Surgical optomics: hyperspectral imaging and deep learning towards precision intraoperative automatic tissue recognition-results from the EX-MACHYNA trial.

BACKGROUND: Hyperspectral imaging (HSI), combined with machine learning, can help to identify characteristic tissue signatures enabling automatic tissue recognition during surgery. This study aims to develop the first HSI-based automatic abdominal tissue recognition with human data in a prospective bi-center setting. METHODS: Data were collected from patients undergoing elective open abdominal surgery at two international tertiary referral hospitals from September 2020 to June 2021. HS images were captured at various time points throughout the surgical procedure. Resulting RGB images were annotated with 13 distinct organ labels. Convolutional Neural Networks (CNNs) were employed for the analysis, with both external and internal validation settings utilized. RESULTS: A total of 169 patients were included, 73 (43.2%) from Strasbourg and 96 (56.8%) from Verona. The internal validation within centers combined patients from both centers into a single cohort, randomly allocated to the training (127 patients, 75.1%, 585 images) and test sets (42 patients, 24.9%, 181 images). This validation setting showed the best performance. The highest true positive rate was achieved for the skin (100%) and the liver (97%). Misclassifications included tissues with a similar embryological origin (omentum and mesentery: 32%) or with overlaying boundaries (liver and hepatic ligament: 22%). The median DICE score for ten tissue classes exceeded 80%. CONCLUSION: To improve automatic surgical scene segmentation and to drive clinical translation, multicenter accurate HSI datasets are essential, but further work is needed to quantify the clinical value of HSI. HSI might be included in a new omics science, namely surgical optomics, which uses light to extract quantifiable tissue features during surgery.

MRI for the Detection of Small Bowel Ischemic Injury in Arterial Acute Mesenteric Ischemia: Preclinical Study in a Porcine Model.

BACKGROUND: MRI is the reference for the diagnosis of arterial cerebral ischemia, but its role in acute mesenteric ischemia (AMI) is poorly known. PURPOSE: To assess MRI detection of early ischemic bowel lesions in a porcine model of arterial AMI. STUDY TYPE: Prospective/cohort. ANIMAL MODEL: Porcine model of arterial AMI obtained by embolization of the superior mesenteric artery (seven pigs). FIELD STRENGTH/SEQUENCE: A 5-T. T1 gradient-echo-weighted-imaging (WI), half-Fourier-acquisition-single-shot-turbo-spin-echo, T2 turbo-spin-echo, true-fast-imaging-with-steady-precession (True-FISP), diffusion-weighted-echo-planar (DWI). ASSESSMENT: T1-WI, T2-WI, and DWI were performed before and continuously after embolization for 6 hours. The signal intensity (SI) of the ischemic bowel was assessed visually and quantitatively on all sequences. The apparent diffusion coefficient (ADC) was assessed. STATISTICAL TESTS: Paired Student's t-test or Mann-Whitney U-test, significance at P < 0.05. RESULTS: One pig died from non-AMI-related causes. The remaining pigs underwent a median 5 h53 (range 1 h24-6 h01) of ischemia. Visually, the ischemic bowel showed signal hyperintensity on DWI-b800 after a median 85 (57-276) minutes compared to the nonischemic bowel. DWI-b800 SI significantly increased after 2 hours (+19%) and the ADC significant decrease within the first hour (-31%). The ischemic bowel was hyperintense on precontrast T1-WI after a median 87 (70-171) minutes with no significant quantitative changes over time (P = 0.46-0.93). The ischemic bowel was hyperintense on T2-WI in three pigs with a significant SI increase on True-FISP after 1 and 2 hours. DATA CONCLUSION: Changes in SI and ADC can be seen early after the onset of arterial AMI with DWI. The value of T2-WI appears to be limited. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

End-to-end invaginated pancreaticojejunostomy during minimally invasive pancreatoduodenectomy: technical description and single center experience.

