NIR-II light in clinical oncology: opportunities and challenges.

Novel strategies utilizing light in the second near-infrared region (NIR-II; 900-1,880 nm wavelengths) offer the potential to visualize and treat solid tumours with enhanced precision. Over the past few decades, numerous techniques leveraging NIR-II light have been developed with the aim of precisely eliminating tumours while maximally preserving organ function. During cancer surgery, NIR-II optical imaging enables the visualization of clinically occult lesions and surrounding vital structures with increased sensitivity and resolution, thereby enhancing surgical quality and improving patient prognosis. Furthermore, the use of NIR-II light promises to improve cancer phototherapy by enabling the selective delivery of increased therapeutic energy to tissues at greater depths. Initial clinical studies of NIR-II-based imaging and phototherapy have indicated impressive potential to decrease cancer recurrence, reduce complications and prolong survival. Despite the encouraging results achieved, clinical translation of innovative NIR-II techniques remains challenging and inefficient; multidisciplinary cooperation is necessary to bridge the gap between preclinical research and clinical practice, and thus accelerate the translation of technical advances into clinical benefits. In this Review, we summarize the available clinical data on NIR-II-based imaging and phototherapy, demonstrating the feasibility and utility of integrating these technologies into the treatment of cancer. We also introduce emerging NIR-II-based approaches with substantial potential to further enhance patient outcomes, while also highlighting the challenges associated with imminent clinical studies of these modalities.

Applications of Near-Infrared Fluorescence Imaging and Angiography of Inferior Vesical Artery in Laparoscopic Lateral Lymph Node Dissection: A Prospective Nonrandomized Controlled Study.

BACKGROUND: Near-infrared imaging with indocyanine green has been used to guide lateral lymph node dissection, yet its efficacy and benefits need further investigation. OBJECTIVE: To investigate the efficacy and feasibility of near-infrared fluorescence imaging and angiography of the inferior vesical artery in laparoscopic lateral lymph node dissection. DESIGN: A prospective nonrandomized controlled study. SETTINGS: Single-center study. PATIENTS: Patients with lower rectal cancer who underwent total mesorectal excision plus lateral lymph node dissection. MAIN OUTCOME MEASURES: A cohort of 108 patients was enrolled. After propensity score matching, 29 patients in the near-infrared group and 50 patients in the non-near-infrared group were matched. The total number of harvested lateral lymph nodes, positive lateral lymph nodes, inferior vesical artery preservation, and postoperative urinary function were compared. RESULTS: After propensity score matching, both groups had similar baseline characteristics. The total number of harvested lateral lymph nodes in the near-infrared group was significantly higher (12 vs 9, p = 0.013), but positive lateral lymph nodes were similar between the 2 groups (1 vs 1, p = 0.439). The inferior vesical artery preservation ratio was significantly increased with the aid of indocyanine green angiography (93.1% vs 56.0%, p < 0.001). The non-near-infrared group required more days for urinary catheter removal than the near-infrared group (5 vs 4, p = 0.046). Urinary recatheterization tended to occur more frequently in the non-near-infrared group, with a marginally significant trend (16% vs 0%, p = 0.059). The non-near-infrared group tended to have more cases with residual urine volume ≥50 mL than the near-infrared group (20.0% vs 3.4%, p = 0.087), especially in the bilateral dissection subgroup (41.2% vs 0%, p = 0.041). LIMITATIONS: Small sample size. CONCLUSIONS: Near-infrared imaging increased the number of harvested lateral lymph nodes, whereas real-time indocyanine green fluorescence angiography ensured the preservation of the inferior vesical artery and tended to improve postoperative urinary function.

Efficacy of Near-Infrared Fluorescence Video-Assisted Thoracoscopic Surgery for Small Pulmonary Nodule Resection with Indocyanine Green Inhalation: A Randomized Clinical Trial.

