Real-time quantification of laser speckle contrast imaging during intestinal laparoscopic surgery: successful demonstration in a porcine intestinal ischemia model.

BACKGROUND: Anastomotic leakage (AL) is a dreaded complication following colorectal cancer surgery, impacting patient outcome and leads to increasing healthcare consumption as well as economic burden. Bowel perfusion is a significant modifiable factor for anastomotic healing and thus crucial for reducing AL. AIMS: The study aimed to calculate a cut-off value for quantified laser speckle perfusion units (LSPUs) in order to differentiate between ischemic and well-perfused tissue and to assess inter-observer reliability. METHODS: LSCI was performed using a porcine ischemic small bowel loop model with the PerfusiX-Imaging® system. An ischemic area, a well-perfused area, and watershed areas, were selected based on the LSCI colormap. Subsequently, local capillary lactate (LCL) levels were measured. A logarithmic curve estimation tested the correlation between LSPU and LCL levels. A cut-off value for LSPU and lactate was calculated, based on anatomically ischemic and well-perfused tissue. Inter-observer variability analysis was performed with 10 observers. RESULTS: Directly after ligation of the mesenteric arteries, differences in LSPU values between ischemic and well-perfused tissue were significant (p < 0.001) and increased significantly throughout all following measurements. LCL levels were significantly different (p < 0.001) at both 60 and 120 min. Logarithmic curve estimation showed an R2 value of 0.56 between LSPU and LCL values. A LSPU cut-off value was determined at 69, with a sensitivity of 0.94 and specificity of 0.87. A LCL cut-off value of 3.8 mmol/L was found, with a sensitivity and specificity of 0.97 and 1.0, respectively. There was no difference in assessment between experienced and unexperienced observers. Cohen's Kappa values were moderate to good (0.52-0.66). CONCLUSION: Real-time quantification of LSPUs may be a feasible intraoperative method to assess tissue perfusion and a cut-off value could be determined with high sensitivity and specificity. Inter-observer variability was moderate to good, irrespective of prior experience with the technique.

Dye-free visualisation of intestinal perfusion using laser speckle contrast imaging in laparoscopic surgery: a prospective, observational multi-centre study.

INTRODUCTION: Intraoperative perfusion imaging may help the surgeon in creating the intestinal anastomoses in optimally perfused tissue. Laser speckle contrast imaging (LSCI) is such a perfusion visualisation technique that is characterized by dye-free, real-time and continuous imaging. Our aim is to validate the use of a novel, dye-free visualization tool to detect perfusion deficits using laparoscopic LSCI. METHODS: In this multi-centre study, a total of 64 patients were imaged using the laparoscopic laser speckle contrast imager. Post-operatively, surgeons were questioned if the additional visual feedback would have led to a change in clinical decision-making. RESULTS: This study suggests that the laparoscopic laser speckle contrast imager PerfusiX-Imaging is able to image colonic perfusion. All images were clear and easy to interpret for the surgeon. The device is non-disruptive of the surgical procedure with an average added surgical time of 2.5 min and no change in surgical equipment. The potential added clinical value is accentuated by the 17% of operating surgeons indicating a change in anastomosis location. Further assessment and analysis of both white light and PerfusiX perfusion images by non-involved, non-operating surgeons showed an overall agreement of 80%. CONCLUSION: PerfusiX-Imaging is a suitable laparoscopic perfusion imaging system for colon surgery that can visualize perfusion in real-time with no change in surgical equipment. The additional visual feedback could help guide the surgeons in placing the anastomosis at the most optimal site.

Experimental evaluation of laparoscopic laser speckle contrast imaging to visualize perfusion deficits during intestinal surgery.

BACKGROUND: Ischemia at the site of an intestinal anastomosis is one of the most important risk factors for anastomotic leakage (AL). Consequently, adequate intestinal microperfusion is essential for optimal tissue oxygenation and anastomotic healing. As visual inspection of tissue viability does not guarantee an adequate objective evaluation of intestinal microperfusion, surgeons are in dire need of supportive tools to decrease anastomotic leakage after colorectal surgery. METHODS: In this feasibility study, laparoscopic laser speckle contrast imaging (LSCI) was used to evaluate intestinal microperfusion in an experimental ischemic bowel loop model. Both large and small ischemic loops were created from the small intestine of a pig; each loop was divided into 5 regions of interest (ROI) with varying levels of ischemia. Speckle contrast and local capillary lactate (LCL) was measured in all ROIs. RESULTS: Both real-time visualization of intestinal microperfusion and induced perfusion deficits was achieved in all bowel loops. As a result, the emergence of regions of intestinal ischemia could be predicted directly after iatrogenic perfusion limitation, whereas without LSCI signs of decreased intestinal viability could only be seen after 30 minutes. Additionally, a significant relation was found between LCL and LSCI. CONCLUSION: In conclusion, LSCI can achieve real-time intraoperative visualization of intestinal microperfusion deficits, allowing for accurate prediction of long-term postoperative ischemic complications. With this revealing capacity, LSCI could potentially facilitate surgical decision-making when constructing intestinal anastomoses in order to mitigate ischemia-related complications such as AL.

