Descrizione attività di ricerca:
Le linee di ricerca principali comprendono:
i) studi sperimentali sui modelli biofisici del segnale di risonanza magnetica funzionale basata sull’effetto BOLD (Blood Oxygenation Level Dependent);
ii) studi basati su acquisizioni combinate BOLD e Arterial Spin Labeling, che permettono di avere informazioni più quantitative su diverse variabili fisiologiche, ampliando le potenzialità della risonanza magnetica funzionale negli studi sull’invecchiamento e negli studi clinici in generale;
iii) sviluppo di metodiche innovative basate su tecniche fMRI veloci per individuare nuovi biomarker di disfunzione cerebrale e per lo studio dei meccanismi di interazione cuore-cervello;
iv) studi con acquisizione simultanea EEG-fMRI e sul mappaggio prechirurgico.
PRIN-PNRR 2022 Funded Project:
Multimodal MRI investigation of novel neuroimaging biomarkers of SUDEP risk
Sudden unexpected death in epilepsy (SUDEP) is the main cause of premature death for patients with epilepsy, with an estimated incidence of 1.20/1,000 person-years. Clinically, risk factors for SUDEP include duration of epilepsy, frequency of generalized tonic-clonic seizures (GTCS), age of epilepsy onset and presence of nocturnal seizures. However, recent evidence highlighted a high incidence of SUDEP also in those patients with anti-seizure medication responsiveness or having low GTCS frequency with only recurrence of focal onset seizures. Unfortunately, despite the major impact on life expectancy in epileptic patients, to date, no reliable biomarkers of SUDEP have been identified.
The pathophysiological mechanism underpinning SUDEP is still unknown. Experimental models focus on seizure-induced autonomic derangement due to abnormal involvement of brain regions forming the “central autonomic network" (CAN), a complex system including cortical, midbrain, and brainstem areas that regulate autonomic cardiovascular and respiratory functions. In this context, the temporal lobe represents a key structure. It is well known that pathological involvement of temporal lobe can generate cardiac and respiratory abnormalities such as heart rate changes, abnormal atrioventricular conduction, breath frequency change, and hypopnea/apnea. Temporal lobe epilepsy (TLE) represents the most common form of focal epilepsy in adulthood and its association with SUDEP has been largely explored.
The use of noninvasive neuroimaging techniques such as structural (MRI) and functional magnetic resonance imaging (fMRI) may help in identifying patients with increased risk of SUDEP. Recent studies revealed changes in volume and cortical thickness in key structures of the CAN. In addition, the same areas showed modifications of resting-state functional connectivity patterns. However, these findings suffer from a small sample size and a limited methodological/technological approach making them uncertain biomarkers of SUDEP.
In this project, we propose an innovative, multimodal MRI and neurophysiological-based approach for identifying the brain structural and functional correlates of autonomic functioning changes in patients with TLE as a potential biomarker of SUDEP. To that aim, advanced multimodal MRI techniques including structural MRI, Arterial Spin Labeling (ASL) and fMRI acquired simultaneously with EEG as well as a set of physiological measurements to evaluate the autonomic function will be employed.
Moreover, cutting edge preprocessing techniques of neuroimaging data will be applied to properly address physiological noise in BOLD time-series obtained from critical regions such as the brainstem. In addition, analysis approaches that take advantage of the multi-echo fMRI technique will be implemented to investigate dynamic resting state functional connectivity and effective connectivity patterns as potential novel biomarkers of SUDEP risk.
Responsabili:
Prof. Antonio Ferretti, Prof. Mauro Gianni Perrucci
Membri del Gruppo di Ricerca:
Prof. Richard Wise, Prof. Massimo Caulo, Dott.ssa Giovanna Bubbico, Dott. Stefano Delli Pizzi, Dott. Federica Tomaiuolo, Dott. Giulia Bosello, Dott. Giordano Ponetti.
Collaborazioni esterne:
Dott. Piero Chiacchiaretta, Prof. Stefano Sensi, Dott. Francesco Gambi, Prof. Richard Edden (The Johns Hopkins School of Medicine, USA), Prof. Dante Mantini (KU Leuven University, BE).
Pubblicazioni rilevanti:
Strumentazione/attrezzatura caratterizzante l'attività di ricerca:
Scanner MRI 3T (Siemens Prisma).
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email: info@unich.it
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Partita IVA 01335970693