram and fDM analyses were performed on co-registered baseline and post-chemotherapy maps. DTI changes were compared with modifications of tumour area and volume [according to Response Assessment in Neuro-Oncology (RANO) criteria], and seizure response. After three cycles of TMZ, 20/21 patients were stable according to RANO criteria, but DTI changes were observed in all patients (Wilcoxon test, P ≤ 0.03). After six cycles, DTI changes were more pronounced (P ≤ 0.005). Seventy-five percent of patients had early seizure response with significant improvement of DTI values, maintaining stability on FLAIR. Early changes of the 25th percentiles of p and MD predicted final volume change (R(2) = 0.614 and 0.561, P < 0.0005, respectively). TMZ-related changes were located mainly at tumour borders on p and MD fDMs. DTI-based histogram and fDM analyses are useful techniques to evaluate the early effects of TMZ chemotherapy in LGG patients. • DTI helps to assess the efficacy of chemotherapy in low-grade gliomas. • Histogram analysis of DTI metrics quantifies structural changes in tumour tissue. • Functional diffusion maps (fDMs) spatially localize the changes of DTI metrics. • Changes in DTI histograms and fDMs precede changes in conventional MRI. • Early changes in DTI histograms and fDMs correlate with seizure response.
    European Radiology 08/2015; DOI:10.1007/s00330-015-3934-6 · 4.01 Impact Factor
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    ABSTRACT: We assessed global and regional hippocampal volume abnormalities in pediatric multiple sclerosis (MS) patients and their correlations with clinical, neuropsychological and magnetic resonance imaging metrics. From 53 pediatric MS patients and 18 healthy controls, global hippocampal volume was computed using a manual tracing procedure. Regional hippocampal volume modifications were assessed using a radial mapping analysis. MS patients with abnormal performance in three or more tests of a neuropsychological battery for children were classified as cognitively impaired. Global hippocampal volume was reduced in MS patients compared with controls, but did not correlate with clinical, neuropsychological and magnetic resonance imaging measures. Compared to controls, MS patients experienced bilateral radial atrophy of the cornu ammonis, subiculum and dentate gyrus subfields as well as radial hypertrophy of the dentate gyrus subfield. Regional hippocampal volume modifications correlated with brain T2 lesion volume as well as attention and language abilities. Global hippocampal volume did not differ between cognitively impaired (n=12) and cognitively preserved MS patients. Compared to cognitively preserved, cognitively impaired MS patients had atrophy of the subiculum and dentate gyrus subfields of the right hippocampus. Hippocampal subregions have different vulnerability to damage in pediatric MS. Regional rather than global hippocampal involvement contributes to global cognitive impairment as well as to deficits of selected cognitive tests. © The Author(s), 2015.
    Multiple Sclerosis 08/2015; DOI:10.1177/1352458515598569 · 4.82 Impact Factor
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    ABSTRACT: Using MR-based radial mapping, we assessed morphological alterations of the hippocampal dentate gyrus (DG) in patients with relapse-onset multiple sclerosis (MS). We analyzed different stages of the disease and the association of DG alterations with hippocampal-related cognitive functions. Using high-resolution morphological imaging, hippocampal radial mapping analysis was performed in 28 relapsing-remitting (RR), 34 secondary progressive, and 26 benign MS patients and 28 healthy controls (HC). Between-groups differences of DG radial distance (from surface points to the central core of the hippocampus) and correlations with clinical, neuropsychological, and radiological measures were evaluated using surface-based mesh modeling. Compared with HC, all MS clinical phenotypes revealed a larger radial distance of the DG, which was more marked on the left side. Radial distance enlargement was more pronounced in RRMS patients compared with the other disease clinical phenotypes and was inversely correlated to disease duration. Radial distance enlargement was correlated with higher T2 lesion volume and a better cognitive performance in RRMS and with a poor cognitive performance in secondary progressive and benign MS patients. Surface expansion of the DG might represent an inflammation-induced neurogenic (reactive) process of the subgranular zone of the hippocampus primarily aimed at rescuing the functional competence of hippocampal circuitry. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Human Brain Mapping 08/2015; DOI:10.1002/hbm.22946 · 5.97 Impact Factor
