Development of Portable, Wireless and Smartphone Controllable Near-Infrared Spectroscopy System.

We have developed portable near-infrared tissue oxygenation monitoring systems, called the "PocketNIRS Duo" and the "PocketNIRS HM", which features wireless data communication and a sampling rate of up to 60 data readings per second. The systems can be controlled by smartphone or personal computer. We demonstrate the efficacy of the systems for monitoring changes in brain and arm muscle hemodynamics and oxygenation in breath-holding and cuff-occlusion tests, respectively.Our systems should prove to be useful as an oxygenation monitor not only in research but also in healthcare applications.

Toward (Hybrid) Navigation of a Fluorescence Camera in an Open Surgery Setting.

With the introduction of the hybrid tracer indocyanine green (ICG)-99mTc-nanocolloid, a direct relation between preoperative imaging and intraoperative fluorescence guidance was established. However, fluorescence guidance remains limited by its superficial nature. This study evaluated the feasibility of a nuclear medicine-based navigation concept that allowed intraoperative positioning of a fluorescence camera (FC) in the vicinity of preoperatively defined ICG-99mTc-nanocolloid containing sentinel nodes (SNs). METHODS: Five patients with penile cancer scheduled for SN biopsy were injected with ICG-99mTc-nanocolloid followed by preoperative SPECT/CT imaging. The navigation device was used to provide a real-time augmented reality overlay of the SPECT/CT images and video output of the FC. This overlay was then used for FC navigation. RESULTS: SPECT/CT identified 13 SNs in 9 groins. FC navigation was successful for all 12 intraoperatively evaluated SNs (average error, 8.8 mm; range, 0-20 mm). CONCLUSION: This study reveals the potential benefits of FC navigation during open surgery procedures.

(Near-Infrared) Fluorescence-Guided Surgery Under Ambient Light Conditions: A Next Step to Embedment of the Technology in Clinical Routine.

BACKGROUND AND PURPOSE: In open surgery procedures, after temporarily dimming the lights in the operation theatre, the Photo Dynamic Eye (PDE) fluorescence camera has, amongst others, been used for fluorescence-guided sentinel node (SN) biopsy procedures. To improve the clinical utility and logistics of fluorescence-guided surgery, we developed and evaluated a prototype modified PDE (m-PDE) fluorescence camera system. METHODS: The m-PDE works under ambient light conditions and includes a white light mode and a pseudo-green-colored fluorescence mode (including a gray-scaled anatomical background). Twenty-seven patients scheduled for SN biopsy for (head and neck) melanoma (n = 16), oral cavity (n = 6), or penile (n = 5) cancer were included. The number and location of SNs were determined following an indocyanine green-(99m)Tc-nanocolloid injection and preoperative imaging. Intraoperatively, fluorescence guidance was used to visualize the SNs. The m-PDE and conventional PDE were compared head-to-head in a phantom study, and in seven patients. In the remaining 20 patients, only the m-PDE was evaluated. RESULTS: Phantom study: The m-PDE was superior over the conventional PDE, with a detection sensitivity of 1.20 × 10(-11) M (vs. 3.08 × 10(-9) M) ICG in human serum albumin. In the head-to-head clinical comparison (n = 7), the m-PDE was also superior: (i) SN visualization: 100 versus 81.4 %; (ii) transcutaneous SN visualization: 40.7 versus 22.2 %; and (iii) lymphatic duct visualization: 7.4 versus 0 %. Findings were further underlined in the 20 additionally included patients. CONCLUSION: The m-PDE enhanced fluorescence imaging properties compared with its predecessor, and provides a next step towards routine integration of real-time fluorescence guidance in open surgery.

Visualization of diffusion of the drug solution during aluminum potassium tannic acid injection therapy: a pilot study.

Sclerotherapy with aluminum potassium tannic acid (ALTA), which was approved in Japan for the treatment of internal hemorrhoids in July 2004 (Takano et al., Int J Colorectal Dis 21:44-51, 2006), has been widely accepted because of its effectiveness and low invasiveness. More than 200,000 patients have received ALTA injection therapy. ALTA is injected directly into 4 points of an internal hemorrhoid (4-step injection) to induce sclerosis and remission of the hemorrhoids, and consequently, resolution of symptoms such as prolapse and bleeding. The precision of the 4-step injection is considered to be a crucial determinant of the success of this therapy and the risk of complications. However, sufficient evidence has not yet been obtained concerning the diffusion and distribution of the injected drug. A pilot study visualized the real-time diffusion/distribution of the drug solution following the 4-step injection, using the ICG (indocyanine green) fluorescence technique, and an infrared camera (Photodynamic EYE; PDE, Hamamatsu Photonics K.K.).

