Towards calibrated resting-state functional MRI – part 2: Combining advanced hemodynamic-oxygenation MRI with dynamic BOLD signal modelling for individualized intrinsic functional connectivity calibration

• Applicants: Professorin Dr. Christine Preibisch; Privatdozent Dr. Christian Sorg
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology ; Medical Physics, Biomedical Technology
• Term: since 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 395030489

The blood oxygenation level dependent (BOLD) effect is widely used in resting state functional magnetic resonance imaging (rs-fMRI) to investigate human brain functional connectivity of ongoing neuronal activity (BOLD-FC) by means of correlated BOLD signal fluctuations. Tight neurovascular coupling between neuronal activity and BOLD signals constitutes the basis for mapping neural connectivity among brain regions. Alterations of BOLD-FC in patients with brain disorders raised hope with respect to both neuroscientific and clinical applications, especially in neuropsychiatric disorders. However, hemodynamic-vascular alterations in brain disorders and healthy aging call for both cautious interpretation of BOLD-FC with respect to underlying neuronal and metabolic activity and, consequently, for calibration approaches of rs-fMRI. The overarching goal of this proposal is to develop a robust calibration technique for resting-state-fMRI-based BOLD-FC of ongoing brain activity. The proposal is motivated by impaired BOLD-FC in patients with brain disorders, e.g., internal carotid artery stenosis, in whom altered neurovascular coupling has been demonstrated to impact on BOLD-FC beyond aberrant neuronal activity. The proposal is based on results of the first funding period, namely the development of innovative hemodynamic-oxygenation MRI and – most importantly – distinct BOLD-FC modelling including neurovascular coupling parameters. Now, we plan to integrate BOLD-FC and hemodynamic-oxygenation MRI by means of our dynamic BOLD-signal model, to finally disentangle neuronal and metabolic functional connectivity from vascular-hemodynamic influences in individual persons. More specifically, we plan (i) to acquire an extensive set of hemodynamic-oxygenation MRI-based parameters in addition to conventional rs-fMRI in controls and unilateral carotid artery stenosis patients as a lesion model. (ii) Because BOLD-FC is influenced by both local neurovascular coupling (NVC) impairments and non-local vascular confounds, we plan to strictly remove systemic non-neuronal BOLD components in order to isolate the influence of local NVC on BOLD-FC by a range of distinct techniques. (iii) We then plan to systematically explore the impact of ‘local’ vascular-hemodynamic processes on BOLD-FC based on both theoretical dynamic BOLD-TC/FC simulations across extended parameter spaces and constraints derived from stepwise hemodynamic-oxygenation MRI in terms of a model-supported graphical solution framework. This will allow for obtaining first insights about potential causal relationships between impaired local NVC processes and BOLD-FC. (iv) Finally, we plan to derive temporally resolved CMRO2-time courses – as basis for metabolic BOLD-FC – by model-based integration of time-resolved, local cleaned BOLD-TCs and non-time-resolved hemodynamic-oxygenation MRI, where the latter serves to constrain the model parameters.

• DFG Programme: Research Grants