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    ABSTRACT: Crossed aphasia has been reported mainly as post-stroke aphasia resulting from brain damage ipsilateral to the dominant right hand. Here, we described a case of a crossed nonfluent/agrammatic primary progressive aphasia (nfvPPA), who developed a corticobasal syndrome (CBS). We collected clinical, cognitive, and neuroimaging data for four consecutive years from a 55-year-old right-handed lady (JV) presenting with speech disturbances. 18-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) and DaT-scan with (123)I-Ioflupane were obtained. Functional MRI (fMRI) during a verb naming task was acquired to characterize patterns of language lateralization. Diffusion tensor MRI was used to evaluate white matter damage within the language network. At onset, JV presented with prominent speech output impairment and right frontal atrophy. After 3 years, language deficits worsened, with the occurrence of a mild agrammatism. The patient also developed a left-sided mild extrapyramidal bradykinetic-rigid syndrome. The clinical picture was suggestive of nfvPPA with mild left-sided extrapyramidal syndrome. At this time, voxel-wise SPM analyses of (18)F-FDG PET and structural MRI showed right greater than left frontal hypometabolism and damage, which included the Broca's area. DaT-scan showed a reduced uptake in the right striatum. FMRI during naming task demonstrated bilateral language activations, and tractography showed right superior longitudinal fasciculus (SLF) involvement. Over the following year, JV became mute and developed frank left-sided motor signs and symptoms, evolving into a CBS clinical picture. Brain atrophy worsened in frontal areas bilaterally, and extended to temporo-parietal regions, still with a right-sided asymmetry. Tractography showed an extension of damage to the left SLF and right inferior longitudinal fasciculus. We report a case of crossed nfvPPA followed longitudinally and studied with advanced neuroimaging techniques. The results highlight a complex interaction between individual premorbid developmental differences and the clinical phenotype.
    Journal of Neurology 07/2015; DOI:10.1007/s00415-015-7845-x · 3.38 Impact Factor
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    ABSTRACT: Quality of life of craniopharyngioma patients can be severely impaired by derangement of hypothalamic function. A classification, taking into account preoperative hypothalamic damage, evaluated by magnetic resonance imaging (MRI), and correlating it with postoperative weight change is still missing in the literature. The aim of our study is to identify objective radiological criteria as preoperative prognostic factors for hypothalamic damage. Pre- and post-operative MRI and clinical data of 47 patients, treated at our Institution for craniopharyngioma, were retrospectively analyzed, based on radiological variables, identified as prognostic factor for hypothalamic involvement. Main factors associated with postoperative obesity were hypothalamic hyperintensity in T2-weighted/FLAIR imaging (p < 0.033), mammillary body involvement according to Müller classification (p < 0.020), unidentifiable pituitary stalk (p < 0.001), dislocated chiasm (p < 0.038), either not visible infundibular recess (p < 0.019) or unrecognizable supra-optic recess (p < 0.004), and retrochiasmatic tumor extension (p < 0.019). Accordingly, postoperative hypothalamic syndrome was associated with peritumoral edema in T2-weighted/FLAIR images (p < 0.003), unidentifiable hypothalamus (p < 0.024), hypothalamic compression (p < 0.006), fornix displacement (p < 0.032), and unrecognizable supra-optic recess (p < 0.031). Ultimately, variables identified as predictive factors of postoperative hypothalamic syndrome were the degree of hypothalamic involvement according to the classification described by Sainte-Rose and Puget (p < 0.002; grade 0 vs 2 p < 0.001), Van Gompel (p < 0.002; grade 0 vs 1, p < 0.027; and grade 0 vs 2, p < 0.002), and Muller (p < 0.006; grade 0 vs 1, p < 0.05; and grade 0 vs 2, p < 0.004). The identification of these predictive factors will help to define and score the preoperative hypothalamic involvement in craniopharyngioma patients.
