Functional Neuroimaging
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The Functional Neuroimaging Group focuses on the assessment of the “individual brain connectome” based on resting-state functional magnetic resonance imaging (fMRI). We work on algorithms to detect and quantify changes in the functional connectivity architecture of individual patients in comparison to large reference cohorts, with the overarching aim to develop imaging biomarkers for diagnosis, treatment monitoring and therapy guidance of neurological and neuropsychiatric disorders. Our main focus comprises neuro-oncological and neuro-degenerative diseases. In order to better understand the adult brain, our group further uses advanced MRI techniques to study brain development perinatally, including fetal and neonatal imaging of the brain, and organ systems that impact brain development such as the cardio-respiratory system.
Our interdisciplinary group is composed of radiologists, neurobiologists, psychologist, engineers, and computer scientists.
Functional connectivity in neurological disorders
New concepts of brain disease suggest that network disruption does not only occur as an epi-phenomenon of underlying brain pathology, but that the formation of aberrant connections can be a major contributor to the progression of brain diseases, including neuro-oncological and neurodegenerative diseases. The current role of MRI in such diseases is to provide structural information about tumors and their close vicinity and to describe patterns of brain atrophy and vascular damage. Here, assessment of functional connectivity alterations on the whole brain level might provide important additional information that is not yet available in vivo in individual patients.
However, despite more than two decades of functional connectivity research no clinically applicable and validated imaging tool is available to assess network dysfunctions quantitatively in the individual patient. We have designed a novel imaging marker based on resting-state fMRI which assesses global functional connectivity in individual patients (Stoecklein et al., 2020), with the aim to detect and quantify alterations of the connectivity architecture of individual patients by comparing individual connectivity profiles to a normative distribution derived from large, healthy reference cohorts.
Neuro-oncology
Current imaging techniques provide information about the tumors itself and its close vicinity. However, e.g., in glioma, tumor cells are not restricted to the macroscopically visible tumor but are also disseminated throughout the entire brain. Currently, there is no tool to non-invasively assess the structurally normal appearing brain parenchyma in vivo.
We successfully tested the dysconnectivty index (DCI) in a cohort of patients with newly diagnosed glioma and found that there was a strong association between DCI and WHO grade and cognitive functioning level.
We are currently investigating the potential of our marker in assessing prognosis, therapy response, and recurrence.
Functional dysconnectivity in individual patients with high-grade and low-grade tumors.
Overlaying connectome maps and anatomical scans visualizes widespread damage to brain functional connectivity in patients with high-grade tumors. In contrast, in patients with low-grade tumors abnormal functional connectivity is largely confined to the lesion and to the lesional hemisphere. Figure adapted from Stoecklein et al., 2020.
Neurodegeneration
Recent advances in functional neuroimaging highlighted disruptions in brain network in neurodegenerative disorders such as Alzheimer’s Disease, and Parkinson’s Disease. We aim to develop a functional imaging marker that predicts disease progression and assesses treatment response. Recent publications suggest the propagation of neurodegenerative pathology, e.g., tau spread, through functional brain network disruptions.
Artificial intelligence for data analysis of large cohort studies
In radiomics research, artificial intelligence (AI) has emerged as a powerful tool to efficiently handle large multidimensional datasets. In particular, graph auto-encoders have proven to be potent instruments for unsupervised anomaly detection. We aim to develop AI algorithms that detect abnormalities in functional connectivity not only based on 4D functional MRI data, but also based on enriched multidimensional input data including demographics (age, sex, gender) and technical parameters (scanner type and protocol specifications). AI-based abnormality detection has been applied to structural MRI data, however moving this field into the fMRI arena and leveraging large publicly available databases as reference samples offers great potential for developing a refined diagnostic tool that is perfectly tailored to each individual patient.Perinatal imaging: Advanced MR imaging for the exploration of brain development in health and disease
To understand the structure and function of the adult brain, it is crucial to understand its earliest development, including potential disruptive factors. We investigate brain development in utero and in the perinatal period, focusing on physiological development but also on early pathology of brain development, and how it might be affected by other organs such as the cardiorespiratory system. -
ALZECA
Alzheimer's disease is characterized by the presence of amyloid plaques - protein depositions - in the brain. Currently, assessing amyloid presence and distribution in the brain requires positron emission tomography (PET). The aim of the ALZECA study is to determine whether this procedure may be replaced by magnetic resonance imaging (MRI) using the contrast agent ADx-001. ADx-001 is a novel, intravenously delivered, Gd-containing molecularly targeted liposomal product that is being developed for use in contrast-enabled MR imaging of amyloid plaques.
