Effect of focused ultrasound neuromodulation of the superior mesenteric plexus on insulin sensitivity and post-operative hyperglycemia in a swine model of surgical stress
Weiguo Song, Khaled Qanud, Dane A. Thompson, Jared M. Huston, Stavros Zanos
Bioelectronic Medicine 2025 · 10.1186/s42234-025-00176-7
Abstract
Metabolic stress during major surgery increases insulin resistance and causes post-operative hyperglycemia (POHG), which may in turn contribute to post-operative morbidity and mortality. Intensive insulin therapy for POHG is often ineffective and may even worsen patient outcomes. Non-invasive focused ultrasound stimulation (FUS) of glucose-sensing abdominal neurons improves glucose metabolism in animal models of diabetes, but its potential role in treating POHG remains unknown. In this study, we explored whether FUS of the superior mesenteric plexus (SMP) alters insulin sensitivity and post-operative fasting blood glucose (FBG) in a swine model of surgical stress-induced POHG. In each of 3 anesthetized animals, FUS targeting the porta hepatis (PH) of the liver or the SMP was delivered and insulin sensitivity was assessed in each case. In another series of experiments, 4 animals received SMP-FUS and 3 sham stimulation, after which surgical stress was induced via small bowel resection. In the 7 surgically operated animals, insulin sensitivity was measured before and after SMP-FUS (or sham), and fasting blood glucose (FBG) was measured before and 16 h after surgery. In all animals, insulin sensitivity was assessed using the hyperinsulinemic-euglycemic clamp (HEC) method. Results: SMP-FUS elicits a greater increase in insulin sensitivity than PH-FUS. On the day of surgery, SMP-FUS increases insulin sensitivity, compared to sham treatment. The day after surgery, surgically operated animals develop mild hyperglycemia. SMP-FUS-treated animals have higher FBG than sham-FUS-treated animals. No clear relationship is observed between FUS-induced changes in insulin sensitivity and next-day FBG. Conclusion: While SMP-FUS improves insulin sensitivity during surgery, it may exacerbate POHG.
Abstract via europepmc.
Exposures
Exposure 1: FUS of superior mesenteric plexus
Target: nerve plexus — “superior mesenteric plexus (SMP)”
Device: other named manufacturer · GE Healthcare · LOGIQ E10 with customized dual-use probe ✓
| Waveform | not reported | |
|---|---|---|
| Fundamental frequency (kHz) | 2,270 | ✓✓✓ |
| Pulse duration (ms) | 0.2 | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | not reported | |
| Duty cycle (%) | not reported | |
| Sonication duration (s) | 1,800 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Image-guided FUS to the SMP for 30 min before bowel resection, at 55% of maximum output in the healthy-animal experiment; hardware only permitted adjusting output power and duration. Sham: probe placed in comparable location without FUS.
Exposure 2: FUS of porta hepatis
Target: other — “porta hepatis (PH) of the liver”
Device: other named manufacturer · GE Healthcare · LOGIQ E10 with customized dual-use probe ✓
| Waveform | not reported | |
|---|---|---|
| Fundamental frequency (kHz) | 2,270 | ✓✓✓ |
| Pulse duration (ms) | 0.2 | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | not reported | |
| Duty cycle (%) | not reported | |
| Sonication duration (s) | 1,800 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Image-guided FUS to the porta hepatis for 30 min in 3 healthy anaesthetised pigs, at 55% of maximum output.
Flags from extraction
exposures[0].timing.pulse_duration_ms— Pulse width 200 us is given for the maximum output setting, not clearly the applied setting; PRF and duty cycle not stated.exposures[0].unspecified_domain.isppa_w_cm2— Only a maximum output intensity of 3321 W/cm2 (domain unspecified; applied level was a fraction of maximum) is given; not recorded as a delivered value.n_subjects— 10 pigs total; 3 healthy animals received PH and SMP FUS, 7 underwent surgery (4 FUS, 3 sham).exposures[1].timing.pulse_duration_ms— Same flag as exposures[0]; frequency and pulse width are for the system maximum output.