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David Neil Manners

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7 papers

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YNICL Journal 2026 Journal Article

Individualized functionnectome for the statistical assessment of white matter circuits underlying task-fMRI activations in glioma patients

Giovanni Sighinolfi
Alexander Leemans
David Neil Manners
Elena Cantoni
Gianfranco Vornetti
Lorenzo Motta
Enrico Franceschi
Caterina Tonon

The Functionnectome framework enables the projection of task-related fMRI signals onto the underlying white matter pathways, using anatomical priors derived from structural connectivity. However, the existing "standardized" priors are based on averaged tractograms from healthy controls and cannot accurately capture the altered anatomy found in patients with brain lesions. This study extends the Functionnectome framework by generating individualized anatomical priors from subject-specific diffusion MRI tractography, allowing for improved integration of functional and structural data in patients with brain tumors. Twenty-six patients with gliomas (9 females; mean age 43 ± 17 years) underwent 3 T MRI, including a multishell diffusion protocol and task-based fMRI targeting motor and/or language functions. Whole-brain tractography was reconstructed using three methods (TensorDet, PFT, and iFOD2) and converted into voxelwise individualized priors. Functionnectome maps were estimated using both standardized and individualized priors, and Z-statistic activation maps were obtained via GLM analysis. Similarity metrics and atlas-based consistency were used to compare standardized and individualized Functionnectomes. Functionnectomes derived from probabilistic tractography showed moderate correlations with standardized Functionnectomes (average Pearson's r ≈ 0.5), highlighting the influence of individual structural variability while maintaining comparable activation patterns. The PFT-based Functionnectome exhibited superior anatomical plausibility, with consistent overlap with expected motor white matter tracts and identification of relevant bundles in up to 100% of cases, compared to 50-60% with standardized priors. The individualized Functionnectome enhances the anatomical validity and subject specificity of structure-function mapping, advancing precision neuroimaging for clinical and neurosurgical applications.

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YNICL Journal 2026 Journal Article

The role of quantitative susceptibility mapping in dementia with Lewy Bodies

Elettra Capogna
Greta Venturi
Lorenzo Motta
David Neil Manners
Davide Braghittoni
Lucia Guidi
Luca Baldelli
Giovanna Calandra-Buonaura

Iron overload has been implicated in the pathology of several neurodegenerative diseases, and quantitative susceptibility mapping (QSM), an MRI-based technique, has identified abnormal iron overload in alpha-synucleinopathies. However, there is a limited understanding of the significance of changes in magnetic susceptibility, assessed by QSM, in patients with Dementia with Lewy Bodies (DLB). In this study, 39 DLB patients (58-88 years) and 30 cognitively unimpaired older adults (OA) (56-86 years) underwent an advanced MRI protocol that included T1w and QSM sequences, and a comprehensive neuropsychological evaluation. This study investigated (1) differences in whole-brain magnetic susceptibility and brain volumes between DLB patients and OA; (2) associations between regional changes in magnetic susceptibility and brain volumes, symptom duration, and cognitive functioning; (3) whether regional changes in magnetic susceptibility could differentiate DLB phenotypes based on earlier symptoms. DLB patients showed higher magnetic susceptibility values than OA in the bilateral substantia nigra, globus pallidus, thalamus, brainstem, and hippocampus, as well as in posterior cortical regions. No significant associations were observed between QSM susceptibility values and brain volumes, symptom duration, or cognitive functions. Using classificatory algorithms, different DLB phenotypes were identified based on iron accumulation values in the basal ganglia, thalamus, brainstem, and frontal cortical regions. Our findings suggest that QSM, assessing in vivo changes in brain iron accumulation, could serve as a useful noninvasive diagnostic biomarker in DLB patients. Longitudinal studies, including the prodromal phase of DLB, are needed to understand the interplay between brain volumetric loss, iron accumulation, and clinical manifestations.

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YNICL Journal 2025 Journal Article

Fully automated pipeline for the fiber tractography of the anterior optic pathway in patients with sellar and parasellar tumors and analysis of the microstructural alterations

Laura Ludovica Gramegna
Matteo Zoli
Giovanni Sighinolfi
Alessandro Carrozzi
Gianfranco Vornetti
Elena Cantoni
Federica Guaraldi
Sofia Asioli

Highlights • Automated tractography of the anterior optic pathway has been developed for both normal controls or patients.• Anterior optic pathway tractography may improve surgical planning in sellar/parasellar tumor patients.• Analysis of diffusion metrics in the anterior optic pathway shows microstructural alteration related to tumor compression.