    Endocrine 07/2015; DOI:10.1007/s12020-015-0683-x · 3.88 Impact Factor
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    ABSTRACT: We investigated resting state functional connectivity (RSFC) of the cerebellar dentate nuclei in paediatric MS patients and its correlations with clinical, neuropsychological and structural MRI measures. RSFC analysis was performed using a seed-region correlation approach and SPM8 from 48 paediatric MS patients and 27 matched healthy controls. In both groups, dentate nuclei RSFC was significantly correlated with RSFC of several cerebellar and extra-cerebellar brain regions. Compared with healthy controls, paediatric MS patients had reduced RSFC between the right dentate nuclei and the bilateral caudate nuclei and left thalamus as well as increased RSFC between the right dentate nuclei and the left precentral and postcentral gyri. Cognitively impaired patients showed a reduced RSFC between the dentate nuclei and bilateral regions located in the parietal, frontal and temporal lobes. Decreased RSFC was correlated with longer disease duration and higher T2 lesion volumes, whereas increased RSFC correlated with shorter disease duration, lower T2 lesion volume and a better motor performance. Modifications of cerebellar RSFC occur in paediatric MS and are influenced by the duration of the disease and brain focal lesions. Decreased RSFC may reflect early maladaptive plasticity contributing to cognitive impairment. © The Author(s), 2015.
    Multiple Sclerosis 07/2015; DOI:10.1177/1352458515592191 · 4.82 Impact Factor
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    ABSTRACT: The identification of antidepressant response predictors in bipolar disorder (BD) may provide new potential enhancements in treatment selection. Repeated total sleep deprivation combined with light therapy (TSD+LT) can acutely reverse depressive symptoms and has been proposed as a model antidepressant treatment. This study aims at investigating the effect of TSD+LT on effective connectivity and neural response in cortico-limbic circuitries during implicit processing of fearful and angry faces in patients with BD. fMRI and Dynamic Causal Modeling (DCM) were combined to study the effect of chronotherapeutics on neural responses in healthy controls (HC, n=35) and BD patients either responder (RBD, n=26) or non responder (nRBD, n=11) to 3 consecutive TSD+LT sessions. Twenty-four DCMs exploring connectivity between anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), Amygdala (Amy), fusiform gyrus and visual cortex were constructed. After treatment, patients significantly increased their neural responses in DLPFC, ACC and insula. nRBD showed lower baseline and endpoint neural responses than RBD. The increased activity in ACC and in medial prefrontal cortex, associated with antidepressant treatment, was positively associated with the improvement of depressive symptomatology. Only RBD patients increased intrinsic connectivity from DLPFC to ACC and reduced the modulatory effect of the task on Amy-DLPFC connection. A successful antidepressant treatment was associated with an increased functional activity and connectivity within cortico-limbic networks, suggesting the possible role of these measures in providing possible biomarkers for treatment efficacy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    07/2015; 233(2). DOI:10.1016/j.pscychresns.2015.07.015
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    ABSTRACT: Facioscapulohumeral muscular dystrophy (FSHD) is characterized by extremely variable degrees of facial, scapular and lower limb muscle involvement. Clinical and genetic determination can be difficult, as molecular analysis is not always definitive, and other similar muscle disorders may have overlapping clinical manifestations. Whole-body muscle MRI examination for fat infiltration, atrophy and oedema was performed to identify specific patterns of muscle involvement in FSHD patients (30 subjects), and compared to a group of control patients (23) affected by other myopathies (NFSHD). In FSHD patients, we detected a specific pattern of muscle fatty replacement and atrophy, particularly in upper girdle muscles. The most frequently affected muscles, including paucisymptomatic and severely affected FSHD patients, were trapezius, teres major and serratus anterior. Moreover, asymmetric muscle involvement was significantly higher in FSHD as compared to NFSHD patients. In conclusion, muscle MRI is very sensitive for identifying a specific pattern of involvement in FSHD patients and in detecting selective muscle involvement of non-clinically testable muscles. Muscle MRI constitutes a reliable tool for differentiating FSHD from other muscular dystrophies to direct diagnostic molecular analysis, as well as to investigate FSHD natural history and follow-up of the disease. • Muscle MRI identifies a specific pattern of muscle involvement in FSHD patients. • Muscle MRI may predict FSHD in asymptomatic and severely affected patients. • Muscle MRI of upper girdle better predicts FSHD. • Muscle MRI may differentiate FSHD from other forms of muscular dystrophy. • Muscle MRI may show the involvement of non-clinical testable muscles.
