Conventional Indocyanine Green Research Articles

ICG-augmented hyperspectral imaging for visualization of intestinal perfusion compared to conventional ICG fluorescence imaging: an experimental study.

Small bowel malperfusion (SBM) can cause high morbidity and severe surgical consequences. However, there is no standardized objective measuring tool for the quantification of SBM. Indocyanine green (ICG) imaging can be used for visualization, but lacks standardization and objectivity. Hyperspectral imaging (HSI) as a newly emerging technology in medicine might present advantages over conventional ICG fluorescence or in combination with it. HSI baseline data from physiological small bowel, avascular small bowel and small bowel after intravenous application of ICG was recorded in a total number of 54 in-vivo pig models. Visualizations of avascular small bowel after mesotomy were compared between HSI only (1), ICG-augmented HSI (IA-HSI) (2), clinical evaluation through the eyes of the surgeon (3) and conventional ICG imaging (4). The primary research focus was the localization of resection borders as suggested by each of the four methods. Distances between these borders were measured and histological samples were obtained from the regions in between in order to quantify necrotic changes 6h after mesotomy for every region. StO2 images (1) were capable of visualizing areas of physiological perfusion and areas of clearly impaired perfusion. However, exact borders where physiological perfusion started to decrease could not be clearly identified. Instead, IA-HSI (2) suggested a sharp-resection line where StO2 values started to decrease. Clinical evaluation (3) suggested a resection line 23mm (±7mm) and conventional ICG imaging (4) even suggested a resection line 53mm (±13mm) closer towards the malperfused region. Histopathological evaluation of the region that was sufficiently perfused only according to conventional ICG (R3) already revealed a significant increase in pre-necrotic changes in 27% (±9%) of surface area. Therefore, conventional ICG seems less sensitive than IA-HSI with regards to detection of insufficient tissue perfusion. In this experimental animal study, IA-HSI (2) was superior for the visualization of segmental SBM compared to conventional HSI imaging (1), clinical evaluation (3) or conventional ICG imaging (4) regarding histopathological safety. ICG application caused visual artifacts in the StO2 values of the HSI camera as values significantly increase. This is caused by optical properties of systemic ICG and does not resemble a true increase in oxygenation levels. However, this empirical finding can be used to visualize segmental SBM utilizing ICG as contrast agent in an approach for IA-HSI. Clinical applicability and relevance will have to be explored in clinical trials. Not applicable. Translational animal science. Original article.

Lymphatic ultrasound (D-CUPS) and multi-point ICG lymphography for successful LVA

Securing dilated lymphatic vessels with good function is challenging when performing lymphaticovenous anastomosis (LVA). To achieve this, we propose multi-point indocyanine green (ICG) lymphography and lymphatic ultrasound (D-CUPS; Doppler, Cross, Uncollapsible, Parallel, and Superficial fascia). With multi-point ICG lymphography, more lymphatic vessels can be found than with conventional ICG lymphography, which leads to better surgical results. Lymphatic ultrasound is more useful because it allows the observation of cross-sections of lymphatic vessels. It is known that lymphatic degeneration occurs in the lymphatic vessels in lymphedematous limbs, and LVA is most effective when dilated lymphatic vessels are anastomosed. The degree of lymphatic degeneration can be diagnosed with lymphatic ultrasound, and the proximity of dilated lymphatic vessels and veins suitable for anastomosis can be reliably identified and selected as the skin incision site for LVA. Lymphatic ultrasound is a safe, versatile and useful imaging technique that does not require a contrast agent and can be performed by anyone. By mastering multi-point ICG lymphography and lymphatic ultrasound (D-CUPS), the operation time can be shortened, and more effective LVA can be performed. In this Technical Note article, we comprehensively describe lymphatic function examinations that we have developed so far.

Handheld photoacoustic imaging of indocyanine green clearance for real-time quantitative evaluation of liver reserve function.

