Holoprosencephaly

This research aims to develop and validate an artificial intelligence (AI) software to recognize fetal brain structures and distinguish between normal and abnormal brain anatomy during the second trimester ultrasound scan. The study focuses on fetal brain abnormalities, which are challenging to diagnose prenatally. AI technology may improve detection, reduce variability between operators, shorten examination time, and optimize healthcare resources. The study is conducted by multiple fetal medicine centers and targets pregnant women undergoing routine screening for fetal anomalies. The study consists of two phases: a retrospective phase and a prospective phase. In the first phase, researchers collect and analyze ultrasound images taken between 19 and 22 weeks of gestation from various centers to develop and train the AI algorithm with both normal and abnormal fetal brain images. The second phase prospectively tests the AI algorithm in real clinical settings on patients from the participating centers to validate its performance in assessing fetal brain anatomy. Participants are singleton pregnant women between 19 and 22 weeks of pregnancy who undergo ultrasound scans. Researchers will collect clinical, ultrasound, prenatal, and postnatal data, anonymize images, and store them securely for analysis. The primary outcome is validating the AI algorithm over two years. Secondary outcomes include improving reproducibility and reducing examination time within one year. The study involves continuous monitoring and assessment of ultrasound images to support routine fetal brain screening.

This research gathers data and biological samples from pregnant women to study prematurity, preeclampsia, and other pregnancy complications. It combines information from four original studies involving women at different stages of pregnancy, including those with low risk and those diagnosed with preeclampsia. The goal is to better understand early onset preeclampsia and related conditions using medical, social, obstetrical, and ultrasound data along with biological markers and genetics. Participants in the biobank provide blood and urine samples along with detailed clinical and demographic information. The studies include women pregnant with singletons or twins at various early gestational ages, some randomized to receive low-dose aspirin or placebo. Ultrasound examinations and blood pressure measurements are also part of the data collection, with access to medical records for pregnancy outcomes and newborn health. Women in the biobank undergo assessments including blood sample collection, urine testing, blood pressure monitoring, and ultrasound scans. Researchers use this information to measure outcomes such as early onset preeclampsia diagnosed between 20 and 34 weeks, severe preeclampsia, fetal growth restriction, spontaneous preterm birth, and fetal anomalies. The study started in 2015 and plans to continue until 2028, offering long-term follow-up of pregnancy complications and their outcomes.

Researchers are creating a database of healthy adult subjects aged 18 to 65 years to study brain structure and function using advanced imaging techniques. This project, part of the European Human Brain Project, focuses on healthy individuals to better understand brain activity and metabolism through a multimodal approach involving MRI, PET, and electrophysiology. The goal is to provide valuable data for scientific collaboration on epilepsy and brain health. Participants will undergo a 18F-FDG PET brain imaging exam, which measures glucose metabolism in the brain by using a small amount of radioactive tracer injected intravenously. The scan lasts about 45 minutes and captures a three-dimensional image at rest, allowing researchers to quantify brain glucose consumption and connectivity. This is a non-therapeutic study involving a single imaging procedure performed at baseline, with a follow-up measurement planned 24 months later. During the study, participants will be monitored through imaging and assessments of cerebral glucose consumption and metabolic connectivity at baseline and after 24 months. The PET scans are part of routine clinical procedures with established safety profiles, and all participants must provide informed consent. The study lasts over two years, including the initial scan and long-term follow-up, aiming to enhance understanding of healthy brain metabolism and function.

