We propose a new noninvasive modality for simultaneous functional and anatomical imaging of the human brain. This will be the first instrument ever to noninvasively measure both anatomical information and direct consequences of neural activity with high temporal resolution. We propose to combine magnetoencephalography (MEG) with ultra-low field magnetic resonance imaging (ULF-MRI). MEG (and electroencephalography - EEG) is unique in the ability to noninvasively measure neural activity in the brain with millisecond temporal resolution. ULF-MRI is an exciting new technique for structural imaging at magnetic fields in the Microtel regime. Signals for MEG and ULF-MRI are both measured by superconducting quantum interference device (SQUID) sensors. Hence MEG and ULF-MRI can be simultaneously acquired by the same sensor array. While MR signals at low field are drastically reduced relative to high-field (HF), the exquisite sensitivity of SQUID sensors and ULF-MRI techniques outlined here will more than compensate. This new functional/structural imaging modality will enhance neuroimaging of the human brain by reducing or eliminating numerous sources of error associated with co-registration (typically 5-10 mm or more), as the function and structure will be acquired with a single instrument. HF-MRI can be accurately co-registered to the MEG neural activity using HF and ULF surface renderings. Moreover, as ULF-MRI is free from distortions caused by susceptibility variations, anatomical surfaces acquired at ULF can be used to correct HF image distortions using existing warping algorithms. Correcting these distortions will improve MEG source localization by more accurately describing the shape of the head volume and the cortical surface (an important source constraint). Finally, acquisition of ULF-MRI by an array of SQUID sensors will enable faster image acquisition using MR sensor array techniques, techniques also being explored at HF. Simultaneous MEG/ULF-MRI will prove to be a powerful and general tool in the quest to understand the dynamic functional/structural relationships in the human brain, basically how and where the brain works. It will be used to study cognitive processes, for noninvasive localization of pathology such as epilepsy, and for determining surgical outcome (by localizing function in relation to pathology), to name a few. While MEG/ULF-MRI will provide a powerful new neuroimaging tool, it will open the door for exciting future developments. A three-fold modality including simultaneous ULF-MRI, MEG and EEG could readily be envisioned with dense array EEG. Ultimately, it has been speculated that NMR signatures of neural currents may eventually lead to unambiguous localization of neural activity. While unambiguous tomographic localization of neural activity appears possible, the temporal resolution will likely be no better than tens of milliseconds. ULF-MRI that may lead to direct imaging of neural activity, even with modest temporal resolution, can be used to constrain the simultaneously acquired MEG signal, providing millisecond or better temporal resolution.
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