BACKGROUND: Small pulmonary nodules (<3 cm) can sometimes be unrecognizable and nonpalpable in video-assisted thoracoscopic surgery (VATS). Near-infrared fluorescence (NIF) VATS after indocyanine green (ICG) inhalation may effectively guide surgeons to locate the nodules. OBJECTIVE: This study aimed to investigate the safety, feasibility, and efficacy of ICG inhalation-based NIF imaging for guiding small pulmonary nodule resections. METHODS: Between February and May 2021, the first-stage, non-randomized trial enrolled 21 patients with different nodule depth, ICG inhalation doses, post-inhalation surgery times, and nodule types at a tertiary referral hospital. Between May 2021 and May 2022, the second-stage randomized trial enrolled 56 patients, who were randomly assigned to the fluorescence VATS (FLVATS) or the white-light VATS (WLVATS) group. The ratio of effective guidance and the time consumption for nodule localization were compared. RESULTS: The first-stage trial proved this new method is safe and feasible, and established a standardized protocol with optimized nodule depth (≤1 cm), ICG dose (0.20-0.25 mg/kg), and surgery window (50-90 min after ICG inhalation). In the second-stage trial, the FLVATS achieved 87.1% helpful nodule localization guidance, which was significantly higher than the WLVATS (59.1%, p < 0.05). The mean nodule locating time (standard deviation) was 1.8 [0.9] and 3.3 [2.3] min, respectively. Surgeons adopting FLVATS were significantly faster (p < 0.01), especially when locating small ground-glass opacities (1.3 [0.6] min vs. 7.0 [3.5] min, p < 0.05). Five of 31 nodules (16.1%) were only detectable by FLVATS, whereas both white light and palpation failed. CONCLUSIONS: This new method is safe and feasible for small pulmonary nodule resection. It significantly improves nodule localization rates with less time consumption, and hence is highly worthy for clinical promotion. Clinical Trial Registration Chinese Clinical Trial Registry Identifier: ChiCTR2100047326.

Indocyanine green inhalation visualizes lung tumour during video-assisted thoracoscopic surgery.

OBJECTIVES: Accurate intraoperative identification of small lung tumours is crucial for precise resection of these lesions during video-assisted thoracoscopic surgery. This study aimed to evaluate the feasibility and safety of indocyanine green (ICG) inhalation for intraoperative visualization of lung tumours. METHODS: From January 2022 to May 2022, 43 patients with lung nodules were included into this study. All patients received intraoperative ICG inhalation for visualization of lung tumours under near-infrared imaging. The primary outcomes of this trial were the detection rate and background-tumour ratio of lung nodules, and the secondary objectives were time to search for nodules and operative time to nodules excision. RESULTS: A total of 50 pulmonary nodules in 43 patients were identified and completely resected. And 44 lung nodules were detected during intraoperative fluorescent exploration with a median inhaled ICG dose of 18.8 mg. In vivo, the median background-tumour ratio was 7.10. The median detection time of nodules was 100 s and the median operative time to nodules excision was 18 min. Quantification analysis showed that the fluorescence intensity of postoperative sputum declined to ∼10% of the first fluorescent sputum within 20 h. No adverse events attributed to ICG inhalation were recorded during the follow-up period. CONCLUSIONS: Intraoperative inhalation of ICG was a feasible and safe method for detection of lung tumours at low dose of ICG. This technique could be a remedial measure for identification of unpalpable lung nodules without preoperative localization. TRIAL REGISTRATION: Chinese Clinical Trial Registry, Identifier: ChiCTR2100053708.

Intraoperative Fluorescence Visualization in Thoracoscopic Surgery.

We report a clinical case of using indocyanine green inhalation to achieve intraoperative near-infrared fluorescence visualization of pulmonary ground-glass opacity in thoracoscopic wedge resection. The patient underwent thoracoscopic wedge resection under the real-time navigation of a near-infrared fluorescence imaging system with the indocyanine green inhalation performed 85 minutes before the surgery. The nebulized inhalation of indocyanine green (dose of 0.25 mg/kg) successfully guided surgeons to localize the small ground-glass opacity due to a filling defect of the fluorescence. The thoracoscopic near-infrared fluorescence navigation system delineated the tumor margin with high contrast and helped to minimize the damage to lung function.

Near-infrared fluorescence imaging of thoracic duct in minimally invasive esophagectomy.

