An ICG test uses indocyanine green, a fluorescent dye approved by the FDA for more than six decades, to measure how well an organ is functioning or to make hidden structures visible during surgery. After a small dose is injected into a vein, ICG binds to proteins in the blood, travels through the circulation, and either glows under near-infrared light or gets cleared by the liver at a measurable rate. That dual nature makes it unusually versatile: the same dye can tell a surgeon whether your liver can handle a major operation and, hours later, light up the bile ducts so those same surgeons can see exactly where to cut.
How the Dye Works Inside the Body
ICG is a water-soluble compound that, once injected, binds almost immediately to proteins circulating in your blood. It absorbs and emits light in the near-infrared range, peaking around 800 nanometers in plasma, which is just beyond what the human eye can detect. Special camera systems tuned to that wavelength pick up the glow and display it on a monitor, turning ICG into a kind of internal highlighter.
The liver does the heavy lifting when it comes to removing ICG from the bloodstream. Hepatocytes, the main working cells of the liver, grab ICG on its first pass through the organ and excrete it unchanged into bile. ICG does not get metabolized, does not pass through the kidneys, and does not linger in other tissues for long. That exclusive liver clearance is what makes it so useful as a liver function probe: the faster your liver clears the dye, the healthier it is.
One physical property worth knowing is that ICG fluoresces much more brightly in blood plasma than in plain water. Researchers have shown that plasma and less-polar solvents like ethanol enhance ICG’s emission, including emission in longer-wavelength windows beyond 1,000 nanometers. In simple saline, the dye barely glows at those wavelengths. This means that ICG works best precisely where you need it: inside living tissue surrounded by blood proteins.
Measuring Liver Function Before Surgery
The oldest and most established use of ICG is testing how well the liver clears substances from the blood, a critical question before any surgery that removes a chunk of liver tissue. The standard version of this test involves injecting a set dose of ICG into a vein and then measuring how much remains in the bloodstream after 15 minutes. That measurement is called the ICG retention rate at 15 minutes, or R15. A healthy liver clears ICG quickly, leaving only a small percentage behind. A struggling liver lets more dye linger.
In patients with cirrhosis, R15 values climb steeply alongside disease severity. One study found retention rates averaging around 15% in milder cirrhosis, 41% in moderate disease, and 58% in advanced cirrhosis, compared to roughly 7% in healthy controls. Those numbers correlated tightly with a more involved, constant-infusion clearance technique that is harder to perform at the bedside. R15 also tracked with portal hypertension and markers of liver failure, making it a practical stand-in for more invasive measurements.
Surgeons use these numbers to decide how much liver they can safely remove. Japanese guidelines, particularly those associated with the Makuuchi criteria, have long incorporated ICG clearance into surgical planning for liver cancer. The idea is straightforward: if the liver is already working below capacity, taking away a large portion could push the patient into liver failure after the operation. Some centers have expanded these criteria by combining ICG clearance data with three-dimensional volumetry of the portion of liver that will remain, estimating whether the future remnant has enough clearing capacity to keep the patient safe.
The test is not equally useful in every patient, though. In people without underlying liver disease, ICG clearance is a weaker predictor of post-surgical liver failure. One study concluded that the test does not meet expectations in noncirrhotic patients and recommended reserving it for those with cirrhosis, hepatocellular carcinoma, chronic hepatitis, advanced fatty liver disease, or a history of chemotherapy that may have damaged the liver. For healthy living liver donors who pass standard screening, the ICG test adds little.
Patients who have received chemotherapy before liver surgery occupy a middle ground. Chemotherapy drugs can injure the liver in ways that standard blood tests do not always capture. Screening with ICG in these patients may flag hidden damage and help surgeons avoid overly aggressive resections that the liver cannot recover from.
Lighting Up the Bile Ducts During Gallbladder Surgery
Gallbladder removal is one of the most common operations in the world, and one of its most feared complications is accidental injury to the common bile duct. ICG fluorescence cholangiography has emerged as a way to reduce that risk. The dye is injected before or during the procedure and, because the liver excretes it into bile, the bile ducts begin to glow under a near-infrared camera. Surgeons can then see the ductal anatomy in real time, without stopping the operation to inject contrast through the bile ducts the old-fashioned way.
The technique works during both robotic and standard laparoscopic cholecystectomy. In a series of 184 consecutive robotic cases, ICG fluorescent cholangiography proved safe and effective for real-time visualization of the biliary tree. A separate observational study of 70 laparoscopic patients reached the same conclusion: ICG fluorescence enabled better identification of biliary anatomy and should be considered a tool for increasing surgical safety.
