An interventional study of Functional neuroimaging in Neurological Disorders, Neuroscience and Epilepsy, sponsored by Imago 7 Fondazione di Ricerca onlus. Recruiting at 1 site in Italy. Open to participants aged 6 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-10-08.
Sponsored by Imago 7 Fondazione di Ricerca onlus · Not applicable, Interventional, and Diagnostic
In recent years, the in vivo study of the central nervous system has undergone significant advancement through the implementation of magnetic resonance imaging (MRI)-based neuroimaging techniques. In particular, the advent of high- and ultra-high-field MRI systems has substantially contributed to a deeper understanding of the pathophysiological mechanisms underlying neurological diseases and has supported the development of personalized approaches in medicine. In the field of neuroimaging, the application of MRI techniques to investigate brain function and connectivity in vivo is increasingly expanding at ultra-high magnetic field strength (7T).
This research project aims to develop, implement, and optimize advanced techniques to improve image quality through deep learning-based approaches and real-time monitoring of magnetic field fluctuations, with the goal of achieving functional neuroimaging at very high spatial and temporal resolution on a 7T scanner.
These techniques will be applied in healthy volunteers to address fundamental questions in basic neuroscience, as well as in clinical populations with central nervous system disorders, including patients with focal epilepsy and patients with congenital brain lesions associated with persistent neurological deficits.
The basic neuroscience component will allow investigation of mechanisms of brain function and connectivity between eloquent cortical regions and subcortical structures. In the clinical setting, improved delineation of activation maps in eloquent brain areas and characterization of their reorganization under pathological conditions are expected to enhance personalized therapeutic decision-making and deepen our understanding of neuroplasticity mechanisms, with potential impact on clinical care pathways.
Background Magnetic Resonance Imaging (MRI) represents a unique tool for the in vivo study of the central nervous system. With the advent of ultra-high-field technologies, such as 7 Tesla (7T) MRI, the accuracy and reproducibility of studies investigating brain structures and functions-such as visual or sensorimotor systems-have increased considerably, increasingly enabling investigations at the single-subject level in addition to group-level analyses (PMID: 29205628).
This aspect is particularly relevant in clinical practice, which increasingly promotes the use of technologies that enable personalized diagnostic and therapeutic approaches in neuroscience. Such approaches integrate structural brain information with functional, molecular, and genetic aspects (PMID: 27613521, 35021279, 36870920).
Compared with clinical field strength systems (up to 3 Tesla), 7T MRI provides a substantial gain in signal-to-noise ratio (SNR), which can be exploited to improve image quality by enhancing contrast and/or spatial and temporal resolution.
Over the last years, 7T MRI has confirmed these advantages in structural neuroimaging, for example by identifying epileptogenic malformations not visible on conventional neuroimaging (PMID: 26778405) and morphological markers of highly epileptogenic areas (PMID: 31727747).
In functional MRI (fMRI) studies, ultra-high-field MRI has enabled segmentation of subcortical structures to reveal their selectivity to specific external stimuli, exploration of the functional organization of eloquent cortical areas, investigation of the cortex at the mesoscopic (submillimetric) scale-revealing cortical columns and laminar profiles-and characterization of cortico-subcortical functional connectivity (PMID: 35384840, 34111403).
In the clinical setting, particularly in acquired pre- or perinatal brain lesions, the use of 7T has been shown to provide benefits in characterizing functional organization compared with conventional clinical MRI systems (PMID: 30595689).
These premises support the hypothesis that ultra-high-field MRI may contribute to clarifying the pathophysiological mechanisms underlying the functional organization of malformed or lesioned human cerebral cortex, with two important potential translational implications:
To investigate connectivity between epileptogenic cortical areas and subcortical structures, which appears crucial for assessing the residual functional capacity of altered cortex and its role in managing synchronized subcortical electrical activity.
To explore cortical reorganization of eloquent areas following brain lesions, in order to better understand mechanisms of neuroplasticity.
Selected patients with drug-resistant epilepsy may benefit from surgical treatment involving resection of the epileptogenic zone. Current standards for pre-surgical assessment require a multimodal approach to accurately identify the epileptogenic zone and define its functional properties (PMID: 24099054). However, when the epileptogenic area overlaps with eloquent cortex, invasive stereo-EEG techniques are often required.
In addition to resection, epilepsy surgery provides the opportunity to perform histological studies on the resected tissue. Specific genetic and molecular alterations underlying dysplastic areas (e.g., those involving the mechanistic target of rapamycin [mTOR] pathway or SLC35A2 gene variants) are associated with characteristic histological abnormalities. However, an unresolved issue concerns the possibility that histologically abnormal cells may be present without forming a mass sufficient to generate an MRI-visible dysplasia eligible for surgery (PMID: 33542949).