A Novel and Generic Workflow of Indocyanine Green Perfusion Assessment Integrating Standardization and Quantification Toward Clinical Implementation.

OBJECTIVE: This study aims to generate a reproducible and generalizable Workflow model of ICG-angiography integrating Standardization and Quantification (WISQ) that can be applied uniformly within the surgical innovation realm independent of the user. SUMMARY BACKGROUND DATA: Tissue perfusion based on indocyanine green (ICG)-angiography is a rapidly growing application in surgical innovation. Interpretation of results has been subjective and error-prone due to the lack of a standardized and quantitative ICG-workflow and analytical methodology. There is a clinical need for a more generic, reproducible, and quantitative ICG perfusion model for objective assessment of tissue perfusion. METHODS: In this multicenter, proof-of-concept study, we present a generic and reproducible ICG-workflow integrating standardization and quantification for perfusion assessment. To evaluate our model's clinical feasibility and reproducibility, we assessed the viability of parathyroid glands after performing thyroidectomy. Biochemical hypoparathyroidism was used as the postoperative endpoint and its correlation with ICG quantification intraoperatively. Parathyroid gland is an ideal model as parathyroid function post-surgery is only affected by perfusion. RESULTS: We show that visual subjective interpretation of ICG-angiography by experienced surgeons on parathyroid perfusion cannot reliably predict organ function impairment postoperatively, emphasizing the importance of an ICG quantification model. WISQ was able to standardize and quantify ICG-angiography and provided a robust and reproducible perfusion curve analysis. A low ingress slope of the perfusion curve combined with a compromised egress slope was indicative for parathyroid organ dysfunction in 100% of the cases. CONCLUSION: WISQ needs prospective validation in larger series and may eventually support clinical decision-making to predict and prevent postoperative organ function impairment in a large and varied surgical population.

Real-time, multi-spectral motion artefact correction and compensation for laser speckle contrast imaging.

Laser speckle contrast imaging (LSCI) is so sensitive to motion that it can measure the movement of red blood cells. However, this extreme sensitivity to motion is also its pitfall as the clinical translation of LSCI is slowed down due to the inability to deal with motion artefacts. In this paper we study the effectiveness of a real-time, multi-spectral motion artefact correction and compensation by subduing an in vitro flow phantom and ex vivo porcine kidney to computer-controlled motion artefacts. On the in vitro flow phantom, the optical flow showed a good correlation with the total movement. This model results in a better signal-to-noise ratios for multiple imaging distances and the overestimation of perfusion was reduced. In the ex vivo kidney model, the perfusion overestimation was also reduced and we were still able to distinguish between ischemia and non-ischemia in the stabilized data whereas this was not possible in the non-stabilized data. This leads to a notably better perfusion estimation that could open the door to a multitude of new clinical applications for LSCI.

Heterogeneity in Utilization of Optical Imaging Guided Surgery for Identifying or Preserving the Parathyroid Glands-A Meta-Narrative Review.

BACKGROUND: Postoperative hypoparathyroidism is the most common complication after total thyroidectomy. Over the past years, optical imaging techniques, such as parathyroid autofluorescence, indocyanine green (ICG) angiography, and laser speckle contrast imaging (LSCI) have been employed to save parathyroid glands during thyroid surgery. This study provides an overview of the utilized methods of the optical imaging techniques during total thyroidectomy for parathyroid gland identification and preservation. METHODS: PUBMED, EMBASE and Web of Science were searched for studies written in the English language utilizing parathyroid autofluorescence, ICG-angiography, or LSCI during total thyroidectomy to support parathyroid gland identification or preservation. Case reports, reviews, meta-analyses, animal studies, and post-mortem studies were excluded after the title and abstract screening. The data of the studies were analyzed qualitatively, with a focus on the methodologies employed. RESULTS: In total, 59 articles were included with a total of 6190 patients. Overall, 38 studies reported using parathyroid autofluorescence, 24 using ICG-angiography, and 2 using LSCI. The heterogeneity between the utilized methodology in the studies was large, and in particular, regarding study protocols, imaging techniques, and the standardization of the imaging protocol. CONCLUSION: The diverse application of optical imaging techniques and a lack of standardization and quantification leads to heterogeneous conclusions regarding their clinical value. Worldwide consensus on imaging protocols is needed to establish the clinical utility of these techniques for parathyroid gland identification and preservation.

Laparoscopic Laser Speckle Contrast Imaging Can Visualize Anastomotic Perfusion: A Demonstration in a Porcine Model.