Replacing PET by MRI would reduce radiation exposure and simplify the diagnostic process by providing detailed information on brain structure and volume while simultaneously identifying amyloid depositions. Animal studies have shown that ADx-001 accumulates in brain regions with amyloid plaques and is detectable by MRI (Badachhape et al., 2020). The objective of this Phase 1 trial is to establish safety of ADx-001 in healthy volunteers, and safety and proof of concept in patients with confirmed amyloid plaques in the brain (confirmed by amyloid PET).
Badachhape, A.A., Working, P.K., Srivastava, M. et al. Pre-clinical dose-ranging efficacy, pharmacokinetics, tissue biodistribution, and toxicity of a targeted contrast agent for MRI of amyloid deposition in Alzheimer’s disease. Sci Rep 10, 16185 (2020)
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Group Leader
Prof. Dr. med. Sophia Stöcklein
Senior physician, head of MRI, head of research organisation
Sophia has been involved in advanced neuroimaging, especially functional connectimocs ever since her doctoral thesis, where she worked on changes of the default network in mild cognitive impairment and Alzheimer’s disease. She went on to gain profound expertise and skills in computational neuroscience and cognitive psychology during a 2-year, DFG-funded postdoctoral fellowship in computational neuroscience at the Martinos Center of Biomedical Imaging (MGH) and the Department of Psychology at Harvard University (Cambridge, USA). Her postdoctoral work focused on the assessment of the reliability and variability of fMRI-based functional connectivity measures and on the explorations of individual differences in the connectivity architecture of the human brain. During her residency training in radiology she went on to apply refined techniques of personalized fMRI analyses to patient cohorts including neuro-degenerative and neuro-oncologic diseases. The overarching aim of her research work is to develop and validate fMRI-based biomarkers that inform personalized diagnostic and therapeutic strategies in the management of patients with neurological disorders.Clinical and Postdoctoral Researchers
Dr. med. Gloria Biechele
Resident
Gloria received her awarded MD in the field of preclinical molecular brain imaging in neurodegenerative diseases, which she still works on translationally. She has a strong clinical focus in fetal MRI with a postdoctoral research scope including the application and advancement of fetal cardiac MRI.Xä:üplg Aliyziäivimsful_vfiuyziu miFranziska Müller, M.Sc.
Resident
Franziska is a radiology resident who also holds a M.Sc. in Human Biology. Her focus has been on systems neuroscience and neuroimaging in both basic and clinical research. She is currently working on functional and structural MRI, and clinical applications of AI solutions in neuroimaging.Äpgußlcog DOfiääipvimsfuln_vfiuyziutmiDr. med. Sarah Schläger
Resident
Sarah is a resident and clinician scientist. Her research focuses on novel MRI techniques and integrating AI in the MRI workflow. Currently, she explores innovative MRI applications, such as quantitative imaging in neuromuscular diseases and advanced sequence techniques in fetal MRI.Rgpgz-Ryzäginxipvim ful_vfiuyziusmiStefan Suvak
Stefan is a radiology resident with a previous research focus and passion for neurofunctional imaging. As part of his doctoral thesis at the Klinikum rechts der Isar, he investigated the growth behavior of gliomas and the effects of radiotherapy on the functional status of patients in terms of motor or language deficits. Cortical functional imaging using transcranial magnetic stimulation (TMS) was combined with DTI via fiber tracking and correlated with radiotherapy.
Rbiwgu-Rfqgovimsfu;l_vfdiuyziusmiPhD and MD students
Stephan Wunderlich, M.Sc.
With a multidisciplinary background in medicine and engineering from TUM, the Martinos Center for Biomedical Imaging in Boston, the Brain Science Center in Edinburgh, and the University of British Columbia, Stephan’s research passion lies at the intersection of technical methodologies and medicine. He specializes in health data analytics and functional neuroimaging using artificial intelligence methods.