The strongest evidence so far comes from a large national cohort study. After statistical adjustment, ICG use during laparoscopic cholecystectomy was associated with a lower rate of common bile duct injury: about 0.25% with ICG versus 0.40% without it. That translated to a roughly 38% relative risk reduction. ICG use was also linked to fewer postoperative biliary procedures, fewer non-biliary complications, and less frequent conversion to open surgery.
Checking Blood Supply During Bowel and Reconstructive Surgery
When surgeons reconnect two ends of the intestine after removing a segment, the join (anastomosis) needs a good blood supply to heal. If the tissue at the connection point is poorly perfused, the anastomosis can leak, which is a serious and sometimes life-threatening complication. ICG fluorescence lets surgeons assess tissue perfusion in real time by injecting the dye and watching how brightly the tissue lights up under near-infrared imaging. Areas with poor blood flow stay dark.
Early experience with this approach in robotic rectal surgery suggested that ICG fluorescence could play a role in perfusion assessment and potentially affect anastomotic leak rates. The concept has since spread to other types of bowel surgery, as well as to reconstructive procedures like tissue flaps, where knowing whether transplanted tissue has adequate blood flow can mean the difference between a successful reconstruction and tissue death.
Finding Tumors and Mapping Lymph Nodes
ICG has carved out a growing role in cancer surgery, where it serves two related but distinct purposes: identifying tumor margins and mapping sentinel lymph nodes.
For liver tumors, ICG administered before surgery tends to accumulate in and around cancerous tissue because tumor cells and the liver tissue surrounding them do not excrete the dye normally. This creates a fluorescent halo visible under near-infrared cameras. In a study of patients undergoing minimally invasive resection of colorectal liver metastases, surgeons used ICG fluorescence to evaluate the margins of their cuts. In about 8.5% of cases, fluorescence prompted them to remove additional tissue, and in nearly 60% of those re-resections, the margin status improved from positive (cancer cells at the edge) to negative (clear margins). That extra step boosted the overall clear-margin rate from about 87% to over 92%.
Sentinel lymph node mapping is the other major oncology application. In breast cancer surgery, finding the first lymph node that drains the tumor helps determine whether cancer has started to spread. The traditional approach uses a radioactive tracer and sometimes a blue dye. ICG offers a radiation-free alternative. A prospective trial comparing ICG to scintigraphy in breast cancer found detection rates of just under 89% for ICG versus 96% for the radioactive method, with no systemic or local side effects from the dye and significantly lower cost. A larger trial of 305 patients found the two techniques much closer: ICG identified sentinel nodes in about 98% of cases versus 98.3% for the radioactive tracer, and ICG detected roughly 95% of nodes that turned out to contain cancer.
The technique extends beyond adult breast cancer. In a prospective study of pediatric and adolescent tumor patients, ICG-guided sentinel lymph node harvesting achieved 100% sensitivity, with every fluorescent node confirmed positive by a radioactive signal as well. No adverse events were recorded.
Uses in Eye Imaging
ICG angiography has been a staple in ophthalmology for decades. Unlike the more common fluorescein angiography, which images the retinal blood vessels well but struggles with deeper structures, ICG’s near-infrared fluorescence penetrates through the retinal pigment and blood to illuminate the choroid, the vascular layer beneath the retina. This makes it particularly valuable for diagnosing diseases that affect the choroidal vasculature, such as polypoidal choroidal vasculopathy and certain forms of age-related macular degeneration. Coupled with newer imaging technology, ICG remains an established technique for identifying a range of retinal and choroidal diseases.
Measuring Cardiac Output and Blood Volume
Before ICG became a surgical fluorescent tool, it was already being used in cardiology and critical care for hemodynamic monitoring. The principle is dye-dilution: inject a known amount of ICG, measure how quickly it appears and how concentrated it is downstream, and you can calculate cardiac output (how much blood the heart pumps per minute) and circulating blood volume.
A technique called pulse dye densitometry reads ICG concentration through the skin using a sensor similar to a pulse oximeter, placed on the nose or fingertip. This is far less invasive than older methods that required threading a catheter into the pulmonary artery. Studies in cardiac surgery patients confirmed that pulse dye densitometry could track changes in blood volume and cardiac output perioperatively, providing clinically useful data without the risks of an additional invasive catheter. One validation study in 30 cardiac surgery patients found that blood volume measurements from the pulse method agreed closely with the standard invasive technique, with patient blood volumes ranging from about 2.5 to 7 liters.
What the Test Actually Looks Like for the Patient
From a patient’s perspective, ICG testing is straightforward. For the liver function version, a nurse places an intravenous line, injects a weight-based dose of ICG, and then either draws blood samples at timed intervals or clips a non-invasive sensor onto your finger or nose. Bedside monitors using pulse dye densitometry technology have made the blood-sampling approach largely unnecessary in many hospitals, turning what used to be a multi-step laboratory test into a quick bedside measurement. The two key numbers that come out are the plasma disappearance rate (PDR), measured in percent per minute, and R15. A PDR below roughly 19.5% per minute or an R15 above roughly 5.6% has been identified as a threshold associated with higher risk of liver dysfunction after surgery, though these cutoffs are not perfectly sensitive or specific.