BACKGROUND: Intestinal resection causes inevitable vascular damage, which cannot always be seen during an intraoperative clinical assessment of local intestinal perfusion. If left unaltered, impaired perfusion can lead to complications, such as anastomotic leakage (AL). Therefore, we demonstrate the use of a novel laparoscopic laser speckle contrast imaging (LSCI)-based approach in order to assess local intestinal perfusion during the construction of intestinal anastomoses. METHODS: Three segments were isolated from the small intestine of a pig, while the perfusion of each was compromised by coagulating 7-8 mesenteric arteries. Both clinical assessments and LSCI were used to detect the induced perfusion deficits and to subsequently guide a transection in either a well perfused, marginally perfused, or poorly perfused tissue area within the segment. Bowel ends were then utilized for the creation of three differently perfused anastomoses: well perfused/well perfused (anastomosis segment 1), well perfused/poorly perfused (anastomosis segment 2), and poorly perfused/poorly perfused (anastomosis segment 3). After construction of the anastomoses, a final perfusion assessment using both clinical assessment and LSCI was executed in order to evaluate the vascular viability of the anastomosis. RESULTS: Laparoscopic LSCI enabled continuous assessment of local intestinal perfusion and allowed for detection of perfusion deficits in real time. The imaging feedback precisely guided the surgical procedure, and, when evaluating the final anastomotic perfusion, LSCI was able to visualize the varying degrees of perfusion, whereas standard clinical assessment yielded only minor differences in visual appearance of the tissue. CONCLUSIONS: In this technical note, we demonstrate a novel LSCI-based approach for intraoperative perfusion assessment. With its ability to continuously visualize perfusion in real time, laparoscopic LSCI has significant potential for the optimization of anastomotic surgery in the near future.

A Guideline for Clinicians Performing Clinical Studies with Fluorescence Imaging.

Fluorescence imaging is an emerging imaging technique that has shown many benefits for clinical care. Currently, the field is in rapid clinical translation, and an unprecedented number of clinical trials are performed. Clinicians are inundated with numerous opportunities and combinations of different imaging modalities. To streamline this process, a multidisciplinary approach is needed with drug discovery, software and systems engineering, and translational medicine. Here, we discuss the main constituents of a uniform fluorescence imaging protocol to match the clinical need and ensure consistent study designs and reliable data collection in clinical trials. In an era in which the potential of fluorescence imaging has become evident, consistent conduct of studies, data analysis, and data interpretation is essential for implementation into the standard of care.

Real-time visualization of renal microperfusion using laser speckle contrast imaging.

SIGNIFICANCE: Intraoperative parameters of renal cortical microperfusion (RCM) have been associated with postoperative ischemia/reperfusion injury. Laser speckle contrast imaging (LSCI) could provide valuable information in this regard with the advantage over the current standard of care of being a non-contact and full-field imaging technique. AIM: Our study aims to validate the use of LSCI for the visualization of RCM on ex vivo perfused human-sized porcine kidneys in various models of hemodynamic changes. APPROACH: A comparison was made between three renal perfusion measures: LSCI, the total arterial renal blood flow (RBF), and sidestream dark-field (SDF) imaging in different settings of ischemia/reperfusion. RESULTS: LSCI showed a good correlation with RBF for the reperfusion experiment (0.94 ± 0.02; p < 0.0001) and short- and long-lasting local ischemia (0.90 ± 0.03; p < 0.0001 and 0.81 ± 0.08; p < 0.0001, respectively). The correlation decreased for low flow situations due to RBF redistribution. The correlation between LSCI and SDF (0.81 ± 0.10; p < 0.0001) showed superiority over RBF (0.54 ± 0.22; p < 0.0001). CONCLUSIONS: LSCI is capable of imaging RCM with high spatial and temporal resolutions. It can instantaneously detect local perfusion deficits, which is not possible with the current standard of care. Further development of LSCI in transplant surgery could help with clinical decision making.

Clinical applications of laser speckle contrast imaging: a review.

When a biological tissue is illuminated with coherent light, an interference pattern will be formed at the detector, the so-called speckle pattern. Laser speckle contrast imaging (LSCI) is a technique based on the dynamic change in this backscattered light as a result of interaction with red blood cells. It can be used to visualize perfusion in various tissues and, even though this technique has been extensively described in the literature, the actual clinical implementation lags behind. We provide an overview of LSCI as a tool to image tissue perfusion. We present a brief introduction to the theory, review clinical studies from various medical fields, and discuss current limitations impeding clinical acceptance.

Application of laser speckle contrast imaging in laparoscopic surgery.

Anastomotic leakage is a worldwide problem in gastrointestinal surgery which seems to be related to the state of microcirculation. Laser speckle contrast imaging (LSCI) could give surgeons insight in the state of microcirculation to attune the site of anastomosis. This work studies the feasibility of LSCI as a tool for this purpose. An experimental setup was developed using a commercially available laparoscopic video system. Laser speckle contrast imaging is capable of detecting ischemic areas on the large intestine. Further research and development are required before adaptation of this technique in the operating room.