What Is Indocyanine Green Angiography?

Indocyanine green angiography is a medical imaging technique that uses a fluorescent dye called indocyanine green (ICG) and near-infrared light to produce real-time maps of blood flow in tissues. Originally developed for eye diagnostics, the technique has spread across surgical specialties over the past two decades, from guiding tumor removal to checking whether a transplanted skin flap has adequate blood supply. The dye itself has been in clinical use for more than 60 years and carries a strong safety record, which partly explains why surgeons keep finding new things to do with it.¹

How the Dye and the Light Work Together

ICG is a water-soluble dye that absorbs light in the near-infrared range, peaking around 780 to 800 nm depending on what it is dissolved in.² When the dye is hit with near-infrared light at the right wavelength, it fluoresces, emitting light at a slightly longer wavelength (roughly 820 nm or above). A camera fitted with special filters picks up that fluorescent glow while blocking all other light, so vessels carrying the dye appear bright against a dark background. The whole process happens in real time: a surgeon or ophthalmologist can watch blood flow through vessels on a screen just seconds after injecting the dye.

Once injected into a vein, ICG binds tightly to plasma proteins, mainly albumin.³ That protein binding keeps the dye inside blood vessels rather than leaking into surrounding tissue, which is what makes it so useful for mapping vascular structures. The liver clears ICG from the bloodstream, and it exits the body through bile without being chemically changed. This predictable clearance route is also what makes ICG valuable for measuring how well the liver is working, a completely separate application from angiography itself.

Near-infrared light penetrates tissue more deeply than visible light, which gives ICG angiography an advantage over techniques that rely on dyes fluorescing in the visible spectrum. The practical result is that you can see blood flow in structures hidden beneath several millimeters of tissue, including the choroidal vessels underneath the retina and blood supply deep inside a surgical wound.

The Classic Use in Eye Imaging

ICG angiography first became a standard clinical tool in ophthalmology. The retina sits atop a dense layer of blood vessels called the choroid, and many sight-threatening conditions involve abnormalities in that deeper vascular layer. The older and more common alternative, fluorescein angiography, uses a different dye that fluoresces in visible light. Fluorescein lights up the retinal vessels nicely, but it cannot penetrate the pigmented layer to show the choroid clearly. ICG angiography can, because near-infrared light passes through the retinal pigment epithelium and blood far more readily than the shorter-wavelength light fluorescein emits.⁴

One of the conditions where ICG angiography is most indispensable is polypoidal choroidal vasculopathy, or PCV, a form of abnormal vessel growth beneath the retina that can cause vision loss. ICG angiography is considered the gold standard for diagnosing PCV because it reveals the characteristic polyp-like vessel bulges and the abnormal vascular network feeding them.⁵ Newer imaging technology like optical coherence tomography angiography (OCTA) can pick up some of these features without an injection, but head-to-head comparisons show that ICG angiography still catches polyps that OCTA misses. In one study, ICG angiography detected polyp-like lesions in every eye examined, while OCTA found them in about three-quarters.⁶

ICG angiography also helps in chronic central serous chorioretinopathy, a condition in which fluid leaks under the retina and can be tricky to distinguish from other diseases. In one series, ICG imaging picked up hidden areas of abnormal vessel growth in roughly one in ten eyes that standard evaluation had not fully characterized.⁷ Catching those areas matters because the treatment approach changes depending on whether abnormal vessels are present.

Checking Blood Supply During Reconstructive Surgery

When a surgeon moves a flap of tissue from one part of the body to another to reconstruct a wound, the success of the procedure depends almost entirely on whether that tissue gets enough blood flow once it is in its new position. Historically, surgeons relied on the color, warmth, and bleeding pattern of the tissue to judge perfusion, a method that is subjective and imperfect. ICG angiography gives them an objective, real-time view of blood flow in the flap while the patient is still on the table.

