Feasibility and comparison of laparoscopic laser speckle contrast imaging to near-infrared display of indocyanine green in intraoperative tissue blood flow/tissue perfusion in preclinical porcine models.

OBJECTIVE: To determine if laser speckle contrast imaging (LSCI) mitigates variations and subjectivity in the use and interpretation of indocyanine green (ICG) fluorescence in the current visualization paradigm of real-time intraoperative tissue blood flow/perfusion in clinically relevant scenarios. METHODS: De novo laparoscopic imaging form-factor detecting real-time blood flow using LSCI and blood volume by near-infrared fluorescence (NIRF) of ICG was compared to ICG NIRF alone, for dye-less real-time visualization of tissue blood flow/perfusion. Experienced surgeons examined LSCI and ICG in segmentally devascularized intestine, partial gastrectomy, and the renal hilum across six porcine models. Precision and accuracy of identifying demarcating lines of ischemia/perfusion in tissues were determined in blinded subjects with varying levels of surgical experience. RESULTS: Unlike ICG, LSCI perfusion detection was real time (latency < 150 ms: p < 0.01), repeatable and on-demand without fluorophore injection. Operating surgeons (n = 6) precisely and accurately identified concordant demarcating lines in white light, LSCI, and ICG modes immediately. Blinded subjects (n = 21) demonstrated similar spatial-temporal precision and accuracy with all three modes ≤ 2 min after ICG injection, and discordance in ICG mode at ≥ 5 min in devascularized small intestine (p < 0.0001) and in partial gastrectomy (p < 0.0001). CONCLUSIONS: Combining LSCI for near real-time blood flow detection with ICG fluorescence for blood volume detection significantly improves precision and accuracy of perfusion detection in tissue locations over time, in real time, and repeatably on-demand than ICG alone.

Real-time quantification of intestinal perfusion and arterial versus venous occlusion using laser speckle contrast imaging in porcine model.

PURPOSE: Real-time intraoperative perfusion assessment may reduce anastomotic leaks. Laser speckle contrast imaging (LSCI) provides dye-free visualization of perfusion by capturing coherent laser light scatter from red blood cells and displays perfusion as a colormap. Herein, we report a novel method to precisely quantify intestinal perfusion using LSCI. METHODS: ActivSight™ is an FDA-cleared multi-modal visualization system that can detect and display perfusion via both indocyanine green imaging (ICG) and LSCI in minimally invasive surgery. An experimental prototype LSCI perfusion quantification algorithm was evaluated in porcine models. Porcine small bowel was selectively devascularized to create regions of perfused/watershed/ischemic bowel, and progressive aortic inflow/portal vein outflow clamping was performed to study arterial vs. venous ischemia. Continuous arterial pressure was monitored via femoral line. RESULTS: LSCI perfusion colormaps and quantification distinguished between perfused, watershed, and ischemic bowel in all vascular control settings: no vascular occlusion (p < 0.001), aortic occlusion (p < 0.001), and portal venous occlusion (p < 0.001). LSCI quantification demonstrated similar levels of ischemia induced both by states of arterial inflow and venous outflow occlusion. LSCI-quantified perfusion values correlated positively with higher mean arterial pressure and with increasing distance from ischemic bowel. CONCLUSION: LSCI relative perfusion quantification may provide more objective real-time assessment of intestinal perfusion compared to conventional naked eye assessment by quantifying currently subjective gradients of bowel ischemia and identifying both arterial/venous etiologies of ischemia.

Real-time quantification of bowel perfusion using Laparoscopic Laser Speckle Contrast Imaging (LSCI) in a porcine model.

BACKGROUND/PURPOSE: Real-time quantification of tissue perfusion can improve intraoperative surgical decision making. Here we demonstrate the utility of Laser Speckle Contrast Imaging as an intra-operative tool that quantifies real-time regional differences in intestinal perfusion and distinguishes ischemic changes resulting from arterial/venous obstruction. METHODS: Porcine models (n = 3) consisted of selectively devascularized small bowel loops that were used to measure the perfusion responses under conditions of control/no vascular occlusion, arterial inflow occlusion, and venous outflow occlusion using laser speckle imaging and indocyanine green fluoroscopy. Laser Speckle was also used to assess perfusion differences between small bowel antimesenteric-antimesenteric and mesenteric-mesenteric anastomoses. Perfusion quantification was measured in relative perfusion units calculated from the laser speckle perfusion heatmap. RESULTS: Laser Speckle distinguished between visually identified perfused, watershed, and ischemic intestinal segments with both color heatmap and quantification (p < .00001). It detected a continuous gradient of relative intestinal perfusion as a function of distance from the stapled ischemic bowel edge. Strong positive linear correlation between relative perfusion units and changes in mean arterial pressure resulting from both arterial (R2 = .96/.79) and venous pressure changes (R2 = .86/.96) was observed. Furthermore, Laser Speckle showed that the antimesenteric anastomosis had a higher perfusion than mesenteric anastomosis (p < 0.01). CONCLUSIONS: Laser Speckle Contrast Imaging provides objective, quantifiable tissue perfusion information in both color heatmap and relative numerical units. Laser Speckle can detect spatial/temporal differences in perfusion between antimesenteric and mesenteric borders of a bowel segment and precisely detect perfusion changes induced by progressive arterial/venous occlusions in real-time.