A simple and effective technique for identification of intersegmental planes by infrared thoracoscopy after transbronchial injection of indocyanine green.

OBJECTIVE: Pulmonary segmentectomy has been recognized as an operative option for complete resection of early-stage lung cancer in patients with poor pulmonary function. However, identification of anatomic pulmonary segments is sometimes difficult in patients with emphysema. We developed an intraoperative method for identifying intersegmental planes of the lung with high-sensitivity infrared fluorescence imaging after transbronchial injection of indocyanine green. METHODS: The study included 10 patients with early-stage lung cancer who underwent thoracoscopic segmentectomy. Under general anesthesia, indocyanine green was injected into the bronchus of target pulmonary segments. The target segments of the lung were identified using the indocyanine green fluorescence endoscope (Hamamatsu Photonics, Hamamatsu, Japan). The intersegmental lines and planes were identified and allowed removal of the segments. To evaluate operative outcomes, we compared the indocyanine green injection group with a retrospective control group with 10 matched-pair patients who underwent traditional thoracoscopic segmentectomy. RESULTS: Accurate, real-time intraoperative detection of indocyanine green with an infrared thoracoscope was confirmed. Sparing of intersegments was safely performed using both staples and electric cautery. Furthermore, infrared thoracoscopy allowed visualization of any residual portion of resected segments after segmentectomy. There was no difference between the experimental indocyanine green and control groups in terms of operative time, duration of postoperative chest drainage, or postoperative complications. Length of stay was shorter in the indocyanine green group than in the control group (P = .055). CONCLUSIONS: Transbronchial indocyanine green injection into the relevant bronchus with the use of an infrared thoracoscope allows identification of intersegmental lines and planes during thoracoscopic segmentectomy.

Intraoperative EC-IC bypass blood flow assessment with indocyanine green angiography in moyamoya and non-moyamoya ischemic stroke.

OBJECTIVE: Superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis has been used in moyamoya disease (MD) and non-moyamoya ischemic stroke (non-MD). It is important to monitor hemodynamic changes caused by bypass surgery for postoperative management. We evaluated the bypass blood flow during STA-MCA anastomosis by using indocyanine green (ICG) fluorescence angiography. METHODS: We evaluated the bypass blood flow in 13 MD and 21 non-MD patients during STA-MCA anastomosis by means of ICG angiography with injection of ICG into the anastomosed STA. The ICG perfusion area was calculated when the ICG fluorescence intensity reached maximum. We measured cortical oxygen saturation before anastomosis by means of visual light spectroscopy. RESULTS: ICG angiography demonstrated bypass blood flow from the anastomosed STA to the cortical vessels in all patients. The ICG perfusion area in MD (20.7 ± 6.6 cm(2)) was significantly larger than that in non-MD (8.4 ± 9.1 cm(2), P < 0.05). The cortical oxygen saturation (58.9% ± 8.3%) in MD was significantly lower than that in non-MD (73.4% ± 9.5%, P < 0.05). CONCLUSIONS: ICG angiography with injection of ICG into the bypass artery allowed quantitative assessment of bypass blood flow. The bypass supplies blood flow to a greater extent in MD than in non-MD during surgery. This might be caused by a larger pressure gradient between the anastomosed STA and recipient vessels in MD. These observations indicate that MD requires careful control of systemic blood pressure after surgery to avoid cerebral hyperperfusion syndrome. ICG angiography is considered useful for facilitating safe and accurate bypass surgery and providing information for postoperative management.

EC-IC bypass function in Moyamoya disease and non-Moyamoya ischemic stroke evaluated by intraoperative indocyanine green fluorescence angiography.