Chylothorax is a serious complication after esophagectomy and there are unmet needs for new intraoperative navigation tools to reduce its incidence. The aim of this study is to explore the feasibility and effectiveness of near-infrared fluorescence imaging (NIR-FI) with indocyanine green (ICG) to identify thoracic ducts (TDs) and chyle leakage during video-assisted thoracoscopic esophagectomy. We recruited 41 patients who underwent thoraco-laparoscopic minimally invasive esophagectomy (MIE) for esophageal cancer in this prospective, open-label, single-arm clinical trial. ICG was injected into the right inguinal region before operations, after which TD anatomy and potential chyle leakage were checked under the near-infrared fluorescence intraoperatively. In 38 of 41 patients (92.7%) using NIR-FI, TDs were visible in high contrast. The mean signal-to-background ratio (SBR) value of all fluorescent TDs was 3.05 ± 1.56. Fluorescence imaging of TDs could be detected 0.5 hours after ICG injection and last up to 3 hours with an acceptable SBR value. The optimal observation time window is from about 1 to 2 hours after ICG injection. Under the guidance of real-time NIR-FI, three patients were found to have chylous leakage and the selective TD ligations were performed intraoperatively. No patient had postoperative chylothorax. NIR-FI with ICG can provide highly sensitive and real-time assessment of TDs as well as determine the source of chyle leakage, which might help reduce TD injury and direct selective TD ligation. It could be a promising navigation tool to reduce the incidence of chylothorax after minimally invasive esophagectomy.

Tumor lesion detection in patients with cervical cancer by indocyanine green near-infrared imaging.

PURPOSE: To investigate the feasibility and accuracy of near-infrared fluorescence (NIRF) imaging for detecting the extent of tumor invasion in cervical cancer using indocyanine green (ICG). METHODS: We enrolled 51 patients who were diagnosed with cervical cancer with FIGO stage IB1-IIA2 disease. Patients were administered indocyanine green (ICG) at a dose of 5 mg/kg 24 h prior to surgery. A customized near-infrared fluorescence (NIRF) imaging system was used to identify the extent of tumor invasion when radical hysterectomy specimens were harvested. The relationship between tumor fluorescence intensity and clinicopathological characteristics was analyzed. RESULTS: Of the 51 enrolled patients, 3 patients did not have residual tumors after cervical conization, and tumor lesions were identified by NIRF imaging in all the remaining 48 patients. The results of NIRF imaging were in agreement with the postoperative pathological findings in 95.8% of the patients with stromal invasion, 100% of those with surgical margin invasion, 100% of those with parametrial tumor involvement, and 100% of patients with uterine corpus invasion. The mean signal-to-background ratio (SBR) of the cervical tumors was 2.91 ± 1.64, and the SBR was independent of clinicopathological characteristics. Fluorescence microscopy confirmed that ICG fluorescence was present in the tumor nests. CONCLUSIONS: NIRF imaging enables objective, accurate, and safe identification of tumor invasion during cervical cancer surgery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT04224467.

Intraoperative near-infrared fluorescence imaging can identify pelvic nerves in patients with cervical cancer in real time during radical hysterectomy.

PURPOSE: Radical hysterectomy combined with pelvic lymphadenectomy is the standard treatment for early-stage cervical cancer, but unrecognized pelvic nerves are vulnerable to irreversible damage during surgery. This early clinical trial investigated the feasibility and safety of intraoperative near-infrared (NIR) fluorescence imaging (NIR-FI) with indocyanine green (ICG) for identifying pelvic nerves during radical hysterectomy for cervical cancer. METHODS: Sixty-six adults with cervical cancer were enrolled in this prospective, open-label, single-arm, single-center clinical trial. NIR-FI was performed in vivo to identify genitofemoral (GN), obturator (ON), and hypogastric (HN) nerves intraoperatively. The primary endpoint was the presence of fluorescence in pelvic nerves. Secondary endpoints were the ICG distribution in a nerve specimen and potential underlying causes of fluorescence emission in pelvic nerves. RESULTS: In total, 63 patients were analyzed. The ON was visualized bilaterally in 100% (63/63) of patients, with a mean fluorescence signal-to-background ratio (SBR) of 5.3±2.1. The GN was identified bilaterally in 93.7% (59/63) of patients and unilaterally in the remaining 4 patients, with a mean SBR of 4.1±1.9. The HN was identified bilaterally in 81.0% (51/63) of patients and unilaterally in 7.9% (5/63) of patients, with a mean SBR of 3.5±1.3. ICG fluorescence was detected in frozen sections of a nerve specimen, and was mainly distributed in axons. No ICG-related complications were observed. CONCLUSION: This early clinical trial demonstrated the feasibility and safety of NIR-FI to visualize pelvic nerves intraoperatively. Thus, NIR-FI may help surgeons adjust surgical decision-making, avoid nerve damage, and improve surgical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04224467.