A large study of 877 consecutive free-flap surgeries found that using ICG angiography to assess perfusion during the operation significantly reduced the rates of partial flap loss and the need for return trips to the operating room.⁸ An international expert panel reached consensus that ICG angiography outperforms a surgeon’s unaided clinical judgment in assessing tissue viability, and that it leads to fewer reoperations during breast reconstruction after mastectomy.⁹

Researchers have also worked on turning the fluorescence signal into a quantitative number that predicts whether tissue will survive or die. One prospective study found that when the fluorescence reading fell below a specific threshold, it predicted postoperative flap necrosis with about 85% sensitivity and 70% specificity.¹⁰ Having a number rather than a gut feeling helps surgeons decide in real time whether to trim back tissue that is unlikely to survive.

Visualizing Bile Ducts During Gallbladder Surgery

Gallbladder removal is one of the most common surgeries in the world, and the most feared complication is accidentally cutting the wrong duct. The bile ducts can follow unpredictable anatomical paths, and in a laparoscopic view they all look similar. Because ICG is cleared through bile, injecting a small dose before surgery causes the bile ducts to glow under near-infrared light, making it much easier to tell which duct is which before cutting anything.

A systematic review pooling data from 13 studies found that ICG fluorescence allowed surgeons to see the cystic duct in about 97% of cases after dissection and in roughly 87% even before dissecting through the surrounding tissue.¹¹ In another single-center series of 184 robotic cholecystectomies, ICG fluorescence visualized at least one biliary structure in 99% of cases, with the common bile duct visible in about 96%.¹² The technique does not require any special catheter or X-ray equipment, which makes it simpler and faster than the traditional method of injecting dye directly into the duct and taking an X-ray.

Guiding Bowel Surgery and Sentinel Lymph Node Mapping

During colorectal surgery, surgeons sometimes need to reconnect two ends of the intestine after removing a section. If the remaining bowel has poor blood supply at the point of reconnection, the join (anastomosis) can leak, a dangerous complication. ICG angiography lets the surgeon check perfusion at the planned connection point before committing to it. In a multicenter randomized trial, ICG imaging revealed inadequate blood flow that led surgeons to extend the bowel resection in about 11% of cases, decisions that would not have been made under ordinary white-light inspection alone.¹³

ICG also plays a growing role in cancer surgery for mapping sentinel lymph nodes, the first nodes draining a tumor that are most likely to harbor cancer cells. Traditionally, surgeons used blue dye or a radioactive tracer to find these nodes. ICG fluorescence provides a radiation-free alternative that lets the surgeon see glowing lymphatic channels and nodes in real time. Studies have confirmed that ICG can reliably identify sentinel lymph nodes in cervical cancer, with researchers recommending a standardized concentration to keep detection rates high.¹⁴ For colorectal cancer, however, the evidence is less clear: a systematic review found that ICG has not yet demonstrated superiority over the older blue dye method, partly because studies vary widely in dose, injection site, and how they define a positive result.¹⁵ So while ICG is a versatile tool, it is not yet the clear winner in every lymph node mapping scenario.

Measuring Liver Function Before Surgery

Beyond imaging blood vessels, ICG has a long history as a liver function test. Because the liver is the sole route for clearing ICG from the bloodstream, the speed at which the dye disappears after injection tells clinicians how well the liver is functioning. The standard measurement, called the ICG retention rate at 15 minutes (ICG-R15), reflects what percentage of the dye remains in the blood after a quarter of an hour. A high retention rate means the liver is sluggish, which raises the risk of liver failure if a large portion of the organ is removed surgically.

Research has shown that ICG-R15 outperforms several other commonly used liver scoring systems at predicting major complications after surgery for liver cancer. In one study of hepatitis-B-related liver cancer patients, the ICG retention test predicted postoperative complications better than the Child-Pugh, MELD, or ALBI scores.¹⁶ Another study identified specific cutoff values for ICG clearance that help flag patients at risk of postoperative liver dysfunction.¹⁷ In many liver surgery centers, especially across East Asia, an ICG retention test is a routine part of preoperative workup.

