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 kk<math><mrow><mi>k</mi></mrow> </math> -values in experimental groups: sham control (SC, n=5n=5<math><mrow><mi>n</mi> <mo>=</mo> <mn>5</mn></mrow> </math> , 0.0mA/0Hz0.0mA/0Hz<math><mrow><mn>0.0</mn> <mtext> </mtext> <mi>mA</mi> <mo>/</mo> <mn>0</mn> <mtext> </mtext> <mi>Hz</mi></mrow> </math> ), stimulation level 1 (SL1, n=5n=5<math><mrow><mi>n</mi> <mo>=</mo> <mn>5</mn></mrow> </math> , 3.4mA/50Hz3.4mA/50Hz<math><mrow><mn>3.4</mn> <mtext> </mtext> <mi>mA</mi> <mo>/</mo> <mn>50</mn> <mtext> </mtext> <mi>Hz</mi></mrow> </math> , and k=2.57k=2.57<math><mrow><mi>k</mi> <mo>=</mo> <mn>2.57</mn></mrow> </math> ), and stimulation level 2 (SL2, n=5n=5<math><mrow><mi>n</mi> <mo>=</mo> <mn>5</mn></mrow> </math> , 6.8mA/100Hz6.8mA/100Hz<math><mrow><mn>6.8</mn> <mtext> </mtext> <mi>mA</mi> <mo>/</mo> <mn>100</mn> <mtext> </mtext> <mi>Hz</mi></mrow> </math> , and k=3.17k=3.17<math><mrow><mi>k</mi> <mo>=</mo> <mn>3.17</mn></mrow> </math> ).
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.
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%+4%/-309%<math><mrow><mo>+</mo> <mn>4</mn> <mo>%</mo> <mo>/</mo> <mo>-</mo> <mn>309</mn> <mo>%</mo></mrow> </math> (SL1/SL2) in phase retardation and −79%/−148%-79%/-148%<math><mrow><mo>-</mo> <mn>79</mn> <mo>%</mo> <mo>/</mo> <mo>-</mo> <mn>148</mn> <mo>%</mo></mrow> </math> in optical attenuation relative to SC. Analysis of immunohistochemistry (IHC) shows a +1%/−36%+1%/-36%<math><mrow><mo>+</mo> <mn>1</mn> <mo>%</mo> <mo>/</mo> <mo>-</mo> <mn>36</mn> <mo>%</mo></mrow> </math> difference in myelin pixel counts and −13%/+29%-13%/+29%<math><mrow><mo>-</mo> <mn>13</mn> <mo>%</mo> <mo>/</mo> <mo>+</mo> <mn>29</mn> <mo>%</mo></mrow> </math> difference in axon pixel counts, and an overall increase in cell nuclei pixel count of +20%/+35%+20%/+35%<math><mrow><mo>+</mo> <mn>20</mn> <mo>%</mo> <mo>/</mo> <mo>+</mo> <mn>35</mn> <mo>%</mo></mrow> </math> . 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.
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 kk<math><mrow><mi>k</mi></mrow> </math> -values in experimental groups: sham control (SC, n=5n=5<math><mrow><mi>n</mi> <mo>=</mo> <mn>5</mn></mrow> </math> , 0.0mA/0Hz0.0mA/0Hz<math><mrow><mn>0.0</mn> <mtext> </mtext> <mi>mA</mi> <mo>/</mo> <mn>0</mn> <mtext> </mtext> <mi>Hz</mi></mrow> </math> ), stimulation level 1 (SL1, n=5n=5<math><mrow><mi>n</mi> <mo>=</mo> <mn>5</mn></mrow> </math> , 3.4mA/50Hz3.4mA/50Hz<math><mrow><mn>3.4</mn> <mtext> </mtext> <mi>mA</mi> <mo>/</mo> <mn>50</mn> <mtext> </mtext> <mi>Hz</mi></mrow> </math> , and k=2.57k=2.57<math><mrow><mi>k</mi> <mo>=</mo> <mn>2.57</mn></mrow> </math> ), and stimulation level 2 (SL2, n=5n=5<math><mrow><mi>n</mi> <mo>=</mo> <mn>5</mn></mrow> </math> , 6.8mA/100Hz6.8mA/100Hz<math><mrow><mn>6.8</mn> <mtext> </mtext> <mi>mA</mi> <mo>/</mo> <mn>100</mn> <mtext> </mtext> <mi>Hz</mi></mrow> </math> , and k=3.17k=3.17<math><mrow><mi>k</mi> <mo>=</mo> <mn>3.17</mn></mrow> </math> ). 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%+4%/-309%<math><mrow><mo>+</mo> <mn>4</mn> <mo>%</mo> <mo>/</mo> <mo>-</mo> <mn>309</mn> <mo>%</mo></mrow> </math> (SL1/SL2) in phase retardation and −79%/−148%-79%/-148%<math><mrow><mo>-</mo> <mn>79</mn> <mo>%</mo> <mo>/</mo> <mo>-</mo> <mn>148</mn> <mo>%</mo></mrow> </math> in optical attenuation relative to SC. Analysis of immunohistochemistry (IHC) shows a +1%/−36%+1%/-36%<math><mrow><mo>+</mo> <mn>1</mn> <mo>%</mo> <mo>/</mo> <mo>-</mo> <mn>36</mn> <mo>%</mo></mrow> </math> difference in myelin pixel counts and −13%/+29%-13%/+29%<math><mrow><mo>-</mo> <mn>13</mn> <mo>%</mo> <mo>/</mo> <mo>+</mo> <mn>29</mn> <mo>%</mo></mrow> </math> difference in axon pixel counts, and an overall increase in cell nuclei pixel count of +20%/+35%+20%/+35%<math><mrow><mo>+</mo> <mn>20</mn> <mo>%</mo> <mo>/</mo> <mo>+</mo> <mn>35</mn> <mo>%</mo></mrow> </math> . 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.