Minimally invasive endovascular stent-electrode array for high-fidelity, chronic recordings of cortical neural activity

Journal name:
Nature Biotechnology
Volume:
34,
Pages:
320–327
Year published:
DOI:
doi:10.1038/nbt.3428
Received
Accepted
Published online

Abstract

High-fidelity intracranial electrode arrays for recording and stimulating brain activity have facilitated major advances in the treatment of neurological conditions over the past decade. Traditional arrays require direct implantation into the brain via open craniotomy, which can lead to inflammatory tissue responses, necessitating development of minimally invasive approaches that avoid brain trauma. Here we demonstrate the feasibility of chronically recording brain activity from within a vein using a passive stent-electrode recording array (stentrode). We achieved implantation into a superficial cortical vein overlying the motor cortex via catheter angiography and demonstrate neural recordings in freely moving sheep for up to 190 d. Spectral content and bandwidth of vascular electrocorticography were comparable to those of recordings from epidural surface arrays. Venous internal lumen patency was maintained for the duration of implantation. Stentrodes may have wide ranging applications as a neural interface for treatment of a range of neurological conditions.

At a glance

Figures

  1. Superficial cortical venous variability in humans and a sheep model.
    Figure 1: Superficial cortical venous variability in humans and a sheep model.

    (a) Three-dimensional reconstruction of human pial surface, motor cortex (Brodmann area 4 (BA4); red) and sensory cortex (BA1; yellow) with co-registered SSS and CSV. Dotted lines represent segments of vessels characterized at 5-mm increments. Scale bar, 3 cm. (b) Incremental diameters and distances (box and whisker plot); median, interquartile range and range of SSS commencing proximally at post-central sulcus (defined as 0 mm in b) to nearest BA4 and BA1 cortical surface (n = 50). (c) Similar values for human CSV, commencing at SSS (defined as 0 mm in c) (n = 50). (d) Three-dimensional reconstruction of sheep SSS and motor (red) and sensory cortex (yellow). Scale bar, 1 cm. (e) Sheep SSS diameters and distance to motor area, (box and whisker plot) (n = 13).

  2. Stentrode delivery.
    Figure 2: Stentrode delivery.

    (a) Pre-implant lateral projection cerebral venography roadmap of external jugular vein, confluence of sinuses and SSS (blue arrows). Scale bar, 20 mm. Circular artifact is a calibration tool. (b) Superior projection of SSS. Lumen diameter (blue arrows) and cortical veins (red arrow), assessed pre and post-implant. Scale bar, 10 mm. (c) Stentrode with 8 × 750 μm electrode discs (yellow arrow) self-expanding during deployment from 4F catheter (green arrow). Scale bar, 3 mm. (d) Post-implantation lateral projection plain X-ray of stentrode in SSS, displaying electrodes (yellow arrow) and delivery catheters (green arrows). Scale bar, 10 mm. (e) Post-implant superior projection contrast study of stentrode (electrodes, yellow arrow). Scale bar, 10 mm.

  3. Stentrode vessel wall integration and electrochemical impedance spectroscopy.
    Figure 3: Stentrode vessel wall integration and electrochemical impedance spectroscopy.

    (ac) High-resolution ex vivo synchrotron X-ray images of time-dependent vessel wall incorporation of stentrode struts at day 0 (a; n = 2 sheep), three weeks (b; n = 4 sheep) and four months (c; n = 4 sheep) after implantation in superior sagittal sinus. Scale bars, 2 mm. (d) Low-resolution image of stentrode after implantation. White arrow shows recording electrodes; dashed arrow shows three proximal markers on expanded stent. Scale bar, 5 mm. (e) Synchrotron measured strut-to-lumen distance over the period of implantation (mean ± s.e.m.) (n = 216 struts; 8 sheep). (f,g) Phase angle (f) and impedance magnitude (g) changes across a 28-d implantation period. Low-frequency capacitive phase changes over the initial 6 d (100 Hz, one-way ANOVA, P < 0.0001). (h,i) Phase angle (h) and impedance measurements (i) (mean ± 95% confidence interval; CI) in saline (n = 39) and after implantation at 0 d (n = 28), 6 d (n = 45) and 28 d (n = 33).

  4. Vascular electrocorticography: somatosensory evoked potentials.
    Figure 4: Vascular electrocorticography: somatosensory evoked potentials.