    European Radiology 06/2015; DOI:10.1007/s00330-015-3890-1 · 4.01 Impact Factor
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    ABSTRACT: Purpose To assess white matter (WM) tract damage in patients with atypical Alzheimer disease (AD), including early-onset AD (EOAD), logopenic variant of primary progressive aphasia (lvPPA), and posterior cortical atrophy (PCA), by using diffusion-tensor magnetic resonance (MR) imaging and to identify similarities and differences across the AD spectrum. Materials and Methods This study was approved by the local ethical committees on human studies, and written informed consent from all subjects was obtained prior to enrollment. WM tract damage and cortical atrophy were assessed by using diffusion-tensor MR imaging and voxel-based morphometry, respectively, in 28 patients with EOAD, 12 patients with lvPPA, and 13 patients with PCA relative to age- and sex-matched healthy subjects. Conjunction and interaction analyses were used to define overlapping and syndrome-specific patterns of brain damage. Results Patients with EOAD, lvPPA, and PCA shared a common pattern of WM damage that involved the body of the corpus callosum, fornix, and main anterior-posterior pathways (P < .05). They also shared cortical atrophy of the left temporoparietal regions and precuneus (P < .05, family-wise error corrected). Patients with EOAD also had specific damage to the genu and splenium of the corpus callosum and parahippocampal tract bilaterally (P < .05). In all patients with AD, particularly in the two focal forms (lvPPA and PCA), WM damage was more severe and widely distributed than expected on the basis of cortical atrophy. Conclusion In atypical AD clinical phenotypes, the distribution of WM damage exceeds cortical atrophy and may reflect the pathologic dissemination through structural connections from atrophic to unaffected cortical regions. WM degeneration may be an early marker of AD pathologic changes in EOAD and focal AD forms. (©) RSNA, 2015 Online supplemental material is available for this article.
    Radiology 05/2015; DOI:10.1148/radiol.2015142766 · 6.87 Impact Factor
  • Physiotherapy 05/2015; 101:e447-e448. DOI:10.1016/ · 1.91 Impact Factor
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    ABSTRACT: Diffusion tensor imaging (DTI) studies have shown a widespread disruption of white matter (WM) microstructure in schizophrenia. Furthermore, higher fractional anisotropy (FA) has been consistently correlated with the severity of psychotic symptoms. Antipsychotic drugs (APDs) affect lipid homeostasis. Gene polymorphisms in sterol regulatory element binding transcription factor (SREBF)-1 and SREBF-2 have been associated with schizophrenia. In a sample of 65 patients affected by chronic schizophrenia, we investigated the effect of ongoing APD medication, SREBF-1 rs11868035 polymorphism and SREBF-2 rs1052717 polymorphism on the WM microstructure, using tract-based spatial statistics with threshold-free cluster enhancement. We reported increased FA associated with the risk rs11868035 G/G genotype in several WM tracts, mainly located in the left hemisphere, and opposite effects of the APD medication load, with reduced FA and generally increased diffusivity. These opposite effects overlapped in the forceps minor, cingulum, uncinate fasciculus, the superior and inferior longitudinal fasciculi, the corticospinal tract, inferior fronto-occipital fasciculus and the anterior thalamic radiation. We suggest that changes of WM structure could be an as yet poorly explored biomarker of the effects of APDs, to be further investigated in prospective studies correlating long-term clinical effects with changes of DTI measures in specific WM tracts contributing to the functional integrity of the brain. © 2015 S. Karger AG, Basel.