Intraoperative fluorescence molecular imaging accelerates the coming of precision surgery in China.

PURPOSE: China has the largest cancer population globally. Surgery is the main choice for most solid cancer patients. Intraoperative fluorescence molecular imaging (FMI) has shown its great potential in assisting surgeons in achieving precise resection. We summarized the typical applications of intraoperative FMI and several new trends to promote the development of precision surgery. METHODS: The academic database and NIH clinical trial platform were systematically evaluated. We focused on the clinical application of intraoperative FMI in China. Special emphasis was placed on a series of typical studies with new technologies or high-level evidence. The emerging strategy of combining FMI with other modalities was also discussed. RESULTS: The clinical applications of clinically approved indocyanine green (ICG), methylene blue (MB), or fluorescein are on the rise in different surgical departments. Intraoperative FMI has achieved precise lesion detection, sentinel lymph node mapping, and lymphangiography for many cancers. Nerve imaging is also exploring to reduce iatrogenic injuries. Through different administration routes, these fluorescent imaging agents provided encouraging results in surgical navigation. Meanwhile, designing new cancer-specific fluorescent tracers is expected to be a promising trend to further improve the surgical outcome. CONCLUSIONS: Intraoperative FMI is in a rapid development in China. In-depth understanding of cancer-related molecular mechanisms is necessary to achieve precision surgery. Molecular-targeted fluorescent agents and multi-modal imaging techniques might play crucial roles in the era of precision surgery.

Efficacy of Near-Infrared Fluorescence-Guided Hepatectomy for the Detection of Colorectal Liver Metastases: A Randomized Controlled Trial.

BACKGROUND: The application of indocyanine green fluorescence-guided hepatectomy for liver metastases from colorectal cancer is in the preliminary stage of clinical practice; thus, its efficacy needs to be determined. This study compared the number of intrahepatic colorectal liver metastases detected intraoperatively and postoperative recovery data between patients who underwent traditional hepatectomy (nonindocyanine green group) and traditional hepatectomy plus intraoperative indocyanine green fluorescence imaging (indocyanine green group). STUDY DESIGN: Between January 2018 and March 2020, patients with potentially resectable colorectal liver metastases were randomly assigned to the nonindocyanine green or indocyanine green group. The number of intrahepatic colorectal liver metastases identified intraoperatively and based on postoperative recovery data were compared between both groups. RESULTS: Overall, we recruited 80 patients, among whom 72 eligible patients were randomly assigned. After allocation, 64 patients, comprising 32 in each group, underwent the allocated intervention and follow-up. Compared with the nonindocyanine green group, the mean number of intrahepatic colorectal liver metastases identified intraoperatively in the indocyanine green group was significantly greater (mean [standard deviation], 3.03 [1.58] vs 2.28 [1.35]; p = 0.045), the postoperative hospital stay was shorter (p = 0.012) and the 1-year recurrence rate was also lower (p = 0.017). Postoperative complications and 90-day mortality were comparable, with no statistical differences. CONCLUSIONS: Indocyanine green fluorescence imaging significantly increases the number of intrahepatic colorectal liver metastases identified and reduces postoperative hospital stay and 1-year recurrence rate without increasing hepatectomy-related complications and mortality rates.

A clinical study of a CD44v6-targeted fluorescent agent for the detection of non-muscle invasive bladder cancer.

BACKGROUND: 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. RESULTS: 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.

Resection and survival data from a clinical trial of glioblastoma multiforme-specific IRDye800-BBN fluorescence-guided surgery.