    (a) Representative example of peak-to-peak amplitude over post-implant time (S4). Scale bars, 30 ms and 100 μV. (b) Peak-to-peak amplitudes over time (linear regression, P = 0.42, n = 703 peaks; 5 sheep). (c) Detection of SSEPs over early implantation period (box and whisker plot, n = 5 sheep). (dg) Electrode positions in four sheep implanted with stentrode, demonstrated with co-registered MRI-CT reconstructions to limb motor (red) and sensory (yellow) areas. Scale bar, 2 cm. (h,i) Three-dimensional reconstructed electrodes within co-registered SSS. Scale bar, 3 mm. Representative variable SSEP morphology with phase reversal dipole (blue dashed line). Scale bars, 30 ms and 50 μV.

  5. Vascular electrocorticography: endogenous activity.
    Figure 5: Vascular electrocorticography: endogenous activity.

    (a) Raw vascular electrocorticography of theta burst-suppression in deep (green, isoflurane mean alveolar concentration (MAC) ≥ 1.5) transitioning to light anesthesia (amber, (MAC) ≤ 1). Scale bars, 0.5 s and 50 μV. (b) Effect of duration of implantation on detection of burst-suppression (two-way ANOVA, F1,8 =1 2.2, P = 0.008, n = 5). (c) Representative frequency spectra from subdural (SD), epidural (ED) and stentrode (ST) recordings, displaying characteristic (1/f) decrease in the power. Dashed vertical lines indicate maximal bandwidth. (d) Maximum bandwidth (top) and spectral content in power bands mu and beta (square and triangle, respectively; middle) and power band gamma (low gamma, diamond; mid gamma, hexagon; high gamma, asterisk; bottom). Error bars show s.e.m. Maximum bandwidth of the stentrode (n = 41 electrodes; 8 sheep) was significantly different compared to subdural arrays (n = 25 electrodes; 5 sheep, one-way ANOVA P < 0.001) but not epidural arrays (n = 44 electrodes; 3 sheep, one-way ANOVA P > 0.5). (e) Raw vascular electrocorticography trace of epileptic seizure in one pilot subject, terminated with intravenous diazepam. Scale bars, 5 s and 200 μV.

  6. Chronic viability of implanted stentrode.
    Figure 6: Chronic viability of implanted stentrode.

    (a) Maximum observable bandwidth from recordings (mean ± s.d.). Number of channels per group (n) is indicated in the graph, measured from a total of 10 sheep implanted with a stentrode within the SSS overlying the motor cortex for up to 190 d. (b) Ex vivo SSS lumen areas. Boxplots indicate the median (line), interquartile range (box) and range (whiskers) Number of sheep per plotted subset is indicated above each box, total n = 20 sheep) assessed using synchrotron imaging in 1 mm slices. Control subset is indicative of lumen area from a sheep that was not implanted. (c) In vivo SSS internal lumen diameter measurements with cerebral angiography after stentrode implantation (2.1 mm median and 1.8−2.4 mm IQR), at day 0 after stentrode implantation (2.2 mm median and 1.9−2.4 mm IQR, n = 5 sheep) to two weeks (2.5 mm median and 2.1−2.7 mm IQR, n = 5 sheep) or 12 weeks (2.5 mm median and 1.9−2.7 IQR, n = 3 sheep).

  7. Human cerebral vein characterization
    Supplementary Fig. 1: Human cerebral vein characterization

    a, Superficial venous structures were identified and reconstructed using post-contrast brain MRI images (n=50). Scale bar, 3 cm. b-c, Vein diameters were manually measured using multi-planar image reconstructions at each 5 mm fiducial point along the course of the vein. Scale bar, 5 mm. d, Pial surfaces were reconstructed and segmented for primary motor (red, Brodmann Area, BA4) and sensory (yellow, BA1) areas. Scale bar, 3 cm. e-f, The shortest distance from each venous fiducial point to the pial surface of BA4 and BA1 was measured using multi-planar reconstructions. Scale bar, 3 mm. g, 3-dimensional reconstructed venous structures and motor and sensory surfaces were superimposed to position within sulci. Scale bar, 10 mm. h, Coronal view demonstrating superior sagittal sinus. Circle of best fit within triangular measurement was recorded as diameter at each fiducial point. Scale bar, 10 mm.

