• Journal of KIISE:Software and Applications
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• v.29 no.3
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• pp.202-210
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• 2002

During the last few years, the extraction and reconstruction of the blood vessels in the medical image has been actively researched and the analysis for the retinal vessel structure has provided important information for diagnosis and remedy of the retinopathy patients. In this research, we propose the algorithm that tracks automatically the entire retinal vessel in retinal image acquired by the ICG(IndoCyanine Green) technology. This algorithm extracts contours and centers by estimating the local maxima and processing directions and detects bifurcations and junctions by comparing direction components of the local maxima from the gradient magnitude profile of each blood vessel. We present experimental results that the entire blood vessel is automatically reconstructed and is excellent in accuracy and connectivity after applying our algorithm to the ICG retinal images of patients.

• Journal of Gastric Cancer
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• v.18 no.2
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• pp.161-171
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• 2018

Purpose: This study assessed the feasibility of near-infrared (NIR) imaging with indocyanine green (ICG) in investigating the completeness of laparoscopic lymph node (LN) dissection for gastric cancer. Materials and Methods: Patients scheduled for laparoscopic gastrectomy for treating gastric cancer were enrolled in the study. After intraoperative submucosal ICG injection (0.05 mg/mL), LN dissection was performed under conventional laparoscopic light. After dissection, the LN stations of interest were examined under the NIR mode to locate any extra ICG-stained (E) tissues, which were excised and sent for pathologic confirmation. This technique was tested in 2 steps: infra-pyloric LN dissection (step 1) and review of all stations after proper radical node dissection (step 2). Results: In step 1, 15 patients who underwent laparoscopic pylorus-preserving gastrectomy (LPPG) and 15 patients who underwent laparoscopic distal gastrectomy (LDG) were examined. Seven and 2 E-tissues were obtained during LPPG and LDG, respectively. From the retrieved E-tissues, 1 and 0 tissue obtained during LPPG and LDG, respectively, was confirmed as LN. In step 2, 20 patients were enrolled (13 D1+ dissection and 7 D2 dissection). Six E-tissues were retrieved from 5 patients, and 1 tissue was confirmed as LN in the pathologic review. Overall, 15 E-tissues were detected and removed, and 2 tissues were confirmed as LNs in the pathologic review. Both nodes were from LN station #6, with 1 case each in the LDG and LPPG groups. Conclusions: NIR imaging may provide additional node detection during laparoscopic LN dissection for gastric cancer, especially in the infra-pyloric area.

• Applied Science and Convergence Technology
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• v.24 no.6
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• pp.284-288
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• 2015

Anionic small molecules are hard to penetrate the cell membranes because of their negative charges. Encapsulation of small molecules into liposome particles can provide target specific delivery of them. In our previous study, siRNA could be efficiently encapsulated into liposome particles using an asymmetric preparation method of liposomes. In this study, the same method was applied for encapsulation of small anionic fluorescent chemicals such as calcein and indocyanine green (ICG). More than 90% fluorescent chemicals were encapsulated in the asymmetric liposome particles (ALPs). No intracellular fluorescent signal was observed in the tumor cells treated with the unmodified calcein/ALPs and ICG/ALPs, whereas the surface modification with a cell-penetrating polyarginine peptide (R8 or R12) allows cellular uptake of the ALPs. The results demonstrate that the ALPs encapsulating small anionic drugs will be useful for target-specific delivery after modification of target-specific ligands.

• Journal of Gastric Cancer
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• v.12 no.1
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• pp.7-12
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• 2012

More than ten years have passed since the sentinel node (SN) concept for gastric cancer surgery was first discussed. Less invasive modified surgical approaches based on the SN concept have already been put into practice for malignant melanoma and breast cancer, however the SN concept is not yet placed in a standard position in gastric cancer surgery even after two multi-institutional prospective clinical trials, the Japan Clinical Oncology Group trial (JCOG0302) and the Japanese Society for Sentinel Node Navigation Surgery (SNNS) trial. What is the problem in the clinical application of the SN concept to gastric cancer surgery? There is no doubt that we need reliable indicator(s) to determine with certainty the absence of metastasis in the lymph nodes in order to avoid unnecessary lymphadenectomy. There are several matters of debate in performing the actual procedure, such as the type of tracer, the site of injection, how to detect and harvest, how to detect metastases of SNs, and learning period. These issues have to be addressed further to establish the most suitable procedure. Novel technologies such as indocyanine green (ICG) fluorescence imaging and one-step nucleic acid amplification (OSNA) may overcome the current difficulties. Once we know what the problems are and how to tackle them, we can pursue the goal.