BACKGROUND: Remarkable progress has been made in pancreatic surgery over the last decades with the introduction of minimally invasive techniques. Minimally invasive pancreatoduodenectomy (MIPD) remains one of the most challenging operations in abdominal surgery and it is performed in a few centers worldwide. The treatment of the pancreatic stump is a crucial step of this operation; however, the best strategy to perform pancreatic anastomosis is still debated. In this article, we describe the technical details of our original technique of modified minimally invasive end-to-end invaginated pancreaticojejunostomy (EIPJ) using video footage. METHODS: In the current study, we retrospectively analyzed a pilot series of 67 consecutive cases of minimally invasive (7 robotic/60 fully laparoscopic) MIPD operated on at the General Surgery Department of the Panico Hospital, Tricase (Italy) between March 2017 and October 2022.The reconstruction phase involved an EIPJ, tailored using an intra-ductal anastomotic plastic stent. The aim of this study was to describe the technique and evaluate the short-term outcomes of patients undergoing MIPD with EIPJ. RESULTS: The mean operative time to perform the EIPJ was 21.57 ± 3.32 min. Seven patients (10.5%) developed biochemical leaks and 13 (19.4%) developed clinically relevant pancreatic fistulas (grade B or C according to the definition of the International Study Group on Pancreatic Surgery). CONCLUSION: The early results confirm that this anastomosis is safe, easy to perform, and effective in the hands of hepatobiliopancreatic (HBP) surgeons with experience in minimally invasive surgery.

One-stage approach to cholecystocholedocholithiasis treatment: a feasible surgical strategy for emergency settings and frail patients.

BACKGROUND: Cholecystocholedocholithiasis (CCL) occurs in up to 18% of patients undergoing laparoscopic cholecystectomy (LC). The two-stage treatment using endoscopic retrograde cholangiopancreatography (ERCP) followed by LC is the treatment of choice for CCL. However, only 10 to 60% of patients have common bile duct (CBD) stones at the time of ERCP, thus exposing patients to unnecessary ERCPs, causing 3 to 15% of post-interventional pancreatitis. One-stage laparoscopic-endoscopic rendezvous (LERV) is an alternative for the treatment of CCL. Given the selective top-to-bottom CBD cannulation, LERV reduces the risk of pancreatitis and failed CBD cannulation. Additionally, LERV is performed exclusively in patients presenting CBD stones at intraoperative cholangiography, avoiding unnecessary ERCPs. Despite its advantages, considering the logistical burden of coordinating different specialties, LERV is performed in few centers. Here, we present the largest retrospective series of LERVs performed at our department, analyzing elective and emergency procedures. METHODS: All consecutive patients undergoing LERV for CCL between January 2014 and December 2021 were included. LERV success rate, operative time, biliary outflow restoration rate, postoperative complications (POC), length of hospital stay (LOS), and recurrences were analyzed. RESULTS: 181 patients were included (61 elective LERVs, 120 emergency LERVs). We reported a 100% LERV success rate, a 97.79% biliary outflow restoration rate, a 0% conversion rate, a mean intraoperative time of 120.17 ± 31.35 min, and LOS of 4.00 ± 2.82 days. POC included 7 Clavien-Dindo type 1, 11 type 2, and 3 type 3 cases. Seven patients presented with CBD stone recurrence: 2 within 30 days after discharge, 3 within 6 months after discharge, and 2 patients at 1 year. No statistically significant difference was found between elective and emergency patients. CONCLUSION: LERV is safe, representing a valid option even in emergency settings, thus enabling the management of CCL within a single procedure, consequently sparing additional anesthesia and decreasing post-ERCP complications.

Intraoperative bowel perfusion quantification with hyperspectral imaging: a guidance tool for precision colorectal surgery.

BACKGROUND: Poor anastomotic perfusion can cause anastomotic leaks (AL). Hyperspectral imaging (HSI), previously validated experimentally, provides accurate, real-time, contrast-free intestinal perfusion quantification. Clinical experience with HSI is limited. In this study, HSI was used to evaluate bowel perfusion intraoperatively. METHODS: Fifty-two patients undergoing elective colorectal surgeries for neoplasia (n = 40) or diverticular disease (n = 12), were enrolled. Intestinal perfusion was assessed with HSI (TIVITA®, Diaspective Vision, Am Salzhaff, Germany). This device generates a perfusion heat map reflecting the tissue oxygen saturation (StO2) amount. Prior to anastomose creation, the clinical transection line (CTL) was highlighted on the proximal bowel and imaged with HSI. Upon StO2 heat map evaluation, the hyperspectral transection line (HTL) was identified. In case of CTL/HTL discrepancy > 5 mm, the bowel was always resected at the HTL. HSI outcomes were compared to the clinical ones. RESULTS: AL occurred in one patient who underwent neoadjuvant radiochemotherapy and ultralow anterior resection for rectal cancer. HSI assessment was feasible in all patients, and StO2-values were significantly higher at proximal segments than distal ones. Twenty-six patients showed CTL/HTL discrepancy, and these patients had a lower mean StO2 (54.55 ± 21.30%) than patients without discrepancy (65.10 ± 21.30%, p = 0.000). Patients undergoing neoadjuvant radiochemotherapy showed a lower StO2 (51.41 ± 23.41%) than non-neoadjuvated patients (60.51 ± 24.98%, p = 0.010). CONCLUSION: HSI is useful in detecting intraoperatively marginally perfused segments, for which the clinical appreciation is unreliable. Intestinal vascular supply is lower in patients undergoing neoadjuvant radiochemotherapy, and this novel finding together with the clinical impact of HSI perfusion quantification deserves further investigation in larger trials.

