? We propose to demonstrate the feasibility of using nuclear magnetic resonance (NMR) techniques at ultra- low fields (ULF) to directly image neuronal currents in the human brain. We hypothesize that neuronal currents (both intra- and extra-cellular) will interact with the proton spins in tissue resulting in a measurable change in the NMR signal that can be imaged with existing magnetic resonance imaging (MRI) techniques at ULF. This proposal is in response to RFA-EB-05-001: """"""""New Ways to Image Neural Activity."""""""" MRI spatially encodes the NMR signature of nuclei, typically protons, in a volume of interest. Today's high-field (HF) MRI machines employ static magnetic fields in the 1.5 T to above 9 T range to yield exquisite anatomical features. The last decade has also witnessed an explosion in functional MRI (fMRI) research that measures hemody- namic responses; however, as this RFA notes, such responses are relatively sluggish and only indirectly related to electrophysiological processes. Magnetoencephalography (MEG) and electroencephalography (EEG) are direct measures of the external magnetic and electric fields generated by neuronal currents. While these modalities yield detailed temporal information, the spatial localization must be inferred from highly-spe-cific spatial modeling priors. The electrophysiological """"""""imaging"""""""" in MEG and EEG is therefore only """"""""indirect"""""""" at best. Recently, several researchers proposed that electrophysiological.activity may interact with the nuclear spins in a measurable manner, such as causing phase and amplitude variations or changing the rate of decay in the NMR signal. Interactions between neuronal currents and spin populations in tissue may enable direct neuronal imaging (DNI) by MRI. Most studies to date have focussed on the feasibility of DNI at HF. Recently, our group (and a few others) has experimentally demonstrated ultra-low field (ULF) MRI, using fields 100,000- 1,000,000 times weaker than HF-MRI. While the NMR signals, known as the free induction decay (FID), at ULF are dramatically weaker than HF, we acquired high signal-to-noise measurements of FIDs at ULF using super- conducting .quantum interference device (SQUID) technology. We also recently presented the world's first simultaneous FID and MEG measurement of the human brain, using SQUID sensors. Our research will pursue demonstrating the feasibility of measuring a neuronal current effect on the NMR signature at ULF using two distinct approaches: 1) we will study interactions between neuronal currents and the proton spin population in tissue that induce dephasing of the spin population; and 2) we will study a novel mechanism based on the interaction of neuronal currents and the spin population that will cause a distinctly different relaxation of the spin population. The first approach is a direct extension of ideas presented for DNI at high fields, but can be greatly enhanced at ULF. Our second approach pursues an exciting possibility unique to ULF. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB006572-03
Application #
7485103
Study Section
Special Emphasis Panel (ZEB1-OSR-A (M1))
Program Officer
Liu, Guoying
Project Start
2006-09-11
Project End
2010-08-31
Budget Start
2008-09-01
Budget End
2010-08-31
Support Year
3
Fiscal Year
2008
Total Cost
$452,390
Indirect Cost
Name
Los Alamos National Lab
Department
Type
DUNS #
175252894
City
Los Alamos
State
NM
Country
United States
Zip Code
87545
Matlashov, Andrei N; Schultz, Larry J; Espy, Michelle A et al. (2011) SQUIDs vs. Induction Coils for Ultra-Low Field Nuclear Magnetic Resonance: Experimental and Simulation Comparison. IEEE Trans Appl Supercond 21:465-468
Mosher, John C; Hämäläinen, Matti S; Pantazis, Dimitrios et al. (2009) GENERALIZED SIDELOBE CANCELLER FOR MAGNETOENCEPHALOGRAPHY ARRAYS. Proc IEEE Int Symp Biomed Imaging 2009:149-152