OBJECTIVE: The current established technique for sentinel lymph node (SLN) biopsy is preoperative injection of 99mtechnetium-labeled nanosized colloids (99mTc) followed by single photon emission computed tomography and standard computed tomography (SPECT/CT) with subsequent intraoperative gamma probe-guided excision of the SLN. It is however time and resource consuming, causes radiation exposure and morbidity for the patient as the injection is done in the awake patient. Recently near-infrared imaging with indocyanine green (ICG) gained importance in SLN biopsy as a faster and more convenient technique. The objective of our study was to investigate the feasibility of SLN biopsy using ICG-imaging in early oral squamous cell carcinoma (OSCC).
METHODS: Single-centre pilot study of five patients with early-stage OSCC. For all patients, both techniques (99mTc and ICG) were performed. We injected 99mTc preoperatively in the awake patient, followed by SPECT/CT imaging. Intraoperatively ICG was injected around the primary tumor. Then the neck incision was performed according to the SPECT/CT images and SLN were detected by using a gamma probe and near-infrared fluorescence imaging of the ICG-marked lymph nodes intraoperatively. The excised lymph nodes were sent to histopathological examination according to the SLN dissection protocol.
RESULTS: In all five patients sentinel lymph nodes were identified. A total of 7 SLN were identified after injection of 99mTc, imaging with SPECT/CT and intraoperative use of a gamma probe. All these SLN were fluorescent and visible with the ICG technique. In two patients, we could identify additional lymph nodes using the ICG technique. Pathological analysis demonstrated occult metastasis in two of the cases.
CONCLUSIONS: Our study shows that ICG-guided SLN biopsy is a feasible technique, especially in combination with conventional radioisotope method and may help for intraoperative localization of SLN. Validation studies with bigger patient cohorts are needed to prove our results.

BACKGROUND: The accuracy and precision of patient position in radiotherapy process have dramatic impacts on the tumor local control and therapy-related side effects, and there exist demands to explore effective positioning solutions, particularly in the era with great progress in imaging recognition and matching.
OBJECTIVE: Superficial vessel-based near infrared-assisted patient position recognition and real-time monitoring system (VIPS) was proposed to develop an automated, operator-independent and skin marker-free imaging system to improve patient setup and intrafractional motion monitoring.
METHODS: VIPS includes two components, the imaging module and the image alignment software. Using a simulated blood vessel model, multiple NIR sources with various wavelength and bolus (pseudo-skin) were evaluated in terms of imaging quality to determine the optimal light source and the upper limit of superficial fatty tissue thickness. Then the performance of VIPS with reference to either CBCT or laser setup system was conducted using 3D phantom and clinical cases enrolled into the registered clinical trial. The position displacement from VIPS and laser system was compared, as well as the systematic and random errors of VIPS setup procedure.
RESULTS: The NIR light source with the combined wavelengths of 760 nm + 940 nm (S760+940 nm ) provided the best performance among multiple tested light sources. The bolus (superficial fatty layer) thickness over 5 mm could dramatically compromise the NIR detection of vessels beneath. In the phantom study, the translational positional displacements according to VIPS guidance were within the submillimeter level with reference to CBCT, indicative of high setup accuracy. The clinical trial showed the prototype VIPS could effectively detect and control position displacement of patients in translational and rotational directions within an acceptable range, which was non-inferior to conventional laser/skin marker system.
CONCLUSIONS: This proof-of-concept study validated the feasibility and reliability of VIPS in guiding radiotherapy setup. However, limitations and technical challenges should be resolved prior to further clinical evaluation, including isocenter alignment, potential NIR image distortion and the impact of the superficial tissues on the recognition of vessels.

Fluorescence-guided surgery can aid in the intraoperative visualization of target tissues, with promising applications in human and veterinary surgical oncology. The aim of this study was to evaluate the performances of two fluoresce camera systems, IC-FlowTM and VisionsenseTM VS3 Iridum, for the detection of two non-targeted (ICG and IRDye-800) and two targeted fluorophores (AngiostampTM and FAP-Cyan) under different room light conditions, including ambient light, new generation LED, and halogen artificial light sources, which are commonly used in operating theaters. Six dilutions of the fluorophores were imaged in phantom kits using the two camera systems. The limit of detection (LOD) and mean signal-to-background ratio (mSBR) were determined. The highest values of mSBR and a lower LOD were obtained in dark conditions for both systems. Under room lights, the capabilities decreased, but the mSBR remained greater than 3 (=clearly detectable signal). LOD and mSBR worsened under surgical lights for both camera systems, with a greater impact from halogen bulbs on VisionsenseTM VS3 Iridium and of the LED lights on IC-Flow due to a contribution of these lights in the near-infrared spectrum. When considering implementing FGS into the clinical routine, surgeons should cautiously evaluate the spectral contribution of the lights in the operating theater.