Corticospinal excitability for flexor carpi radialis decreases with baroreceptor unloading during intentional co-contraction with opposing forearm muscles.

Concurrent activation of antagonistic muscles (co-contraction) is used for stiffening a joint, whereas its neural control under hemodynamic stress (e.g., posture change, high gravity, and hemorrhage) is unknown. Corticospinal excitability during co-contraction may be altered with baroreceptor unloading due to potential modulations in spinal and/or inhibitory pathways (e.g., disynaptic group I inhibition and GABA-mediated intracortical inhibition). The purpose of this study was to understand the effect of baroreceptor unloading on corticospinal excitability during co-contraction in humans. Motor evoked potential and cortical silent period in a wrist flexor muscle were examined using transcranial magnetic stimulation in two groups of healthy young adults. All subjects performed isometric contraction of the wrist flexors (flexion) and co-contraction of the wrist flexors and extensors (co-contraction). Spinal disynaptic inhibition was also assessed with the ratio of H-reflex responses to unconditioned and conditioned electrical stimulations of the peripheral nerves for the muscles. In one of the groups, baroreflex unloading was induced by applying lower body negative pressure. There was no significant effect of baroreflex unloading on cortical silent period or H-reflex measure of disynaptic inhibition. With baroreflex unloading, motor evoked potential area in the flexor carpi radialis was decreased during co-contraction but not during flexion. The results indicated that baroreceptor unloading decreases corticospinal excitability during co-contraction of antagonistic muscles, apparently by influencing neural pathways that were not probed with cortical silent period or spinal disynaptic inhibition.

Motor cortical disinhibition with baroreceptor unloading induced by orthostatic stress.

Unloading of the baroreceptors due to orthostatic stress increases corticospinal excitability. The purpose of this study was to examine the effects of baroreceptor unloading due to orthostatic stress on intracortical excitatory and inhibitory pathways in the motor cortex. With transcranial magnetic stimulation, measures of intracortical excitability for a hand muscle were tested on 2 days in healthy young adults. Lower body negative pressure (LBNP) of 40 mmHg was applied during one of the days and not during the Control day. During application of LBNP heart rate and the low-frequency component of heart rate variability increased, while mean arterial blood pressure was maintained. In the resting state, LBNP decreased short-interval intracortical inhibition (SICI) and had no effect on intracortical facilitation (ICF) or short-interval intracortical facilitation (SICF) compared with the Control day. During isometric contraction, no effects of LBNP were observed on tested measures of intracortical excitability including SICI, SICF, and cortical silent period. It was concluded that baroreceptor unloading due to orthostatic stress results in diminished intracortical inhibition, at least in the resting muscle.

Laser speckle contrast imaging compared with indocyanine green in renal perfusion of a porcine model.

Background: When viewed under near-infrared light, indocyanine green (ICG) signal for kidney perfusion can be utilized in partial nephrectomy. Laser speckle contrast imaging (LSCI) uses coherent light to detect perfusion during real-time laparoscopic surgery. Materials and methods: Laser speckle contrast imaging or ActivSight, an imaging sensor adapter, was used during laparoscopy of an anesthetized porcine kidney model. ActivSight's "perfusion mode" and "quantification mode" displayed the blood flow as a heatmap and numerical signal intensity, respectively. Results: After the upper segmental renal artery was clamped, ICG was seen in the lower pole, and LSCI showed low unit (dark color) quantification and perfusion in the upper pole. Indocyanine green was retained in the lower pole after the upper segmental artery was unclamped, and LSCI perfusion was demonstrated in the entire kidney. Conclusions: Laser speckle contrast imaging is a dye-free, repeatable, real-time adjunct for renal parenchymal perfusion assessment applicable to minimally invasive renal surgery to complement the technology of ICG near-infrared fluorescence and advance digital surgery.

Enhanced corticospinal excitability with physiologically heightened sympathetic nerve activity.

Corticospinal excitability is modulated differently with norepinephrine and dopamine agonists, although both monoamines are released with heightened sympathetic nerve activity. The purpose of this study was to investigate the influence of physiological heightening of sympathetic nerve activity on corticospinal excitability in healthy humans. Subjects were divided into control and experimental groups. In each participant, motor-evoked potentials (MEPs) were measured from the resting first dorsal interosseous muscle of the right hand with transcranial magnetic stimulation (TMS) in two trials separated by 1 h. In the experimental group, sympathetic nerve activity was physiologically heightened during the second trial by applying lower body negative pressure (LBNP). In the control group, sympathetic nerve activity was not altered between the two trials. MEP peak-to-peak amplitude increased from trial 1 to trial 2 in the experimental group only. This increase was evident at a TMS intensity of 130% resting motor threshold and higher. It was concluded that physiological heightening of sympathetic nerve activity with LBNP enhances corticospinal excitability.