Although recent classification systems for cortical dysplasias integrate histological, genetic, and MRI data (PMID: 35706131), some of this information is only available post hoc and therefore cannot be considered during the critical phase of neurosurgical planning. In this context, identifying morpho-functional patterns using high spatial and temporal resolution neuroimaging techniques, such as ultra-high-field functional MRI, could facilitate pre-surgical planning, reduce the need for invasive procedures, and contribute to the implementation of personalized treatment strategies (PMID: 34145582; 34742103; 30064388).
Regarding pre- or perinatal brain lesions, it is well established that different brain structures show varying vulnerability across different stages of the pre-perinatal period. This results in distinct patterns of injury, with predominant involvement of white matter or cortical/subcortical gray matter. The topography and severity of the lesion, in turn, lead to different clinical outcomes, particularly with respect to motor or sensory deficits and the recruitment of compensatory plasticity mechanisms (PMID: 33613420; 17254004).
As in cortical malformations, in vivo knowledge of mechanisms underlying reorganization of eloquent brain functions in acquired lesions may contribute to better understanding clinical presentations and identifying personalized rehabilitation pathways based on morpho-functional characteristics of the lesion.
The current project aims to develop and evaluate novel advanced 7T functional neuroimaging methods with very high spatial and temporal resolution to investigate minimal MRI signal fluctuations. Two complementary approaches will be pursued in parallel.
The first approach will focus on improving and optimizing the quality of structural and functional images using Deep Learning (DL) techniques for image correction and acceleration, as well as magnetic field monitoring through a field camera to characterize and correct local field perturbations responsible for image distortions and artifacts.
The second approach will involve the development of novel functional neuroimaging sequences (cine-fMRI) capable of detecting signal variations at temporal resolutions approaching that of neuronal action potentials. Cine-MRI techniques have thus far been applied primarily in animal models and in two-dimensional imaging (PMID: 36227975; 36227975).
Cine-fMRI will be implemented on the 7T MRI system for whole-brain studies. This technique enables dynamic imaging based on the assumption of repeated signal behavior following a specific trigger, such as an external or internal stimulus in functional MRI. Such stimuli may include neuronal events elicited externally or generated internally, such as epileptogenic activity.
Because these neuronal events are unpredictable, pseudo-random spatial encoding is required for retrospective data sorting and reconstruction into consistent images for subsequent processing.
For data acquisition, ZTE and Looping Star sequences will be explored, as both are compatible with the cine-fMRI approach. ZTE is a 3D sequence with spiral sampling that enables detection of potential direct functional fluctuations (i.e., not dependent on the BOLD effect as in conventional fMRI sequences). Looping Star is based on a multi-gradient echo sequence that allows pseudo-random data sampling with conventional T2*-weighted BOLD contrast.
After validation and optimization in phantoms and healthy volunteers, these techniques will be applied in functional studies in both basic neuroscience and two clinical populations: patients with drug-resistant epilepsy who are candidates for epilepsy surgery, and patients with acquired brain lesions.
The study will be structured into four Work Packages (WPs). WP1 and WP2 will focus on the technological development of novel processing techniques and imaging sequences for brain imaging. These two WPs will operate in close interaction, continuously informing each other and exchanging results bidirectionally throughout the project.
WP1 - Development and implementation of state-of-the-art image correction approaches. IMAGO7 and IRCCS Stella Maris, in collaboration with GEHC and THI, will develop and implement on the 7T MRI scanner new methods to enhance image quality based on: a) Deep learning (DL) algorithms to accelerate acquisition, reduce noise, and mitigate subject motion effects; b) Correction of geometric distortions through offline monitoring of local magnetic field inhomogeneities using a dynamic field camera, a device capable of directly recording the magnetic field during pulse sequences and simulating the presence of the subject without the subject being physically inside the magnet.
WP2 - Development and implementation of cine-fMRI sequences. GEHC and THI, in collaboration with IMAGO7, will lead WP2, which will focus on the development, implementation, and optimization of innovative cine-fMRI sequences on the 7T MRI scanner.
WP3 - Implementation of UHF-MRI techniques for Neuroscience. WP3 and WP4 will provide data to support and validate the implementations developed in WP1 and WP2 through their application in basic neuroscience and clinical studies. Activities within WP3, conducted in collaboration between the University of Pisa, IRCCS Stella Maris, and IMAGO7, will involve translating the newly developed functional neuroimaging methods into advanced neuroscience applications, including both task-related studies and investigations of cortico-cortical and cortico-subcortical connectivity.