For surgical fluorescence applications, the injection happens in the operating room while you are already under anesthesia. The surgical team switches their camera to a near-infrared mode, and the dye’s glow appears as a bright overlay on the live video feed. The patient never sees or feels anything different.
Safety Profile and Allergic Reactions
ICG has an excellent safety record overall. In a prospective evaluation of over 1,900 cases of intravenous ICG use for video angiography, mild adverse reactions occurred in 0.15% of cases, moderate reactions in 0.2%, and severe reactions in 0.05%. There were no deaths in that series. A separate large series of nearly 3,800 ICG angiography cases reported an overall adverse reaction rate of only 0.34%, with most reactions being mild, though two patients experienced significant drops in blood pressure.
Severe anaphylactic reactions, while exceedingly rare, have been documented. Case reports describe anaphylactic shock during robotic surgery, and at least two deaths attributed to anaphylaxis from ICG have been reported in the broader literature. The doses used in angiography (sometimes 25 to 75 milligrams) tend to be substantially higher than the small doses used during robotic or laparoscopic procedures, which may partially explain the dose-related spectrum of reactions.
ICG contains sodium iodide, which means patients with known iodine allergies are typically excluded from receiving it. This is one of the few absolute contraindications. A large study of over 900 patients undergoing ICG injection for sentinel lymph node mapping in endometrial cancer found zero anaphylactic or other adverse reactions either during or immediately after surgery. Ten patients did develop skin reactions in the first week, but investigation attributed all of them to other causes like antiseptic solutions, surgical tape, or new medications rather than to ICG itself.
Safety data in neonates and children also looks reassuring. A review of eight studies involving ICG fluorescence angiography in neonates found a favorable safety profile with no serious adverse events.
When the Test Can Mislead
No diagnostic test is perfect, and ICG clearance has some well-known blind spots. Acute cholestasis, a sudden blockage of bile flow, directly interferes with ICG excretion because the dye depends on being flushed into the bile ducts. If a patient has a blocked bile duct from a gallstone or other cause, their ICG retention will look abnormally high even if the liver cells themselves are functioning well. Clinicians interpreting an ICG test need to account for this.
Thyroid function is another confounding factor. Thyroid hormones influence hepatic blood flow and liver cell uptake, so both hyper- and hypothyroidism can skew results. Similarly, certain drugs that compete for the same liver uptake pathways can alter ICG clearance without reflecting any real change in liver health.
For the fluorescence imaging applications, body composition matters. In sentinel lymph node mapping for breast cancer, a body mass index above 40 was identified as a limiting factor because the near-infrared signal has trouble penetrating through thick layers of tissue. This means ICG fluorescence may be less reliable in patients with severe obesity, potentially requiring the traditional radioactive tracer approach instead.
Veterinary Applications
ICG is not limited to human medicine. Veterinary surgeons have adopted it for similar purposes, particularly in oncologic liver surgery in dogs. A study of canine hepatic masses found that ICG fluorescence imaging had clinical value for identifying tumors and evaluating surgical margins. While the fluorescence pattern alone could not reliably distinguish between different types of liver tumors, it was useful for confirming complete resection. In cases of hepatocellular carcinoma in dogs, achieving complete resection appeared to carry a survival benefit.
Nanoparticle Formulations and Targeted Delivery
One of ICG’s practical drawbacks is that it does not naturally home in on tumors with much specificity. After injection, it circulates broadly and accumulates in tumors mainly through passive mechanisms like leaky blood vessels or impaired biliary excretion. Researchers are working on nanoparticle-based formulations that package ICG into tiny carriers engineered to seek out cancer cells more precisely. The goal is a higher signal from the tumor and less background noise from surrounding healthy tissue.
One approach loads ICG into ferritin nanocages, which are natural protein-based particles that have an inherent tendency to home in on tumors. In laboratory testing and an animal model of triple-negative breast cancer, ferritin-encapsulated ICG delivered the dye to tumors more efficiently than free ICG alone. Other strategies involve pairing ICG with antibodies or peptides that bind to specific receptors on cancer cells. These formulations are still in early-stage research, but they illustrate where the technology is heading: from a general-purpose dye to a precision tool that could make tumor borders even clearer during surgery.
The appeal of building on ICG rather than starting from scratch with a new dye is regulatory. Because ICG itself already has FDA approval and a long safety track record, nanoparticle formulations that use it as the fluorescent component may face a smoother path through clinical trials than an entirely novel fluorophore would. Whether that regulatory advantage holds up in practice remains to be seen, but it gives ICG-based research a meaningful head start.