Safety Profile and the Iodine Allergy Myth

ICG has an excellent safety track record. In one of the largest early safety studies of nearly 2,000 ophthalmic procedures, adverse reactions occurred in about 0.4% of patients, and the vast majority of those were mild. There were no deaths.¹⁸ Severe reactions like anaphylaxis are extremely rare, though case reports exist.¹⁹ People with a history of drug allergies have a somewhat higher reaction rate. In one study comparing patients with and without drug allergy histories who received simultaneous fluorescein and ICG angiography, about 7% of those with a drug allergy history had a reaction compared to about 4% of those without.²⁰

One of the most persistent myths around ICG is that people with iodine or shellfish allergies cannot receive it. ICG is manufactured with a small amount of sodium iodide as a stabilizer, which led to the traditional warning. But the actual immunology does not support this concern. The iodide in ICG is a tiny, simple molecule that the immune system does not recognize as a threat, unlike the large iodine-containing molecules found in X-ray contrast dyes. Multiple recent studies have specifically tested ICG in patients with documented iodine contrast allergies and found no adverse reactions.²¹ ²² That said, the one population that does face a genuine risk from the iodide content is people with uncontrolled hyperthyroidism, because even a small iodide load can potentially trigger a thyroid storm. Pregnancy is considered a relative contraindication as well, because safety data in that setting are limited.

The Equipment Behind the Glow

The hardware for ICG angiography ranges from multimillion-dollar integrated operating-room platforms to surprisingly simple handheld setups. All systems share the same basic design: a near-infrared light source to excite the dye and a camera with a filter that passes only the fluorescence wavelength while blocking everything else. In neurosurgery, surgical microscopes have been fitted with filter arrangements that pass excitation light in the 700 to 850 nm range and capture fluorescence from 780 to 950 nm, allowing the surgeon to switch between normal white-light viewing and ICG mode without moving the microscope.²³

On the other end of the cost spectrum, researchers have built functional ICG imaging devices by modifying ordinary action cameras. One prototype used an LED flashlight with a band-pass filter transmitting at 780 nm for excitation and a modified action camera with an 830 nm filter for detection.²⁴ Devices like this could bring ICG-guided surgery to resource-limited settings where the flagship commercial systems are out of reach.

Research Frontiers for ICG

Plain ICG drifts wherever the bloodstream carries it, which is useful for mapping vessels but does not help much for pinpointing tumors. A wave of research is now trying to change that by packaging ICG inside nanoparticles or attaching it to tumor-targeting molecules. In animal studies, ICG encapsulated in nanoparticles delivered significantly stronger tumor fluorescence than free ICG alone, making tumor margins easier to see during surgery.²⁵ Other groups have conjugated ICG to peptides that home in on specific tumor receptors, creating probes that combine diagnostic imaging with the potential for photothermal or photodynamic therapy, using the near-infrared light not just to see the tumor but to heat or generate toxic oxygen species that destroy it.²⁶ A separate effort produced ICG-p28, a probe pairing ICG with a tumor-targeting peptide for near-infrared fluorescence-guided breast cancer surgery.²⁷ None of these targeted probes have reached routine clinical use yet, but they represent the most active area of ICG-related development.

Artificial intelligence is also entering the picture. A recent study in skull base surgery used a publicly available AI vision model to measure ICG fluorescence intensity and compared those readings to manual measurements by clinicians. The AI-derived values closely matched the human readings for most tissue areas, suggesting that automated, standardized perfusion scoring during surgery is feasible.²⁸ Automating the interpretation could reduce the variability that comes from each surgeon eyeballing the fluorescence on a screen.

ICG in Veterinary Medicine

Veterinary surgeons have picked up ICG techniques as well. In dogs undergoing liver mass removal, ICG fluorescence imaging helped surgeons identify tumor margins and assess whether the mass had been completely excised. In one study, complete resection of liver tumors detected by ICG fluorescence appeared to carry a survival benefit.²⁹ Near-infrared fluorescence with ICG has also been explored for mapping blood vessels supplying skin flaps in dogs, with potential to improve planning for reconstructive procedures that are notoriously tricky in veterinary patients because of differences in skin blood supply between breeds.³⁰ These veterinary applications are still in relatively early stages compared with the human surgical uses, but they follow the same underlying principle and largely the same hardware.