• Journal of Korean Neurosurgical Society
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• v.63 no.2
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• pp.178-187
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• 2020

Objective : The extensive vasa vasorum network functions as a conduit for the entry of inflammatory cells or factors that promote the progression of angiogenesis and plaque formation. Therefore, we investigated the correlation between the carotid vasa vasorum activities and carotid plaque vulnerability using indocyanine green video angiography (ICG-VA) during carotid endarterectomy (CEA). Methods : Sixty-nine patients who underwent CEA were enrolled prospectively from September 2015 to December 2017. During CEA, a bolus of ICG was injected intravenously before and after resecting the atheroma. Additionally, we performed immunohistochemistry using CD68 (a surface marker of macrophages), CD117 (a surface marker of mast cells), and CD4 and CD8 (surface markers of T-cells) antibodies to analyze the resected plaque specimens. Results : The density of active vasa vasorum was observed in all patients using ICG-VA. The vasa vasorum externa (VVE) and interna (VVI) were seen in 11 (16%) and 57 patients (82.6%), respectively. Macroscopically, the VVE-type patterns were strongly associated with preoperative angiographic instability (81.8%, p=0.005) and carotid plaque vulnerability (90.9%, p=0.017). In contrast, the VVI-type patterns were weakly associated with angiographic instability (31.6%) and plaque vulnerability (49.1%). CD68-stained macrophages and CD117-stained mast cells were observed more frequently in unstable plaques than in stable plaques (p<0.0001, p=0.002, respectively). Conclusion : The early appearance of VVE, along with the presence of many microvessel channels that provided nutrients to the developing and expanding atheroma during ICG-VA, was strongly associated with unstable carotid plaques. The degree of infiltration of macrophages and mast cells is possibly related to the formation of unstable plaques.

• Current Optics and Photonics
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• v.3 no.3
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• pp.256-262
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• 2019

Extensive tumor resection accompanied by radiotherapy and chemotherapy is the standard of care for malignant gliomas. However, there is a significant obstacle to the complete resection of the tumor due to the difficulty of distinguishing tumor and normal brain tissue with a conventional surgical microscope. Recently, multiple studies have shown the possibility of fluorescence-guided surgery in malignant gliomas. The most used fluorescence dyes for brain tumor surgery are 5-aminolevulinic acid (5-ALA) and indocyanine green (ICG). In this paper, a new fluorescence guided operation system, which can detect both 5-ALA and ICG fluorescent images simultaneously, is presented. This operation system consists of light emitting diodes (LEDs) which emits 410 nm and 740 nm wavelengths. We have performed experiments on rats in order to verify the operation of the newly developed operation system. Oral administration and imaging were performed to observe the fluorescence of 5-ALA and ICG fluorescence in rats. When LEDs at wavelengths of 410 nm and 740 nm were irradiated on rats, 628 nm wavelength with a violet fluorescence color and 825 nm wavelength with a red fluorescence color were expressed in 5-ALA and ICG fluorescent material, respectively, thus we were able to distinguish the tumor tissues easily. Previously, due to the poor resolution of the conventional surgical microscope and the fact that the color of the vein is similar to that of the tumor, the tumor resection margin was not easy to observe, thus increasing the likelihood for cancer recurrence. However, when the tumor is observed through the fluorescence guided operation system, it is possible to easily distinguish the color with the naked eye and it can be completely removed. Therefore, it is expected that surgical removal of cancerous tumors will be possible and surgical applications and surgical microscopes for cancer tumor removal surgery will be promising in the future.

• Archives of Plastic Surgery
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• v.49 no.1
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• pp.99-107
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• 2022