Researchers are investigating genes responsible for epilepsy, brain malformations, and disorders affecting human cognition. This study aims to identify genetic factors involved in conditions such as polymicrogyria, lissencephaly, pachygyria, heterotopias, microcephaly, cerebellar hypoplasia, familial intellectual disability, and familial autism. These conditions often coexist with epilepsy and are diagnosed using brain MRI or CT scans. The study focuses on understanding the genetic basis of these disorders by comparing DNA from affected individuals and families to that of the general population. Participants include adults and children diagnosed with brain malformations or cognitive disorders such as familial intellectual disability or autism. Family members of affected individuals are also invited to participate. This observational study collects genetic data to help identify and characterize genes important in normal brain development and related abnormalities. There are no experimental treatments or interventions involved. During the study, participants provide genetic samples and share medical information related to their condition. Researchers analyze these samples to discover genetic links to the studied conditions. The primary outcome is the ongoing identification and characterization of genes linked to brain development and malformations. Participants remain under their usual care throughout the study, which may continue for several years as the research progresses.

Researchers are studying individuals with MEHMO syndrome or related eIF2-pathway conditions, which involve symptoms such as intellectual disability, seizures, hormone and blood sugar irregularities, and reduced motor skills. This observational natural history study aims to better understand these rare conditions by identifying clinical and biochemical markers to track disease progression and to improve knowledge about their course and impact. Participants include those diagnosed with MEHMO syndrome or related disorders, carriers of EIF2S3-related variants, and unaffected family members. The study involves regular health assessments, imaging tests, laboratory evaluations, and collection of biological samples including blood, urine, spinal fluid, and skin biopsies. It follows individuals over time to gather comprehensive data and biological materials. During the study, participants will undergo evaluations of their general health and disease symptoms, imaging exams, and various laboratory tests. Researchers will monitor clinical signs and fluid biomarkers to develop a severity rating scale and classification system. The study also aims to build a repository of data and samples for future research. This observational study does not involve any treatment but focuses on detailed monitoring to support future therapeutic development.

Researchers are studying individuals with autism spectrum disorders (ASD) who have germline heterozygous PTEN mutations, a genetic subgroup that may represent a significant portion of ASD cases. This study aims to compare medical, behavioral, and cognitive differences between PTEN ASD and other groups, and to identify specific cognitive, neural, and molecular biomarkers for PTEN ASD. The research will also create and maintain a biorepository and linked phenotypic database focused on this condition. Participants will include individuals with PTEN ASD, those with macrocephalic ASD without PTEN mutations (macro-ASD), healthy controls, and individuals with PTEN mutations but no ASD (PTEN no-ASD). The study involves three on-site visits over two years, each lasting about 4 to 6 hours. Visits include physical exams, medical history reviews, neuropsychological assessments, and blood draws for lab studies. Children aged 2 to 11 may also participate in an EEG portion. Participants with clinically indicated MRIs can optionally provide scans for analysis. During participation, individuals will undergo various assessments such as changes in verbal abilities, communication, visual perception, working memory, and processing speed at 12 and 24 months. The study also includes physical exams and collection of medical and behavioral data. Participants will be monitored over the two-year period with three visits to track longitudinal changes and biomarkers associated with PTEN ASD. The research is observational and includes healthy volunteers as well.

Researchers are investigating how sleep disorders are related to structural differences in children with Chiari Malformation Types 1 and 2. The study aims to understand the connection between sleep-disordered breathing (SDB) severity and measurements of airways, cranial base openings, and the volume of the back part of the skull. This study focuses on pediatric patients to provide insights into how these brain malformations may impact breathing during sleep. Participants will undergo diagnostic tests including magnetic resonance imaging (MRI) to measure the volume of the posterior cranial fossae, airway size, and cranial base foramina area. They will also have polysomnographic evaluations to assess the presence and type of sleep-disordered breathing, distinguishing between central and obstructive origins. The study compares two groups of children with Chiari Malformation Type 1 and Type 2. During the study, children will be closely monitored through these imaging and sleep tests over a period of three years. Researchers will measure the prevalence of sleep-disordered breathing and analyze how it relates to anatomical differences in the brain and airway structures. The study includes clinical evaluations and informed consent processes, allowing careful observation of sleep breathing patterns and brain structure relationships in this young population.