  8. Human superficial cortical veins
    Supplementary Fig. 2: Human superficial cortical veins

    a, Post-central sulcal vein (PostCSV, dotted line) reconstructed in relation to sensory cortex (yellow, Brodmann Area 1, BA1), with representative tributary feeding angle into superior sagittal sinus (SSS, dashed line). Scale bar, 2 cm. b, PostCSV lumen diameters at 5 mm increments, commencing proximally at SSS (median, IQR, range, n = 41). c, PostCSV distances to BA1 at 5 mm increments (median, IQR, range, n = 41). d, Central sulcal vein (CSV) route in relation to motor (red, BA4) and sensory (yellow, BA1) cortex. Scale bar, 2 cm. e, Angles of all veins entering SSS. PostCSV (mean 66.3° [95%CI 57.1 - 75.4], n = 30); CSV (mean 78.7° [95%CI 73.7 - 83.8], n = 49); PreCSV (mean 83.7° [95%CI 75.1 - 92.4], n = 25). f-h, Pre-central sulcal vein (PreCSV) diameters and distances in relation to motor cortex (red, BA4)(median, IQR, range). Scale bar, 2 cm.

  9. Human vein diameter measurement reliability
    Supplementary Fig. 3: Human vein diameter measurement reliability

    a, Overall inter-observer reliability between two observers for superficial cortical vein diameter measurements were in almost perfect agreement (ICC = 0.84; Lin’s CCC = 0.84 [95%CI 0.82 - 0.87]; reduced major axis slope = 0.97, intercept = 0.02). b, Proximal vein diameters demonstrated moderate-to-substantial agreement (ICC = 0.63; Lin’s CCC = 0.63 [95%CI 0.53 - 0.75]; reduced major axis slope = 1.09, intercept = -0.63) with identifiable proportional bias. c, Overall intra-observer repeat diameter measurements were also in almost perfect agreement (ICC = 0.89; Lin’s CCC = 0.89 [95%CI 0.88 - 0.9]; reduced major axis slope = 1.04, intercept = -0.11). d, Proximal vein region intra-observer diameters also demonstrated mildly lower values of agreement (ICC = 0.7; Lin’s CCC = 0.7 [95%CI 0.64 - 0.76]; reduced major axis slope = 1.1, intercept = -0.3), indicative of substantial agreement.

  10. Benchtop stentrode testing
    Supplementary Fig. 4: Benchtop stentrode testing

    a, Ovine vasculature mechanical model of major stress points along venous pathway indicating the jugular foramen (b) and the confluence of sinuses (c), scale bar, 1 cm. b, Internal catheter frictional force measured as stentrodes were deployed through catheters with varying internal diameters. Electrode detachment occurred only with attempts via 0.89 mm catheter (n = 3; all other catheter trials n = 9). c, Repeated measures (n = 3) compression test indicating superelasticity of stent is maintained with wire wrapping and attached electrodes. Average compression force comparison between d, long stentrodes with seven (n = 4) and eight (n = 4) electrodes, e, short stentrodes with six (n = 3) and seven (n = 4) electrodes and f, short and long stentrodes with seven electrodes each (n = 4).

  11. Coaxial catheter technique
    Supplementary Fig. 5: Coaxial catheter technique

    a, Coaxial system including 6F sheath, 6F, 4F, 2F and microwire, all preloaded into one another. Commencing with microwire, entire system is telescoped over itself to negotiate the venous pathway toward the superior sagittal sinus (SSS). Scale bar, 5 mm. b, Plain x-ray demonstrating microwire (blue arrow) with a J shape to assist with negotiation of complex venous channels and bifurcations. 2F catheter (yellow arrow) is advanced over microwire to support entry into the SSS. Scale bar, 1 cm. c, Lateral projection digital subtraction angiography of SSS following access with 4F and prior to stentrode deployment. Scale bar, 1 cm.

