Quantitative Fluorescence Imaging of Perfusion-An Algorithm to Predict Anastomotic Leakage.

This study tests fluorescence imaging-derived quantitative parameters for perfusion evaluation of the gastric tube during surgery and correlates these parameters with patient outcomes in terms of anastomotic leakage. Poor fundus perfusion is seen as a major factor for the development of anastomotic leakage and strictures. Fluorescence perfusion imaging may reduce the incidence of complications. Parameters for the quantification of the fluorescence signal are still lacking. Quantitative parameters in terms of maximal intensity, mean slope and influx timepoint were tested for significant differences between four perfusion areas of the gastric tube in 22 patients with a repeated ANOVA test. These parameters were compared with patient outcomes. Maximal intensity, mean slope and influx timepoint were significantly different between the base of the gastric tube and the fundus (p < 0.0001). Patients who developed anastomotic leakage showed a mean slope of almost 0 in Location 4. The distance of the demarcation of ICG to the fundus was significantly higher in the three patients who developed anastomotic leakage (p < 0.0001). This study presents quantitative intra-operative perfusion imaging with fluorescence. Quantification of the fluorescence signal allows for early risk stratification of necrosis.

Quantitative change of perfusion in gastric tube reconstruction by sidestream dark field microscopy (SDF) after esophagectomy, a prospective in-vivo cohort study.

BACKGROUND: Anastomotic leakage is one of the most severe complications in patients undergoing esophagectomy with gastric tube reconstruction. Transection of the left gastric and gastro-epiploic artery and vein results in compromised perfusion which is seen as the major contributing factor for anastomotic dehiscence. The main objective of this prospective, observational, in-vivo pilot study is to microscopically evaluate gastric tube perfusion with Sidestream Darkfield Microscopy (SDF). METHODS: Intra-operative microscopic images of gastric-microcirculation were obtained with SDF directly after reconstruction in 22 patients. Quantitative perfusion related parameters were: velocity, Microvascular Flow Index(MFI), Total Vessel Density(TVD), Perfusion Vessel Density(PVD), Proportion of Perfused Vessels(PPV) and De Backer Score(DBS). Dedicated software was used to assess parameters predictive for compromised perfusion. RESULTS: SDF was feasible to accurately visualize and evaluate microcirculation in all patients. Velocity(µm/sec) was significantly decreased towards the fundus (p = 0.001). MFI, PVD and PVD were decreased distal of the watershed - between the right and left gastro-epiploic artery and vein - and in the fundus, compared to the base of the gastric tube(p = 0.0002). No differences in TVD and DBS were observed; because of vessel-dilation in the fundus-area. This suggests that venous congestion results in comprised inflow of oxygen rich blood and plays a role in the development of ischaemia. CONCLUSION: We present quantitative perfusion imaging with SDF of the gastric tube. Velocity, MFI, TVD and PPV are accurate parameters to observe perfusion decrease. Also, venous congestion is visible in the fundus, suggesting an important role in the development of ischaemia. These parameters could allow early risk stratification, and, potentially, can accomplish a reduction in anastomotic leakage.

Estimation of microvascular perfusion after esophagectomy: a quantitative model of dynamic fluorescence imaging.

Most common complications of esophagectomy stem from a perfusion deficiency of the gastric conduit at the anastomosis. Fluorescent tracer imaging allows intraoperative visualization of tissue perfusion. Quantitative assessment of fluorescence dynamics has the potential to identify perfusion deficiency. We developed a perfusion model to analyze the relation between fluorescence dynamics and perfusion deficiency. The model divides the gastric conduit into two well-perfused and two anastomosed sites. Hemodynamics and tracer transport were modeled. We analyzed the value of relative time-to-threshold (RTT) as a predictor of the relative remaining flow (RRF). Intensity thresholds for RTT of 20% to 50% of the maximum fluorescence intensity of the well-perfused site were tested. The relation between RTT and RRF at the anastomosed sites was evaluated over large variations of vascular conductance and volume. The ability of RTT to distinguish between sufficient and impaired perfusion was analyzed using c-statistics. We found that RTT was a valuable estimate for low RRF. The threshold of 20% of the maximum fluorescence intensity provided the best prediction of impaired perfusion on the two anastomosed sites (AUC = 0.89 and 0.86). The presented model showed that for low flows, relative time-to-threshold may be used to estimate perfusion deficiency.