Researchers are examining how various maternal lifestyle and environmental factors such as smoking, alcohol use, drug abuse, prescription medicines, and exposure to chemicals can affect human fetal development. The study focuses on fetuses between 7 and 20 weeks of gestation, a critical period for development, to better understand the mechanisms by which these exposures may cause long-term health issues like obesity, hypertension, metabolic syndrome, and infertility. This observational study aims to provide fundamental knowledge about normal fetal development and how adverse maternal influences can alter it, ultimately affecting health in adulthood. The study involves collecting multiple fetal organs and body fluids from normal pregnancies as well as pregnancies where the mother experiences challenges such as smoking, obesity, or exposure to pollutants. Researchers will use various laboratory and microscopic techniques to analyze hormones, genes, proteins, chemicals, and DNA from fetal tissues. The investigation covers many systems including the endocrine, reproductive, nervous, metabolic, cardiovascular, immune, musculoskeletal, and placental development. There is also a focus on maternal emotional health and its impact on the fetus, as well as a study on nerve repair potential. No active intervention is performed; this is a detailed observational research program. Participants will be involved during early pregnancy, with fetal tissue collection occurring between 7 and 20 weeks of gestation. Researchers will gather extensive data on fetal development and maternal lifestyle, including questionnaires related to alcohol use and emotional wellbeing. The main outcome is the creation of a large dataset describing normal fetal development and the effects of maternal environment, which will be used for future research to improve health outcomes. The study includes long-term follow-up of up to 10 years to assess how early fetal exposures relate to adult health and disease risks.

Researchers are investigating how brain development in infants up to 6 years old relates to their social emotions and communication skills. The study also examines the influence of genetic factors and maternal exposures during pregnancy, such as environmental factors and maternal inflammatory conditions. The goal is to provide a foundation for targeted interventions to improve infants' social and emotional abilities and overall brain development. The study uses advanced brain imaging techniques, including functional magnetic resonance imaging (fMRI) with multiple methods like blood-oxygen-level dependent imaging and perfusion weighted imaging. These imaging methods, combined with cloud-based analysis and artificial intelligence, help map brain structure, function, connectivity, and development trajectories. Researchers also assess children's social-emotional behavior using the Chinese Urban Children's Emotion and Social Assessment Scale and neurological development with the Gesell Developmental Scale. Blood samples are collected for genetic and biomarker analysis, and family and maternal health information during pregnancy is gathered through questionnaires and clinical history. Participants will undergo brain scans and assessments at the start of the study and again six months later, with intelligence quotient measured annually from ages 3 to 6. Researchers will monitor changes in brain structure, function, blood flow, EEG, social-emotional behavior, brain development, and child mental health. Biomarker screening occurs once at baseline. The study spans from infancy through early childhood, with data collected to understand brain development changes and predict developmental outcomes over time.

This research aims to explore the relationship between new ultrasound imaging patterns and malformations of the fetal central nervous system (CNS). It focuses on understanding brain development during pregnancy by analyzing ultrasound scans, seeking to identify clearer patterns that may improve the diagnosis of fetal brain abnormalities. The study compares ultrasound images from fetuses diagnosed with CNS malformations to those from healthy fetuses, helping to better characterize these malformations. The study involves reviewing ultrasound images routinely taken during pregnancy for two groups: fetuses with CNS malformations and healthy fetuses without such abnormalities. Data collected includes maternal age, pregnancy history, conception method, family history, type and timing of CNS malformation diagnosis, pregnancy outcomes, and newborn health measures such as sex, weight, and neurological assessment shortly after birth. Participants will provide information about their pregnancies and allow access to ultrasound images previously obtained. Researchers will assess correlations between ultrasound patterns and fetal CNS malformations as the main outcome. Additional comparisons between affected and healthy fetuses are planned. The study spans up to 100 weeks, including prenatal imaging review and postnatal newborn assessments, with ongoing monitoring of pregnancy outcomes and neurological health.