Automatic optical biopsy for colorectal cancer using hyperspectral imaging and artificial neural networks.

BACKGROUND: Intraoperative identification of cancerous tissue is fundamental during oncological surgical or endoscopic procedures. This relies on visual assessment supported by histopathological evaluation, implying a longer operative time. Hyperspectral imaging (HSI), a contrast-free and contactless imaging technology, provides spatially resolved spectroscopic analysis, with the potential to differentiate tissue at a cellular level. However, HSI produces "big data", which is impossible to directly interpret by clinicians. We hypothesize that advanced machine learning algorithms (convolutional neural networks-CNNs) can accurately detect colorectal cancer in HSI data. METHODS: In 34 patients undergoing colorectal resections for cancer, immediately after extraction, the specimen was opened, the tumor-bearing section was exposed and imaged using HSI. Cancer and normal mucosa were categorized from histopathology. A state-of-the-art CNN was developed to automatically detect regions of colorectal cancer in a hyperspectral image. Accuracy was validated with three levels of cross-validation (twofold, fivefold, and 15-fold). RESULTS: 32 patients had colorectal adenocarcinomas confirmed by histopathology (9 left, 11 right, 4 transverse colon, and 9 rectum). 6 patients had a local initial stage (T1-2) and 26 had a local advanced stage (T3-4). The cancer detection performance of the CNN using 15-fold cross-validation showed high sensitivity and specificity (87% and 90%, respectively) and a ROC-AUC score of 0.95 (considered outstanding). In the T1-2 group, the sensitivity and specificity were 89% and 90%, respectively, and in the T3-4 group, the sensitivity and specificity were 81% and 93%, respectively. CONCLUSIONS: Automatic colorectal cancer detection on fresh specimens using HSI, using a properly trained CNN is feasible and accurate, even with small datasets, regardless of the local tumor extension. In the near future, this approach may become a useful intraoperative tool during oncological endoscopic and surgical procedures, and may result in precise and non-destructive optical biopsies to support objective and consistent tumor-free resection margins.

Near infrared fluorescence imaging of the urethra: a systematic review of the literature.

BACKGROUND: Urethral injury is a dreaded complication during laparoscopic, perineal and transanal surgery and is mainly a result of a failed visualization of the urethra. The aim of this systematic review is to provide an overview of the available literature on the near-infrared fluorescence (NIRF) imaging technique using contrast agents for the intra-operative visualization of the urethra. MATERIAL AND METHODS: A systematic review of the literature was conducted including studies on NIRF imaging using contrast agents to visualize the urethra. All studies describing a NIRF imaging technique and demonstrating visual findings of the urethra were included. RESULTS: Five studies were identified. Four studies examined indocyanine green, one of which also studied the IRDye® 800BK agent and one examined the CP-IRT dye. All studies showed that the NIRF imaging technique was feasible for an early identification of the urethra. No complications related to NIRF imaging were reported. CONCLUSION: We conclude that the use of a NIRF imaging technique is feasible and that it can contribute to prevent iatrogenic injury to the urethra. However, based on the limited available data, no solid conclusion can yet be drawn and further translation to the clinical practice is necessary.

Comparison of hyperspectral imaging and fluorescence angiography for the determination of the transection margin in colorectal resections-a comparative study.