  12. Identification of viable stent-mounted electrodes using electrochemical impedance spectroscopy
    Supplementary Fig. 6: Identification of viable stent-mounted electrodes using electrochemical impedance spectroscopy

    a, Impedance magnitude and b, phase angle of stentrode electrodes (blue) and bare metal stent (grey) immersed in saline [mean ± SD]. Dashed lines represent peak-resistance-frequency and access resistances for the stentrode electrodes (blue, 200 kHz and 816 ± 15 [mean ± SD], n = 39 electrodes) and bare stent (grey, 16 kHz and 625 ± 27 , n = 12 stents) immersed in saline. In saline, 10 kHz measurements are comparable with peak-resistance-frequency measured access resistance. c, Bar graph showing 10 kHz impedance of stentrode electrodes in saline (blue, 979 ± 20 [mean ± SD], n = 39 electrodes), bare metal stents in saline (grey, 625 ± 27 , n = 12 stents), stentrode in vivo immediately following implantation (green, 2662 ± 486 , n = 28 electrodes) and stentrode in vivo with electrodes shorted to the stent (red, 659 ± 113 , n = 7 electrodes). Dashed black line at 1 k indicates in vivo electrode exclusion criteria for viability.

  13. Equivalent circuit model of electrode-tissue interface in comparison to saline bath and in vivo measurements
    Supplementary Fig. 7: Equivalent circuit model of electrode-tissue interface in comparison to saline bath and in vivo measurements

    a, Simple equivalent circuit model showing solution resistance (RS), electrode-tissue interface charge transfer resistance (RE) and double-layer capacitance constant phase element (CPEE), and the tissue resistance (RT) and capacitance (CT). b, Comparison between equivalent circuit model impedance (dashed black line) and phase (dotted black line) and electrochemical impedance spectroscopy measurements [mean ± 95%CI] of average impedance (red) and phase angle (blue) of stentrodes immersed in saline (n = 39 electrodes) and in vivo at c, Day 0 (n = 28 electrodes) and d, Day 28 (n=33 electrodes). e, Change in α (black trace) and capacitive magnitude (F, blue trace) of the constant phase element as a function of implant duration, suggestive of incorporation and adherence of proteins to the electrode-tissue interface.

  14. Schematic of experimental set up
    Supplementary Fig. 8: Schematic of experimental set up

    a, Endovascular stent-electrode array (stentrode) is shown implanted within the superior sagittal sinus within the brain. b, The electrode lead wire is shown to exit the brain within the internal jugular vein. c, The lead wire protrudes through the wall of the common jugular vein in the neck, and tunnels subcutaneously to (d) a custom-made hermetic connector secured to a muscle, and exiting the skin in a percutaneous micro circular plug (Omnetics, Minneapolis MN, USA). e,f, Two ground electrodes implanted subcutaneously: a large, stainless steel ground electrode implanted in the back of the sheep (e), and a platinum c-shaped ground electrode under the scalp in close proximity to the stentrode (f). Electrode lead wires and ground electrodes are connected to omnetics connectors (g) that are connected to a data acquisition system (TMSi Porti, Twente Medical Systems International, Oldenzaal, Netherlands) (h) and computer (i) to record neural information.

  15. Somatosensory evoked potential latencies
    Supplementary Fig. 9: Somatosensory evoked potential latencies

    a, Histogram of all rectified peak latencies (n = 703 peaks, n = 5 animals, n= 57 [40-70] trials/session [median, interquartile range]) demonstrating occurrence of physiological peaks at 20 ms, 28 ms, 38 ms and 51 ms. b-d, Representative SSEP morphologies from individual subjects by individual electrode (b, S4; c, S2; d, S3; e, S1). Insert image displays the distribution of electrodes per subject within the superior sagittal sinus (blue circles, functional and represented electrodes). Blue dashed line represents phase reversal and dipole between peaks. Scale bar, 40 μV, 20 ms.

  16. Stentrode electrode correlation coefficients
    Supplementary Fig. 10: Stentrode electrode correlation coefficients

    a, Image plot of the correlation coefficients between electrodes for an example subject. Electrodes (n = 6) on the rostral end of the electrode were positively correlated with each other (yellow, > 0.5), with signals on the caudal end of the array exhibiting a phase shift reflected in the negative correlation coefficients (blue, < 0). b, Correlation coefficients of electrodes (n = 6) from an example subject (mean, SEM) showing a positive to negative change in correlation coefficient indicative of electrode location and phase shift of the acquired signal. c, Population average [mean] image plot of the correlation coefficients (n = 31 electrodes in 5 animals) showing electrodes with high correlation (yellow, >0.2) and low correlation (blue, < 0). The maximum of the color scale has been reduced to 0.45 to allow for easier comparisons, however coefficients for all electrodes against themselves (diagonal values) are 1.