Medical diagnosis heavily relies on the use of bio-imaging techniques. One such technique is the use of ICG-based biological sensors for fluorescence imaging. In this study, we aimed to improve the fluorescence signals of ICG-based biological sensors by incorporating liposome-modified ICG. The results from dynamic light scattering and transmission electron microscopy showed that MLM-ICG was successfully fabricated with a liposome diameter of 100-300 nm. Fluorescence spectroscopy showed that MLM-ICG had the best properties among the three samples (Blank ICG, LM-ICG, and MLM-ICG), as samples immersed in MLM-ICG solution achieved the highest fluorescence intensity. The NIR camera imaging also showed a similar result. For the rat model, the best period for fluorescence tests was between 10 min and 4 h, where most organs reached their maximum fluorescence intensity except for the liver, which continued to rise. After 24 h, ICG was excreted from the rat\'s body. The study also analyzed the spectra properties of different rat organs, including peak intensity, peak wavelength, and FWHM. In conclusion, the use of liposome-modified ICG provides a safe and optimized optical agent, which is more stable and efficient than non-modified ICG. Incorporating liposome-modified ICG in fluorescence spectroscopy could be an effective way to develop novel biosensors for disease diagnosis.

Bladder cancer is the fifth most common malignancy in humans. Cystoscopy under white light imaging is the gold standard for bladder cancer diagnosis, but some tumors are difficult to visualize and can be overlooked, resulting in high recurrence rates. We previously developed a phage display-derived peptide-based near-infrared imaging probe, PLSWT7-DMI, which binds specifically to bladder cancer cells and is nontoxic to animals. Here, we report a clinical research of this probe for near-infrared fluorescence endoscopic detection of bladder cancer.
The purity, efficacy, safety, and nontoxicity of PLSWT7-DMI were confirmed prior to its clinical application. Twenty-two patients diagnosed with suspected non-muscle invasive bladder cancer were enrolled in the present study. Following intravesical administration of the probe, the entire mucosa was imaged under white and near-infrared imaging using an in-house developed endoscope that could switch between these two modes. The illuminated lesions under near-infrared light were biopsied and sent for histopathological examination. We observed a 5.1-fold increase in the fluorescence intensity in the tumor samples compared to normal tissue, and the probe demonstrated a sensitivity and specificity of 91.2% and 90%, respectively. Common diagnostic challenges, such as small satellite tumors, carcinoma in situ, and benign suspicious mucosa, were visualized and could be distinguished from cancer. Furthermore, no adverse effects were observed in humans. These first-in-human results indicate that PLSWT7-DMI-based near-infrared fluorescence endoscopy is a safe and effective approach for the improved detection of bladder cancer, and may enable thorough resection to prevent recurrence.

BACKGROUND: A current challenge for endometriosis surgery is to correctly identify the localizations of disease, especially when small or hidden (occult endometriosis), and to exactly define their real extension. The use of near-infrared radiation imaging (NIR) after injection of indocyanine green (ICG) represents one of the most encouraging method. The aim of this study is to assess the diagnostic value of NIR-ICG imaging in the surgical treatment of endometriosis compared with the standard of treatment.
METHODS: The Gre-Endo trial is a prospective, single-arm study (NCT03332004). After exploring the operatory field using the white light (WL) mode, patients were injected with ICG and then observed in NIR mode. All suspected areas were classified and chronicled according to lesions visualized only in WL, NIR-ICG, or in the combination of both. Lesion not visualized in WL was considered as suspect occult lesion (s-OcL). In addition, a random control biopsy from an apparent negative peritoneum visualized in WL and NIR-ICG imaging was taken for all patients (control cases). All lesions removed were considered \"suspect endometriosis\" until pathology.
RESULTS: Fifty-one patients were enrolled between January 2016 and October 2019. A total of 240 suspected lesions have been identified with both methods (WL + NIR-ICG). Two hundred and seven (86.2%) lesions out of the overall 240 were visualized with WL imaging, and 200 were confirmed to be pathologic (true positive for WL). The remaining 33/240 (13.75%) (false negative for WL) lesions were identified only with NIR-ICG imaging and collected as s-OcL. All 33 s-OcLs removed were confirmed to be pathologic (c-OcL = 100%). NIR-ICG vision showed PPV of 98.5%, NPV of 87.1%, Se of 87%, and Sp of 98.5%, confirming that this kind of imaging is an excellent diagnostic and screening test (p = 0.001 and p = 0.835, according to McNemar\'s and Cohen\'s kappa tests, respectively).
CONCLUSIONS: The use of NIR-ICG vision alone and combined with WL showed good results in intraoperative detection rate and fluorescence-guided surgery of endometriosis. Furthermore, NIR-ICG allowed surgeons to remove occult lesions that otherwise would remain, leading to possible greater postoperative pain and a higher risk of persistence and relapse.

