[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100659459":3},{"organization":4,"outcomesModule":7,"designInfo":38,"detailedDescription":45,"studyPopulation":41,"armGroups":46,"interventions":53,"overallOfficials":41,"centralContacts":59,"locations":68,"responsibleParty":86,"collaborators":88,"id":95,"slug":96,"hasResults":97,"nctId":98,"briefTitle":99,"officialTitle":100,"acronym":101,"eligibilityCriteria":102,"healthyVolunteers":103,"sex":104,"minAge":105,"maxAge":106,"enrollmentInfo":107,"targetDuration":41,"studyType":110,"phases":111,"briefSummary":112,"conditions":113,"keywords":118,"overallStatus":71,"whyStopped":41,"lastUpdateSubmitDate":124,"lastUpdatePostDateStruct":125,"startDateStruct":128,"completionDateStruct":130,"leadSponsor":132,"locationsCount":133},{"fullName":5,"class":6},"Imago 7 Fondazione di Ricerca onlus","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":16,"otherOutcomes":26},[9,13],{"measure":10,"description":11,"timeFrame":12},"Spatial Resolution of Acquired Images","\\- Comparison of spatial resolution (voxel size in mm) of images acquired using the different implemented techniques","0-36 months",{"measure":14,"description":15,"timeFrame":12},"Temporal Resolution of Acquired Images","\\- Comparison of temporal resolution (in seconds) of images acquired using the different implemented techniques",[17,20,23],{"measure":18,"description":19,"timeFrame":12},"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;",{"measure":21,"description":22,"timeFrame":12},"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;",{"measure":24,"description":25,"timeFrame":12},"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;",[27,31,35],{"measure":28,"description":29,"timeFrame":30},"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\u002Fstereo-EEG data","0 - 36 months",{"measure":32,"description":33,"timeFrame":34},"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","12-36 months",{"measure":36,"description":37,"timeFrame":12},"Functional Signal Change and Reproducibility Across Imaging Techniques","\\- Analysis of functional activation maps\u002Fresponses and connectivity measures acquired with the different techniques in terms of percentage signal change and reproducibility.",{"allocation":39,"interventionModel":40,"interventionModelDescription":41,"primaryPurpose":42,"observationalModel":41,"timePerspective":41,"maskingInfo":43},"NA","SINGLE_GROUP",null,"DIAGNOSTIC",{"masking":44,"maskingDescription":41,"whoMasked":41},"NONE","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).\n\nThis 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).\n\nCompared 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\u002For spatial and temporal resolution.\n\nOver 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).\n\nIn 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).\n\nIn 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).\n\nThese 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:\n\nTo 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.\n\nTo explore cortical reorganization of eloquent areas following brain lesions, in order to better understand mechanisms of neuroplasticity.\n\nSelected 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.\n\nIn 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).\n\nAlthough 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).\n\nRegarding 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\u002Fsubcortical 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).\n\nAs 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.\n\nThe 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.\n\nThe 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.\n\nThe 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).\n\nCine-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.\n\nBecause these neuronal events are unpredictable, pseudo-random spatial encoding is required for retrospective data sorting and reconstruction into consistent images for subsequent processing.\n\nFor 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.\n\nAfter 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.\n\nThe 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.\n\nWP1 - 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.\n\nWP2 - 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.\n\nWP3 - 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.\n\nWP4 - Validation and clinical translation of advanced 7T MRI methods in subjects with epilepsy or malformed\u002Flesioned 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.\n\nThe 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.",[47],{"label":48,"type":49,"description":50,"interventionNames":51},"Deep-Learning to achieve higher spatial and temporal resolution for functional neuroimaging","EXPERIMENTAL","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).\n\nNo 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.",[52],"Diagnostic Test: Functional neuroimaging",[54],{"type":55,"name":56,"description":57,"armGroupLabels":58,"otherNames":41},"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:\n\n1. 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).\n2. 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",[48],[60,65],{"name":61,"role":62,"phone":63,"phoneExt":41,"email":64},"gilda gallucci","CONTACT","0039 050886233","gilda.gallucci@fsm.unipi.it",{"name":66,"role":62,"phone":63,"phoneExt":41,"email":67},"chiara bernardi","chiara.bernardi@fsm.unipi.it",[69],{"facility":70,"status":71,"city":72,"state":73,"zip":74,"country":73,"countryCode":75,"cosmosGeoPoint":76,"geoPoint":81,"contacts":82},"Imago7 Foundation","RECRUITING","Pisa","Italy","56128","IT",{"type":77,"coordinates":78},"Point",[79,80],10.4036,43.70853,{"lat":80,"lon":79},[83],{"name":84,"role":85,"phone":41,"phoneExt":41,"email":41},"Renzo Guerrini, Professor","PRINCIPAL_INVESTIGATOR",{"type":87,"investigatorFullName":41,"investigatorTitle":41,"investigatorAffiliation":41,"oldNameTitle":41,"oldOrganization":41},"SPONSOR",[89,91,93],{"name":90,"class":6},"Meyer Children's Hospital IRCCS",{"name":92,"class":6},"IRCCS Fondazione Stella Maris",{"name":94,"class":6},"University of Pisa","100659459","advanced-space-time-resolved-techniques-for-functional-neuroimaging-at-7-tesla-mri-100659459",false,"NCT07865546","Advanced Space-time Resolved Techniques for Functional Neuroimaging at 7 Tesla MRI","Advanced Space-time Resolved Techniques for fUnctional neuROimaging Characterization of Structurally Abnormal Eloquent coRtical Areas","AURORA","Inclusion criteria Healthy Volunteers\n\n* Age ≥ 18 years;\n* No history of diagnosed psychiatric disorders;\n* Sufficient understanding of the Italian language (required both for informed consent and for comprehension of fMRI task instructions);\n* Provision of written informed consent.\n\nPatients\n\n* Age 6-65 years;\n* Diagnosis of drug-resistant epilepsy (PMID: 19889013), with or without structural brain abnormalities, and candidate for surgical treatment (PMID: 21145290, 24497269, 31876960), or presence of pre-, peri-, or post-natal brain lesions documented by prior brain MRI;\n* Normal intellectual functioning or mild cognitive impairment sufficient to ensure adequate collaboration during the 7T functional neuroimaging study;\n* Sufficient understanding of the Italian language (required both for informed consent and comprehension of fMRI task instructions);\n* Provision of written informed consent (and assent when applicable, according to age and regulations).\n\nExclusion Criteria (All Participants)\n\n* Contraindications to 7T MRI;\n* Neuropsychiatric comorbidities preventing adequate collaboration during functional neuroimaging;\n* Pregnancy;\n* Refusal to receive information regarding incidental findings identified during MRI examination.",true,"ALL","6 Years","65 Years",{"count":108,"type":109},180,"ESTIMATED","INTERVENTIONAL",[39],"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).\n\nThis 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.\n\nThese 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.\n\nThe 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.",[114,115,116,117],"Neurological Disorders","Neuroscience","Epilepsy","Brain Injuries, Focal",[119,120,121,122,123],"epilepsy","7T MRI","functional MRI","brain lesion","ultra-high field MRI","2026-10-04",{"date":126,"type":127},"2026-10-08","ACTUAL",{"date":129,"type":127},"2024-10-16",{"date":131,"type":109},"2027-10-16",{"name":5,"class":6},1]