Supra-maximum surgical tumor resection without neurological damage is highly valuable for treatment and prognosis of patients with glioblastoma multiforme (GBM). We developed a GBM-specific fluorescence probe using IRDye800CW (peak absorption/emission, 778/795 nm) and bombesin (BBN), which (IRDye800-BBN) targets the gastrin-releasing peptide receptor, and evaluated the image-guided resection efficiency, sensitivity, specificity, and survivability. Twenty-nine patients with newly diagnosed GBM were enrolled. Sixteen hours preoperatively, IRDye800-BBN (1 mg in 20 ml sterile water) was intravenously administered. A customized fluorescence surgical navigation system was used intraoperatively. Postoperatively, enhanced magnetic resonance images were used to assess the residual tumor volume, calculate the resection extent, and confirm whether complete resection was achieved. Tumor tissues and nonfluorescent brain tissue in adjacent noneloquent boundary areas were harvested and assessed for diagnostic accuracy. Complete resection was achieved in 82.76% of patients. The median extent of resection was 100% (range, 90.6-100%). Eighty-nine samples were harvested, including 70 fluorescence-positive and 19 fluorescence-negative samples. The sensitivity and specificity of IRDye800-BBN were 94.44% (95% CI, 85.65-98.21%) and 88.24% (95% CI, 62.25-97.94%), respectively. Twenty-five patients were followed up (median, 13.5 [3.1-36.0] months), and 14 had died. The mean preoperative and immediate and 6-month postoperative Karnofsky performance scores were 77.9 ± 11.8, 71.3 ± 19.2, and 82.6 ± 14.7, respectively. The median overall and progression-free survival were 23.1 and 14.1 months, respectively. In conclusion, GBM-specific fluorescent IRDye800-BBN can help neurosurgeons identify the tumor boundary with sensitivity and specificity, and may improve survival outcomes.

A new method of near-infrared fluorescence image-guided hepatectomy for patients with hepatolithiasis: a randomized controlled trial.

BACKGROUND: Hepatectomy is a definitive treatment for hepatolithiasis because it simultaneously removes intrahepatic duct (IHD) stones and biliary tract strictures together with the involved liver region en bloc. Unlike cystic or solid liver tumors, hepatolithiasis is usually associated with alterations of anatomical structures and perihepatic adhesions because of chronic recurrent inflammation. This complicates identification of the target hepatic region and location of biliary strictures. METHODS: To determine the efficacy of near-infrared fluorescence (NIRF) imaging using indocyanine green (ICG), we performed a comparative trial and developed a white-light and near-infrared dual-channel image-guided device (DPM-I) for both open and endoscopic surgery. Forty-four eligible patients were randomly assigned to Group A (NIRF imaging) or Group B (traditional hepatectomy). We injected ICG via peripheral veins for patients in Group A. RESULTS: The NIRF imaging method was associated with less blood loss (OR 1.004, 95% CI 0.999-1.010; P = 0.016), briefer hospitalization (OR 1.336, 95% CI 1.016-1.756; P = 0.001), lower rates of margins with dilated bile ducts (OR 1.278, 95% CI 1.030-1.585; P = 0.023), lower postoperative white blood cell counts (OR 1.262, 95% CI 0.931-1.712; P = 0.038), lower procalcitonin levels (OR 1.316, 95% CI 1.020-1.513; P = 0.002), and lower alanine aminotransferase levels (OR 1.013, 95% CI 1.003-1.023; P = 0.002) compared with traditional hepatectomy. CONCLUSIONS: These data demonstrate the efficacy of NIRF imaging with ICG using DPM-I for treating hepatolithiasis.

Phage Display-Derived Peptide-Based Dual-Modality Imaging Probe for Bladder Cancer Diagnosis and Resection Postinstillation: A Preclinical Study.

Bladder cancer is a common human malignancy. Conventional ultrasound and white-light cystoscopy are often used for bladder cancer diagnosis and resection, but insufficient specificity results in a high bladder cancer recurrence rate. New strategies for the diagnosis and resection of bladder cancer are needed. In this study, we developed a highly specific peptide-based probe for bladder cancer photoacoustic imaging (PAI) diagnosis and near-infrared (NIR)-imaging-guided resection after instillation. A bladder cancer-specific peptide (PLSWT7) was selected by in vivo phage-display technology and labeled with IRDye800CW to synthesize a bladder cancer-specific dual-modality imaging (DMI) probe (PLSWT7-DMI). The feasibility of PLSWT7-DMI-based dual-modality PAI-NIR imaging was assessed in vitro, in mouse models, and ex vivo human bladders. An air-pouch bladder cancer (APBC) model suitable for probe instillation was established to evaluate the probe-based bladder cancer PAI diagnosis and NIR-imaging-guided resection. Human bladders were used to assess whether the PLSWT7-DMI-based DMI strategy is a translatable approach for bladder cancer detection and resection. The probe exhibited excellent selectivity and specificity both in vitro and in vivo Postinstillation of the probe, tumors <3 mm were detectable by PAI, and NIR-imaging-guided tumor resection decreased the bladder cancer recurrence rate by 90% and increased the survival in the mouse model. Additionally, ex vivo NIR imaging of human bladders indicated that PLSWT7-DMI-based imaging would potentially allow precise resection of bladder cancer in clinical settings. This PLSWT7-DMI-based DMI strategy was a translatable approach for bladder cancer diagnosis and resection and could potentially lower the bladder cancer recurrence rate. Mol Cancer Ther; 17(10); 2100-11. ©2018 AACR.