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YNICL Journal 2023 Journal Article

Methods of diffusion MRI tractography for localization of the anterior optic pathway: A systematic review of validated methods

Alessandro Carrozzi
Laura Ludovica Gramegna
Giovanni Sighinolfi
Matteo Zoli
Diego Mazzatenta
Claudia Testa
Raffaele Lodi
Caterina Tonon

The anterior optic pathway (AOP) is a system of three structures (optic nerves, optic chiasma, and optic tracts) that convey visual stimuli from the retina to the lateral geniculate nuclei. A successful reconstruction of the AOP using tractography could be helpful in several clinical scenarios, from presurgical planning and neuronavigation of sellar and parasellar surgery to monitoring the stage of fiber degeneration both in acute (e. g. , traumatic optic neuropathy) or chronic conditions that affect AOP structures (e. g. , amblyopia, glaucoma, demyelinating disorders or genetic optic nerve atrophies). However, its peculiar anatomy and course, as well as its surroundings, pose a serious challenge to obtaining successful tractographic reconstructions. Several AOP tractography strategies have been adopted but no standard procedure has been agreed upon. We performed a systematic review of the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 guidelines in order to find the combinations of acquisition and reconstruction parameters that have been performed previously and have provided the highest rate of successful reconstruction of the AOP, in order to promote their routine implementation in clinical practice. For this purpose, we reviewed data regarding how the process of anatomical validation of the tractographies was performed. The Cochrane Handbook for Systematic Reviews of Interventions was used to assess the risk of bias and thus the study quality We identified thirty-nine studies that met our inclusion criteria, and only five were considered at low risk of bias and achieved over 80% of successful reconstructions. We found a high degree of heterogeneity in the acquisition and analysis parameters used to perform AOP tractography and different combinations of them can achieve satisfactory levels of anterior optic tractographic reconstruction both in real-life research and clinical scenarios. One thousand s/mm2 was the most frequently used b value, while both deterministic and probabilistic tractography algorithms performed morphological reconstruction of the tract satisfactorily, although probabilistic algorithms estimated a more realistic percentage of crossing fibers (45. 6%) in healthy subjects. A wide heterogeneity was also found regarding the method used to assess the anatomical fidelity of the AOP reconstructions. Three main strategies can be found: direct visual direct visual assessment of the tractography superimposed to a conventional MR image, surgical evaluation, and computational methods. Because the latter is less dependent on a priori knowledge of the anatomy by the operator, computational methods of validation of the anatomy should be considered whenever possible.

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YNICL Journal 2018 Journal Article

Brain functional connectivity in sleep-related hypermotor epilepsy

Stefania Evangelisti
Claudia Testa
Lorenzo Ferri
Laura Ludovica Gramegna
David Neil Manners
Giovanni Rizzo
Daniel Remondini
Gastone Castellani

Objectives: To evaluate functional connectivity (FC) in patients with sleep-related hypermotor epilepsy (SHE) compared to healthy controls. Methods: Resting state fMRI was performed in 13 patients with a clinical diagnosis of SHE (age = 38.3 ± 11.8 years, 6 M) and 13 matched healthy controls (age = 38.5 ± 10.8 years, 6 M).Data were first analysed using probabilistic independent component analysis (ICA), then a graph theoretical approach was applied to assess topological and organizational properties at the whole brain level. We evaluated node degree (ND), betweenness centrality (BC), clustering coefficient (CC), local efficiency (LE) and global efficiency (GE). The differences between the two groups were evaluated non-parametrically. Results: < 0.05 uncorrected). Discussion and conclusions: The higher FC of the sensorimotor cortex and thalamus might be in agreement with the hypothesis of a peculiar excitability of the motor cortex during thalamic K-complexes. This sensorimotor-thalamic hyperconnection might be regarded as a consequence of an alteration of the arousal regulatory system in SHE. An altered topology has been found in structures like basal ganglia and limbic system, hypothesized to be involved in the pathophysiology of the disease as suggested by the dystonic-dyskinetic features and primitive behaviours observed during the seizures.