Preoperative assessment of liver function reserve (LFR) is essential for determining the extent of liver resection and predicting the prognosis of patients with liver disease. In this paper, we present a real-time, handheld photoacoustic imaging (PAI) system-based noninvasive approach for rapid LFR assessment. A linear-array ultrasound transducer was sealed in a housing filled with water; its front end was covered with a plastic wrap. This PAI system was first implemented on phantoms to confirm that the photoacoustic (PA) intensity of indocyanine green (ICG) in blood reflects the concentration of ICG in blood. In vivo studies on normal rabbits and rabbits with liver fibrosis were carried out by recording the dynamic PA signal of ICG in their jugular veins. By analyzing the PA intensity-time curve, a clear difference was identified in the pharmacokinetic behavior of ICG between the two groups. In normal rabbits, the mean ICG clearance rate obtained by PAI at 15 min after administration (PAI-R15) was below 21.6%, whereas in rabbits with liver fibrosis, PAI-R15 exceeded 62.0% because of poor liver metabolism. The effectiveness of the proposed method was further validated by the conventional ICG clearance test and pathological examination. Our findings suggest that PAI is a rapid, noninvasive, and convenient method for LFR assessment and has immense potential for assisting clinicians in diagnosing and managing patients with liver disease.

Super‐stable homogeneous embolic agents advance the treatment of hepatocellular carcinoma

Super‐stable homogeneous embolic agents advance the treatment of hepatocellular carcinoma

What is a precise anatomic resection of the liver? Proposal of a new evaluation method in the era of fluorescence navigation surgery.

Indocyanine green (ICG) fluorescence navigation has been adapted for anatomic liver resection (AR) but an objective method for evaluation of its validity is required. This pilot study aimed to propose a new method to evaluate the accuracy of parenchymal division along the plane between hepatic segments and estimate the real-time navigation efficacy for AR by the Medical Imaging Projection System (MIPS), which continuously demonstrates the transection plane using projection mapping with ICG fluorescence. Ten patients who underwent open AR using liver segmentation with ICG fluorescence technique between August 2016 and July 2019 were included: six patients under MIPS guidance (MIPS group), while four using only conventional ICG fluorescence technique before parenchymal resection (non-MIPS group). Densitometry of the captured fluorescence image was performed to evaluate the fluorescence area ratio of each transection plane. The accurate fluorescence area ratio was calculated by subtracting the fluorescence area rate on the resected side from that on the remnant side. The accurate fluorescence area ratio of the MIPS group and the non-MIPS group was 23.0±12.6% and 5.6±9.5%, respectively (P=.038). Based on the results of our new method, real-time navigation using the MIPS may facilitate performing AR along the plane between hepatic segments.

Use of finger-piece method for indocyanine green clearance test.

The indocyanine green (ICG) finger-piece method (FPM), which allows measurement of the ICG concentration by mounting a light sensor onto a finger, is used to assess liver function. We compared the ICG FPM with the conventional ICG blood sampling method (BSM) in patients with liver disorders. Ninety consecutive patients simultaneously underwent the ICG BSM and ICG FPM. After ICG administration, blood samples were collected at 5, 10, and 15min for the ICG BSM. The ICG concentration was measured through the finger piece by an ICG clearance meter. Seventy-one patients (78.9%) had Child-Pugh class A liver disease, and 19 (21.1%) had class B or C. The FPM-measured ICG plasma disappearance rate was positively correlated with the BSM-measured values (r = 0.886, P <0.001). Bland-Altman analysis showed good agreement between the two methods (mean difference, 0.012 ± 0.018). The FPM-measured ICG plasma disappearance rate was positively correlated with the BSM-measured values both in patients with Child-Pugh class A liver disease (r = 0.821, P <0.001) and class B or C liver disease (r = 0.859, P <0.001). The ICG FPM may be an alternative to the ICG BSM for liver function assessment.

Near-infrared indocyanine dye permits real-time characterization of both venous and lymphatic circulation

We investigated the optical properties of a near-infrared (NIR) fluorochrome, di-β-cyclodextrin-binding indocyanine derivative (TK-1), and its pharmacokinetic differences with indocyanine green (ICG). TK-1 was designed to have hydrophilic cyclodextrin molecules and, thus, for higher water solubility and smaller particle sizes than the plasma protein-bound ICG. We compared optical properties such as the absorption and fluorescence spectra, quantum yield, and photostability between both dyes in vitro. In addition, we subcutaneously injected a 1 mM solution of TK-1 or ICG into the hind footpad of rats and observed real-time NIR fluorescence intensities in their femoral veins and accompanying lymphatics at the exposed groin site to analyze the dye pharmacokinetics. These optical experiments demonstrated that TK-1 has high water solubility, a low self-aggregation tendency, and high optical and chemical stabilities. Our in vivo imaging showed that TK-1 was transported via peripheral venous flow and lymphatic flow, whereas ICG was drained only through lymphatics. The results of this study showed that lymphatic and venous transport can be differentially regulated and is most likely influenced primarily by particle size, and that TK-1 can enable real-time NIR fluorescence imaging of whole fluids and solute movement via both microvessels and lymphatics, which conventional ICG cannot achieve.

