Person: Cavallari, Michele
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Cavallari
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Michele
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Cavallari, Michele
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Publication Longitudinal microstructural changes of cerebral white matter and their association with mobility performance in older persons(Public Library of Science, 2018) Moscufo, Nicola; Wakefield, Dorothy B.; Meier, Dominik S.; Cavallari, Michele; Guttmann, Charles; White, William B.; Wolfson, LeslieMobility impairment in older persons is associated with brain white matter hyperintensities (WMH), a common finding in magnetic resonance images and one established imaging biomarker of small vessel disease. The contribution of possible microstructural abnormalities within normal-appearing white matter (NAWM) to mobility, however, remains unclear. We used diffusion tensor imaging (DTI) measures, i.e. fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), to assess microstructural changes within supratentorial NAWM and WMH sub-compartments, and to investigate their association with changes in mobility performance, i.e. Tinetti assessment and the 2.5-meters walk time test. We analyzed baseline (N = 86, age ≥75 years) and 4-year (N = 41) follow-up data. Results from cross-sectional analysis on baseline data showed significant correlation between WMH volume and NAWM-FA (r = -0.33, p = 0.002), NAWM-AD (r = 0.32, p = 0.003) and NAWM-RD (r = 0.39, p = 0.0002). Our longitudinal analysis showed that after 4-years, FA and AD decreased and RD increased within NAWM. In regional tract-based analysis decrease in NAWM-FA and increase in NAWM-RD within the genu of the corpus callosum correlated with slower walk time independent of age, gender and WMH burden. In conclusion, global DTI indices of microstructural integrity indicate that significant changes occur in the supratentorial NAWM over four years. The observed changes likely reflect white matter deterioration resulting from aging as well as accrual of cerebrovascular injury associated with small vessel disease. The observed association between mobility scores and regional measures of NAWM microstructural integrity within the corpus callosum suggests that subtle changes within this structure may contribute to mobility impairment.Publication Dual‐Sensitivity Multiple Sclerosis Lesion and CSF Segmentation for Multichannel 3T Brain MRI(John Wiley and Sons Inc., 2017) Meier, Dominik S.; Guttmann, Charles; Tummala, Subhash; Moscufo, Nicola; Cavallari, Michele; Tauhid, Shahamat; Bakshi, Rohit; Weiner, HowardABSTRACT BACKGROUND AND PURPOSE A pipeline for fully automated segmentation of 3T brain MRI scans in multiple sclerosis (MS) is presented. This 3T morphometry (3TM) pipeline provides indicators of MS disease progression from multichannel datasets with high‐resolution 3‐dimensional T1‐weighted, T2‐weighted, and fluid‐attenuated inversion‐recovery (FLAIR) contrast. 3TM segments white (WM) and gray matter (GM) and cerebrospinal fluid (CSF) to assess atrophy and provides WM lesion (WML) volume. METHODS To address nonuniform distribution of noise/contrast (eg, posterior fossa in 3D‐FLAIR) of 3T magnetic resonance imaging, the method employs dual sensitivity (different sensitivities for lesion detection in predefined regions). We tested this approach by assigning different sensitivities to supratentorial and infratentorial regions, and validated the segmentation for accuracy against manual delineation, and for precision in scan‐rescans. RESULTS Intraclass correlation coefficients of .95, .91, and .86 were observed for WML and CSF segmentation accuracy and brain parenchymal fraction (BPF). Dual sensitivity significantly reduced infratentorial false‐positive WMLs, affording increases in global sensitivity without decreasing specificity. Scan‐rescan yielded coefficients of variation (COVs) of 8% and .4% for WMLs and BPF and COVs of .8%, 1%, and 2% for GM, WM, and CSF volumes. WML volume difference/precision was .49 ± .72 mL over a range of 0–24 mL. Correlation between BPF and age was r = .62 (P = .0004), and effect size for detecting brain atrophy was Cohen's d = 1.26 (standardized mean difference vs. healthy controls). CONCLUSIONS This pipeline produces probability maps for brain lesions and tissue classes, facilitating expert review/correction and may provide high throughput, efficient characterization of MS in large datasets.Publication Microstructural Changes in the Striatum and Their Impact on Motor and Neuropsychological Performance in Patients with Multiple Sclerosis(Public Library of Science, 2014) Cavallari, Michele; Ceccarelli, Antonia; Wang, Guang-Yi; Moscufo, Nicola; Hannoun, Salem; Matulis, Christina R.; Jackson, Jonathan S.; Glanz, Bonnie; Bakshi, Rohit; Neema, M; Guttmann, CharlesGrey