Near-infrared Intraoperative Imaging of Thoracic Sympathetic Nerves: From Preclinical Study to Clinical Trial.

The sympathetic nervous system controls and regulates the activities of the heart and other organs. Sympathetic nervous system dysfunction leads to disease. Therefore, intraoperative real-time imaging of thoracic sympathetic nerves (ITSN) would be of great clinical significance for diagnosis and therapy. The aim of this experimental study was to evaluate the feasibility and validity of intraoperative ITSN using indocyanine green (ICG). METHODS: ITSN using ICG was performed on 10 rabbits to determine its feasibility. Animals were allocated to two groups. The rabbits in one group received the same dose of ICG, but were observed at different times. The rabbits in the other group were administered different doses of ICG, but were observed at the same time. Signal to background ratio (SBR) was measured in regions of interest in all rabbits. Furthermore, fifteen consecutive patients with pulmonary nodules were intravenously injected with ICG 24 h preoperatively and underwent near-infrared (NIR) fluorescence imaging (FI) thoracoscopic surgeries between July 2015 and June 2016. A novel self-developed NIR and white-light dual-channel thoracoscope system was used. SBRs of thoracic sympathetic nerves were calculated in all patients. RESULTS: In the preclinical study, we were able to precisely recognize each rabbit's second (T2) to fifth (T5) thoracic ganglia on both sides of the spine using ITSN with ICG. In addition, we explored the relationship between SBR and the injection time of ICG and that between SBR and the dose of ICG. Using the novel dual-channel thoracoscope system, we were able to locate the ganglia from the stellate ganglion (SG) to the sixth thoracic ganglion (T6), as well as the chains between these ganglia in all patients with a high SBR value of 3.26 (standard deviation: 0.57). The pathological results confirmed our findings. CONCLUSION: We were able to use ICG FI to distinguish thoracic sympathetic nerves during NIR thoracoscopic surgery. The technique may replace the rib-oriented method as standard practice for mapping the thoracic sympathetic nerves.

Sparse Reconstruction of Fluorescence Molecular Tomography Using Variable Splitting and Alternating Direction Scheme.

PURPOSE: Fluorescence molecular tomography (FMT) is a novel imaging modality for three-dimensional preclinical research and has many potential applications for drug therapy evaluation and tumor diagnosis. However, FMT presents an ill-conditioned and ill-posed inverse problem, which is a challenge for its tomography reconstruction. Due to the importance of FMT reconstruction, it is valuable and necessary to develop further practical reconstruction methods for FMT. PROCEDURES: In this study, an efficient method using variable splitting strategy as well as alternating direction strategy (VSAD) was proposed for FMT reconstruction. In this method, the variable splitting strategy and the augmented Lagrangian function were first introduced to obtain an equivalent optimization formulation of the original problem. Then, the alternating direction scheme was used to solve the optimization problem and to accelerate its convergence. To examine the property of the VSAD method, three numerical simulation experiments (accuracy assessment experiment, robustness assessment experiment, and reconstruction speed assessment experiment) were performed and analyzed. RESULTS: The results indicated that the reconstruction accuracy, the reconstruction robustness, and the reconstruction speed of FMT were satisfactory by using the proposed VSAD method. Two in vivo studies, which were conducted by using two nude mouse models, further confirmed the advantages of the proposed method. CONCLUSIONS: The results indicated that the proposed VSAD algorithm is effective for FMT reconstruction. It was accurate, robust, and efficient for FMT imaging and was feasibly applied for in vivo FMT applications.

The identification of sub-centimetre nodules by near-infrared fluorescence thoracoscopic systems in pulmonary resection surgeries.

