A CMOS NMR Needle for Probing Brain Physiology

Magnetic resonance imaging and spectroscopy are versatile tools for probing brain physiology, but their intrinsically low sensitivity limits the achievable spatial and temporal resolution. Here, we introduce a monolithically integrated NMR-on-a-chip needle that co-integrates an ultra-sensitive 300-µm NMR coil with a complete NMR transceiver, enabling for the first time in-vivo measurements of blood oxygenation and flow in nanoliter volumes at a sampling rate of 200 Hz. Our monolithic needle-shaped NMR-on-a-chip transceiver (Figure) is a new versatile tool for brain research that makes the advantages of IC-based NMR directly available for applications in neuroscience. With its miniaturized on-chip coil, very low noise performance and ultra-compact, 450-µm wide needle design our NMR-on-a-chip detector simultaneously improves sensitivity as well as spatial and temporal resolution. In contrast to conventional microcoils, the micron-scale interconnecting wires between the on-chip coil and the electronics combined with the fully-differential design greatly reduce the pickup of parasitic MR signals and electromagnetic interference. This enables interference-free in-vivo experiments on a precisely defined region of interest. Compared to conventional fMRI, the on-chip MR microcoil removes the need for time-consuming spatial encoding and allows for a continuous recording of MR signals in a well-defined nanoliter volume with millisecond resolution. The proposed NMR needle offers an exceptionally high sensitivity – a 150- to 300-fold increased volume-normalized tSNR compared to a reference EPI fMRI – combined with unparalleled spatial selectivity inside an ultra-compact form factor. We were able to detect oxygenation and flow-related signal changes confined to a volume of only 9.8 nl at an unprecedented temporal resolution of 5 ms.

The fully integrated CMOS NMR-on-a-chip spectrometer with an on-chip planar broadband detection coil is inserted into the target brain area, e.g. the somatosensory cortex, to perform highly localized and ultra-fast functional MR experiments. The needle detects the change of blood oxygenation via changes in the transverse relaxation time and blood flow.



1.
Handwerker J, Pérez-Rodas M, Beyerlein M, Vincent F, Beck A, Freytag N, Yu X, Pohmann R, Anders J, Scheffler K.:
A CMOS NMR needle for probing brain physiology with high spatial and temporal resolution.
Nat Methods. 2020 Jan;17(1):64-67.
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