PURPOSE: One relevant aspect for anastomotic leakage in colorectal surgery is blood perfusion of both ends of the anastomosis. The clinical evaluation of this issue is limited, but new methods like fluorescence angiography with indocyanine green or non-invasive and contactless hyperspectral imaging have evolved as objective parameters for perfusion evaluation. METHODS: In this prospective, non-randomized, open-label and two-arm study, fluorescence angiography and hyperspectral imaging were compared in 32 consecutive patients with each other and with the clinical assessment by the surgeon. After preparation of the bowel and determination of the surgical resection line, the tissue was evaluated with hyperspectral imaging for 5 min before and after cutting the marginal artery and assessed by 6 hyperspectral pictures followed by fluorescence angiography with indocyanine green. RESULTS: In 30 of 32 patients, the image data could be evaluated and compared. Both methods provided a comparable borderline between well-perfused and poorly perfused tissue (p = 0.704). In 15 cases, the surgical resection line was shifted to the central position due to the imaging. The border zone was sharper in fluorescence angiography and best assessed 31 s after injection. With hyperspectral imaging, the border zone was visualized wider and with more differences between proximal and distal border. CONCLUSION: Hyperspectral imaging and fluorescence angiography provide similar results in determining the perfusion border. Both methods allow a good and safe visualization of the blood perfusion at the central resection margin to create a well-perfused anastomosis. TRIAL REGISTRATION: This study was registered at Clinicaltrials.gov ( NCT04226781 ) on January 13, 2020.

Precision image-guided colonic surgery: proof of concept for enhanced preoperative and intraoperative vascular imaging.

BACKGROUND: Colorectal surgery has benefited from advances in precision medicine such as total mesorectal resection, and recently, mesocolon resection, fluorescent perfusion imaging, and fluorescent node mapping. However, these advances fail to address the variable quality of mesocolon dissection and the directed extent of vascular dissection (including high ligation) or pre-resection anastomotic perfusion mapping, thereby impacting anastomotic leaks. We propose a new paradigm of precision image-directed colorectal surgery involving 3D preoperative resection modeling and intraoperative fluoroscopic and fluorescence vascular imaging which better defines optimal dissection planes and vascular vs. anatomy-based resection lines according to our hypothesis. METHODS: Six pigs had preoperative CT with vascular 3D reconstruction allowing for the preoperative planning of vascular-based dissection. Laparoscopic surgery was performed in a hybrid operating room (OR). Superselective arterial catheterization was performed in branches of the superior mesenteric artery (SMA) or the inferior mesenteric artery (IMA). Intraoperative boluses of 0.1 mg/kg or a continuous infusion of indocyanine green (ICG) (0.01 mg/mL) were administered to guide fluorescent-based sigmoid and ileocecal resections. Fluorescence was assessed using proprietary software at several regions of interest (ROI) in the right and left colon. RESULTS: The approach was feasible and safe. Selective catheterization took an average of 43 min. Both bolus and continuous perfusion clearly marked pre-identified vessels (arteries/veins) and the target colon segment, facilitating precise resections based on the visible vascular anatomy. Quantitative software analysis indicated the optimal resection margin for each ROI. CONCLUSION: Intra-arterial fluorescent mapping allows visualization of major vascular structures and segmental colonic perfusion. This may help to prevent any inadvertent injury to major vascular structures and to precisely determine perfusion-based resection planes and margins. This could enable tailoring of the amount of colon resected, ensure good anastomotic perfusion, and improve oncological outcomes.

Computer-assisted quantification and visualization of bowel perfusion using fluorescence-based enhanced reality in left-sided colonic resections.

BACKGROUND: Fluorescence-based enhanced reality (FLER) is a computer-based quantification method of fluorescence angiographies to evaluate bowel perfusion. The aim of this prospective trial was to assess the clinical feasibility and to correlate FLER with metabolic markers of perfusion, during colorectal resections. METHODS: FLER analysis and visualization was performed in 22 patients (diverticulitis n = 17; colorectal cancer n = 5) intra- and extra-abdominally during distal and proximal resection, respectively. The fluorescence signal of indocyanine green (0.2 mg/kg) was captured using a near-infrared camera and computed to create a virtual color-coded cartography. This was overlaid onto the bowel (enhanced reality). It helped to identify regions of interest (ROIs) where samples were subsequently obtained. Resections were performed strictly guided according to clinical decision. On the surgical specimen, samplings were made at different ROIs to measure intestinal lactates (mmol/L) and mitochondria efficiency as acceptor control ratio (ACR). RESULTS: The native (unquantified) fluorescent signal diffused to obvious ischemic areas during the distal appreciation. Proximally, a lower diffusion of ICG was observed. Five anastomotic complications occurred. The expected values of local capillary lactates were correlated with the measured values both proximally (3.62 ± 2.48 expected vs. 3.17 ± 2.8 actual; rho 0.89; p = 0.0006) and distally (4.5 ± 3 expected vs. 4 ± 2.5 actual; rho 0.73; p = 0.0021). FLER values correlated with ACR at the proximal site (rho 0.76; p = 0.04) and at the ischemic zone (rho 0.71; p = 0.01). In complicated cases, lactates at the proximal resection site were higher (5.8 ± 4.5) as opposed to uncomplicated cases (2.45 ± 1.5; p = 0.008). ACR was reduced proximally in complicated (1.3 ± 0.18) vs. uncomplicated cases (1.68 ± 0.3; p = 0.023). CONCLUSIONS: FLER allows to image the quantified fluorescence signal in augmented reality and provides a reproducible estimation of bowel perfusion (NCT02626091).

