Development of polarization-sensitive optical coherence tomography imaging platform and metrics to quantify electrostimulation-induced peripheral nerve injury in vivo in a small animal model

Guillermo L Monroy; Mohsen Erfanzadeh; Michael Tao; Damon T DePaoli; Ilyas Saytashev; Stephanie A Nam; Harmain Rafi; Kasey C Kwong; Katherine Shea; Benjamin J Vakoc; Srikanth Vasudevan; Daniel X Hammer

doi:10.1117/1.NPh.10.2.025004

Development of polarization-sensitive optical coherence tomography imaging platform and metrics to quantify electrostimulation-induced peripheral nerve injury in vivo in a small animal model

Neurophotonics. 2023 Apr;10(2):025004. doi: 10.1117/1.NPh.10.2.025004. Epub 2023 Apr 17.

Authors

Guillermo L Monroy¹, Mohsen Erfanzadeh^{2

3}, Michael Tao¹, Damon T DePaoli^{2

3}, Ilyas Saytashev¹, Stephanie A Nam^{2

3}, Harmain Rafi¹, Kasey C Kwong^{2

3}, Katherine Shea⁴, Benjamin J Vakoc^{2

3

5}, Srikanth Vasudevan¹, Daniel X Hammer¹

Affiliations

¹ U. S. Food and Drug Administration, Center for Devices and Radiological Health, Office of Science and Engineering Laboratories, Division of Biomedical Physics, Silver Spring, Maryland, United States.
² Massachusetts General Hospital, Harvard Medical School, Wellman Center for Photomedicine, Boston, Massachusetts, United States.
³ Harvard Medical School, Boston, Massachusetts, United States.
⁴ U. S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Clinical Pharmacology, Office of Translational Science, Division of Applied Regulatory Science, Silver Spring, Maryland, United States.
⁵ Massachusetts Institute of Technology, Division of Health Science and Technology, Cambridge, Massachusetts, United States.

Abstract

Significance: Neuromodulation devices are rapidly evolving for the treatment of neurological diseases and conditions. Injury from implantation or long-term use without obvious functional losses is often only detectable through terminal histology. New technologies are needed that assess the peripheral nervous system (PNS) under normal and diseased or injured conditions.

Aim: We aim to demonstrate an imaging and stimulation platform that can elucidate the biological mechanisms and impacts of neurostimulation in the PNS and apply it to the sciatic nerve to extract imaging metrics indicating electrical overstimulation.

Approach: A sciatic nerve injury model in a 15-rat cohort was observed using a newly developed imaging and stimulation platform that can detect electrical overstimulation effects with polarization-sensitive optical coherence tomography. The sciatic nerve was electrically stimulated using a custom-developed nerve holder with embedded electrodes for 1 h, followed by a 1-h recovery period, delivered at above-threshold Shannon model $k$ -values in experimental groups: sham control (SC, $n = 5$ , $0.0 mA / 0 Hz$ ), stimulation level 1 (SL1, $n = 5$ , $3.4 mA / 50 Hz$ , and $k = 2.57$ ), and stimulation level 2 (SL2, $n = 5$ , $6.8 mA / 100 Hz$ , and $k = 3.17$ ).

Results: The stimulation and imaging system successfully captured study data across the cohort. When compared to a SC after a 1-week recovery, the fascicle closest to the stimulation lead showed an average change of $+ 4 % / - 309 %$ (SL1/SL2) in phase retardation and $- 79 % / - 148 %$ in optical attenuation relative to SC. Analysis of immunohistochemistry (IHC) shows a $+ 1 % / - 36 %$ difference in myelin pixel counts and $- 13 % / + 29 %$ difference in axon pixel counts, and an overall increase in cell nuclei pixel count of $+ 20 % / + 35 %$ . These metrics were consistent with IHC and hematoxylin/eosin tissue section analysis.

Conclusions: The poststimulation changes observed in our study are manifestations of nerve injury and repair, specifically degeneration and angiogenesis. Optical imaging metrics quantify these processes and may help evaluate the safety and efficacy of neuromodulation devices.

Keywords: nerve stimulation; neuromodulation; optical metrics; peripheral nerve injury; polarization-sensitive optical coherence tomography; rat; sciatic nerve.

Abstract

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