DIRECT-fMRI | Sensing activity-induced cell swellings and ensuing neurotransmitter releases for in-vivo functional imaging sans hemodynamics

Summary
Functional-Magnetic Resonance Imaging (fMRI) has transformed our understanding of brain function due to its ability to noninvasively tag ‘active’ brain regions. Nevertheless, fMRI only detects neural activity indirectly, by relying on slow hemodynamic couplings whose relationships with underlying neural activity are not fully known.
We have recently pioneered two unique MR approaches: Non-Uniform Oscillating-Gradient Spin-Echo (NOGSE) MRI and Relaxation Enhanced MR Spectroscopy (RE MRS). NOGSE-MRI is an exquisite microstructural probe, sensing cell sizes (l) with an unprecedented l^6 sensitivity (compared to l^2 in conventional approaches); RE MRS is a new spectral technique capable of recording metabolic signals with extraordinary fidelity at ultrahigh fields.
This proposal aims to harness these novel concepts for mapping neural activity directly, without relying on hemodynamics. The specific objectives of this proposal are:
(1) Mapping neural activity via sensing cell swellings upon activity (μfMRI): we hypothesize that NOGSE can robustly sense subtle changes in cellular microstructure upon neural firings and hence convey neural activity directly.
(2) Probing the nature of elicited activity via detection of neurotransmitter release: we posit that RE MRS is sufficiently sensitive to robustly detect changes in Glutamate and GABA signals upon activation.
(3) Network mapping in optogenetically-stimulated, behaving mice: we propose to couple our novel approaches with optogenetics to resolve neural correlates of behavior in awake, behaving mice.
Simulations for μfMRI predict >4% signal changes upon subtle cell swellings; further, our in vivo RE MRS experiments have detected metabolites with SNR>50 in only 6 seconds. Hence, these two complementary –and importantly, hemodynamics-independent– approaches will represent a true paradigm shift: from indirect detection of neurovasculature couplings towards direct and noninvasive mapping of neural activity in vivo.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/679058
Start date: 01-03-2016
End date: 31-08-2021
Total budget - Public funding: 1 787 500,00 Euro - 1 787 500,00 Euro
Cordis data

Original description

Functional-Magnetic Resonance Imaging (fMRI) has transformed our understanding of brain function due to its ability to noninvasively tag ‘active’ brain regions. Nevertheless, fMRI only detects neural activity indirectly, by relying on slow hemodynamic couplings whose relationships with underlying neural activity are not fully known.
We have recently pioneered two unique MR approaches: Non-Uniform Oscillating-Gradient Spin-Echo (NOGSE) MRI and Relaxation Enhanced MR Spectroscopy (RE MRS). NOGSE-MRI is an exquisite microstructural probe, sensing cell sizes (l) with an unprecedented l^6 sensitivity (compared to l^2 in conventional approaches); RE MRS is a new spectral technique capable of recording metabolic signals with extraordinary fidelity at ultrahigh fields.
This proposal aims to harness these novel concepts for mapping neural activity directly, without relying on hemodynamics. The specific objectives of this proposal are:
(1) Mapping neural activity via sensing cell swellings upon activity (μfMRI): we hypothesize that NOGSE can robustly sense subtle changes in cellular microstructure upon neural firings and hence convey neural activity directly.
(2) Probing the nature of elicited activity via detection of neurotransmitter release: we posit that RE MRS is sufficiently sensitive to robustly detect changes in Glutamate and GABA signals upon activation.
(3) Network mapping in optogenetically-stimulated, behaving mice: we propose to couple our novel approaches with optogenetics to resolve neural correlates of behavior in awake, behaving mice.
Simulations for μfMRI predict >4% signal changes upon subtle cell swellings; further, our in vivo RE MRS experiments have detected metabolites with SNR>50 in only 6 seconds. Hence, these two complementary –and importantly, hemodynamics-independent– approaches will represent a true paradigm shift: from indirect detection of neurovasculature couplings towards direct and noninvasive mapping of neural activity in vivo.

Status

CLOSED

Call topic

ERC-StG-2015

Update Date

27-04-2024
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Horizon 2020
H2020-EU.1. EXCELLENT SCIENCE
H2020-EU.1.1. EXCELLENT SCIENCE - European Research Council (ERC)
ERC-2015
ERC-2015-STG
ERC-StG-2015 ERC Starting Grant