Hyperspectral enhanced reality (HYPER) for anatomical liver resection.

BACKGROUND: Clinical evaluation of the demarcation line separating ischemic from non-ischemic liver parenchyma may be challenging. Hyperspectral imaging (HSI) is a noninvasive imaging modality, which combines a camera with a spectroscope and allows quantitative imaging of tissue oxygenation. Our group developed a software to overlay HSI images onto the operative field, obtaining HSI-based enhanced reality (HYPER). The aim of the present study was to evaluate the accuracy of HYPER to identify the demarcation line after a left vascular inflow occlusion during an anatomical left hepatectomy. MATERIALS AND METHODS: In the porcine model (n = 3), the left branches of the hepatic pedicle were ligated. Before and after vascular occlusion, HSI images based on tissue oxygenation (StO2), obtained through the Near-Infrared index (NIR index), were regularly acquired and superimposed onto RGB video. The demarcation line was marked on the liver surface with electrocautery according to HYPER. Local lactates were measured on blood samples from the liver surface in both ischemic and perfused segments using a strip-based device. At the same areas, confocal endomicroscopy was performed. RESULTS: After ligation, HSI demonstrated a significantly lower oxygenation (NIR index) in the left medial lobe (LML) (0.27% ± 0.21) when compared to the right medial lobe (RML) (58.60% ± 12.08; p = 0.0015). Capillary lactates were significantly higher (3.07 mmol/L ± 0.84 vs. 1.33 ± 0.71 mmol/L; p = 0.0356) in the LML versus RML, respectively. Concordantly, confocal videos demonstrated the absence of blood flow in the LML and normal perfusion in the RML. CONCLUSIONS: HYPER has made it possible to correctly identify the demarcation line and quantify surface liver oxygenation. HYPER could be an intraoperative tool to guide perfusion-based demarcation line assessment and segmentation.

Simultaneous multipurpose fluorescence imaging with IRDye® 800BK during laparoscopic surgery.

BACKGROUND: IRDye® 800BK is a fluorophore, currently undergoing clinical translation, which has both biliary and renal clearance. To date, there is no description of a fluorophore, which can be simultaneously used for non-invasive, near-infrared fluorescence-based (NIRF) visualization of different structures and perfusion evaluation. The purpose of this study was to evaluate IRDye® 800BK for the simultaneous assessment of bowel perfusion, lymphography, ureter and bile duct delineation. METHODS: Six pigs received a 0.15 mg/kg dye as a single bolus intravenous injection (IV). With the FLER (fluorescence-based enhanced reality) software, fluorescence intensity (FI) of 5 regions of interest (ROI) in an ischemic bowel loop was measured along with the time to reach the FI peak, and capillary lactate was measured from the same ROI, followed by the assessment of the ureters and bile ducts for a maximal duration of 180 min after dye administration. In 3 animals, the procedure was initiated via gastroscopic injection of a 0.6 mg (1 mg/mL) dye in the gastric submucosa followed by lymphography in a NIRF setting. RESULTS: Excellent visualization of the ureters and bowel perfusion was obtained under NIRF imaging. Additionally, the bile duct and gastric lymph ducts and nodes were visualized. A positive correlation was found between the time to peak FI in the ischemic bowel loop and the corresponding capillary lactate levels (rho 0.59, p < 0.001). CONCLUSION: In this study, we successfully demonstrated the simultaneous multipurpose IRDye® 800BK applicability during laparoscopic surgery. This fluorophore has the potential to become a powerful and versatile image-guided surgery tool.

Preoperative endoscopic marking of the gastrointestinal tract using fluorescence imaging: submucosal indocyanine green tattooing versus a novel fluorescent over-the-scope clip in a survival experimental study.

