title: Assessing the sensitivity of diffusion MRI to detect neuronal activity directly.
abstract: Functional MRI (fMRI) is widely used to study brain function in the neurosciences. Unfortunately, conventional fMRI only indirectly assesses neuronal activity via hemodynamic coupling. Diffusion fMRI was proposed as a more direct and accurate fMRI method to detect neuronal activity, yet confirmative findings have proven difficult to obtain. Given that the underlying relation between tissue water diffusion changes and neuronal activity remains unclear, the rationale for using diffusion MRI to monitor neuronal activity has yet to be clearly established. Here, we studied the correlation between water diffusion and neuronal activity in vitro by simultaneous calcium fluorescence imaging and diffusion MR acquisition. We used organotypic cortical cultures from rat brains as a biological model system, in which spontaneous neuronal activity robustly emerges free of hemodynamic and other artifacts. Simultaneous fluorescent calcium images of neuronal activity are then directly correlated with diffusion MR signals now free of confounds typically encountered in vivo. Although a simultaneous increase of diffusion-weighted MR signals was observed together with the prolonged depolarization of neurons induced by pharmacological manipulations (in which cell swelling was demonstrated to play an important role), no evidence was found that diffusion MR signals directly correlate with normal spontaneous neuronal activity. These results suggest that, whereas current diffusion MR methods could monitor pathological conditions such as hyperexcitability, e.g., those seen in epilepsy, they do not appear to be sensitive or specific enough to detect or follow normal neuronal activity.
authors.affiliation: Section on Quantitative Imaging and Tissue Science, Division of Imaging, Behavior and Genomic Integrity, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892; Biophysics Program, Institute for Physical Science and Technology, University of Maryland, College Park, MD 20740;
authors.forename: Ruiliang
authors.initials: R
authors.lastname: Bai
authors.affiliation: Section on Critical Brain Dynamics, Laboratory of Systems Neuroscience, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Craig V
authors.initials: CV
authors.lastname: Stewart
authors.affiliation: Section on Critical Brain Dynamics, Laboratory of Systems Neuroscience, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Plenz
authors.affiliation: Section on Quantitative Imaging and Tissue Science, Division of Imaging, Behavior and Genomic Integrity, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892; pjbasser@helix.nih.gov.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Basser
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001834:Body Water; D002118:Calcium / Q000032:analysis; D004058:Diffusion; D038524:Diffusion Magnetic Resonance Imaging; D066298:In Vitro Techniques; D065186:Interrupted Time Series Analysis; D007608:Kainic Acid / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D064847:Multimodal Imaging; D059906:Neuroimaging / Q000379:methods*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D009994:Osmolar Concentration; D009997:Osmotic Pressure; D010852:Picrotoxin / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D013003:Somatosensory Cortex / Q000166:cytology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D002118:Calcium; D007608:Kainic Acid; D010852:Picrotoxin; D011189:Potassium Chloride; D013779:Tetrodotoxin
keywords: diffusion MRI; functional; intracellular calcium; neuronal activity; organotypic culture