Feasibility of Optical Coherence Tomography (OCT) for Intra-Operative Detection of Blood Flow during Gastric Tube Reconstruction.

In this study; an OCT-based intra-operative imaging method for blood flow detection during esophagectomy with gastric tube reconstruction is investigated. Change in perfusion of the gastric tube tissue can lead to ischemia; with a high morbidity and mortality as a result. Anastomotic leakage (incidence 5⁻20%) is one of the most severe complications after esophagectomy with gastric tube reconstruction. Optical imaging techniques provide for minimal-invasive and real-time visualization tools that can be used in intraoperative settings. By implementing an optical technique for blood flow detection during surgery; perfusion can be imaged and quantified and; if needed; perfusion can be improved by either a surgical intervention or the administration of medication. The feasibility of imaging gastric microcirculation in vivo using optical coherence tomography (OCT) during surgery of patients with esophageal cancer by visualizing blood flow based on the speckle contrast from M-mode OCT images is studied. The percentage of pixels exhibiting a speckle contrast value indicative of flow was quantified to serve as an objective parameter to assess blood flow at 4 locations on the reconstructed gastric tube. Here; it was shown that OCT can be used for direct blood flow imaging during surgery and may therefore aid in improving surgical outcomes for patients.

Intraoperative evaluation of perfusion in free flap surgery: A systematic review and meta-analysis.

BACKGROUND: Free flap survival relies on adequate tissue perfusion. We aim to give an overview of the available literature of all objective methods to intraoperatively assess free flap tissue perfusion, and the effects on (partial) flap loss. METHODS: A systematic review and meta-analysis according to the PRISMA guidelines was performed (PubMed, Cochrane Library, Embase) regarding English language articles. Meta-analyses were performed by pooling means and slopes using random-effect models. RESULTS: Sixty-four articles were included reporting on 2369 procedures in 2009 patients with various indications. Reported methods were fluorescence imaging (FI), laser Doppler, oxygen saturation, ultrasound, (dynamic) infrared thermography, venous pressure, and microdialysis. Intraoperative tissue perfusion was adequately measured by the use of FI and laser Doppler, leading to surgical intervention or altered flap design, and increased flap survival. Meta-analysis showed a mean time until onset of the dye to become visible of 18.4 (7.27; 29.46, Q P < 0.001) sec. The relative intensity of the flap compared to the intensity curve of normal tissue was 75.92% (65.85; 85.98, Q P = 0.719). The mean difference in the slope value of the oxygen tensions before and after the anastomosis was -0.09 (-0.12; -0;06 Q P = 0.982). No convincing evidence was found for the use of other methods. CONCLUSIONS: Based on the current literature, FI and laser Doppler are most suitable to intraoperatively measure free flap tissue perfusion, resulting in improved flap survival. However, this review was limited by the available literature. Additional studies are necessary to investigate the predictive value of intraoperative perfusion measurement.

Can we predict necrosis intra-operatively? Real-time optical quantitative perfusion imaging in surgery: study protocol for a prospective, observational, in vivo pilot study.