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YNICL Journal 2016 Journal Article

Accuracy of MR markers for differentiating Progressive Supranuclear Palsy from Parkinson's disease

Stefano Zanigni
Giovanna Calandra-Buonaura
David Neil Manners
Claudia Testa
Dino Gibertoni
Stefania Evangelisti
Luisa Sambati
Maria Guarino

BACKGROUND: Advanced brain MR techniques are useful tools for differentiating Progressive Supranuclear Palsy from Parkinson's disease, although time-consuming and unlikely to be used all together in routine clinical work. We aimed to compare the diagnostic accuracy of quantitative morphometric, volumetric and DTI metrics for differentiating Progressive Supranuclear Palsy-Richardson's Syndrome from Parkinson's disease. METHODS: 23 Progressive Supranuclear Palsy-Richardson's Syndrome and 42 Parkinson's disease patients underwent a standardized 1.5T brain MR protocol comprising high-resolution T1W1 and DTI sequences. Brainstem and cerebellar peduncles morphometry, automated volumetric analysis of brain deep gray matter and DTI metric analyses of specific brain structures were carried out. We determined diagnostic accuracy, sensitivity and specificity of MR-markers with respect to the clinical diagnosis by using univariate receiver operating characteristics curve analyses. Age-adjusted multivariate receiver operating characteristics analyses were then conducted including only MR-markers with a sensitivity and specificity exceeding 80%. RESULTS: Morphometric markers (midbrain area, pons to midbrain area ratio and MR Parkinsonism Index), DTI parameters (infratentorial structures) and volumetric analysis (thalamus, putamen and pallidus nuclei) presented moderate to high diagnostic accuracy in discriminating Progressive Supranuclear Palsy-Richardson's Syndrome from Parkinson's disease, with midbrain area showing the highest diagnostic accuracy (99%) (mean ± standard deviation: 75.87 ± 16.95 mm(2) vs 132.45 ± 20.94 mm(2), respectively; p < 0.001). CONCLUSION: Although several quantitative brain MR markers provided high diagnostic accuracy in differentiating Progressive Supranuclear Palsy-Richardson's Syndrome from Parkinson's disease, the morphometric assessment of midbrain area is the best single diagnostic marker and should be routinely included in the neuroradiological work-up of parkinsonian patients.

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YNICL Journal 2016 Journal Article

Relationship of white and gray matter abnormalities to clinical and genetic features in myotonic dystrophy type 1

Stefano Zanigni
Stefania Evangelisti
Maria Pia Giannoccaro
Federico Oppi
Roberto Poda
Antonio Giorgio
Claudia Testa
David Neil Manners

BACKGROUND: Myotonic dystrophy type 1 (DM1) represents a multisystemic disorder in which diffuse brain white and gray matter alterations related to clinical and genetic features have been described. We aimed to evaluate in the brain of adult patients with DM1 (i) white and gray matter differences, including cortical-subcortical gray matter volume and cortical thickness and (ii) their correlation with clinical disability, global neuropsychological performance and triplet expansion. METHODS: We included 24 adult genetically-confirmed DM1 patients (14 males; age: 38.5 ± 11.8 years) and 25 age- and sex-matched healthy controls (14 males; age: 38.5 ± 11.3 years) who underwent an identical brain MR protocol including high-resolution 3D T1-weighted, axial T2 FLAIR and DTI sequences. All patients underwent an extensive clinical and neuropsychological evaluation. Voxel-wise analyses of white matter, performed by using Tract Based Spatial Statistics, and of gray matter, with Voxel-based Morphometry and Cortical Thickness, were carried out in order to test for differences between patients with DM1 and healthy controls (p < 0.05, corrected). The correlation between MRI measures and clinical-genetic features was also assessed. RESULTS: Patients with DM1 showed widespread abnormalities of all DTI parameters in the white matter, which were associated with reduced gray matter volume in all brain lobes and thinning in parieto-temporo-occipital cortices, albeit with less extensive cortical alterations when congenital cases were removed from the analyses. White matter alterations correlated with clinical disability, global cognitive performance and triplet expansions. CONCLUSION: In patients with DM1, the combined smaller overall gray matter volume and white matter alterations seem to be the main morpho-structural substrates of CNS involvement in this condition. The correlation of white matter differences with both clinical and genetic findings lends support to this notion.

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