Indocyanine green (ICG) emits near-infrared fluorescence when it is excited by near-infrared light. The near infrared fluorescence of ICG was applied to the imaging of cerebral vessels during neurosurgical operations such as clipping of aneurysms. In this study, ICG angiography was applied to extracranial-intracranial (EC-IC) bypass surgery to evaluate the hemodynamic changes induced by bypass in moyamoya disease (MD) and non-moyamoya ischemic diseases (non-MD). These patients underwent superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis. We compared the cortical areas where the bypass supplied blood flow between MD and non-MD. ICG angiography clearly demonstrated the bypass blood flow from the anastomosed STA to the cortical vessels including arteries, capillaries, and veins in both MD and non-MD. Interestingly, the anastomosed STA supplied blood flow to a larger cortical area in MD than non-MD. The bypass supplied greater extent of blood flow to the ischemic brain in MD than in non-MD. This difference might be caused by the fact that the perfusion pressure was lower in MD than in non-MD.

Colonic tattooing using fluorescence imaging with light-emitting diode-activated indocyanine green: a feasibility study.

PURPOSE: We investigated the feasibility of a fluorescence imaging technique using light-emitting diode (LED)-activated indocyanine green (ICG) fluorescence. METHODS: Indocyanine green injections were given to patients undergoing preoperative colonoscopy for early colon cancer or colon adenoma. During subsequent laparotomy, the colon was first observed with the naked eye, and then using a prototype machine with a charge-coupled device (CCD) video camera equipped with a cutoff filter and a LED at a wavelength of 760 nm as the light source. RESULTS: LED-induced fluorescence showed tumor localization clearly and accurately in all ten patients (100%) enrolled in this study, whereas it was seen with the naked eye as a green spot in only two patients (20%) (P = 0.0077; Wilcoxon's signed-rank test). There were no complications of LED-induced fluorescence and no inflammatory signs were noted on the hematoxylin-eosin-stained slides for the identified injection sites in the resected specimens. CONCLUSIONS: Colonic tattooing using this fluorescence imaging technique of LED-activated ICG fluorescence is a new concept of colonic marking based on the characteristics that ICG is a near infrared fluorescent dye, and is useful, without any adverse effects, to identify perioperatively the tumor localization.

ICG fluorescence endoscope for visualization of the placental vascular network.

Intrauterine laser photocoagulation for twin-twin transfusion syndrome (TTTS) needs accurate in-situ recognition of placental vascular anastomosis. Because the conventional procedure is highly dependent upon the operators' skill and experience, we developed a new way to visualize the placental vascular network by a rigid-type fluorescence endoscope coupled with intravenous administration of Indocyanine green (ICG). The feasibility of the fluorescence endoscope was examined with monkey placentas and pregnant rats. The ICG fluorescence endoscope can visualize the placental vascular network in detail even in the presence of turbid amniotic fluid. Thus, this method is potentially useful for in-situ definition of the placental vascular anastomoses during the treatment for TTTS. In addition, our rigid-type fluorescence endoscope will also be a useful tool for lymph node dissection using ICG by endoscopic surgery.

Sentinel node mapping guided by indocyanine green fluorescence imaging in gastric cancer.

OBJECTIVE: In this study, we determined the possible usefulness of sentinel node (SN) mapping guided by indocyanine green (ICG) fluorescence imaging in the management of gastric cancer. SUMMARY BACKGROUND DATA: ICG fluorescence imaging system has recently been developed for obtaining biochemical information from living tissues. METHODS: Our series consisted of 56 patients with gastric cancer who underwent standard gastrectomy with lymphadenectomy. Two milliliters of ICG solution (0.5%) was injected into the submucosa around the tumor endoscopically before the operation or into the subserosa intraoperatively. ICG fluorescence imaging was conducted using a charge-coupled device camera with a light-emitting diode having a wavelength of 760 nm as the light source and a cut filter to filter out light with wavelengths below 820 nm as the detector. RESULTS: SNs were detected in 54 (96.4%) of the 56 patients, and the mean number of SNs was 7.2 +/- 7.0. Even SNs that were not green in color could be easily and clearly visualized by ICG fluorescence imaging. cT1-stage cancers were associated with a significantly higher accuracy rate (97.2% vs. 72.2%, P = 0.0127) than cT2-or cT3-stage cancers. Preoperative ICG injection was associated with a significantly higher incidence of cT1-stage cancers (87.1% vs. 40.0%, P = 0.0004), a larger mean number of SNs (9.9 +/- 7.5 vs. 4.1 +/- 5.0, P < 0.0001), a higher accuracy rate (100% vs. 73.9%, P = 0.0039), and a lower false negative rate (0% vs. 60.0%, P = 0.0345) as compared with intraoperative ICG injection. CONCLUSIONS: This study shows that ICG fluorescence imaging allows highly sensitive image-guided intraoperative SN mapping in cases of gastric cancer. Our data suggest that SN mapping guided by ICG fluorescence imaging might be useful for predicting the metastatic status in lymph nodes in cases of gastric cancer, especially those with cT1-stage cancer.