Estimation of indocyanine green 15-minute retention rate using Hitachi 7180 automatic analyser

The indocyanine green (ICG) clearance test has been used to assess the reserve of hepatic function. This method is based on the spectrometric measurement of its plasma concentration at maximum wavelength of 805nm, which requires a spectrophotometer and associated maintenance. We established an ICG measurement method using a Hitachi 7180 automatic chemistry analyser that can be tuned to a wavelength of approximately 800nm. The retention rate of ICG at 15min was determined for 41 patients using a conventional method and our method. The ICG clearance test using the automatic analyser showed excellent agreement. It is expected that the ICG test using the automatic analyser can replace the conventional ICG clearance test.

Establishment of an indocyanine green test using an automatic chemistry analyzer

The indocyanine green (ICG) clearance test has been used to assess the reserve of hepatic function. This method is based on the spectrometric measurement of its plasma concentration at maximum wavelength of 805 nm, which requires a spectrophotometer and associated maintenance. We established an ICG clearance test using a Toshiba 200FR automatic chemistry analyzer that can be tuned to a wavelength of approximately 805 nm. Five pooled sera spiked from 0 to 4.0 mg/dL were analyzed for linearity test and precision was determined at five levels in the range 0.1-2.0 mg/dL. The ICG retention rate at 15 min (R15) was determined for 38 patients using a conventional method and our method. The ICG clearance test using the automatic chemistry analyzer showed good linearity, and precision ranged from 0.3% to 1.0% for within-run CVs and from 0.6% to 4.7% for total CVs. The degree of agreement between the two methods was also acceptable (mean difference of 1.5%). It is expected that the ICG test using the automatic chemistry analyzer can replace the conventional ICG clearance test, considering the excellent agreement, good precision and linearity over a clinically relevant range.

Selective occlusion of subfoveal choroidal neovascularization in angioid streaks by using a new technique of ingrowth site treatment

Purpose To evaluate the visual and angiographic effects, as well as optical coherence tomography (OCT) findings, after a new treatment—neovascular ingrowth-site photothrombosis—in patients with subfoveal choroidal neovascularization (CNV) secondary to angioid streaks. Design Prospective noncomparative small case series. Participants Five eyes of 5 patients with angioid streaks in whom fluorescein and conventional indocyanine green (ICG) angiography clearly demonstrated distinct CNV vessels supplying the subfoveal neovascular complex. Intervention All five eyes were submitted to ICG-mediated photothrombosis of the neovascular ingrowth site. This novel, laser/dye-mediated technique uses large-spot, lower-intensity 810-nm light for continuous application of laser energy to ICG concentrated in vascular lesions. Main outcome measures Visual outcome and the results of fluorescein angiography, ICG angiography, and OCT evaluation. Results Fluorescein and conventional ICG angiography were sufficient to identify the CNV ingrowth site, which was juxtafoveal in 2 and extrafoveal in 3 of the 5 eyes in this series. Obliteration of the entire neovascular lesion was achieved in all patients within the first hour after ICG-mediated photothrombosis of the CNV ingrowth site. At 1 week, the mean change in best-corrected visual acuity from baseline was +3.2 (±1.4) lines. Twelve months after treatment, visual acuity improved by 3 or more lines in all patients, and decreased leakage of fluorescein from the CNV, as well as OCT evidence of reduced or resolved retinal edema, was seen at the last follow-up visit. Major complications, such as immediate severe visual loss and retinal vessel occlusion in the early posttreatment period, were not identified in the 5 patients submitted to the procedure. Conclusions Photothrombosis of the CNV ingrowth site by using lower-intensity light to direct laser energy continuously after IV ICG infusion is a safe and effective technique for rapid induction of CNV hypoperfusion in selected patients and is associated with considerable improvement in visual acuity and partial restoration of the retinal architecture up to 12 months after treatment.