  17. Validation ECoG recordings from stentrode and epidural array
    Supplementary Fig. 11: Validation ECoG recordings from stentrode and epidural array

    Representative example demonstrating x-ray of co-implanted stentrode (yellow arrow) and epidural array (green arrow) for validation recording acute experiments. Scale bar, 5 mm.

  18. Chewing artifact comparison between recording arrays
    Supplementary Fig. 12: Chewing artifact comparison between recording arrays

    Individual raw ECoG recordings from a, epidural (ED, orange), b, endovascular stentrode (ST, green) and c, subdural (SD, blue) electrode arrays. Red boxes indicate the identified chewing artifacts and the brown boxes indicate the baseline period. Scale bar, 50 µV, 500 ms. d, Artifact-to-baseline ratio for the epidural arrays (2.2 ± 0.1, n = 29 electrodes in 3 sheep), stentrode arrays (2 ± 0.1 [mean ± SE] n = 49 electrodes in 11 sheep) and subdural arrays (1.8 ± 0.1, n = 30 electrodes in 6 sheep). A Tukey-corrected one-way ANOVA showed that there was no statistically significant difference between the subdural, epidural, or stentrode arrays (p=0.109).

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Author information

Affiliations

  1. Vascular Bionics Laboratory, Melbourne Brain Centre, Department of Medicine, The University of Melbourne, Melbourne, Australia.

    • Thomas J Oxley,
    • Nicholas L Opie,
    • Sam E John,
    • Gil S Rind,
    • Stephen M Ronayne,
    • Timothy J H Lovell,
    • Yan T Wong,
    • Ewan S Nurse,
    • Kishan A Liyanage,
    • Nicole R van der Nagel,
    • Katherine P Gill,
    • David B Grayden &
    • Clive N May
  2. Departments of Medicine and Neurology, Melbourne Brain Centre at The Royal Melbourne Hospital, The University of Melbourne, Melbourne, Australia.

    • Thomas J Oxley,
    • Nicholas L Opie,
    • Sam E John,
    • Gil S Rind,
    • Stephen M Ronayne,
    • Timothy J H Lovell,
    • Christopher Steward,
    • Nawaf Yassi,
    • Bruce C V Campbell,
    • Piero Perucca,
    • Bernard Yan,
    • Christopher R French,
    • Lynette Kiers,
    • Stephen M Davis &
    • Terence J O'Brien
  3. The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Australia.

    • Thomas J Oxley,
    • Nicholas L Opie,
    • Sam E John,
    • Gil S Rind,
    • Stephen M Ronayne,
    • Alan J McDonald,
    • Anthony Dornom,
    • Timothy J H Lovell,
    • Leonid Churilov,
    • Malcolm K Horne &
    • Clive N May
  4. NeuroEngineering Laboratory, Department of Electrical & Electronic Engineering, The University of Melbourne, Melbourne, Australia.

    • Thomas J Oxley,
    • Nicholas L Opie,
    • Sam E John,
    • Yan T Wong,
    • Ewan S Nurse,
    • Anthony N Burkitt &
    • David B Grayden
  5. Craig H. Neilsen Foundation, Encino, California, USA.

    • Tracey L Wheeler
  6. Nanoscience Institute for Medical and Engineering Technology, University of Florida, Gainesville, Florida, USA.

    • Jack W Judy
  7. Department of Radiology, Royal Melbourne Hospital, Melbourne Health, Melbourne, Australia.

    • Christopher Steward,
    • Bradford A Moffat,
    • Elaine H Lui,
    • Patricia M Desmond &
    • Peter J Mitchell
  8. Department of Radiology, The University of Melbourne, Melbourne, Australia.

    • Christopher Steward,
    • Bradford A Moffat,
    • Elaine H Lui,
    • Patricia M Desmond &
    • Peter J Mitchell
  9. School of Physics, The University of Melbourne, Melbourne, Australia.

    • David J Garrett,
    • Kate E Fox,
    • Arman Ahnood &
    • Steven Prawer
  10. The Bionics Institute, East Melbourne, Victoria, Australia.