Low-coherent quantitative phase microscope for nanometer-scale measurement of living cells morphology.

We have developed a Linnik-type interference microscope provided with a low-coherent light source to obtain topographic images of an intact cellular membrane on a nanometer scale. Our technique is based on measurement of the interference between light reflected from the cell surface and a reference beam. The results show full field surface topography of cultured cells and reveal an intrinsic membrane motion of tens of nanometers.

Image-guided liver mapping using fluorescence navigation system with indocyanine green for anatomical hepatic resection.

BACKGROUND: In malignant hepatic neoplasm, anatomic resection could improve survival and limit complications from hepatectomy. Our purpose was to develop an intraoperative method for identifying segment and subsegment of the liver with high-sensitivity near-infrared fluorescence imaging. METHODS: The subjects were 35 patients with hepatic malignant liver disease who received hepatectomy in 2006. The segments of liver method of identification that used infrared observation camera system termed Photo Dynamic Eye-2 (PDE-2) with indocianine green (ICG) for the patient with malignant liver tumor (hepatocellular carcinoma: 13 cases; metastatic liver cancer: 18 cases; intrahepatic cholangio carcinoma: 4 cases) were performed before liver resection. RESULTS: Although greenish stain of the liver surface after the injection of ICG via portal vein is not visible clearly without infrared observation camera system PDE-2, 1 minute after injection of ICG with fluorescent using infrared observation camera system PDE-2, demarcation of liver segment and subsegment was clearly detected. Ten minutes after injection of ICG with fluorescent using infrared observation camera system PDE-2, fluorescence of liver subsegment remained. Stained subsegment and segment of liver were identifiable in 33 (94.3%) of the 35 patients. There were no complications or side-effects related to the injection of patent blue dye. CONCLUSION: We demonstrated here that near-infrared fluorescence imaging system is a novel and reliable intraoperative technique to identify hepatic segment and subsegment for anatomical hepatic resection.

Sentinel node mapping guided by indocyanine green fluorescence imaging: a new method for sentinel node navigation surgery in gastrointestinal cancer.

BACKGROUND: Recently, gastrointestinal cancer has also been identified as a target for sentinel node navigation surgery (SNNS). This study is the first to determine the feasibility of sentinel node (SN) mapping guided by indocyanine green (ICG) fluorescence imaging in gastrointestinal cancer. METHODS: Our series consisted of 22 patients with gastric cancer and 26 patients with colorectal cancer who had undergone standard surgical resection. ICG solution was injected intraoperatively into the subserosa around the tumor. Fluorescence imaging was obtained by a charge-coupled device (CCD) camera with a light-emitting diode with a wavelength of 760 nm as the light source and a cut filter to filter out light with wavelengths below 820 nm as the detector. RESULTS: Immediately after the ICG injection, lymphatic vessels draining the tumor and round-shaped SNs were visualized by their bright fluorescence. Even SNs that were not green in color could be easily and clearly visualized by ICG fluorescence imaging. The SN detection rate and mean number of SNs were 90.9% and 3.6 +/- 4.5 (mean +/- SD), respectively, in patients with gastric cancer, and 88.5% and 2.6 +/- 2.4, respectively, in patients with colorectal cancer. Among the patients with gastric cancer, the accuracy and false-negative rates were 88.9 and 33.3%, respectively, in patients with T(1) stage cancer, and 70.0 and 60.0%, respectively, overall, in all the patients. Among the patients with colorectal cancer, the corresponding values were 100 and 0%, respectively, in patients with T(1) stage cancer, and 82.6 and 66.7%, respectively, overall, in all the patients. CONCLUSIONS: Our preliminary results show that ICG fluorescence imaging allows easy, highly sensitive and real-time imaging-guided SN mapping in patients with gastric or colorectal cancer. SN mapping guided by ICG fluorescence imaging could be a promising tool deserving further clinical exploration.

Fluorescence navigation with indocyanine green for detecting sentinel lymph nodes in breast cancer.