Selective occlusion of subfoveal choroidal neovascularization in pathologic myopia using a new technique of ingrowth site treatment

Purpose To evaluate the visual and angiographic effects as well as optical coherence tomography findings after a new technique of ingrowth site treatment of subfoveal choroidal neovascularization (CNV) secondary to pathologic myopia with the use of indocyanine green (ICG)-mediated photothrombosis. Design Interventional, noncomparative case series. Methods In the setting of a tertiary referral center, patients with pathologic myopia in whom fluorescein and conventional ICG angiography demonstrated distinct CNV vessels supplying the subfoveal neovascular complex were submitted to focal ingrowth site treatment using a new therapeutic modality termed ICG-mediated photothrombosis. Prospective evaluation including visual acuity assessment, fluorescein and ICG angiography, and optical coherence tomography (OCT) evaluation was performed at weeks 1, 12, 24, and 48 after treatment. Results Six consecutive patients (six eyes) had treatment using a single session of ICG-mediated photothrombosis at the CNV ingrowth site. Obliteration of the entire neovascular complex was achieved immediately after treatment in all patients. At last follow-up, visual acuity improvement of 1 or more Early Treatment Diabetic Retinopathy Study lines was observed in five of six patients, and fluorescein angiography showed an absence (four eyes) or minimal leakage (two eyes) from CNV. Indocyanine green angiography demonstrated selective obliteration of the neovascular complex. Accordingly, reduction of retinal edema was observed in the OCT evaluation in all patients. There was no significant complication related to the procedure. Conclusions The use of lower irradiances of 810- nm continuous light application and intravenous ICG infusion for neovascular ingrowth site photothrombosis induced selective CNV hypoperfusion, as demonstrated by fluorescein and ICG angiography in patients with pathologic myopia. These findings were either consistent with the visual acuity improvement observed in five of six patients or with the partial restoration of the retinal architecture seen in OCT evaluation 12 months after treatment.

Comparison of the effects of sevoflurane, isoflurane and halothane on indocyanine green clearance

We have examined the effects of inhalation anaesthetics on indocyanine green (ICG) clearance, as an index of hepatic function, in patients undergoing elective surgery. Recently, a new method has been developed to measure in real-time the disappearance rate of ICG from plasma. This method eliminates the multiple sampling and delay of the conventional ICG test. ICG clearance is displayed as two indices: K (ICG disappearance rate) and R15 (ICG retention rate 15 min after injection of ICG 0.5 mg kg-1). This measurement was performed in patients before and after 1 MAC of sevoflurane (n = 6), 2 MAC of sevoflurane (n = 6), 1 MAC of isoflurane (n = 6), 2 MAC of isoflurane (n = 6), 1 MAC of halothane (n = 6) or 2 MAC of halothane (n = 6) without surgical stress. Although mean arterial pressure decreased significantly at 1 and 2 MAC of sevoflurane, 2 MAC of halothane, and 1 and 2 MAC of isoflurane, ICG clearance was maintained at awake levels, except at 2 MAC of halothane (K = mean-33 (sem 3)%, R15 = +90 (3)% from awake values). We conclude that sevoflurane and isoflurane have a more favourable effect on liver circulation than halothane.

Clinical applications of ICG Finger Monitor in patients with liver disease

The indocyanine green (ICG) Finger Monitor system is a non-invasive indication of ICG concentrations in the blood. In this study, significant correlation was found between the sensor signal voltage and plasma ICG concentrations ranging from 0.04 mg/dl to 1.0 mg/dl (r = 0.998, P < 0.001) in vivo. The ICG clearance curve showed an initial sharp rise 20-30 s after bolus injection, followed by a small rise. The concentration then deceased exponentially. In 196 patients with chronic liver disease, there was a close correlation between the KICG (plasma disappearance rate) and R15 (blood retention ratio at 15 min) (r = 0.886, P < 0.001, r = 0.912, P < 0.001) and corresponding values calculated by the conventional ICG method. In 263 cases with chronic liver disease, the plasma disappearance rates calculated using this monitor (mean +/- S.D.) were 0.156 +/- 0.064 (n = 20) in the control group, 0.129 +/- 0.060 (n = 92) in the chronic hepatitis group, 0.048 +/- 0.025 (n = 59) in the cirrhosis group and 0.059 +/- 0.03, (n = 92) in the group with hepatocellular carcinoma. A significant difference in the plasma disappearance rate and blood retention ratios 15 min after injection of ICG using this system was observed between control cases and the chronic hepatitis and cirrhosis groups (P < 0.0001). In 36 cases, the time from injection to the appearance of ICG in the fingertip significantly decreased in the cirrhosis group (P < 0.01). The ICG Finger Monitor system was shown to be useful clinically as well as for research due to its accuracy and non-invasive nature.