matter (GM) damage is a clinically relevant feature of multiple sclerosis (MS) that has been previously assessed with diffusion tensor imaging (DTI). Fractional anisotropy (FA) of the basal ganglia and thalamus might be increased in MS patients, and correlates with disability scores. Despite the established role of the striatum and thalamus in motor control, mood and cognition, the impact of DTI changes within these structures on motor and neuropsychological performance has not yet been specifically addressed in MS. We investigated DTI metrics of deep GM nuclei and their potential association with mobility and neuropsychological function. DTI metrics from 3T MRI were assessed in the caudate, putamen, and thalamus of 30 MS patients and 10 controls. Sixteen of the patients underwent neuropsychological testing. FA of the caudate and putamen was higher in MS patients compared to controls. Caudate FA correlated with Expanded Disability Status Scale score, Ambulation Index, and severity of depressive symptomatology. Putamen and thalamus FA correlated with deficits in memory tests. In contrast, cerebral white matter (WM) lesion burden showed no significant correlation with any of the disability, mobility and psychometric parameters. Our findings support evidence of FA changes in the basal ganglia in MS patients, as well as deep GM involvement in disabling features of MS, including mobility and cognitive impairment. Deep GM FA appears to be a more sensitive correlate of disability than WM lesion burden.Publication Mobility impairment is associated with reduced microstructural integrity of the inferior and superior cerebellar peduncles in elderly with no clinical signs of cerebellar dysfunction☆(Elsevier, 2013) Cavallari, Michele; Moscufo, Nicola; Skudlarski, Pawel; Meier, Dominik; Panzer, Victoria P.; Pearlson, Godfrey D.; White, William B.; Wolfson, Leslie; Guttmann, CharlesWhile the cerebellum plays a critical role in motor coordination and control no studies have investigated its involvement in idiopathic mobility impairment in community-dwelling elderly. In this study we tested the hypothesis that structural changes in the cerebellar peduncles not detected by conventional magnetic resonance imaging are associated with reduced mobility performance. The analysis involved eighty-five subjects (age range: 75–90 years) who had no clinical signs of cerebellar dysfunction. Based on the short physical performance battery (SPPB) score, we defined mobility status of the subjects in the study as normal (score 11–12, n = 26), intermediate (score 9–10, n = 27) or impaired (score < 9, n = 32). We acquired diffusion tensor imaging data to obtain indices of white matter integrity: fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). Using a parcellation atlas, regional indices within the superior, middle, and inferior cerebellar peduncles (ICP, MCP, SCP) were calculated and their associations with mobility performance were analyzed. Subjects with impaired mobility showed reduced FA and AD values in the ICP and SCP but not in the MCP. The ICP-FA, ICP-AD and SCP-FA indices showed a significant association with the SPPB score. We also observed significant correlation between ICP-FA and walk time (r = − 0.311, p = 0.004), as well as between SCP-AD and self-paced maximum walking velocity (r = 0.385, p = 0.003) and usual walking velocity (r = 0.400, p = 0.002). In logistic regression analysis ICP-FA and ICP-AD together explained 51% of the variability in the mobility status of a sample comprising the normal and impaired subgroups, and correctly classified more than three-quarters of those subjects. Our findings suggest that presence of microstructural damage, likely axonal, in afferent and efferent connections of the cerebellum contributes to the deterioration of motor performance in older people.Publication Xanthurenic Acid Activates mGlu2/3 Metabotropic Glutamate Receptors and is a Potential Trait Marker for Schizophrenia(Nature Publishing Group, 2015) Fazio, Francesco; Lionetto, Luana; Curto, Martina; Iacovelli, Luisa; Cavallari, Michele; Zappulla, Cristina; Ulivieri, Martina; Napoletano, Flavia; Capi, Matilde; Corigliano, Valentina; Scaccianoce, Sergio; Caruso, Alessandra; Miele, Jessica; De Fusco, Antonio; Di Menna, Luisa; Comparelli, Anna; De Carolis, Antonella; Gradini, Roberto; Nisticò, Robert; De Blasi, Antonio; Girardi, Paolo; Bruno, Valeria; Battaglia, Giuseppe; Nicoletti, Ferdinando; Simmaco, MaurizioThe kynurenine pathway of tryptophan metabolism has been implicated in the pathophysiology of psychiatric disorders, including schizophrenia. We report here that the kynurenine metabolite, xanturenic acid (XA), interacts with, and activates mGlu2 and mGlu3 metabotropic glutamate receptors in heterologous expression systems. However, the molecular nature of this interaction is unknown, and our data cannot exclude