Rbiözgu Ufumipälyzvim fulGvfiduyzi,uemiArtur Toloknieiev
A doctoral medical student and programmer autodidact, Artur brings to the table a profound understanding of the physiology behind the clinical pictures and a wealth of skill in software engineering with a focus on artificial intelligence. He works on machine learning and data operations, communicates with engineers on medical aspects of the technology and works on the optimization data acquisition, data enrichment and model training processes.
büäüoulilSWiqsgpbfpygvönf:ceävf miTobias Prester
Tobias successfully completed his medical studies at the LMU and is currently working on his medical doctor’s degree in the field of fetal MR imaging. His doctoral research project focuses on the effects of a SARS-CoV-2 infection during pregnancy on the fetus and the placenta.
Undergraduate students
Hlib Kholodkov
Dmytro Voitsekhivskyi
Technicians
Boris Papazov
Scientific Project Management
PD Dr. Enrico Schulz
Enrico is a psychologist by training and provides scientific and administrative support to the team.
Dr. rer. nat. Julia Ruat
Julia is a neurobiologist by training and provides scientific and administrative support to the team.
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Selected publications
Stoecklein S, Wunderlich S, Papazov B, Winkelmann M, Kunz WG, Mueller K, Ernst K, Stoecklein VM, Blumenberg V, Karschnia P, Bücklein VL, Rejeski K, Schmidt C, von Bergwelt-Baildon M, Tonn JC, Ricke J, Liu H, Remi J, Subklewe M, von Baumgarten L, Schoeberl F. Functional connectivity MRI provides an imagingcorrelate for chimeric antigen receptor T-cell-associated neurotoxicity. Neurooncol Adv 2023 Oct 24;5(1).
Stoecklein S*, Koliogiannis V*, Prester T, Kolben T, Jegen M, Hübener C, Hasbargen U, Flemmer A, Dietrich O, Schinner R, Dinkel J, Fink N, Muenchhoff M, Hintz S, Delius M, Mahner S, Ricke J, Hilgendorff A. Effects of SARS-CoV-2 on prenatal lung growth assessed by fetal MRI. Lancet Respir Med 2022 Apr;10(4):e36-e37 *shared first.
Stoecklein VM*, Stoecklein S*, Galiè F, Ren J, Schmutzer M, Unterrainer M, Albert NL, Kreth FW, Thon N, Liebig T, Ertl-Wagner B, Tonn JC, Liu H. Resting-state fMRI Detects Alterations in Whole Brain Connectivity Related to Tumor Biology in Glioma Patients. Neuro Oncol 2020 Sep 29;22(9):1388-1398 *shared first.
Stoecklein S, Hilgendorff A, Li M, Förster K, Flemmer AW, Galiè F, Wunderlich S, Wang D, Stein S, Ehrhardt H, Dietrich O, Zou Q, Zhou S, Ertl-Wagner B, Liu H. Variable functional connectivity architecture of the preterm human brain: Impact of developmental cortical expansion and maturation. Proc Natl Acad Sci U S A 2020 Jan 14;117(2):1201-1206.
Mueller S, Wang D, Fox MD, Yeo BT, Sepulcre J, Sabuncu MR, Shafee R, Lu J, Liu H. Individual variability in functional connectivity architecture of the human brain. Neuron 2013 Feb 6;77(3):586-95.
Full publication list
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The Functional Neuroimaging group currently receives research funding by
Netzwerk Universitätsmedizin
German Research Foundation
Medical Faculty of the LMU
LMUexcellent Investment Fund
Deutsche Gesellschaft für Muskelkranke e.V.
Bruno und Helene Jöster Stiftung
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Deutsches Zentrum für Lungenforschung (DZL)
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)
German Center for Brain Stimulation (GCBS)
Helmholtz Zentrum München
Hôpital Necker-Enfants malades, Paris
Medizinische Universität Wien, Abteilung für Neuroradiologie und muskuloskelettale Radiologie
Northh Medical
Institut für Schlaganfall- und Demenzforschung (ISD), LMU Klinikum
Klinik und Poliklinik für Neurochirurgie, LMU Klinikum
Klinik und Poliklinik für Neurologie, LMU Klinikum
Klinik und Poliklinik für Nuklearmedizin, LMU KlinikumKlinik für Psychiatrie und Psychotherapie, LMU Klinikum