OBJECTIVES: Current surgical procedures lack high-sensitivity intraoperative imaging guidance, leading to undetected micro tumours. In vivo near-infrared (NIR) fluorescence imaging provides a powerful tool for identifying small nodules. The aim of this study was to examine our experience of using 2 different NIR devices in pulmonary resection surgery. METHODS: From August 2015 to October 2016, 36 patients with lung nodules underwent NIR fluorescence imaging thoracoscopic surgery. Two NIR devices: a D-Light P system and a SUPEREYE system were used. Patients were administered an injection of indocyanine green (ICG) through the peripheral vein 24 h preoperatively. During surgery, traditional white-light thoracoscopic exploration was performed first, followed by ICG-fluorescent-guided exploration. All detected nodules were resected and examined by a pathologist. RESULTS: Of the 36 patients, 76 nodules were resected. ICG-fluorescent imaging identified 68 nodules during in vivo exploration. The mean signal-to-background ratio of lung nodules in NIR exploration was 3.29 ± 1.81. The application of NIR devices led to the detection of 9 additional nodules that were missed using traditional detection methods (1 mm computed tomography scan and white-light thoracoscopic exploration) in 7 patients (19.4%). Four of the 9 nodules were confirmed as malignant or atypical adenomatous hyperplasia (44.4%). The other 5 nodules were confirmed as false-positive nodules. The sensitivities and positive predictive values of the ICG-fluorescent imaging for lung tumours were 88.7% and 92.6%, respectively. CONCLUSIONS: This study demonstrated the feasibility and safety of using ICG-fluorescent imaging for multiple lung nodules identification in video-assisted thoracoscopic surgery pulmonary resection. CLINICALTRIAL.GOV NUMBER: NCT02611245.

Development and application of the near-infrared and white-light thoracoscope system for minimally invasive lung cancer surgery.

In minimally invasive surgery, the white-light thoracoscope as a standard imaging tool is facing challenges of the low contrast between important anatomical or pathological regions and surrounding tissues. Recently, the near-infrared (NIR) fluorescence imaging shows superior advantages over the conventional white-light observation, which inspires researchers to develop imaging systems to improve overall outcomes of endoscopic imaging. We developed an NIR and white-light dual-channel thoracoscope system, which achieved high-fluorescent signal acquisition efficiency and the simultaneously optimal visualization of the NIR and color dual-channel signals. The system was designed to have fast and accurate image registration and high signal-to-background ratio by optimizing both software algorithms and optical hardware components for better performance in the NIR spectrum band. The system evaluation demonstrated that the minimally detectable concentration of indocyanine green (ICG) was 0.01 ?? ? M , and the spatial resolution was 35 ?? ? m . The in vivo feasibility of our system was verified by the preclinical experiments using six porcine models with the intravenous injection of ICG. Furthermore, the system was successfully applied for guiding the minimally invasive segmentectomy in three lung cancer patients, which revealed that our system held great promise for the clinical translation in lung cancer surgeries.

Comparison between the indocyanine green fluorescence and blue dye methods for sentinel lymph node biopsy using novel fluorescence image-guided resection equipment in different types of hospitals.

Sentinel lymph node biopsy (SLNB) has become a standard of care to detect axillary lymph metastasis in early-stage breast cancer patients with clinically negative axillary lymph nodes. Current SLNB detection modalities comprising a blue dye, a radioactive tracer, or a combination of both have advantages as well as disadvantages. Thus, near-infrared fluorescence imaging using indocyanine green (ICG) has recently been regarded as a novel method that has generated interest for SLNB around the world. However, the lack of appropriate fluorescence imaging systems has hindered further research and wide application of this method. Therefore, we developed novel fluorescence image-guided resection equipment (FIRE) to detect sentinel lymph nodes (SLNs). Moreover, to compare the ICG fluorescence imaging method with the blue dye method and to explore the universal feasibility of the former, a different type of hospital study was conducted. Ninety-nine eligible patients participated in the study at 3 different types of hospitals. After subcutaneous ICG allergy testing, all the patients were subcutaneously injected with methylene blue and ICG into the subareolar area. Consequently, 276 SLNs (range 1-7) were identified in 98 subjects (detection rate: 99%) by using the ICG fluorescence imaging method. In contrast, the blue dye method only identified 202 SLNs (range 1-7) in 91 subjects (detection rate: 91.92%). Besides, the results of the fluorescence imaging method were similar in the 3 hospitals. Our findings indicate the universal feasibility of the ICG fluorescence imaging method for SLNB using the fluorescence image-guided resection equipment in early breast cancer detection.