that XA acts primarily on other targets, such as the vesicular glutamate transporter, in the CNS. Systemic administration of XA in mice produced antipsychotic-like effects in the MK-801-induced model of hyperactivity. This effect required the presence of mGlu2 receptors and was abrogated by the preferential mGlu2/3 receptor antagonist, LY341495. Because the mGlu2 receptor is a potential drug target in the treatment of schizophrenia, we decided to measure serum levels of XA and other kynurenine metabolites in patients affected by schizophrenia. Serum XA levels were largely reduced in a large cohort of patients affected by schizophrenia, and, in patients with first-episode schizophrenia, levels remained low after 12 months of antipsychotic medication. As opposed to other kynurenine metabolites, XA levels were also significantly reduced in first-degree relatives of patients affected by schizophrenia. We suggest that lowered serum XA levels might represent a novel trait marker for schizophrenia.Publication Quantitative MRI study of Pineal Gland in MS.(2016) Egorova, Svetlana; Denes, Palma; Polgar-Turcsanyi, Mariann; Anderson, Mark; Cavallari, Michele; Guttmann, Charles; Glanz, Bonnie; Chitnis, Tanuja; Bove, Riley; Buckle, Guy; De Jager, Philip; Severson, Cristopher; Stankiewicz, James; Houtchens, Maria; Quintana, Francisco; Gandhi, Roopali; Webb, Pia; Meier, Dominik; Healy, Brian; Weiner, HowardPublication Novel Method for Automated Analysis of Retinal Images: Results in Subjects with Hypertensive Retinopathy and CADASIL(Hindawi Publishing Corporation, 2015) Cavallari, Michele; Stamile, Claudio; Umeton, Renato; Calimeri, Francesco; Orzi, FrancescoMorphological analysis of the retinal vessels by fundoscopy provides noninvasive means for detecting and staging systemic microvascular damage. However, full exploitation of fundoscopy in clinical settings is limited by paucity of quantitative, objective information obtainable through the observer-driven evaluations currently employed in routine practice. Here, we report on the development of a semiautomated, computer-based method to assess retinal vessel morphology. The method allows simultaneous and operator-independent quantitative assessment of arteriole-to-venule ratio, tortuosity index, and mean fractal dimension. The method was implemented in two conditions known for being associated with retinal vessel changes: hypertensive retinopathy and Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). The results showed that our approach is effective in detecting and quantifying the retinal vessel abnormalities. Arteriole-to-venule ratio, tortuosity index, and mean fractal dimension were altered in the subjects with hypertensive retinopathy or CADASIL with respect to age- and gender-matched controls. The interrater reliability was excellent for all the three indices (intraclass correlation coefficient ≥ 85%). The method represents simple and highly reproducible means for discriminating pathological conditions characterized by morphological changes of retinal vessels. The advantages of our method include simultaneous and operator-independent assessment of different parameters and improved reliability of the measurements.Publication Head Circumference as a Useful Surrogate for Intracranial Volume in Older Adults(Cambridge University Press (CUP), 2016-01) Hshieh, Tammy; Fox, Meaghan L.; Kosar, Cyrus M.; Cavallari, Michele; Guttmann, Charles; Alsop, David; Marcantonio, Edward; Schmitt, Eva M.; Jones, Richard N.; Inouye, SharonBackground Intracranial volume (ICV) has been proposed as a measure of maximum lifetime brain size. Accurate ICV measures require neuroimaging which is not always feasible for epidemiologic investigations. We examined head circumference as a useful surrogate for intracranial volume in older adults. Methods 99 older adults underwent Magnetic Resonance Imaging (MRI). ICV was measured by Statistical Parametric Mapping 8 (SPM8) software or Functional MRI of the Brain Software Library (FSL) extraction with manual editing, typically considered the gold standard. Head circumferences were determined using standardized tape measurement. We examined estimated correlation coefficients between head circumference and the two MRI-based ICV measurements. Results Head circumference and ICV by SPM8 were moderately correlated (overall r=0.73, men r=0.67, women r=0.63). Head circumference and ICV by FSL were also moderately correlated (overall r=0.69, men r=0.63, women r=0.49). Conclusions Head circumference measurement was strongly correlated with MRI-derived ICV. Our study presents a simple method to approximate ICV among older patients, which may prove useful as a surrogate for cognitive reserve in large scale epidemiologic studies of cognitive outcomes. This study also suggests the stability of head circumference correlation with ICV throughout the lifespan.