    Neuropsychobiology 04/2015; 71(2):112-119. DOI:10.1159/000370076 · 2.26 Impact Factor
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    ABSTRACT: Using advanced MRI techniques, we investigated the presence and topographical distribution of brain grey matter (GM) and white matter (WM) alterations in dominant optic atrophy (DOA) patients with genetically proven OPA1 mutation as well as their correlation with clinical and neuro-ophthalmologic findings. Nineteen DOA patients underwent neurological, neuro-ophthalmologic and brainstem auditory evoked potentials (BAEP) evaluations. Voxel-wise methods were applied to assess regional GM and WM abnormalities in patients compared to 20 healthy controls. Visual acuity was reduced in 16 patients. Six DOA patients (4 with missense mutations) had an abnormal I peripheral component (auditory nerve) at BAEP. Compared to controls, DOA patients had significant atrophy of the optic nerves (p < 0.0001). Voxel-based morphometry (VBM) analysis showed that, compared to controls, DOA patients had significant WM atrophy of the chiasm and optic tracts; whereas no areas of GM atrophy were found. Tract-based spatial statistics (TBSS) analysis showed that compared to controls, DOA patients had significantly lower mean diffusivity, axial and radial diffusivity in the WM of the cerebellum, brainstem, thalamus, fronto-occipital-temporal lobes, including the cingulum, corpus callosum, corticospinal tract and optic radiation bilaterally. No abnormalities of fractional anisotropy were detected. No correlations were found between volumetric and diffusivity abnormalities quantified with MRI and clinical and neuro-ophthalmologic measures of disease severity. Consistently with pathological studies, tissue loss in DOA patients is limited to anterior optic pathways reflecting retinal ganglion cell degeneration. Distributed abnormalities of diffusivity indexes might reflect abnormal intracellular mitochondrial morphology as well as alteration of protein levels due to OPA1 mutations.
    Journal of Neurology 03/2015; 262(5). DOI:10.1007/s00415-015-7696-5 · 3.38 Impact Factor
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    ABSTRACT: Diffusion tensor (DT) magnetic resonance imaging (MRI) provides several quantities with the potential to disclose white matter (WM) microstructural abnormalities. We explored alterations of WM architecture in pediatric migraine patients using DT MRI and two different methods of analysis. Dual-echo and DT MRI scans were acquired from 15 pediatric migraine patients and 15 age-matched controls. Whole-brain voxel-wise comparisons of WM DT MRI abnormalities were performed using tract-based-spatial-statistics (TBSS). A DT probabilistic tractography analysis was also run. Both TBSS and DT tractography analysis showed that, compared to controls, pediatric migraine patients had significant lower mean (MD), axial (AD) and radial (RD) diffusivity of WM tracts located in the brainstem, thalamus and fronto-temporo-occipital lobes, bilaterally. Patients also experienced increased fractional anisotropy (FA) of the optic radiations. No correlation was found between WM tract abnormalities and disease duration and attack frequency. Pediatric migraine patients harbor diffuse brain WM microstructural abnormalities. High FA and low MD, AD and RD in these patients might be explained by repeated neuronal activation, which may lead to cell swelling and stimulate activity-dependent myelin-modulation, or by increased fiber and dendritic densities. Both these mechanisms might reflect a hyperexcitability of the brain in migraineurs. © International Headache Society 2015 Reprints and permissions:
    Cephalalgia 03/2015; DOI:10.1177/0333102415578428 · 4.89 Impact Factor