WP4 - Validation and clinical translation of advanced 7T MRI methods in subjects with epilepsy or malformed/lesioned brain areas. AOU Meyer IRCCS, together with IRCCS Stella Maris and the University of Pisa, will conduct WP4. This WP will focus on the clinical application of the advanced fMRI techniques developed in WP1 and WP2 for: non-invasive localization of cortical responses, characterization of epileptogenic areas, genotype-phenotype correlations.
The application of the techniques developed in WP1 and WP2 across two substantially different contexts-basic neuroscience studies in highly cooperative healthy volunteers and clinical pediatric populations, where intrinsic image noise may be considerable-is essential to evaluate the robustness, versatility, and added value of these methods under markedly different experimental conditions.
974 studies on the registry are indexed under Nervous System Diseases; 252 are open to participants now.
This study's planned enrollment of 180 is above the median of 48 across 623 interventional studies indexed under Nervous System Diseases.
Browse Nervous System Diseases studies →This is the only study on the registry with Imago 7 Fondazione di Ricerca onlus as lead sponsor.
Counted across the registry records on this site, refreshed daily.
Patients
Exclusion Criteria (All Participants)
The intervention consist of the execution of the 7T MRI functional study of eloquent brain areas (including at least one among visual, sensorimotor or language function). No further visit following the MRI study will be scheduled for any participant. Each MRI study requires approximately 2 hours, including preparation. For a subgroup of volunteer subjects, two MRIs will be performed approximately two hours apart, before and after a specific research procedure (monocular deprivation) which serves to quantify plasticity of the visual system. For each volunteer, a total time commitment of approximately 5 consecutive hours is expected.
Diagnostic Test: Functional neuroimaging
Novel advanced method based on Ultra High Field-MRI for personalised functional neuroimaging by depicting tiny neuronal MR signal fluctuations at high spatial and temporal resolution. Two approaches will be investigated: 1. Enhanced image quality for both structural and functional MRI through: a) DL-based denoising and sharpening reconstruction (arXiv:2008.06559) developed, tested and optimized for functional and connectivity studies; b) anti-aliasing DL reconstruction techniques (PMID: 31247254) implemented to achieve higher spatial and temporal resolution with respect to the current state of the art; c) field monitoring using the field camera developed and implemented to correct several dynamic field disturbances that result in image distortions and artifacts (PMID: 28077303). 2. Development of a novel, non-invasive, 3D whole-brain, direct functional neuroimaging method, with unprecedented sensitivity in order to resolve tiny neuronal MR signal fluctuations
Spatial Resolution of Acquired Images
\- Comparison of spatial resolution (voxel size in mm) of images acquired using the different implemented techniques
Time frame: 0-36 months
Temporal Resolution of Acquired Images
\- Comparison of temporal resolution (in seconds) of images acquired using the different implemented techniques
Time frame: 0-36 months
Image Signal Quality Across Imaging Techniques
\- Evaluation of signal-to-noise ratio (SNR) obtained with the implemented techniques, including comparison of images before and after the application of noise correction algorithms;
Time frame: 0-36 months
Image Noise Across Imaging Techniques
\- Evaluation of contrast-to-noise ratio (CNR) in images obtained with the implemented techniques, including comparison of images before and after the application of noise correction algorithms;
Time frame: 0-36 months
Artifacts Across Imaging Techniques
\- Evaluation of artifacts types in images obtained with the implemented techniques, including comparison of images before and after the application of noise correction algorithms;
Time frame: 0-36 months
Electrophysiological Correlates of Functional Imaging
In patients with epilepsy (with or without brain malformations or lesions), comparison between activation maps obtained using optimized 7T fMRI sequences and EEG/stereo-EEG data
Time frame: 0 - 36 months
Functional Activation and Connectivity in Patients and Controls
In clinical populations, including patients with drug-resistant epilepsy, with or without structural brain abnormalities (malformations or lesions) who are candidates for surgery, and patients with brain lesions acquired in the pre- or perinatal period, to compare activation patterns in eloquent cortical areas (visual and sensorimotor), cortico-subcortical connectivity, and signal propagation between patients and controls
Time frame: 12-36 months
Functional Signal Change and Reproducibility Across Imaging Techniques
\- Analysis of functional activation maps/responses and connectivity measures acquired with the different techniques in terms of percentage signal change and reproducibility.
Time frame: 0-36 months
Plan to share: No
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.