    • David J Garrett,
    • Anthony N Burkitt &
    • David B Grayden
  11. Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, Australia.

    • Bradford A Moffat
  12. Centre for Additive Manufacturing, School of Aerospace, Mechanical and Manufacturing Engineering, RMIT University, Melbourne, Australia.

    • Kate E Fox
  13. Department of Surgery, Royal Melbourne Hospital, The University of Melbourne, Melbourne, Australia.

    • Iwan E Bennett
  14. Translational Research and Clinical Trials (TRACTs), Veterinary Hospital, Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Melbourne, Australia.

    • Sébastien H Bauquier
  15. School of Mathematics and Geospatial Sciences, RMIT University, Melbourne, Australia.

    • Leonid Churilov
  16. Centre for Neural Engineering, The University of Melbourne, Melbourne, Australia.

    • David B Grayden

Contributions

T.J.O., N.L.O., S.E.J., G.S.R., S.M.R., T.L.W., J.W.J., E.H.L., S.H.B, P.P., C.R.F., P.M.D., M.K.H., S.P., A.N.B., D.B.G., C.N.M. and T.J.O'B. designed the experiments. T.J.O., N.L.O., S.E.J., G.S.R., S.M.R., A.J.M., A.D., T.J.H.L., C.S., D.J.G., B.A.M., E.H.L., N.Y., B.C.V.C., Y.T.W., K.E.F., E.S.N., I.E.B., S.H.B., K.A.L., N.R.v.d.N., A.A., K.P.G., B.Y., L.C., L.K., A.N.B., P.J.M., D.B.G., C.N.M. and T.J.O'B. performed the experiments and analysis. T.J.O., N.L.O., S.E.J., G.S.R., S.M.R., T.L.W., L.C., S.M.D., A.N.B., P.J.M., D.B.G. and C.N.M. wrote the paper.

Competing financial interests

T.J.O. and N.L.O. hold stock in SmartStent. Patent application US20140288667A1 filed by T.J.O. applies to the method described in the paper.

Corresponding author

Correspondence to:

Author details

Supplementary information

Supplementary Figures

  1. Supplementary Figure 1: Human cerebral vein characterization (595 KB)

    a, Superficial venous structures were identified and reconstructed using post-contrast brain MRI images (n=50). Scale bar, 3 cm. b-c, Vein diameters were manually measured using multi-planar image reconstructions at each 5 mm fiducial point along the course of the vein. Scale bar, 5 mm. d, Pial surfaces were reconstructed and segmented for primary motor (red, Brodmann Area, BA4) and sensory (yellow, BA1) areas. Scale bar, 3 cm. e-f, The shortest distance from each venous fiducial point to the pial surface of BA4 and BA1 was measured using multi-planar reconstructions. Scale bar, 3 mm. g, 3-dimensional reconstructed venous structures and motor and sensory surfaces were superimposed to position within sulci. Scale bar, 10 mm. h, Coronal view demonstrating superior sagittal sinus. Circle of best fit within triangular measurement was recorded as diameter at each fiducial point. Scale bar, 10 mm.

  2. Supplementary Figure 2: Human superficial cortical veins (378 KB)

    a, Post-central sulcal vein (PostCSV, dotted line) reconstructed in relation to sensory cortex (yellow, Brodmann Area 1, BA1), with representative tributary feeding angle into superior sagittal sinus (SSS, dashed line). Scale bar, 2 cm. b, PostCSV lumen diameters at 5 mm increments, commencing proximally at SSS (median, IQR, range, n = 41). c, PostCSV distances to BA1 at 5 mm increments (median, IQR, range, n = 41). d, Central sulcal vein (CSV) route in relation to motor (red, BA4) and sensory (yellow, BA1) cortex. Scale bar, 2 cm. e, Angles of all veins entering SSS. PostCSV (mean 66.3° [95%CI 57.1 - 75.4], n = 30); CSV (mean 78.7° [95%CI 73.7 - 83.8], n = 49); PreCSV (mean 83.7° [95%CI 75.1 - 92.4], n = 25). f-h, Pre-central sulcal vein (PreCSV) diameters and distances in relation to motor cortex (red, BA4)(median, IQR, range). Scale bar, 2 cm.