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    ABSTRACT: To identify overlapping and unique grey (GM) and white matter (WM) signatures within the frontotemporal lobar degeneration (FTLD) continuum, and discriminate likely FTLD-TAU and FTLD-TDP patients using structural and diffusion tensor (DT) magnetic resonance imaging (MRI). T1-weighted and DT MRI were collected from 121 subjects: 35 motor neuron disease (MND), 14 behavioral variant of frontotemporal dementia, 12 semantic and 11 nonfluent primary progressive aphasia, 21 progressive supranuclear palsy syndrome patients, and 28 healthy controls. Patterns of GM atrophy were established using voxel-based morphometry. Tract-based spatial statistics was used to perform a WM voxelwise analysis of mean diffusivity and fractional anisotropy. In all clinical FTLD phenotypes, the pattern of WM damage was more distributed than that of GM atrophy. All patient groups, with the exception of MND cases with a pure motor syndrome, shared a focal GM atrophy centered around the dorsolateral and medial frontal cortex and a largely overlapping pattern of WM damage involving the genu and body of the corpus callosum and ventral frontotemporal and dorsal frontoparietal WM pathways. Surrounding this common area, phenotype (symptom)-specific GM and WM regions of damage were found in each group. In the FTLD spectrum, WM disruption is more severe than GM damage. Frontal cortex and WM pathways represent the common target of neurodegeneration in these conditions. The topographic pattern of damage supports a "prion-like" protein propagation through WM connections as underlying mechanism of the stereotyped progression of FTLD. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Human Brain Mapping 03/2015; 36(7). DOI:10.1002/hbm.22794 · 5.97 Impact Factor
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    ABSTRACT: Purpose: To test a multimodal magnetic resonance (MR) imaging-based approach composed of cortical thickness and white matter (WM) damage metrics to discriminate between variants of primary progressive aphasia (PPA) that are nonfluent and/or agrammatic (NFVPPA) and semantic (SVPPA). Materials and methods: This study was approved by the local ethics committees on human studies, and written informed consent from all patients was obtained before their enrollment. T1-weighted and diffusion-tensor (DT) MR images were obtained from 13 NFVPPA patients, 13 SVPPA patients, and 23 healthy control participants. Cortical thickness and DT MR imaging indices from the long-associative and interhemispheric WM tracts were obtained. A random forest (RF) analysis was used to identify the image features associated with each clinical syndrome. Individual patient classification was performed by using receiver operator characteristic curve analysis with cortical thickness, DT MR imaging, and a combination of the two modalities. RESULTS RF analysis showed that the best markers to differentiate the two PPA variants at an individual patient level among cortical thickness and DT MR imaging metrics were diffusivity abnormalities of the left inferior longitudinal and uncinate fasciculi and cortical thickness measures of the left temporal pole and inferior frontal gyrus. A combination of cortical thickness and DT MR imaging measures (the so-called gray-matter-and-WM model) was able to distinguish patients with NFVPPA and SVPPA with the following classification pattern: area under the curve, 0.91; accuracy, 0.89; sensitivity, 0.92; specificity, 0.85. Leave-one-out analysis demonstrated that the gray matter and WM model is more robust than the single MR modality models to distinguish PPA variants (accuracy was 0.86, 0.73, and 0.68 for the gray matter and WM model, the gray matter-only model, and the WM-only model, respectively). Conclusion: A combination of structural and DT MR imaging metrics may provide a quantitative procedure to distinguish NFVPPA and SVPPA patients at an individual patient level. The discrimination accuracies obtained suggest that the gray matter and WM model is potentially relevant for the differential diagnosis of the PPA variants in clinical practice.
    Radiology 02/2015; 276(1):141869. DOI:10.1148/radiol.15141869 · 6.87 Impact Factor

Publication Stats

6k Citations
1,383.01 Total Impact Points


  • 2002–2015
    • Università Vita-Salute San Raffaele
      • Faculty of Psychology
      Milano, Lombardy, Italy
  • 2006–2014
    • University of Milan
      • Department of Neurological Sciences
      Milano, Lombardy, Italy
  • 2001–2014
    • San Raffaele Scientific Institute
      Milano, Lombardy, Italy
  • 2010
    • Università Telematica San Raffaele
      Milano, Lombardy, Italy
    • Università degli Studi di Torino
      Torino, Piedmont, Italy
  • 2008
    • Ospedale di San Raffaele Istituto di Ricovero e Cura a Carattere Scientifico
      Milano, Lombardy, Italy
  • 1998
    • McGill University
      Montréal, Quebec, Canada
  • 1996
    • Fox Chase Cancer Center
      Filadelfia, Pennsylvania, United States