BACKGROUND: Intraoperative localization of endoluminal lesions is can be difficult during laparoscopy. Preoperative endoscopic marking is therefore necessary. Current methods include submucosal tattooing using visible dyes, which in case of transmural injection can impair surgical dissection. Tattooing using indocyanine green (ICG) coupled to intraoperative near-infrared (NIR) laparoscopy has been described. ICG is only visible under NIR-light, therefore, it doesn't impair the surgical workflow under white light even if there is spillage. However, ICG tattoos have rapid diffusion and short longevity. We propose fluorescent over-the-scope clips (FOSC), using a novel biocompatible fluorescent paint, as durable lesion marking. METHODS: In six pigs, gastric and colonic endoscopic tattoos using 0.05 mg/mL of ICG and markings using the fluorescent OSC were performed (T0). Simultaneously, NIR laparoscopy was executed. Follow-up laparoscopies were conducted at postoperative day (POD) 4-6 (T1) and POD 11-12 (T2). During laparoscopy, fluorescence intensity was assessed. In one human cadaver, FOSC was used to mark a site on the stomach and on the sigmoid colon, respectively. Intraoperative detection during NIR laparoscopy was assessed. RESULTS: Gastric and colonic ICG tattooing and OSC markings were easily visible using NIR laparoscopy on T0. All FOSC were visible at T1 and T2 in both stomach and colon, whereas the ICG tattooing at T1 was only visible in the stomach of 2 animals and in the colon of 3 animals. At T2, tattoos were not visible in any animal. FOSC were still visible in both stomach and colon of the human cadaver at 10 days. CONCLUSION: Endoscopic marking using FOSC can be an efficient and durable alternative to standard methods.

Quantitative serosal and mucosal optical imaging perfusion assessment in gastric conduits for esophageal surgery: an experimental study in enhanced reality.

INTRODUCTION/OBJECTIVE: Gastric conduit (GC) is used for reconstruction after esophagectomy. Anastomotic leakage (AL) incidence remains high, given the extensive disruption of the gastric circulation. Currently, there is no reliable method to intraoperatively quantify gastric perfusion. Hyperspectral imaging (HSI) has shown its potential to quantify serosal StO2. Confocal laser endomicroscopy (CLE) allows for automatic mucosal microcirculation quantification as functional capillary density area (FCD-A). The aim of this study was to quantify serosal and mucosal GC's microperfusion using HSI and CLE. Local capillary lactate (LCL) served as biomarker. METHODS: GC was formed in 5 pigs and serosal StO2% was quantified at 3 regions of interest (ROI) using HSI: fundus (ROI-F), greater curvature (ROI-C), and pylorus (ROI-P). After intravenous injection of sodium-fluorescein (0.5 g), CLE-based mucosal microperfusion was assessed at the corresponding ROIs, and LCLs were quantified via a lactate analyzer. RESULTS: StO2 and FCD-A at ROI-F (41 ± 10.6%, 3.3 ± 3.8, respectively) were significantly lower than ROI-C (68.2 ± 6.7%, p value: 0.005; 18.4 ± 7, p value: 0.01, respectively) and ROI-P (72 ± 10.4%, p value: 0.005; 15.7 ± 3.2 p value: 0.001). LCL value at ROI-F (9.6 ± 4.7 mmol/L) was significantly higher than at ROI-C (2.6 ± 1.2 mmol/L, p value: 0.04) and ROI-P (2.6 ± 1.3 mmol/L, p value: 0.04). No statistically significant difference was found in all metrics between ROI-C and ROI-P. StO2 correlated with FCD-A (Pearson's r = 0.67). The LCL correlated negatively with both FCD-A (Spearman's r = - 0.74) and StO2 (Spearman's r = - 0.54). CONCLUSIONS: GC formation causes a drop in serosal and mucosal fundic perfusion. HSI and CLE correlate well and might become useful intraoperative tools.

Dual Color Imaging from a Single BF2-Azadipyrromethene Fluorophore Demonstrated in vivo for Lymph Node Identification.

