Measurement of neuronal activity with combined multifunctional micro NMR probes and micro electrodes
Medical Physics, Biomedical Technology
Molecular Biology and Physiology of Neurons and Glial Cells
Final Report Abstract
Magnetic resonance imaging and spectroscopy are versatile tools for probing brain physiology, but their intrinsically low sensitivity limits the achievable spatial and temporal resolution. In the DFG funded project IC-MONA, we have researched and developed the prototype of 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. 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. Moreover, all this can be achieved in a compact form factor that is – thanks to its differential design – intrinsically robust against static magnetic fields and electromagnetic interference (EMI), enabling in-vivo experiments at elevated magnetic field strengths. Compared to conventional MR imaging, the on-chip 300-µm MR detection coil eliminates the need for time-consuming spatial encoding, such that MR signals can be continuously recorded in a precisely defined volume at millisecond resolution. The proposed CMOS-integrated microcoil MR spectrometer offers an exceptionally high NMR sensitivity – a 40-fold increased sensitivity compared to an 8-mm conventional surface coil – combined with unparalleled spatial selectivity inside an ultra-compact form factor of 450 µm width and 100 µm thickness. We were able to detect oxygenation and flow-related signal changes upon electrical forepaw stimulation confined to a volume of only 10 nl at an unprecedented temporal resolution of 5 ms. Although preliminary in nature, the presented results clearly demonstrate the power of CMOS-based in-vivo MR experiments and its potential for future applications in neuroscience that can possibly reveal so far unknown dynamics in the laminar-specific hemodynamic response and the underlying physiology of fMRI with layer-specific resolution, or even new effects that are not related to hemodynamics. As the presented CMOS NMR needle achieves a similar spatiotemporal resolution as electrophysiology or optical brain imaging while offering the specificity and versatility of NMR, IC-based in-vivo NMR is a promising approach to close the gap between these complementary imaging modalities. Therefore, we believe that the presented approach can serve as a new tool within the toolbox of neuroimaging technologies that can help to disentangle physiologic processes within the working neural network, and that the new hardware platform can potentially uncover novel MR effects beyond the conventional blood.
Publications
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(May-11-2016): Towards fast and highly localized spectroscopy using miniaturized coils in a 14.1T animal scanner, 24th Annual Meeting and Exhibition of the International Society for Magnetic Resonance in Medicine (ISMRM 2016), Singapore
Pérez Rodas MA, Engelmann J, Merkle H, Pohmann R and Scheffler K
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(May-2017) Towards CMOS-based in-vivo NMR spectroscopy and microscopy, IEEE International Symposium on Circuits & Systems (ISCAS 2017), IEEE, Piscataway, NJ, USA, 1-4
Handwerker J, Pérez-Rodas M, Ortmanns M, Scheffler K and Anders J
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(June-19-2018): 10µm isotropic voxels acquired with a CMOS-based planar microcoil at 14.1T: Preliminary results, Joint Annual Meeting ISMRM-ESMRMB 2018, Paris, France
Pérez Rodas M, Handwerker J, Merkle H, Pohmann R, Anders J and Scheffler K