  3. Supplementary Figure 3: Human vein diameter measurement reliability (210 KB)

    a, Overall inter-observer reliability between two observers for superficial cortical vein diameter measurements were in almost perfect agreement (ICC = 0.84; Lin’s CCC = 0.84 [95%CI 0.82 - 0.87]; reduced major axis slope = 0.97, intercept = 0.02). b, Proximal vein diameters demonstrated moderate-to-substantial agreement (ICC = 0.63; Lin’s CCC = 0.63 [95%CI 0.53 - 0.75]; reduced major axis slope = 1.09, intercept = -0.63) with identifiable proportional bias. c, Overall intra-observer repeat diameter measurements were also in almost perfect agreement (ICC = 0.89; Lin’s CCC = 0.89 [95%CI 0.88 - 0.9]; reduced major axis slope = 1.04, intercept = -0.11). d, Proximal vein region intra-observer diameters also demonstrated mildly lower values of agreement (ICC = 0.7; Lin’s CCC = 0.7 [95%CI 0.64 - 0.76]; reduced major axis slope = 1.1, intercept = -0.3), indicative of substantial agreement.

  4. Supplementary Figure 4: Benchtop stentrode testing (465 KB)

    a, Ovine vasculature mechanical model of major stress points along venous pathway indicating the jugular foramen (b) and the confluence of sinuses (c), scale bar, 1 cm. b, Internal catheter frictional force measured as stentrodes were deployed through catheters with varying internal diameters. Electrode detachment occurred only with attempts via 0.89 mm catheter (n = 3; all other catheter trials n = 9). c, Repeated measures (n = 3) compression test indicating superelasticity of stent is maintained with wire wrapping and attached electrodes. Average compression force comparison between d, long stentrodes with seven (n = 4) and eight (n = 4) electrodes, e, short stentrodes with six (n = 3) and seven (n = 4) electrodes and f, short and long stentrodes with seven electrodes each (n = 4).

  5. Supplementary Figure 5: Coaxial catheter technique (154 KB)

    a, Coaxial system including 6F sheath, 6F, 4F, 2F and microwire, all preloaded into one another. Commencing with microwire, entire system is telescoped over itself to negotiate the venous pathway toward the superior sagittal sinus (SSS). Scale bar, 5 mm. b, Plain x-ray demonstrating microwire (blue arrow) with a J shape to assist with negotiation of complex venous channels and bifurcations. 2F catheter (yellow arrow) is advanced over microwire to support entry into the SSS. Scale bar, 1 cm. c, Lateral projection digital subtraction angiography of SSS following access with 4F and prior to stentrode deployment. Scale bar, 1 cm.

  6. Supplementary Figure 6: Identification of viable stent-mounted electrodes using electrochemical impedance spectroscopy (176 KB)

    a, Impedance magnitude and b, phase angle of stentrode electrodes (blue) and bare metal stent (grey) immersed in saline [mean ± SD]. Dashed lines represent peak-resistance-frequency and access resistances for the stentrode electrodes (blue, 200 kHz and 816 ± 15 [mean ± SD], n = 39 electrodes) and bare stent (grey, 16 kHz and 625 ± 27 , n = 12 stents) immersed in saline. In saline, 10 kHz measurements are comparable with peak-resistance-frequency measured access resistance. c, Bar graph showing 10 kHz impedance of stentrode electrodes in saline (blue, 979 ± 20 [mean ± SD], n = 39 electrodes), bare metal stents in saline (grey, 625 ± 27 , n = 12 stents), stentrode in vivo immediately following implantation (green, 2662 ± 486 , n = 28 electrodes) and stentrode in vivo with electrodes shorted to the stent (red, 659 ± 113 , n = 7 electrodes). Dashed black line at 1 k indicates in vivo electrode exclusion criteria for viability.

  7. Supplementary Figure 7: Equivalent circuit model of electrode-tissue interface in comparison to saline bath and in vivo measurements (263 KB)

    a, Simple equivalent circuit model showing solution resistance (RS), electrode-tissue interface charge transfer resistance (RE) and double-layer capacitance constant phase element (CPEE), and the tissue resistance (RT) and capacitance (CT). b, Comparison between equivalent circuit model impedance (dashed black line) and phase (dotted black line) and electrochemical impedance spectroscopy measurements [mean ± 95%CI] of average impedance (red) and phase angle (blue) of stentrodes immersed in saline (n = 39 electrodes) and in vivo at c, Day 0 (n = 28 electrodes) and d, Day 28 (n=33 electrodes). e, Change in α (black trace) and capacitive magnitude (F, blue trace) of the constant phase element as a function of implant duration, suggestive of incorporation and adherence of proteins to the electrode-tissue interface.