UNASSIGNED: Fluorescent cholangiography (FC) during laparoscopic cholecystectomy (LC) is a novel method to facilitate real-time visualization of extrahepatic biliary structures that avoiding risk of bile duct injury. Aims of this study are to investigate the feasibility and the safety of FC during LC.
UNASSIGNED: We evaluated the outcomes of FC during elective LC at our hospital from August 2017 to April 2018. Fifty-five patients who underwent FC during elective LC were enrolled in this study. Demographic and peri-operative data were recorded and analyzed. The primary endpoints were visualization rate of FC during LC. The secondary endpoint was the optimal conditions and technical details for FC included to detect any potential adverse event.
UNASSIGNED: The visualization rate after FC of the cystic duct, common hepatic duct and common bile duct were increased significantly compared to before FC. The identification rate of the cystic duct and common bile duct were not associated with BMI and history of acute cholecystitis.
UNASSIGNED: FC enabled real-time visualization of extrahepatic biliary structures during LC. FC appears to be a safe and efficient approach for elective LC.

UNASSIGNED: This study aimed to evaluate the clinical value of indocyanine green sentinel lymph node (SLN) mapping in patients with vulvar cancer. The conventional procedure of SLN mapping in vulvar cancer includes peritumoral injection of technetium-99m nanocolloid before surgery and intraoperative injection of a blue dye. However, these techniques harbor some limitations. Near-infrared fluorescence imaging with indocyanine green has gained popularity in SLN mapping in different types of cancer.
UNASSIGNED: We analyzed retrospectively vulvar cancer patients at our institution between 2013 and 2020 undergoing indocyanine green SLN mapping by applying video telescope operating microscope system technology.
UNASSIGNED: 64 groins of 34 patients were analyzed. In 53 groins we used technetium-99m nanocolloid, in four patent blue, and in five both techniques, additionally to indocyanine green for SLN detection. In total, 120 SLNs were identified and removed. The SLN detection rate of indocyanine green was comparable to technetium-99m nanocolloid (p=.143) and higher than patent blue (p=.003). The best results were achieved using a combination of ICG and technetium-99m nanocolloid (detection rate of 96.9%). SLN detection rates of indocyanine green were significantly higher in patients with positive lymph nodes (p=.035) and lymphatic space invasion (p=.004) compared to technetium-99m nanocolloid.
UNASSIGNED: Indocyanine green SLN mapping in vulvar cancer is feasible and safe, with reasonable detection rates. Due to its easy application and few side effects, it offers a sound alternative to the conventional SLN mapping techniques in vulvar cancer. In patients with lymph node metastasis, indocyanine green even outperformed technetium-99m nanocolloid in terms of detection rate.

The aim of this study was to develop a low-cost prototype near-infrared fluorescence device that enables contrast-free, real time, high-resolution intraoperative visualization of normal and pathological parathyroid glands (PGs) by imaging their autofluorescence (AF).
A novel near-infrared parathyroid AF (NIR-PAF) imaging device with visible laser PG targeting was developed. The device was evaluated during parathyroid and thyroid operations in a pilot clinical study.
Overall, of the 6 parathyroidectomies carried out in the study population a parathyroid adenoma was found to exhibit AF ex vivo in 6/6 (100%) of cases, and in vivo in 3/3 (100%) of these cases. Two of 4 thyroidectomies were evaluated in vivo and all PGs (6 PGs total) were identified by the NIR-PAF device. The NIRPAF device cost less than $1200 Canadian to build.
The inexpensive NIR-PAF device that we developed can successfully intraoperatively identify both normal and pathological PGs.

To evaluate feasibility of near-infrared (NIR)-indocyanine green (ICG) imaging for bowel vascularization assessment after full-thickness bowel resection for rectosigmoid endometriosis (RSE).
This is a prospective, single-center, preliminary study on consecutive patients who were symptomatic submitted to discoid or segmental resection for RSE and NIR-ICG evaluation for vascular assessment of the anastomotic line from May 2018 to January 2020.
Tertiary university hospital.
Thirty-two women with RSE meeting eligibility criteria were included for study analysis.
NIR-ICG evaluation of anastomotic line vascularization after RSE removal.
Fluorescence degree of the anastomotic line was assessed with a 0 to 2 Likert scale, as follows: 0 or \"absent\" (no fluorescence observed), 1 or \"irregular\" (not uniform distribution or weak fluorescence), and 2 or \"regular\" (uniform distribution of fluorescence and similar to the proximal colon). In all the patients included in the study (100%), NIR-ICG imaging allowed the evaluation of fluorescence degree of the anastomotic line. No adverse reaction related to ICG use was recorded. The protocol did not greatly lengthen operating time (median, 4 [range, 3-5] minutes). Excellent interoperator agreement was observed. Most of the patients (31 of 32, 96.9%) showed regular fluorescence on the anastomotic line; in 1 patient with irregular fluorescence at NIR-ICG after discoid excision, the anastomotic suture was reinforced through interrupted stitches. We had 1 case of anastomotic leakage after segmental resection with intraoperative good fluorescence at NIR-ICG evaluation.
NIR-ICG imaging for anastomotic perfusion assessment after discoid or segmental resection for RSE seems to be a feasible, safe, and reproducible method.