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Tsen-Hsuan Lin, William M Spees, Michael Wallendorf, Yen-Yu Ian Shih, Anne Cross, Sheng-Kwei Song; Diffusion fMRI of mouse optic nerve with antidromic electrical stimulation. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3099.
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© ARVO (1962-2015); The Authors (2016-present)
Previously, we successfully reported diffusion fMRI (dfMRI) to assess axonal activation (decreased ADC⊥, apparent diffusion coefficient perpendicular to axon tracts) with visual stimulation in healthy and experimental autoimmune encephalomyelitis mouse optic nerves (ON). In this study, we antidromically stimulated ON using tungsten microelectrodes implanted at LGN during dfMRI. This technique allows direct interrogation of ON function without confounding factors from the retina.
A 35- or 50-µm diameter tungsten electrode was implanted at right LGN of C57BL/6 mice (n=15) stimulated with biphasic square-waves of 5 or 10 Hz, 10Vp-p, 50- and 100-ms pulse width. MRI scans of ON were performed on a 4.7-T small-animal MR scanner using a multiple-echo spin-echo imaging sequence with: TR=1.5 s, TE=34.4 ms, inter-echo delay=18.2 ms, in-plane resolution=78 × 78 µm2, and slice thickness=1.3 mm. A pair of diffusion-weighted image (DWI), perpendicular to ON, was acquired with b-value=0.1 and 1.4 ms/µm2, δ=5 ms, and Δ=18 ms. Acquisition time was 12.8 minute for each pair of DWI.
Electrical stimulation of right LGN lead to left ON ADC⊥ decrease without affecting the right ON. We observed a 15% and 19% of ADC⊥ decrease with 10Hz stimulation using 35- and 50-µm diameter tungsten wires, respectively. A 19% and 24% ADC⊥ decrease was seen with 10 and 5 Hz stimulation using 50-µm electrode.
DfMRI with electrical stimulation in mouse ON bypassing the retina input provides a direct measure to assess axonal function.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
Figure 1 Tungsten electrode was implanted at right LGN (red arrows). Left ON ADC⊥ decreased during electrical stimulation.
Figure 2 Normalized (A) and raw ADC⊥ (B) with different stimulation parameters. * indicates p < 0.05, comparing to its baseline
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