Dual emissions at ~700 and 800 nm have been achieved from a single NIR-AZA fluorophore 1 by establishing parameters in which it can exist in either its isolated molecular or aggregated states. Dual near infrared (NIR) fluorescence color lymph node (LN) mapping with 1 was achieved in a large-animal porcine model, with injection site, channels and nodes all detectable at both 700 and 800 nm using a preclinical open camera system. The fluorophore was also compatible with imaging using two clinical instruments for fluorescence guided surgery. Methods: An NIR-AZA fluorophore with hydrophilic and phobic features was synthesised in a straightforward manner and its aggregation properties characterised spectroscopically and by TEM imaging. Toxicity was assessed in a rodent model and dual color fluorescence imaging evaluated by lymph node mapping in a large animal porcine models and in ex-vivo human tissue specimen. Results: Dual color fluorescence imaging has been achieved in the highly complex biomedical scenario of lymph node mapping. Emissions at 700 and 800 nm can be achieved from a single fluorophore by establishing molecular and aggregate forms. Fluorophore was compatible with clinical systems for fluorescence guided surgery and no toxicity was observed in high dosage testing. Conclusion: A new, biomedical compatible form of NIR-dual emission wavelength imaging has been established using a readily accessible fluorophore with significant scope for clinical translation.

[New intraoperative fluorescence-based and spectroscopic imaging techniques in visceral medicine - precision surgery in the "high tech"-operating room]. / Neue intraoperative fluoreszenzbasierte und spektroskopische Bildgebungsverfahren in der Viszeralmedizin ­ Präzisionschirurgie im "Hightech"-OP.

INTRODUCTION: Fluorescence angiography (FA) with indocyanine green (ICG) and hyperspectral imaging (HSI) are novel intraoperative visualization techniques in abdominal, vascular and transplant surgery. With the purpose of precision surgery, and in order to increase patient's safety, these new tools aim at reducing postoperative morbidity and mortality. This review discusses and highlights recent developments and the future potential of real-time imaging modalities. METHODS: The underlying mechanisms of the novel imaging methods and their clinical impact are displayed in the context of avoiding anastomotic leaks, the most momentous complications in gastrointestinal surgery after oncologic resections. RESULTS: While FA is associated with the admission of a fluorescence agent, HSI is contact-free and non-invasive. Both methods are able to record physiological tissue properties in real-time. Additionally, FA also measures dynamic phenomena. The techniques take a few seconds only and do not hamper the operative workflow considerably. With regard to a potential change of the surgical strategy, FA and HSI have an equal significance. Our own advancements reflect, in particular, the topics of data visualization and automated data analyses together with the implementation of artificial intelligence (AI) and minimalization of the current devices to install them into endoscopes, minimal-invasive and robot-guided surgery. CONCLUSION: There are a limited number of studies in the field of intraoperative imaging techniques. Whether precision surgery in the "high-tech" OR together with FA, HSI and robotics will result in more secure operative procedures to minimize the postoperative morbidity and mortality will have to be evaluated in future multicenter trials.

Hyperspectral Imagery for Assessing Laser-Induced Thermal State Change in Liver.

This work presents the potential of hyperspectral imaging (HSI) to monitor the thermal outcome of laser ablation therapy used for minimally invasive tumor removal. Our main goal is the establishment of indicators of the thermal damage of living tissues, which can be used to assess the effect of the procedure. These indicators rely on the spectral variation of temperature-dependent tissue chromophores, i.e., oxyhemoglobin, deoxyhemoglobin, methemoglobin, and water. Laser treatment was performed at specific temperature thresholds (from 60 to 110 °C) on in-vivo animal liver and was assessed with a hyperspectral camera (500-995 nm) during and after the treatment. The indicators were extracted from the hyperspectral images after the following processing steps: the breathing motion compensation and the spectral and spatial filtering, the selection of spectral bands corresponding to specific tissue chromophores, and the analysis of the areas under the curves for each spectral band. Results show that properly combining spectral information related to deoxyhemoglobin, methemoglobin, lipids, and water allows for the segmenting of different zones of the laser-induced thermal damage. This preliminary investigation provides indicators for describing the thermal state of the liver, which can be employed in the future as clinical endpoints of the procedure outcome.

Prediction of In Vivo Laser-Induced Thermal Damage with Hyperspectral Imaging Using Deep Learning.

Thermal ablation is an acceptable alternative treatment for primary liver cancer, of which laser ablation (LA) is one of the least invasive approaches, especially for tumors in high-risk locations. Precise control of the LA effect is required to safely destroy the tumor. Although temperature imaging techniques provide an indirect measurement of the thermal damage, a degree of uncertainty remains about the treatment effect. Optical techniques are currently emerging as tools to directly assess tissue thermal damage. Among them, hyperspectral imaging (HSI) has shown promising results in image-guided surgery and in the thermal ablation field. The highly informative data provided by HSI, associated with deep learning, enable the implementation of non-invasive prediction models to be used intraoperatively. Here we show a novel paradigm "peak temperature prediction model" (PTPM), convolutional neural network (CNN)-based, trained with HSI and infrared imaging to predict LA-induced damage in the liver. The PTPM demonstrated an optimal agreement with tissue damage classification providing a consistent threshold (50.6 ± 1.5 °C) for the damage margins with high accuracy (~0.90). The high correlation with the histology score (r = 0.9085) and the comparison with the measured peak temperature confirmed that PTPM preserves temperature information accordingly with the histopathological assessment.

