Experimental optical fiber: Rotation and translation model

In another set of experiments (Dieter et al., 2019), we studied the spread of the light at the level of the inferior colliculus by placing the fiber at three different positions, one the round window and two through cochleostomies in the mid- and low frequency-ranges of the cochlea. In this occasion, we used our Monte Carlo model to estimate where the fibers were placed. Our initial model was a snapshot: we only considered one single position for the fiber: the one it had when it was fixed by dental acrylic before the imaging. This however does not take into account the inherent experimental variability of the fiber position within a range in terms of angle of illumination and distance of the plane of emission from Rosenthal’s canal. To calculate more accurately the mean location of the fiber’s tip for each of the insertion positions, we generated two more realistic model: One with five different angle per position and other with five different separations from the ganglion. The averages from both models retrieved comparable target location: the rotational model pinpointed that the target tonotopic locations were 1.01, 6.9 and 22.89 kHz (Figure 8A and B), respectively, whereas the translational model yielded 1.02, 6.34 and 21.81 kHz (Figure 8C and D).

38

Figure 8. Verifying fiber positions by Monte Carlo ray tracing. 3D model reconstructed from x-ray tomography including fiber positions (pos. 1-3), roughly corresponding to the ones used in physiological experiments. In the model, original positions as well as their respective rotation in two orthogonal planes (a and b, panel A.) and four different coaxial translations (C.) have been used to account for variability in fiber placement. Light grey: bone; grey:

scala media, vestibuli and tympani, as well as semicircular canals; purple: peripheral processes and Rosenthal’s canal that houses the spiral ganglion neuron’s somata; fiber position and their corresponding rotations and translations, respectively, are indicated by different colors (see legend). (B. and D.) irradiance profiles obtained from 300 query points located along the tonotopic axis, defined in the centerline of the Rosenthal’s canal, upon Monte Carlo ray tracing from the three different fiber positions using a source radiant flux of 2.67 mw. Peak irradiances of the mean traces indicate that fibers from these different positions were stimulating areas around 1.01, 6.9 and 22.89 kHz, according to the rotation model in panel b, and 1.02, 6.34 and 21.81 khZ according to the translational model in panel d.. Reproduced from (Dieter et al., 2019)

39

3.2. M ODEL OF THE M ARMOSET COCHLEA

Finally, for late preclinical work in non-human primates, we wanted to study a marmoset cochlea implanted with an oCI (constructed with an array of µLED embedded in a flexible biocompatible substrate). We also included query points not only in the Rosenthal´s canal but also at the level of the peripheral SGN processes, to also consider the spread of excitation in case of surviving fibers.

I defined threshold irradiances as the minimal maximal irradiance across the 10 µLEDs, using an arbitrary source radiant flux of 3 mW. The irradiance threshold values were are 1.81 mW/mm2 for the query points at the peripheral processes and 0.87 mW/mm2 for those at the Rosenthal´s canal. To measure the spread in suprathreshold octaves (ie. tonotopic regions that have irradiance values above threshold), I retrieved the tonotopic localization corresponding to the crossing points of the irradiance profile with these threshold values.

For every light source at 10 mW, a different peak can be identified covering in total 2.3 octaves (2.35-11.55 kHz). The irradiance profiles show certain degree of overlap and spreads ranging from 0.91 to 1.19 octaves at the Rosenthal´s canal and from 0.29 to 0.53 at the peripheral processes. For every source, a slight shift, between 0.09 to 0.47 octaves, in the peak of activation can be observed when the profiles from the Rosenthal´s canal and those from the peripheral processes are compared. However, it cannot be discarded to be an artifact of the tonotopy map calculation and its extrapolation to the Rosenthal´s canal.

40

Figure 9. Model of marmoset cochlea with an optical cochlear implant containing the µLEDs CREE 2227. A.

Upper and mid panel, Different views of the reconstructed volumes from X-Ray tomography used in the simulations, depicting a Marmoset cochlea with a oCI implanted. Lower panel, Close-up displaying the localization of the query points in the apical turn. Purple, Rosenthal´s canal and peripheral processes; light gray, Scalae vestibuli, media and tympani; oCI: Blue, µLED; Dark grey, flexible substrate. The light sources are numbered 1-10 from the most apical one. B. Light irradiance profiles obtained from µLED 1, 5 and 10 at the query points placed in the Rosenthal´s canal and the outermost edge of the peripheral processes. Orange line displays irradiance threshold values (1.81 mW/mm2 for peripheral processes; 0.87 mW/mm2 for Rosenthal´s canal). C. Light irradiance profiles from all the light sources interrogated at a radiant flux of 10 mW. The suprathreshold illumination area ranges from 0.91 to 1.19 octaves at the Rosenthal´s canal and from 0.29 to 0.53 at the peripheral processes. Dashed lines displays irradiance threshold values (1.81 mW/mm2 for peripheral processes; 0.87 mW/mm2 for Rosenthal´s canal)

41

Table 3. Summary of Monte Carlo simulation of the light spread in the Marmoset cochlea from modelled µLEDs. For every LED, the suprathreshold octaves (area with irradiance values higher than the threshold value expressed in octaves) for every radiant flux considered, the shift between the peaks at the peripheral processes and the Rosenthal´s canal and the tonotopic positions in which the irradiance profile is maximum are displayed Irradiance threshold values are 1.81 mW/mm2 for query points place at the peripheral processes; 0.87mW/mm2

for those at the Rosenthal´s canal. Note that for high radiant fluxes, interturn stimulation is possible, according to this model.

42