Final Report Summary - FABRIC (Exploring the Formation and Adaptation of the <br/>Brain Connectome)
The FABRIC project aimed to advance our knowledge about human brain development and neuroplasticity through the lenses of clinical diagnostic magnetic resonance imaging and advanced image analysis technologies. The project team utilized two new magnetic resonance imaging approaches: fetal diffusion tensor and resting-state functional acquisitions, and established normative data sets of developing fetal brains. The results of the FABRIC project are directly applicable to the pathological development of the brain during gestation, and hence can represent feasible markers of disease presence in critical periods of pregnancy. It has a direct implication for the current clinical practices: by providing normative measurements of functional and structural brain development, we can quantitatively evaluate pathological development as well. The technical challenges related to the project were successfully solved by novel image analysis technologies, which can form the basis of similar investigations in the future.
The main scientific breakthrough related to the project is the development of effective data processing that enabled the analysis of prenatal functional brain activity, and allowed its observation in a fetal population of the second and third trimester of gestation. The majority of our knowledge regarding the normal prenatal development of the central nervous system is based on post mortem examinations of fetuses or in vivo / post mortem evaluations of extremely preterm infants. In contrast to such examinations, where the normal functional activity of the brain is not directly observable, the FABRIC project paved the way for more effective examinations using fetal MRI technologies, and the first provided normative observations on the unfolding functional synchronicity within the fetal brain.
(1) Observations of the developing functional brain activity of human fetuses. The project team revealed that the gestational period between the 21st and 35th weeks holds key events in functional brain development that is detectable through functional MRI of the fetus. The functional cooperation on the macroscopical scale is characterized by functional connectivity, which is a synchronicity of detectable low-frequency signals. This synchronicity extensively increases between the 26th and 29th gestational weeks, and this type of rapid development has a certain predisposition to parts of the brain. For example, brain regions associated with lower-level processing of sensory information appear to synchronize first, while areas that will later enable higher-level cognitive functions (such as frontal/prefrontal lobe) synchronizes later. (Jakab et. al.: Fetal functional imaging portrays heterogeneous development of emerging human brain networks, 2014). The project team developed approaches to track the eye motion of fetuses on functional MRI scans, and correlated the changing activity of the fetal brain with the eye movement patterns. It was revealed that the fetal brain already prepares itself for visual stimuli presumably by increased synchronicity in visual but also non-visual related brain areas (Schoepf et al.: The Relationship Between Eye Movement and Vision Develops Before Birth., 2014).
(2) Methodological support and database building for examining the developing fetal brain. Through the project, a normative dataset of resting-state functional MRI scans and diffusion tensor scans was established. Furthermore, pathological fetuses were included and relevant methodology was developed for the alignment of fetal neuroimages to gestational week specific anatomical template sets and to form coherent models of morphological brain development (Schwartz et al.: A locally linear method for enforcing temporal smoothness in serial image registration, 2014). The recent advances of methodology, fetal imaging in normal and pathological circumstances was summarized in a review journal article (Jakab et al.: Fetal cerebral magnetic resonance imaging beyond morphology, 2015).
(3) Pathologically developing fetal brains: altered structural wiring of the fetal brain in the absence of cross-hemispheric axonal connections. Corpus callosum agenesis is a disease in which the cross-hemispheric connections are partially or completely missing. The project team used a dataset of 12 normally developing fetuses and 12 fetuses with corpus callosum agenesis to investigate the rewiring of the fetal brain connections. A globally re-organized structure was discovered, which not only involves midline and callosal white matter structures, but short-range connections in the lateral hemispheres as well (Jakab et al.: Disrupted developmental organization of the structural connectome in fetuses with corpus callosum agenesis., 2015).
(4) Extensive scientific networking, communication and dissemination of results. The FABRIC project triggered active collaboration between various disciplines, such as neuroradiology, neuropathology, computer science and mathematics. During the project, new international research collaborations have been established or were made stronger, in order to enhance the European competitiveness (for example: UCL, University of Zagreb, University Hospital Zürich, ETH Zürich). The project team carried out extensive research communication activities, in the form of television documentary, interviews, social and printed media presence.
The main scientific breakthrough related to the project is the development of effective data processing that enabled the analysis of prenatal functional brain activity, and allowed its observation in a fetal population of the second and third trimester of gestation. The majority of our knowledge regarding the normal prenatal development of the central nervous system is based on post mortem examinations of fetuses or in vivo / post mortem evaluations of extremely preterm infants. In contrast to such examinations, where the normal functional activity of the brain is not directly observable, the FABRIC project paved the way for more effective examinations using fetal MRI technologies, and the first provided normative observations on the unfolding functional synchronicity within the fetal brain.
(1) Observations of the developing functional brain activity of human fetuses. The project team revealed that the gestational period between the 21st and 35th weeks holds key events in functional brain development that is detectable through functional MRI of the fetus. The functional cooperation on the macroscopical scale is characterized by functional connectivity, which is a synchronicity of detectable low-frequency signals. This synchronicity extensively increases between the 26th and 29th gestational weeks, and this type of rapid development has a certain predisposition to parts of the brain. For example, brain regions associated with lower-level processing of sensory information appear to synchronize first, while areas that will later enable higher-level cognitive functions (such as frontal/prefrontal lobe) synchronizes later. (Jakab et. al.: Fetal functional imaging portrays heterogeneous development of emerging human brain networks, 2014). The project team developed approaches to track the eye motion of fetuses on functional MRI scans, and correlated the changing activity of the fetal brain with the eye movement patterns. It was revealed that the fetal brain already prepares itself for visual stimuli presumably by increased synchronicity in visual but also non-visual related brain areas (Schoepf et al.: The Relationship Between Eye Movement and Vision Develops Before Birth., 2014).
(2) Methodological support and database building for examining the developing fetal brain. Through the project, a normative dataset of resting-state functional MRI scans and diffusion tensor scans was established. Furthermore, pathological fetuses were included and relevant methodology was developed for the alignment of fetal neuroimages to gestational week specific anatomical template sets and to form coherent models of morphological brain development (Schwartz et al.: A locally linear method for enforcing temporal smoothness in serial image registration, 2014). The recent advances of methodology, fetal imaging in normal and pathological circumstances was summarized in a review journal article (Jakab et al.: Fetal cerebral magnetic resonance imaging beyond morphology, 2015).
(3) Pathologically developing fetal brains: altered structural wiring of the fetal brain in the absence of cross-hemispheric axonal connections. Corpus callosum agenesis is a disease in which the cross-hemispheric connections are partially or completely missing. The project team used a dataset of 12 normally developing fetuses and 12 fetuses with corpus callosum agenesis to investigate the rewiring of the fetal brain connections. A globally re-organized structure was discovered, which not only involves midline and callosal white matter structures, but short-range connections in the lateral hemispheres as well (Jakab et al.: Disrupted developmental organization of the structural connectome in fetuses with corpus callosum agenesis., 2015).
(4) Extensive scientific networking, communication and dissemination of results. The FABRIC project triggered active collaboration between various disciplines, such as neuroradiology, neuropathology, computer science and mathematics. During the project, new international research collaborations have been established or were made stronger, in order to enhance the European competitiveness (for example: UCL, University of Zagreb, University Hospital Zürich, ETH Zürich). The project team carried out extensive research communication activities, in the form of television documentary, interviews, social and printed media presence.