BACKGROUND: Sentinel lymph node biopsy using a vital dye is a convenient and safe method to assess lymph node status in breast cancer. However, intensive training is necessary to obtain a satisfactory detection rate and to avoid false-negative results. This paper presents a novel method using indocyanine green fluorescence imaging to detect sentinel lymph nodes. METHODS: Fluorescence images were obtained using a charge coupled device camera with a cut filter as the detector, and light emitting diodes at 760 nm as the light source. When indocyanine green was injected around the areola, subcutaneous lymphatic channels draining from the areola to the axilla were visible by fluorescence within a few minutes. The sentinel lymph node was then dissected by fluorescence navigation. RESULTS: Sentinel lymph node biopsy using the present method was performed on eighteen patients. Subcutaneous lymphatics were detectable by fluorescence in all patients, and sentinel nodes were successfully identified in 17 of 18 cases (detection rate:94%). It was possible to detect the lymphatic channels and nodes receiving indocyanine green with higher sensitivity by the fluorescence signal than by the green color. CONCLUSION: Sentinel node biopsy guided by indocyanine green fluorescence imaging is a promising technique for further clinical exploration.

Optical analysis of the cirrhotic liver by near-infrared time-resolved spectroscopy.

PURPOSE: To assess the histological severity of liver cirrhosis in relation to the optical properties of liver tissue. METHODS: Various grades of liver cirrhosis were induced in rats by giving intraperitoneal injections of thioacetamide (TAA) over periods ranging from 4 to 16 weeks. The optical properties of the liver, absorption coefficient (mu(a)) and scattering coefficient (mu(s)'), were measured by near-infrared time-resolved spectroscopy. RESULTS: Histological examination confirmed cirrhotic changes in the liver, which were more severe in the rats given TAA for longer periods. The mu(a) increased in the 4- and 8-week rats, then decreased in the 12- and 16-week rats. The mu(a) of the blood-free liver decreased as liver cirrhosis progressed. The hemoglobin concentration in the liver, calculated from the mu(a) values, increased in the 4- and 8-week rats and decreased in the 12- and 16-week rats. The mu(s)' decreased in the cirrhotic liver, probably reflecting the loss of volume of hepatocytes. The product of mu(a) and mu(s)' proved useful to evaluate the severity of cirrhosis. CONCLUSIONS: These results showed that the optical properties correlated well with the severity of liver cirrhosis, indicating that the clinical application of this method is encouraging.

Impact of endothelin-1 on microcirculatory disturbance after partial hepatectomy under ischemia/reperfusion in thioacetamide-induced cirrhotic rats.

BACKGROUND: Endothelin (ET)-1 contributes to hepatic ischemia and reperfusion (HIR) injury in normal liver. This study was conducted to clarify the role of ET-1 in HIR injury in cirrhotic state. MATERIALS AND METHODS: Using thioacetamide-induced cirrhotic rats with spontaneous portosystemic shunt, we determined the changes in plasma aspartate aminotransferase (AST) levels, plasma and hepatic ET-1 values, 7-day survival rates, and hepatic oxygen saturation (SO(2)) by time-resolved spectroscopy as an indicator of hepatic microcirculation under intermittent or continuous total hepatic ischemia with subsequent partial hepatectomy. RESULTS: Hepatic ET-1 levels in cirrhotic rats were significantly higher than those in noncirrhotic rats. Plasma and hepatic ET-1 levels at 1, 3 and 6 h of reperfusion after intermittent hepatic ischemia were significantly lower than those after continuous hepatic ischemia. In cirrhotic animals subjected to intermittent hepatic ischemia, the elevation of plasma AST levels at 1, 3 and 6 h of reperfusion and the decline in hepatic SO(2) at the end of 60-min hepatic ischemia and after reperfusion were significantly suppressed when compared with those subjected to continuous hepatic ischemia. Pretreatment with a nonselective endothelin receptor antagonist in continuous hepatic ischemia significantly ameliorated plasma AST levels and hepatic SO(2) values with less hepatic sinusoidal congestion, resulting in an improvement in the 7-day survival rate. CONCLUSIONS: Continuous hepatic ischemia in the cirrhotic liver has disadvantages relating to microcirculatory derangement with more ET-1 production in partial hepatectomy. In liver surgery, pharmacological regulation of ET-1 production may lead to attenuation of reperfusion injuries for ischemically damaged cirrhotic liver.