Background Dermal backflow (DBF), which refers to lymphatic reflux due to lymphatic valve insufficiency, is a diagnostic finding in lymphedema. However, the three-dimensional structure of DBF remains unknown. Photoacoustic lymphangiography (PAL) is a new technique that enables the visualization of the distribution of light-absorbing molecules, such as hemoglobin or indocyanine green (ICG), and can provide three-dimensional images of superficial lymphatic vessels and the venous system. This study reports the use of PAL to visualize DBF structures in the extremities of patients with lymphedema after cancer surgery. Methods Patients with a clinical or lymphographic diagnosis of lymphedema who previously underwent surgery for cancer at one of two participating hospitals were included in this study. PAL was performed using the PAI-05 system. ICG was administered subcutaneously in the affected hand or foot, and ICG fluorescence lymphography was performed using a near-infrared camera system prior to PAL. Results Between April 2018 and January 2019, 21 patients were enrolled and examined using PAL. The DBF was composed of dense, interconnecting, three-dimensional lymphatic vessels. It was classified into three patterns according to the composition of the lymphatic vessels: a linear structure of lymphatic collectors (pattern 1), a network of lymphatic capillaries and lymphatic collectors in an underlying layer (pattern 2), and lymphatic capillaries and precollectors with no lymphatic collectors (pattern 3). Conclusions PAL showed the structure of DBF more precisely than ICG fluorescence lymphography. The use of PAL to visualize DBF assists in understanding the pathophysiology and assessing the severity of cancer-related lymphedema.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.5 no.1
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• pp.101-107
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• 2002

We experienced two cases of Rotor syndrome in brothers who were a 13 year-old boy and an 11 year-old boy, respectively. They presented with icteric scleras for a few months. Their common laboratory characteristics were as follows: Direct bilirubin was more increased than indirect bilirubin, but aminotransferases were normal. Plasma indocyanine green (ICG) test revealed hepatic excretory defect: plasma ICG concentrations 15 minutes after intravenous injection were 80.45% and 78.28%, respectively. 99mTc-DISIDA Hepatobiliary scan showed that severely decreased hepatic extraction with mild cardiac blood pool, markedly delayed biliary excretion in both intra- & extra- hepatic bile ducts, delayed visualization of gall bladder, and markedly delayed intestinal biliary passage. Needle liver biopsy showed normal hepatic histology without pigmentation.

• Archives of Plastic Surgery
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• v.48 no.3
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• pp.323-328
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• 2021

Background Lymphaticovenular anastomosis (LVA) is a minimally invasive surgical procedure used to treat lymphedema. Volumetric measurements and quality-of-life assessments are often performed to assess the effectiveness of LVA, but there is no method that provides information regarding postoperative morphological changes in lymphatic vessels and veins after LVA. Photoacoustic lymphangiography (PAL) is an optical imaging technique that visualizes the distribution of light-absorbing molecules, such as hemoglobin or indocyanine green (ICG), and provides three-dimensional images of superficial lymphatic vessels and the venous system simultaneously. In this study, we performed PAL in lymphedema patients before and after LVA and compared the images to evaluate the effect of LVA. Methods PAL was performed using the PAI-05 system in three patients (one man, two women) with lymphedema, including one primary case and two secondary cases, before LVA. ICG fluorescence lymphography was performed in all cases before PAL. Follow-up PAL was performed between 5 days and 5 months after LVA. Results PAL enabled the simultaneous visualization of clear lymphatic vessels that could not be accurately seen with ICG fluorescence lymphography and veins. We were also able to observe and analyze morphological changes such as the width and the number of lymphatic vessels and veins during the follow-up PAL after LVA. Conclusions By comparing preoperative and postoperative PAL images, it was possible to analyze the morphological changes in lymphatic vessels and veins that occurred after LVA. Our study suggests that PAL would be useful when assessing the effect of LVA surgery.

• Journal of Breast Cancer
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• v.21 no.4
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• pp.447-452
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• 2018

Purpose: The recent trend in breast cancer treatment is to minimize axillary dissection. However, no pattern of axillary metastasis has been precisely established. The purpose of this study was to evaluate the metastatic lymphatic pattern using near-infrared fluorescence imaging with indocyanine green (ICG) in breast cancer with cytologically proven axillary metastasis. Methods: This was a prospective single-center study. We evaluated 147 patients with breast cancer involving cytologically proven axillary metastasis, and compared physiological and nonphysiological lymphatic metastasis. Results: We performed lymphatic mapping for 64 patients who exhibited level II lymphatic flow on near-infrared fluorescence imaging with ICG, and found that all had axillary metastasis: 51 patients who did not receive neoadjuvant chemotherapy (NAC) and 13 patients post-NAC. Of patients who did not receive NAC, 32 had physiological lymphatic metastasis and 19 had nonphysiological lymphatic metastasis. The risk factors for nonphysiological lymphatic metastasis were age ${\geq}55$ years, high Ki-67 index (>20%), and perinodal extension in both univariate and multivariate analysis (p<0.05). Conclusion: Patients with identified risk factors in cytologically-proven axillary metastasis who did not receive NAC may have nonphysiological lymphatic metastasis.