  8. Supplementary Figure 8: Schematic of experimental set up (165 KB)

    a, Endovascular stent-electrode array (stentrode) is shown implanted within the superior sagittal sinus within the brain. b, The electrode lead wire is shown to exit the brain within the internal jugular vein. c, The lead wire protrudes through the wall of the common jugular vein in the neck, and tunnels subcutaneously to (d) a custom-made hermetic connector secured to a muscle, and exiting the skin in a percutaneous micro circular plug (Omnetics, Minneapolis MN, USA). e,f, Two ground electrodes implanted subcutaneously: a large, stainless steel ground electrode implanted in the back of the sheep (e), and a platinum c-shaped ground electrode under the scalp in close proximity to the stentrode (f). Electrode lead wires and ground electrodes are connected to omnetics connectors (g) that are connected to a data acquisition system (TMSi Porti, Twente Medical Systems International, Oldenzaal, Netherlands) (h) and computer (i) to record neural information.

  9. Supplementary Figure 9: Somatosensory evoked potential latencies (211 KB)

    a, Histogram of all rectified peak latencies (n = 703 peaks, n = 5 animals, n= 57 [40-70] trials/session [median, interquartile range]) demonstrating occurrence of physiological peaks at 20 ms, 28 ms, 38 ms and 51 ms. b-d, Representative SSEP morphologies from individual subjects by individual electrode (b, S4; c, S2; d, S3; e, S1). Insert image displays the distribution of electrodes per subject within the superior sagittal sinus (blue circles, functional and represented electrodes). Blue dashed line represents phase reversal and dipole between peaks. Scale bar, 40 μV, 20 ms.

  10. Supplementary Figure 10: Stentrode electrode correlation coefficients (222 KB)

    a, Image plot of the correlation coefficients between electrodes for an example subject. Electrodes (n = 6) on the rostral end of the electrode were positively correlated with each other (yellow, > 0.5), with signals on the caudal end of the array exhibiting a phase shift reflected in the negative correlation coefficients (blue, < 0). b, Correlation coefficients of electrodes (n = 6) from an example subject (mean, SEM) showing a positive to negative change in correlation coefficient indicative of electrode location and phase shift of the acquired signal. c, Population average [mean] image plot of the correlation coefficients (n = 31 electrodes in 5 animals) showing electrodes with high correlation (yellow, >0.2) and low correlation (blue, < 0). The maximum of the color scale has been reduced to 0.45 to allow for easier comparisons, however coefficients for all electrodes against themselves (diagonal values) are 1.

  11. Supplementary Figure 11: Validation ECoG recordings from stentrode and epidural array (139 KB)

    Representative example demonstrating x-ray of co-implanted stentrode (yellow arrow) and epidural array (green arrow) for validation recording acute experiments. Scale bar, 5 mm.

  12. Supplementary Figure 12: Chewing artifact comparison between recording arrays (323 KB)

    Individual raw ECoG recordings from a, epidural (ED, orange), b, endovascular stentrode (ST, green) and c, subdural (SD, blue) electrode arrays. Red boxes indicate the identified chewing artifacts and the brown boxes indicate the baseline period. Scale bar, 50 µV, 500 ms. d, Artifact-to-baseline ratio for the epidural arrays (2.2 ± 0.1, n = 29 electrodes in 3 sheep), stentrode arrays (2 ± 0.1 [mean ± SE] n = 49 electrodes in 11 sheep) and subdural arrays (1.8 ± 0.1, n = 30 electrodes in 6 sheep). A Tukey-corrected one-way ANOVA showed that there was no statistically significant difference between the subdural, epidural, or stentrode arrays (p=0.109).

PDF files

  1. Supplementary Text and Figures (1,831 KB)

    Supplementary Figures 1–12

  2. Supplemental Material (909 KB)

    Supplementary Tables 1–6 and Supplementary Notes 1–6

Additional data