Fluorescence-enabled assessment of adrenal gland localization and perfusion in posterior retroperitoneoscopic adrenal surgery in a preclinical model.

BACKGROUND: The posterior retroperitoneoscopic adrenal access represents a challenge in orientation and working space creation. The aim of this experimental acute study was to evaluate the impact of computer-assisted quantitative fluorescence imaging on adrenal gland identification and assessment of intraoperative remnant perfusion for adrenal resection in the posterior retroperitoneoscopic approach. METHODS: Six pigs underwent simultaneous (n = 5) or sequential (n = 1) bilateral posterior retroperitoneoscopic adrenalectomy (n = 12). Fluorescence imaging was obtained via intravenous administration of 3 mL of Indocyanine Green (ICG) and by switching the camera systems to near-infrared mode (D-LIGHT P, KARL STORZ; Germany). Fluorescence-based visualization of adrenal glands before vascular division (n = 4), after the main vascular pedicle ligation (negative control, n = 1) or after adrenal resection (n = 7), was followed by completion adrenalectomy. The fluorescence signal intensity dynamics were recorded and analyzed using proprietary software. For each pixel, the slope of fluorescence signal intensity evolution over time was translated into a color-coded perfusion cartography, which was superimposed onto real-time images obtained with the corresponding left and right camera systems. Quantitative fluorescence signal analysis in the regions of interest (ROIs) served to assess adrenal remnant perfusion in divided adrenal glands. RESULTS: In the retroperitoneum, the vascular anatomy was illuminated in fluorescence imaging first. The adrenal glands were promptly highlighted after primary intravenous ICG administration (n = 9) or showed a fluorescence signal intensity increase upon reinjection (n = 3). Quantitative fluorescence analysis showed a statistically significant difference between perfused and ischemic segments in divided glands (p = 0.0156). CONCLUSIONS: Fluorescence imaging provides real-time guidance during minimally invasive adrenal surgery. Prior to dissection, it allows to easily discriminate the adrenal gland from surrounding retroperitoneal structures. After adrenal gland division, ICG injection associated with a computer-assisted quantitative analysis helps to distinguish between well-perfused and ischemic segments. Further studies are underway to establish the correlation between remnant perfusion and viability.

HYPerspectral Enhanced Reality (HYPER): a physiology-based surgical guidance tool.

BACKGROUND: HSI is an optical technology allowing for a real-time, contrast-free snapshot of physiological tissue properties, including oxygenation. Hyperspectral imaging (HSI) has the potential to quantify the gastrointestinal perfusion intraoperatively. This experimental study evaluates the accuracy of HSI, in order to quantify bowel perfusion, and to obtain a superposition of the hyperspectral information onto real-time images. METHODS: In 6 pigs, 4 ischemic bowel loops were created (A, B, C, D) and imaged at set time points (from 5 to 360 min). A commercially available HSI system provided pseudo-color maps of the perfusion status (StO2, Near-InfraRed perfusion) and the tissue water index. An ad hoc software was developed to superimpose HSI information onto the live video, creating the HYPerspectral-based Enhanced Reality (HYPER). Seven regions of interest (ROIs) were identified in each bowel loop according to StO2 ranges, i.e., vascular (VASC proximal and distal), marginal vascular (MV proximal and distal), marginal ischemic (MI proximal and distal), and ischemic (ISCH). Local capillary lactates (LCL), reactive oxygen species (ROS), and histopathology were measured at the ROIs. A machine-learning-based prediction algorithm of LCL, based on the HSI-StO2%, was trained in the 6 pigs and tested on 5 additional animals. RESULTS: HSI parameters (StO2 and NIR) were congruent with LCL levels, ROS production, and histopathology damage scores at the ROIs discriminated by HYPER. The global mean error of LCL prediction was 1.18 ± 1.35 mmol/L. For StO2 values > 30%, the mean error was 0.3 ± 0.33. CONCLUSIONS: HYPER imaging could precisely quantify the overtime perfusion changes in this bowel ischemia model.