BACKGROUND: Compromised perfusion as a result of surgical intervention causes a reduction of oxygen and nutrients in tissue and therefore decreased tissue vitality. Quantitative imaging of tissue perfusion during reconstructive surgery, therefore, may reduce the incidence of complications. Non-invasive optical techniques allow real-time tissue imaging, with high resolution and high contrast. The objectives of this study are, first, to assess the feasibility and accuracy of optical coherence tomography (OCT), sidestream darkfield microscopy (SDF), laser speckle contrast imaging (LSCI), and fluorescence imaging (FI) for quantitative perfusion imaging and, second, to identify/search for criteria that enable risk prediction of necrosis during gastric tube and free flap reconstruction. METHODS: This prospective, multicenter, observational in vivo pilot study will assess tissue perfusion using four optical technologies: OCT, SDF, LSCI, and FI in 40 patients: 20 patients who will undergo gastric tube reconstruction after esophagectomy and 20 patients who will undergo free flap surgery. Intra-operative images of gastric perfusion will be obtained directly after reconstruction at four perfusion areas. Feasibility of perfusion imaging will be analyzed per technique. Quantitative parameters directly related to perfusion will be scored per perfusion area, and differences between biologically good versus reduced perfusion will be tested statistically. Patient outcome will be correlated to images and perfusion parameters. Differences in perfusion parameters before and after a bolus of ephedrine will be tested for significance. DISCUSSION: This study will identify quantitative perfusion-related parameters for an objective assessment of tissue perfusion during surgery. This will likely allow early risk stratification of necrosis development, which will aid in achieving a reduction of complications in gastric tube reconstruction and free flap transplantation. TRIAL REGISTRATION: Clinicaltrials.gov registration number NCT02902549. Dutch Central Committee on Research Involving Human Subjects registration number NL52377.018.15.

Electrosclerotherapy for capillary malformations: study protocol for a randomised within-patient controlled pilot trial.

INTRODUCTION: The current state-of-the-art treatment modality for hypertrophic capillary malformations (CMs), laser therapy, has a considerable rate of non-responders and recurrence. Intralesional bleomycin injections (or 'sclerotherapy') are commonly used to treat venous and lymphatic malformations with an excellent effect, but these intravascular injections are not possible in CMs due to the small diameter of the vessels. Electroporation-an electric field applied to the tissue-could increase the permeability of endothelial cells, which could theoretically facilitate targeted localised bleomycin delivery. We therefore hypothesise that bleomycin injections in combination with electroporation-'electrosclerotherapy' (EST), also known as 'electrochemotherapy'-could potentially be a novel alternative treatment option for CMs. METHODS AND ANALYSIS: In this randomised within-patient controlled pilot trial, 20 patients with hypertrophic CMs will be enrolled. Three regions of interest (ROIs) within the CM will be randomly allocated for treatment with (A) EST, (B) bleomycin sclerotherapy without electroporation and (C) no treatment. Patients and outcome assessors are blinded for the treatment allocation. Treatment outcome for each ROI will be measured approximately 7 weeks after the treatment procedure, using patient-reported and physician-reported global assessment scores, colorimetry, laser speckle imaging and reporting of adverse events. ETHICS AND DISSEMINATION: The study protocol is approved by the ethics review committee of the Academic Medical Center, Amsterdam. Results will be published in peer-reviewed medical journals and will be presented at international conferences and scientific meetings. Study results will be fed back to the patient population through website and social media notifications. TRIAL REGISTRATION NUMBER: NCT02883023;Pre-results. NTR6169.

Applicability of quantitative optical imaging techniques for intraoperative perfusion diagnostics: a comparison of laser speckle contrast imaging, sidestream dark-field microscopy, and optical coherence tomography.

Patient morbidity and mortality due to hemodynamic complications are a major problem in surgery. Optical techniques can image blood flow in real-time and high-resolution, thereby enabling perfusion monitoring intraoperatively. We tested the feasibility and validity of laser speckle contrast imaging (LSCI), optical coherence tomography (OCT), and sidestream dark-field microscopy (SDF) for perfusion diagnostics in a phantom model using whole blood. Microvessels with diameters of 50, 100, and 400 µm were constructed in a scattering phantom. Perfusion was simulated by pumping heparinized human whole blood at five velocities (0 to 20 mm/s). Vessel diameter and blood flow velocity were assessed with LSCI, OCT, and SDF. Quantification of vessel diameter was feasible with OCT and SDF. LSCI could only visualize the 400-µm vessel, perfusion units scaled nonlinearly with blood velocity. OCT could assess blood flow velocity in terms of inverse OCT speckle decorrelation time. SDF was not feasible to measure blood flow; however, for diluted blood the measurements were linear with the input velocity up to 1 mm/s. LSCI, OCT, and SDF were feasible to visualize blood flow. Validated blood flow velocity measurements intraoperatively in the desired parameter (mL·min-1·g-1) remain challenging.